INSULIN AND CHRONIC DISEASE

Insulin: Its Crucial Role in Chronic Illness Ron Rosedale, M. D. 25th Inaugural congress meeting in Chicago.  A medical doctors conference pertaining to new  advancements in medicine.  This is likely the first talk that really discussed the role that Insulin plays in chronic illness.  Part One of Two

SPEAKER UNKNOWN: It is my extreme pleasure to introduce to you, Dr. Ron Rosedale, who will speak on INSULIN AND ITS CRUCIAL ROLE IN CHRONIC ILLNESS. Dr. Rosedale is associated with our President-Elect, Dr. John Wilson, and he will have some things to say that I believe will open our eyes. Thank you.

Dr. Ron Rosedale: Thank you for the privilege of speaking. The reason actually that I am speaking is that John asked me to, after the last AAEM meeting, and a very prominent speaker lectured on merits of a high carbohydrate diet. At the end of the talk, during the question-answer period, John got up, asked a reasonable question, “What about insulin?” The lecturer, who has written multiple books, basically just derided John, and said that he just hadn’t been keeping up the with the literature. This started a little bit of a heated discussion that went back and forth, and John knew of my interest in insulin for a long time.

First, let’s just take a look at what the literature has to say. First, we have to turn on the slide.

So, what about insulin?

A carbohydrate diet is currently the diet of choice by the American Heart Association, The American Diabetes Association, The American Cancer Association, most weight loss experts, most nutritionists, and also, I should say, most sports physiologists. Carbo-loading is almost gospel in sports.

Let’s talk a little bit about hyperinsulinemia, because a high carbohydrate diet certainly causes high insulin levels. Hyperinsulinemia adversely affects almost all degenerative diseases. That includes coronary artery disease, hypertension, cancer, stroke, diabetes, of course, obesity, autoimmune disorders, and mental disease and decline. In fact, I think you’ll come to know, and it is not just my opinion, that it may be the chemical mediator of all of the degenerative diseases of aging. It may be the leading killer in our society. We are going to discuss what it is, what cause it, and why.

First, let’s just look back at other populations.

They have already tried a number of different diets; let’s see what happened to them. Going way back let’s talk about agriculturalist, and hunter/gatherers. Anthropologists can almost immediately identify a particular society of people when they do diggings, and dig up a bunch of bones. They know almost immediately whether that society was considered a hunter/gatherer, or whether they were considered agriculturalists. Agriculturalists grew grains, and they grew their food, where the hunter/gatherers lived mostly on meat. The bones, if they are nice and strong, and long, and if the teeth are in very good repair, and if the skeletons generally showed a large body-build, those are almost uniformly hunter/gatherers. The agriculturalists have much shorter bones, and their bones are much weaker. So, the assumption, and generally being very correct, is that the hunter/gatherers were the much healthier of the people.

Let’s talk about the Egyptian diet. Now, the Egyptians are kind of unique, in that they left an excellent record. There are considered to be more mummies than there are currently Egyptians, and many of these were preserved very well. Mummifying was probably the ultimate antioxidant. What did they eat? There are multiple records in the papyrus writings, and in the examinations of the digestive systems of the Egyptians were very excellent documentations of the diets of the ancient Egyptians. What was it? Well, they ate a lot of fresh vegetables. They ate a lot of lettuce, cucumbers, garlic, onion, lentils, peas, and they used a lot of olive oil. The only oils they essentially used for cooking were olive oil and sesame oil. They used no lard. They ate a lot of bread, and the bread was made by freshly stone-grinding wheat and barley. There were no processed foods; they didn’t have cans then. They used a little bit of honey, and no refined sugar; obviously, they didn’t have refined sugar then; that didn’t come for another thousand years. They ate no red meat. They ate a little bit of fish, they ate some chicken, and of course, it was free-range chicken. They ate a very low-cholesterol diet, and a very low-saturated fat diet. Does this diet sound familiar? Sounds like a diet that was previously recommended in this mornings talk as being a very excellent and healthy diet. I mean, you couldn’t go into a health food store and buy that good a diet.

So, what was the health of these people like? Well, a gentleman by the name of Iden Cogburn, who is the founder of the Paleopathology Association (this is a group of pathologists and other physicians who are very interested in studying scientifically the remains of ancient societies), wrote a book called MUMMIES, DISEASE, AND ANCIENT CULTURES. I’d like to quote him: “Atheromatous disease of the arteries is a common finding in mummies. Nowadays, a great deal of emphasis is placed on the stress of modern life. Once modern diet is factored in the high incidence of this disorder in our present-day industrialized civilization, but the etiological influences were certainly there in the ancient world, and this thought should be taken into account in any theorizing regarding causation.” It is well known that ancient Egyptians had a very high incidence of coronary disease. In analyzing the arteries, and they had a high incidence of calcified plaque in the arteries, and these people did not live long. They died young; even at a young age, their plaque was highly calcified, indicating it had been there for a while. We also know that they had hypertension, and they had rampant obesity. These people were not thin like you see in writings. Now of course, when we take pictures in magazines, we only take pictures of beautiful, live models. The ancient Egyptians were actually an obese society. They also had very poor dental hygiene. They had a lot of infection, a lot of parasites, and they were not a healthy society, and yet, they ate a diet that would be the choice of diet that is currently recommended. The diet that the Egyptians ate, and the diet that is currently recommended, is a high-carbohydrate diet. Now, their diet was a very high complex carbohydrate diet; there was nothing refined at all about it, yet they were not very healthy. This is uniformly found in ancient cultures.

I would also like to take a look at the Eskimos. The Eskimos eat a diet that for most people would be considered horrendous. Anywhere between 70 to 90% of the calories derived in Eskimo diets are from fat, depending on the season. Sometimes they will eat a high-protein diet, high protein or fat. They eat very little carbohydrates. In wintertime, they eat no carbohydrates. Coronary disease is almost unknown; so is diabetes. Look it up!

In the last, well, especially 15 years, but even 20 or 30 years, our consumption of fat has declined. You cannot go into a grocery store anymore without seeing row after row of nonfat foods. We’ve got nonfat Fig Newtons, nonfat cheese cake, and nonfat everything – fat has gone down, I mean, Snackwell’s from Nabisco is one of the hottest companies, nonfat cookies. What’s happening to us? In a very short period of time, in the last 12 years, the incidence of clinical obesity, which is considered 20% over ideal weight by the Metropolitan Life Insurance tables, has gone from 25% to 33%. We’re the fattest country on earth. So, if the fat consumption has gone down, our fat has gone up. We are substituting the fat calories for carbohydrate calories.

Well, let’s talk about insulin.

Insulin really is the master hormone of metabolism. It tells our energy where to go, and what to do, and how to do it. It regulates our energy intake. When you’re talking about obesity, and when you’re talking about anything that has to do with fat, or coronary disease, you cannot ignore insulin. It’s there to tell that fat where to go, and how to get there. Of course, we know it is made in the pancreas, in the beta cells of the islet cells of the pancreas, it is initially stored as granules, and those granules are released when there is a sensation of blood sugar, and that quick release is lost in type II diabetes. I’ll kind of breeze over this; I don’t want to dwell too much on some of this. One thing I do want to mention is, in the molecule itself, there is a small peptide called C-peptide, and that C-peptide is cleaved when it is released into the blood stream. You can use that little peptide to determine how much insulin a pancreas is putting out. So, if you have a patient who is on insulin, how can you tell if their own pancreas is working? How much insulin are they actually manufacturing themselves, without getting poisoned by exogenous insulin? Well, you can measure the C-peptide level, and you can know whether they are producing their own insulin or not. That is a very important test, because that is going to tell you ultimately whether that person really needs to be on insulin or not.

Let’s look at the evolutionary role of insulin.

Why is insulin really there? You talk about insulin, and you think about decreasing blood sugar, and insulin is there to lower blood sugar. I wasn’t around at the time, but I don’t think that was really the reason that insulin came about. I mean, insulin really came about to manufacture, and to regulate energy. Way back when, I don’t think lowering blood sugar was a major problem; there wasn’t that much of it. There wasn’t much carbohydrate out there; nobody had sugar. Nobody ate Twinkies. We have one hormone to lower blood sugar – that’s insulin. We’ve got a bunch of them to raise blood sugar. I maintain that it was actually increasing blood sugar that was our main problem. Our brain burns glucose. There are a few tissues in our body that actually prefer to burn sugar; that’s our RBC’s, our retinas, and certain tissues in our gonads. The rest of the body would prefer to burn fat, but it is due to the tissue’s requiring glucose that we need to maintain a certain level of blood sugar, and so we have developed multiple hormones to keep the sugar up, if we are not taking in very much carbohydratewhich, millions of years ago, just wasn’t there.

Let’s talk quickly about glucose homeostasis. You eat sugar, you eat carbohydrates, cause an increase in blood sugar, at least to the release of insulin from the pancreas, and the production of the insulin in the pancreas, which is important. That goes right to the liver, which shuts off hepatic gluconeogenesis. That is a very important concept. One of the main effects of insulin is to turn off the liver’s production of glucose, and we will get to that a little bit later, too.

The sugar goes to the receptors throughout the body, especially fat and muscle cells, and that stimulates the number of reactions which cause glucose uptake and utilization, glycogen synthesis, and then decreased serum glucose, straight forward. Now, what happens when you have a high-carbohydrate meal? That causes the output of quite a bit of insulin. This causes a lot of large numbers – large numbers, large mistakes. You eat a bunch of carbohydrates, this forms a bunch of blood sugar, and your pancreas senses that you’ve got a very high blood sugar level, so it just dumps all those insulin granules, to try and get that blood sugar stored. That can cause generally an overshoot, and the sugar goes a bit too low. Now, what happens? Your body puts out the multitude of regulatory hormones to increase blood sugar that has evolved over the years, many years ago. Glucagon, and in particular cortisone, epinephrine, and growth hormone, to some extent. That is a frequent cause of stress. It’s probably your main stress: the constant stress on the adrenal to produce cortisone to raise your blood sugar after it has gone too high, and then too low. It goes up and down and up and down, and it’s a constant cycle that we are going through all day long. It has multiple repercussions. In addition, we still have quite a bit of insulin out there. Now, that insulin is turning off the production of sugar, and it signals the brain when that sugar is low, to crave sugar and carbohydrates. When your levels drop, one of the main effects is that you crave carbohydrates to get that sugar back up. This is one of the main causes of sugar craving. What happens, you’ll go for that nearest bag of potato chips you can. What happens? Blood sugars go way up again, and we repeat the cycle, day in and day out, week after week, year after year.

Glucagon – you don’t hear much about Glucagon. Glucagon is also manufactured in the pancreas, right next to where insulin is manufactured, in the alpha cells. This essentially has the opposite effect of insulin. It stimulates the burning effect, it stimulates the breakdown of glycogen to increase blood sugar, it stimulates gluconeogenesis, the manufacturer of sugar from amino acids, and it increases your blood sugar, and it is secreted in response to eating proteins, and not carbohydrates. You never hear of alpha cell burn out. Beta cell burn out is common, as it is happening to all of us. You never hear about alpha cell burn out. Why is that?

Okay, let’s talk a little about insulin physiology.

What does it do? You talk insulin, you could talk to an endocrinologist. “What does insulin do?” “It lowers your blood sugar.” Yeah, but you’ll see, it does a lot more. It increases fat storage and uptake through an enzyme called lipoprotein lipase. A ton of research right now is going on lipoprotein lipase; insulin turns it on. You cannot get fat without it. Lipoprotein lipase allows fatty acids to get into cells. Basically, what it does, is it takes the fatty acids from triglycerides. Triglycerides themselves cannot get right into a fat cell. It has to be broken down into fatty acids. The fatty acids then enter the adipose tissue, and then turn into fat. Lipoprotein lipase is turned on, and you get fat. It is a very important enzyme.

Insulin decreases gluconeogenesis in the liver. That is really, in a 24-hour period, how insulin lowers your blood sugar, not so much by transporting into cells. Your total amount of blood sugar in a 24-hour period is increased more by gluconeogenesis in the liver than it is by your dietary intake. The regulation of gluconeogenesis by insulin is extremely important. We’ll get to that a little bit later. It increases the amino acids in the muscle tissue. Insulin is an anabolic hormone. It is a very powerful anabolic hormone! Growth hormone works very minimally without insulin. The two work together. Growth hormone and insulin allow different amino acids in the cells. Without both of them, you really cannot get a complete protein into your cells. Weight lifters are starting to recognize this, because insulin is not banned. It increases fat storage, especially visceral and abdominal, and that’s very important. That is where it packs the fat. We’ll talk about that in a little bit. I don’t know if you heard about the apple shape and the pear shape. Apple shape is much more detrimental to your health, especially in women. That’s where you get fat belies. You get fat thighs, and you might not look so great, but you’re not hurting your health as much. Insulin puts it in your belly, packs it in your liver, packs it in your kidneys, and inhibits function.

Another very important aspect; insulin decreases fat lipolysis. You cannot burn fat when insulin levels are high. It is very difficult. You try to go on a diet, and you have high insulin levels, you might lose weight, but you’re not going to burn fat. You’ll burn everything else that can turn to sugar, that could include your heart, first. You lose lean body tissue. You get increased saturated fat production delivered from sugar. Insulin tells your liver to make fat from your excess sugar floating around that you’re not burning. Your liver gets fat. That’s where fat production takes place. Another type of fat that your liver will synthesize is cholesterol. Again, insulin is an anabolic hormone; it manufactures fat, and it also manufactures the house for it. There are not enough cells to hold it, so it tells your body to manufacture more fat cells. Cholesterol is required in the manufacturing of all cells. It is an integral component of all cell membrane. So, as it is telling your body to manufacture cells, it is telling it to manufacture cholesterol. It is a very potent cholesterol synthesizer. In fact, it is by far the most potent. We’ll talk about this a bit later, but if you want to lower somebody’s cholesterol, pay attention to insulin, because you can do so very quickly and very powerfully. You can take cholesterol levels that were 400 or 500, and get them down to 200 in weeks if you lower a person’s insulin. Cortisol becomes increased both by a direct effect of insulin, and as a secondary effect by lowering blood sugar.

Growth hormone is decreased in light of work on DHEA. We’ve heard a lot about DHEA recently, and how wonderful DHEA is. The only known way to increase DHEA naturally is to lower insulin. High insulin lowers DHEA. We’ll show you that later. The so-called good eicosanoids are decreased, and the bad icosanoids are increased. Extremely important: Eicosanoids control so much of your body! They are the most powerful hormones known. We’ll get to eicosanoids a bit later. I won’t dwell on them right now. When we talk about eicosanoids, we’ll talk about delta-5 desaturate. That is increased by insulin. That is one of the most important enzymes in the body, in the regulation of hormones. You’re going to hear a lot about delta-5 desaturate in the future. If you regulate delta-5 desaturate, you can either be healthy, or you’re going to be sick. We’ll get into that. Insulin increases fluid retention, it increases the excretion of magnesium, potassium, and it increases sympathetic tone. It increases smooth muscle cell proliferation. It enhances endothelial cell production, and if there is ever a prescription for high blood pressure, that’s it. Essential hypertension in many circles now is being considered as caused by insulin. Where did they get “essential hypertension?” Essential for what? You talk a lot about endothelial health, and there is a lot of work, especially by George Kindness, who spoke this morning, about platelet adhesiveness. We all know that it’s really the clot that ends up actually killing us in coronary disease. When the blood is hypercoagulatable, if that’ a word, you’re going to be much more prone to coronary disease and stroke, and all sorts of other illnesses. It’s quite well known that insulin increases platelet adhesiveness.

It increases plasminogen activator inhibitor, and increases fibrinogen. It happens when we go on a chronic high-carbohydrate diet. This is new to humans. It’s an experiment. We’ve really been on a high-carbohydrate diet. We haven’t been there, not until we started cultivating lots of grains. What was around way back when, during cave man times, or whatever you call it. There is a lot of debate; were we animal eaters, or were we plant eaters. Frankly, I don’t think we cared. We just wanted to eat what was there. We ate a lot of plants. We have to examine our anatomy, the length of our intestines, our jaw, our teeth. We were somewhere between a carnivore and an herbivore. We ate both, probably a bit more toward plants because they didn’t run away. They were easier to get to. We ate a lot of plants. If there was a wounded animal, we’d eat it. We didn’t eat a bowl of rice. We didn’t eat a big bowl of pasta. We didn’t eat two loaves of bread; it wasn’t there. So, now, we’re eating a high-carbohydrate diet. That causes insulin resistance, and there is a lot of work being done. How does it cause insulin resistance. You can use the analogy: If you eat a lot of salt, (you start using salt to salt your foods, you never did before, but you do now), you start burning out the taste receptors for salt. You have to use more and more of it for foods to taste salty. Pretty soon, you have to use five tablespoons of salt, whereas a pinch of salt would have tasted just as salty months ago. It’s the same with sugar. Your taste receptors become desensitized. You walk into a smelly room, stay there a half an hour, and it doesn’t smell. Somebody else walks in, they faint. The olfactory nerve becomes desensitized. A cell becomes resistant to insulin in the same way after constantly being bombarded with it. There is a lot of work being done about insulin receptivity. That’s why the main thrust in research now in diabetes. They know that there are a fewer number of receptors when cells are constantly bombarded with insulin. They also know that with each receptor that there is decreased signal transmission. The receptor is a very complex molecule. I’m not going to get into it, because that would be an hour’s discussion right there, but there are multiple proteins involved. The insulin receptor transcends the entire membrane, and there are a number of chemical reactions that go along, — that transmit the signal into the cell. Most of them are proteins, and somehow, that receptor becomes burned out, and doesn’t work as well. You need more insulin to do the job, and you get what’s called hyperinsulinemic; you have hyperinsulinemia, to maintain your blood sugar. You’re not diabetic yet; your blood sugars are maintained. Your pancreas has a great capacity to put out a lot of insulin to keep that sugar down. Sometimes, it takes ten times as much, and we have seen patients who are putting out ten times as much insulin as a normal person to maintain their blood sugar. This person was not a diabetic. His fasting blood sugar was perfectly normal; he was just like you and me, but guess what? What did he see me for? Obesity. He was very big. He was young. What are the main causes of insulin resistance? Well, again, a lot of work is being done. We’re not sure what all the causes are. One thing we do know is that a chronic high-carbohydrate diet does that. One of the ways is by the chronic high blood sugar. You get what are called glycosylation of protein. We’ll talk a little bit more about that later, but one of the problems of high blood sugar is that that sugar combines with proteins, and causes glycosylation, and most people here have probably heard about hemoglobin A1C. That’s how you can measure long-term sugar control in a diabetic. Sugar glycosolates all proteins, and it does it to everybody, not just diabetics. If you measured your or my hemoglobin A1C, we hall have hemoglobinA1C, and all our proteins are glycosylated, and how glycosylated they are depends on how much sugar you’ve eaten. The insulin receptors themselves are made of of proteins, and they glycosylate, too. We’ll talk a little more about about the problems with glycosylation later.

Insulin resistance.

Saturated fats are known to increase insulin resistance – well known. There you go with blood sugar again. Your liver makes saturated fats out of excess blood sugar. The type of fat that your liver makes from excess sugar is a fully saturated fat. It’s not a good healthy fat; it’s a sticky, unhealthy, saturated fat; the kind you were avoiding when you ate the nonfat Fig Newton, and increasing your carbohydrates, and you just manufactured that saturated fat you were trying to avoid, but in doing so, you also increased your insulin. Is there a genetic component to insulin resistance? Well, maybe, that’s really under debate, too. There was a recent study one to two months ago in Science And Medicine that showed that insulin resistance can actually begin in utero. The mother is eating a high-carbohydrate diet, eating a lot of sugar, — partial beta cell burnout in the fetus. Perhaps it’s not so genetic. It is also known that low polyunsaturated fats increase insulin resistance. Supplementing with good polyunsaturated fat, omega 3, increases insulin sensitivity, and does so quite strongly. I cannot really go into the talk about fats, because there is s lot of controversy, but the controversy really arises in that fats can either be the healthiest component of your diet, or the most toxic. Polyunsaturated fats oxidize readily. Now try to remove it. When you go into a grocery store, you cannot find a good polyunsaturated fat; they have to take it out because it oxidizes so readily; it has no shelf life. It has to be protected. Your body has a ton of mechanisms to protect the polyunsaturated fats from becoming oxidized, and that’s really the main purpose of vitamin E. It’s incorporated into the cellular membranes right along with the polyunsaturated fat. This is a very important concept: Polyunsaturated fats are good for you; they just have to be protected. One saying to avoid polyunsaturated fats because it can oxidize readily is like saying avoid oxygen because it can oxygenate tissues. It’s crazy.

There are three main sites of insulin resistance: The liver, muscle, and fat. We’re going to talk about that a little bit more, and how important that is.

What’s the problem?

What’s the problem with hyperinsulinemia, insulin resistance, and why it is so bad? Well, the obvious problem is diabetes. We’ll talk just a little bit about diabetes. Diabetes type I is a different story and the two diabetes are really two totally different diseases with the same name. Diabetes type I is where the beta cells are destroyed. There is a strong autoimmune component, and there are autoimmune antibodies that are floating around, and something destroys the beta cells. Nobody is sure what it is; maybe it’s a virus. A lot of people implicate weak protein, but there is some sort of autoimmune reactions that is wiping out the beta cells. A true type I has very little autogenous insulin production, and that person is likely going to need insulin the rest of their life. Insulin is necessary, it’s not all bad, it is an anabolic hormone. You need it for muscle systhesis. Now, type II is a totally different story. The large majority of diabetics are type II. It is an acquired disease. It’s caused by insulin resistance; it is when insulin reduction can no longer keep up with insulin resistance. Type II diabetics produce too much insulin; I should say they produce much more insulin than the non-diabetic. It’s not a problem with not producing enough insulin, it’s a problem with insulin resistance, as cells aren’t listening, and so, the pancreas has to put out a ton of insulin to get the job done. If you want to go into details, you’re considered a diabetic if your fasting blood sugar is greater than 140, or if it is greater than 200 within the first two hours of glucose tolerance testing. I’m not big on numbers, but that means that if your fasting blood sugar is 139, you’re non-diabetic. Now, that increased insulin resistance causes an increase in hepatic glucose production. It’s no longer inhibited by the insulin. That’s very important, because the pancreas is free to churn out sugar, and continues to make a lot of sugar. It is a sugar-making factory, and does so mostly from amino acids. Again, most of the blood sugar in a 24-hour period is from hepatic production, not immediately from your diet. One of the definitions of type II diabetes is that it is a disorder in control of gluconeogenesis normally inhibited by insulin. There is also decreased muscle and fat glucose uptake, and also not on there, there is a decrease in the amino acid uptake in muscles, when you have insulin resistance. It’s very important, it gives you a fine, end-stage diabetic when the cells are no longer listening to insulin, and they cannot absorb amino acids, and they become muscle-depleted, approaching wasting.

Now, what about us in-between? Is your fasting blood sugar less than 140? Does your tolerance test never go above 200? We eat a high carbohydrate diet, our insulin levels are high, and we have what’s known as impaired glucose tolerance. It’s totally unknown how many people have that. It’s not normally tested. You go get a checkup, and they’ll check your blood sugar. A tiny fraction of physicians might test the fasting insulin. I told you, it’s very little. One estimation is that a third of the elderly people, another estimation is a third of the entire population, and I heard another estimation is 2/3 of all people over 65. Anyway, a lot of us have impaired glucose tolerance. We have normal blood sugar, but we have higher and delayed insulin output.

What of the affects of increased blood sugar?

Why is that so bad? Well, short-term, it’s not good because it can create an osmotic gradient in the kidney, and we pee a lot. We dehydrate, going to the bathroom all the time. We need very little insulin, actually, to prevent acidosis. That’s not really a major problem for most of us. Very high blood sugars cause fatigue, mostly because of dehydration. That’s the most immediate effect, but that’s not the real bad effect of it. The chronic effect of constant sugar in the diet is glycosylation of proteins. Constant sugar in the diet also depletes magnesium, manganese, chromium, it depletes manganese SOD, and it also reduces receptor activity. To quote from JOURNAL OF DIABETES, 03/91, “Diabetes with complications is associated with increased chemical modification of proteins and lipids, and this damage appears to be largely oxidative in origin, and is sufficient to explain the altered function of proteins in the extra-cellular matrix.”

I want to talk a little bit more about glycosylation of proteins. It affects all of our proteins, not just hemoglobin. It affects our lipoproteins. The lipoproteins become glycosylated. It’s also known that when a protein becomes glycosylated, it is a much greater target for oxidation. It increases the oxidized ability of protein when sugar is attached. Sugar becomes also a sticky baggage for that protein, and the protein can no longer function properly. It is constantly having to drag that sugar around for the life of that protein. It increases the oxidized ability of glycosylated LDL. The LDL becomes glycosylated. The HDL becomes glycosylated, it cannot function properly when it is glycated. We all have known about the damage that oxidized LDL can do. Well, glycosylated LDL is extremely oxidizable. In addition, we have sugar attached to a protein, and if there is also an attached lipid, it increases the likelihood of poor oxidation of that lipid, which also increases the oxidizability of lipoprotein. This is very important. There is an article called “The World Of Oxidative Stress and The Development of Complications of Diabetes.” This is in DIABETES, Volume 40, April 1991. “There is evidence of increased oxidative damage to collagen,” (which is a long-lived protein, and most of the oxidative damage of consequence is going to have the long-lived protein), “in diabetes. Because of the interplay between glycation and oxidation in their formation, we have termed these compounds glycosidation products. Because these products accumulate in collagen normally as a function of age, and at an accelerated rate in diabetes mellitus, diabetes mellitus may be legitimately described at the chemical level as a disease characterized by accelerated aging of collagen by glycative and oxidative mechanisms.

What are the consequences of hyperinsulinemia?

There are a lot of names for hyperinsulinemia. Syndrome X you might have heard about, and we call it CAOS, which stands for coronary artery disease, hypertension, hyperlipidemia, adult onset diabetes, obesity, and stroke. I just call it the IRS, insulin resistant syndrome; I’m not sure which is worse. There are extreme cardiovascular and cerebrovascular complications. This has been known for a long time. It takes a long time for information to get down the pipeline. Inatola Cruz did what at the time was a very famous study. Most of us, and most cardiologists, and endocrinologists have totally forgotten about this. This was done in 1961, and published in the journal CIRCULATION RESEARCH. It was titled “The effect of Intra-arterial Insulin on Tissue Cholesterol, And Fatty Acids In Diabetic Dogs.” They made dogs diabetics, and they infused insulin into the femoral arteries of those dogs for eight months. They sacrificed the dogs and examined them, and lo and behold, the femoral artery that had the insulin effused was covered with fatty streaks. The contralateral femoral artery was clear. Another study. This was done by R. W. Stout, who is still doing a lot of research. This is published in the BRITISH MEDICAL JOURNAL IN 1970. This is entitled “The Development of Vascular Lesions In Insulin Treated Animals Fed A Normal Diet.” This was done in Belfast.

Long term treatment with insulin.

“We took chickens, and we injected them with insulin for 19 weeks. We chose chickens because birds develop similar atherosclerosis as humans, and chickens in particular, because they are omnivorous. After 19 weeks, he examined their aortas, and found that there was a great increase in lipid deposits in the aortas of the insulin treated chickens as opposed to the ones who didn’t have insulin. He quotes that this provides further evidence in favor of the hypothesis that insulin and atheroma are causally related.” This was in 1970. He is continuing to do research, and he published another summation. This is in DIABETES CARE, 1990.

“Long-term treatment of insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals.” This time, they are talking about human trials.

“Insulin often inhibits regression of diet-induced experimental atherosclerosis, and insulin insufficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue.”

A quick chart, and I will not draw on it too long, but it shows the rise in incidence of coronary disease, with fasting serum insulin. One-vessel, two-vessel disease, fasting insulin rises.

Gerald Ravin is one of the pioneers in insulin resistance research, and I won’t dwell too long on this, but he is talking about some of the diseases that are clustered in insulin resistance. It talks about hypertension, glucose intolerance, hyperglycemia, upper body obesity, and they found out further now that there is a – hypertension resistance to the insulin hyperinsulinemia, glucose intolerance, increased VLDL triglyceride, reduced HDL cholesterol activator inhibitor, and fibrinogen levels.

What else does it do? We just talked about hyperlipidemia, and increased cholesterol synthesis. It increases small, dense LDL particles. We go on in our research about the detrimental effects of lipids, and first it was cholesterol, and if not cholesterol, it’s LDL cholesterol and cholesterol is good, and then we find that it is oxidized LDL. There is a type of LDL particle that is called a small, dense LDL particle, and that is the type of particle that is preferentially manufactured in the liver by insulin. We’ll talk about that in a minute. It increases HMG coenzyme A reductase. When you lower insulin, you inhibit that. When you increase glucagon, you inhibit that. Sounds like Mevacor, only without the adverse side affects of stopping co Q-10 production, (and other enzymatic reactions in the liver). It increases LDL oxidizability, and that is very important. It decreases HDL, it increases arterial wall thickening via endothelial proliferation. It increases fluid retention, as we talked about earlier. It increases blood pressure, and it increases clot formation. It decreases natural killer cells, and it increases cancer because of that, it decreases T-helper cells. It increases sympathetic tone. It increases prostaglandin E-2. Solvetti out of ——Italy, in an article titled “The Interrelationship Between Insulin Resistance And Hypertension.”

“Insulin can increase blood pressure via several mechanisms: increased renal, sodium, re-absorption, activation of sympathetic nervous system, alteration of trans-membrane, ion transport, and hypertrophy of resistance vessels. Hypertension can cause insulin resistance by altering delivery of insulin, and glucose into the muscle cells, resulting in impaired glucose uptake.” You have a vicious cycle.

In ——-, by Dr. Austin, called “Low Density Lipoprotein Subclass patterns, and Risk of MI.”

“The LDL subclass pattern characterized by small dense LDL particles was significantly associated with a three-fold increase risk of MI, independent of age, sex, and relative weight.”

Going on in the journal CIRCULATION, in 1993, “Small dense LDL is an integral feature of the insulin resistance syndrome.”

Gerald Reavin, in reviewing some of the literature titled “Syndrome X,” Six Years Later, “resistance to insulin stimulated glucose uptake, the common phenomenon, occurring in approximately 25% of the population, is associated with a number of risk factors for coronary heart disease, including hyperinsulinemia, abnormal glucose tolerance, non-insulin dependent diabetes mellitus, increased plasma triglycerides, and decreased HDL, denser LDL particles, hypertension, and abnormalities of fibrinolysis.”

It is hard to be healthy like that.

Another important researcher, Zavaroni in Italy, JOURNAL OF INTERNAL MEDICINE, entitled “Hyperinsulinemia, or ——- syndrome X.

“Hyperinsulinemic subjects are found to be relatively glucose intolerant, have higher triglyceride and uric acid concentrations in blood pressure, lower HDL cholesterol when compared with normal insulinemic individuals, but importantly, the difference in the degree of obesity had little affect on the variables measured when individuals were matched for insulin response.” In other words, it’s not their obesity that’s causing this. That is an important article.

Insulin causes obesity. Obesity can also lead to insulin resistance, but it isn’t the obesity that is causing the hypertension, and all these other problems; it’s the insulin. This is from David Belle.

“Insulin resistance, an often unrecognized problem, accompanying chronic medical disorders. Several population studies have shown that hyperinsulinemia is the independent risk factor for atheroschlerosis.” I think we are figuring that out. “Insulin resistance is associated with a number of risk factors for atherosclerisis, including glucose intolerance, hypertension, and dyslipidemia. Management should include attempts to reduce insulin resistance, and certainly not increase it.” Remember that! This is another article that we will get to a little bit later.

This is a very recent article, January 1996. This is a Japanese group, out of Osaka, Japan, that decided to do angiograms, and measure insulin. They put it in language that cardiologists can understand. They can understand angiograms, and anything else is a foreign language.

In conclusion;

“In conclusion, these data suggest that in patients with coronary artery disease, insulin-medicated glucose metabolism is significantly impaired, and correlation is noted between insulin resistance and severity of coronary artery disease. Hyperinsulinemia may stimulate the artheromatous process.” This is in DIABETES CARE, January 1996.

What about obesity? Insulin makes you fat. Insulin is an anabolic hormone. It is a storage hormone. Its’ main purpose in life is to store energy. Another important aspect of insulin is that it inhibits lipolysis very strongly. It wants you to store that energy, and it doesn’t want you to burn it. It’s a protective mechanism. Food, way back when in caveman times, wasn’t abundant all the time. It was feast or famine. We had a lot of it sometime, and we didn’t have a lot of it sometimes, especially in the wintertime. Insulin is really developed to store that energy. It was a protective mechanism. Insulin causes an increased abdominal fat. It is an independent risk factor. Apple versus pear shape; we talked about being an independent risk factor. Insulin increases fat cell number. That is important.

This talk was given in 1995, and it is quite surprising that it is still new information today.  It has long been said by experts in the field that Dr. Rosedale is a pioneer and at least 10 years ahead of the curve.

The post Insulin: Its Crucial Role in Chronic Illness – Ron Rosedale. Part 1 of 2. appeared first on Ron Rosedale, M.D..

Interview by Shelley Schlender, KGNU radio, Boulder, Colorado. 

Ron Rosedale, M.D.,
“To get the right answers you need to ask the right questions”.

Listen (30 minutes)

Ron Rosedale, there are about a thousand ways that a person can look at health research and a thousand details to check.  It’s so confusing. To understand how we work and how our metabolism works, what if we start by figuring out what questions to ask?  

RON ROSEDALE:  - Sorting through confusion—that’s really the way to go. Number one is to ask the right questions. If you don’t ask the right questions, you’re never going to get a useful answer. That’s why, for instance, in my blog on the “safe starch” debate, I posed four questions that really to me summarize what the debate is about, and then I answered them.  People often ask the wrong questions, and so they keep getting answers that create a wild goose chase, or bad information.  Getting the questions right – that’s a major key.

When it comes to questions, and what “kind of animal” are we, I’m thinking about the recent debates about metabolism.  One question that few people ask is, “What’s the point of seeking a high metabolism?  Instead, most people simply assume that a higher metabolism is a better one.  For instance, in discussions of the recent Harvard study regarding the merits of high carb/low fat, versus other ways to eat, many experts and reporters focused on how many calories the test subjects burned.  As background, in the Harvard Study, people ate one of three ways.  Two were higher in carbs.  The third was high in protein and fat and lower in carbs. 

High Thermogenic Meal

ALL the people were fed a deficit of calories that meant they lost weight, and then they were returned to a weight-stable level of calories, but rotated throughout the three different kinds of diets, keeping the calories the same on each diet.  The researchers measured plenty – inflammatory markers, hormone signaling, and so on.  What many researchers and reporters focused on is that people eating a lower-carbohydrate diet tended to burn more calories than people whose diets included more carbs.  I’ll say that again:  On the low-carb diet, the test subjects burned more calories a day than people burned on other kinds of diets.  That caught people’s attention.  Many praised that finding, saying a high metabolism is a good thing, because then, someone can eat more without gaining weight.  Does that make sense? Is asking whether someone’s metabolism is higher, with the assumption that higher is a good thing, well, is that the right question?

High Thermogenic Car (from Denverexpresscare.com)

RON ROSEDALE

No, not at all. We shouldn’t be asking the question, “How do I get a higher metabolism?” We should be asking the question, “How do I improve the quality of my metabolism?” Which is a very different story. Anybody can have a higher metabolism.  You can do it, for instance, with recreational drugs and diet pills, many of which have been taken off the market,. These for the most part, will actually increase the rate of aging and its symptoms, as will many other ways to “raise” metabolism just for the sake of raising it such as the many “thermogenic aids” in “health food” stores.  If you simply seek to increase metabolism, you’re just going to increase the rate of whatever kind metabolism you’ve got going, good or bad. So if you’ve got a less than optimal metabolism, and you just increase the rate of it, you’re just going to increase the damage that it’s doing.  That’s what you see in many, many people. And that’s a major problem.

A related problem is a misunderstanding about how the thyroid, and diet, interact with metabolism.  One of the major issues that one sees in the so-called safe starch debate, is that the advocates of eating more starches often warn that when you don’t eat carbs, you end up with a  lower amount of the thyroid hormone, T3, in the blood, and this is a warning sign of hypothyroidism–meaning too little thyroid function. And that’s just such a wrong way of looking at it. Certainly when you eat a very low-carbohydrate, high-fat diet, the amount of T3 in your blood goes down—but in most cases, even though T3 goes down, your TSH – thyroid stimulating hormone – does not go up.   TSH is a kind of thermostatic regulator.  When the body actually needs more thyroid hormone, TSH generally rises, and pushes the thyroid to make more T3.  When the body is getting enough thyroid, TSH generally stays low.  So if your thyroid hormone levels go down while your TSH also stays in the low to normal ranges, it’s probably not because your thyroid is sick, any more than your pancreas is sick when your insulin level goes down on a very low-carbohydrate diet, and your blood sugars stay low as well.   When insulin levels go down and blood sugar becomes more normal as well, it’s a clue that your cells are finally becoming less insulin resistant and are getting sensitive to a healthy, low level signal of insulin.  In a similar way, a low TSH, coupled with a lower T3 level, is indicative, not of a sick thyroid, but more of proper signaling.  You might say it indicates that your cellular resistance to the signals of thyroid is letting up.  Your cells are getting more sensitive to thyroid signals, and your T3 level is going down precisely because cells can finally hear the signal properly.  So a lower thyroid level, with low- to normal TSH, can indicate that your metabolism is now functioning at a higher-quality level. In other words, you’re getting more bang for each energy buck.

More bang for the buck is also happening, for instance, in calorie-restricted animals who live longer than animals fed a regular amount of calories.  In calorie-restricted animals, researchers generally see a lower free T3.  They also see lower T3 in centenarians, people who live past 100. When you see a lower free T3, it’s really indicative of kind of a longevity phenotype. It’s indicative of what you might even call, non-hibernating hibernation. And one clue that this lower T3 is healthy is that people who have it generally report that they function better.  If it happens to you, on a low-carb diet that you’ve become adapted to over time, you’re not weak. You generally have more energy.

Having your T3 level go lower, in a healthy way, is like being able to turn down the idle of a car when it’s tuned properly, so that at rest it doesn’t have to waste as much energy.  In an efficiently running car, the resting “metabolism” of the car is lower.  And if you want to get power from that car, if you want to accelerate, that’s better too.  When a car is well tuned, it allows for a lower idle speed, and it will actually accelerate faster, and the engine itself certainly will have a much longer lifespan. It’s functioning better.

Well, I suppose that metabolism can go TOO low.  For instance, if we wanted our cars to have as low a metabolism as possible, we should keep them in the garage all the time and never drive them.

Zero Thermogenic Car

 RON ROSEDALE

That’s true. Certainly one would have to then get into the depths of a discussion on what is life, and is the car really being a car if it’s really not doing anything? Is it being any more than a rock? It’s not functioning at all. That gets into more of a philosophical argument, and actually a scientific argument, but that’s probably a story for another day.

That’s a story for another day, but this issue regarding, how do we tell if our metabolism is at the right “idle speed”, it isn’t a question that most people ask. And it’s a concept that’s often missing in debates among experts about what kind of diet is the healthiest.  For instance, in the Harvard study, their “low-carb/high fat diet” was actually a rather high protein diet.  For years, high-protein advocates said that eating a high level of protein is wonderful, because when you eat a lot of protein, it burns with more heat, and since it burns with more heat, you can eat more of it and not gain as much weight. Does that make sense to you?

RON ROSEDALE

It makes sense, but again, it’s the wrong question.  Improving health is not whether we gain or lose weight, it’s the kind of weight, number one.  For instance, I don’t think anybody really wants to lose just any kind of weight.  They don’t want to lose their muscle or their brain or their bones.  They want extraneous adipose belly fat to be lost, typically.  And if you’re seeking health, it’s not a matter of whether heat is produced, but really where that heat is going.  If your body makes extra heat, you want to get rid of heat, number one.  You have to get rid of it quickly.  Inside the body, excess heat destroys.  How about a fever?

High Thermogenic Human

 A normal body temperature is less damaging for the body than the higher temperature of a fever.  However, our body can handle a fever better than many invading organisms do, because a multicellular creature, such as a human, has more ways to protect against excess heat such as having heat shock proteins than, for instance, a virus does.  Furthermore, the temporary higher temperature increases the activity of our immune system, and helps a body produce white blood cells faster.  For all these reasons, occasionally, the body will produce a fever in order to kill an invader.  If the fever goes too high, it kills too much of us as well.  But if it stays at a level the body can handle, it kills off the invader faster.  So short-term bursts of high fever, for our bodies, can be a valuable tool.  But bodies don’t maintain a fever as a regular thing.  Heat is a double-edged sword. It’s part and parcel of any type of energy exchange, and in some cases, we can use heat as a weapon for our body defense, but certainly excess heat destroys. That’s because our bodies, including each and every cell, need to work in a healthy, coordinated way.  In contrast, heat is totally random, nonsensical motion that promotes incoordination.

Now, if heat-generation such as a fever, is only good for a short-term battle, it surprises me that some very well-respected scientists will say that it’s good news that eating protein causes thermogenesis, meaning it increases heat.  The most common reason that many health experts praise thermogenesis is that, they say it means you can eat more food without gaining weight.  Those same experts tend to say that the plague of modern society is that people get too fat when they eat as much as they want and so, the question to answer is, “How can people continue to eat as much as they want, and still keep their weight down?”  And for them, the answer is, “Eat foods that take more energy to metabolize, because they make heat in the body and then the body supposedly stores less of the fuel as energy–that is, as fat.”  Do you think it’s time for people to stop saying that this approach is healthy?

RON ROSEDALE

Yeah, it is.

So, whether it’s a car or a person, simply “fueling up” on something to increase the heat isn’t improving metabolic quality.

RON ROSEDALE

It isn’t a good thing.  Producing excess heat can contribute to a whole lot of damage.

High Thermogenic Human – from revolutionpersonaltraining.com

On the other hand, is it always bad to produce extra heat?  As an example, an athlete who’s exercising is making heat. Is that okay?

RON ROSEDALE

That’s part of their training, to adapt to getting rid of heat fast. In other words, as they adapt to training, they will sweat more than they did when they began training. They’ll have better circulation to get rid of heat. It’s certainly part of the training, part of what will adapt them to being a better athlete, adapting to excreting heat.

And that’s true with ourselves as well, you think?

RON ROSEDALE

That’s true.

Now, some studies indicate that when people exercise more, their resting metabolism actually goes down.  So they’re sort of like that car you described, which can idle at a lower speed, but performs faster and better when it’s time to put the pedal to the metal.  That is, when they exercise, they produce more heat than someone who’s not exercising as hard.  But when they’re resting, they have a lower metabolism.  But is an athlete’s way of generating heat a reason to say that producing heat by eating more protein –ie– eating a more thermogenic diet — is that a good thing?

RON ROSEDALE

No, not at all. Again, it’s not—I think what you’re referring to then is the rate of metabolism. When a person switches to a low-carb diet, their metabolism overall isn’t necessarily increasing. The rate of metabolism might increase somewhat if they feel more energetic and start exercising more, and resting on the sofa less. And they might lose weight not because they’re burning more calories but instead because their hormones are signaling correctly and they’re less hungry.  In other words, what’s happening on a very low-carbohydrate diet is, they’re improving the quality of their metabolism such that they’re able to burn fat properly and more importantly, ultimately enable better leptin and insulin signaling that will more appropriately apportion which fuel to burn when, in other words, when to burn fat and when not to.  Most people are not able to burn fat — certainly not as readily as they need to or would want to. And the reason for that is because of inappropriate—or inaccurate, really—leptin signaling and even insulin signaling, more widely known as leptin and insulin resistance.

If somebody switches to eating fewer carbohydrates and they feel wiped out, do you wonder whether that person has adapted to fat-burning yet?  

RON ROSEDALE

That’s correct. They’re not. For most of the people, and I’ve questioned a number, including many who attended the August, Ancestral Health Symposium at Harvard, most people who mention that they felt poorly when they went on a very low-carbohydrate diet, when you question them in detail, you find they were eating way too much protein–two, three, four times as much protein as I normally recommend. People have within themselves such a fear that fat is a bad thing to eat, unconsciously they avoid it, and the only thing you can eat if you’ve eliminated most carbs and you don’t eat fat, is protein. So when people go on a very low-carbohydrate diet, unless they consciously think about it all the time, they go high-protein, which can make them miserable.

So when people report feeling poorly when they go on a very low-carbohydrate diet—and by the way, most people don’t feel poorly, and many feel much more energetic.  But among those who report they feel bad, it’s usually either that they haven’t given the switch to low carb, high fat eating a long enough time to get through the physiological adaptation this switch requires, or, they never get through that adaptation because they’re eating too much protein, or too much carbohydrate.  Excess of either of these will prevent you from actually getting through that adaptation. For instance, they lower their carbohydrate some but not enough to really start burning fat. It only takes 100 grams of carbohydrate a day to prevent a person from properly going into ketosis, and therefore supplying the necessary “ketone” fuel for many different body functions that can’t simply burn fatty acids, such as the brain.  Or, they eat so much protein, the excess protein raises insulin and also leads the excess protein to be burned or transformed by the body into sugar, and all that keeps them out of ketosis as well.  And if you’re not generating ketones because you’re eating too many carbohydrates, or you’re eating too much protein, then certainly initially you’re going to have a difficult time and you’re not going to feel well.

And I wonder whether some people, for instance, Type 1 diabetics who give themselves shots of insulin and also shots of sugar to balance out the insulin, I wonder if the shots and the sugar mean that they never get to the point where their bodies are resilient about adapting to just burning fat.

RON ROSEDALE

I totally agree. What you really have to do is, you have to maintain low-sugar in your blood long enough to kind of turn down the glucostat.  It’s like a thermostat, only with sugar, with glucose, so that the glucose goes down because you don’t need it so much. You’re training your body so that it’s just keeping a minimal amount of sugar available, and the ability to produce sugar if needed, for anaerobic emergencies, such as running from a tiger.  But you’re not keeping excess sugar stores at the ready, because you have to burn sugar all the time because you’re unable to burn fat.  Unfortunately, the vast majority of people on earth have trouble burning fat, meaning that they have too much sugar in their diets and in their blood, so they crave sugar all the time because they’re unable to properly burn fat, and I think it really is the base cause of the mass amounts of chronic diseases and premature aging that people are experiencing.  These chronic diseases, such as diabetes and heart attacks, wouldn’t be happening if people would eat foods that are very low-sugar-forming carbohydrates, and if they would eat appropriate protein, but not high protein, and then fill in the appetite gaps by eating fat when necessary.

In addition to asking what foods improve hormone signaling, you’re also asking another question.  You’re asking “What foods generate the most metabolic heat, simply to digest them, and what foods generate the least amount of heat?  The answer to that question gives you a good strong predictor of what is going to lead to the least wear and tear on the body.

RON ROSEDALE

It is as simple as that.  I don’t know if you read my last blog post on safe starches, where I posed four questions about “safe starches” and then answered them. Afterwards, some people posting comments about my blog brought forth the correct biochemistry, which is that you get many more ATP molecules from an equivalent gram amount of fat compared to glucose or protein.  This supported my simple premise that fat is by far the most preferable fuel to burn.  Fat producing the least heat and the most usable energy is taken right out of biochemistry textbooks.

High Carb Hummingbird

 Well, even if burning fat is so “useful”, is it healthy for everything?  Could you feed  fat to a hummingbird?

RON ROSEDALE

I think you probably could, actually, and perhaps it would live longer. I wouldn’t say it would live necessarily better–for it might have to give up the life of flitting from one flower to another–and eating fat wouldn’t necessarily be ideal to perpetuate a hummingbird genome – for if you could adapt a hummingbird to live off of fat, and you kept it near a great fat source, that individual hummingbird might live longer.  But if all wild hummingbirds required fat, they would probably starve to death for lack of available food.   They probably wouldn’t have babies.  So Nature has adapted hummingbirds to be sugar eaters.  And that’s the “nature” of Nature.  Nature is not concerning itself totally with longevity. It doesn’t care. It’s concerned about the longevity of the genome, not about the temporary caretakers of that genome, the soma, that is, the cells that keep our body going — in contrast to the cells that are designed to make new babies.  Nature’s only concern with our soma, our body, is to keep it going long enough for us to get to the next generation going and help it stand on its own two feet.

What’s natural, I think, is not necessarily what’s healthiest for one particular hummingbird, or person — after all, most people would consider health as meaning that you, as an individual, lead a long, healthy—including post-reproductive-life health—life. Nature, I don’t think, ever really cares much about post-reproductive health and longevity, other than as it pertains to parenting and perhaps grand parenting so that the baby can grow old enough to essentially fend for itself.   If you ask the question, “How does longer life of the parents affect survival of the next generation?”  then you can answer some puzzles.  For instance, why do humans live much longer than chimpanzees?

We take longer to grow up?

RON ROSEDALE

That’s right.  Human babies are helpless when they’re born, and it takes a long time for them to have a reasonable chance of survival.  Longer than it takes for a chimpanzee baby.  So Nature has endowed human parents and even grandparents with a long enough lifespan to enable to children to grow old enough to take care of themselves.  That’s probably why humans live longer than chimpanzees.   But even among humans, there’s a time when the advantages of living longer don’t clearly add benefit to the lives of our offspring.  So I think that we have to get away from constantly thinking that what’s natural is what’s best for individual health.  So, just looking at the the idea of what’s natural. Just do what’s natural. Eat what’s natural. There’s a big argument about what “natural” actually is.  And simply asking the question, “What has been mankind’s ‘natural’ way to eat?” is not the same as asking, “How can I eat to maintain my health and life as long as possible?”  But that question of individual longevity is a question we can strive to answer.  We can work to use the best science that tells you how nature allowed a human, or perhaps any life, to live a long and healthy lifespan, especially during the time period before reproduction begins, when the needs are highest to preserve vitality.  As we find out more about what those secrets are to living a healthy life before the time comes to produce offspring, then we can apply those secrets to both the reproductive and the post-reproductive years. You can apply them at any time of life. For instance, what we’re seeing is that nature has endowed virtually all animal life with a means of outliving a famine so that it could then reproduce at a future, more opportune time.  As part of this, all life maintains chemical sensors, hormonal pathways that tell the genes and the genome, and every cell, what the nutrient availability is. And when a body senses food is low, it up-regulates instructions to virtually every cell, making maintenance and repair of that cell a greater priority.  It increases each cell’s DNA repair and intracellular antioxidant systems and heat shock proteins and what’s called autophagy, which kind of cleans up the garbage inside the cell faster and better.

One can take what you just said about gearing up to survive a famine to assume that humans are doomed to have to eat and eat and eat because we’re programmed to deal with famines. Is that what you’re saying?

RON ROSEDALE

Not really.  In fact, eating low-carb/high fat tends to keep appetite very low.  When it comes to health, and longevity, and maintaining an ideal body weight, the major secret to this way of eating, is that the “famine signal” that leads to hunger and all the rest is extremely ancient. It must have arisen shortly after life began itself, even with single-cell organisms in the ocean, which means it occurred before there was oxygen in the atmosphere. And life was flourishing for millions, even billions of years, before there was enough oxygen in the atmosphere that “life” was allowed to even use fat as fuel. You have to have oxygen to be able to burn fat. You don’t need oxygen to burn glucose. And therefore these famine signals are dependent on two major nutrients, glucose and protein, certain amino acids, but not fat. And that’s a real key. In other words, if you keep your glucose intake low, such that insulin signaling and leptin signaling stay down, and yes, by the way — the secretion of leptin is largely dependent on how much glucose a person ate.  Leptin signaling is influenced by sugar more than fat, even, and that’s something that everybody just argues about, but it’s very, very clear in the literature.  But in any event, if you keep your sugar levels low, and also if you don’t eat excess protein, such that you don’t raise a pathway known as mTOR, which senses amino acid and protein availability, you keep those low, it then mimics calorie restriction.  Caloric restriction increases longevity in all kinds of animals.  But you don’t have to be calorie restricted to gain those benefits, because you can eat fat. It’s kind of a free ride. It doesn’t get the body into believing that you’ve got nutrient excess that needs to be stored away in order to survive a famine, or used to produce a new generation of cells or offspring.  It allows the body to stay in the mode of maintenance and repair.

You’re talking about the evolution of our signaling pathways, and how fat helps them stay settled down and promotes more health in us.  But could it also be that eating and storing fat is also doing something even more basic?  Could it be causing less heat damage in terms of how it’s stored and how it’s metabolized?  

RON ROSEDALE

That’s exactly true. So one can look at fat as being a much cleaner-burning fuel than sugar, which it is. It does cause less damage than if you were to burn sugar as your everyday fuel. But people around the world are being forced to burn sugar all the time because they can’t burn fat properly, and the reason for that is because the signals that tell you whether to burn fat or glucose, namely leptin and insulin, have been so corrupted over time because of our modern, high-carb diets, in particular, that their bodies can’t properly so-call “fuel partition.” They can’t switch over between fat and sugar properly.

Many animals DO have the ability to switch between fat and sugar fuels very quickly.  For instance, a hummingbird drinks basically soda water, and during the day, its blood sugars are sky-high.  Over 600-a blood sugar that could kill a human.  But a hummingbird burns the sugar fast, and any excess goes into its liver.  The liver gets incredibly fatty, but then at night, the hummingbird burns most of that fat away.  So it’s got an incredibly balanced system for switching from sugar burning to fat burning.

RON ROSEDALE

So when you look at a lot of the animal examples, number one, the key is that nature isn’t really caring if they live a long life. Nature is just trying to get them to live long enough to be able to reproduce. But two, they continue to have proper fuel partitioning, like you mentioned. They can burn fat where and when appropriate. So even though they might store fat in their livers, they can then get it out of their livers very easily and readily. In modern people, the problem with leptin resistance,, is that they can’t easily switch from burning sugar to burning fat. And then they store a lot of abdominal fat that they’re not able to access properly. So it continues to build and then infringe on the vital organ system, such as liver function and heart function, etc. So that is the main problem, and that might take a long time to develop, but once it’s there, it’s a problem.  And humans face another challenge that many animals don’t, simply because most animals don’t live long enough to get stuck with this long-term problem.  For instance, in humans and in hummingbirds, certain molecular processes, like, advanced glycated end products, take a while to accumulate, and it could be that some of these animals that survive on high-carb fuels just don’t live long enough to be able to accumulate glycation to any great degree that would impair their insulin and leptin signaling.

We know, for instance, that humans live a fairly healthy life through childhood, although now we’re starting to get even so-called adult-onset diabetes in the young. But for the most part, children are much healthier than adults. They can eat, and they do eat lots of junk food, but they don’t suffer from diabetes and obesity and heart disease generally until later in life. And the reason for that is because a young body can make proper compensations for eating poorly. It can burn the excess off faster. Their bodies can increase thermogenesis, so to speak. That extra burning off of energy is not necessarily healthy, but the kids don’t notice it at the moment. But what it does is, it starts the leptin and insulin signaling going wrong at an early stage, which increases the chance that later in life, their bodies can no longer make the appropriate compensations for eating poorly. And then they get problems that we currently call diseases. Their blood sugars go up, and we call it diabetes. They become obese.  If we started measuring insulin and leptin resistance or sensitivity early in life, you’d find that there was a progression almost from a moment they were born, in fact even before they were born, depending on what their mothers ate.  If a mom is eating a high carb diet, her child can be born already insulin and leptin resistant.

Are some people more fortunate, and their bodies are more resilient at dealing with the hit of transitioning back and forth between fat burning and sugar burning?  After all, some athletes say that all their exercise keeps their bodies strong and more resilient at dealing with different foods and also dealing with the generation of heat.

RON ROSEDALE

That’s exactly true.  The statement that I made decades ago now I think still holds true.  The more fat you burn, the healthier you’ll be, and the more sugar you burn, the less healthy you’ll be. Provided you don’t get hit by a Mack truck.

Thank you Shelley for the article, graphics and the interview above.  You can learn more about Shelley and her passion for exposing the truth of health at her website, www.meandmydiabetes.com

The post Thermogenesis – Not So Good For Health – Ron Rosedale appeared first on Ron Rosedale, M.D..

I heard once again during the Ancestral Health Symposium conference at Harvard that it is important to recognize ones differences.  Actually, what is most important to life, health and disease are not the differences but the similarities.  It brought to mind an essay that I wrote many years ago.

The Transcendence of Commonality amongst Individuality

Essay by Ron Rosedale M.D. November 21, 2005

Throughout the course of human history, biologic individuality has been emphasized. Many times this has been used for one’s own gain as people would like to think that they are better than the next. Often, this is unfortunate as issues of race are raised. However, this actually speaks more to sameness than differences as the similarities of members of the same race are emphasized when compared to others.

It is especially “politically correct” to speak of biologic individuality when one refers to health and nutrition. How often is it heard, “Everybody is different and therefore each requires their own specific individualized recommendations and treatment”? We hear that “no one diet is good for all since everybody is different”.

However, even though this is spoken, and even emphasized, in practice one pays particular attention to similarities, though not realized. Diseases are sorted into particular categories and treated accordingly. It is determined whether one has diabetes, high blood pressure, or heart disease. In other words, all those “individuals” who have diabetes automatically become similar, and have in common elevated blood sugar, and it is this shared malady of high blood sugar that is treated similarly in all diabetics.

This is very fortunate, for otherwise there would be even more drugs, one or more for every individual on earth. (Conversely, there may be no drugs for it would not be economically feasible to develop them.)

The fact is, people are much more similar than different. Humans share a 98% genomic homology with chimpanzees, and even have at least a 40% homology with worms. Comparing then one human to another, our similarities greatly exceed 99% especially among members of the same sex. The only significant difference lies between the sexes yet even they share much in common. The deeper we look, the more similar we all are.

It is said that everybody has slightly different fingerprints, yet everybody has fingerprints. Everyone has slightly different eye color, yet all intact eyes function similarly and for the same reason in everyone. Though there most certainly are differences, the differences are mostly cosmetic compared to similarities. Humankind’s overwhelming similarities should certainly be kept in mind in the midst of racial turmoil.

It is important, in fact critical to discover commonalities among people with different “diseases”, for this is what may lead to the discovery of the “roots” of disease — the real cause of illness common to all individuals. An example could be given of a simple upper respiratory infection, the common “cold”. This could be manifested by a variety of symptoms, including a stuffy, runny nose, a cough, or perhaps a sinus infection. Though the symptoms may be different, everyone may have taken a breath of the same infected air and received a dose of the same strain of rhinovirus. It is from our individual uniqueness that an underlying common disorder will manifest as different symptoms. Though everyone, with their own physical (and environmental) uniqueness, had the same underlying cause, or “disease” if you will, the manifestations, the symptoms, were different and each patient with their own perceived biologically unique illness, would walk out of a doctor’s office with a different “disease” diagnosis of rhinitis, bronchitis, or sinusitis and therefore each likely received a different treatment. The patient with the runny, stuffy nose likely received a decongestant and perhaps told to take some Tylenol to reduce fever. This treated their “disease” of rhinitis…or did it?

Eons of evolution have taught our mucous membranes to produce more mucus to cleanse itself in case of infection in the hope of washing the offending organisms away. This symptom of a runny nose, called the disease of “rhinitis” by the medical profession, is put there by nature in the hope of combating a more fundamental underlying disease that is in fact made worse by the doctor prescribing a decongestant. Likewise is the treatment for the fever. We get a fever to increase our temperature that increases the rate of the chemistry of our immune system to combat the infection. Taking a medication to reduce our fever most of the time merely reduces our ability to combat the underlying infection. In fact, most of the time treating a symptom rather than the underlying disease undoes what eons of evolution has taught us, and will make the underlying disease worse.

What then is really a disease and what is a symptom? Could it be that other, more serious so-called “diseases” are really symptoms, and could it be that they have more fundamental underlying roots? Could it be that the major “diseases” of mankind such as diabetes, heart disease, obesity, cancer, osteoporosis, and even Alzheimer’s are really not diseases, and in actuality could they be instead symptoms of a more fundamental underlying root disorder common to all? Could medical “science” be nearly always treating symptoms?

Let’s go back to our example of an upper respiratory infection, but this time let the patient be an inquisitive boy named Brandon who keeps asking the question “why”. The doctor tells Brandon that he “caught a cold”. Brandon states that he was a good boy and wasn’t trying to catch anything. The doctor says that he, Brandon, unknowingly breathed in a cold virus. Brandon asks, “Doesn’t everybody breathe these in?” The doctor thinks and says yes. Then Brandon asks, “Why did I catch the cold, and not someone else?” The doctor states, “Because you aren’t like the others; you are biologically unique.” So Brandon asks, “What was different about me that I would catch the cold and not others around me?” The doctor is not sure, and states that he’s too busy now to answer. But Brandon wants to know, so he sees another doctor and asks “Why did I catch a cold, and not someone else?” This doctor is a bit more informed, or perhaps has more time and answers, “Perhaps your immune system was weakened.” Brandon asks why. The doctor cannot be sure but answers, “Perhaps you are deficient in vitamin C”. He tells Brandon that he needs to take vitamin C supplements. But Brandon asks, “Why me? I eat healthier than most of my friends.” The doctor does not know, and so he refers Brandon to an immune specialist. Brandon asks the specialist, “Why do I need to take extra vitamin C?” Brandon is told that white blood cells, a major part of the immune system, require lots of vitamin C to be able to engulf, to eat, viruses and bacteria, to protect him from infection. Linus Pauling, a Nobel laureate, discovered this. Brandon thinks a little bit, and states, “But I drink two glasses of orange juice daily, and my dad doesn’t drink any, and he didn’t catch this cold. Why?” The doctor answers, “Because you’re different than your dad”. “What’s different that caused me to catch this cold?” Brandon asks. The doctor does not know, so he refers Brandon to a metabolic specialist–me.

Brandon, my son, asks me why he caught this cold. “Brandon”, I say to my son, “you caught this cold because fundamentally your body works like everyone else’s. As you were told by the immunologist, your white blood cells, like everyone else’s, requires vitamin C to be able to function properly and be able to engulf viruses, bacteria, and even cancer cells. Like everyone, it is not how much vitamin C you have, but how the vitamin C is being utilized. Like everybody, the vitamin C must get into the white blood cells to be able to be utilized. Vitamin C is derived from glucose and, in everybody, competes with glucose for entry into the white blood cells. Your cells, being like everybody’s, must listen to insulin to let glucose or vitamin C in (with few exceptions such as nerve cells). If there’s too much glucose around, or if cells cannot “hear” insulin properly, the vitamin C cannot get into the white blood cells sufficiently for them to function properly, and your immune system will be depressed as would anybody else’s. You, as all people, will not need to take as much vitamin C if you eat food that will not raise your blood sugar as much. Your drinking lots of sugary orange juice will both raise your blood sugar and reduce your cell’s ability to listen to insulin, as would happen to anyone who drinks a lot of orange juice, though in some more than others. Though there may be differences in the magnitude of harm that sugar will inflict, be sure that some harm nevertheless will result, and that everybody’s immune system will be depressed when their blood sugar becomes elevated, accelerating infection and also diabetes, obesity, heart disease, osteoporosis, cancer, and all of the diseases of aging, and even aging itself. Drink water, or herbal tea rather than lots of orange juice and reduce other sugary foods and you will, as would anyone, get healthier”.

All people, in fact all life shares the most important similarity of all — life itself. Certainly, one of my endeavors is to endow each and every one of you with a life that is long and healthy, and therefore more apt to be happy. You must, as a foundation of health, each persist in having the common endowment of life. The fundamental cause of death is a lack of life. One of my life’s goals is to determine life’s commonalities rather than its differences.

Everyone suffers from the same basic root of all chronic degenerative diseases of aging… aging itself. It is the common cause, the common root of aging that must be treated in anyone wishing to become healthier. (Here, and elsewhere, what we are really referring to as aging is the damage associated with aging, called senescence. I cannot, nor can anyone, prevent you from becoming a day older tomorrow. What I wish to do is reduce the damage associated with that day.) The science of the biology of aging is revealing, amazingly enough, that aging has common biological roots that appears to pervade nearly all life. It is these virtually identical causes of aging that afflict everybody, that must be treated, and these “root” treatments would be of fundamental importance in allowing anyone, everyone to walk the path of greater health and longevity.

It appears that an individual life may persist as long as it serves nature’s purpose. Nature’s purpose is simple; it wants Life, all life as a whole, to persist. Individual components of Life are less important. For instance, you are a collective of individual lives called cells — a community or republic of cells. If one of your skin cells happens to die, as happens continually, you care not; not as long as the cells can replace themselves enough for the republic to remain “alive” and “healthy”. Our cells are constantly making a decision of whether to maintain themselves, or replace themselves with new, less damaged cells. It is the same decision that we make about whether it is more economically feasible to fix the car, or to ultimately buy a new one. It takes considerable funds, or energy, to do either, and energy must be allocated towards one or the others. That energy allocation, towards reproduction or maintenance and repair, is dictated by the amount and quality of available energy itself, and the amount and kind of energy that is available is signaled by hormones. Hormones are how cells speak to each other to tell them what to do and how to behave for the betterment of the collective whole, the republic of cells — you.

The most important hormones regulate energy, reproduction, and the rate that cells maintain themselves. They do this for you, for everyone, and for all life. In humans, and indeed in all other mammals and most animals, these fundamentally important hormones are insulin and leptin. It is their ability to get their message across to all the cells of the republic that is of fundamental importance in health, disease, aging and death.

The same hormones regulate reproduction, maintenance and repair, health, longevity, and death. This is not a coincidence. It takes lots of energy to make babies. If there is insufficient energy available, reproduction is delayed and energy is allocated towards maintenance and repair, towards preservation so as to be able to reproduce at a future, more opportune time. The major hormones that signal energy availability, the amount of sugar and fat, are insulin and leptin. They turn on or off the genes that signal whether individual cells (insulin) or the republic of cells (leptin) should reproduce or preserve themselves. It should be noted that unrelenting cellular reproduction as signaled for by elevated insulin [or a newer metabolic pathway called mTOR that signals protein availability] may result in what we call cancer. These hormones regulate health, aging, disease and death. This is not just true for Bill. It is true for Sally, for Michael, for Tiffany, for Maia, for Ron, for monkeys, mice, grasshoppers, worms, flies, and even single cell yeast. Hormones that regulate energy are a common denominator for life. We must pay attention to them if we wish to preserve life, and health.

Life lies in the communication of our cells. The parts are less important. Were I to die, the parts would still remain. There would be essentially the same amount of carbon, hydrogen, oxygen calcium, sulfur and phosphorus. Even the vast majority of my individual cells could be kept alive in petri dishes almost indefinitely long after my demise. My life lies not in its parts, but in the ability of those parts to communicate. It is the ability to communicate, that cannot be put into a bottle, that one might call the “life force”. All disease originates from faulty or mis-communication. When one talks about disease, we can paraphrase the famous quote from the movie “Cool Hand Luke” when the warden speaks of the recalcitrant inmate played by Paul Newman when he shoots him, depriving him of life, “What we have here is a failure to communicate”.

Life’s most important messages tell us what to do with energy. They tell us how much sugar or fat is readily available, which to burn, and whether our cells should reproduce or preserve themselves. Just as we lose our hearing from repeated loud noises, so to do cells lose the ability to “hear” hormones if overexposed. The exposure to these vital hormones is determined by our diet and emotions. It is repeated elevations in blood sugar levels with concomitant spikes in insulin and leptin that cause cells to become “deaf” to the critical signals from these hormones. The messages about how to use energy to stay alive become filled with static. How much static might be determined by individual differences, but static to all nevertheless. Burning fat will produce less static. Therefore, a truth for everybody is that health, disease, and longevity will largely be determined by the proportion of fat versus sugar that is burned over a lifetime. That proportion might be determined by individual differences in both genetics and diet, but nevertheless, the more fat that one burns as opposed to sugar, the healthier that individual will become.

(The most critical supplements, therefore, are those that will help burn fat, and otherwise augment insulin and leptin signaling. Individualized supplementation might be necessary to get to that point. For instance, if one has joint pain/arthritis, fear, or mental stress, this raises cortisol and therefore sugar, diminishing one’s ability to burn fat. Giving an individual a supplement to repair cartilage and reduce pain would aid in reducing sugar and increase fat burning that is beneficial to all.)

The republic of cells, you, makes the same decision as your individual cells, whether you realize it or not, of whether to maintain yourself or reproduce. We are certainly familiar with hunger and the drive for sex. Without going into great detail, it is sex that allows for death. It is sex that allows all humans to be different (by mixing up the genetic pool), and also allows for the sameness of fundamental knowledge, the sameness of instructions on how to make life, maintain, and then transmit life through the generations. The individual, temporary carriers of those instructions, you and I, like runners in a relay race handing off the baton, are then allowed the luxury of being able to stop running… to die.

We cannot stop this, however we can delay it. The more we dig deeper, the more we get to the roots of disease, the more we see that our so-called unique biological individuality does not extend to the roots of disease. Here we see that the sameness of life — and death — transcends individuality. The roots of disease are common to us all. Here indeed, what’s good for one is good for all. Cheers… to Life.

© Copyright 2005 – 2012

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We have received a lot of questions regarding this study pertaining to calorie restriction in rhesus monkeys.   Here are a few quick, off-the-cuff thoughts that I will expand on at a later date.

It should be noted that there was a small reduction in mortality (24% in the control group versus 20% in the CR group in young onset CR initiation). Their results contrasted sharply with life prolonging affects seen in rhesus monkeys at the Wisconsin National Primate Research Center trial, where 37% of monkeys in the control group died compared to 13% in the CR (caloric restriction) group at the time of publication a few years ago..

Click on the link below to see the study.

Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study

One factor that is mentioned in this NIA study to try to explain why their results contrasted quite significantly from the primate study done at the Wisconsin Primate Research Center is that “diet composition may strongly affect the life prolonging effect of calorie restriction in a long-lived nonhuman primate”. I would have to see exactly what they were feeding the monkeys at each of the centers to ascertain a difference, however, I do know that they were feeding the monkeys approximately a 60% carbohydrate diet at NIA. That may be way too much to ascertain a clear benefit of CR (caloric restriction) to life extension. Additionally, triglycerides increased throughout life in both the control and calorie restricted groups. This indicates that burning energy from fat was quite limited in both groups.  I believe that what I have said for two decades is very true; that health and longevity will be determined by the proportion of fat verses sugar one burns over a life time.  The monkeys in this study were likely still being forced to burn sugar and minimal fat as their primary fuel, secondary to the high carbohydrate diet they were still being fed.

I have long maintained that it is not calorie restriction but carbohydrate and protein restriction that mediates effects of longevity, and that typical calorie restriction reduces calories from both proteins and carbohydrates to a very limited extent. I feel one can go much further in showing benefits of CR (caloric restriction) with a very low carbohydrate, high-fat, and low to moderate protein diet.

It is now becoming known that the health and life prolonging effects of calorie restriction are not due primarily to calorie restriction per se but are mediated through lowering of metabolic pathway signaling, namely insulin, mTOR, and likely leptin in “higher” animals that use fat as a primary fuel. Therefore the macronutrient content of the diet is extremely important, however this was not well known to the experimenters when these rhesus monkey experiments were initiated over two decades ago.

Check out my comments on the new Harvard Study published late in June, 2012, where the Journal of the American Medical Association raised a challenge by publishing a Harvard study involving three different diets, and how each diet affects the likelihood of gaining weight.

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“All truth passes through three stages: First, it is ridiculed; Second, it is violently opposed; and Third, it is accepted as self-evident.” 
— Arthur Schopenhauer

A shorter summary is first, followed by a more complete version with additional comments about Kitavans, thyroid, nature, and more…

Short Summary…

Even in a state of starvation blood glucose is maintained right up until death. What this really shows is that even if you are starving, and eating no carbohydrates, or fat, or protein, there is no such thing as “glucose deficiency”.  The body can easily make what it needs.

Question #1;

Is it better to eat the requisite glucose, or let the body make it?

The ‘safe starch’ debate boils down to whether it is better to eat the requisite glucose, or let the body make it when necessary.  I believe strongly in the latter.  We can never know exactly how much and when we will need extra glucose depending on environmental circumstances.

When you eat the glucose, there are different effects than if your liver makes it, namely it circulates for hours and leads to a spike in insulin and leptin, that circulates for hours, that over time will contribute to insulin and leptin resistance…that ultimately contributes to metabolic chaos resulting in chronic diseases of aging including obesity, diabetes, cardiovascular disease, osteoporosis, autoimmune disease, cancer, and others.

I have long summarized health by the ability to burn fat… or not.

Eating glucose i.e. “safe starches” will spike insulin and will, at least temporarily, prevent one from burning fat… in anyone… a worm, a mouse or any human.  It will raise leptin that will prevent one from changing to the healthy calorie restriction phenotype (see below).

Glucose, like all parts, must be orchestrated; where, when, how it is used is what will determine health and life.  When we talk about significance of starches, safe or otherwise, the most important factor is their effect on hormones and other biochemical pathways that affect the harmony of 15 trillion cells needing to act as one for life and health.  And all starches raise insulin and leptin levels… a lot… having a long term adverse effect of insulin and leptin resistance; cells not being able to properly hear their life-giving messages.

Paul Jaminet and all the other safe starch advocates concentrate on blood glucose… and though it is unwise, to say the least, to eat glucose when one is trying to keep blood glucose down, diabetes is not a disease of blood glucose, but of insulin, and more importantly, leptin resistance.  It is the effect of eating “safe starches” on insulin and leptin resistance that must be acknowledged and stressed.

Disease is not as much from the parts but much more from the misinformation given them.

It is not an excess of cholesterol that causes heart disease.

It is not a lack of calcium that causes osteoporosis.

Disease is not due to glucose, excess or deficiency, but the communication that tells it what to do…and sugars, more than most anything, by non-enzymatic glycation and insulin and leptin resistance, messes up that communication.

Question #2;

If the body can make all the glucose it needs from other biochemicals, called gluconeogenesis, are there potential adverse effects from this?

Any potential adverse effect of gluconeogenesis would be determined from the initial substrate; whether one is using amino acids to manufacture glucose or other precursors that are extremely benign such as from ketones, the glycerol backbone of fats, or from lactate and pyruvate recycling. Those latter sources of glucose substrates separate from amino acids, under adapted carbohydrate and protein restricted conditions, can virtually make up the entirety of precursors for whatever glucose might be necessary.

Most people on my diet actually gain lean mass without increasing exercise, via protein sparing and increased sensitivity to insulin. Therefore, one can’t be burning much of their lean mass/protein, if any.  They are deriving their fuel from ketones, glycerol, recycled lactate and pyruvate.  This is perfectly healthy, more so than burning glucose.

Fat is a great fuel, the best fuel, furnishing fatty acids, ketones, and glycerol (that can turn into glucose if necessary), to burn.  However, one needs at least two weeks to adapt to properly burning fat, more if older or overtly metabolically challenged.  I will maintain that the symptoms that people are experiencing occasionally and calling glucose deficiency are nothing but inadequate adaptation to properly burning fat by either consuming too much carbohydrate or eating excess protein.

Gluconeogenesis from protein requires deamination, and the nitrogen molecule is then used to manufacture ammonia and urea that are both poisonous. This is why urine is called urine.  Burning protein is not healthy, but if you can’t burn fatty acids or ketones and you are limiting carbohydrates you will have no choice but to make glucose from protein, either from what you eat, or from your muscles, bone, or other protein sources.  The trick then is to not eat more sugar, but adapt to burning ketones and fats…by eating less sugar, not eating too much protein, and eating fat if hungry.  You learn to ski by skiing.  You learn to burn fat by burning fat.

Question #3;

Is it that important to eat less than 100 gm starch?

Answer; Yes; that is where the deeper benefits lie. That is when one gets into ketone burning and when one can get into the calorie restriction, longevity phenotype.

The worst diet to be on is high fat along with moderate and sometimes even “low” (as opposed to very low) carb.  If you are going to eat fat, you have to be able to burn it, and as little as 100 gm non-fiber carb/day can prevent one from adequately burning fat.

According to George Cahill, perhaps the world’s foremost expert on the metabolism of ketones and starvation, 100 gms/day of sugar forming carbohydrates i.e. starches, is all it takes to prevent one from burning and therefore adapting to burning, ketones.

As one follows my diet more closely, meaning as little non fiber carbs as possible and avoiding excess protein (above 1 gm/day/kg lean mass for most), the beneficial returns not only increase, but accelerate.

Question #4;

Is the VLC diet only better for “sick” people?

What I said 20 years ago is just as true today; Carbohydrates should be defined as fiber or not fiber. Any carb that is not a fiber will turn to sugar and will cause harm…for any and everyone, males, females, monkeys and worms. The only difference among the sugars and non-fiber carbs is how fast and how much harm will be caused.  ‘Safe starches’ is an oxymoron.

One should not discuss effects of starch only on blood glucose. What about intracellular glucose?  If you eat that sugar and it’s not in the circulation, where is it?  Much gets pushed inside cells causing intracellular glycation and cellular harm.  Lots will turn into liver fat. It has to go somewhere, and wherever it goes it will do damage.

EVERYONE who eats starch will raise their glucose and/or insulin.  Keeping glucose down by raising insulin is doing one no favors; just trading one evil, elevated glucose, by an even worse evil, high insulin.  (See “Insulin and its Metabolic Effects“).  This was shown clearly by the ACCORD study.

If diabetes were properly diagnosed as improper metabolic signals, especially from insulin and perhaps even more importantly from leptin, then we all have diabetes to one degree or another..

Life’s commonalities are much more critical to life than the differences, since life can’t live without them.  (See my next blog, an essay I had written a few years back called “The Transcendence of Commonality Amongst Individuality”)

The basics of metabolism are true for all people, in fact virtually all life.  This is why worm studies are important to us.  Human insulin and glucose will work in a worm just as it does in a human, causing damage and shortening lifespan when elevated.

The major benefit of a very low carbohydrate, moderate protein, high-fat diet, and what will get you to the next level of health, is the adaptation to constantly burning fat and ketones and thus requiring less glucose. By forcing the intake of 100 gm or more/day of glucose into the body you would prevent that adaptation.

The lowering of free T3 is a sign of that adaptation, and, according to Paul Jaminet, when you follow his diet you prevent the lowering of free T3.  That is powerful indication that following a “safe starch” diet is preventing one from changing into a calorie restriction phenotype and preventing the genetic expression and adaptation to deeper maintenance and repair that equates to health and longevity that a very low carbohydrate, high-fat diet would otherwise allow the opportunity for.

 A Conclusion to the ‘Safe Starch’ Debate

Ron Rosedale M.D.

A more complete version with additional comments about Kitavans, thyroid, nature, and more…

I understand where Paul Jaminet, Chris Kresser and other ‘safe starch’ advocates are coming from, sort of; that if we have to maintain a certain level of blood glucose anyway, then why not eat it?  I don’t need to hear more arguments that say that glucose is necessary for mucus; glucose is necessary for protein, etc.  I could even add that glucose is needed much more importantly for self-recognition to help prevent autoimmunity (and I believe non-enzymatic glycation can mess that self recognition up), and many other purposes.  I agree.  I repeat; I agree that glucose is a necessary component of life.  Few, I believe, deny that.  However, this does not imply that glucose is an essential dietary nutrient or that we must, or even should, eat it.  Being a necessary component of life and being a dietary necessity are far from the same.  Cortisol is necessary for human life yet you don’t need to eat it, and rarely should.  As with so many biomolecules, it’s far preferable to let the body adjust the levels depending on needs.

Paul Jaminet correctly states, as an example of glucose’s importance, that even in a state of starvation blood glucose is maintained right up until death.  However, what this really shows is that even if you are starving, and eating no carbohydrates, or fat, or protein, there is no such thing as “glucose deficiency” (unless insulin toxic or relatively rare conditions where glucose cannot be made sufficiently, such as cortisol deficiency, but the ‘safe starch’ advocates are not referring to this).  The body can easily make what it needs.

When you eat starch it is digested into glucose and before it goes anywhere it first enters the bloodstream.  All you will accomplish then by eating starch is to raise the blood glucose further. Therefore, one cannot correctly talk about a glucose deficiency from not eating enough.

One needs to rephrase the question from, “Are ‘safe starches’ necessary to eat or even beneficial?” to…

Question #1;

Is it better to eat the requisite glucose, or let the body make it?

The ‘safe starch’ debate boils down to whether it is better to eat the requisite glucose, or let the body make it when necessary.  I believe strongly in the latter.  We can never know exactly how much and when we will need extra glucose depending on environmental circumstances.  

Furthermore, when you eat the glucose, there are different effects than if your liver made it, namely it circulates for hours and leads to a spike in insulin and leptin, that circulates for hours, that over time will contribute to insulin and leptin resistance…that ultimately contributes to metabolic chaos and resulting chronic diseases of aging including obesity, diabetes, cardiovascular disease, osteoporosis, autoimmune disease, cancer, and others.

I have long summarized health by the ability to burn fat… or not. 

Eating glucose i.e. “safe starches” will spike insulin and will, at least temporarily, prevent one from burning fat…anyone.. a worm, a mouse or any human. It will raise leptin and will remove one from the healthy calorie restriction phenotype (see below).

Glucose, like all parts, must be orchestrated; where, when, how it is used is what will determine health and life.  The use of glucose, just like cholesterol and all biochemicals in our body, must be orchestrated.  Let’s not mess that orchestration up by forcing that glucose on us at a time, place, or purpose that is likely not in tune with what the body, or brain, wants or needs.  Let’s not mess with the orchestra unless we are absolutely sure that we totally know the score.

When we talk about significance of starches, safe or otherwise, the most important factor is their effect on hormones and other biochemical pathways that affect the harmony of 15 trillion cells needing to act as one for life and health.  And all starches raise insulin and leptin levels…a lot…having a long term adverse effect of insulin and leptin resistance; cells not being able to properly hear their life-giving messages.

Paul Jaminet and all the other safe starch advocates concentrate on blood sugar…and though it is unwise, to say the least, to eat glucose when one is trying to keep blood glucose down, diabetes is not a disease of BS, but of insulin, and more importantly, leptin resistance.  It is the effect of eating “safe starches” on insulin and leptin resistance that must be acknowledged and stressed.

Disease is not as much from the parts but much more from the misinformation given them.

Life is in the instructions, not the parts. It is not a lack of substrates, parts, that is generally the problem, but the instructions of what to do with the part; the effect on hormones that tell the part what it needs to be doing to maintain the health of the republic of parts and cells..

It is not an excess of cholesterol that causes heart disease.

It is not a lack of calcium that causes osteoporosis.

Disease is not due to glucose, excess or deficiency, but the communication that tells it what to do…and sugars, more than most anything, by non-enzymatic glycation and insulin and leptin resistance, messes up that communication.

Question #2;

If the body can make all the glucose it needs from other biochemicals, called gluconeogenesis, are there potential adverse effects from this?

This is a whole different story than talking about glucose deficiency. Furthermore, any potential adverse effect of gluconeogenesis would be determined from the initial precursor; whether one is using amino acids to manufacture glucose or other substrates that are extremely benign such as from ketones, the glycerol backbone of fats, or from lactate recycling. Those latter sources of glucose substrates separate from amino acids, under adapted carbohydrate and protein restricted conditions, can virtually make up the entirety of precursors for whatever glucose might be necessary.

Most people on my diet actually gain lean mass without increasing exercise, via protein sparing and increased sensitivity to insulin. Therefore, one can’t be burning much of their lean mass/protein, if any.  They are deriving their fuel from ketones, glycerol, recycled lactate and pyruvate.  This is perfectly healthy, more so than burning glucose.

Fat is a great fuel, the best fuel, furnishing fatty acids, ketones, and glycerol (that can turn into glucose if necessary), to burn.  I encourage you to see the fine summary of the great advantages of burning ketones at AHS 2012 by Nora Gedgaudas.  However, one needs at least two weeks to adapt to properly burning fat, more if older or overtly metabolically challenged.  I maintain that the symptoms that people are experiencing occasionally and calling glucose deficiency are nothing but inadequate adaptation to properly burn fat by either consuming too much carbohydrate or eating excess protein. 

Gluconeogenesis from protein requires deamination (cutting off the nitrogen), and the nitrogen molecule is then used to manufacture ammonia and urea that are both poisonous. This is why urine is called urine.  Burning protein is not healthy, but if you can’t burn fatty acids or ketones and you are limiting carbohydrates you will have no choice but to make glucose from protein, either from what you eat, or from your muscles, bone, or other protein sources.  You will not be too happy.  The trick then is to not eat more sugar/starch, but to adapt to burning ketones and fats…by eating less sugar, not eating too much protein, and eating fat if hungry.  You learn to ski by skiing.  You learn to burn fat by burning fat.

Question #3;

Is it that important to eat less than 100 gm starch?

Answer; Yes; that is where the deeper benefits lie. That is when one gets into ketone burning and when one can get into the calorie restriction, longevity phenotype. 

The worst diet to be on is high fat along with moderate and sometimes even low (as opposed to very low) carb.  If you are going to eat fat, you have to be able to burn it, and as little as 100 gm non-fiber carb/day can prevent one from adequately burning fat and ketones.  If one is going to properly follow my high fat diet, one must go all the way; very low sugar forming carbohydrates, and no more than adequate protein.

According to George Cahill, perhaps the world’s foremost expert on the metabolism of ketones and starvation, 100 gms/day of sugar forming carbohydrates i.e. starches is all it takes to prevent one from burning and therefore adapting to burning, ketones.

The best diet allows for maximal burning of fat and ketones.  This is also a high fat diet, but where non-fiber carbs are kept very low and protein is not consumed in excess.  (For most, this is between 50-70 gm protein/day depending on lean mass, exercise, growth and pregnancy.) There is a tipping point where a high fat diet goes from not so good to great as non-fiber carbs and protein are further lowered.

As one follows my diet more closely, meaning as little non fiber carbs as possible and avoiding excess protein (above 1 gm/day/kg lean mass for most), the beneficial returns not only increase, but accelerate.

In a diabetic, as one lowers their sugar intake, one will generally lower their blood glucose, at least to some extent.  But don’t get fooled into believing that the greatest results possible have been obtained.  Do not confuse better with best or even good.  It is easy to do better.  The typical diet is so bad that most any change will lead to improvement.

You won’t see the really deep benefits of actually lowering the “glucostat” and reversing hormone signaling resistance in the hypothalamus and morphing into a longevity phenotype until you get into what the brain and body thinks is not necessarily starvation in general but glucose starvation, whereby genetic expression will be totally shifted towards maintenance, repair, and longevity that would relate to both disease prevention and reversal. This metabolic adaptation to nutritional availability was set during extremely ancient times shortly after life began around 4 billion years ago and long before fat was used as a fuel, long before paleolithic man, when glucose dominated the oceans and was what to eat.

Question #4;

Is the VLC diet only better for “sick” people?

What I said 20 years ago is just as true today; Carbohydrates should be defined as fiber or not fiber.  Any carb that is not a fiber will turn to sugar and will cause harm…for any and everyone, males, females, monkeys and worms.  The only difference among the sugars and non-fiber carbs is how fast and how much harm will be caused.

In everyone, when one eats starches it quickly turns to sugar, glucose, fructose, galactose, etc. that will circulate and glycate the collagen that lines the arteries causing inflammation and cardiovascular disease and all of the other adverse effects of glycation.  This causes inflammation secondary to the AGE-RAGE reaction. Raising glucose raises insulin increasing risk of cancer. This is not safe and should not be called a safe starch.   ‘Safe starches’ is an oxymoron.

One should not discuss effects of starch only on blood glucose. What about intracellular glucose?  If you eat that sugar and it’s not in the circulation, where is it?  Much gets pushed inside cells causing intracellular glycation and cellular harm.  Lots will turn into liver fat. It has to go somewhere, and wherever it goes it will do damage. This is why it is better to talk about glycemic load than glycemic index. All sugar eaten will cause damage.

EVERYONE who eats starch will raise their glucose and/or insulin…a lot. Keeping glucose down by raising insulin is doing one no favors; just trading one evil, elevated glucose, by an even worse evil, high insulin.  (See “Insulin and its Metabolic Effects“). This was shown clearly by the ACCORD study.

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If diabetes were properly diagnosed as improper metabolic signals, especially from insulin and perhaps even more importantly from leptin, then we all have diabetes to one degree or another..

Paul Jaminet and Chris Kresser have stated that maybe a very low carb diet is better for those who are sick with metabolic diseases, but not for ‘healthy’ people.  However, we all are in various stages of metabolic disease.  We all have some degree of insulin and leptin resistance.  Most wake up recovering from their dietary insults and are the most insulin sensitive they will be the whole day.  In other words, we all have some degree of diabetes, if it were diagnosed properly.

When you eat a so-called ‘safe starch’ meal, many people’s blood glucose, if not most, will go above 126 mg/dl, meaning that if they were fasting, they would by definition be called a diabetic.  The fact that they were not fasting does not mean that the glucose does not do the same harm as if they were fasted.  Eating several such meals/day would mean that the supposed ‘healthy’ person was ‘diabetic’ most of the day and perhaps only upon awakening was the BS at a healthier range…and this is saying nothing about insulin and leptin levels and resistance, where the underlying disease actually resides.

Life’s commonalities are much more critical to life than the differences, since life can’t live without them. (See my next blog, an essay I had written a few years back called “The Transcendence of Commonality Amongst Individuality”.)

The basics of metabolism are true for all people, in fact virtually all life. This is why worm studies are important to us.  Human insulin and glucose will work in a worm just as it does in a human, causing damage and shortening lifespan when elevated.

Starches, “safe” or otherwise turn quickly to glucose in any animal that can digest them and all will get the same side effects; it will cause glycation, AGEs, raise insulin, leptin, whether you have blue eyes, brown eyes, are a mouse or a worm… This is the advantage of getting further down, closer to the roots of disease; differences fade away and the commonalities are left to see…and treat.

Yes people are different, but the basics that we are talking about here are not only true for all people but transcends humans and are true for virtually all animal life. It is worth repeating; if you eat a non-fiber carbohydrate (sugar or starch), it will raise your blood sugar, as it would your neighbor’s blood sugar, and it will raise virtually every person’s blood sugar in the world…and every dog’s, and every worm’s blood sugar… In turn, raising glucose raises insulin and leptin and accelerates the rate of aging, and the symptoms of aging, including cardiovascular disease, diabetes, obesity, osteoporosis, and cancer.

OTHER POINTS

Kitavans and Okinawans are poor examples to use in defense of carbohydrates.

I have consistently heard those in the Paleo, higher carbohydrate camp refer to the Kitavans as an example of a population eating a high carbohydrate diet and supposedly being much healthier, and the conclusion often made is that their high carbohydrate diet is causing the improved health of Kitavans.

It’s interesting to look at small subpopulations such as the Kitavans, but not more. Basing dietary recommendations on that is fraught with error. They are a very small, isolated group of people that easily could have certain genetic anomalies that might allow for longevity (even though they don’t particularly live a long life).  Kitavans also mostly eat one major meal a day and that offers benefits in spite of any starches since most of the day they are calorie and protein restricting.  Both are highly correlated with longevity in many animal studies.  Partly because of this they’re much smaller than the average Western population, the average male being 5’4″ tall and female being 5’1″.  It is known that smaller members of a species such as dogs live longer, and there is evidence that this may also apply to humans.  This is likely related to lower IGF-I levels, a well studied longevity factor in animals. Was this measured in the Kitavans?  How about mTOR, also associated with lower protein intake and strongly associated with longevity?

Little mentioned of the Kitavans is their high intake of coconut oil.  This is very high in medium chain triglycerides that have been shown to have numerous and powerful metabolic advantages. That is the trouble with population studies. It is impossible to control all of the variables in diet and lifestyle.

But do Kitavans have extended longevity?  That’s quite debatable. They do not have a higher number than average of centenarians (if any) and do not apparently have higher than (even post 50 year old to account for high infant death rate) average lifespans.

A serious mistake so frequently made in health and medical studies is confusing correlation with causation. This is well illustrated with virtually all of the studies that correlate cholesterol with heart disease.  But even here, in the Kitavan study, the most one can say is that their health and longevity, if indeed they have increased longevity, is correlated with a diet and not caused by it. It could be that the diet is an innocent bystander and that the real cause of their enhanced health is from their short stature and the possibly related low IGF-1 and mTOR.  They may even be healthier in spite of their diet.

Being short and thin, with likely low IGF-1 levels, eating a somewhat protein restricted diet high in MCT’s, the Kitavans have several known reasons to live long, healthy lives. Even so, they do not have remarkably long lifespans. It is this that needs to be explained. Why not? Perhaps because they are eating high amounts of starches. In other words, rather than the notion that is being perpetuated by starch proponents that Kitavans live a long, healthy life secondary to eating starches, it could be that whatever health benefits that are being experienced by Kitavans are in spite of the starches rather than because of them. It is very possible, in fact probable, that they would live even longer and healthier lives if they ate a high-fat, very low carbohydrate diet in addition to their other advantages, thus keeping glucose and insulin lower to go along with their likely lower IGF and mTOR.

All one can say is that Kitavans, with their diet of far less junk food, higher (cellulose) vegetables, high MCTs, lower protein, that may help result in short and lean stature likely secondary to lower IGF-1and mTOR (known longevity factors in animals), with their less stressed lifestyle gives them low rates of heart disease and diabetes but with only an average lifespan with few centenarians, that may likely be despite eating starches than because of it.  And this is the best example that ‘safe starch’ advocates can come up with??

As far as the Okinawans; simple. They are calorie restricted, eating a diet higher in fish and vegetables, and lower in rice than their mainland counterparts.  In the most comprehensive study pertaining to the Okinawan diet and longevity, the following was found;

“Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI…and survival patterns consistent with extended mean and maximum life span.”

The study concluded…

“This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.”

I have not seen a breakdown of the calories eaten, but since they eat more fish and fibrous vegetables than their mainland counterparts and lower calories, simple logic could conclude that they eat fewer non-fiber carbohydrates, which, along with reduced stress, may account for their increased average lifespan.

Caloric Restriction, the Traditional Okinawan Diet, and Healthy Aging,  Annals of the New York Academy of Sciences, Volume 1114, Healthy Aging and Longevity: 3rd International Conference, p 434–455, October 2007

We must understand the limited information allowed by laboratory tests to interpret them properly.

Lowering thyroid (or raising rT3) is not hypothyroidism.

Lowering WBC does not mean impaired immunity, but perhaps less stress on the immune system, or stronger WBCs as far as phagocytic activity, therefore requiring fewer of them. Lowering insulin does not necessarily mean T1 diabetes.

Centenarians and CR (calorie restricted) animals including humans have lower free T3.

I don’t doubt that Paul’s diet is a good one.  There lots of good diets and virtually any diet that is different than the typical American diet will be better.  But we are not just talking about better. We’re not talking about improving diabetes but reversing diabetes, heart disease, and slowing down the aging process itself.  The major benefit of a very low carbohydrate, moderate protein, high-fat diet, and what will get you to the next level of health, is the adaptation to constantly burning fat and ketones and thus requiring less glucose. By forcing the intake of 100 gm or more of glucose into the body you would prevent that adaptation (according to George Cahill) and would prevent experiencing the truly deep benefits of a very low carbohydrate, high-fat diet.

The lowering of free T3 is a sign of that deep adaptation, and, according to Paul, when you follow his diet you prevent the lowering of free T3. That is powerful indication that following a “safe starch” diet is preventing one from changing into a calorie restriction phenotype and preventing the genetic expression and adaptation to deeper maintenance and repair that equates to health and longevity that a very low carbohydrate, high-fat diet would otherwise allow the opportunity for.

Age and Ageing 2010; 39: 723–727

“Down-regulation of thyroid hormones, due to either genetic predisposition or resetting of thyroid function favours longevity.” [emphasis mine]

It is important to understand nature, and to understand what its primary directive is…and its primary directive is not longevity, and certainly not post reproductive health and longevity.  For that we have no footsteps to follow. As far as I know, no other species is purposely trying to live a long, healthy post reproductive lifespan.  For that we only have the best science go by.

What, or even whom, is evolution selecting for? Evolution does not select for (somatic) longevity.  However it wants to keep the genome immortal.  If one looks at an individual human or any animal or any life, it can be broken down into the soma, the body, and the germline.  The soma is there to take care of the germline and see it through to the next generation. The soma is taking the chromosomal baton that had been handed to it and passing it to the next soma to take care of that chromosomal information so that it too can do the same to the next generation. As such, our germline has stayed immortal since the beginning of life.  The soma becomes expendable and takes the environmental hits, the oxidation and glycation and other insults.  It is the shield that protects your genetic information from that damage.  It is why we even age.  Therefore, the only longevity that can be talked about is the immortal longevity of our germline and the “expendableness” of our soma. The longevity of the soma becomes, at least for nature, irrelevant outside of that.

Until we understand that nature cares little for us living a long and healthy life and until we go beyond what is typically “natural”, we will continue to do what is very natural, and it is inevitably natural to get sick and die soon after our children can stand on their own two legs, as it were.

Any discussion of health and medicine should at least take into account the biology of aging.

Life is a constant battle between damage and repair. It is repair that we have the most control over, and is therefore the most important.

As far as damage; there are at least 2 major sources.  We have only limited control over oxidation. This, by definition is from oxygen. However, you shouldn’t stop breathing.

Glycation.  Don’t eat glucose.  Any excursion increases glycation.

Repair; The biology of aging convincingly shows nutrient sensors including insulin for glucose and mTOR for protein, control a genetic pathway that is almost universally conserved among all animal life from single celled yeast onward to humans.  Science also is showing that leptin controls the healthy phenotype imparted by calorie restriction in so-called higher organisms that use fat as a primary fuel. 

It appears that nature has all sorts of tricks up her sleeve to allow the members of the species to live as long as necessary to impart a reasonable chance of reproductive success. Tricks such as intracellular antioxidant up regulation, DNA repair, increased autophagy (cellular garbage collection), are all enhanced when nature believes this is necessary, including times of hardship such as perceived famine. Those nutrient sensors are controlled by the amount of macronutrients in each meal, sugars and proteins raising all of them…but not fat.  When these nutrient pathways are raised, cells are told to multiply and repair is diminished, accelerating aging and increasing risk of cancer in complex multi-celled people.

Paul Jaminet and the other ‘safe starch’ advocates seem to be concentrating only on the on potential damage, or lack thereof, secondary to glucose, including mitochondrial damage.  I, along with many biology of aging experts, believe strongly that glucose is a major cause of molecular damage in all life and that it contributes to aging.  However, the “accumulated damage” school of aging, especially as it pertains to reactive oxygen species is really quite archaic today.  Being ignored is the effect of eating glucose on the above extremely important nutrient sensing pathways that help regulate the genetic expression of extremely powerful repair mechanisms.  To dig into this ancient health-promoting pathway, one must simulate glucose deprivation and eat far less glucose forming carbs than recommended by ‘safe starch’ advocates.

Controlling intake of protein is very important.  I believe that I was the first low carb advocate to disavow high protein and instead recommend higher fat.  I was then and am now extremely confident that I am right.  I had plenty of friendly disagreements with the Eades about protein when we worked together, as they believed high was good as did almost all low carb advocates.  My public talk/debate with the Eades at ASBP (American Society of Bariatric Physicians) in 2006 that is posted on my site – Protein: The Good, The Bad and The Ugly and several others, where I introduced the science of mTOR and the relationship between protein, cancer, and aging changed a lot of minds about high protein including apparently Jeff Volek and Steve Phinney who are now embracing the lower protein and higher fat diet in their books.

A quote by Oscar Wilde that is very apt, “Everything popular is wrong”…

A low fat diet to lose weight and treat diabetes and even that diabetes is a disease of blood sugar…

Take calcium to strengthen bones…

Cholesterol causes heart disease…

Even low carb advocates pushing high protein…

I have long said these were all wrong, and I have argued against them all for 2 decades…and I will be shown ultimately to be correct on all counts…

I have used my diet to save many lives. I have been fighting for my VLC, high fat and no more than adequate protein diet and the importance of insulin, leptin and mTOR to be accepted, since I am certain this can save millions more.  No offense, but comparatively ‘safe starches’ is just a speed bump.

© Copyright 2012 Ron Rosedale, M.D.

The post A Conclusion to the ‘Safe Starch’ Debate by Answering Four Questions appeared first on Ron Rosedale, M.D..

For years now, it’s been said that telomeres – the tips of your chromosomes – are the key to cancer and aging. The shorter they are, the worse off you are – so the story goes. But what do we really know about them? Can the length of your telomeres help predict how long you’ll live? Could telomere research unlock a modern fountain of youth? Could humans one day live to be hundreds of years old?

Dr. Ron Rosedale of DrRosedale.com and The Rosedale Diet is here to answer some of these questions in this special guest post. In it he will introduce you to these little bits of genetic sequences, and provide his expert commentary on the state of telomere science. It will get somewhat technical in parts, but it’s well worth the read.

Thanks to Mark Sisson of Mark’s Daily Apple asking me to write this article.

Now, Dr. Rosedale…

Summary – The Good, the Bad, and the Ugly

The Good: With considerably more research in the control of telomere length specific to different issues, it may be a new and powerful therapeutic tool to improve health.

The Bad: It is not likely a modality to extend maximal lifespan. It is far from the fountain of youth.

The Ugly: Without proper and exact knowledge of when and where to control telomere length, it will likely greatly increase one’s risk of cancer. In other words, it may very well increase healthspan as it reduces lifespan.

Introduction

Can the length of very simple, short genetic sequences at the tips of chromosomes called telomeres determine how healthy you are and how fast you will age? This has become a popular idea in paleo blogs and in the lay world of “anti-aging medicine”, especially now that telomere length (TL) can be relatively easily measured.

First, let’s examine very briefly the history of that idea. In 1961 Leonard Hayflick discovered that cells in a petri dish could only divide a limited number of times before cell division would cease permanently. This famously became known as the “Hayflick limit”. 10 years later Olovnikov, a Russian researcher, linked the tails of chromosomes to this cell division arrest. It was found that the enzymes that duplicate the DNA of chromosomes cannot continue this duplication all the way to the ends of linear chromosomes. If cells were to divide without telomeres, with each cell division they would lose a chunk of critical and functional DNA. The telomeres act as sacrificial lambs for DNA duplication. They are repeating nucleotide segments (TTAGGG) of relatively meaningless segments of chromosomes such that the loss of a small chunk of these when cells divide is genetically harmless… up to a point. If a cell divides too much, and its telomeres become too short, at best it can no longer divide. Worse, genetic harm befalls that cell. A process is initiated within the cell causing it to self-destruct (called apoptosis). Later, it was found that a natural enzyme that some cells manufacture called telomerase is capable of lengthening telomeres and potentially immortalizing that cell. The finding that telomeres shorten with increasing age has led to the theory that telomeres are at least a biomarker of aging, if not at least partially causative of the damage associated with aging (called senescence). It was, and still is in some circles, thought that increasing telomere length slows, if not reverses, aging. The telomere theory of aging was born. Should it continue to live, or die a peaceful apoptotic death as shortened telomeres themselves are apt to cause?

A full discourse on telomeres and the biology of aging would consume an excessive amount of all of our already telomere challenged lives. I will instead focus on telomeres as a potential biomarker and/or “anti-aging” therapy and the deeper meaning of this.

First, let’s get our terms straight. What is mean by “anti-aging”. The word itself is controversial. In the more scientific, biology of aging community where researchers are genetically manipulating specific (i.e. insulin) metabolic pathways and extending lifespan a hundred or more percent in some animals, that word has a negative connotation. To them, it conjures up images of modern day snake oil salesmen promising longevity treatments such as growth hormone therapy, that if anything, might likely shorten lifespan. To them, a slowing down of the typical aging process results in a lengthening of maximal lifespan as opposed to average lifespan. The two are quite different. The maximum human life span (that has been well-documented) is considered to be 122 years that Jean Calment, a French woman lived before dying in 1997. The average lifespan in the United States is roughly 78 years. If one greatly increased the health of the general population, one might increase average lifespan to be hypothetically 85 years. However, if no one still lived over 122 years, the maximal known human lifespan would continue to remain unchanged.

A treatment such as lengthening telomeres might well improve some, and possibly many, symptoms of aging and even the average or median lifespan, while leaving maximum lifespan unchanged…or perhaps even shortening it. It would not and should not then be considered an “anti-aging” treatment though possibly a good therapeutic modality.

On the other hand, biology of aging experts such as a friend of mine, Andrzej Bartke, past president of the American Aging Association, are able to extend the maximum lifespan in laboratory animals such as mice…a lot. He is the last recipient of one of the most prestigious and lucrative awards in aging research, the Methuselah Prize. He did this by genetically suppressing the growth hormone receptor in a strain of mouse such that it lived about twice as long as usual; the equivalent of a human living to be approximately 180 years old. In the published study that won the prize he states, “We propose that mechanisms linking GH [growth hormone] deficiency and GH resistance with delayed aging include reduced hepatic synthesis of insulin-­like growth factor 1 (IGF­-1), reduced secretion of insulin, increased hepatic sensitivity to insulin actions, reduced plasma glucose…An important role of IGF­1 and insulin in the control of mammalian longevity is consistent with the well­-documented actions of homologous signaling pathways in invertebrates.” (Life extension in the dwarf mouse; Curr Top Dev Biol. 2004;63). I mention this also, since a similarly hyped and very popular “anti-aging” treatment is growth hormone therapy, whereby growth hormone is regularly injected with supposed rejuvenating properties…exactly opposite to what was done to win the coveted Methuselah Prize… Caveat emptor.

Many so-called experts on health and longevity talk a lot about increasing telomere length as proof of efficacy of some sort of diet or other health modality. Let’s look at that statement. What do they mean by increasing their telomeres? They have about 15 trillion cells. Did they increase the telomere length of all chromosomes in all cells? Were they all measured? Was a representative sample measured? Is telomere length even indicative of health, or aging? Is it even a biomarker of aging, and if so, is that relevant?

One of several major problems with all this; less than 1% of a person’s cells have the enzyme telomerase and thus are even capable of increasing their chromosome’s telomere length. The other 99% are incapable of doing so. What about neurons, and heart cells that typically do not divide and where their telomeres do not shorten with age? The large majority of liver and kidney cells can’t lengthen telomeres, etc., etc. Perhaps the 1% that can are the most critical. They include white blood cells (WBCs) and many stem cells. We will examine that a bit more later.

Is it even good to increase telomere length? Maybe not. 90% of cancer cells do it. The fact that telomeres shorten may actually allow us to live longer, as it may reduce the risk of cancer. The good news is that the telomeres in almost all the cells other than WBCs and stem cells do not increase, for if they did, dying of cancer would be all but certain.

The chromosomes of nearly all multicellular life are linear; they have a beginning and an end. As such, for these cells, telomeres are essential to life. The exception are bacteria whose chromosomes are circular. They do not have a beginning or an end and thus telomeres are a moot point. Thus, there are no telomeric restrictions on bacterial reproduction. They continue to reproduce as often and as fast as they can; like cancer, that seems to be their singular goal. The purpose of linear chromosomes and telomeres is often thought to be secondary to our evolution from single celled bacteria to large, complex, multicellular individuals such that their now linear chromosomes with telomeres prevent cells from easily reverting back to their ancestral bacterial ways, i.e. the singular purpose of reproduction, that in multicellular life is cancer. It is a must to continually lengthen telomeres to lift the restriction on cell division if a cell hopes to stay a cancer cell.

Another major problem with the telomere theory of aging; if anything there is a negative correlation between telomere length and lifespan of different species. For instance, mice have much longer telomeres than humans but live a small fraction as long.

However, numerous studies have shown a correlation within a particular species between telomere length and length of life. This has therefore been used as strong evidence that length is a good biomarker of aging within a particular species and even that telomere attrition causes aging itself. Hopefully they mean the damage associated with aging. It is unlikely that you would not be a day older tomorrow.

A major mistake made so frequently in medicine, but rarely in other sciences, is the confusion and interchange between correlation and cause. An example is the consistent reference to cholesterol being a cause of heart disease, when in fact it is an association, and even a weak one at that. An entire industry and economy has been built over that “mistake”. I digress; that is a story for another day (or you can read on the web what I have already said about that long ago).

Getting wrinkles is far more correlated, and is therefore a far better biomarker for aging than telomere length, however undergoing a dermabrasion is not likely to extend lifespan. Once again, it is science 101 to not confuse correlation with cause. It could very well be, and in fact is likely, that reduced telomere length is a byproduct of the cell damage and turnover associated with aging, rather than a prime cause of it, though it likely does have some adverse repercussions especially to the immune system and possibly stem cells.

How about current laboratory testing for telomere length? It merely requires a tube of blood since one of the very few cell types that is easily accessible and where telomerase is present such that telomere length can increase are white blood cells. Is the test meaningful? Probably not very. The rate of telomere attrition, the rate of decrease in telomere length that may be more important than absolute length, will increase with increased cellular damage and turnover such as that caused by oxidation, free radical damage, glycation, and inflammation. In other words, all that a higher rate of telomere shortening of any kind might indicate is an increased rate of cellular damage, but it doesn’t tell you what is causing the damage. Glucose perhaps?

Many, including myself, believe that all shortening of WBC telomere length in particular reflects, is the state of inflammation. There are many other much simpler and less expensive, albeit less glamorous markers for this such as a C-reactive protein or even the sedimentation rate. Furthermore, both a healthy, though at the time less active immune system, and an overly stressed or suppressed immune system might, at least theoretically, lead to less telomere attrition due to less cellular proliferation.

Though the rate of white blood cell TL shortening has been shown to decrease and TL may even increase with certain changes in lifestyle such as exercise and diet (that might just reflect improved immune response), TL also has been shown to oscillate even if you don’t do anything; not change your diet, nor exercise, take antioxidants, or think positively about your TL.

However, the biggest problem in measuring TL in WBC’s is that there are many different telomeres of different lengths in many different kinds of cells with differing rates of attrition. An increase in white blood cell TL or reduced rate of shortening does not necessarily reflect a change in other telomeres, especially from other cell types. For instance, in cells that don’t divide, such as heart and nerve cells, TL is somewhat meaningless. Telomere length even varies depending on the kind of white blood cells.

Robust evidence also shows that it is not the length of telomeres, or even the rate of telomere reduction with age that matters, but rather that telomeres must get to a critically short length for adverse genetic repercussions to take place. Measuring WBC TL only measures average WBC telomere length and not the number of critically short telomeres.

For all of the above reasons, I feel that current measurement of WBC TL is not a very good biomarker of aging and is virtually meaningless as an important independent indicator of the rate of aging.

What about the other major cell type that produces telomerase and is capable of increasing telomere length? What about measuring stem cell TL? This is done, but currently only in research laboratories and generally only in animals. Not very many people would volunteer for heart biopsies, for instance. A jilted lover might volunteer their ex perhaps. However, stem cell TL is actually where the rubber meets the road. Stem cells are very important as is their preservation. They are certainly capable of regenerating many tissues, including those not producing telomerase. Unfortunately, WBC TL does not necessarily reflect stem cell TL, nor does it reflect telomere attrition, especially since there are so many different types of stem cells from so many different types of tissue with so many different rates of cellular turnover and damage. I discuss this more below when I show excerpts from some studies that are quite revealing.

Telomere length is correlated with rate of cellular replication, and cellular replication is increased with increasing mTOR, IGF-I and inflammation. Therefore, it very well could be that the correlation between telomere length and longevity is only just that, a correlation, and not a cause, and the underlying mechanism of aging has much more to do with levels of glucose, mTOR, IGF-I…and insulin and leptin. That is likely true. Indeed, telomere length, has been shown to be highly (negatively) correlated with leptin levels (see below).

As I was actually writing this article, one of the most significant studies to be published pertaining to telomeres in recent years came out of Maria Basco’s lab from Spain. I will discuss it more at length below. It shows just how important it is to orchestrate telomere length and telomerase. It must be turned on, or off, at a certain time and place for there to be any chance at significantly improved health without increasing cancer risk.

Conclusion

The telomere theory as a cause of aging was hotly debated over a decade ago in many biology of aging conferences where university researchers got together to discuss their latest findings. Now, this is barely discussed outside of pseudoscientific circles… Perhaps the latest Basco study will reinvigorate this debate.

I believe that lengthening telomeres, most specifically in stem cells, and then only temporarily to mitigate against increasing cancer risk, may offer potential to increase health span and delay the onset and even treat certain chronic diseases of aging. However, this is not the same or as powerful as increasing maximal lifespan and stretching out youth that research into genetic pathways of aging regulated by nutrient sensors (insulin, leptin, and mTOR) offer, as illustrated by the increase in maximal lifespan of many species by 200% and more when insulin, IGF-I, and mTOR are genetically suppressed.

One must accurately define health before directions to be healthy are given and just like health is not low cholesterol, health is not defined or synonymous with long telomeres.

Life is dependent on the coordination of its constituent parts. This is especially true pertaining to the length of telomeres of the various cells and organs to maintain health but prevent a high risk of cancer.

As I have said so frequently in the past, we are 15 trillion cells and 90 trillion bacteria that must work harmoniously as one for us to be healthy and remain alive. This requires an intricate orchestration of communication between the different parts. That includes the genes, telomeres, and telomerase. It is where, when, and how much they are played, like the keys of a piano playing an infinite variety of music from the same keys, that determine who we are, diabetic or not, and if we stay alive or die.

What we do want to do is slow down the reduction in the length of our telomeres in an organ and tissue-specific manner that can be orchestrated only through proper genetic expression. Leptin and insulin are among the most, if not the most powerful influences of this. And these in turn are controlled by what you eat.

Review of Telomere Literature

Need more convincing? Confused? Have insomnia? Quotes from various references with brief discussions will follow. (Paper titles are bolded and hyperlinked, quotes from the papers are in the quote boxes, and my comments follow each box).

Telomere biology in healthy aging and disease, Hisko Oeseburg, Eur J Physiol (2010) 459:259–268

In contrast to the similarity of the sequence, the telomere length is highly variable among species, within species, within an organism, and even between chromosomes.

Telomere length of a few different species;
Humans 5–15 kb [kilobase; 1000 base pairs]
Mice Up to 150 kb
Rats 20–100 kb
Birds 5–20 kb
Ants 9–13 kb

…mice strains with longer telomeres do not seem to have an increased lifespan compared to mice strains with shorter telomeres…in African Americans telomeres generally are longer than in White Americans.

Rosedale: …yet have shorter average lifespans. All of this well known data will tell you immediately that telomere length, per se, is not critical to biological aging.

Telomere length [is] highly variable between organs from one subject. This may be explained by variable telomere attrition rate.

Rosedale: One could postulate that rather than absolute telomere length, telomere attrition rate might be significant. However, this could and indeed likely is a reflection of the rate of cellular damage, death, and degree of cellular multiplication to replace that damage. In other words, telomere length would be secondary to aging rather than a cause of it. Measuring telomere attrition rate would, of course, necessitate the measurement of telomere length over time.

The major disadvantage of using leukocyte telomere length is that it is a measure of the activity state of the immune system and one might argue that leukocyte telomere length is rather a representation of increased inflammation than of aging.

Rosedale: The state of inflammation is quite variable over time. A strep throat, upset stomach, and a scraped knee could increase your general state of inflammation for weeks and this could reflect in variably lower WBC telomere length secondary to a healthy immune system.

Blood Cell Telomere Length Is a Dynamic Feature, Ulrika Svenson, PLoS ONE June 2011 Volume 6 Issue 6

Irrespective of the biological background, leukocyte telomeres appear to oscillate in length over time [months].

Rosedale: Therefore many measurements over time in a single individual would be necessary to know if a change in TL was due to normal oscillation or not.

Shortening telomeres are more secondary to aging and disease than a cause of it.

Telomere length and cardiovascular aging: The means to the ends?, Tim De Meyer, Aging Research Reviews, Vol 10, #2 April 2011, Pages 297–303

Conclusion: Shorter inherited telomeres do not appear to predispose to early atherosclerosis. Atherosclerosis related factors accelerate telomere attrition.

Rosedale: Shortening telomeres may have a huge evolutionary advantage, especially for larger animals…

Telomerase activity coevolves with body mass, not lifespan, Andrei Seluanov, Aging Cell. 2007 February ; 6(1): 45–52

Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk.

Rosedale: What about the potential of increasing telomere length?…

Telomere length, stem cells and aging, Maria A Blasco, Volume 3 Number 10 October 2007 Nature Chemical Biology

The fact that the vast majority of human tumors seem to depend on telomerase reactivation to prevent critical telomere loss and to divide indefinitely suggests that telomerase inhibition could be an effective way to abolish tumor growth.
The fact that telomerase deficiency only results in loss of organismal viability when telomeres reach a critically short length is an important point when considering possible secondary effects of these therapies.
In particular, this predicts that putative anticancer therapies based on temporary telomerase inhibition will only trigger loss of viability in those cells with short telomeres that depend on telomerase activity. Presumably, these include tumor cells but not healthy tissues, which generally lack telomerase activity and have sufficiently long telomeres to maintain viability during the human lifetime, thus providing a window of opportunity for intervention.

Therapeutic agents that could be designed to [re-activate telomerase temporary] would preferentially target those cell types that normally divide to maintain organ homeostasis—such as stem cells, which, although telomerase-proficient, do not have sufficient telomerase activity to maintain telomere length over time.

Rosedale: As in all disease, especially having to do with genes, it is where, when, and how they are read that determines their contribution to health, disease, and even who you are.

Telomere Length of Circulating Leukocyte Subpopulations and Buccal Cells in Patients with Ischemic Heart Failure and Their Offspring, Wong LSM, PLoS ONE 6(8) August 18, 2011

For instance, it has been shown that vascular endothelial cells that endure more hemodynamic sheer stress have shorter telomeres than endothelial cells in low pressure arteries [secondary to a greater rate of turnover]

Rosedale: i.e. TL is a secondary byproduct of aging, not a primary cause of it.

To further dissect the association of ischemic heart disease with mean overall leukocyte TL we need to establish whether mean overall leukocyte TL is a reflection of TL in different cell types or whether it is more or less specific for leukocytes. Of particular interest in this regard are the CD34 positive (CD34+) cells as it is thought that these cells might be cardiovascular progenitor [stem] cells and play a role in cardiovascular repair…Furthermore, mean leukocyte telomere length has not been compared to non-circulating non-vascular cells and it is unknown whether leukocytes might merely be a reflection of overall TL of the whole body… One of the aims of this study was determining whether telomere length of CD34+ cells is different in IHF patients compared to healthy controls. We did not find a difference in TL between IHF patients and controls in CD34+ cells. These results clearly indicate that there is no significant difference in CD34+ cell TL between IHF patients and controls.

The major difference in telomere length between IHF patients and controls was observed in the overall leukocyte pool, not specifically in CD34+, MNCs or buccal cells as a source of non-blood derived cells.

The comparable TL of CD34+ cells in cases and controls strongly suggest that telomere shortening of CD34+ cells is not a major player in the pathophysiology of IHD…In the elderly, specific immune responses might be diminished, but many other functions are unchanged or even augmented compared to young persons.

Rosedale: This study is important for several reasons, the main one being to illustrate that even though WBC TL may correlate with a disease state such as ischemic heart failure (secondary to correlating with cellular damage and turnover), WBC TL did not correlate, at least in this study, with representative cells of the only major cell group that may have significant therapeutic potential, stem cells. One cannot extrapolate WBC telomere length to other tissues.

Telomerase, senescence and ageing., Shawi M, Autexier C., Mech Ageing Dev. 2008 Jan-Feb;129(1-2):3-10. Epub 2007 Dec 14

Paradoxically, the introduction of telomerase is proposed as a method to combat ageing via cell therapy and a possible method to regenerate tissue, while telomerase inhibition and telomere shortening is suggested as a possible therapy to defeat cancers..
Rosedale; In other words, telomerase must be turned on and turned off at the appropriate time and location, i.e. it must be orchestrated.

Rosedale: And again, one cannot extrapolate WBC telomere length to other tissues.

Measuring relative telomere length: Is tissue an issue?, Monica M. Gramatges and Alison A. Bertuch. AGING, November 2010, Vol 2 N 11

Although the number of subjects was small, strong correlations between blood, buccal cells, and fibroblasts were observed in the study population as a whole. When taken individually, however, only cells from subjects with DC demonstrated significant correlation. [dyskeratosis congenita (DC). DC is a rare genetic disorder stemming from a defect in telomere maintenance.]

Rosedale: Can TL predict centenarians? Not in the following study. Also, WBC TL was again not correlated with another representative tissue type.

Telomere length in fibroblasts and blood cells from healthy centenarians., Mondello C, Exp Cell Res. 1999 Apr 10;248(1):234-42.

In this paper we analyzed the mean length of the terminal restriction fragments (TRF) [frequently how TL is measured] in fibroblast strains from 4 healthy centenarians, that is, in cells aged in vivo, and from 11 individuals of different ages. No correlation between mean TRF length and donor age was found.

…chromosome analysis did not show the presence of telomeric associations in early passage centenarian fibroblasts. In blood cells from various individuals, the expected inverse correlation between mean TRF length and donor age was found. In particular, a substantial difference (about 2 kb) between telomere length in the two cell types was observed in the same centenarian.

No Association Between Telomere Length and Survival Among the Elderly and Oldest Old, Bischoff C, Epidemiology: March 2006 – Volume 17 – Issue 2 – pp 190-194

This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for.

Rosedale: We have lots of telomeres. We have at least 500 trillion of them and measuring a select few from one cell type is not necessarily going to tell you what the other telomeres are doing…

Ageing and telomeres: a study into organ and gender-specific telomere shortening, H. Cherif*, 1576±1583 Nucleic Acids Research, 2003, Vol. 31, No. 5

In humans, telomere length is relatively short, highly variable between tissues and individuals and, with regard to replicating somatic cells, inversely related to donor age

We show clearly in this study that the mean TRF length method is unable to detect small changes in telomere size or to visualise the length of individual short telomeres in a distribution of TRFs. There is increasing evidence suggesting that it is not average telomere length, but rather individual critically short telomeres that trigger cellular responses to the loss of telomere function

The latest study and the most promising to show health benefits in telomerase expressed mammals was published last week…

Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer, Bruno Bernardes de Jesus, Maria Blasco, EMBO Mol Med march 16, 2012 4, 1–14

Importantly, telomerase-treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors telomerase treated mice, both at 1-year and at 2-year of age, had an increase in median lifespan of 24 and 13%, respectively.

Owing to its ability to confer with unlimited proliferative potential, over-expression of the telomerase reverse transcriptase (TERT) is a common feature of human cancers and can increase cancer incidence in the context of classical mouse TERT transgenesis.

A drawback of mTERT over-expression in transgenic mouse studies has been an increased cancer incidence, except for cancer-resistant backgrounds.

Telomerase expression late in life leads to overall telomere lengthening and decreased abundance of short telomeres in various tissues.

…telomerase activation can delay normal mouse aging in cancer resistant mice…

However, with the exception of mice genetically engineered to be cancer resistant, increased telomerase expression is associated with a higher susceptibility to develop cancer both in mice and humans…

Notably, in these studies increased TERT expression is forced since early embryo development through germ line modifications, which may favour the expansion of cancerous cells and the development of cancer later in life…Here, we show that increased TERT expression later in life (adult and old mice) by using a gene therapy strategy has rejuvenating effects without increasing cancer risk…the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms. Finally, re-introduction of mTERT in both 1- and 2-year old mice increased significantly its median lifespan (24 and 13%, respectively).

Rosedale: It generally takes at least several years for cancer to reveal itself. These mice only live 2 to 3 years. Therefore expressing telomerase when these mice only had one or less years to live likely did not give cancer cells enough time to manifest themselves. This would not be the case when using this sort of therapy in humans with more than 1 to 2 years to live. Note further that it is median lifespan that was modestly increased rather than maximal lifespan.] Also note that humans have much more body mass than mice, and therefore artificially activating telomerase in humans may have significantly greater negative consequences especially relative to cancer rate as compared to mice. See study above.

A commentary to the above article in the same journal:

Telomerase gene therapy: a novel approach to combat aging, Virginia Boccardi, Utz Herbig, EMBO Molecular Medicine 4, 1–3

…numerous studies using mouse models have demonstrated that critically short and dysfunctional telomeres indeed present a powerful barrier to cancer growth.

A question that has therefore intrigued researchers for many years is whether it is possible to slow aging and improve health span by re-activating telomerase in all of our cells. Constitutive expression of telomerase, unfortunately, is a characteristic of almost all cancer cells. It is therefore no surprise that transgenic animals over-expressing the catalytic subunit of mouse telomerase (mTERT), develop cancers earlier in life, thereby masking the potential beneficial lifespan extending properties of telomerase.

While these studies provide a proof-of-principle that telomerase gene therapy is a feasible and generally safe approach to improve healthspan and treat disorders associated with short telomeres [in mice], a clinical application in humans is likely still some time away. Low levels of integration of rAAV vectors into genomic DNA have been observed, raising the possibility that rare integration events of constitutively overexpressed TERT into genomes of long lived species might eventually promote cancer growth.

Furthermore, as with other gene therapeutic approaches, targeting the virus to specific cells in the body remains an obstacle. Also uncertain is specifically which cells should be targeted using a telomerase gene therapy.

Rosedale: Conclusions?

Association Between Telomere Length, Specific Causes of Death, and Years of Healthy Life in Health, Aging, and Body Composition, a Population-Based Cohort Study, Omer T. Njajou, J Gerontol A Biol Sci Med Sci 2009. Vol. 64A, No. 8, 860–864

In conclusion, we did not find any evidence of association between [WBC] TL [telomere length] and overall survival or between TL and specific causes of death. We also report for the first time that longer TL is associated with self-reported health status and greater YHL. Findings suggest that TL, although not a strong biomarker of survival in older individuals, may be an informative biomarker of healthy aging.

Is Telomere Length a Biomarker of Aging? A Review, Karen Anne Mather, J Gerontol A Biol Sci Med Sci. 2011 February; 66A(2):202–213

The observation that telomeres shorten with increasing age and are implicated in cellular aging has led to the proposal that telomere length is a biomarker of aging.

Currently, telomere length does not fully meet American Federation of Aging Research criteria that telomere length is (a) a better predictor of life span than chronological age (Criterion 1) and that (b) it monitors a basic process underlying normal aging at the pop-ulation level (Criterion 2).

Interestingly, an increase in intra-individual telomere length for a minority of participants at follow-up (ie, with increasing chronological age) has also been observed in three independent studies (27,39,78). However, this may not represent an increase in overall telomere length but rather could reflect the loss of cells with shorter telomeres.

Rosedale: It has been found that likely only cells with extremely short telomeres are so adversely affected that the process of apoptosis is initiated.

Could the significance of TL be secondary to leptin levels? TL is inversely correlated with leptin levels.

Obesity may accelerate the ageing process., Rowan Hooper, New Scientist 14 June 2005

But animal studies have failed to reveal any simple relationship between telomere length and lifespan… the youngest women had telomeres that were around 7500 base pairs long. Their length declined with age at an average rate of 27 base pairs per year.

When lifestyle factors were taken into account, however, dramatic differences emerged. The difference between being obese and being lean corresponds to 8.8 years of extra aging…

Smoking was the other big factor… Obesity accelerates the ageing process even more than smoking. Intriguingly, the link between high leptin concentrations and telomere shortening was even stronger than the link with obesity…The damage to telomeres is probably done by free radicals. Smoking causes oxidative stress ­ a source of free radicals ­as does obesity [and high leptin]

Free radicals can cause mutations in DNA, and there is some evidence that mutations in telomeres cause larger chunks than normal to be lost during cell division. In other words, it is a byproduct of aging that results in cellular turnover and molecular damage and therefore shortening of telomeres and not the other way around.

The post The Tall Tail of Telomeres appeared first on Ron Rosedale, M.D..

Ron Rosedale Interviewed by Shelley Schlender of www.meandmydiabetes.com

Ron Rosedale challenges the new Harvard Study, published this week in the Journal of the American Medical Association.  He says the study itself has many good points regarding the importance of noting that not all calories are equal, and reducing carbs may be more important than reducing fat.  But in press reports, he’s concerned that the “winning” diet that the Harvard group prefers does not deserve the crown  . . .

LISTEN (1 Hour)

I’m Shelley Schlender, for Me and My diabetes. U-S nutrition policies are based on ” calories in, calories out,” meaning count your calories and burn off any excess with exercise.  Late in June, 2012, the Journal of the American Medical Association raised a challenge to that idea by publishing a Harvard study involving three different diets, and how each diet affects the likelihood of gaining weight.  The diets being studied were a low-fat diet, a low carbohydrate diet, and a diet with some protein, and then equal amounts of calories from carbohydrates and fats – the so-called Mediterranean diet.  The research group measured health markers such as blood triglycerides, metabolic rate, blood sugars, hormones such as insulin, leptin and cortisol, and inflammation markers that included C-Reactive protein.  It was a studied that challenged current policies about “calorie in-calorie out” because changes to the health markers were strongly influenced by just which diet the test subjects ate.  In many ways, it’s a first-rate study. But then, the study was interpreted in the media in a number of wildly varying ways, and much of that interpretation was influenced by just who got interviewed for the reports. David Ludwig, one of the study’s leaders, was a prominent voice in the media reports, and Ludwig told many media outlets that while the low-carb diet had the MOST improvement in health markers overall, the fact that it raised cortisol levels and didn’t lower C-Reactive protein as much as the Mediterranean diet did, means the Mediterranean diet is the best one.  Now, the Harvard School of Nutrition has been a long-time advocate of Mediterranean Diets.  So to check out their conclusion from someone who is NOT an major advocate for Mediterranean Diets, up next, we talk with an advocate for Low-Carb, High Fat diets, Dr. Ron Rosedale.  (Transcript Follows)

Calories In/Calories Out VS. Hormones Signaling

Ron Rosedale, do you believe current dietary policy that stresses a calorie in is a calorie out, that what we need to focus on is how many calories we take in and then exercise enough that we don’t end up with excess calories?

RON ROSEDALE:   Well, I guess that’s been the dogma for decades. I suppose if it had been correct, you wouldn’t see not only the maintenance but the ever-increasing incidence of obesity and diabetes that’s occurring worldwide as that supposed dogma has been followed. What I think the literature shows and has shown for at least a couple of decades, but the scientific evidence for this is just being ignored continually, is that the story is a bit more complex than that, and that whether we burn fat or not, which is what will determine whether we’re obese or not and whether we in most cases contract diabetes or not, is controlled by very specific hormones that regulate metabolism, the main ones being insulin and, even more importantly, leptin. It’s those hormones that are in turn controlled by what we eat.

And it isn’t just the levels of a hormone that are relevant, but much more relevant, in fact, the only relevance, is their activity. The activity is determined not just by the level of the hormone, but more importantly, by the cell’s ability to listen to that hormone. An example is the well-known phenomenon of insulin resistance, which occurs in the vast majority of cases of diabetes and essentially is the sine qua non of so-called type 2 diabetes, which is better called insulin-resistant diabetes, where the person has plenty of insulin but the cells aren’t able to listen to it and therefore they behave as if the insulin level is too low and then ultimately blood sugar goes up, but the consequences are much deeper than that. The disease is not from too little insulin, it’s not from too weak a signal, it’s from an inability to listen to that signal. And the inability to listen to that signal is most likely caused from an overactivity of that communication over time.

It’s too much, so the cells tune out?

RON ROSEDALE:   Exactly. It’s kind of like being overexposed to noise. You lose your hearing faster. Or sitting in a smelly room for a long time, pretty soon you can’t smell it. The stimulus becomes too much, as you mentioned, and the chemical mediators of that signaling basically become depleted, and the pathway becomes resistant to the signal. And that resistance is paramount to virtually all of the chronic diseases of aging, and perhaps even aging itself. The same thing happens with leptin, where obese people have plenty of leptin that normally signals that you have too much fat and you’d better burn it off, and you curtail your hunger so you don’t eat as much. But the actual event that occurs with leptin resistance is the opposite, where although leptin should be telling the brain that you have too much fat, the brain is hearing that you have too little and that you won’t be able to survive a famine and that therefore you should be hungry and you should store more fat and you should not burn the fat that you’ve got.

That’s really the ultimate basis of almost all cases of obesity around the world. It goes even beyond that, because then there are inflammatory markers, and many people believe that the same processes control the actual rate of aging. These are all tied into a genetic pathway that we know controls the rate of aging in many species of laboratory animals, as indicated by calorie restriction studies. It goes on and on and on.

So the simple adage that a calorie in is a calorie out is really, really archaic and really needs to be thrown out.

The Harvard Study

There’s a new study out of Harvard where the headlines about it today are that a calorie is not a calorie. There’s a different process that’s governing whether or not what we eat is helping us lose weight or whether what we eat is helping us maintain our weight, which may be even a bigger deal, because there are a lot of ways that people can lose weight, and in the U.S. and in modern countries, it seems the biggest problem is keeping that weight off. This study compared three different diets, a low-carbohydrate diet, a high-carbohydrate, low-fat diet, and then Mediterranean diet where supposedly there wasn’t anything quick-to-absorb starch or sugar that caused blood sugars to spike, there were a lot of complex carbohydrates, and there was a moderate, not low, amount of fat. The researchers compared these diets and got different results. What do you think of the idea of doing that kind of study?

RON ROSEDALE:   First I want to say that what really surprised me about the study is that it’s news. It’s been shown for a couple of decades by myself and many others that a calorie is not a calorie. They’re certainly far from the first people who have shown anything like this.

As far as the study is concerned, I hate to say it, but as in so many medical and nutritional studies, it really  is designed to try and support a preconceived conclusion. The Harvard/Boston researchers wanted to try to support a dietary protocol that they’ve been using for many years, which is the so-called Mediterranean diet.

Let’s give a bit more detail about the study. It was published today in the Journal of the American Medical Association, this is June 27th, 2012. The title of the study is “Effects of Dietary Composition on Energy Expenditure During Weight Loss and Maintenance.” One of the authors is David Ludwig. The lead author is Cara Ebbeling, who I hope to speak with. As you say, this is a group that overall has been strong advocates of the Mediterranean diet . You’re saying, though, that in the study and in their media reports about it, they stacked the deck in favor of the Mediterranean diet?

RON ROSEDALE:   They tried to stack the deck, but the results actually didn’t support their conclusions. It kind of surprised me that they concluded what they concluded, that the Mediterranean diet was the best diet. What their research really showed, and what they even said in the research paper, was shown, was that the very low carbohydrate diets actually had the best results as far as metabolic markers, with what they said were two exceptions.

Cortisol – Total Daily Level VERSUS Diurnal Pattern Throughout the Day

RON ROSEDALE:  One of the major exceptions that they mentioned, which they said was an adverse result, was that cortisol levels were increased with the very low-carbohydrate diet.   And that’s probably true.

It’s true that cortisol levels were increased, or that it was an adverse effect?

RON ROSEDALE:   It’s true that cortisol levels were probably increased and would probably increase with a properly administered very low-carbohydrate diet. What was wrong with the conclusion is that it’s an adverse effect. It’s actually a very beneficial effect. You will see with calorie-restricted studies in animals that it has been shown to extend lifespan for the last 80 years and what’s seen in centenarians, people who live to be over 100, in all of these groups, one of the common findings is that cortisol levels increase. The study was saying that this is a bad thing, implying that an increased cortisol level shows that there must be increased inflammation.

But one of the reasons that cortisol levels increase as theorized is to suppress inflammation. Cortisol itself is a very powerful anti-inflammatory.

Are you saying, then, that depending on the composition of a diet, some of these hormones have different effects? That in a diet that high in carbohydrates and more than enough calories, extensive time with high cortisol might be more of a problem than it is with a high-fat, low-carbohydrate diet where people are not eating too many calories?

RON ROSEDALE:   If you just measure hormone levels, and this is kind of what I was getting at at the beginning of the conversation, it doesn’t give you the full story. The fact, for instance, going back to diabetes and insulin, where insulin is elevated and yet the signal is very low, causing higher blood sugars, and the actual frank definition of diabetes, because of a low signal. So the fact that cortisol levels go up does not necessarily mean that the signal is up. You have to look at why it’s going up. Is it going up because it has to go up, because there is an overabundance of inflammation, or is it going up as one of the protective mechanisms to reduce inflammation long-term, as seen in calorie-restricted long-lived animals and centenarians?

Leptin went down the most on Low Carb

RON ROSEDALE:  It’s even theorized that one of the reasons calorie restriction works to extend lifespan and greatly improve health is because reducing calories reduces inflammation.  For instance, one of the major markers shown  to go down in the Harvard study, was leptin. Leptin went down the most on a very low carbohydrate diet.  That’s extremely significant, because we know that leptin controls many inflammatory markers. And again, one of the numerous papers now that have theorized that one of the reasons behind the health benefits and longevity behind caloric restriction is a lowering of leptin, which controls the neuroendocrine access via the hypothalamus in the brain, which then controls every other hormone in the body and also controls inflammation and by going down, greatly suppresses many different markers of inflammation. As part of a long-term maintenance to improve lifespan, it reduces inflammation and also by reducing blood sugar, which lowering leptin can do irrespective of insulin, improving insulin sensitivity and leptin sensitivity also greatly reduces the cause of inflammation and not just the mediators of it, since we know that glucose itself is highly inflammatory, as is insulin and as is leptin.

So what the study really showed is that if you go much further than their Mediterranean diet and you reduce carbs by not just slowly absorbable carbs, but just reduce them altogether, because even the slowly absorbable carbohydrates will cause a spike in carbohydrates, will cause a spike in blood sugar, just not as severe as some other carbohydrates.

Am I correct in saying that you think that just looking at one hormone without looking at the whole symphony doesn’t give you the entire picture? You seem to be saying that, for instance, in somebody who was a diabetic, who had insulin resistance, who was obese and had high blood pressure, if that person’s cortisol levels were high, that might not be the same as when someone who is thin and fit and caloric restricted or has the markers of the centenarians, the people who live to be in their hundreds and are healthy, or the people who are on a restricted calorie diet, that’s a different kind of high cortisol for them than it is for somebody who is a type 2 diabetic or somebody who’s a post-traumatic stress victim.

CORTISOL – Was it High in the Morning and Low at Night?

RON ROSEDALE:   That’s absolutely true beyond the obvious. The reasons behind an elevation in a hormone are extremely important, but also what is mediating the elevation and when. For instance, in this study, in which they’re trying to hang their hat on cortisol as the reason that their Mediterranean diet might still be better than a very low-carbohydrate diet, even though the very low-carbohydrate diet showed an improvement in all other metabolic markers, what’s relevant on cortisol is that we know that it is normally secreted in a diurnal pattern, meaning that typically if you’re healthy, it ought to be released in high quantities in the morning and low quantities at night.

This would have had to have been measured. Many, many studies now have shown that a disruption in that diurnal secretion of cortisol is what can cause many of the problems in cortisone, not the absolutely amount, but when it’s released. That’s extremely important. So what’s found in centenarians, for instance, is that the diurnal variation in cortisol is maintained, so even though the cortisol levels are increased in centenarians, the good part is that they’re increased appropriately. They go up in the morning and down at night, and that diurnal variation in many disease states becomes decreased.

You’re saying that a bigger clue of whether or not cortisol is healthy isn’t the amount, but whether it is being released in an appropriate way from morning through night?

RON ROSEDALE:   Right. And in this study they didn’t measure that. They measured urinary 24-hour secretion, which doesn’t—you can’t just measure the total amount of cortisol. They didn’t measure cortisol binding protein, I don’t believe. So it’s not just the amount of cortisol but when it’s released in any of the fatty especially steroid molecules, such as HDL and LDL and testosterone and all the steroids that are derived from cholesterol, which by the way is a precursor for all the steroid hormones, including cortisol and testosterone and estrogen. Cholesterol is not that evil monster that the medical profession is making it out to be, but in fact is a life-giving molecule.

But the metabolites from cholesterol are all kind of a steroid waxy, fatty substance and have to be carried around the bloodstream. They’re carried by binding proteins to make them soluble in the watery environment of the blood. So LDL is low-density lipoprotein and HDL is high-density lipoprotein. These shuttle cholesterol to and from tissues. You have the same type of molecules that shuttle cortisol and shuttle testosterone and shuttle estrogen. For cortisol, they’re called cortisol-binding proteins, and the proportion that is bound to a protein is inactive. It’s only the free fraction that is active. So if you just measure cortisol levels, you don’t know the amount that’s active and the amount that’s inactive. And if you just measure 24-hour secretion, you don’t know when it’s secreted and when it’s not secreted.

In other words, it gives you almost no information. So trying to hang your hat on the fact that cortisol levels were elevated and saying that therefore, their Mediterranean diet is better than a very low-carbohydrate diet is extremely misguided.

Is there a way to measure the kind of cortisol that is in the active form? Did they measure that?

RON ROSEDALE:   Oh, yeah, there’s definitely a way to measure it, and no, they didn’t measure it. You can measure it directly in the blood, or more appropriately, you can measure it in the saliva, which in most cases is an easier way to measure it because then you can easily collect it both in the morning and the evening, so that you can at least get two measurements, and the salivary measurements of cortisol are free fractions, the amount of cortisol that actually got into the saliva, that actually had activity.

And then again, you have to go beyond that, go beyond the assumption that cortisol is bad. It’s not. You need cortisol. Again, it’s an anti-inflammatory. It’s not a pro-inflammatory.

Are you somebody who would give someone a cortisol shot if their hip or their knee was sore?

RON ROSEDALE:   No, I wouldn’t. You don’t want it in super-physiologic doses, typically.

So there are ways that you think that it’s good and ways you think that it’s bad. But when it appears in the blood or the saliva in higher amounts in the right pattern during the day and the night, that generally tends to be an indicator of health, not disease?

RON ROSEDALE:   Exactly. Like any hormone. Insulin is not a bad thing, it’s a good thing. Leptin is not bad, it keeps you alive. You have to get the signal’s message across to the cells. That’s really what you want. You want to cells to listen appropriately, at the appropriate time and at the appropriate location. That’s what is necessary for any type of health.

I wondered also with cortisol, in the case of somebody on a very low-carbohydrate diet who’s eating a lot of fat, which a third of the people in this Harvard study were doing, whether that would affect cortisol levels.  You see, when someone’s not eating many carbs, the body has to send out signals for the body to make its own sugar now and then, just to keep the levels regulated. One way to do that is for the body to send out a cortisol signal, is my guess. Is that correct?

RON ROSEDALE:   That’s correct. One of the purposes of cortisol is as a gluco-regulatory hormone. If sugar levels go low, then cortisol is one of the hormones that will be secreted so that you can raise glucose to a level that the body deems appropriate. The real key is to get that level as low as possible.

But when the body gets to call the shots on maintaining the blood sugar level with something like cortisol, it gets to choose what that level will be?

RON ROSEDALE:   It gets to choose, and over time, and this is another key, the level becomes lower. In the Harvard Study, they didn’t allow enough time for research subjects to adapt to the low carb diet in order to show this effect..

You mean that the level of cortisol over time is likely to go down further if somebody gets even more adapted to a low-carbohydrate, higher-fat diet?

RON ROSEDALE:   Yeah. They only carried out the experimental diets for four weeks. That’s just about enough time to get a person adapted, and not longer. They were measuring cortisol at a time when their tests subjects were not really adapted yet to a very low-carbohydrate diet. You need to partake in that metabolic change much longer, and the set point then for glucose goes down, and therefore the need for gluconeogenesis goes down. But more importantly, there is a metabolic adaptation that will increase the ability to manufacture glucose from other metabolic precursors such as lactates and glycerol in the body, such that the need for the major gluconeogenic pathways is greatly reduced. But that takes quite a few more weeks than they carried the study out.

Your comments makes it sound as though it would be helpful to ask the Harvard Researchers whether the cortisol levels in people on a low-carb, high-fat diet went down more at the end of the four-week period when they were eating low-carb, than at the beginning.

RON ROSEDALE:   That would be, and I didn’t really see how many times the Harvard researchers actually measured cortisol. I don’t know if it was a before-and-after or if there were any intervening measurements. But again, you don’t know necessarily whether it’s a good or a bad thing. As I mentioned, cortisol is increased in all of the parameters that we know that increase health and lifespan in calorie restriction and in centenarians. And I think one can’t ignore that there might be some sort of benefit, then, to increased cortisol. My guess is that that would definitely be true, and my guess is that it is likely due to its anti-inflammatory effect.

Ron Rosedale Likes a Low Carb, High Fat, Adequate Protein Diet

Ron Rosedale, you have been suggesting that the Harvard Boston Hospital study stacked the deck in favor of the Mediterranean diet, and the way that cortisol was measured didn’t reveal some key elements of why an elevated cortisol level might not be an issue.  You’ve said that the Harvard researchers have a vested interest in recommending a Mediterranean style diet.  It’s fair to say that you’re someone who likes to stack the cards in favor of a high-fat, low-carb diet.

RON ROSEDALE:   That’s because I’ve found that to be by far a better diet. I’ve used the Mediterranean diet in the past and didn’t get anywhere close to the results one can get if you just get rid of sugar. There is no biological necessity to eat sugar, and we know all sorts of adverse consequences, secondary to glycation, advanced glycated end products. We know that it increases inflammation in aging, it increases spikes in insulin and leptin, which promote insulin and leptin resistance, and if you increase glucose levels, whether it be by fast-acting glucose or by longer-acting glucose, the so-called resistant starches that they’ve maintained is beneficial on their Mediterranean diet, you accelerate aging. And in fact, we know through Cynthia Kenyon’s study and others, and what I’ve shown in studies, that if you keep glucose levels very low, and only if you keep glucose intake very low, only if you follow a very low-carbohydrate, not a high-protein diet, and a high beneficial fat diet, you can mimic the effects of calorie restriction as far as the laboratory parameters. And that can only be a good thing.

Harvard Study Used HIGH Protein in Low-Carb Branch

RON ROSEDALE:  I also want to mention one thing on this study, that it is quite notable that they put people on a high-protein diet.

The characterization of this diet was that it was an Atkins-style diet that was high in fat and low on carbs. Are you saying that that was actually a high-protein diet?

RON ROSEDALE:   They were putting people on an average of 150 grams of protein a day. That’s two to three times the protein that I recommend for people. And elevated protein has a lot of adverse consequences as far as many different parameters, including inflammation, which could be one of the reasons that they noted an increase, but a non-significant, I should mention, increase in CRP, which is their second so-called adverse effect that they encountered. C-reactive protein is a so-called marker of inflammation, but it’s really a marker of the immune system increasing. It’s like one of the first responders to increase the phagocytic activity, the ability of white blood cells to engulf intruders and clean up debris.

So once again, it’s certainly possible that short-term CRP could go up on a very low-carbohydrate diet secondary to the anti-aging effect, actually slowing the aging. One of the events that take place in calorie restriction and in other genetic modalities that greatly increase health and lifespan in laboratory animals is that you increase something called autophagy, which is the ability of the body to basically clean up garbage. That requires a more active immune system. It’s possible in a short term that you can increase immune activity to increase autophagy so you can get rid of some of the garbage that is poisonous to the body.

But I should mention that long-term, what I’ve seen in people on a very low-carbohydrate diet and what’s seen in calorie restriction is a reduced CRP longer term. After the initial several-week adaptation, I think you’ll see CRP come down. But it also should be noted that what their data showed and many other data showed, including myself, is what will lower leptin the most is a very low-carbohydrate diet, and when you lower leptin, you greatly reduce many different markers of inflammation, including, interleukins, many markers of inflammation. Leptin itself is an inflammatory chemicals. It’s a cytokine.

So other markers, had they been measured, they would have found secondary to lowering leptin, would have been greatly reduced, other markers of inflammation.

So one concern that you have here is, these are markers where in the short term, they can go up for beneficial reasons, and after a person is adapted to a high-fat, low-carb diet, they both tend to go down for again benign, helpful reasons. Another question to ask the researchers would be, did the C-reactive protein levels for the people on the high-fat, low-carb diet tend to start out higher and end up lower after four weeks?

RON ROSEDALE:   Two things. Number one, what they are calling two inflammatory markers, cortisol is not an inflammatory marker. It’s an anti-inflammatory marker. They are misinterpreting cortisol.

You believe that cortisol depends on a lot of other things besides just that number alone?

RON ROSEDALE:   Yeah. And again, cortisol, we know, and it’s being used therapeutically as an anti-inflammatory. It’s not pro-inflammatory, as they’re making it out to be, like an adverse event. It’s not an adverse event. I think they were trying to find some reason to downplay the beneficial laboratory results that were obtained with the very low-carbohydrate diet, even though they style of low-carb diet used much more protein than I would have recommended. Had they used a diet that I recommended, which would have been a much more moderated protein intake, probably a higher beneficial fat intake, and a very low-carbohydrate intake, you would get even far greater beneficial results. I’ve written much about it, and I think you can find on the Internet many adverse consequences of high-protein.

And when they mentioned an Atkins-type diet, that is true. An Atkins-type diet is basically very low carbohydrate and anything else goes. I maintain very strongly that that is not so. It’s not anything else goes. There’s a huge difference between a very low-carbohydrate, high-protein diet and a very low-carbohydrate, low-to-moderate protein diet. There are huge differences in longevity and other metabolic parameters on different metabolic pathways.

The current experts on the Atkins diet, who have written the New Atkins for a New You, are Eric Westman, Jeff Volek, and Steve Phinney. In their current writings about it, and in conversations with them, they would agree with you that you don’t want to have high protein as part of a low-carb diet.

Yeah. They agree with me because I taught them that. They were actually very pro-protein up until a meeting where I spoke at the American College of Bariatric Physicians quite a few years ago that kind of pitted me against everybody else who then was recommending a high protein intake. I showed them quite a bit of literature that high protein was not beneficial. I’m quite happy to hear that they’ve changed their tune since then.

If all of you “low carb” guys are saying that high-protein should not be part of a low-carb diet, then why did the Boston Harvard team use a high-protein diet as their high-fat, low-carb diet?

RON ROSEDALE:   That’s a great question. Again, I think there are so many studies in health and medicine where the experiment is not particularly performed to find some ultimate truths but is performed as a marketing effort. I think they were trying to bolster their recommendation for a higher-carbohydrate, Mediterranean-type diet by the setup of the experiment to begin with, but also then in their conclusion, the data that was forthcoming from their study didn’t support their conclusions. And yet they tried to make it seem, and they popularized through their PR department and all the popular media, that their Mediterranean diet was far healthier than a very low-carbohydrate diet. That is not what their data showed at all.

C-Reactive Protein Differences were NOT significant in Harvard Study

RON ROSEDALE:  Again, on the cortisol levels, the high cortisol is almost synonymous with longevity and health in centenarians and calorie-restricted animals, which are two of the major modalities of aging studies. And the other so-called adverse effect that they’re reporting was C-reactive protein. And they have to emphasize and I have to emphasize that the difference in C-reactive protein between the very low-carbohydrate diet, which was a high-protein diet, and their Mediterranean diet was not significant. It did not approach statistical significance. And yet they mentioned it anyway.

I was listening to National Public Radio today.   The short report that they broadcast said that the inflammatory markers were higher on the low-carb, high-fat diet, and so that’s why the Mediterranean diet wins.  The idea that C-Reactive Protein differences between the three diets wasn’t mentioned in the national report in that group. I haven’t seen that mentioned in the way that you’re mentioning it now. You have a concern that the data were trumpeted in some ways that they didn’t deserve ?

RON ROSEDALE:   It was spun and twisted in a way to make their type of Mediterranean diet look beneficial compared to the very low-carbohydrate diet, which in fact their own data showed had considerably, significantly better metabolic results.

Do you think that if I talked with somebody who is an expert and a fan of high-carb, low-fat diets, say Dean Ornisch, for instance, do you think he would have some gripes about how they did the study?

RON ROSEDALE:   It very well could be. I don’t know.

I don’t know either, but I’m curious whether someone who has an expertise there could look at this and say whether they felt like the low-fat, high-carb diets were fairly represented. I even find myself wondering whether or not the Harvard group could have invited an expert like you or Steve Phinney or Eric Westman to check how they were doing the high-fat, low-carb protocol to see if it was OK. It’s puzzling to me why your views are so different from the kind of diet that they chose.

RON ROSEDALE:   That’s a great question. I think I’ve tried to maybe not be so politically correct in saying why that would be. I think one finds all too often a lack of true wonderment about scientific truths and instead studies are done more for marketing efforts than true science.

 Let’s us do some wondering, then.

RON ROSEDALE:  Great.

There were some other aspects of the hypotheses, the premises and the beliefs going into this study, that were interesting. This study began by saying that lots of people can lose weight, but very few people can maintain that weight loss, and one reason is because it’s hard to keep going when you have an unusual diet that’s supposed to be for your health and everyone around you is eating differently. But the other side of the premise was that people’s bodies change metabolically when they change how they eat, and the ways that their bodies change metabolically and with hormone signaling fight against them being able to keep the weight off. Do you think that’s true?

RON ROSEDALE:   I think it is true short-term. But we know now that there are metabolic pathways that are instrumental in dictating what our wants and desires are as far as what we eat, what we burn, whether we burn fat or sugar and therefore whether we need to eat fat or sugar to sustain our energy requirements.

Do those metabolic pathways make a difference on whether we feel hungry or full or anxious or content with how we’ve been eating?

RON ROSEDALE:   They dictate those things. They don’t just make an impact, they are those things. We know, for instance, that leptin is one of the major hormones, and there are multiple hormones that dictate hunger because of how important it is. Nature knows that the only way a person is not going to overeat is if they’re not hungry. We know now that one of the major defects in metabolism that causes people to overeat is because leptin is not being heard properly, i.e., leptin resistance. I strongly believe that leptin resistance is caused from spikes in leptin secondary to what people have been eating for years causing a down-regulation in the ability of the brain and the hypothalamus in particular to listen to what leptin is trying to say, such that if a person has too much leptin, where normally it would reduce hunger and increase the ability to burn fat, the brain is hearing a different message. It’s hearing too little leptin, even though there’s a lot of it, and thinking that the person might be starving and therefore will increase their hunger and prevent the ability to burn fat properly.

So there’s a disregulation in leptin signaling which we know occurs in almost all overweight and obese people. And the way to correct it, I’ve found, at least 15 years ago now, I think I wrote one of the first books, maybe the first book on leptin and its clinical application to disease, is that you have to eat to maintain a low leptin, and the lower the leptin, the greater the signal. Just like we know that if a person eats appropriately, insulin levels will go down, their serum insulin will go down along with their blood sugar, so that we know that insulin is being heard better and you can alleviate the vast majority of cases of type 2 diabetes by eating a diet that is very low in carbohydrate, not high-protein, just enough protein to meet your needs, which is normally between 50 and 70 grams a day, depending on your size and activity level, and that will keep both insulin and leptin down and improve their signaling.

So even though the levels are coming down, the power of the signal is increasing, and therefore hunger will go down, the person will eat less long-term and they will burn more fat. And that’s really what this study showed. They just don’t want to admit it.

Hunger and Weight Maintenance

One of the premises of this study has been that it’s hard to do prevent hunger from getting out of control, and so people gain weight back. The study hints that it may not be as hard as they thought, but the idea that it’s hard to maintain your weight once your leptin levels have been high and then they go down, that comes from the 1990s, maybe early 2000s, where Rudy Leibel and Michael Rosenbaum out of Columbia had studies of leptin where they believe that they showed very consistently that once somebody has been fat and overweight or obese, if they lose weight, that leptin signal is always going to haunt them and push them to have their weight go back up again.

RON ROSEDALE:   That’s correct, unless you eat a diet that will consistently keep leptin low and you go through a transformation period of several weeks that increases leptin sensitivity. I’m well aware of their study, and they are very wrong in their conclusion, just like this paper was.

You may believe that they’re very wrong, but their conclusions are governing nutritional policy in the U.S.

RON ROSEDALE:   Which is why we are seeing a record number of obese and diabetic people around the world.

Maybe I should call them up and ask them some questions about whether in their studies they ever put someone on a truly high-fat, low-carb, adequate-protein diet after they had lost weight to see if then they would maintain their weight.

RON ROSEDALE:   That would be great, and I think they will say they haven’t, because if they did, they would have seen exactly what I have seen for the last 20 years, that weight loss can usually be maintained, and that maintenance is almost parallel to leptin and insulin levels.

I did talk with one of those scientists many years ago and I think I remember him saying that when people were losing weight, they weren’t hungry, but once they had to be maintaining weight, their hunger came back.

RON ROSEDALE:   And they were “maintaining” their research subjects on a higher-carbohydrate diet.

So when their test subjects were losing weight, they were basically burning their own body fat, so that they were on a high-fat diet.

RON ROSEDALE:   They were burning their body fat and their muscle because they weren’t really putting them on a proper diet. They were putting them on a high-carbohydrate diet that maintained their essentially addiction to burning sugar as a primary fuel. One of the things I’ve said many, many times and really, I think, should dictate all health and nutrition policy, is that the person’s health and longevity is going to be determined by the proportion of fat versus sugar they burn over a lifetime. The more fat you burn, the healthier you’ll be. The more sugar you have to burn, the more unhealthy you’ll be. And that’s your choice in fuels. You can burn sugar or you can burn fat or byproducts of fat metabolism called ketones. If you burn fat and ketones, you’re going to be healthy.

Whether you burn fat and ketones is going to be dictated by hormones, such as leptin and insulin. And those hormones, in turn, are dictated by what you eat. So you have to eat to regulate the hormones that regulate whether you burn fat or sugar, and that in turn will dictate health.

That’s a good thing for people to remember, a helpful thing if they want to try a high-fat, low-carb diet and reasons to stay with it.

Is a Higher Metabolic Rate Healthy?

Getting back to the study, one of its premises is that it’s not a good thing when people lose weight and their metabolism goes down because if their metabolism goes down, it doesn’t take as many calories for them to maintain their body. So one of the measures that this study used for whether people were having a diet that worked for them is whether their metabolism stayed revved up. What do you think about that?

RON ROSEDALE:   I think that really shows an ignorance of metabolism. I hate to put it that way, but it’s true. Again, in calorie-restricted animals and centenarians, one of the few commonalities that is very powerful is that free T3, the active thyroid, goes down, as does body temperature. In other words, the body goes into a more thrifty state so that it can maintain itself longer and healthier.

So the metabolism goes down?

RON ROSEDALE:   It goes down because it’s healthier. It’s not metabolism going up or down, really, that is even relevant. It’s the quality of metabolism rather than the quantity of metabolism. For instance, on a person’s car, you can increase so-called thermogenesis, the metabolism of your car, as indicated by the standing RPMs. In other words, you’re at a stop sign. Would you want high RPMs or low RPMs? You want lower RPMs that are nice and smooth. So let’s say you’re at a stop sign and your car is running rough and it’s stalling out on you. You can go to a shop and one thing they could do is increase the metabolism of your car by increasing the baseline RPMs. In other words, instead of 600 they might put it to 1,000 or 1,200, so that it’s revving high.

What you’ll notice on your car, then, is that the temperature of the car, of the engine, will be hotter. It’s increasing thermogenesis. It’s increasing its heat output.

Does it also mean that it would take more gas to have it go the same amount of miles?

RON ROSEDALE:   It will take more gas to go the same amount of miles, which burns it out, but it also gets far less mileage. So the longevity of the engine will go way down. The mileage, which will dictate basically how long that car is going to live, will go way down. The pick-up of the car, even, will go down. So even though the metabolism is up, the useful energy of that car goes down. And that’s not what we want.

That’s true. I don’t buy a car because I want it to take more gas to get the same amount of miles, and I don’t buy a car because it’s going to burn out faster.

RON ROSEDALE:   No. Most people wouldn’t. In fact, if a person was pulling into a gas station and they could get one of two fuels, and on one gas tank it said, “This gas will cause your car to run hotter and get less gas mileage,” as opposed to the other tank that will say, “This will cause your car to run cooler,” in other words, lower metabolism, “and get better mileage,” which do you think people would get? They would always get the one that gets better mileage and causes their car to run cooler, because they know that’s better.

We operate under the exact same laws of physics. There’s no difference. Science in science. It permeates everything, including humans. And it amazes me how people can go to a health food store and how comments as in this paper talking about increasing metabolism as if it’s a good thing, and then have actually zero knowledge about the baseline science behind it.

It’s often said that it’s a good thing about a diet if it keeps your metabolism revved up, and it’s a bad thing to have metabolism go down. And here you are saying that having some of these indicators of how hot your body is running go down actually means that your body’s just running better.

RON ROSEDALE:   Exactly correct. There’s so much misinformation and myth out there in health and nutrition and medicine in general. This is not new information. I’ve been saying the same thing for 20 years, and one of these days, hopefully the message will get through. I just hope I’m alive to see it.

Here you are where you and Eric Westman and Steve Phinney and Jeff Volek see the same way on protein now. That’s something that has evolved over time. I think it was Isaac Asimov, the science fiction writer, who pointed out that the world really is sort of flat, because it’s only a tiny bit round. But that small degree of roundness is enough to make the whole world round. It’s taken time to take all of those different ideas about roundness and flatness to refine them into what our world looks like. Maybe it’s the same way with nutrition.

RON ROSEDALE:   Certainly we hope so. The major problem these days, which is quite different from Isaac Asimov’s time, is that knowledge now can be disseminated very easily. There’s no excuse to not be up to date. All you have to do is go on the Internet, and read. The problem is that there is less of a motive to actually learn science as there is a profit motive. That’s the major impediment to the advancement of science. It’s really unfortunate.

I’m not making any money by talking with you, and I don’t know that you’re making any money by talking with me, so let’s ask another question of wonderment. You said that having a metabolism be revved up just to make it hotter is not so good. But sometimes metabolism can go up for good reasons, and since you were talking about cars, I’m picturing the difference between a car that is running efficiently on the fuel that it has and getting lots of miles to the gallon and a car that doesn’t use a lot of gallons of gas because it’s too sluggish to run at all. I guess that that kind of slow metabolism in a car is not a good, healthy metabolism. Is there a kind of metabolism that could be measured in people where it indicates that their bodies are efficient, but also that their bodies have access to energy and can use it?

RON ROSEDALE:   Definitely. Certainly if your metabolism is very low, and probably it’s at its lowest point when you die, that obviously wouldn’t be good, it would be one extreme. What you want, basically, as I mentioned, is the ability to burn fat. That can be easily determined by many different laboratory parameters. You can measure insulin, leptin, blood glucose, thyroid, especially free T3 or reverse T3, which actually should go up. It’s another misconception that reverse T3 indicates a disease state. It does not. It’s one of the ways that your body has of regulating thyroid activity.

There are many different metabolic markers that can be measured to indicate a healthy metabolism as opposed to a deranged metabolism that is unable to perform. The difference is, for instance, there’s a lot of misconceptions about thyroid. We know in calorie-restricted animals and in very low-carbohydrate diets, in the vast majority of modalities that increase lifespan and health in laboratory animals, the active thyroid, free T3, goes down. So many people use that as an excuse, really, or a reason that very low-carbohydrate diets are detrimental, saying that it causes hypothyroidism. And again, that’s really misguided knowledge. That’s not hypothyroid. The TSH, thyroid-stimulating hormone, from the pituitary does not go up. In other words, it’s a purposeful down-regulation of thyroid to allow the body to run in a healthier, more beneficial state, not because it has to, but because it wants to.

Whereas in hypothyroidism, what you’ll see is the body trying to make more thyroid but it can’t. So the TSH is high while active thyroid is low. That’s a big difference if your body wants higher thyroid but can’t do it, as opposed to the body purposefully lowering the thyroid because it’s healthier to do so.

Want versus can’t. That’s a pretty big difference. You’re implying that when it comes to the metabolism of a person, if a person’s body is running hot all the time, that’s different from a body where when a body needs to get extra energy it can. Going back to the study, do you think the higher metabolic rate of the people on the high-fat, low-carb diet was because their bodies were running better or because they had too much protein increasing the metabolism?

RON ROSEDALE:   One of them definitely had to do with the protein content. We know that protein is very thermogenic. It’s unhealthy, and the body will essentially be forced to burn excess protein, and in this particular case there were probably 100 grams of excess protein a day, which is a huge amount. That’s number one. Number two is that leptin went down considerably, more in the very low-carbohydrate diet, even with the high protein. It would have gone down further, I believe, if it hadn’t been a high-protein diet. But even with the high-protein, very low-carbohydrate diet, leptin went down the most. When it goes down over time, it improves the signaling and it improves leptin sensitivity, which will allow your body to want to start burning off excess fat. It’ll notice then, “Whoa! We’ve got way too much fat to be healthy.” In our ancestral times, carrying around extra fat would be a death sentence, because any animal chasing a group of people would go after the fattest one that couldn’t make it up the tree, and also the fat person wouldn’t be able to hunt and gather very well to even feed themselves.

So being fat in our ancestral history was very disadvantageous. Your body doesn’t want you to be fat. One of the major regulatory methods that the body has to keep a person healthy and prevent fatness is proper leptin signaling. So by going on a very low-carbohydrate diet that does lower leptin more than any of the other diets, even in this study, you improve leptin sensitivity, so you actually improve the signaling more, and you’ll end up burning more fat, which will at least temporarily, until you burn off the excess fat, increase your metabolism, if you want to look at it as such.

Then are you glad this study measured leptin?

RON ROSEDALE:   Yes, I’m glad it measured leptin. I’m glad it measured insulin and glucose and some of the other metabolic markers. It would have been quite a travesty had it not.

So there are some things that you’re glad they did in this study, but there are some areas where you have questions. I will see if I can ask some of these questions and share with you the answers when I get them.

RON ROSEDALE:   That would be great. As I say, it wasn’t a bad study per se. I think the conclusions that were drawn were a bit misguided, and I think what they were trying to do is essentially reach for straws to try to support a diet that they’ve been supporting now for years.

And you have some wishes that they had done a little bit different choices in the study, for instance, how they measure cortisol is a big one, and the timing of when they measured C-reactive protein also so that they could see whether there were changes over time. And you sure wish that they hadn’t used so much protein for the high-fat, low-carb branch of the study.

RON ROSEDALE:   That would have been, I think, far superior. For instance, on the CRP, had they just been looking at it from an objective standpoint and not trying to support one diet over another, all they would have said was that there was no statistically significant difference. If you’re going to use statistical significance the way it’s typically done in these studies, you can’t use it for certain parameters and not for others.

If you ever do a study of a high-fat, low-carb, adequate-protein diet, do you think you’d like to invite these researchers that like the Mediterranean diet to look over your shoulder so that they can give some input ahead of time?

RON ROSEDALE:   You really want the truth on that?

[laughs] Sure!

RON ROSEDALE:   The real truth is, no, because I know that they don’t know a tiny fraction of what I know about metabolism. I don’t think there’s any input that they could give me that would be worthwhile.

I’m thinking in terms of how if you have a lot of people looking at the elephant from their different perspectives, if they talk about it first to say what they’re looking for and how to sketch in the picture, it does sound like, from your perspective, the Harvard group overlooked some obvious things on how to make this be a better study. And whether that was intentional or not is hard to say.

RON ROSEDALE:   I think not only did they overlook some things as far as what they measured, but I think the biggest detriment was the perhaps lack of knowledge in interpreting the data. Perhaps they don’t know that high cortisol is not necessarily bad but in fact is seen in centenarians and calorie-restricted animals and is actually viewed by many as one of the reasons that they live longer, due to its anti-inflammatory effect. So either they didn’t know that, or they purposely ignored that, which is something that shouldn’t have been done.

I’ll look forward to talking with them.

Thanks to Sandy Grabowski for the transcription.   sandy (@) csd.net

Wonderful article brought together by Shelley Schlender, thank you for your continue great work and dedication to the truth.  Learn more about Shelley and her passion for exposing the truth of health, www.meandmydiabetes.com.

The post New Harvard Study comparing diets. appeared first on Ron Rosedale, M.D..

I (Dr. Rosedale) have been talking about this subject matter for over 20 years. It is wonderful that Tony Robbins has recognized this and has taken an interest in the truth of health. I hope you will enjoy and learn from my article that I wrote for Tony as my response to an LA Times article that typifies how frequently medical ‘science’ is falsely interpreted.

“Why dieters tend to regain weight”..

“A study shows that various hormones conspire to make us hungrier for at least another year, telling us to eat more, conserve energy and store fuel as fat. The report, published Wednesday in the New England Journal of Medicine, helps explain why roughly 4 in 5 dieters wind up gaining back lost pounds within a year or two of losing them — and, sometimes, pack on a few extra pounds for good measure… It is a close look at the disheartening pattern: In the wake of weight loss, ‘multiple compensatory mechanisms’ spring to life, the study illustrates, and work together to ensure that weight loss is reversed quickly and efficiently.”

But does the study really show that weight loss causes these ‘compensatory mechanisms’? …or is it a kind of diet that almost everyone is eating, and that doctors and nutritionists alike have been telling everyone to eat for over half a century, that forces thosehormones and ‘compensatory mechanisms’ to ensure that we get fat, diseased, and stay that way?  And is there another diet that might allow us to use these same mechanisms for our benefit instead to burn fat instead of detriment to store too much?  The answer to both those questions is yes.

To summarize this study, participating overweight and obese human subjects had several appetite regulating hormones measured, and were then placed on a very calorie restricted (500 calorie) diet for 10 weeks, after which they (predictably) lost on average 28 lbs and the same hormones were rechecked. The participants were then asked to voluntarily adhere to a less, though still somewhat restrictive, low fat diet with regular dietary counseling for a year. An average of 11 lbs was regained.  It was also found that hormones such as leptin that reduce appetite were decreased, and this decrease was partially maintained for a year as was increased hunger.  It was concluded that the decrease in appetite suppressing hormones was causing increased appetite and is the cause of weight regain after dieting (so-called yo-yo dieting). It was further concluded that because of this, multiple drug therapy may be necessary.

Like happens so much in nutritional research and medicine in general, the conclusions presented in the article represent a very simplistic, and false, view of how the body…and life…works (and that just so happens to greatly benefit the massive profits of pharmaceutical companies by treating symptoms rather than the root disease).

For a deeper understanding of the major so-called ‘compensatory mechanism’, a history and summary of the hormone leptin is in order.

The Ob mouse is a strain of mouse that has a genetic mutation that makes it obese and unhealthy.  It had been used for almost half a century as a research model of obesity, though the reason that it was obese had eluded scientists.  This changed when, in 1994, Jeffrey Friedman of Rockefeller University discovered that this mouse lacked a previously unknown hormone called leptin, and when it was injected with leptin it became thin, vibrant, and very healthy within weeks.  This made headlines around the world, “The Cure for Obesity Found” and pharmaceutical companies started tripping over themselves with trillion dollar signs in their eyes to be the first to genetically manufacture leptin on a large-scale.  This did not last long, for when people were tested for leptin it was found that, unlike the Ob mouse, they did not lack leptin; on the contrary almost all overweight and obese people have excess leptin.  These people were “leptin resistant” and giving extra leptin did little good.  The financial disappointment was extreme and scientists working for pharmaceutical companies said that leptin was no longer financially worth pursuing.

To make money in medicine one needs a patent and this generally means remedies which are not commonly or easily available — that are not natural.  This illustrates two extremely unfortunate principles in modern medicine; only those therapies that will make lots of money (generally for the pharmaceutical industry or hospitals), ever get pursued and thus taught to physicians (since most of medical education after medical school takes place by pharmaceutical corporations), and these therapies, almost by definition, will be unnatural.  This inhibition of extremely important knowledge is not only unfortunate, it is deadly, and is exemplified by how few people, including doctors, know much about leptin, let alone how to control it to greatly improve health. I would consider leptin, along with insulin, to be the most important biochemicals in your body that will determine your health and lifespan, and they are not controlled by drugs. They are controlled by what you eat.

What exactly is leptin?  Leptin is a very powerful and influential hormone produced by fat cells that has totally changed the way that science (real science, outside of medicine) looks at fat, nutrition, and metabolism in general.  Prior to leptin’s discovery, fat was viewed as strictly an ugly energy storage depot that almost everyone would prefer to get rid of.  After it was discovered

that fat produced the hormone leptin (and subsequently it was discovered that fat produced other very significant hormones), fat became an endocrine organ like the ovaries, pancreas and pituitary, influencing the rest of the body and, in particular, the brain.  Leptin, as far science currently knows, is the most powerful regulator that tells the brain what to do about life’s two main biological goals: eating and reproducing.  It takes lots of fuel to make babies.  Just ask any pregnant mom-to-be at the supermarket staring wide eyed at the ice cream.  Your fat, by way of leptin, tells your brain whether you should be hungry, eat and make more fat, whether the time is nutritionally ripe to make babies, or (along with insulin) whether to “hunker down” and work overtime to maintain and repair yourself to reproduce at a future more energy available time. I believe I could now make a very convincing and scientifically accurate statement that that rather than your brain being in control of the rest of your body, the most ancient and critical parts of your brain are, in fact, subservient to your fat — and leptin.

In short, leptin is the way that your fat speaks to your brain to let your brain know how much energy is available and, very importantly, what to do with it.  It not only takes lots of energy to make babies, it takes a lot of energy to keep you healthy.  Therefore, leptin may be “on top of the food chain” in metabolic importance and relevance to disease.

It has been known for many years that fat stores are highly regulated.  It appears that when one tries to lose weight the body tries to gain it back.  This commonly results in “yo-yo” dieting and in scientific circles one talks about the “set point” of weight. It had long been theorized that hormones must exist that determine this.  Science points now to leptin as being the most powerful and influential.

Nature knows that to make someone obtain more energy if necessary, it must make that person hungry.  Likewise, nature knows that the only way to not eat too much, to not make too much fat, is to not be hungry.  Asking somebody to not eat, to just use willpower even though they might be hungry, in other words “to count calories” is asking the near impossible.  Hunger is way too powerful a force that has been instilled into us by nature almost since life began to make us eat. The only way to eat less in the long-term is to not be hungry, and the only way to do this is to control the hormones that nature designed to regulate hunger.  We must control leptin to control hunger, health and life.

For our ancestors, life was a time of feast and famine.  We needed to store some fat for the times of inevitable famine. However, it was equally dis

advantageous to be too fat.  For most of our evolutionary history, it was necessary to run, hunt and gather, and to avoid being prey. If a lion was chasing a group of people, who would it chase?  It would catch, and eliminate from the gene pool, the slowest runner and the one who could not make it up the tree — the fattest one that would also give that lion the most energy bang for its having to get-up-and-exercise buck.

Thus, it is so critical that fat storage or burning be highly regulated, that this is  done via several hormones, the most significant
again being leptin. When leptin levels are low, it is supposed to signal an area of the deep brain in the hypothalamus that you have too little fat, and if there is a bit of a famine you’ll be a goner.  This will override most any other thought, and you will be made to be hungry, and your prime directive as instilled in you by millions of years of evolution will be to find food, eat, turn that food into fat, and save, not burn, the fat that you’ve got.

On the other hand, if a person is getting too fat, the extra fat produces more leptin which is supposed to tell you that there is too much fat stored, lions are being tempted, more fat should not be stored, and the excess needs to be burned. The key words there are “is supposed to”.  Leptin must function properly… and there are no drugs that will make this happen, now or in the foreseeable future.

Insulin is another hormone, one of whose primary functions is to regulate energy stores.  Its effect on blood glucose is merely a side effect of this.  I first spoke of the importance of insulin in health and disease almost 2 decades ago, and I am even more convinced now.  Aside from its obvious role in diabetes, it plays a very significant role in hypertension, cardiovascular disease, and cancer.  However, new research is revealing that in the long run glucose and therefore insulin levels may be largely determined by leptin.

It had been previously believed that the insulin sensitivity of muscle and fat tissues were the most important factor in determining whether one would become diabetic or not.  Elegant new studies are showing that the brain and liver are most important in regulating a person’s blood sugar levels especially in type 2 or insulin resistant diabetics.  It should be noted again that leptin plays a vital role in regulating the brain’s hypothalamic activity which in turn regulates much of a persons “autonomic” functions; those functions that you don’t necessarily think about but which determines much of your life (and health) such as thyroid levels, body temperature, heart rate, hunger, the stress response including adrenal function and cortisol action, fat burning or storage, reproductive behavior, and newly discovered roles in bone health (osteoporosis), autoimmune diseases (MS), even playing a dominant role in what’s considered insulin’s primary domain; blood sugar levels. This is because recent studies reveal leptin’s importance in directly regulating how much glucose the liver manufactures (gluconeogenesis).  How many doctors treat diabetes by regulating leptin?  The sad truth is, almost none.

Leptin not only changes brain chemistry to do nature’s bidding, it can also “rewire” the very important areas of the brain that control hunger and metabolism, especially in the very young and even in a fetus.  I believe that it was the first chemical in the body that had been shown to accomplish this “mindbending” event. Thus a future mom can pass on the predilection for her child to become obese and diabetic depending on what the mom eats that effects leptin.

Many chronic diseases are now linked to excess inflammation, such as heart disease and diabetes.  High leptin levels are very pro-inflammatory, and leptin also helps to mediate the manufacture of other very potent inflammatory chemicals from fat cells that also play a significant role in the progression of heart disease and diabetes. It has long been known that obesity greatly increased risk for many chronic diseases, but no one really knew why.  Leptin appears to be that missing link also.

Leptin will not only determine how much fat you have, but also where that fat is put.  When you are leptin resistant, you put that fat mostly in your belly, your viscera, causing the so-called “apple shape” that is linked to much disease.  Some of that fat permeates the liver, impeding the liver’s ability to listen to insulin, and further hastening diabetes.  Leptin plays a far more important role in your health than, for instance, cholesterol, yet how many doctors measure leptin levels in their patients, know their own level, even know that it can be easily measured, or even what it would mean?

Leptin appears to play a significant role in the so-called “chronic diseases of aging”.  Could it perhaps affect the rate of aging itself?  Scientists who study the biology of aging are beginning to look at that question.  As mentioned previously, there are two drives that life has been programmed, since its inception, to fulfill, succeed at, and succumb to.  These are to eat and to reproduce.  If every one of our ancestors had not succeeded in doing these, we would not be here, you would not be reading this, and I wouldn’t have written it.   All of your morphological characteristics from your hair to your toenails are designed to help you succeed at those two activities.  That is what nature wants us fundamentally to do.

It is important to know what mother nature wants. Otherwise, she can get downright ornery.  Nature does not necessarily want you to live a long and healthy life, but instead wants you to perpetuate the instructions, the genes that teach the progeny how to perpetuate life.  Even so-called “paleolithic” diets, though undoubtedly far better than what is generally eaten today, were not necessarily designed by nature to help us live a long and healthy life but, at best,  to maximize reproduction.  Nature appears to not care much about what happens to us after we have had a sufficient chance to make babies and get them on their feet. That is why we die.  But it is vital to nature that we do stay healthy long enough to make babies to perpetuate the instructions of life, and therein lies the rub.  Nature gives us clues about how to stay alive and healthy.  And that brings us once again to fat– and leptin.

Energy was, and always will be, a coveted commodity.  Nature, and evolution hates wasting it.  It makes no sense to try and make babies when it appears that there’s not enough energy available to successfully accomplish that goal.  Instead, it seems that virtually all living forms can “switch gears” and direct energy away from cell division and reproduction and towards mechanisms that will allow a life to “hunker down” for the long haul and thus be able to reproduce at a future more nutritionally opportune time.  In other words, nature will then let you live longer to accomplish its primary directive of reproduction.  It does this by up regulating maintenance and repair genes that increase production from within the cells, of antioxidant systems, heat shock proteins (that help maintain protein shape), DNA repair enzymes, and garbage collection (called autophagy).  This is what happens when you restrict calories (without starvation) in animals, that has been shown convincingly for 70 years to greatly extend the life and health span of many dozens of species.

Thus, there is a powerful link between cellular reproduction, energy stores, and longevity.  Genetic studies in simple organisms have shown that that link is at least partially mediated by insulin (which in simple organisms also functions as growth hormone), and that when insulin signals are kept low, indicating scarce glucose availability, maximal lifespan can be extended– a lot; several hundred percent in worms and flies, and even doubling the lifespan in some mammals.  Glucose is an ancient fuel used even before there was oxygen in the atmosphere, for life can burn glucose without oxygen; it is an anaerobic fuel, kept around today for just that purpose; fight or flight emergencies.  The use of fat as fuel came later, after life in the form of plants soaked the earth in oxygen, for you cannot burn fat without oxygen.  The primary source of energy stores in people is fat by far, as many unfortunately are all too aware of.  The primary signal that indicates how much fat is stored is leptin, and it is also leptin that allows for reproduction, or not. It has long been known that women with very little body fat, such as marathon runners, stop ovulating.  There is not enough leptin being produced to permit it.  Paradoxically, one of the first pharmaceutical uses of leptin was approved to give to skinny women to allow them to ovulate and get pregnant.

To summarize thus far; both insulin and leptin work together to control the quality of one’s metabolism and, to a significant extent, the rate of metabolism.

Metabolism can roughly be defined as the chemistry that turns food into life, and therefore insulin and leptin are critical to health and disease.  The purpose of insulin goes way beyond the control of blood sugar. It works mostly at the individual cell level, telling the vast majority of cells whether to burn or store fat or sugar and whether to utilize that energy for cellular division/reproduction (that, when too loud, can lead to cancer) or for maintenance and repair (youth and longevity).  In this way it actually helps to control the rate of aging, and therefore the chronic diseases of aging such as heart disease, diabetes, and cancer. It is so critical to life that is found in virtually all animal life, and has apparently been evolutionarily conserved all the way back to worms and beyond.

Leptin, on the other hand, controls energy storage and utilization by the entire republic of our 15 or so trillion cells allowing the body to communicate with the brain about how much energy (fat) the republic has stored, and whether it needs more, or should burn some off, and whether it is an advantageous time nutritionally-speaking for the republic to make new baby republics.

But for leptin to properly regulate these all-important mechanisms critical to life and health, leptin has to be heard, and if the brain and body cannot properly hear what it is trying to say, people become so-called “leptin resistant”…and sick; obese, diabetic, heart diseased, osteoporotic…not happy campers.

In part 2 we dig even deeper…

The post A Closer Look At What Really Is A Disheartening Pattern…Medicine Itself.…as revealed by a recent LA Times article… Part 1 of 2 appeared first on Ron Rosedale, M.D..

‘All Things Leptin (Leptin 101)’ | Dr. Ron Rosedale Come join us and hear all about Leptin live with Dr. Ron and Jimmy Moore. If you have a question about leptin that you would like for Dr. Rosedale to address, then feel free to send it to the email below, e-mailing your name, question, and put in the subject line “Dr. Ron Rosedale” to AskTheLowCarbExperts@gmail.com. You can also ask your question LIVE on my show by calling (712) 432-0900 or Skype the show for FREE by calling the username freeconferencing.7124320900. Whether you call or Skype, be sure to use the access code 848908. http://www.askthelowcarbexperts.com/2012/01/2-all-things-leptin-leptin-101-dr-ron-rosedale/

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Ron Rosedale , Sunday, November 20, 2011

What’s the big deal about 100 grams of carbohydrate from starch? That’s 1 and 1/2 large baked potatoes, or 2 cups of cooked rice.  Paul Jaminet, an astrophysicist from Harvard with a strong interest in health and diet, believes that these so-called “safe starches” are healthy, and that if these are not consumed, one might experience what he calls “a glucose deficiency”. I do not.  We have been going back and forth on different blogs debating this.

I believe, quite simply, that all sugars, and foods that convert into sugar, will have a detrimental effect if eaten, and therefore the fewer non-fiber carbohydrates that a person has, the better, and that the difference should be made up by consuming more beneficial fats and oils.  Besides that, our diets are fairly similar in that they are both, compared with a standard diet, higher in fat and lower in carbohydrates.   My view is considered extreme by some, including many in the ‘safe starch’ camp who do not believe that glucose should be looked upon as that detrimental.   I also realize that not eating any foods that can convert into glucose is, from a practical sense, impossible.   I recommend that people have all the vegetables that they want, except for the overly sugary ones such as corn and beets.  This makes our diets that much closer.  Then why is this debate such a big deal?

One may think that a bowl of rice difference in carbohydrate per day in a diet is a small difference, and perhaps it is, but I also believe that that small difference can make a big difference, especially in those with overt diseases such as diabetes and heart disease.  Furthermore, I believe that we all have, at least some degree, corruption in insulin and leptin signaling, that lie at  the heart of the chronic diseases of aging such as (type 2) diabetes, cardiovascular disease, osteoporosis, obesity, and even many cancers, and therefore everyone can and should benefit from an optimal, not just better, diet.  I had written a book a number of years back entitled The Rosedale Diet that talked about the connection between insulin, leptin, and the diseases of aging, especially obesity.  I believe that diet to be the most scientifically advanced diet in the world, that has been shown to mimic the effects of calorie cutting on health and youthful life extension, without having to even think about cutting calories.

There are three major reasons why I believe it is very important to carry this discussion forward as far as possible. Firstly, I feel that what a person eats is instrumental in determining health. Secondly, I feel that it is extremely important for people to know the truth in science, whether or not it is “politically correct”, or, as Al Gore has stated “inconvenient”.  This way they can make their own educated decisions about what to eat and whether it is “worth it”.  This debate is about what constitutes an optimal or“perfect health diet” that is the name of Jaminet’s book.  If one wants to deviate from that and have a few more likely subclinical ramifications such as glycated molecules, or resistant receptors, to enjoy a bowl of rice, that is up to them. I just do not want that person to think it is healthy to do so. It should be looked upon as we view a piece of chocolate cream pie; unhealthy, but we want it now anyway, and not that we are biologically better off for having eaten it. The point is that there is no such thing as a glucose deficiency or a healthy need to eat starches. If one wants to endure a bit of tolerable biological harm for some momentary pleasure, that’s great, but the person should know what he/she is doing. I drive occasionally without a seatbelt, but I do not want anyone telling me that this is safe.  If there is some unbelievably great bread at a restaurant, I might have a small bit, and savor it, not because I am deluded into thinking it is healthy, but because I am willing to take the risk.

The third reason is less philosophical and more basic scientifically.  I believe that many venues of science, from basic physiology to the biology and genetics of aging point to a simple, but very powerful statement concerning health, that I have stated for many years and has yet to be disproven. That is; one’s health and lifespan will be determined by the proportion of fat versus sugar that one burns over a lifetime. The more fatty acids and ketones from fat that you burn, the healthier you will be and the longer you will likely live.  The more glucose that is burned as fuel, the more unhealthy you will be, the faster you will age, and the sooner you will likely die.. This, of course, is predicated on not getting hit by a semi truck. There are no absolutes.  It is the chance of disease or health that I want to swing in our favor.

This brings us back to that bowl of rice that is the basis of the difference of Paul’s and my diet. That rice consumption spread throughout the day may, at least for a significant part of that day, prevent one from burning fat.  Also, the biochemical and hormonal basis of the extreme health and longevity advantages of calorie restriction that has been shown for over 80 years is being uncovered, and it appears we can use that knowledge applied to diet without calorie restricting to experience the same or similar benefits (that is what I’ve done with The Rosedale Diet).  Once again, eating that bowl of rice may undo that powerful effect.

There appears to me to be, not a point of diminishing returns by further reducing carbohydrate consumption (without increasing protein consumption, but by increasing beneficial fats and oils), but a point of accelerating returns the lower one goes below that 100 g of glucose consumption.

This debate started  on Jimmy Moore’s fine blog where paleo and low-carb luminaries give their opinion for or against safe starches that was followed by a post on that blog by Jaminet, that was then followed by an even more extensive rebuttal on Jimmy’s blog by me.  Jaminet then followed with a long reply on his blog and this was all summarized in Joe Mercola’s extremely popular newsletter just before Thanksgiving.  I am now replying here to Jaminet’s last blog.  Did you follow all that? No matter.

The debate continues.  My rebuttal to Paul Jaminet’s last blog espousing the benefits of “safe starches” follows.  Paul has been a gentleman throughout this discourse, and I only can hope to follow suit. I hope that no offense is taken, and that the effort at education for both the audience and myself is what shines through.

We very much wish to extend our appreciation to Joe Mercola, Jimmy Moore , and Paul Jaminet for their active participation, promotion and dissemination of the discussion from their websites. We hope you find this debate both enjoyable and educational.   We Look forward to hearing your thoughts and opinions.

I start with Paul Jaminet; “Dr Rosedale argues that glucose is toxic, so we should want to have less of it in our bodies; and that low-carb diets deliver less of it. He cites a lot of papers on the relationship between blood glucose levels and health, and uses blood glucose levels as a proxy for the level of glucose in the body.”

The studies presented previously on glucose levels and health are to be taken as a whole to show that there is no threshold for a safe level of blood glucose that Paul has based his ‘safe starch’ recommendations on; no more, no less. That glucose can be toxic is very well known, however it is the effect of glucose on hormonal signals that is the most important.

Jaminet continues, “Two basic matters are at issue: (1) What blood glucose level is best for health? (2) Which diet will generate those optimal blood glucose levels?”

I have said often that we must get to the root of a problem, and that would certainly pertain to this discussion. I believe that the issues stated above are not the root issues that I have frequently referred to in the prior posts. The issue does not have much to do with blood glucose levels per se, but much more to do with the effects of glucose on nutrient signaling, in particular leptin and insulin.

As I have also so often stated, all disease is a disease of communication. This is particularly true with biological illness, but also happens with any form of communication, including written.  There appears to have been a miscommunication resulting in a misunderstanding of what the primary issue(s) is (are).  This must be clarified to arrive at appropriate answers.

The fundamental claim by Paul, as far as his diet is concerned, is that ‘safe starches’ are, well, safe, and do no harm and in fact are healthy to include to prevent what Paul terms a ‘glucose deficiency’.

So, we must keep that in mind as the major point of Jaminet’s argument. Paul’s new point above, “What blood glucose level is best for health?” circumvents the ‘safe starch’ threshold of damage issue, perhaps admitting that there is none, and now essentially asks, what levels of glucose might be the most ‘tolerably harmful’, that I had coined in the last post. This is not just a play on words. It rightfully acknowledges that glucose will cause some degree of damage at virtually any level, as I had previously maintained, and now puts the onus of health on the repair of that damage.

This is as it should be. In other words, the fundamental question should be stated as such;

Is there a diet (Rosedale’s or Jaminet’s) or glucose (starch) intake that can better maximize the repair/damage ratio that life, health, and youthful longevity depends on, admitting the inevitability of damage from glucose at any level? It is important to recognize that this is not just dependent on baseline levels of glucose, but more on the effects of the repeated glucose spikes that are known to occur from eating starches, ‘safe’ or otherwise, on critical hormones, particularly insulin and leptin, that ‘sense’ the amount of glucose and powerfully adjust the genetic expression of repair and the longevity phenotype depending on perceived nutritional circumstance.

I give a summary and conclusion near the end of this article that answers this very important question that is critical to determining an optimal diet.  Those wanting the ‘Cliff Notes’ version of this rather long post can go directly there.  Those wanting more details and my latest full rebuttal to Jaminet’s latest ‘safe starch’ arguments, read on.

Let’s see if Jaminet addresses this primary repair/damage ratio question.

From here I will comment (in black) after passages from Paul’s last blog (in red). Some links and more relevant statements from studies will be in blue.

Let’s look at what the evidence shows.

What Blood Glucose Level is Best for Health?

In my [Jaminet's] main reply I had written: What is a dangerous level of blood glucose?

In diabetics, there seems to be no detectable health risk from glucose levels up to 140 mg/dl, but higher levels have risks… In people not diagnosed with diabetes, there is also some evidence for risks above 140 mg/dl. 

Dr Rosedale seemed to feel that this was the weakest point in my argument, and directed his fire here. My statement was a description of what the scientific literature shows, and the adjective “detectable” carries a lot of weight here. To refute my statement, you would have to find study subjects whose blood glucose never goes above 140 mg/dl, and yet show health impairments attributable to glucose.

… and many studies have been found that show that, at least for a short period of time, damage from glycation and other adverse molecular events occur with far lower blood glucose.  Jaminet has admitted as much by stating below, “the number of glycation reactions may be proportional to the concentration of glucose, and if glycation products are health damaging toxins then toxicity may be proportional to glucose levels..”

Indeed, glycation events have been shown to be very damaging to health. On the other hand, to support Jaminet’s claim, even if it were true that glucose must rise above 140 to cause damage and that therefore his higher carbohydrate diet is ‘safe’, one would have to show that in everyone eating Jaminet’s diet, blood sugar never went above 140. Obviously, this cannot feasibly be shown, so one has to use the best science available to extrapolate most accurately. All human studies pertaining to health and longevity are inferences and not proofs as, I’m sure Jaminet will agree, it is not feasible to carry these experiments out lifelong in people.

It is true that the word “detectable” carries a lot of weight when it comes to health risk.  For instance, if one is just looking for a person to drop dead in the next couple of hours after consuming high glycemic starches, then in most cases the risk of glucose would not be detectable. But not in all;

When speaking of his research linking glucose spikes to endothelial dysfunction;

“The Acute Effect of Various Glycemic Index Dietary Carbohydrates on Endothelial Function in Nondiabetic Overweight and Obese Subjects”

J. Am. Coll. Cardiol. 2009;53;2283-2287

Dr. Shechter states, “..doctors know that high glycemic foods rapidly increase blood sugar. Those who binge on these foods have a greater chance of sudden death from heart attack. Our research connects the dots…”

However, as one looks deeper to detect adverse effects from raising insulin, leptin, or glycation, then yes, there would be detectable levels of health risk from even a single glucose excursion.  In the last post I cited studies showing such risk.

Dr. Rosedale argues there is no threshold separating safe from harmful levels of glucose, because glucose acts as a toxin at all concentrations:

[Dr. Rosedale states]; “I will spend a fair amount of time and show a fair number of studies to show that there is no threshold. Very simply, the higher the blood sugar rise, the more damage is done in some linear upward slope.”

I emailed Ron to make sure that he really did mean there was no threshold, so that glycemic toxicity begins at 0 mg/dl. He replied:

[Dr. Rosedale]; “I mean the former; that glucose will cause some damage when above 0 mg/dl … obviously a moot point and theoretical when glucose very low and incompatible with life and likely a minute amount of damage when that low. At any level of glucose compatible with life some more meaningful degree of glycation, hormonal response and genetic expression will take place. We will always want/need to repair the damage done to stay alive, but with age the repair mechanisms become damaged also. Eventually damage outdoes repair and we “age”, acquire chronic disease, and die.”

Ron’s view can be graphed like this:

This view makes sense as a matter of molecular chemistry: the number of glycation reactions may be proportional to the concentration of glucose, and if glycation products are health damaging toxins then toxicity may be proportional to glucose levels.  Good graph Paul; thanks.

The trouble with this is that it doesn’t really get at what we want to know: what blood glucose level optimizes human health?

Actually, what we really want to know is what level of glucose consumption optimizes human health. The consumption of glucose causes a much wider range of effects than just affecting baseline, fasting blood glucose. It causes large excursions in blood glucose temporarily at least. It effects nutrient signals that are perhaps the most powerful hormones in the body that detect nutrient levels, and have an extremely powerful effect on energy use and storage and genetic expression of health (or not), as I discuss more later.

If we change the y-axis so that it doesn’t measure glycemic toxicity, but rather overall health of the human organism, then the shape of the curve is going to change in two major ways:

First, in translating toxicity to its impact on health, we have to account for Paracelsus’s rule: “the dose makes the poison.” The body can readily repair small doses of a toxin with no ill effect – possibly even a hormetic benefit – but large doses of a toxin multiply damage exponentially and can prove fatal. So the impact of a toxin on health will not rise linearly, but non-linearly with a steeper slope as one moves to the right.

Second, we have to account for the fact that glucose has a role as a nutrient. As Ron himself says, having too little blood glucose is “incompatible with life.” So low blood glucose – depriving us of the benefits of normal levels of this nutrient – is a catastrophic negative for health. This means that the left side of the curve needs radical adjustment.

With these two changes, our graph becomes something like this:

It now has a U-shape.

I must point out, as Paul did, that it is not the previous graph that has changed. The prior graph remains unchanged. This is now a completely different graph with a totally different y-axis. The prior graph remains valid and shows detriment with increasing glucose.

Jaminet does bring up the matter of repair here, “The body can readily repair small doses of a toxin…” but I don’t believe this is discussed further by Jaminet, as he focuses, as we have done previously, on risk of damage.  However, the issue of repair is paramount.  Not only is the damage that life encounters somewhat variable, but the ability of a life to repair that damage is also quite variable, and depends to a large extent on genetic expression of repair mechanisms, such as intracellular (from within the cell; not from eating them) antioxidant manufacture, heat shock proteins, DNA repair mechanisms, waste removal (autophagy), and other tricks that nature has to keep a life alive, if nature believes that is beneficial.  That genetic expression is, in turn, largely regulated by nutrient level detecting hormones, of which insulin, leptin and mTOR are primary, and they in turn are controlled by what you eat. Therefore, what a person eats can turn up repair, or lower it, and this arguably is the most important impact of diet on health and longevity, and must be primary when recommending a diet to promote health and longevity.  That brings us back to how I had stated earlier the major issue here should be expressed; which diet, Jaminet’s or Rosedale’s best up-regulates the repair vs. damage equation.  I discuss this more near the end of this post.  

I’ve drawn the inflection point where toxicity starts rising rapidly at around 140 mg/dl, and the inflection point on the other side where hypoglycemia causes substantial health damage at around 60 mg/dl. But the precise numbers don’t matter much; the point is that there is a U-shape, and somewhere in that U is a bottom where health is optimized. [my emphasis]

I believe, that there is a very important clarification that needs to be made here, at least as it concerns this current post. Fasting glucose, and therefore this graph, will be pertinent in showing perhaps a correlation between fasting glucose and health, and perhaps more importantly if changing fasting glucose levels changes that correlation. The point of the studies that I cited previously pertaining to glucose levels was to show that there is no specific threshold for glucose above baseline that determines health or not, as Jaminet believes. I do not believe, nor might Jaminet, that fasting blood glucose is the sine qua non for health, and it should not be used as such.  Again, it is the excursions in glucose and effects on corrupting insulin and leptin signaling that are much more significant. Therefore, most of the remainder of Jaminet’s post that deals only with potential risk to health of glucose levels takes on less significance, but let’s look further for more clarifications and explanations.

What do we know about the precise shape of that U, and the location of the bottom?

We can’t intuit the shape of the bottom of the U using theoretical speculations. Theory doesn’t allow us to balance risks of hypoglycemia against toxicity on such a fine scale. 

Empirical evidence is limited. Most studies relating blood glucose levels to health have been done on diabetics eating high-carb diets. There are few studies on healthy people… Actually, most of the studies that I cited in my last response were on ‘healthy’ people.

His first cite is “Is there a glycemic threshold for mortality risk?” from Diabetes Care, May 1999,http://pmid.us/10332668. 

For both fasting and 2-h postprandial blood glucose, the [relative risk of death was] lowest between about 4.5 and 6.0 mmol/l, which translates to 81 to 108 mg/dl. However, note that there is very little rise in mortality – only about 10% higher relative risk – in 2-h glucose levels of 7 mmol/l, which is 126 mg/dl. Since the postprandial peak is rarely at 2-h (45 min is a common peak), most of these people may well have been experiencing peak levels above 140 mg/dl. [emphasis mine]

That is a possibility but still speculative.  In this study we do not know.  Some people might have gone above 140, some might not have; just like the general population that might eat Jaminet’s diet.  This is important, as Paul claims risk only above 140, not at or below.

I also find it quite doubtful that those following Pauls’s diet will consistently measure postprandial glucose after a “safe starch” meal to make sure that blood glucose has always stayed below 140. In fact, that likely will not happen in anyone all of the time given the variability in environmental circumstances such as daily stress and sleep.

I find it particularly interesting when Jaminet says above that “there is very little rise in mortality – only about 10% higher relative risk – in 2-h glucose levels of 7 mmol/l, which is 126 mg/dl.”  Is he going from saying that keeping sugars under 140 is completely safe, to now saying that a 10% rise in risk is minimal and apparently acceptable for those whose 2 hr glucose is under 140, or saying that in all of these people their glucose must have risen above 140?

However, when one is looking only at glucose, one is looking only at the tip of an iceberg. It is what’s going on underneath (insulin, leptin) that is much more significant. If it was only blood sugar, than the initial graph would still hold, showing an increase in glycation correlating with an increase in glucose. Jaminet has even admitted as much. But we know there is more to the story.

My [Jaminet] interpretation: I would say that this study demonstrates that mortality is a U-shaped function of blood glucose levels, but it doesn’t tell us the shape of the bottom of the U. It is consistent with the idea that significant health impairment occurs only with excursions of blood glucose above 140 mg/dl or below 60 mg/dl.

That would depend what one’s definition of significant is.  What the study illustrates is that there is a 10% additional risk of death at 126 mg, that is significant to me, and that is well below Paul’s safe limit of 140 mg and is at a level that most people would obtain after eating what Jaminet refers to as ‘safe starches’.  There is added risk at any level above a relatively low baseline, and that was my point. The study does show a U-curve with 2 hr glucose, less so with fasting, with the bottom of the curve showing the mortality as stated in the conclusion of the paper; the lowest mortality is with glucose levels averaging approximately 90 fasting and 100 mg/dl 2 hrs after a glucose load.  Does this study add support to the author’s premise, and mine, that there is no glycemic threshold above baseline (and above that which is overtly hypoglycemic) that is healthy and below which is not. Yes it does.

I will once again repeat the conclusion of the authors;

CONCLUSIONS: In the Paris Prospective Study, there were no clear thresholds for fasting or 2-h glucose concentrations above which mortality sharply increased; in the upper levels of the glucose distributions, the risk of death progressively increased with increasing fasting and 2-h glucose concentrations.

Jaminet saying that there was only a 10% increase in mortality at 126 mg supports their conclusion and mine… that there is a gradual increase in mortality above a baseline of approximately 90 mg/dl  that Jaminet previously called safe.  To fit his paradigm, he must assume that in all of these people, their blood glucose rose above 140 mg/dl at some point, and there is no evidence to support that, and indeed that is not feesible.

Dr Rosedale’s second cite is actually to a commentary: “‘Normal’ blood glucose and coronary risk” in the British Medical Journal, http://pmid.us/11141131, commenting on a paper by Khaw et al, “Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk),” http://pmid.us/11141143.

This study used glycated hemoglobin, HbA1c, which can serve as a measure of average blood glucose over the preceding ~3 weeks. (As a point of fact, HbA1C actually is meant to indicate blood glucose over 3 months.)

This supports the “blood sugar should be as low as possible” thesis, since lower HbA1c levels were associated with lower mortality. However, this study has a few flaws:

It includes diabetics. Diabetics have poor glycemic control, and episodes of hypoglycemia as well as hyperglycemia, so HbA1c levels (which represent average blood sugar levels) may be a poor proxy for the levels of glycemic toxicity. Also, diabetics are usually on blood-glucose lowering medication, which may distort the blood sugar – mortality relationship.

It lumps the population together in very large cohorts. Effectively there were only three cohorts, since the highest HbA1c cohort had only 2% of the sample; the other three cohorts contained 27%, 36%, and 36% of the study population respectively.

We can get a finer grip on what happens by looking at studies that lack these flaws. Here’s one: “Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes,”Circulation, 2010, http://pmid.us/20923991.

This study is an an analysis of NHANES III; it excludes diabetics and has 3 cohorts, not 1, with HbA1c below 5%. The U-shaped mortality curve is very clear. In raw data and all models, the lowest mortality is with HbA1c between 5.0 and 5.4. Mortality increases with every step down in HbA1c: in Model 1, mortality is 8% higher with HbA1c between 4.5 and 4.9, 31% higher between 4.0 and 4.4, and 273% higher below 4.0.

So the minimum mortality HbA1c range of 5.0 to 5.4 translates to an average blood glucose level of 96.8 to 108.3 mg/dl (5.36 to 6.00 mmol/l). This result is almost identical to the finding in Dr Rosedale’s first cite, from which Dr Rosedale quoted: “the lowest observed death rates were in the intervals centered on 5.5 mmol/l [99mg/dl] for fasting glucose.”

My interpretation: Once again, we find that there is a U-shaped mortality curve, and minimum mortality occurs with average or fasting blood glucose in the middle of the normal range – in the vicinity of 100 mg/dl or 5.5 mmol/l.

I’m really not sure what the point is that Jaminet is making. That too low of blood glucose can be detrimental?  Certainly, especially under certain unhealthy circumstances that may or may not have anything directly to do with the glucose per se. Low average glucose can occur with adrenal insufficiency such that cortisol levels are inadequate, or growth hormone deficiency, etc. Certainly, just like with the thyroid studies that he has pointed out below and that I believe are misunderstood, the detrimental effects of lowering glucose would be determined by how and why it is being done; as part of illness, or as part of a physiological and “purposeful” regulation to extend longevity.   Lower than typical blood glucose is found in almost all models of extended lifespan (and healthspan) including caloric restriction and centenarians. What this study once again shows is an incremental increase in mortality far below a glucose level that Paul has said is healthy.  This study once again supports my contention that the increase in blood sugar brought about by eating ‘safe starches’ is anything but safe.

Let’s finish our examination of this issue with a quick look at Dr Rosedale’s third cite.  (Does this mean that Paul is OK with the other 17 or so studies that I had cited previously showing a detriment of glucose at levels well below those that Jaminet had proposed were safe?  That would be a pretty good batting average.) That paper, “Post-challenge blood glucose concentration and stroke mortality rates in non-diabetic men in London: 38-year follow-up of the original Whitehall prospective cohort study,”Diabetologia, http://pmid.us/18438641, is a familiar one; it was cited in our book (p 36, fn 35).

This study looked at blood glucose levels 2 hours after swallowing 50 grams of glucose, and then followed the men for 38 years to observe mortality rates. CarbSane makes an important observation: this study used whole blood rather than plasma to assay blood glucose. Whole blood has more volume (due to inclusion of cells) but the same glucose, and so less glucose per deciliter. According to this paper, standard (plasma) values are about 25 mg/dl higher, so 95 mg/dl in whole blood actually corresponds to a plasma value of about 120 mg/dl.

That was a 1965 paper. There have been considerable advances in the measurement of glucose since then, such that the differences are less, though still present. Actually, to convert from whole-blood glucose, multiplication by 1.10 (~10% difference) has been shown to generally give the serum/plasma level…

From the Joslin Diabetes Center at Harvard website; “The difference is that plasma numbers read about 10 – 12% higher than the older whole blood numbers. So if your fasting and pre-meal blood glucose target is 90 – 130 mg/dl plasma glucose, it would be 80 – 120 mg/dl if your meter reads whole blood.”

Though this is known among clinicians in the field, without having clinical experience, CarbSane would not know this. Furthermore, anyone checking glucose using a home monitor (other than perhaps some newer ones calculating serum glucose), is using whole blood.

The diagnosis of diabetes, by conventional standards, (though I believe that diabetes ought to be diagnosed by insulin and leptin values rather than blood glucose), is defined as a fasting plasma/serum measurement of 126. Using the conversion factor that Jaminet indicates would translate to a blood monitor level of 101. That, in turn, would translate to a whole lot more diabetics, that may benefit to a greater extent, as he mentioned in Jimmy Moore’s post, by using a more “diabetic” diet such as mine.  My statement that we all should be treated as diabetics would start to ring true.

There is no significant difference in mortality among any group with post-challenge whole blood glucose up to 5.29 mmol/l (95 mg/dl), corresponding to 120 mg/dl or 6.7 mmol/l in standard measurements..

(…or 105 mg/dl if the correct conversion factor was used.)

My [Jaminet] interpretation: This study wasn’t designed to observe the lower end of the U. At the higher end, it is consistent with the other studies: mortality rises with 2-hr plasma glucose above 120 mg/dl.

Actually in this study, mortality correctly rises significantly above 95 mg/dl blood, but that correlates to 105 mg/dl plasma if the much more modern and accurate conversion of 10% is used. This again is far lower than the 140 mg/dl that Jaminet has deemed safe.

Summary: Optimal Blood Glucose Levels

All of the papers cited by Dr Rosedale are consistent with this story:

1. Mortality and health have a U-shaped relationship with blood glucose.

2. Optimum health occurs at blood glucose levels around 100 mg/dl – at normal levels, not exceptionally low levels.

It does not show this. It shows a correlation with lower mortality of fasting blood glucose at approximately 90-100 mg/dl. This is not the same. There is more to health than just fasting blood glucose. Excursions in blood glucose are at least as important.

3. The impaired health seen with fasting or 2-hr blood glucose levels of 110 or 120 mg/dl may be largely attributable to the portion of the day in which those people experience blood glucose levels over 140 mg/dl.

This is not indicated in any of these studies, or the many studies that I cited previously … It is possible, but so then is any speculation of impaired health. It could be due to that portion of the day in which people were in car accidents as they were texting on their phone… in other words, since other variables were not measured, we can speculate about any other cause other than the most likely and that all the studies cited here and in my last post point to; that elevations in glucose above baseline are not healthy.

I should note that Dr Rosedale acknowledges that high-normal blood glucose is better than low blood glucose for some aspects of health, like fertility:

[Rosedale said]; “Safe starch proponents say that raising blood glucose and raising insulin is a very natural phenomenon and needn’t be avoided. However, if we evolved in a certain way and with certain physiologic responses to the way we eat, it was not for a long, healthy, post-reproductive lifespan. It was for reproductive success. The two are not at all synonymous, in fact often antagonistic.”

He’s saying that higher blood glucose favors “reproductive success,” while lower blood glucose favors “post-reproductive lifespan.”

Not exactly, but partly correct never-the-less.  Keeping blood glucose low even after eating does favor a longer and healthy post-reproductive  life.  What I did indicate was that ‘safe starch’ proponents should not use the proposition that since raising blood sugar is a natural phenomenon, that it is a reason for that being healthy.  Nature’s concern for us only goes so far; namely for us to be healthy to have reproductive success, after which she loses interest. It is also natural to die, but we are reading this to avoid that natural event. I have no qualms about saying that what I’m doing and teaching to be healthy is quite unnatural, as it is the quest to be able to live a long, happy, and youthful life after making babies. Humans appear to be unique in that quest. This concern of nature and evolution began with the beginning of life to include single-celled organisms…like the 15 or so trillion cells that make you up.  Increasing pressure to make more cells can increase risk of cancer, that elevations in glucose can promote. Many studies are now showing a correlation between glucose and insulin levels and cancer risk.  However, large, multi-celled walking and talking organisms such as us can still reduce risk of cells multiplying in excess, while still even increasing our ability to make multi-celled babies.  Insulin resistance, and especially leptin resistance is powerfully associated with infertility. One of the best ways to improve fertility is to improve leptin signaling that my diet has been shown to do.

I guess one has to choose one’s priorities. Not everyone will choose maximum lifespan.

They should…since extending maximal lifespan (as opposed to average lifespan) also entails extending “youthspan” and healthspan.

But suppose Dr Rosedale is right, and that low blood glucose levels are most desirable for at least some persons. I’m willing to stipulate, for the sake of argument, that optimal health for some persons may occur at below-normal blood glucose levels – say, 80 mg/dl. That brings us to the second issue: which diet will produce these low blood glucose levels?

Which Diet Minimizes Blood Glucose Levels?

If the key to health is achieving below-normal blood glucose levels, then low-carb diets are in trouble.

My low-carb diet is not, and that is far from the key to health.

In general, very low-carb diets tend to raise fasting blood glucose and 2-hr glucose levels in response to an oral glucose tolerance test.

This is a well-known phenomenon in the low-carb community. When I ate a very low-carb diet, my fasting blood glucose was typically 104 mg/dl. Peter Dobromylskyj of Hyperlipid has reported the same effect: his fasting blood glucose is over 100 mg/dl.

I don’t agree that low carb diets raise fasting BG (blood glucose) levels; perhaps certain kinds do, such as high-protein diets. I have never seen this in people following my diet; only in those perhaps who were following a high protein diet. I have treated many dozens of people, diabetics and otherwise, who have supposedly been on other low carbohydrate diets, and lowered their blood sugars considerably when I put them on my diet, that generally entailed reducing protein while increasing fat.

However a main point of my argument is that BG levels are only a small part of the story; What higher carb intake does to insulin and leptin is even more important; it raises them promoting insulin and leptin resistance.

From one of Peter’s posts:

Back in mid summer 2007 there was this thread on the Bernstein forum. Mark, posting as iwilsmar, asked about his gradual yet progressively rising fasting blood glucose (FBG) level over a 10 year period of paleolithic LC eating. Always eating less than 30g carbohydrate per day. Initially on LC his blood glucose was 83mg/dl but it has crept up, year by year, until now his FBG is up to 115mg/dl….

A high protein diet that many, if not most in the paleo community adopt by substituting protein for carbohydrates, is not healthy. I have noticed higher BG from higher protein diets many times, compared to my recommended higher (beneficial fat) diet with lower protein.

I’ve been thinking about this for some time as my own FBG is usually five point something mmol/l whole blood. Converting my whole blood values to Mark’s USA plasma values, this works out at about 100-120mg/dl.

Peter notes that low-carb dieters will generally perform poorly on glucose tolerance tests, but that increasing carb intake to about 30% of calories is sufficient to produce a normal response to a glucose challenge:

Again, a GTT is not at all sufficient to assess metabolic health. It is necessary to know the ihe insulin and leptin response. At the least, an insulin level measured concurrently with each glucose is necessary for any meaningful results pertaining to health. I must keep saying this; diabetes, and health, are not primarily a disease of glucose. They are a disease of improper signals being given to glucose, especially those coming from insulin and leptin. These need to be measured to have any meaningful idea about the roots of health. They effect many other, even more significant aspects of health, such as a massive shift in genetic expression. Though a mistake to focus on fasting blood glucose only as an index of  diabetes or health as is conventionally being done, I must say that it is my experience that fasting glucose is uniformly reduced on my diet… as are insulin and leptin levels. I do not think that Paul can say the same.

The general opinion in LC circles is that you need 150g of carbohydrate per day for three days before an oral glucose tolerance test.

Not in the low carb circles that I have kept; in the low carb circles of those of us who helped found the field, or in those circles of clinicians who have regularly treated patients with glucose problems. You cite Jeff Volek’s work below. Let’s look at another of his papers;

Comparison of a Very Low-Carbohydrate and Low Fat Diet on Fasting Lipids, LDL Subclasses, Insulin Resistance, and Postprandial Lipemic Responses in Overweight Women

Journal of the American College of Nutrition, Vol.23, No.2, 177–184

Numbers given in order; baseline, very low carb, high carb;

Glucose(mg/dL) 86 83 88

Insulin(pmol/L) 41 37 50

InsulinResistanceHOMA 1.28 1.10 1.63

Please note that a very low 9%, 28 gm. carbohydrate diet did not raise blood glucose, in fact kept it in a healthy range. What’s more important is that it did so concurrent with lowering insulin, thus improving insulin sensitivity. The high carb diet also kept blood glucose low, and if this is all that was looked at, there would be little to conclude. However the real and big story is that the high carb diet kept the BG down at the expense of raising insulin significantly, and thus worsening insulin resistance, and this is a very detrimental effect to overall health, risk of virtually all chronic diseases of aging, and confers a high risk to shortened lifespan. I will emphasize again; only measuring blood glucose without knowing what insulin and leptin are doing gives very incomplete and often misleading information when it comes to effects of any intervention such as diet. Basing conclusions on this is fraught with danger. This is also why the standard of current medical care for diabetics generally makes them worse. (See results of the ACCORD study.)

Although I did show many studies showing the correlation of glucose on aspects of health and even mortality, it was done to disprove the notion that only glucose above 140 is detrimental, which they did, including in context of studies pertaining to insulin and leptin. The conclusion based on the totality of those studies was that detriments of glucose on various aspects of health are seen well below values that Jaminet claims are safe.

This is at the high end of the 20% to 30% of energy (400 to 600 calories on a 2000 calorie diet) that is the Perfect Health Diet recommendation for carbs.

The Kitavans eat more than 60% of calories as carbohydrate, mostly from starches. Their fasting blood glucose averages 3.7 mmol/l (67 mg/dl) (http://pmid.us/12817903).

I have consistently heard those in the Paleo, higher carbohydrate camp refer to the Kitavans as an example of a population eating a high carbohydrate diet and supposedly being much healthier, and the conclusion is drawn that the high carbohydrate diet is causing the improved health.

Trying to draw conclusions from population groups is extremely difficult and can lead to very poor science. There are far too many variables to fully account for, and the best one can do is associate a particular variables such as a high carbohydrate diet with health. However, association does not mean cause, as I have talked so often about pertaining to cholesterol studies.

Little mentioned of the Kitavans, is their high intake of coconut oil. This is very high in medium chain triglycerides that have been shown to have numerous and powerful metabolic advantages. That is the trouble with population studies. It is impossible to control all of the variables in diet and lifestyle.

How about this for a variable that I do not hear accounted for much pertaining to Kitavans;

“Should we be concerned over increasing body height and weight.”

Experimental Gerontology 44 (2009) 83–92

“Researchers have found that people in traditional societies have much lower rates of certain chronic diseases compared to developed populations . Virtually all of these populations are much shorter than northern Europeans…Kitavan males have averaged 163 cm (5’4″) and females 155 cm (5’1″) for several generations…The greater longevity of smaller animals within the same species became widely known when it was found that mice fed low calorie diets grew to be smaller than normal but had extended longevities.”

BMI and weight: their relation to diabetes, CVD, cancer and all cause mortality. In: Samaras, T. (Ed.), Human Body Size and The Laws of Scaling:

Physiological, Performance, Growth, Longevity and Ecological Ramifications.

Nova Science Publishers, New York, pp. 113–146.

“Shorter people experience lower BMI, lower levels of various risk factors for CHD, diabetes, and all-cause mortality, such as glucose, insulin, IGF-1, CRP, homocysteine, Apo B, total cholesterol, triglycerides, and LDL; however, they experience higher levels of desirable HDL, Apo A and SHBG.”

Why are they short? Kitavans eat less protein than in western societies, most of which is concentrated in 1 meal, further reducing IGF and mTOR, both of which have been shown to extend longevity.

But do Kitavans even have extended longevity? That’s quite debatable. They do not have a higher number than average of centenarians (if any) and do not have higher than (even post 50 year old to account for high infant death rate) average lifespans.

All one can say is that Kitavans with their diet of far less junk food, lower protein, higher (cellulose) vegetables, high MCTs, that may help result in short and lean stature, with their less stressed lifestyle gives them low rates of heart disease and diabetes but with an approximately average lifespan with few centenarians. I don’t understand what the big deal is there.

I would not hang my hat on Kitavans as a reason to eat carbohydrates, as the hatrack is not secure. I don’t know about you, but I am striving for better health than revealed by the Kitavans.

Studies confirm that high-carb diets tend to lower fasting glucose and to lower the blood glucose response to a glucose challenge. CarbSane forwarded me some illustrative studies:

“High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults,” http://pmid.us/2168124. Switching healthy adults to a higher carb diet reduced fasting blood glucose from 5.3 to 5.1 mmol/L (95.5 to 91.9 mg/dl) and reduced fasting insulin from 66 to 49.5 pmol/l.

I will spend a bit of time going over this and the next study cited by CarbSane and presented here, as they are excellent examples of really bad science (if that word should even be used at all) that are very misleading, and they in no way support the position that increasing carbohydrate intake is healthy… at best perhaps only somewhat less unhealthy than worse diets.

In the prior study, let’s look at the feeding method;

“In the young subjects the usual ad libitum (control) diet composition was determined from a 2-wk dietary recall [that many studies have shown fail to 'remember' the unhealthiest foods. No one wants you to know that they downed a pizza chased by a hot fudge sunday as a midnight snack]. The HCF [high carbohydrate/fiber] diet was prepared in the metabolic kitchen at MIT and consumed by the subjects under supervision.”

Yup; an even playing field. The usual at home, unsupervised, ad-lib diet that could be recalled from 2 weeks prior, was compared to a very high fiber diet consumed under supervision containing on average 60 grams more fiber than the 15 gm “control” daily, the vast majority of which was insoluble and thus, though virtually totally excreted, is counted toward calorie intake. Have any of you tried to eat 75 grams of fiber daily? That’s 22 tablespoons of Metamucil a day.. Talk about in and out..

This study compared a standard high fat, high carb, low fiber diet to a diet much higher in fiber. I have stated innumerable times that the typical diet is so bad that making any changes to it leads to improvement. The worst diet to be on is a high fat, high carbohydrate diet, as the (non-fiber) carbs prevents the fats from being burned. In this case the high fat, high non-fiber carb diet was being compared to a low fat, very high fiber high carb diet.

Jaminet uses another study from CarbSane;

“Effect of high glucose and high sucrose diets on glucose tolerance of normal men,”http://pmid.us/4707966. On diets with glucose as the only carb source, 2-hr plasma glucose after a glucose challenge was 184 mg/dl on a 20% carb diet, 183 mg/dl on a 40% carb diet, 127 mg/dl on a 60% carb diet, and 116 mg/dl on an 80% carb diet. The 80% carb diet was the only one on which blood glucose never went above 140 mg/dl.

It is important to know the diets being talked about. These are the glucose diets being referred to in this above second study;

“The glucose diets contained 3,000 kcal with 15% of calories as calcium caseinate; 20, 40, 60, or 80% as glucose; and the remaining calories as corn oil.”

That’s right, 65% of the lowest carb diet was force fed corn oil…the ‘low-carb’ group was force fed high quantities of liquid corn oil to bring calories up to 3000 cal/day, and it’s not a revelation that these people didn’t do too well. Jaminet is attributing their poor relative results to their low carb intake that is, by the way, 20% glucose = 600 cal. that is exactly what Jaminet calls a ‘safe starch’ amount and type. I think there are other reasons; lucky for Jaminet.

Insulin was not measured. See my comments above. This is a usual and critical mistake. It is very possible that the very rapid and large spike in glucose secondary to eating carbs with a glycemic index of 100, caused an equally rapid spike in insulin that rapidly reduced the blood glucose. It is also well known that eating fat with sugar slows the absorption and “flattens” the blood glucose and insulin curve, resulting in perhaps higher 2 hour glucose values. But is this very rapid rise and decline i.e. high spike in blood glucose and insulin healthier? Quite the opposite.

Again, what I have said for decades is that lowering glucose by raising insulin is trading one evil for an even worse one. Spikes in glucose may even be worse than a high but steady BG (see studies below), and spikes in glucose and insulin may, and I believe do, bring about insulin and leptin resistance, and therefore a whole new realm of metabolic devastation.

Furthermore, in these studies, the low-carb group was not well adapted, and necessary nutrient supplementation was not given. It is well known that those people who are not adapted to a low carbohydrate diet may not fare well in the first few weeks following the initiation of this, especially if they have not supplemented with potassium and magnesium that will be lost as excess fluid is excreted in urine as insulin is reduced. Magnesium is also required for proper insulin signaling. Also, the almost infinitely high omega 6/omega 3 ratio seen in the first study would cause extreme inflammation that is known to damage islet cells and prevent proper insulin and leptin function while also impairing the metabolism of fatty acids and membrane function.  I do not think that the authors were unaware of this.

Once again, what those two studies merely show is that eating carbs and fat (as pure corn oil !) together is very bad, that eating large amounts of pure glucose will rapidly spike blood glucose and therefore insulin that (at least for a while before insulin resistance kicks in) is known to rapidly lower the blood glucose, that force feeding copious amounts of corn oil to maintain high calorie intake might have deleterious effects, especially in conjunction with improper implementation and without proper supplementation of at least magnesium, potassium, and omega 3 oils.

The proper very low carbohydrate (higher beneficial fat, moderate only protein) diet, a few very simple precautions, and a little bit of time is necessary before significant benefits are realized,,,and they will be realized if this diet is properly implemented.

But wait; there’s more;

Medical and nutrition studies are now often (usually?) undertaken, not to discover some underlying truth, but rather designed to obtain a predetermined and biased outcome as part of a marketing effort.

Both of the previously cited studies, one from 1973, and the other from 1990, were authored by James Anderson, whom I am quite familiar with. Dr. James Anderson happens to be the chairman of the National Fiber Council, an organization that is funded by HCF [High Carbohydrates and Fiber] Nutrition Research Foundation (a nonprofit foundation reputedly funded by large carbohydrate containing food corporations and whose chairman happens to be Dr. Anderson), and other not very unbiased entities such as Procter & Gamble.

Furthermore, these studies are irrelevant to our discussion that ought to be comparing, as much as possible, a very low carb, high (healthy, not corn) fat and moderate protein diet in which the participants had enough time to become adapted, to a higher carb diet. The studies by CarbSane and Jaminet are like comparing a fat 40-year-old to a fat 50-year-old in the 100 yard dash, and assuming that the winner is fit for the Olympics.

This last study did not report fasting glucose, but did track blood glucose for 4 hours after the glucose challenge. If we take the 4-hr blood glucose reading as representative of fasting glucose, we find that dieters eating 60% or 80% carb diets had fasting glucose of 76 and 68 mg/dl, respectively.

With all due respect for Paul, he is taking way too much liberty here. Rarely do 4 hr post prandial glucose levels reflect fasting levels. They are often higher, sometimes lower depending on insulin response (i.e. reactive hypoglycemia). This is why fasting blood tests are done at least 8 hrs and usually 12 hrs after eating. Furthermore the inadequacy of testing may have covered up the rapid, and detrimental spikes in glucose (that Jaminet also alluded to earlier) and insulin that may have likely occurred, especially with the higher glucose diets. If Jaminet really believed in these studies, then why is he not recommending very high sugar diets? I believe that he knows them to be less than healthy.

interpretation of the evidence from multiple sources: A plausible conclusion is that a high-carb diet produces a low fasting glucose (let’s say, 80 mg/dl), a PHD type 20% carb diet an intermediate fasting glucose (95 mg/dl), and a very low-carb diet a high fasting glucose (say, 105 mg/dl).[my emphasis]

Let’s not just “say”. With all due respect, these are hypothetical numbers, and likely incorrect (see above). They appear designed to fit the following graph, based loosely on a couple of old and highly controversial studies and a couple of anecdotal reports. One cannot come to any conclusions, let alone what Paul is calling plausible, from those studies. There are a multitude of studies easily found that show the opposite; that eating a high carbohydrate diet is associated with raising fasting and post prandial glucose.

Just for fun, I decided to see where these fasting glucose levels show up on the mortality plot from Balkau et al:

The 20% carb diet lines up pretty well with the mortality minimum, and both high-carb and very low-carb diets wind up at bins with slightly elevated mortality.

…only when, shall we say, imaginative numbers are used.. and again, no insulin results. Also see my study cited also below that shows a resultant average fasting glucose of 99 mg/dl on my very low carb diet associated with great insulin and leptin results (cutting nearly in half!).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831640/

Now, I don’t believe we can infer from data on high-carb dieters what the relationship between blood glucose levels and mortality will be in low-carb dieters. It was Dr Rosedale, not me, who introduced this study into evidence.

But if we believe that lowest mortality really does occur with 2-hr post-challenge blood glucose around 100 mg/dl and fasting blood glucose below 100 mg/dl, as argued by the studies Dr Rosedale cited, and that this result applies to low-carb dieters, then I think the evidence is clear. One must eat some carbohydrates – at least 20-30% of energy.

…Whoa. That conclusion is hardly warranted. What the overwhelming preponderance of evidence had shown, and what the conclusions by the authors themselves had shown, is that there is no specific threshold for glucose below which is healthy. Raising glucose above baseline increases indexes of disease and mortality. That is all that can be concluded. More than that is speculation from using studies (a 65% corn oil diet?!) that I doubt Jaminet has faith in either. Regardless, there are way too many studies that show the opposite; that eating glucose and glucose forming foods impair glucose tolerance and insulin sensitivity, and worsens diabetes, if not being a major etiologic factor, to draw opposing conclusions.

This is the standard Perfect Health Diet recommendation. It seems that Dr Rosedale is supporting my diet, not his!

Oh No.. Keep me away from that Kool Aid!!

What About Diabetics?

Perhaps the boldest passage in Dr Rosedale’s reply was this:

“We are all metabolically damaged to some extent. None of us has perfect insulin and leptin sensitivity…. It is for that reason that I say that we all have diabetes, some more than others, and should all be treated as such.”

Well, if we all have diabetes, more or less, then I guess I have to consider whether our regular diet – which recommends about 20% of energy (400 calories) as carbs – is healthy for diabetics.

Now, before I begin this discussion, let me say that I don’t claim that this is optimal for diabetics. I think it is still an open question what the optimal diet for diabetics is, and different diabetics may experience a different optimum. I have often said that diabetics may benefit from going lower carb (and possibly higher protein) than our regular dietary recommendations. However, Dr Rosedale is here saying that even a healthy non-diabetic should eat a diet that is appropriate for diabetics. I want to see whether our regular diet meets that standard.

How do diabetics do on a 20% carb diet? Here’s some data that I found in a post by Stephan Guyenet at Whole Health Source. It’s from a 2004 study by Gannon & Nuttall (http://pmid.us/15331548) and the graph is from a later paper by Volek & Feinman (http://pmid.us/16288655/). Over a 24 hour period, blood glucose levels were tracked in Type II diabetics on their usual diets (blue and grey triangles) and after 5 weeks on a 55% carb – 15% protein – 30% fat (yellow circles) or 20% carb – 30% protein – 50% fat diet (blue circles):

The low-carb diet was a little higher in protein and lower in fat than we would recommend, but very close overall to our recommendations and spot-on in carbs.

What happened to blood glucose? It came close to non-diabetic levels. Fasting blood glucose dropped to 7 mmol/l (126 mg/dl), roughly the level at which diabetes is diagnosed. Postprandial blood glucose elevations were modest – peaking below 160 mg/dl which is about 20 mg/dl higher than in normal persons. Average daily blood glucose looks to be around 125 mg/dl.

What would have happened on a zero-carb diet? Fasting blood glucose probably would still have been elevated, near 126 mg/dl;

That’s fairly fanciful, and I don’t agree that lowering carbs further would start raising blood glucose. The opposite will typically happen. See Cahill cited below and in my Jimmy Moore post.  Starvation (0 carb) lowers glucose dramatically. Properly implemented, lowering carbohydrates leads to further improvements. Regardless, no one is really recommending a 0 carbohydrate diet, as this would have to be laboratory fabricated. However, what my experience has been with my VLC (very low carb) and higher fat diet, is that fasting and post prandial glucose become further improved, into completely healthy, non-diabetic, non impaired glucose tolerant ranges. I do not and have not disputed that Paul’s diet may lead to (much) better results than the french fries (whoops, potatoes allowed by Paul) and coke diet that the average person may eat. But to make it “perfect”, the starch consumption would need to be reduced.

It is interesting that Jaminet would use Jeff Volek for support. I am quite familiar with Jeff and his work through Eric Westman who has collaborated with Jeff often and me previously; he is a co-author on my paper cited here. It is extremely unlikely that Jeff (or Eric) would agree with that statement or Jaminet’s conclusions about a very low carbohydrate diet raising blood glucose.

Let’s see what Jeff Volek has to say;

Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets [VLCKD]

Jeff S. Volek and Matthew J. Sharman

Obesity Research Vol. 12 Supplement November 2004

The studies were conducted on healthy volunteers.

Aside from having higher protein than I would recommend, this is close to my diet..

Volek’s VLCD; Protein ~28%, Carbohydrate 7% (39 gms), Fat (%) 64

“…there were significant decreases in insulin (28%) and leptin (64%) concentration after the VLCKD [very low carbohydrate ketogenic diet]. Postprandial insulin responses immediately after the fat-rich meal were significantly lower after the VLCKD.

…Another consistent effect we have seen in our studies is a reduction in fasting glucose and insulin [on a VLCD]… Fasting glucose, insulin, and insulin resistance were all significantly lower after the VLCKD compared with the low-fat diet…we propose that VLCKD may be particularly suitable for preventing and treating metabolic syndrome.”

And in;

Lipids 2009 Apr;44(4):297-309. Epub 2008 Dec 12.

Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet.

Volek, JS, Phinney SD

CRD (carbohydrate restricted diet; % carbohydrate:fat:protein = 12:59:28) vs. a low-fat diet (LFD) (56:24:20)

“…subjects following the CRD [12% carbs] had consistently reduced glucose (-12%) and insulin (-50%) concentrations, insulin sensitivity (-55%), weight loss (-10%), decreased adiposity (-14%), and more favorable triacylglycerol”

…this is common in diabetics because the loss of pancreatic beta cells creates a glucagon/insulin imbalance that leads to elevated fasting blood glucose. This blood glucose level would have been maintained throughout most of the day, with the postprandial peaks and troughs flattening. Average daily blood glucose level would have been similar to that on the 20% carb diet.

There are too many “would have” speculations (likely false) in this argument. I believe that I was the first person to use a low carbohydrate, relatively high-fat diet to treat diabetics and taught most of the others in one way or another who are doing this today, And I will emphatically say that lowering carbohydrates as much as possible, without the consumption of excess protein, is by far the best way to lower glucose and insulin (and leptin), i.e. to reverse insulin (and leptin) resistance, and in fact to frequently totally reverse the disease of T2 diabetes (or impaired glucose tolerance). Any additional carbohydrate or protein will adversely affect these results. I do believe that if Paul were to treat diabetics and compare results, his ideas would be quite different.

So the big benefit, in terms of glycemic control for diabetics, comes from reducing carbs from 55% to 20%. Further reductions in carb intake do not reduce average 24 hour blood glucose levels, but may reduce postprandial glucose spikes.[my emphasis]

I am happy that Jaminet said that, since reducing glucose spikes may be even more important than reducing fasting glucose. There are in fact quite a few articles that are now showing that spikes in glucose are worse than steady high glucose. Here’s one;

Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells

Schisano, Diabetologia, Volume 54, Number 5, 1219-1226

“Conclusions/interpretation; Exposure to oscillating glucose was more deleterious than constant high glucose and induced a metabolic memory after glucose normalisation. Hyperactivation of p53 during glucose oscillation might be due to the absence of consistent feedback inhibition during each glucose spike and might account for the worse outcome of this condition.”

And another;

Effects of intermittent high glucose on oxidative stress in endothelial cells.

Qin-Min Ge, Acta Diabetologica, Volume 47, Supplement 1, 97-103

“Intermittent high glucose induced a greater over-production of ROS [reactive oxygen species] than constant high glucose…and may be involved in the development of vascular complications.”

…and I do not think that I need to show studies that eating ‘safe starches’ such as rice and potatoes will spike and oscillate blood glucose…The glycemic index again shows that well.

In fact, we have some Type II diabetics eating Perfect Health Diet style. Newell Wright reports good results:

I am a type II diabetic and a Perfect Health Diet follower, so I want to chime in with my experience….

I switched from the Atkins Induction diet to the Perfect Health Diet. I have been eating rice, potatoes, bananas, and other safe starches ever since, as well as fermented dairy products, such as plain, whole milk yogurt. I have also slowly lost another seven pounds. I enthusiastically recommend the book, Perfect Health Diet by Paul and Shou-Ching Jaminet.

Today, my fasting blood glucose reading was 105. Note that since following the Perfect Health Diet, my fasting blood glucose reading has gone down. Previously, I was suffering from the “dawn phenomenon.” My blood glucose levels overall were well below 140 one hour after a meal and 120 two hours after a meal. Only my fasting BG reading was out of whack, usually between 120 and 130, first thing in the morning.

For dinner tonight, I had a fatty pork rib, green beans, and a small baked potato with butter and sour cream. For dessert, I had a half cup of vanilla ice cream. One hour after eating, my blood glucose level was 128 and two hours after, it was 112.

So not only am I losing weight on the Perfect Health Diet, my blood glucose levels have actually improved, thanks to the increased carbs counteracting the dawn phenomenon, just as Dr. Kurt Harris (another proponent of safe starches) said it would.

So for me, as a type II diabetic, this “safe starches” exclusion is pointless…. [D]espite the type II diabetes, I am doing just fine on the Perfect Health Diet, thank you. I reject the diabetic exclusion of safe starches.

Note that Newell’s fasting blood glucose went down from 125 to 105 mg/dl when he raised his carb intake from Atkins Induction to Perfect Health Diet levels, and postprandial glucose levels on PHD were no higher than his fasting levels on Atkins Induction. It looks like he reduced blood glucose levels by adding starches to his diet.

Mine is not the Atkins diet. Furthermore Newell’s blood sugar is still not healthy. It appears likely he is talking about his home measurement of glucose being 105. Using Jaminet’s conversion, that would equate to a laboratory serum value of 130 mg/dl, that would still place him very much in the diabetic range; not such a great result. Using a more accurate conversion, it would be 118; still very unhealthy and considered impaired glucose tolerant. It is extremely unfortunate that this is being touted as healthy by Newell himself, who will have to suffer the consequences of being misinformed. Also, do we know what his insulin is? Has it ever even been measured? As I have stated so often; lowering glucose at the expense of raising insulin is doing someone no favors. Newell may be doing better than bad on the surface (only in-so-far as blood glucose levels go), but I consider it a failure if a type II diabetic of mine is not completely reversed, such that healthy blood sugars are obtained without medication and associated with lower insulin. It is so important, that I have to keep repeating it; diabetes is not a disease of blood glucose, but a disease of the signals being given to glucose. These are what need to be treated and measured. Giving only glucose measurements tells me little about the health of a “diabetic”.

To repeat: I’m not claiming that our regular diet, providing 20% of energy from “safe starches,” is optimal for diabetics. I don’t know what the optimal diabetes diet is, and it may be different for different diabetics. But I think there is plentiful evidence that even for diabetics, our “regular” diet is not a bad diet. And for some, it might be optimal.

Here I am happy to finally agree, and it feels good to be able to do so. Jaminet’s diet is certainly not a bad diet, and I hope that I have never given the impression that it is. It is better than most other diets generally being touted. Optimal for some? I can’t say.

I truly believe that the closer that any diet comes to mine, the better it is. This has been shown to me over the last 2 decades of patient experience, the continual outpouring of supporting science, first pertaining to insulin, then leptin, then mTOR and the now very robust science over the last decade pertaining to the biology of aging…and also by the numerous well known low carb diets that have ultimately modified their original programs to try to morph into mine.

Summary: Putting It All Together

It looks like 20% of energy is a sort of magic number for carbs. It: 

Averts glucose deficiency symptoms while achieving normal insulin sensitivity and glycemic control on oral glucose tolerance tests;

Avoids significant hyperglycemic toxicity even in diabetics.

Why does this magic number, which happens to be the Perfect Health Diet recommendation for carb intake, do so well?

Perhaps a chart will make the science a little clearer.

“Dietary glucose in” (blue) represents the amount of carbs obtained from diet. “The body’s glucose utilization” (maroon) is how much glucose will be put to useful purposes at a given daily carb consumption. Glucose utilization does not vary as strongly as glucose intake.

Actually, glucose utilization can vary tremendously depending on the activity of many hormone levels, including insulin, leptin and their level of sensitivity, cortisol, thyroid, growth hormone. When one eats glucose there will be glucose spikes of varying amplitude, and as shown above, this is particularly detrimental.

At low intakes a deficit is made up by gluconeogenesis (manufacture of glucose from protein) and at high intakes an excess of glucose is destroyed by thermogenesis or conversion of glucose to fat. Where the blue and maroon lines cross, dietary glucose in matches the body’s glucose utilization.

But it is critical to note that this point, where the body’s glucose utilization and needs meet, are a constantly moving target that a person can never consciously know, and therefore one cannot eat accordingly. This is a major point I made in my last response and post on Jimmy’s blog in answer to my question that I had asked on Paul’s behalf, “Is it healthier to consume the required glucose (though much less required than Paul had assumed) or is it better to let the body manufacture its own needs?” I will repost my answer;

Is it healthier to get the glucose, any glucose, from the diet, or from gluconeogenesis? Is it healthier to eat starches, and in fact go out of one’s way to do it, for the necessary glucose, or is it better to let the body make its own from other sources, i.e. gluconeogenesis via glycerol from fat or from lactate and amino acids.

It first needs to be pointed out that in reality one cannot eat a zero carbohydrate/sugar diet. Although not necessary, one will always eat some sugar or sugar forming carbohydrate even on a good very low carbohydrate (VLC) diet. Even plain green vegetables will have some sugar, as will nuts. However, for purposes of this discussion we will assume that a VLC diet has almost no non-fiber, sugar forming carbohydrates.

Eating rice or potatoes or any bolus of starch will result in at least three adverse consequences in everyone.

#1. They will be quickly converted into glucose that will spill into the circulation in a relatively uncontrolled way raising blood glucose as a bolus…in some more than others, but will raise blood glucose significantly in everyone.

#2. This will raise insulin (if one still has functioning islet cells) and it will raise leptin. This is meant for relatively short-term survival, but not so good and has not evolved for a long, post reproductive and healthy lifespan. The immediate physiological consequences of raising insulin are well known, are in every medical physiology textbook, and was the topic of a talk that I gave 15 years ago “Insulin and its Metabolic Effects“ that is easily found all over the internet. It reduces if not prevents one’s ability to burn fat. This also reduces production of glycerol substrates to make glucose.. It causes fluid retention and sodium retention. It causes vasoconstriction, both increasing blood pressure, etc.

#3. Repeated elevations and insulin and leptin cause insulin and leptin resistance. Now we are into a whole new realm of poor health. Now insulin and leptin are not staying high for a few hours a day, but staying high throughout the entire day…and night, whether one eats or not… Causing more and more insulin and leptin resistance in a vicious cycle until, at least for insulin, the islet cells start burning out…lowering insulin but further raising glucose…and now we are into full-blown diabetes. Raising insulin and leptin repeatedly has extremely adverse consequences that I feel are instrumental in the early onset of virtually all of the chronic diseases of aging and in fact accelerating aging itself..

When glucose is consumed, that bolus of glucose circulates, potentially doing damage before being picked up by the liver for metabolism and controlled redistribution.

Eating starch and therefore a bolus of glucose will, at least to some extent, by spiking blood glucose, insulin, and leptin, mimic the stress response.  I, for one, do not need any help with that.

When, however, the liver makes the requisite glucose, the amount and distribution is immediately regulated. The liver will only make what is necessary…unless it has become resistant to signals that tell it what to do, as in insulin and leptin resistance brought about from spiking those hormones by constantly eating boluses of glucose/starch.

Under typical, non stressed conditions, there is far less of an insulin and leptin excursion if glucose is made via gluconeogenesis then if taken by diet. In fact, one of the major signals to shut off gluconeogenesis is elevated insulin.

The ancient, deep brain (as opposed to cortex) and body knows its constantly changing, biologically complex needs far better than ‘thinking’ we do and if kept healthy, will only make the glucose that is necessary.  I would far prefer to keep my liver sensitive to the bodies’ signals and let it do its thing, than to think for one minute that I could outthink it by forcing 400 cal. glucose daily [or even 600 cal.]

For most sedentary adults, this level will be around 600 carb calories per day.

Not so.  A VLC well adapted person has a glucose requirement closer to 300 cal, all of which can easily come from non carbohydrate sources, including glycerol from fat and recycled lactose. See Cahill and my entire last post on Jimmy’s site.

We recommend eating close to or slightly below this point (“PHD Recommendation”).

There are dangers in straying too far from this intersection point:

Eating too few carbs creates a risk of health impairment due to insufficient glucose or protein.

Jaminet is speaking here I assume about what he had previously referred to as “glucose deficiency”. I had refuted the existence of this quite thoroughly in that last post on Jimmy Moore’s blog. There is no such entity in a non clinically hypoglycemic individual. As opposed to my repeating this here, those interested should refer back to that last response.

As far as too few carbs creating insufficient protein; I don’t get the connection there.

Eating too many carbs results in unnecessary exercise of glucose disposal pathways, and possible unhealthy fluctuations in blood glucose levels if those disposal pathways fail.

I totally agree. That’s twice in one day…on a roll… though I would argue that consistently eating 600 cal. glucose forming carbs and even less will at least sometimes, if not nearly always, cause unhealthy fluctuations in blood glucose.

Hitting just below the intersection is a safe, low-stress point which will work well for most people.

I would move that intersection considerably to the left.

For diabetics, the excess glucose disposal pathways are broken. However, this is not a major problem if you have no excess glucose to dispose of. Eating up to 20% of calories from carbs doesn’t require the use of disposal pathways – glucose can be stored as glycogen and then released as needed, so the effect of dietary glucose is primarily to reduce the amount of gluconeogenesis. Suppressing gluconeogenesis requires some residual insulin secretion ability, so Type I diabetics cannot achieve this, but most Type IIs can.

The upshot: A 20% carb diet meets the body’s glucose needs without much risk of hyperglycemic toxicity even in diabetics.

I see the shift starting to happen…from a 20% carb diet being healthiest, to now resulting in not too much risk. Just a little more time may be needed for Paul to come over to my camp. As I’ve said, it takes a little time to adapt to my diet; even conceptually…

The Issue of Thyroid Hormones and Anti-Aging

The most distinctive element of Dr. Rosedale’s diet is its emphasis on longevity as the supreme measure of health, and its emphasis on calorie restriction (especially, carb and protein restriction) and metabolic suppression as the means to long life.

Our book, Perfect Health Diet, relied strongly on evidence from evolutionary selection to guide us toward the optimal diet.

Dr. Rosedale rejects evolutionary selection as a helpful criterion, since evolution did not necessarily select for longevity:

[Rosedale says], “If we evolved in a certain way and with certain physiologic responses to the way we eat, it was not for a long, healthy, post-reproductive lifespan. It was for reproductive success. The two are not at all synonymous, in fact often antagonistic. We have no footsteps to follow as far as the best way to eat for long healthy post reproductive life. We can only use the best science pertaining to the biology of aging and apply it to proper nutrition. That is what I feel I am doing.”

We actually share much of Dr Rosedale’s perspective on what influences longevity; it is for longevity that we recommend slightly under-eating carb and protein compared to what evolution selects for. However, we don’t go as far in that direction as Dr Rosedale does.

We have written of the suppression of T3 thyroid hormone levels which is part of the body’s strategy for conserving glucose in times of scarcity, and how this is a risk factor for “euthyroid sick syndrome.” See Carbohydrates and the Thyroid, Aug 24, 2011.

Dr Rosedale acknowledges this (I am not acknowledging that this leads to euthyroid sick thyroid syndrome; quite the opposite) and believes it to be beneficial:

[Rosedale says], “I believe that Jaminet and most others misunderstand the physiologic response to low glucose, and the true meaning of low thyroid. Glucose scarcity (deficiency may be a misnomer) elicits an evolutionary response to perceived low fuel availability. This results in a shift in genetic expression to allow that organism to better survive the perceived famine…. As part of this genetic expression, and as part and parcel of nature’s mechanism to allow the maintenance of health and actually reduce the rate of aging, certain events will take place as seen in caloric restricted animals. These include a reduction in serum glucose, insulin, leptin, and free T3…The reduction in free T3 is of great benefit, reducing temperature, metabolic damage and decreasing catabolism…. We are not talking about a hypothyroid condition. It is a purposeful reduction in thyroid activity to elicit health. Yes, reverse T3 is increased, as this is a normal, healthy, physiologic mechanism to reduce thyroid activity.”

This is an explanation of why this is not “sick thyroid”.

Note that Dr Rosedale acknowledges that his glucose-scarce diet reduces body temperature. Many Rosedale dieters have had this experience. Darrin didn’t like it:

This comment from Rosedale support may be of interest to you;

“The best place to measure is under the tongue. Ideal basal temperature is what you have when you first wake up in the morning, and on the Rosedale diet should be upper 96′s lower 97′s. We have found that when someone starts our diet, their basal temperature will go down about 1-2 degrees Fahrenheit which is a great improvement”.

Personally, i did not feel good on a lower body temp when i was low carb (sub 50g) & have been working hard (following phd diet & supps) to get my body temp back up. i would say my basal/morning oral temp is now around the 97.5F on average (up from around 96.5F average pre PHD).

As far as Darrin; I have not known anyone who had difficulty in maintaining my diet because of low body temperature that was not hypothyroid (from disease) or had deficient adrenal function. The fact that he had to work hard to get his temperature up leads me to believe that there were/are other problems involved, as getting temperature higher is typically extremely easy and can happen in as short as one day by eating more carbs. This should be looked into.

As stated before, single anecdotal stories are not very good science. I have literally hundreds of testimonies indicating extreme benefit when switching to my diet from many other diets.

Low body temperatures are associated with a variety of negative health outcomes. For instance,low body temperature is immunosuppressive, leads to poor outcomes in infections, and is a significant independent predictor for death in medical patients. Fever is curative for most infections, low body temperature is a risk factor for infections.

Again, I am not talking about a sick thyroid. I am not talking about a thyroid that is low because it has to be, or a body temperature that is low because the body does not have enough lean mass or proper physiology to maintain a higher temperature, which is all that the above examples and studies indicate. I am not talking about hypothyroidism. I am talking about a thyroid that is purposefully being lowered to enhance the wellness and survivability of that life. Please understand that this is very different. One is very healthy; one is very not.

This is analogous to fasting insulin. Almost always, a high fasting insulin indicates insulin resistance and poor health. Properly treated, fasting insulin goes down and the person is healthier. You don’t say that that person now has a sick pancreas. The same is true for thyroid. As part and parcel of making that person healthier, fasting insulin is reduced, fasting leptin is reduced, and so is free T3 reduced.

Also, as in my previous post, temperature must be orchestrated for maximal health. As we age, one of the major problems is that our temperature does not go as high with infection as it did when we were children. This is what can predispose to serious infection. My diet does not relegate people to low temperature. It keeps temperature a little bit lower when that is healthiest, but does not prevent a rise in temperature, a fever, when necessary as with infection, but instead would promote it. This is very healthy. Having a “fever” when not necessary, and is promoted by the thermogenesis of burning ‘healthy starches’ and excess protein is what is not.

Readers of our book know that we think infections are a major factor in aging and premature death. Whether a diet so restricted in carbs that it significantly lowers body temperature is really optimal for longevity is, I think, open to question.

it is extremely important to have the confusion and misunderstanding by many if not most in the medical and health community of the true meaning of free T3 and body temperature being lowered, resolved.

In caloric restricted animals where body temperature and free T3 goes down, the immune response is markedly increased, and their mortality rate is well known to be significantly reduced while lifespan significantly increased. There is also a huge reduction in autoimmune diseases, secondary to improving immune function, not lowering it. The reason for the difference between the sick thyroid in the above-cited studies and the healthy thyroid in CR and my diet, is the reason that T-3 and body temperature is being lowered. In the former, it is being lowered because of sickness not because it generally is causing the sickness (though it may also). Certainly I can give the more extreme example that body temperature is lower when one is dead. In calorie restricted animals and in those on my diet, on the other hand, free T3 and body temperature are reduced as part and parcel of a shift in genetic expression towards maintenance, repair, and longevity, in the same way that the temperature of your car is reduced when it is functioning best; when it is getting the best mileage, has the best acceleration, and where the engine will live longest. In both cases, it is making the best use of available resources, and wanting to reduce waste. In the former, thyroid is low because it is sick. In the latter, and with my diet, thyroid goes lower to keep one healthy. If the car is running hotter, you know that is sick. It does so because it must and perhaps better than not running at all.

Furthermore, it is now a fairly well stablished finding that free T3 is reduced in centenarians. One example;

“A cross-section analysis of FT3 age-related changes in a group of old and oldest-old subjects, including centenarians’ relatives, shows that a down-regulated thyroid function has a familial component and is related to longevity”

Andrea Corsonello, et al

Age and Ageing 2010; 39: 723–727

“Down-regulation of thyroid hormones, due to either genetic predisposition or resetting of thyroid function [emphasis mine], favours longevity.”

The key is that we can reset our thyroid function to be that of centenarians, even if we were not so genetically predisposed. We can make our own luck, but not by adding carbohydrates..

If ketosis is an indication of fatty acid utilization as fuel, and if this is a marker of a shift in metabolism towards that seen in caloric restriction that has been shown to confer tremendous health benefits including longevity, then what Cahill states in his previously cited paper must be strongly noted; as little as 100 grms. of carbohydrate (that Jaminet recommends) will prevent this.

Fuel Metabolism in Starvation

Annu. Rev. Nutr. 2006.26:1-22.

George F. Cahill, Jr.

Department of Medicine, Harvard Medical School

There is a plausible case to be made for the Rosedale diet as a diet that sacrifices certain aspects of current health in the hope of extending lifespan. It cannot however claim to be the optimal diet for everyone. It is certainly not optimized for fertility, athleticism, or immunity against infections.

I suppose my diet may not be optimized for every single person, but not for the reasons that Jaminet states.  Those with impaired digestive function, that produce insufficient lipase or bile, may have difficulty with a high fat diet, but this would pertain to Paul’s diet also.  As far as the fertility, immunity, and athletic performance; ‘The Rosedale Diet’ actually improves fertility and immunity compared to a higher carbohydrate diet, and can be excellent for sports, with certain adjustments, depending on the type. The control of leptin is essential for immune function and fertility, and many studies show this.

Both Paul and I are asking people to sacrifice a little for the reward of better health. I may be asking for a little bit more (and that is debatable as ones addiction and desire areas of the brain become rewired as leptin is lowered), but I believe that the reward is exponential as one follows a diet that I have recommended, lowering non-fiber carbs as much as possible.

After all, we are not talking about a better health diet. We are talking about an optimal diet, a “Perfect Health” diet, as it were. That diet, as far as promoting a long, healthy and happy life would be as I have recommended for so many years, and would entail reducing consumption of sugars and starch as much as possible.

Jaminet Conclusion;

I am sympathetic to the broad perspective that underlies Dr Rosedale’s diet. Both our diets are low-carb, low-protein, and high-fat, and studies of longevity are the biggest factor motivating the recommendation to eat a fat-rich diet.

Thank you, and I agree…and ultimately, when this ‘debate’ settles down, we should join to fight the much larger battle against those recommending and even prescribing a low fat, high carbohydrate diet to the masses, that I think we both believe is largely contributory to the epidemic of chronic disease worldwide.

However, Dr Rosedale takes low-carb and low-protein dieting to an extreme that I think is not well supported by the evidence.

Dr Rosedale’s direct attempt at refuting our diet consists mainly of two claims:

Lower blood glucose is better than higher blood glucose.

The way to lower blood glucose is by eating fewer carbs.

Not exactly. As often previously stated, the major detriment of Jaminet’s diet are the spikes in glucose, insulin, and leptin that his diet results in, and the resultant contribution to insulin and leptin resistance. Unfortunately, this has been addressed only to a minor degree. I do agree, that this would happen less on Paul’s diet then the typical American diet, but considerably more than with the diet I recommend.

Neither claim is supported. Mortality is a U-shaped function of blood glucose and blood glucose levels around 90 to 100 mg/dl are healthiest, not low blood glucose levels. Moreover, the diet that delivers the lowest blood glucose levels is a high-carb, insulin-sensitizing diet, such as the Kitavans eat, not a low-carb diet.

This last statement is highly debatable, likely false, and disputed by many researchers and studies, some of which I have previously cited. A high carb diet only appears to be insulin sensitizing if compared to an even worse diet. Otherwise the phrase, “a high carb, insulin sensitizing diet”, is an oxymoron.

Calorie restriction results in very low blood glucose… and enhanced health and longevity. Furthermore,… Paul has just told us that the lowest blood glucose levels are not healthy, and yet cites the Kitivans with very low fasting BG for being so healthy. I’m confused.

If I truly believed Dr Rosedale’s argument for lower blood glucose, he would have persuaded me to eat a high-carb Kitavan-style diet. However, I am not persuaded.

I believe that:

Optimal blood glucose levels are in the 90 to 100 mg/dl range. High-carb diets cause below-optimal levels of blood glucose, especially during fasts. (Indeed, high-carb dieters routinely experience hunger and irritability during long fasts.) Very low-carb diets cause elevated blood glucose due to the body’s efforts to conserve glucose by suppressing utilization. Excessive suppression of glucose utilization is unhealthy.

A 20% carb diet, while not optimal for every single person, is healthy for nearly everyone. Twenty percent may be the best single prediction of the optimal carb intake for the population as a whole. Even diabetics can do well eating 20% carbs.

And that is why we recommend moderate consumption of safe starches.

While I maintain that fasting glucose is a much poorer index compared to measuring glucose excursions and insulin and leptin resistance, I must again show results from my own study;

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831640/

Here the fasting glucose on my diet fell to 99 mg/dl or that value that Jaminet says indicates the healthiest of diets, but here this occurs concurrent with lowering insulin and leptin, indicating much improved insulin and leptin sensitivity.

Rosedale Summary and Conclusions;

The studies and statements presented in my Jimmy Moore post and here should be understood by what they altogether point to.

1) The requirement for glucose is much less, even half of what Paul has indicated.

2) These requirements can easily be met without the consumption of a single gram of glucose in a very low carbohydrate adapted individual.

3) There is no such thing as a glucose deficiency.

4) Any excursion of glucose above baseline will result in some increment of damage and/or mortality. There is no threshold.

5) Repeated excursions of glucose above baseline cause excursions of insulin and leptin, and repeated excursions of these contribute to, if not cause insulin and leptin resistance, and this results in a significant acceleration of the chronic diseases of aging and aging itself. This is the major significance and detriment of eating a food that raises blood glucose.

6) One can’t pin one’s hope on only doing what is natural. Post reproductive death is extremely natural. We can only rely on science, especially the science of the biology of aging, to show how to live a long, post-reproductive lifespan. We have no footsteps to follow. Not the Kitavans, not the Okinawans.

7) We all have some degree of metabolic derangements including insulin and leptin resistance, and this really should be considered the hallmark of diabetes. We should therefore all be treated as such, especially with a diet known to improve those parameters as much as possible. That would be my Rosedale diet, as revealed in the only research paper that I am aware of (cited previously here) that correlates a particular diet with nearly all of the laboratory parameters associated with and perhaps causative of enhanced health and lifespan in a well known model of this, caloric restriction, though without having to caloric restrict.

8 ) I talked considerably about the meaning of the purposeful genetic expression of reduced thyroid levels that my Rosedale Diet accomplishes, particularly reduced free T3, and especially as it relates to point 7 above.

Jaminet’s major emphasis in this blog is the significance of fasting and 2 hr post prandial glucose. Unfortunately, that is likely the least important variable pertaining to glucose, insulin, leptin that is influenced by diet. There are many determinants of fasting blood glucose; sleep patterns, cortisol, sympathetic overdrive, growth hormone, to name but a few, that not only raise blood glucose but may increase mortality irrespective of blood glucose. I had used some studies of glucose levels to merely show a lack of toxic threshold.

Furthermore, I have shown that oscillations in glucose that undeniably occur after the consumption of ‘safe starches’, as any table of glycemic index would show, may result in damage to a more significant extent than even elevated fasting glucose.

Much of Jaminet’s argument is illustrated by his statement,

“Studies confirm that high-carb diets tend to lower fasting glucose and to lower the blood glucose response to a glucose challenge.”

Studies do not confirm anything of the sort. One study cited by Paul supports only that if a person eats a very high carbohydrate diet containing the equivalent of 22 tablespoons of Metamucil made up by a lab and eaten under supervision, that it can lead to some improvement over a standard American diet eaten at home, especially if that study is funded by large corporations with a huge financial interest in the outcome. This only serves as an example of the very poor science that permeates medicine and nutrition that unfortunately often is not realized…as does the other study that Jaminet uses to illustrate his point, where a high carbohydrate diet is compared to a low carbohydrate diet, and where the difference in calories is made up by force feeding 65% calories from corn oil. Moreover, it is confusing that this statement is made to support Jaminet’s diet, since he does not recommend a high carbohydrate diet, but a diet containing only a moderate consumption of ‘safe starches’ that these studies did not come close to following.

Furthermore, the support that Jaminet is able to muster from other articles he presents, is only derived by his improbable assumption that, since glucose spikes were not measured, that they mustn’t have ever gone above 140 mg/dl. Further ‘support’ was only secondary to a large error in conversion between blood and plasma glucose.

I believe the only conclusion that can be drawn from these and related studies that were presented, is the same as the authors’ conclusions; that fasting and 2 hr. glucose above some number, 100 mg/dl?, 105 mg/dl?, is correlated with some incremental degree of damage and/or mortality, and this is considerably less than 140 mg/dL that Jaminet has said is safe.

Little argument is given about the detrimental effects of eating ‘safe starches’ and glucose spikes on raising insulin, and resultant insulin resistance, with the exception of the (very poor) study that compared people eating a standard American diet to those eating a controlled, very high fiber (22 tablespoons!) diet, in which the latter did predictably better. I’m still not sure what the relevance of that study is.

Nothing was mentioned about leptin.

I believe that all of the 8 points that I have stated above are still standing strong, with little evidence to the contrary.

Further arguments given by Jaminet misinterpret the concept I had presented of the natural selection of reproductive success over a long post reproductive lifespan. He assumes that my diet would impair fertility, when, in fact proper leptin signaling, that my diet has been shown to promote, is essential to fertility. However the concept that nature doesn’t much care whether we live a long, healthy (post-reproductive) life is important, in that it tells us that we should not necessarily copy what we perceive to be natural. After all, hemlock is natural. So is dying.

So now, let’s take this debate deeper, and where it belongs.

Though nature doesn’t care whether we live a long, healthy life, nature does want us to live long enough to make (and raise) babies. We can use nature’s secrets about how to stay alive and healthy to make babies, and apply those secrets to post reproductive years, so that we can also live a younger and longer post reproductive life, whether nature cares about that or not.

We have no footsteps to follow in that quest, but must use the best science currently available related to a long and healthy life.

That gets us to the main issue and most important question that I had asked earlier;

Is there a diet (Rosedale’s or Paul’s) or glucose (starch) intake that can better maximize the repair/damage ratio that life, health, and youthful longevity depends on? Has this been answered here yet?

A little bit, as it pertains to thyroid. Paul has said that his diet would not have the effects on thyroid as my diet, namely lowering T3, and he is likely right; see below. However, though Paul thinks lowering thyroid is disadvantageous, it is far from; in fact quite the opposite. The purposeful lowering of thyroid likely helps to mediate metabolic advantages that help confer longevity in centenarians and in calorie restriction. Note that calorie restriction has been shown to greatly improve health and increase maximal lifespan in almost every species studied since the 1930s. The holy grail of aging research (including the giant pharmaceutical corporations) has been to find a way (drug) to mimic the effects of calorie restriction without having to do so. Read on.

In the study cited previously,

[In centenarians] “Down-regulation of thyroid hormones, due to either genetic predisposition or resetting of thyroid function, favours longevity.”

…as my diet has been shown to do.

And the effect of calorie restriction on thyroid;

Effect of Caloric Restriction and Dietary Composition on Serum T3 and Reverse T3 in Man

The Journal of Clinical Endocrinology & Metabolism jan1, 1976 vol. 42 no.1197-200

“Subjects receiving the no-carbohydrate hypocaloric diets for two weeks demonstrated a similar 47% decline in serum T3 [as caloric restriction] … In contrast, the same subjects receiving isocaloric diets containing at least 50 g of carbohydrate showed no significant changes in either T3 or rT3 concentration.”

Very low carbohydrates such as mine has similar effects on thyroid as caloric restriction. Keep in mind that I do not calorie restrict. People are told to eat whenever they are hungry, except for 3 hrs before bedtime.

Of interest is that the authors’ note in this study that the (isocaloric) addition of 50 gm of carbohydrate totally reversed this beneficial effect of lowering T3. Paul recommends at least 100 g of carbohydrate to be added everyday.

Some more clues..

Centenarian indicators of longevity;

Evaluation of neuroendocrine status in longevity.

Neurobiol Aging. 2007; 28(5):774-83

Baranowska B

“Our data revealed several differences in the neuroendocrine and metabolic status of centenarians, compared with other age groups, including the lowest serum concentrations of leptin, insulin and T3…”

Calorie Restriction indicators of longevity;

The Fall in Leptin Concentration Is a Major Determinant of the Metabolic Adaptation Induced by Caloric Restriction Independently of the Changes in Leptin Circadian Rhythms

The Journal of Clin. Endocrinology & Metabolism Sept 1, 2011 vol 96, no 9

Virgile Lecoultre, Eric Ravussin and Leanne M. Redman

Leptin is involved in the hormonal regulation of the reproductive, somatotropic, thyroid, and autonomic axes and ultimately in the regulation of energy balance. In parallel to the metabolic adaptation observed in response to caloric restriction (CR), plasma leptin concentrations are substantially decreased…Conclusion: Our results confirm an important role for leptin as an independent determinant of the metabolic adaptation in response to CR.

Note also that the reduction in leptin may be primary to elicit the metabolic adaptations of caloric restriction, including the reduction in thyroid/free T3, and therefore the extreme beneficial effects on health and lifespan.

That brings us back to my study;

Clinical Experience of a Diet Designed toReduce Aging

Journal of Applied Research, vol 9, no 4, 2009

Rosedale, Westman, Konhilis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831640/

“This retrospective analysis of patients from a private clinic adhering to a high-fat, low carbohydrate, adequate protein diet [the Rosedale diet] demonstrated reductions in critical metabolic mediators including insulin, leptin, glucose, triglycerides, and free T3… Patients in this study demonstrated a similar directional impact on the measured parameters when compared to studies using more established models of longevity such as caloric restriction.”

We may have found a way to mimic caloric restriction, at least to some extent and any extent is extraordinary. It appears that my diet can mimic the hormonal changes in T3, insulin, and leptin seen in calorie restriction studies that are instrumental to mediate the major physiological and extremely beneficial effects of calorie restriction, but without having to calorie restrict. This could more rightfully be called the perfect diet.

There are no studies that indicate that Jaminet’s diet would have similar benefits. However, there are clues that it would not. Cahill has shown that a carbohydrate intake of 100 grams/day (that coincidently Paul recommends) reverses ketoses, impedes the ability to burn fat, and likely prevents the full physiology and genetic expression of health and longevity as revealed by caloric restriction. Furthermore, adding 50 gm of carbohydrate may at least contribute to reversing the beneficial effect of lowering T3 that mediates much of the advantages of CR, as shown in the above study. Jaminet’s diet adds double that intake. Paul himself claims that his diet doesn’t lower thyroid, as he feels this to be unhealthy.

What is good pertaining to Jaminet’s diet, is that part of it that parallels mine, namely the higher fat and lower carbohydrate. That which is less good is the part of it that deviates from my diet, namely the addition of approximately 100 g of so-called ‘safe starches’ per day. However this is a significant difference in that it may undo the metabolic advantages that are seen in CR.

What is becoming clear, is that a high fat diet, that I believe to be far superior to high carbohydrate, low fat diets, must be accompanied by very low (non fiber) carbohydrate consumption for the deeper health benefits to be realized.

What I believe to be the crystallization of nutritional, biochemical, and biology of aging studies, and what the bottom line really is, is this; one’s health, youthspan, and lifespan, is predicated on burning fat. The more one burns fat as their primary fuel, the healthier and longer will likely be one’s life. Burning glucose will likely lead to far greater disease and a shorter life. Whether one burns glucose or fatty acids, or ketones from fatty acids, will be determined by powerful nutrient sensing hormones particularly insulin and leptin, and to be healthy these must be able to have their messages heard. Eating glucose will raise insulin and raise leptin, will impede the ability to burn fat, and contribute in some degree to progressive insulin and leptin resistance that is a hallmark of accelerated aging and its associated symptoms of cardiovascular disease, diabetes, obesity, osteoporosis, immunity disorders, brain and neurological diseases, and cancer.

My endeavor has been, and will be, to support ways to ward this off, and so far science has robustly supported a diet such as mine being the best way to do this.

I am very confident that virtually everything I have said for most of the last 20 years will eventually be shown to be correct. Much of it already has; insulin, insulin resistance, leptin resistance, mTOR and excess protein, even reducing calcium intake, and the myths of cholesterol… I have not had to revise my original premises, while most, if not all of the other original low carbohydrate advocates have tried to morph their diets into mine. My assertions and theories of nearly 20 years ago are still standing strong, and have yet to be disproven. Few, if any, in this field can claim that.

I believe that Jaminet’s diet can improve one’s health, but if you want to go to the next frontier, to that frontier where it is possible to slow down the effects of aging and reverse to a great extent many of the chronic diseases of aging, as revealed by calorie restriction and other elegant studies being done by scientists around the world studying the biology of aging, such as Cynthia Kenyon, you will have to take the next step that my diet will take you to. To do this, one has to reduce the consumption of sugar and starch to a further extent than recommended by Paul to be more in line with my recommendations. Adding glucose to my diet, as essentially done by Jaminet, has been shown to undo the beneficial effects (including youthful life extension) of reduced insulin signalling, as revealed by Cynthia Kenyon’s study that we had discussed over lunch many years previously…

Glucose Shortens the Lifespan of Caenorhabditis elegans by

Down-Regulating Aquaporin Gene Expression

Seung-Jae Lee, Coleen T. Murphy, and Cynthia Kenyon

Cell Metab. 2009 November ; 10(5): 379–391

“We found that adding a small amount of glucose to the medium (0.1-2%) shortened the lifespan of C. elegans…Together these findings raise the possibility that a low-sugar diet might have beneficial effects on lifespan in higher organisms”

Would I use Jaminet’s diet over the vast majority of diets out there? Yes I would. Would I recommend Jaminet’s “Perfect Health Diet” over my Rosedale Diet?  No way..

My email to Paul, that he himself quotes me as saying earlier in his response, especially rings loud and clear;

“At any level of glucose compatible with life some more meaningful degree of glycation, hormonal response and genetic expression will take place. We will always want/need to repair the damage done to stay alive, but with age the repair mechanisms become damaged also. Eventually damage outdoes repair and we ‘age’, acquire chronic disease, and die.”

My diet results not only in less damage, but in greater and prolonged ability to repair that damage, and this is of critical importance. That is the holy grail of diet, the ‘Most Perfect Diet’ so to speak.

Paul has been a wonderful partner in this discourse, allowing me to think about some of these topics that I may have forgotten about during the last 20 years. It has forced me to think about good arguments he has presented and to undertake a refresher course from myself.  Our basic premises about diet, as he mentioned, are very similar. We are talking refinements, though important ones. However a much bigger battle looms…with the American Diabetes Association, the American Medical Association, and standard of medical care, that still believes in that archaic and deadly notion that fat is the Darth Vader of health and the primary cause of disease.

It’s time to join forces and shift this debate to them. However, if Paul would like to continue this game of tag, he’s it…and I’m going to Maui…

The post Is the term, ‘safe starches’ an oxymoron? appeared first on Ron Rosedale, M.D..

This is an interview with Shelley Schlender, KGNU radio, Boulder, Colorado. Thank you Shelley for the article, graphics and the interview below. You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

Ron Rosedale recommends adequate protein and warns that excess protein is bad for health.

He gave this talk at the American Society of Bariatric Physicians (ASBP) meeting Oct 31, 2006.  They’re medical experts who work to reduce obesity.  As part of the 2006 presentations, the ASBP included a special segment that featured low-carb diets, researchers and scientists who are connected to the Nutrition and Metabolism Society.  Special thanks to Instatapes for recording this presentation.

Listen to Ron Rosedale speechListen to Ron Rosedale speech (40 minutes)

The good, the bad, and the ugly of protein.

The good, and that’s pretty good, is that we can’t live without it. It is a required nutrient. It’s an essential nutrient. Unlike carbohydrates, which is a nonessential nutrient, which means you don’t have to have any. With carboydrates, you can make whatever you need. With amino acids, you have to take some of them in.

Then we could go into a lot of the miscellaneous problems with proteins. I’m not going to go into that a lot. A lot of articles will show detriments to protein, and as Mike Eades mentioned, there’s a lot of articles will show it’s not detrimental. So it’s confusing. Whenever it’s confusing, it means you’re not going into it deep enough. You’re not go-ing deep enough into the basic science of it all.

Dairy products aside, when past and present meat consumption is factored in, there’s a three times risk of developing Alzheimer’s in meat eaters as opposed to vegetarians. Is that true or not? I don’t know. I don’t place a lot of emphasis on this kind of study. I want to go deeper because there is a lot of confusion. Here’s another study: High protein diet may precipitate a progression of coronary artery disease. Through an increase in lipid deposition and through inflammatory and coagulation pathways. Now if this is true, there must be underlying causes of this. That’s really what you want to get into to determine the truth of something.

We know that high protein can raise glucose. And I’m sure Mike Eades showed you studies where a high protein diet reduced blood sugars and was better for diabetics. But the question is, compared to what. If you compare a diet to the average American diet. If you change anything in the average American diet you’re going to improve it. Improving the American diet is not a trick. It’s like a race between a one-legged man and a grandmother. Who cares who wins that?

Here we’ve seen, if you eat a high protein diet, we’re going to go deeper and deeper and deeper into the science of all this. To see if there’s something to really tell us whether excess protein is good or bad. If you eat a high protein diet, there is excess stimulation of the transport to the liver. You flood the liver with amino acids, and it’s got to do something with them. You can do two things with protein. You can make protein, you can replenish the parts that have been torn down, or you can burn it for fuel. Hopefully, you’re not going to excrete it. Food was too precious in our evolutionary his-tory to waste it. Certainly, if you have protein in your urine, something is wrong. Burn it, or use it.

Rapid stimulation of the liver glycine cleavage system in rats fed a high protein diet. In other wods, you’re going to break down a lot of it if you eat a lot of it.

Glycine metabolism is stimulated by high protein feeding.

Effect of high protein intake on Insulin secretion and glucose. Hepatic glucose was sig-nificantly increased with high protein intake. It makes sense. If you have a bunch of amino acids floating around, your liver breaks extra protein into glucose forming carbon shells.

Insulin mediated suppression of hepatic glucose production was impaired with high protein intake but not in patients with a normal protein intake. Gluconeogensis was increased with a high protein diet. We conclude that a normal protein diet is accompanied by delayed progression of the continuous loss of endogenous insulin. We know that in diabetics, there’s a loss of islet cell function over time, and here they’re saying that high protein may contribute to that.

After adaptation to a protein restricted diet, if you restrict protein, diabetics experienced a 30% decrease in daily glucose concentrations, and I know from my practice, and this wasn’t in everybody, but if I had a diabetic, and I put all of them on a low carbohydrate diet. It doesn’t make sense to feed diabetics sugar. But in those that had more trouble processing sugar, the next step was reducing their protein, and I’d restrict it a lot, for an average size adult, I’d put them down to 50 grams a day, maybe 30 grams a day, and their sugar would then go down. So this isn’t just theoretical.

We conclude that severe protein restriction decreases insulin requirements in Type 1 diabetics and fasting hepatic glucose output and basal insulin levels in normal people. Not just diabetics.

We know that protein increases levels of insulin. We know that there’s an insulingenic effect in eating high protein. That’s well known. There’s also a leptin increase with pro-tein. Amino acids increase leptin. Continual high levels of insulin and leptin cause insulin resistance and leptin resistance. So you might get a short term benefit from high protein, but it may be at a price of a long-term detriment, If you keep those levels high. If you raise insulin you’re going to lower sugar temporarily until you become more insulin resistant, and if you raise leptin, you’re going to be less hungry, temporarily, until your hypothalamus becomes more resistant to its action. Which is will become by overexposure. It’s like if you’re in a smelly room, after a while you can’t smell it, the longer you stay in there.

Your cells work the same way. If they’re over-stimulated, they just put in earplugs. They don’t want to be yelled at.

Central nervous system. There’s a more critical role for leptin than insulin in mammalian energy homeostasis. People are ignoring leptin, but it’s probably more important than insulin in diabetes. And in all of the energy storage diseases. Metabolic syndrome, aging.

Why isn’t this really being told? Because there are no drugs that control leptin. So drug reps aren’t telling you about this. But, It can easily be controlled through diet. It is what tells you how to eat. You eat to control insulin and leptin. It’s very simple. Certain eating behaviors extend lifespan. They’ve shown that with dietary restriction. They thought it was calorie restriction, but it’s not. It’s restricting certain elements in the diet. Sugar and protein. Not fat. That’s a critical thing to understand.

In obesity, results of several studies show that chronically elevated central leptin, decreases hypothalamic leptin receptor expression and impairs receptor protein levels and impairs leptin signaling. So chronically elevated leptin contributes to leptin resistance, and leptin resistance leads to further obesity, leading to a vicious cycle of escalating metabolic devastation.

You can find a vicious cycle in almost any chronic disease. That’s why your body can’t deal with it. The way it deals with it ends up worsening the problem.

Lower leptin concentrations appeared to occur without evidence of increased hunger. If you lower leptin you improve leptin sensitivity. It’s suggesting a functional improvement in the resistance to leptin. The way to fix leptin and therefore obesity and therefore aging and diabetes and all sorts of things is by chronically keeping leptin down, your hypo-thalamus can increase sensitivity to it and listen to it. Not just by trying to up it. When leptin was first discovered that’s what they tried to do. Just give more leptin. How have they been treating diabetes? Give more insulin. Just up and up and up the insulin. No! You have to down and down and down the insulin. And give the cells more room to listen.

Communication is more dependent on listening actually, than speaking. Cells have to be able to listen to the signal.

If I were to start screaming at you, how many people will stay in this room? You’d cover your ears.

Response to energy restriction involving leptin concentrations is affected by dietary composition, not drugs. Macro-nutrient composition of the diet affects leptin. This is just saying that different protein compositions, different macro-nutrient compositions affected leptin.

On the high protein diet, the leptin messenger RNA did not decline upon fasting after a meal. It stayed up for a while. Chronically elevated leptin causes leptin resistance and leads to metabolic devastation.

Regulation of leptin secretion from white adipocytes by insulin glycolated substrates and amino acids. So the two things that will cause leptin spikes and chronically elevated leptin are sugar through a pathway called the hexosamine pathway and amino acids.

Amino acid precursors of citric acid cycle intermediate potently stimulates basal leptin secretion, insulin having an additive effect.

And the MTOR is one most people don’t know about yet, which is unfortunate. Because the MTOR pathway is intriguing, and may be one of the most, if not the most, important nutrient sensing pathway in the body, aside from insulin. And here, if you get nothing out of this talk, but this one sentence, MTOR is activated by free amino acids. MTOR is a pathway that senses protein concentrations. More specifically, amino acid concentrations. MTOR is also linked to leptin, and amino acids stimulates MTOR stimulates leptin.

Protein increases leptin, also triggers the hexosamine pathway, and the ugly. High protein apparently accelerates aging and therefore all the chronic diseases associated with aging.

The role of specific nutrients in caloric restriction. Dietary restriction has been shown to increase longevity which indicates it’s having positive results. However, it appears it is not caloric restriction but the carbohydrate and protein restrictions in the diet, the medi-ate the effects, at least in flies, and it appears in other organisms, also.

Why would protein be so important in the regulation of aging. Life is a constant battle between damage and damage control. If we could repair damage as fast as it occurs, we would live forever. Ultimately, unfortunately, we damage the damage control mechanisms, and that’s really what does us in.

Excess protein actually increases damage and reduces our ability to repair it, so it’s a double whammy.

Life at higher temperatures leads to a greater accumulation of irreversible damage that leads to death. One of the advantages you’ll hear all over the place is that it’s good to be thermogentic. If you go to a health food store, there are thermogenic aids all over the place. And one of the advantages given to a high protein diet is that it’s thermogenic. And it is. Without question, protein is the most thermogenic nutrient you can eat. It will produce the most heat. Well producing heat and living a long life are just not compatible.

If you went to a gas station and there were two pumps, and one said this pump will produce the most fuel efficiency and give you the most mileage, and this other pump will cause your car to run hotter . . .

Which one are you going to get? You’d never get the one that makes your car run hotter because what’s that going to do to your engine. Not good things. That’s why you have a radiator.

Protein increases glycation, oxidation damage, and we know that protein increases growth hormone and IGF-1. In the last talk, I constantly hammered that high IGF-1, and insulin promotes aging, through a separate pathway. We know that protein increases IGF 1 and AGES, the short term for Advanced glycated end products. There are two major causes of aging. One is oxidative damage and the other is advanced glycated end products, that’s when glucose combines with proteins and DNA. Basically glucose is a sticky molecule that changes the shape and function of whatever it sticks to. It forms what are called advanced glycated end products, the acronym being AGES and that was intentional because it plays such a major role in the chemistry of aging.

In some cells AGES increase with amino acids. In another study, profibrotic injury response occurred in messengial cells exposed to amino acids with or without high glucose by formation of AGES, oxidative stress and activation of the protein kinase Beta and Map Kinase pathways. Which are cell proliferation pathways. Calorie restriction slowing aging and extending life. Mice with pituitary glands devoid of growth hormone producing cells exhibit a remarkably extended lifespan, as do genetically altered mice where they targeted the disruption of the growth hormone receptor, which results in low concentrations of IGF. Andre Barke has done a lot of work on this. Wonderful man, and he’s now head of the American Aging Associaton. And he’s shown convincingly that when you keep insulin and IGF down, animals live a lot longer. And he recently won the Methuselah prize for the longest lived mouse.

Reducing protein extends life. If you restrict methionine, you decrease visceral fat mass and you preserve insulin action. Reduced dietary methionine and caloric restriction pro-long lifespan. In other words, it isn’t just caloric restriction. If you reduce dietary methionine without caloric restriction, you get the same thing, Methionine restricted rats shows reduced visceral fats, with decreases in insulin, glucose and leptin. Insulin responses in older methionine-restricted animals as measured by oral glucose challenge are similar to young animals. By 16 weeks, methionine restricted animals show a 40% reduction in IGF, which is sustained throughout life.

For 60 years, the only dietary manipulation showed to retard aging was Calorie restriction, and more recently, they’ve shown that it isn’t necessarily calories. If you decrease tryptophan, and you decrease cystine and methionine, you get the same thing. Methionine restriction is not a consequence of reduced energy intake. The intervention alters the rate of aging and not by correcting a single defect.

Recent work has shown that dietary restriction in fruit flies is a product of acute effect on genetic transcription that causes fully fed flies to adopt the mortality profile of lifelong dietary restricted flies within 40 hours of initiation. In other words, you don’t have to do this starting from an infant. If you adopted some of these today, you can get the same genetically healthy profile, the same healthy genetic transcription profile, as if you had been dietary restricted all your life.

In other words, you can do this at any time. You can experience the benefits of this. You can go back in time, essentially.

You can reduce your aging to a certain extent and therefore the diseases associated with aging, if you just adopt this now.

Alterations in nutrient related signaling pathways are thought to initiate the cascade of changes that underlie longevity assurance by dietary alterations.

The nutrient sensing pathways, that’s what is critical.

Insulin and IGF alter lifespan in rodents and many other species. Insulin is known to be involved in regulation of homeostasis in response to a diet, and is know to be a link between the calorie of the diet and extended action. However, two lines of evidence indicate that insulin and IGF are not the only pathway. If you reduce insulin IGF activity and then put them on a dietary restricted program, you have an added effect. They seem to function by two separate, parallel pathways. Reducing insulin and IGF are definitely good. You go further and what’s that pathway? MTOR. It’s a parallel pathway that operates alongside the insulin pathway, but apparently, separately.

These studies provide further support to the argument that protective effects of dietary restriction are not limited to calories alone but involve an aspect of protein metabolism as well. Sugar and protein. That’s what was available when all these signals arose, evolutionarily.

Lifespan is important not because Nature cares about you, but it cares about reproduction, and it wants you to reproduce at a future, more opportune time, if the nutrient availability isn’t good now. But we can use that knowledge. We can still dig into pathways that affect aging and health by what we eat.

A little more on MTOR. The amino-sensitive MTOR pathway from yeast to animals. The target of rapamycin, which is a drug being investigated for cancer, and heart disease and autoimmune diseases and many things. It’s a natural substance discovered by accident. They didn’t know how it worked, but that’s how MTOR pathway was found. Maybe less than 10 years ago. They found it was extremely important, and we’re going to understand that any effect of rapamycin is paralleled by low amino acids.  Rapamycin  inhibits MTOR. That’s what it does. That’s how it works. How it works to reduce cancer.

In a 2002 study, they reported that the process through which nutrients, amino acids, activate MTOR are largely unknown. They said then that evidence exists for both an intracellular and membrane bound sensor for the amino acid. Since then, they have a clearer idea of how it works.

Studies performed in fat cells, in ovarian cells, in liver cells, in muscles, pancreatic beta cells all show a sensitivity of phosphorylation status of MTOR subtrates and amino acid concentrations. In other words, it appears to work everywhere. All cells have apparently an MTOR signaling pathway that is sensitive to amino acid concentrations.

Indeed, activity of MTOR was determined by amino acid availability in each cell line tested. That is the main thing that will stimulate MTOR. It is an amino acid sensing pathway.

Here’s an interesting comment: Future studies that examine the link between amino acid transports and MTOR activity will resolve the initial signaling events that result in the activation of MTOR targets and will provide insights into the scavenging of nutrients by malignant cells. Malignant cells try to hoard amino acids, and when they do so, they upregulate MTOR, and when they up-regulate MTOR, they stimulate cell division.

Here we show that inhibition of MTOR activates apoptosis. One of the ways that cancer is allowed to progress by shutting off P53. P53 is one of the ways that we kill cancer. It’s a checkpoint. P53 triggers cell suicide, which is known as apoptosis. Course, cancer cells don’t want that. So they mutate, or inIn some way, P53 got mutated, and it can’t trigger that cell suicide. And here, it’s showing that rapamycin, by down-regulating MTOR, can trigger cell suicide without P53. It’s another checkpoint. In other words, keep amino acids low, and you can check that cancer in its tracks.

The TOR pathway regulates genetic expression by linking nutrient sensing to histone acetylation, and the promise of rapamycin as a cancer drug is being explored. This is in 2003. It’s been showing remarkable antitumor activity in cells. We therefore find it intriguing that rapomycin results in a gene profile seen in amino acid limitation.

There are two things seen in cancer cells require to keep going.

Two things any cell requires. Fuel and parts, the main parts being protein. It’s a requirement for cancer. It doesn’t take a lot of intelligence to know that if you want to suppress it, just don’t eat it.

Don’t give it sugar. Sugar can be used as an anaerobic fuel. You can burn sugar without oxygen. You have to have oxygen to burn fat. Cancer cells are rapidly dividing, and they mostly will outplace the supply of oxygen. The most aggressive cancer has to use sugar as a fuel source. One way to suppress cancer is just not to feed it sugar. But this isn’t some elegant drug, or some profit induced therapy, so it’s not being used. I’ve seen remarkable results by just eliminating sugar form the diet. And that means potatoes, pasta, rice and all that stuff that turns into sugar immediately. Another way is by toning down the amino acids. Now you have to have some. But we know that if you restrict amino acids, your body goes into an amino acid conservation mode.

Extension of chronological lifespan in yeast by decreased TOR signaling. TOR signaling regulates multiple cellular processes in response to nutrients, especially amino acids, raising the possibility that decreased TOR signaling mediates extended lifespan in caloric restriction. In support of this possibility, removal of either aspartame or glutamine from the media feeding the yeast significantly increased survival. Pharmacological Inhibition of TOR by rapomycin also increased lifespan.

We propose an up-regulation of a highly conserved response to starvation-induced stress is important lifespan extension by decreased TOR signaling in yeast and higher eukaryotes. Us.

There’s distinct signaling down stream. A lot of research going into MTOR. Key roles in regulating cell and animal growth. The cell cycle, gene expression. Recent studies have shown that MTOR is essential for cell growth and proliferation Rapamycin as a specific inhibitor of MTOR is in clinical use or potential use in graft rejection, restonosis after angioplasty, cancer angiogenesis, liver fibrosis and many other diseases. There is general agreement that amino acids do indeed stimulate the phosphorylation of MTOR downstream targets. Amino acid infusion during a euglycemic hyperinsulemic clamp in fasted humans decreased rather than increased glucose disposal. Raising glucose. Although these data may be explained by substrate competition. Ie, the Amino acids were oxidized instead of glucose. Which it is. Certainly partially. But there are indications the amino acids cause a time dependent rapamycin sensitive down regulation of protein kinase B and of glucose transport by insulin. In other words, it causes insulin resistance.

Another example suggesting that amino acids may cause insulin resistance is that of glutamine. This amino acid, which is a potent stimulator of glycogen synthesis is also a substrate for the hexose monophosphate shunt, and has been shown to highly regulate insulin sensitivity.

The importance of amino acid signaling in the coordination of whole body metabolism is also indicated by its involvement in the regulation of leptin production by adipocytes. Amino acids upregulate MTOR. Cause spikes in leptin.

There is an amino acid dependent signaling that controls lepin production via adipocytes.

The MTOR signaling pathway is frequently over-activated during cancer. Thus, the importance of amino acid signaling in cancer is evident.

When we’re talking about life extension in animals, we’re generally talking about reduction of cancer. Most laboratory animals die of cancer or autoimmune disease, so if you extend lifespan in laboratory animals, it’s synonymous with reducing cancer.

Another way that lifespan appears to be enhanced is by regulating protein turnover. You have to get rid of rotten proteins. We talked about AGES, and how glucose sticks to proteins and cause Proteins become malformed and do nasty things, so we have to get rid of them. Tear them down. We know with caloric restriction and other methods that enhance lifespan, you accelerate the breakdown of old proteins and manufacture of new proteins.

Proteozome mediated proteolysis and autophagic proteolysis declined with age. However, the last two pathways can be considered an anti-aging repair mechanism because they remove aberrant proteins and defective cellular organelles.

Caloric restriction not only increases proteozome proteolysis. But also autophagic proteolysis, which may contribute to increased longevity. When you upregulate MTOR you down regulate proteolysis.

The best drug to reduce MTOR signaling, to slow aging and the chronic diseases associated with it is already available. Avoid high protein.

But what is that? What is high protein. You can go to a lot of textbooks that talk about .6 grams per kilogram. But one study that I think is very interesting . . . You can get into a ballpark. When you talk about 2 to 3 grams of protein per kilogram of lean body mass, that is certainly too much protein.

But what is the requirement in an infant, infant, being breastfed. Young infants, 2 months old, have the highest protein need. They’re growing rapidly. Brain is growing. The protein content in breastmilk is about 1 gram per 100 milliliters, and the daily intake is approximately on 1 gram per kilogram per day. That’s what nature says is the requirement of a growing, breast-feeding infant.

When other foods are introduced during the weaning period the protein intake Increases remarkably to 3 or 4 grams of protein per kilogram per day in spite of the fact that the protein requirements are decreasing. The long-term consequences are obscure. Although I think the MTOR signaling are telling us what those long-term consequences might be. A high protein intake has endocrine effects such as it increases insulin, increases IGF, and we know these hormones increase the rate of aging. Furthermore the metabolic effect of high urea and many amino acids may exceed the kidney and hepatic system’s ability to metabolize and excrete the excess nitrogen.

In other words, when you use protein as a fuel, you take off the excess nitrogen, and then you have to do something with it. Because, it’s a poison. If you take too much, It causes acidosis in the blood and that causes redistribution of calcium and magnesium, and all sorts of things, and what the consequence are for that is manifold.

So what’s high.  Certainly above 1 gram per kilogram of lean mass is probably high.

Most people, I’ll put on .7 or .75 grams per kilogram of lean body mass.

But if I’ve got a diabetic, and I really want to reverse their aging, which means reverse their diabetes, because diabetis is a model of aging, I’ll put them down to .5 or .6 grams per kilogram of lean body mass per day.

So what’s left to eat?

We know that sugar, foods that turn into sugar, raise insulin, IGF accelerate aging, worsens diabetes. It’s horrible for you. Now I’m telling you that extra protein isn’t good for you either. It appears to accelerate the MTOR pathway and has all kinds of debilitating effect, not the least of which is stimulating cancer.

Fat. Eat fat.

Fat appears not to stimulate insulin. It does not stimulate the MTOR pathway. It does not cause an increase of leptin and in fact it keeps it down. And our health is going to be dependent on what our hormones tell our brains to do, whether to be hungry or not. If you keep leptin down and your hypothalamus can listen to leptin, you are not going to overeat. When leptin is down it stimulates fat burning. It helps diabetes. It helps all sorts of things. I’ve been doing this for over two decades now, and I can tell you for sure it happens.

You have to regulate the hormones that regulate your brain, and you do this by diet, and then you can affect the rate of aging and the incidence of the diseases associated with aging.

Special thanks to Greg and April at Instatapes for helping to track down the audio of this talk, and to Ron for permission to post the audio and transcript of the citations used in the talk.

The post Protein: The Good, The Bad and The Ugly appeared first on Ron Rosedale, M.D..

This is an interview with Shelley Schlender, KGNU radio, Boulder, Colorado. Thank you Shelley for the article, graphics and the interview below. You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

New research published in the British Medical Journal indicates men and women over 40 who take calcium supplements increase their risk of heart attack by 30%, compared to people who don’t take the supplements.  The study points out that often, people take calcium supplements hoping that this will reduce their risk of breaking bones,  even though in actual fact, taking more calcium only reduces bone fractures by a marginal amount.  Baron and coauthors caution that the benefit of reducing bone fracture risk by taking calcium supplements may be outweighed by the likelihood of increasing heart attacks.

Listen to Ron Rosedale Interview – Short Version (7 minutes, Broadcast on KGNU, also same as the video below)

Listen to Ron Rosedale Interview – Short Version (7 Minutes, Broadcast on KGNU)

Listen to Ron Rosedale Interview – Long Version (25 minutes which starts with the first 7 minutes of KGNU interview)

Listen to Ron Rosedale Interview – Long Version (25 Minutes – Starts with first 7 Minutes of KGNU Interview)

The study is being hotly contested by many supplement manufacturers.  One person who says it’s a predictable result is Dr. Ron Rosedale, who has been speaking out against calcium supplements for years.  Dr. Rosedale points out that often, people who have “thin bones” have high amounts of calcium plaque in their blood vessels, a condition which is well-documented for increasing the chance of heart attacks.  People with thin bones also can have calcium deposits in their joints . . .  for instance, with arthritis.  Dr. Rosedale says that when people have osteoporosis, it’s generally not the case that they need more calcium.  Instead, they need clearer signaling instructions in their body, so the calcium goes where it’s needed, not stuck in places that cause trouble.  For more, here’s Dr. Rosedale.

Watch this video on YouTube.

The post Death by Calcium, why Calcium Supplements Increase Heart Attacks – Ron Rosedale, M.D. interviewed by Shelley Schlender, KGNU appeared first on Ron Rosedale, M.D..

This is an interview with Shelley Schlender, KGNU radio, Boulder, Colorado. Thank you Shelley for the article, graphics and the interview below. You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

 Dr. Ron Rosedale discusses a woman who nearly died from a deadly side effect of statin drugs, called, Rhabdomyolysis.

LISTEN: Cholesterol Medication Side Effects: Cholesterol Medications Side Effects – Ron Rosedale MD

Millions of people take cholesterol lowering medications.  But many of those who do complain about weakness and muscle pain.  Why do these side effects happen?  What if these symptoms turn deadly?  To find out, up next, we’ll talk with Dr. Ron Rosedale.

Dr. Rosedale is the author of The Rosedale Diet.

An article written by Dr. Rosedale titled: Cholesterol is NOT the cause of heart disease

The full article can be downloaded here: Cholesterol is NOT the cause of heart disease

Cholesterol is not the major culprit in heart disease or any disease. If it becomes oxidized it can irritate/inflame tissues in which it is lodged in, such as the endothelium (lining of the arteries). This would be one of numerous causes of chronic inflammation that can injure the lining of arteries. However, many good fats are easily oxidized such as omega-3 fatty acids, but it does not mean that you should avoid it at all costs.

Common sense would indicate that we should avoid the oxidation (rancidity) of cholesterol and fatty acids and not get rid of important life- giving molecules. Using the same conventional medical thinking that is being used for cholesterol would lead one to believe that doctors should reduce the risk of Alzheimer’s disease by taking out everybody’s brain.

In fact, cholesterol is being transported to tissues as part of an inflammatory response that is there to repair damage.

The fixation on cholesterol as a major cause of heart disease defies the last 15 years of science and deflects from real causes such as the damage (via glycation) that sugars such as glucose and fructose inflict on tissues, including the lining of arteries, causing chronic inflammation and resultant plaque.

Insulin & Leptin Resistance

Hundreds of excellent scientific articles have linked insulin resistance and more recently leptin resistance to cardiovascular disease much more strongly than cholesterol, and they are in fact at least partially responsible for cholesterol abnormalities. For instance, insulin and leptin resistance result in “small dense” LDL particles and a greater number of particles.

This is much more important than the total cholesterol number. Because of particle size shift to small and dense, the total LDL cholesterol could still be low even though the number of particles and the density of the particles is greater. Small, dense LDL particles can squeeze between the cells lining the inside of the arteries, the “gap junction” of the endothelium, where they can get stuck and potentially oxidize, turn rancid, and cause inflammation of the lining of the arteries and plaque formation.

Importantly, many solid scientific studies have shown a mechanistic, causal effect of elevated insulin and leptin on heart and vascular disease, whereas almost all studies with cholesterol misleadingly only show an association. Association does not imply cause. For instance, something else may be causing lipid abnormalities such as elevated cholesterol and triglycerides, and also causing heart disease.

This “something else” is improper insulin and leptin signaling. Similarly, sugar does not cause diabetes; sugar is just listening to orders. Improper insulin and leptin signaling is the cause of diabetes. Likewise, cholesterol does not cause heart disease, but improper metabolic signals including improper signals to cholesterol (causing it to oxidize) and perhaps to the liver that manufactures the cholesterol, will cause heart and vascular disease and hypertension.

Removing cholesterol will do nothing to improve the underlying problems, the real roots of chronic disease, which will always have to do with improper communication, and the generals of metabolic communication are insulin and leptin. They are really what must be treated to reverse heart disease, diabetes, osteoporosis, obesity, and to some extent aging itself.

 .. continue reading the full article as seen on Dr. Mercola’s site.

 Should I take cholesterol lowering drugs?

The post Cholesterol Medication Side Effects – Radio Interview appeared first on Ron Rosedale, M.D..

Dr. Ron Rosedale, interviewed by Shelley Schlender.  Wonderful article brought together by Shelley, all credits below for graphics and content.  Learn more about Shelley and her passion for exposing the truth in health, www.meandmydiabetes.com

A study published in the New England Journal of Medicine made headlines this week by showing that palliative care for terminal cancer patients, meaning pain and stress reduction care, extended their lives more than conventional chemo and radiation alone, and more than aggressive cancer treatments.  The study focused on lung cancer patients whose cancer had spread.  On average, those with conventional care alone lived six to twelve months.  Those with palliative care as well lived three months longer and reported better quality of life.  This study is a strong indicator that stress and pain reduction have powerful benefits.  For an alternative perspective on why these make a difference . . . and why another alternative treatment that might make a difference as well, here’s anti-aging expert, Dr. Ron Rosedale.  We caution you that while Dr. Rosedale’s views are intriguing . . . they’re also controversial, and they are not a substitution for the advice of your medical doctor.  Here’s Ron Rosedale:

Listen to Short Interview – Broadcast on KGNU (6 minutes)

That’s Ron Rosedale, discussing the New England Journal of Medicine study that indicates how, adding stress and pain reduction care to conventional care for terminal cancer patients adds to an extension of their life, and an improvement in the quality of their life.

Extended Version of the Interview

 Listen to Extended Interview (25 Minutes)

RON ROSEDALE: One of the reasons given in the New England Journal of Medicine Study for the life extension is that palliative care reduced stress, reduced pain, and these may have allowed for improved immune system.  But if you look at it in the bigger picture, what you’re seeing is that aggressive care, or more of the care that is considered conventional will make a person worse.  And that begs the question, will conventional care make a person worse in the chronic diseases of aging.  So is the typical conventional treatment of heart disease, diabetes, heart disease and other chronic diseases of aging worsening the underlying disease instead of improving it?  And my answer would be yes.

It’s a sad statement and would raise a lot of eyebrows, but I’ve said it for quite some time that if Medicine did nothing to these chronic diseases of aging, if they didn’t treat them at all, I think they’d be better off, and I think that’s very sad.

In the cancer study on palliative care, what I think is being revealed is the underlying science that aggressive cancer feeds on glucose.  It requires an anaerobic fuel because it outpaces the blood supply.  It can’t allow itself enough fuel to multiply quickly, if it were to burn fat, so it is an obligate glucose burner when it’s multiplying fast.  Just like a sprinter has to burn sugar when they’re running fast.  When cancer cells are multiplying rapidly, they require glucose because glucose can be burned without oxygen.

When someone’s under stress, whether it’s from pain or excessive use of anti-cancer drugs, or they’re just plain worrying, does that increase blood sugar levels in the body?

RON ROSEDALE: Exactly.  The potential reasons why palliative care improved outcomes in cancer patients is because it lowered glucose.  But the most impressive way to lower glucose is just to not eat it. And yet that is not part of standard medical care for cancer patients. It totally eludes me.  It’s very well known that the most aggressive cancers have to burn sugar and yet they don’t tell people not to eat it.  When we’re talking about sugar, we’re not just talking about white table sugar.  We’re talking about potatoes and rice and bread, cereals, starches will almost immediately turn into glucose in the body, or at least within a few minutes in the body, and that will feed the cancer cells.  More importantly, they’ll also up-regulate an important hormone well-known in diabetes, but which plays a critical role in everybody’s lives, and that’s insulin.  Insulin itself is a growth factor, and when insulin is raised, it stimulates cells to multiply, and that just stimulates cancer.  So two of the best ways to reduce both the risk of cancer and to treat cancer, are to keep glucose levels as low as possible, and insulin levels as low as possible.   So not one at the expense of the other.  So you don’t want to take drugs that raise insulin in order to lower blood sugar. The only way to lower glucose and insulin at the same time is through dietary approaches.   And yet that’s not even on the radar in standard cancer therapy treatments.

Last year, there was a study done on laboratory animals where researchers gave them intermittent fasting, meaning on some days they were given less food than on other days.  There was reduction in the breast cancer tumors that had been injected into the lab animals that were doing this intermittent fasting.  This was a dietary change.

RON ROSEDALE: Intermittent fasting is a modality that has been looked at for caloric restriction and extension of life.  Caloric restriction is a known way to increase lifespan in virtually all species of animals ever tested.  You don’t have to restrict calories all the time.  You can just greatly restrict calories every other day.  When they talk about increasing lifespan, and biology of aging studies, it’s really analogous to reducing cancer because that’s what most lab animals die of.  It’s been known for over 70 years that restricting calories of lab animals will increase their lifespan.  And therefore reduce both incidence and progression of cancer.  One of the things we know in the biology of aging is that when you keep insulin levels low, it reduces the growth factors that cancer cells require to multiply.  The importance of glucose is exemplified by the fact that PET scans all over the world are used to diagnose cancer, and they work by identifying areas of high glucose metabolism, and yet they still don’t people on a low glucose, low non-fiber carbohydrate, meaning starchy and sugary, diet.

It is not a disease that I would say I specialize in but I have treated cancer patients and I put all of them on a low to moderate protein, very low carbohydrate, high beneficial fat diet and they’ve done extremely well and have reversed quite a few cases of so-called met static and so-called cancer.  Some have been studied worldwide actually.  One was the first known case of survival.  I can’t say there’s a cure for cancer but certainly one can at least use the science we know of.  But the problem is, there’s really no money in it.

Unfortunately, the modalities that generally get widely used are the ones that have income, and not just for greed—income for supposed medical studies that would then get published.  In other words, a pharmaceutical company, or any large corporation is not going to spend 50 to 100 million dollars on a treatment modality where they aren’t going to get any  money back.  So many of these treatments never get publicized because there aren’t good studies to back them.  There are some animal studies because those are cheaper.

In India, I spent a couple of years in India for their diabetic problem, their heart disease problems.  But I also wanted to look at cancer.  There was a hospital that wished to do it, and they had accepted the dietary approach and wished to do it, but they said it can only be done in conjunction with standard therapy.  Because otherwise it would never pass the ethics committee.

What I wanted to do is just test two groups of patients.  Even two groups of patients where they were considered to be very terminal, which essentially means they had nothing to lose, and compare a dietary approach to a standard or aggressive chemotherapy approach.  And that wasn’t passed.  They wouldn’t allow that.  They would only allow it in conjunction with chemotherapy, but that would have messed it up.

Is your concern that if you gave a dietary approach to slow down cancer growth and added chemotherapy, they would be fighting each other?

RON ROSEDALE: Yes.  I think the adverse effect of the chemotherapy would really overwhelm some of the beneficial things you would see from the dietary approach.  One of the major endeavors really in anybody who is sick in any way is to enhance the functioning of the immune system, and chemotherapy in a devastating manner impairs the function of the immune system.  It almost seals many people’s death, when they have cancer.  You will never, no matter what treatment you use, whether chemotherapy or radiation, wipe out all the cancer cells.  There will always be some left over.  Your immune system has to mop up the remainder.  And you require a powerful immune system, and the chemotherapy really wipes out the immune system, so you don’t have that capability.

Even if you, through chemotherapy or radiation, kill 98% of the cancer, which would be largely unachievable in metastatic tumors, the other 2% will come back because you don’t have an immune system that would be able to take care of the rest.  Whereas with a dietary approach, you increase the functioning of the immune system, and it’s one of the major ways it works, and it’s one of the major ways it extends lifespan in laboratory animals, is by improving the functioning of the immune system, which is what has to happen whenever someone is diseased, but especially, when someone has cancer.

In 2008, there were some startling studies about breast cancer and how women who had mammograms more frequently also had cancer diagnosed more frequently.  Researchers concluded that in women who have less frequent mammograms, some of the tumors that would have been treated, if they were getting mammograms, are taken care of spontaneously by their bodies.

RON ROSEDALE: Yes, and there have been a lot of verifying studies that everybody gets cancer.  Cancer cells develop in everybody most of the time.  As long as you have a healthy immune system, it will recognize the cancer and eat it up.  Also we’ve talked about the importance of proper signaling between the 20 billion cells that make us up.  These signals are mediated mostly through hormones, and quite a few studies have shown that when insulin is kept low, the risk of breast cancer and prostate cancer and several other cancers is very much minimized.  They’ve even shown that you can treat prostate cancer by lowering insulin and by inference, by lowering glucose.

There are studies that show these results.  They’re not that rare, and I remember a study that showed that women who ate the least amount of pasta, and therefore, had a lower glucose load, had a lower incidence of breast cancer, and I believe that study was done in Italy.  So there are studies that show these correlations at the very least between glucose, insulin and cancer, for both treatment and prevention.  But unfortunately, it’s not commonly used, and it wouldn’t cost anything, and I strongly believe it’s the most powerful defense we have against both the risk of cancer and to treat cancer.

Right now, you’re talking about dietary approaches to treating cancer.  The New England Journal of Medicine report regarding palliative care was looking more at how reducing stress can help the body, but you’re saying the mechanism might be similar – that by reducing stress, you reduce the kind of hormones and high blood sugars that can feed cancer.

RON ROSEDALE: For the same reason that when you reduce stress,  you reduce epinephrine, nonepinephrin and corrison.  Your body worries about living the next five minutes.  If you’re going into battle with a lion, you’d like those hormones to enhance your fighting performance or your running performance.  You don’t want the extra sugar.  You’re not really going to be burning it.  The article also talked about painkillers.  Palliative care is essentially about reducing pain.  When researchers gave people pain reduction medications in earlier studies, they seemed to have an enhanced survival.  A plausible explanation is that also reduces blood sugar.  Pain is a very powerful stress, and we know that when a person is under pain it will increase epinephrine, norepinephrine and other hormones.  Any diabetic will tell you when they have pain, their blood sugar goes up.  That’s certainly something I’ve seen in my patients for decades.

In your estimation it might be a wise choice for someone to take the gamble of focusing on noninvasive treatments such as reducing stress levels and changing their diet as a way to deal with cancer.  But just as in India, medical ethics committees challenged you about using a dietary approach alone to treat cancer, without chemotherapy, people would probably be challenged in the United States for trying your approach.   Especially for a disease such as small cell lung cancer, which was the focus of this palliative care study.  The reason that conventional care is chosen so often is that the survival rate for metastasized small cell lung cancer, WITHOUT conventional chemotherapy and radiation, the average survival was two to three months.  Whereas the average survival with chemotherapy and radiation is six months to a year.  Statistics seem to make it very evident that conventional chemotherapy and radiation extends the life of someone with small cell lung cancer that has metastacized.

RON ROSEDALE: First of all, and this is what becomes so difficult now, there are so many studies that have been shown, subsequently to be false.  When there is lots of money to be made, there is lots of incentive for drug companies to skew statistics in their favor.  I think that’s now being brought before congress with Avandia.  But we’ve seen it with many, many other drugs.  Chemotherapy is very expensive.  It makes lots of money for drug companies.  So can you believe the statistics?  My answer is I don’t know.  Number two, what I feel might happen is that chemotherapy might extend certain people’s lifespan, but it also might sign their death certificate.  In other words, it might extend your life a couple of months, but it will assure you die afterward, because you won’t have an immune system.  And that’s not looked at.  Negative statistics will never get published.  There’s no mandate to publish negative results like that. If it did occur, any drug company would hide it, and you’d never see that.  So it’s really hard to tease fact from fiction in a lot of these studies.  All you can do is go much deeper into the basic science of it.  And understand that glucose feeds cancer, insulin is a signal for cells to multiply.  Leptin plays a role.  All of these are dietary signals.  And then we have other pathways that involve protein that are very powerful in cancer progression, so much so that pharmaceutical companies are looking for ways to manipulate these pathways with drugs, even though we can do that just with what people eat, but there’s no money in that.  So, it’s a problem.

Before we close of the day, how about if we talk about related topic regarding cancer that might tie in with this discussion?  Angiogenesis is a big word right now.  Lots of people are interested in what can reduce the chance of angiogenesis is in cancer.  Do you want to explain what angiogenesis is and how a dietary change might affect that?

RON ROSEDALE: Angiogenesis literally means to build blood vessels, and it takes a lot of fuel for cancer cells to multiply, just as it takes more fuel for pregnant women to make a baby, and the fuel has to be transported through the bloodstream.  For cancer cells to be able to multiply the body has to deliver the nutrients for the multiplications.  That’s going to be through blood vessels, so cancer cells put out signals to build blood vessel into the tumor to feed itself.    There are inhibitors of that blood building process that have been shown to reduce the growth of cancer.

But there’s another way one can look at it, too.  What is it that the cancer cells are getting delivered?  The major nutrients that cancer cells need delivered are going to be glucose and protein, and there are signals we know also that are required for angiogenesis.  One of those would be insulin.  Also leptin.  And if a person eats too much protein, that will increase a pathway known as mTOR that will increase cell multiplication.  It doesn’t take a big leap of faith or leap of science to just want to not deliver those nutrients to a cancer cell in your diet.

There are only two fuels your body can burn.  This is major.  You can only burn sugar or fat.  Or byproducts of fat metabolism called ketones.  And that’s it.  You don’t have any other choice of fuel. And all of your cells in your body would actually much prefer to burn fat or ketones than glucose, with a few exceptions, with red blood cells being the major one.  Whereas, cancer much prefers glucose.  So that’s a major difference between cancer cells and healthy cells in your body.  That difference has to be made use of, because there aren’t a lot of differences otherwise.

Cancer cells are regular human cells.  They’re just healthy cells that have reverted back to their bacterial heritage that is telling them to multiply.  They require the same nutrients that the rest of your cells require, with that one big difference.  And that is, they prefer glucose and the rest of your cells essentially prefer fat.  You have to utilize that difference.  Don’t eat glucose.  It’s as simple as that.  The minimum daily requirement for glucose or any sugar and that means starch consumption is zero.  You don’t have to have any.  And if I had cancer, my intake of sugars and starches would be zero.  That doesn’t mean you’d get your blood sugar down to zero.  But you don’t have to give cancer cells any more sugar than your body would otherwise make.  I also would not eat excess protein.  You have to eat some because protein is an essential nutrient and otherwise you would die.  I would eat lots of fats and good fats and fish oils.  And I would eat coconut oil, olive oil, nuts, avocados.  I would eat the fuel that the rest of your body would really be happy to burn and that cancer cells can’t use.  We know that low levels of both of those hormones are associated with a very low risk of cancer.  And an extension of lifespan otherwise.  You’ll increase maintenance and repair.

Would also hang out with good friends and go for walks in the park and smell the flowers?

RON ROSEDALE: That sounds like a great idea.  I most certainly would do that.

The post Cancer, Pain Relief & Diet: Ron Rosedale and Shelley Schlender appeared first on Ron Rosedale, M.D..

Ron Rosedale, M.D. interviewed by Shelley Schlender, KGNU radio, Boulder, Colorado.

We are very grateful to Shelley for the interview, the article, graphics and audio below.  You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

Download Audio MP3 version

RON ROSEDALE

No, we don’t want diseases, period. Unfortunately, it is part of life. The major problem is not that we’re getting the diseases, but that we’re getting them more frequently and younger. The rise in these chronic diseases—in fact, virtually all chronic diseases—correlates with the patterns of dietary changes that we’ve been seeing, perhaps delayed by 20 or 30 years for the results of the dietary changes to actually manifest themselves. But I think there’s a strong link between diet, metabolism, and all of the chronic diseases of aging, including neurodegenerative diseases.

Not everybody agrees that diet is a major contributor to this increase in neurodegenerative disease.   A more widely held medical theory is called the hygiene hypothesis.  It says autoimmune and neurodegenerative diseases are increasing because our world has gotten too clean. We don’t have enough germs and dirtiness in the world, we have more vaccines and antibiotics used.

RON ROSEDALE

I recall hearing that at least 20 years ago, and I totally agree with it. I see no fault with that argument. The only fault I see is that that’s the only reason. I think there’s ample evidence to show that the dietary changes, exclusive of cleanliness, have a huge impact on neurodegenerative diseases in addition to our lack of early exposure to antigenic stimuli for our immune system. So I think that that certainly plays a role. I think when you’re exposed early in life to the typical antigens, the typical bacteria and viruses and other immune stimulating effects, it does program our immune system to do what it evolutionarily is supposed to do and therefore help fight disease and not fight itself, not fight your own body. In other words, it helps the body to become less confused as to what is self and what is non-self. That’s a very, very important bit of information that the body requires for its immune system, so the regulatory T cells and inhibitory T cells that prevent overactivity of the immune system are properly developed.

Leptin “Spikes” Increase Risk of Multiple Sclerosis (MS)

But I think there is at least as much evidence to show that the regulatory T cells and the immune system are also very much affected by dietary changes and that these effects can occur almost from day to day, but that metabolic diseases such as leptin resistance have a huge impact on the immune system. Studies show that autoimmune diseases such a animal models of MS almost uniformly show a big rise in leptin prior to the clinical onset of the disease.

When you mentioned that there’s a big rise in leptin before the onset of the disease, I’m trying to picture that. Does that mean that there is a sudden spike one day where leptin levels go 100 times higher than usual? Or does that mean that over time, if you check the fasting level of somebody, that their leptin levels, that hormone in their blood increases consistently and stays high?

RON ROSEDALE

I’ve seen studies to show both. (see If you have a chronically high leptin level, your instance of autoimmune neurological diseases such as MS is greatly increased, and if you suppress leptin chemically, although I would recommend doing it dietarily, you can reduce the risk of onset by a great deal of MS. But I’ve also seen articles that showed a sudden spike, it was 100 times as much, but certainly a several-fold spike in leptin in the weeks prior to the onset of MS, even with a consistent diet. All of the knowledge, all of the pieces have not been put together, but what it does show is a powerful connection between leptin and autoimmune disease, especially MS.

(Editor’s Note – Here are links to some of these studies:  A Key Role of Leptin in the control of T-Cell Proliferation, De Rosa V,

Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephaloymelitis, De Rosa V,

The intricate interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis? Giuseppe Matarese

I’m trying to picture how scientists were able to figure out that a leptin spike could make a difference in this autoimmune disease MS. Very few people get their leptin levels checked very often. How did they figure this out?

I don’t know what was the light bulb initially, other than perhaps the fact that scientists now have been linking leptin with virtually all chronic diseases, so why leave out autoimmune diseases? In addition, leptin levels have been linked with longevity, signs of aging, and certainly autoimmune diseases are a big part of that. Most of the studies on aging, of course, are done on animals, very difficult to do lifespan studies on humans, because they take such a long time. But two of the main causes of death in laboratory animals are cancer and autoimmune disease, so both of those diseases have been studied quite intensively with leptin. Another piece of information that was discovered is that regulatory T cells, part of the white blood cells that tend to regulate the immune response, regulate information, basically keeps it from being like a fire burning out of control, you want a controlled fire, not one that just burns down the forest. Regulatory T cells have receptors for leptin and it has even been found that they can secrete leptin, that the immune system and leptin have a power connection.

T cells I think of as the ones you hear about, attacking the wrong thing when somebody has an autoimmune disease.  You hear that their T cells, instead of going after invaders in the body go after the body.

RON ROSEDALE

Right. It gets confused as to what is yourself that should not be attacked and what is something foreign that ought to be attacked. Sometimes it can be difficult to distinguish to two, especially when some of the foods we’re eating are so similar to ourselves. All life, really, is quite similar genetically, and all the cells are quite similar, so it actually takes a very, very acutely intelligent immune system to figure out what is you and what isn’t once things are actually digested. It’s a very important piece of the puzzle in autoimmune diseases, and certainly antibiotics, I feel, play a huge role. Their use is wildly out of control. Everybody’s getting antibiotics. If you get a sore throat, you’ll get an antibiotic, even though 90% of those sore throats are caused by viruses, and the antibiotic, if it does anything, will make it worse. That antibiotic will not just kill so-called pathogenic, disease-causing bacteria, it will also kill the good bacteria that inhabit your throat and your gut and your sinuses and your skin. We need those bacteria. We have evolved with those bacteria. The majority of people don’t realize that in a normal healthy state, we have four times as many bacteria inhabiting our bodies as we have cells. So we’re not talking about a small amount. We’re talking about the majority of cells that actually are part of us, are beneficial bacteria, that we end up at least partially killing when we take antibiotics.

And when we kill those bacteria, they don’t necessarily come back as they were. It allows other pathogenic bacteria to permanently become part of our flora and cause continual problems in our gut, for instance. It’s quite known that when you take antibiotics, you can have an intestinal yeast infection, although many times it’s sub clinical. If it’s bad it’ll cause diarrhea and bloating and gas and somebody will speak up and they still generally don’t find it. But many times you don’t have those overt symptoms, but you can have various stomach aches and pains, or food tolerance becomes less. What it does do is impair, permanently alter your immune system and immune response until you change that bacterial flora, you reduce the amount of yeast, kill off some of the pathogenic bacteria that inhabit the gut secondary to the use of antibiotics and then reintroduce some of the more beneficial bacteria.

But that’s, again, just one small portion of the story. Then you have the dietary impact on insulin and leptin and their impact on the T cells and other immune modulators and its effect on bone and the effects of bone on the immune system, as we’ve talked about in the past. There’s a huge connection between autoimmune disease, the immune system, and survivability, disease, and diet. The reason, really, is that diet is important. You can’t live without eating, you can’t reproduce without eating, and that’s what nature wants. Nature wants you to be able to at least reach reproductive age. Nature has all sorts of mechanisms to try and ensure that at least we get to reproductive age. After that it doesn’t really care that much.

That’s why some of these autoimmune diseases are so troubling, because some of them right now, more frequently than ever before, are disabling and killing people in their reproductive years.

RON ROSEDALE

That’s why it’s becoming more known, I think if a person gets a disease when they’re 90 years old, we say, “You’re 90 years old, what do you expect?” Now that they’re starting to get these diseases at a younger age, during and even before reproductive age, it starts raising alarms. We have so many different adverse lifestyle changes now that are extremely unnatural, we’ve not seen in our evolutionary history until recently. Some of what you mentioned before, the cleanliness, we’re just not exposed to the proper antigens, adverse bugs, that we should be when we’re young so our immune system doesn’t develop properly. And then we have chronically high levels of glucose, of insulin, of leptin, all of which then further impair the ability of our immune system to properly function. And all of these things are coming together to cause disease such that for the first time in mankind, its predicted lifespan is going to decrease, as opposed to constantly increasing throughout our known history.

You mentioned one way that we might be able to reduce this tide, and that is what we put in our mouths. If we can reduce the amount of antibiotic we put in our mouths, that might give our guts a better chance to be healthy for when we digest food, so we don’t end up with a confused immune system because of poor digestion. That’s one side that you’ve described. But you’re also saying that the actual food that people eat and how it affects the hormones in our bodies will also affect how well our immune system makes sense of what’s going on. What is it that makes leptin levels go up? What makes insulin levels go up?

RON ROSEDALE

Let’s talk about insulin first. It actually is a bit simpler. What we know makes insulin go up are glucose levels in the blood. When they go up, insulin goes up to store the excess, not to lower the blood sugar. That’s a huge misconception not just among the public but among almost all physicians. We’re taught in medical school that the purpose of insulin is to regulate blood sugar, and that couldn’t be further from the truth. The purpose of insulin is to store excess nutrients for a future time of need. That’s even a minor purpose of insulin. We can get into the major purpose of insulin later.

When sugar goes up in your bloodstream, when it spikes up, you have food that increases blood sugar, which might be an innocuous as a potato, or rice, which the whole world seems to be eating in overabundance, bread and pasta and cereals, Breakfast of Champions, all of these things will cause the body to manufacture a lot of sugar from the food. Starch in your mouth will be broken down by the amylase in the saliva into blood sugar, and the blood sugar will rise quite rapidly. You won’t be able to burn it as rapidly, unless you’re sprinting while you’re eating, and then you will raise your blood sugar, and that’s a sign that you’ve got more nutrients available now than you can burn, so your body wants to save that. We come from a history of feast and famine, and your body is not going to want to waste those nutrients, so you’ll save it for a future less opportune time when food might not have been available. Tomorrow you might have to fast. In our evolutionary history, food wasn’t available all the time. It was feast or famine. If it was famine tomorrow, you wanted to save those excess nutrients from today. You’ll store them. You’ll store a little bit as a biological starch called glycogen, but mostly you’ll convert it into fat, which is our major energy supply and major energy storage, or it least it’s supposed to be our major energy supply.

The signal to do all these physiologic things with the excess nutrient is mostly insulin. Insulin will go up and change the way that your genes are being read and it will say, “Hey, you’ve got a bunch of fuel right now. Let’s take the excess and store it and let’s do something with what we’ve got.” In our evolutionary history, when there was an overabundance of food or just an abundance of food, it’ll say that cells should reproduce. You’ve got enough energy now that you can reproduce, make a new you, make a new cell. So when we talk about reproduction here, we’re not necessarily talking about making a new person, we’re talking about making a new cell. You’ve got energy available. You can now make cells to replace old damaged cells, but it will do so by changing certain genetic pathways, turning the switch to on, which when left unregulated because of impaired immune system, let’s say, will lead to cancer.

So not only are you giving a switch that is telling cells to reproduce, but you’re also then damaging the control of that reproduction from the immune system and the end result is an increase in cancer. Now we know, and I mentioned this at least 20 years ago, that when insulin levels are high, you will have an increase in cancer, and that’s proving to be somewhat prophetic, because now they’re showing that many different kinds of cancer are related to glucose and insulin levels, and leptin levels, too, by the way. They’re all related.

Nerve Attack in MS – Image from Wikicommons

It’s very, very important not to let glucose and insulin levels spike by the foods that will generally raise those, which are sugars, obviously, and starches. When I mention the sugars, it has to be recognized we’re not just talking about the glycemic index here. The glycemic index just measures glucose, it just measures sugar. So many people now feel that they can have fructose, things like agave are being espoused on talk shows as a wonderful thing to have, when in fact agave is 90% fructose, and fructose doesn’t raise blood glucose, it raises blood fructose. And so it doesn’t have a high glycemic index, which is why they’re saying it’s healthy, but it does many other really adverse things, such as cause the liver to produce fat, some of which then ends up standing in the liver and causing a fatty liver, so that your liver actually gets obese and it can’t then have proper blood circulation and can’t receive proper hormonal signals from insulin, which normally tells the liver to stop manufacturing sugar, so the liver overmanufactures glucose so you wake up in the morning and your sugars are high, even though you haven’t eaten, and that’s what you see in diabetics.

We’re talking about diseases such as diabetes and cancer and heart disease, too, which have these kinds of connections. How does this tie in with autoimmune diseases, with the fact that T cells can get confused and other hormonal signals in the body can get messed up so that, for instance, nerves in the body start to be attacked by the body and don’t get repaired?

Our Body Works Best Like an Orchestra

RON ROSEDALE

The way the body functions really is, I guess, more akin to the music being played by an orchestra. If you impair one part of that orchestra, some of the signaling from the violins, all the rest of the music becomes impaired. But especially if the conductor starts having a twitch in his arm, you’re going to have a real problem. That conductor to me right now is leptin. I was one of the first people to talk about the importance of insulin decades ago, and insulin is still extremely important, but leptin, in humans, anyway, perhaps might even be more important. It’s so universally dysfunctional in people that it then trickles down to every biological process in the body, including the way the liver functions or diabetes. It controls insulin production and reception. It controls bone growth and repair. It controls the vascular function, having to do with hypertension and cardiovascular diseases. It has a lot to do with cancer. And as we’ve talked about previously, it has a whole lot to do with autoimmune disease in many different ways, part of which is the regulation or at least partial regulation of the regulatory T cell by blood cells, which help keep the immune system from going overboard.

Ron Rosedale, I’m confused. I’ve done a very light look at some of the medical treatments for autoimmune diseases. For a lot of diseases there are anti-inflammatory drugs given. Lots of steroids are used in treating autoimmune diseases. Also different drugs that either boost or tamp down on a neurotransmitter kind of signal that goes to the nerves. I don’t see very many medical treatments that have to do with cooling off leptin.

RON ROSEDALE

No, there aren’t, and the reason for that is, there’s no money in it. It might sound kind of a simple and flippant remark, but it’s true. The only therapies that make their way into standard medical care are those that can be patented and profited from, huge profits. It takes quite a bit of money to get FDA approval for something, and you have to make money off o it. All of these are corporate-sponsored and corporate-controlled, and the purpose of corporations is to make money.

You might be right about that. But I can’t go to a pharmaceutical company and ask them about their motivation. It’s not something that I can double-check with them to see what they say about that. But one thing that I can do is look at what some of the treatments are for some autoimmune diseases and start to compare them. What if I pretend that I’m a consumer who wants to make an informed decision, and I want to look at what the treatments out there are and what some of the alternatives are. What if we focused on something like multiple sclerosis, for instance, MS? It’s a disease that’s on the rise in the U.S. It’s hitting people at younger ages. There are a lot of different ways it can be treated.

There are drugs called acetylcholinesterase inhibitors that are one of the common treatments for MS, I believe. Steroids are another. There are different interferons that are given. I don’t know exactly what all these things are. Is it worthwhile to explain some of them?

RON ROSEDALE

The real short answer is no, because none of them work.

If somebody wants to take these kind of medication because they’re desperate or worried or they’ve been told they might work, what’s the harm?

Shotgun Hit

RON ROSEDALE

The harm is that they have adverse side effects. Most of these medication inhibit the immune system. They’re kind of shotguns. They don’t just inhibit the immune system attacking the myelin sheath of nerves, which is what causes MS, so some of the bigger nerves have a fatty layer above them basically as an insulator, just like when you insulate an electrical wire. If you don’t have that insulation, the electrons can just go everywhere instead of to the intended target. That’s one of the major purposes of the myelin fatty sheath that’s around the major nerves. It also can aid in the speed of transmission to the nerves. So the myelin sheath is quite important. What happens in MS, for instance, is that the immune system attacks that myelin sheath, basically pokes holes in it, and that interferes with electrical connectivity in those nerves.

You make it sound like the nerves get frayed, just like an electrical wire.

RON ROSEDALE

The sheath of the nerves gets frayed, you might say. They have holes in them. It’s I think fairly accepted that it’s because of the overactive immune system that a person’s own immune system attacks the myelin sheath, so it’s in the class of disease we call autoimmune disease.

When you say that the problem is that it’s an overactive immune system, that puzzles me, because a number of the treatments for these kinds of diseases and other diseases is to look at the disease and say, “These nerves are not working as well, so we need to boost the signal, push them harder, because the signal isn’t getting through.” Someone with MS, for instance, may have trouble walking, using their hands. In more severe cases, they may have trouble breathing, and it’s because the nerve signal isn’t getting through. So one logic of medical treatments can be to figure out whatever way they can to boost the signal, because the instruction isn’t getting through to the nerves, so why not push the signal louder?

RON ROSEDALE

The problem with that is, global movements, instead of fine-tuned movement, it takes a hammer and just pounds away at the piano instead of nicely playing tunes with one’s fingers. When you just increase nerve signals, you’re not just increasing it in those areas of the nerves that require it. You’re increasing it everywhere. You might benefit a couple nerves that maybe have a big of slow transmission because of myelin damage, but then what about all the other nerves that have the right transmission that you’re now overaccelerating? This is how people die in most cases of severe snakebite and other toxic animal bites. What these venoms do is inhibit our ability to break down that neurotransmitter called acetylcholine, so when your nerves produce acetylcholine, it goes from one nerve to the next as kind of a messenger, and it tells the next nerve to go ahead and transmit your signal. But then you have to get rid of that acetylcholine or it keeps telling the same message over and over again long after it shouldn’t. You have to then break that acetylcholine down, and the body does it through a chemical called a cholinesterase. The toxins that nature produces for animals to kill other animals is called an acetylcholinesterase inhibitor.

I’ve seen that as the mechanism of action for drug treatments that are designed to treat these nerve-destroying conditions.

RON ROSEDALE

Right. And the problem is that it won’t just do it in one particular nerve, let alone one particular place or a few different places on a particular nerve or even a few nerves. It does it everywhere, because that acetylcholine is universal throughout the body, it’s one of the major neurotransmitters, and it’s used everywhere. So by increasing the message in one place that maybe you need to increase the signal in that place because it’s damaged, you don’t want to increase it everywhere else because you’re doing the same thing, then, that a venomous snakebite does. You’re damaging the other nerves and the other signals and that actually then will ultimately cause resistance to acetylcholine, so it first will cause damage from too much and then you cause damage from too little.

We don’t know enough to specific exactly where, when, and how to place a signal. Not just in this disease, but in any disease. The problem with diabetes, for instance, is the orchestration of the signals. People take insulin when their insulin resistance—for instance, the vast majority of diabetics are diabetic because their cells are not able to listen to insulin. They have enough of it. In fact, most of them have too much of it. But certain cells are not able to listen to it. Other cells are getting too much. Not all the cells in the body are equally resistant. The liver might be more resistant than the cells that line the arteries. So then when you give the person more insulin so that the liver gets the message to stop making excess sugar, that same more insulin is going to expose the cells that line the arteries, the endothelial cells, to even more insulin signal, which will cause the endothelium to proliferate, it is a signal for the endothelial cells that lines the arteries to multiply, high insulin is a signal to reproduce, the signal that you’ve got lots of nutrition available and it’s a good time to reproduce. The endothelial cells will reproduce, it’ll produce fat and plaque and it will plug your arteries. And that’s just one simple example. And it’s not a hypothetical example, it’s a real example.

So when you take excess insulin, when you’re taking insulin for a type 2 diabetic, it might lower your sugar, but it’s causing all these other effects that are adverse because of the high insulin effects on the cells that are already exposed to high insulin. And that’s the problem with a lack of orchestration. That’s just uniform. We are not advanced enough in medicine to treat a particular signal in a particular spot at a particular time. That’s what it required for health. That’s how you play music. You don’t just constantly press one key all the time. You’ve got to press it now and then let, and then press a different key now and then let go. And then you get a musical score. And that musical score you might consider to be health.

A lot of medical doctors and pharmaceutical companies would say that they have very finely calibrated their medications for diseases such as autoimmune diseases so they’re at just the right level that they don’t cause harm but instead cause benefit in the same way that a signal from our own body is able to go in and get a signal to the nerves to do some kind of action and then step back. The rationale that I’ve heard from medical researchers and doctors about why to give these kinds of medications is that overall, on the balance, the whole body is pulled back from where it should be in sending out signals, for instance in someone with MS, so what else can they do but use their very finely calibrated, very carefully played drug applications to improve the signal to those nerves?

RON ROSEDALE

None of the drugs for MS work. They have no cure for MS. They have no help for MS in standard medical care.

That’s not what I hear from people who support these kinds of applications, this kind of medication.

RON ROSEDALE

That’s what the studies will say. In fact, a friend of mine was just diagnosed with MS and is seeing one of the top MS doctors, supposedly, in the world, who is going to put her on one of the newest and bestest drugs for MS called Copaxone. The generic name is glatiramer acetate. Very expensive, I think it costs in the neighborhood of $10,000 or $20,000 a month. It’s ridiculous. It’s given by injection only. And that’s one of the newest and bestest drugs for MS, given by one of the top experts in the field. Here is a summary from the Cochrane Report. The Cochrane Collaboration is a group that synthesizes all of the known information and they make a report. They take all of the studies and reports of drugs and look at it all together and they essentially give their opinion as to the effectiveness of this drug. Here is what it says about glatiramer acetate, one of the supposedly best drugs for MS. It’s a very long report. At the end there is a plain-language summary: “The data show no beneficial effects on disease progression in both MS forms.” Period. Both MS forms is, there’s a relapsing-remitting form and a progressive form of MS, otherwise known as RRMS and PMS. I will repeat that. “The data show no beneficial effects on disease progression in both MS forms. Adverse effects such as flushing, chest tightness, sweating, complications, anxiety, and local injection site reactions occurred quite frequently.”

And I would add, after looking at that drug a little bit more, that what you will see, although they can’t show it in a short period of it, is a great increase in cancer due to its adverse effects on the immune system.

(Editor’s Note: Here is a link to the Cochrane Collaboration Report on Glatriamer Acetate for Multiple Sclerosis)

T Cells attack cancer – from PNAS

If there’s no benefit, why is it out there on the market?

RON ROSEDALE

It essentially works by reducing the immune system, by reducing T cell activity. It reduces the effectiveness of the immune system and therefore it will supposedly reduce the immune system’s effect on the myelin sheath. But the problem is, it doesn’t just reduce the effects on the myelin sheath, it reduces the effects on everything. Everything the immune system is for, to protect you from infections, from cancer. I didn’t say that early, but you require a very powerful immune system to protect yourself from cancer. Cancer, if it gets by other regulatory systems in the body, is hopefully recognized as a foreign agent like a bacteria or a virus, and that cancer cell will be mopped up by your immune system and won’t give you overt kinds of cancer. You won’t come up with what we call cancer, even though you might have millions of cancer cells in your body. People are getting cancer every five minutes, every hour, I don’t know. Cancer is very common. The body has mechanisms to keep it in check or even succumb to it or even know that we have had it. But that requires a very powerful immune system.

Most of the treatments for cancer basically wipe out the immune system, such as chemotherapy, and then people end up dying. That’s why I say that unfortunately our medical system really is in an infantile stage, and we’re going to be looked at by future generations just like we look at medicine from the medieval ages. We are no more advanced, perhaps less advanced now, then we were then.

I can sympathize with a doctor who rationalizes that cancer tends to kill people slowly, further out in time. Severe incidents of MS can kill someone quickly. Can it be that this drug is suggested as a way to buy somebody more time by increasing the risk of a disease that might happen later to stop a disease that’s happening right now?

RON ROSEDALE

No, not if it doesn’t help the disease. This isn’t saying that the drug just has side effects, it’s saying that it doesn’t help MS. It doesn’t help MS, but has bad side effects. There’s no excuse for that. Doctors when they get their licenses take a Hippocratic oath, the joke goes that it’s a hypocritic oath. And it really is a hypocritic oath, because the doctors take the oath and throw it away. The first thing they’ll do is forget about it, because virtually every drug they prescribe has adverse effects. So the Hippocratic oath, paraphrased, “At least do no harm.” And doctors do harm all the time, but they’re trying to weigh, like you just mentioned, the benefits versus the risks. Unfortunately, the risk generally far outweighs the benefit, or the benefit is short-term or a long-term, even more detrimental adverse effect.

We’re supposed to have a whole system of checks and balances to try to keep the risk-benefit ratio in the favor of the patient who needs better health. We have the FDA that’s supposed to safeguard people against drugs that aren’t supposed to be—that might harm them. We have a huge layer of different agencies and different regulations to try to prevent a drug that is not going to be useful and might cause more side effects that are harmful than it causes benefits.

RON ROSEDALE

We could talk for hours about how the system is broken. And then there’s the way that the pharmaceutical companies do studies. There’s many way to statistically twist results or even when they design the study to begin with, they’ll design it basically for deceptive purposes. They’ll design a study to show benefit and mask the side effects. For instance, if you knew it took so many patients so many years to show a positive cancer effect, you’ll make s you’re that you use fewer years and fewer patients so that that cancer effect doesn’t show up, and so that the positive effect might show up in a particular age group after the results are done, and then you can throw away the results of all the other age groups, because you’re not required to show negative results.

So you’re not in favor of medications that knock out the immune system’s T cells? You don’t think that’s the way to go. What about ones that—and you’re not in favor of medications that boost the signal of the neurotransmitter acetylcholine. You’re not in favor of medications that either repress how quickly the body recycles or just simply rev up that signal, because that can end up ripping up a lot of the nervous system. How about steroids?

RON ROSEDALE

Steroids are known to impair the immune system, and yes, they definitely are a common treatment, and it’s been shown over many decades that the negative side effects there far outweigh the benefits. Steroids will impair your immune system, so we know that it increases your risk of infection, of cancer. We know that it also increases blood sugar and can actually cause overt diabetes. It also breaks down protein tissues that can make you more osteoporotic, make you weaker. There are so many adverse effects of taking corticosteroids that it really is almost beyond the scope of this discussion. One should totally forget that as a treatment for any type of chronic disease.

What you do see are certain treatments being totally ignored because there is no money behind it. A pharmaceutical company is not going to be going around to doctors and saying that there is a key role of leptin in the control of regulatory T cell proliferation. And that is the title of an article that came out quite a while ago that when leptin is high, it reduces regulatory T cells. Really one of the Holy Grails of autoimmune diseases is to increase regulatory T cells, not reduce the immune system, but reduce the part of the immune system that is attacking one’s own tissue. That is the function of the regulatory T cells. They regulate T cell function, as their name implies. They prevent out-of-control burning, you might say, of tissues by the immune system. Regulatory T cells are a real hot topic in autoimmune disorders. It’s been known now for several years that one of the major regulators of regulatory T cells is leptin. When you inhibit leptin, it increases regulatory T cells. There have been many more than one study that have shown this.

But the key there is that leptin levels change with every meal. So if you eat a meal to keep your leptin levels low, you will up-regulate your regulatory cells. And that’s what you want for autoimmune diseases, that’s what you want for cancer, that’s what you want for virtually anything that has to do with proper functioning and health. That’s very important.

And then there’s another article, “The interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis.” It’s not just in the treatment, but it shows that disregulation [?] of leptin might be a major cause of multiple sclerosis in the first place. Why not go right to the source.

Ron, would you be comfortable if I posted on the Internet not only the title of those articles but the authors and a way to find the citation?

RON ROSEDALE

No, that’d be fine.

Here’s my hope. Today there’s enough information that’s available to people that they can do their own checking to see what makes sense to them. It’s also my hope that if something makes enough sense, it might actually be worth doing and it might make a difference. Perhaps we’re in a time where people look for a path of information that they can check out for themselves, and they might find some good answers.

RON ROSEDALE

They might. People really have to start taking their health into their own control, because unfortunately, standard medical care really is controlled by large corporations. No, you can’t necessarily look into their minds, but I think most people understand what the major purpose of large corporations is, and it has very little if anything to do with health and much more to do with wealth. Another thing I want to mention is, when you get a lot of different lines of research intersecting at one point, you really have to start paying attention. Another line of research, for instance, is just showing how sugar itself, high glucose, is associated with multiple sclerosis, and when you prevent high glucose, MS can be reduced. Again, that gets you back to insulin and gets you back to leptin and metabolic control in general. The two major metabolic hormones are insulin and leptin, and they’re called metabolic hormones because their major influence is what you eat. So it’s extremely important—and there’s mechanistic actions. We even know why. There’s good scientific physiology as to why this even might be so. It’s not just hocus-pocus. With glucose, for instance, they talk about the glycation of cholinesterase and cholinesterase inhibitors. We’ve known about glycation for quite some time. We’ve talked about it before. Glycation can really mess up proper functioning of proteins.

I think I hear you saying that if you make  acetylcholinesterase, which is the nerve transmitter, get too sticky and gummed up with sugar stuck to it, it’s going to do some things that it shouldn’t, and it’s not going to work in some places that it’s needed. If you glycate, if you gum up acetylcholinesterase, the stuff that inhibits and recycles the nerve transmitter, then it may not be there to act when it’s needed, or it may bungle into something else because it’s all gummed up and hurt it just because it’s all gummed up.

RON ROSEDALE

And even more so the receptors. The receptors are proteins, too. They can get glycated or, as you mentioned, “gummed up” by glucose, “caramelized,” another scientifically colloquial term for glycation is “caramelization.” It’s not just a picture but it’s true. Caramel is basically caramelization of cream. So if you add glucose and cream, you get caramel. The same thing happens in your body. It’s one of the major mechanisms that is studied in the biology of aging. We know that glycation can came damage and that damage will accrue, and a lot of that accrual we see as the damage or senescence associated with getting older. So wrinkles and cataracts and all these things we know are directly attributable to glycation or caramelization. But other things caramelize, receptors or hormones, even the neurotransmitters are a type of hormone like acetylcholine. They glycate and the acetylcholine itself can glycate, but that may not be as important because it doesn’t last that long, so it gets mopped up.

What does happen is, whenever anything glycates, the body has to get rid of that glycation. That’s now a damaging protein, so we know that it stimulates the immune system and stimulates macrophages, which are part of the immune system, to clean up that gummed-up, caramelized protein, so it will then attack the caramelization, which could be one of the causes also of MS. So when you glycate nerves, you stimulate the immune system to have to clean up that caramelization, and it might go a little overboard and damage some of the nerves even more so as a result of having been glycated.

So there’s a lot of damaging effects of the glucose itself, but glucose’s effects on other very powerful hormones such as insulin and leptin, which then have global effects throughout the body on all of the chronic diseases of aging because of their effects on the actual biology and rate of aging itself. And that aging then has symptoms that we know of as the damage associated with aging, such as autoimmune disease and cancer and obesity and diabetes and rheumatoid arthritis and osteoporosis. All of these are symptoms of getting older that are accelerated, we know, when insulin and leptin and certain other metabolic signals are elevated.

Ron Rosedale, you have spent your career looking at these diseases and focusing on the disease initially as insulin. Does it surprise you to see a resonance of some of the mechanisms you’ve seen for what causes a disease like diabetes happen in a disease such as multiple sclerosis?

RON ROSEDALE

It just makes sense. I went out on a limb many year ago and predicted a lot of these things, but there was no real science behind it. Now, 20 years later, a lot of the science is supporting it. But it made sense then, and it makes more sense now. The science was just so powerful and in some cases so obvious that it really is frustrating that it is not being utilized. It’s very basic. When I still see studies coming out that low-carbohydrate, so-called ketogenic diets can help epilepsy or be beneficial for diabetics as if it’s new information, when 20 years ago I started talking about this, we’ve talked about this before, too, but when I first started talking about this, I was very shy to talk about it. I started treating my patients, I was working in basically a practice that had lots of cardiovascular patients, they were there to treat their cardiovascular disease, and many of these people also had diabetes. I was treating them with a diet that I will maintain to this very day hasn’t changed one bit, not anything about this diet has changed. All I did literally, probably in an hour, I sat down, thought of a diet that would not raise blood sugar. In grade school we’re taught that starches turn to sugar. So there go the starches. A little research showed that we don’t need any in the diet, that the minimum daily requirement of carbohydrate is zero. So I just wiped those out.

I knew that proteins could turn to sugar, but we needed some protein, it is required, so I moderated the protein and figured out how much protein a person should have depending on their lean mass and realized that what you have left is fat. A little research on fat showed that it was metabolized differently, was actually a much cleaner fuel, and that the medical degradation of fat, what’s the word? desecration of fat was totally wrong. We were being told to eat a low-fat diet, when in fact it should be quite the opposite. That should be our major source of fuel. So I started people on essentially a higher-fat, very low-carb, very low starch, moderate-protein diet. All the other low-carb diets are kind of going towards what I was espousing originally.

And it shows up in many places in surprising ways. I’m hoping to talk to some researcher who are close to Johns Hopkins who have been doing some studies with rodents where they poison the rodents with something called soman poisoning. It basically does what a snakebite does. It’s a poison that was used in wars. Interestingly enough, in this study, the rodents that they had on a glucose diet died very quickly, the ones on a standard died about half as fast or as slowly. But they put some of these rodents on a ketogenic diet, high-fat, adequate protein, very low-carb. Those rodents for the most part survived the poisoning. It was very interesting to read some of the possibilities. They talked about glycation, about the fact that basically the body stayed cooler, and they didn’t use quite that word, but they described a situation where the toxic effects were able to be processed out more efficiently.

There were some interesting things about that. If I were to be persuaded that the kind of diet that you recommend might be therapeutic, that would be a scary step for somebody who’s at the point of one of these diseases where it’s threatening their health, it’s painful, it’s threatening their mobility or maybe even their life. If I put myself in the shoes of someone like that, that would be a very scary time to try to raise my hopes towards changing how I eat to see if it could make a difference. Is there’s a point where it’s too late to even try?)

RON ROSEDALE

No, no, there’s never a point where it’s too late to try, until they’re basically beyond dead.

Even in the study of the rodents that was done close to Johns Hopkins at an Army Institute, what they noticed was that if they shifted animals to this kind of diet for just 24 hours, they got sicker. They showed more signs of illness. If instead they had been accustomed to this diet for 48 hours, just another day, they did much better. I don’t know whether they poisoned the rodents after they were adapted for 48 hours or if they tried to switch them. I don’t know what would happen if someone sick and you switched their diet in the middle of them being sick to something that’s different—

IRON ROSEDALE

I can virtually assure you that the adverse feelings that one gets by switching their diet will be far less than what they would feel with chemotherapy or with a drug akin to snake venom. The adaptation to this type of diet exists. One must adapt. In humans it takes between two and three weeks to adapt to this form of diet. But with adaptation, we know that when you adopt and adapt to this diet, you will lose excess fluid that you’ve been retaining perhaps for decades because of high insulin, one of the ramifications being fluid and sodium retention, so when your insulin goes down, you’ll lose that fluid loss, and with fluid loss you lose potassium, and many people who adopt this diet and who do not supplement with potassium, just like you would do if you had a diuretic, you have to do the same thing, if you do that, the adaptation really is much less. Most of the adverse side effects one gets when they adopt this sort of diet is that they don’t take certain supplements that should be taken to ease that transition. But they don’t really notice great improvement for several weeks, as your body starts learning how to burn fat. Basically, the mechanisms to burn fat have been hibernating for so long that it takes a while to wake up that genetic machinery to manufacture the enzymes and other chemicals necessary to process fat as fuel. The adaptation is so much less, and the benefits are so great, as opposed to the side effects and lack of benefits when they take some of the ___ treatment for MS or cancer or any of the things that basically are really treated inadequately at best.

Medicine is pretty much held on a pedestal. You have all this fancy machinery and you walk around in white coats and you get something that’s $10,000 to $20,000 a month therapy, it’s got to be doing something. You can’t believe that it really does nothing and it’s more harmful than not. People want some sort of hope. They want to do something. And when you have supposed experts telling you to do something, that this will be good for you, you listen to them, because you figure you’re not an expert and they’re more of an expert and they know what they’re doing. They might have very nice personalities. Maybe they’re even great people. Maybe they want to help. Maybe they even believe that they’re helping. But the cold, hard, scientific facts are that they’re not, and the vast majority of chronic diseases, including heart disease, the control of cholesterol and cancer therapies and the treatment for diabetes, all of these things really are causing much more harm, not just a little bit more harm, but much more harm than if they did nothing. And I’m not even saying do nothing. I’m saying, just change your diet. Diet is really, really powerful. I know that everybody says, “OK, we know that eating well is helpful.” If you eat just right to control really powerful hormones such as leptin and insulin, you can make huge changes in your health. You can not just help prevent disease, we’re not talking about preventive medicine here. We’re talking about therapeutic medicine. We’re talking about treating cancer, treating autoimmune disease, reversing heart disease and high blood pressure and diabetes and obesity. We’re doing that by really getting much further to the root of those diseases, because we’re delving into the actual aging process and therefore the symptoms of aging, because we know that these hormones are not just—probably control the rate of aging. It’s been shown now in many species of laboratory animals that there’s a genetic mechanism that actually regulates the rate of aging, which has to do with nature’s desire to have animals live long enough to reproduce. There’s a strong synergy between diet, reproduction, and rate of aging. All animals that are on earth today evolved with that synergy in mind. So diet, what a person eats, controls and expresses, changed genetic expression of very powerful genes that then essentially affect every process in the body.

It basically boils down to one thing. If you just have to summarize all of this stuff we’ve been saying, you can make huge changes in your health if you switch from burning sugar to burning fat. The body functions really, really differently. You will be much healthier, you will improve your immune system function, not just in fighting infections and fighting cancer, but also preventing it from overfighting, which would manifest as autoimmune diseases, by burning fat. It’s a totally different type of fuel. The body functions extremely different when you burn fat from when you burn sugar. We were never designed to burn sugar extensively. It’s a major problem with the diseases of civilization. The whole world is not primarily burning sugar as its primary fuel, and that has to do with what people are being fed and what the medical profession has told people to eat. The medical profession told people, “Don’t eat fat. Eat carbohydrates. Eat a high-carbohydrate, low-fat diet.” That’s been their mantra over half a century. That’s been a killer. There has never been in the history of mankind worse advice than that. It was actually based on nothing. You don’t get any nutritional training in medical school, so why they said that in the first place is really beyond me. It was what I would call “kindergarten medicine.” They noticed fatty fats in arteries, so they said, “If you eat fat, it’s going to stick to your arteries and kill you.” And that’s literally what caused fat to be blamed for heart disease. No scientific merit, no studies, nothing really of substance to implicate that.

The body doesn’t work that way. The body is far more complex than that. The body is regulated by instructions and by signals, and if you have signals to build up plaque in your arteries, you’ll do it. If you have signals to burn fat or to burn sugar, you’ll do that. Your cells are living that line your arteries, and they can burn fat or sugar, too. If they’re burning fat, they’re going to keep themselves clean. Whether you burn fat or sugar is regulated by the same powerful hormones that regulate aging, leptin and insulin. It regulates all of the—since it affects and even controls, to a great extent, the rate of aging, it will affect those processes that also affect the rate of aging, such as immunity, autoimmunity, cancer, diabetes, overabundance or not of fat. Everything that we notice detrimental that happens when we age is going to be controlled by those hormones that are controlled by what we eat.

The Rosedale Diet, book in hardback or paperback.

Finally — the ultimate diet for fast, safe weight loss, lifelong health, and longer life, based on more than twenty years of research and the latest findings on appetite and weight. Metabolic specialist Ron Rosedale, M.D., has designed the Rosedale Diet to regulate the powerful hormone leptin, which controls appetite and weight loss by telling the brain when to eat, how much to eat — and when to stop. New research shows that leptin may be one of the body’s most important hunger control mechanisms. Control leptin, and you control your weight.

Most people’s leptin levels are out of control, causing them to overeat and to store fat rather than burn it. The only way to flip the “hunger switch” back to normal is through a diet high in healthy fats and low in carbohydrates, saturated fat, and trans-fatty acids often found in processed food — plus just 15 minutes of daily exercise.

Dr. Rosedale’s 21-day diet plan is simple

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Thank you and good luck to your friend. Sometimes I think the hardest thing is to watch someone you care about, where you hope that they could get better, and they don’t want to do it your way.

RON ROSEDALE

It’s rather frustrating. There’s a lot of money and advertising, lots of marketing that goes behind the standard of medical care. It’s very hard to fight, but we have to.

Tags: acetylcholine, acetylcholinesterase, autoimmune, autoimmune system, Cancer, Copaxone, copexone, Diabetes, digestion, glatiramer acetate, glycate, glycation, High-Fat, hormone, hygiene hypothesis, immune system, insulin, interferon, leptin, Low-carb, memory cell, memory T cell, MS, multiple sclerosis, myelin sheath, nerve, nervous system, neurodegenerative, poison, receptor, Ron Rosedale, Rosedale, soman, steroid, sugar, T cell, venom

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Great interview with the amazing Jimmy Moore. Thank you Jimmy for the article, graphics and the interview below. You can learn more about Jimmy and his passion for exposing the truth in health at his website, www.thelivinlowcarbshow.com

Click the Audio button below to listen to the interview with Dr. Rosedale and Jimmy Moore.

Hello and welcome back to The Livin’ La Vida Low-Carb Show with Jimmy Moore!

Today we are lucky enough–at long last–to bring you an interview with a true pioneer in the study of the low-carb way of eating and its implications for weight and general health. His name is Dr. Ron Rosedale. Dr. Rosedale worked with the Eades early on and has continued with his career ever since espousing the benefits of a controlled-carb nutritional approach. Sit back and listen to a LONG and in-depth conversation that may be controversial at times but will surely be highly informative and engaging to this audience!

The post Jimmy Moore interview with world-Renowned Low-Carb Physician Dr. Ron Rosedale appeared first on Ron Rosedale, M.D..

Thank you Shelley Schlender for interviewing Dr. Ron Rosedale, and putting together this article and audio recordings below.  We are very grateful for all the work you do to bring the truth of health to the people.  You can learn more about Shelley at, www.meandmydiabetes.com

Here’s an in-depth conversation with Ron Rosedale about how bones evolved, and what kind of hormone signaling helps bones stay healthy.

Download Audio MP3 version Part 1

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Download Audio MP3 version Part 2

Audio part 2

Ron Rosedale, recently, health news has featured many articles that have to do with bone. I’m wondering if you can help me with this. The three questions I have are:

1.  Calcium supplements that people take to make their bones strong, have been associated with an increased risk of heart attacks and cardiovascular problems.

2.  Drugs designed to strengthen bones are in some cases leading to an increased risk of  bone fractures, especially in the thigh bone, rare but documentable.

3.  More and more evidence is showing that hormones may influence healthy bones more than taking calcium. And healthy bones may influence hormones, such as insulin and leptin, meaning sick bones may increase the risk of diabetes and messing up the leptin signals can mess up your bones.

RON ROSEDALE

Nothing surprising.

Before we get into how you would answer those questions, I’m also thinking of a young man who has a disease where his bones are very thin and very prone to breaking. Maybe in looking at these more newsworthy topics, we’ll figure out something to do for this young man. Let’s start by talking about bones. I brought with me two show-and-tells that are bones. These are soup bones for cooking. They’re the kind of bones that you can give to dogs that they love to chew on. One thing that struck me, if you look at this one that’s cooked, is it mostly bone or mostly hollow?

RON ROSEDALE

The one that’s cooked, I’d say about half of each. It’s mostly hollow, if I had to do volume. It’s a trabecular bone, so there would be more air than bone in this piece.

That’s right, we think of bones as these very strong, sturdy things, but even this, which I’m guessing was maybe a cow’s thigh bone—

RON ROSEDALE

—and probably would not be considered osteoporotic at all.

It’s got this thick outer bark that’s the bone, but most of what you’d see that you think is solid is actually a hole in the middle. That’s the cooked one, where the hole in the middle has been taken out. But this bone here has not been cooked.

RON ROSEDALE

In so-called Paleolithic times, this would be a real gourmet feast.

I’ve heard that in Paleolithic time and in hunter-gatherer cultures, they loved to eat the marrow of a bone.

RON ROSEDALE

Yeah. Some of the scientists who study such things have proposed the theory as how brains might have evolved, and one of those is, as brains evolved and became a little bit smarter, and human ancestors were scavengers, smart enough to know not to compete with lions and tigers for a kill, they’d let the lions and tigers kill and have their fill, and then try to eat what was left over, as we became a bit smarter and more adept at the use of tools, we could break open bones, and what was left is the commodity that is revered in animal cultures, and that is fat.

Is fat what’s inside of this bone?

RON ROSEDALE

It’s mostly fat. Bone marrow is very high in fats. The Mediterranean diet is bone marrow, it’s mostly mono-unsaturated fat and a lot of other good nutrients. It’s a very nutritious meal, also some protein. So bone marrow is an excellent meal for especially a scavenger, to have something like that left over.

Our ancestors may have become more human-like because they could crack open a bone and eat the inside of it when other creatures couldn’t get to it, because they used tools. I wonder how long ago that could have happened. Could it have been 2 million years ago, 15 million years ago?

RON ROSEDALE

Probably longer than 2 million years ago. Probably not as long as 15 million years ago. I think that’s a pretty good range right there, somewhere between 15 and 2 million years ago, as we evolved a bigger brain.

The 15 million years is an interesting moment, because it is a time when primates lost some ability to process uricase, and it’s a possibility that it was just a random mutation that gave them more ability to store fat through fructose. I’ve always wondered, when I’ve heard that, though, whether if there were primates that had gone to Europe and then they got caught in an Ice Age kind of cold, if some of them survived because they ate bone marrow, and if they ate bone marrow and fats, maybe that ability to process some of the byproducts of eating a lot of fruit, because they were fruit-eating primates that went north, maybe they lost that ability to process fruits because they were eating so much bone marrow they didn’t need it any more.

RON ROSEDALE
Yeah, bone marrow is a great meal. I think it perhaps initiated a very beneficial cycle where the more bone marrow they were able to acquire, as they got smarter, the smarter they got, because they were able to fuel then the very high-energy needs of a growing brain.

That’s a question that would take some paleoanthropologist to figure  out. We’ll just leave that as a question for now. You’re saying that this is actually pretty nourishing stuff here in the middle. But I’ll bet that’s not why this animal made this stuff in the middle of its bone. It didn’t just make it just so we could eat it some day.

RON ROSEDALE

I don’t think any animal makes anything so that somebody else can eat it. Well, maybe bees make honey. No, I don’t think they made marrow for us to eat.

Instead of being hard, why do our bones have this stuff in the middle of them?

RON ROSEDALE

The typical function of bone marrow is to make red and white blood cells. It has a very good energy store to fuel the constantly replicating cells that are necessary for that animal’s life.

Why did they make it inside of their bones?

RON ROSEDALE

Because they can, [laughs] more than anything. It’s a good place for it. I think nature likes to have dual uses. It’s also very well protected, so it’s a very well-protected place to make very, very vital components of our physiology. The immune system is extremely important, making blood, red cells, is extremely important. This is a very safe place to make it that is kind of out of the way.

It’s out of the way, in a safe place that’s avoiding free radicals and all of those insults. Does it make bone any stronger to have it be solid, or is it just fine to have it in the middle of it like that?

RON ROSEDALE

One of the major endeavors of any type of architecture is to weigh strength versus weight. It could certainly be solid. You could make bones solid, but they then would be much heavier, which would entail greater musculature to stand upright. It wouldn’t be a very architecturally sound way of making any type of structure. We could make a building, a house, with a solid framework, but instead they have 2×6’s or 2×4’s to hold up a frame that’s hollow in the middle, very much like our bones. So it’s a good balance between strength and weight.

When you said hollow in the middle, it reminded me of this book I have here called Inside the Body. It has beautiful pictures that start out showing things like the skeleton and what different bones look like in the skeleton, and then it gets closer and closer to the actual bone cells. At some point, it actually shows the structure of bone cells. One thing that’s quite amazing to look at with these is that bone cells, side by side, they have all this hard stuff around them, but the bone cells start with a hollow core. Even the cell starts with a hollow core. Aren’t those beautiful?

RON ROSEDALE

Yeah, they are beautiful. Nature is incredibly wise. That’s why I think we really have to listen to nature, both in healing and treating people. Listen to what nature does, what nature’s ideas are for healing, for structure, for life, and then don’t fight them, go along with them.

Looking at these pictures where there’s a hollow center and lots of layers of hardness around them reminds me of a story you told me about how nature doesn’t say, “Some day, we need creatures that have bones in them, so let’s plan to make bones.” You told me that bones started because sea organisms were spitting out a lot of calcium. Sea creatures started out by being soft-bodied animals that had a lot of calcium to spit out. It’s not that they even wanted to make shells, they just wanted to spit out calcium. And in a way, it almost looks like in our bone cells that spitting out of calcium is still going on. There’s a hollow center and then there’s all this hardness around them. Can you tell the story about seashells?

RON ROSEDALE
A simplified version evolution, how life came to be as it is. We’re fairly certain that life started with single-celled organisms. We could start even earlier, but that’s close enough. As cells divided, they formed colonies of cells, families of cells that were fairly identical. From a very, very early age, it was critical that once life began, once life evolved, one of the requisites of staying alive was to get rid of calcium. Not to acquire calcium, but actually to get rid of it. Top biologists to this day will know that if cells start accumulating calcium on the inside, if calcium levels start rising on the inside and the intracellular calcium isn’t kept extremely low, cells start dying.

This began almost at the beginning of life. The cell started excreting calcium, and as you had colonies of cells grouping together, and they all were excreting calcium, it would mix with certain elements in the oceans and precipitate from rocks, kidney stones, you might say. These rocks would form adjacent to these columns of cells. Nature is quite smart, all animals are quite smart, and they have to be, or you’re not going to survive in a world that is not easy to survive in, especially back when life was evolving. It was actually much refer than it is now. We have a few tsunamis now, a few hurricanes and volcanoes. Well, life back then was infinitely more treacherous, with much more severe hurricanes and tsunamis. It wasn’t easy. You had to be pretty ingenious to survive, and you didn’t want to waste things.

So these colonies found, quite naturally, that the precipitated calcium that was adjacent to them could be used as protection, as a structure to protect themselves.

So perhaps initially some of them spitting out this calcium, it smothered them, they died in their own calcium, but every now and then one of them survived in that they ended up spitting out the calcium in a way that protected them.

RON ROSEDALE

Exactly. This is kind of the leading theory of how shells evolved. The shells didn’t just happen from the ocean, they actually emanated from within, that the colony of cells would excrete the calcium, it would precipitate, form a nice protective shell-like layer that then became part of the organism.

And here in this picture of the bone cell, it has that look of spitting out calcium in a very specialized way. It’s an organized way to spit it out. The center stays hollow. It’s almost like a reminder of that initial creature that wanted to get the calcium out of it in a way that was not going to hurt it and might even help it.

RON ROSEDALE

All life is incompatible with high calcium. There are reasons for that.

If calcium is so bad, why does a cell let it into itself in the first place?

RON ROSEDALE

It has no choice. [laughs] For that matter, calcium is one of the common elements that surrounds the world, so there will be calcium. But calcium has advantages, too. It isn’t a matter of just getting rid of it and not wanting to ever see it again. It can form a very hard structure, calcium carbonate, and you can use that hardness for protection.

Is that why cells let it in? There’s things where cells say, “I don’t even want this in. I’m going to keep it out.” Why do cells let calcium in? Is it helpful in some way to have it inside the cell?

RON ROSEDALE

Calcium is used in many different chemical processes. One of the major chemical processes that calcium is used in is as a signal. It’s kind of an intermediary hormonal signal. When the hormone tells a cell what to do, it doesn’t tell it directly. It usually kind of knocks on the door of the cell and says, “I’m here.” The cell then has to hear the doorbell. And just like somebody coming to the door in your home, it’ll ring the doorbell, and then wires will take it to a bell and allow you to hear it, and you know something’s happening. You have maybe a delivery. Maybe the mailman is here, maybe UPS came to deliver a package that’s quite important, a new hard drive for your computer, and if you don’t pick it up, you’re out of luck in doing your further work. One of calcium’s major uses is as a messenger that when the hormone arrives at your cell, a little trickle of calcium is released, which then sets off a cascade of chemical reactions with calcium being involved in most of those, that then go to the nucleus of the cell and tell certain genes to be read. So the message from a particular hormone can tell a cell what to do. That’s how it works. So it’s important for the proper concentration of calcium to be there so that the message can get across.

I’m imagining it as the sound of the doorbell ringing discreetly to let the whole cell know, “Here comes the message.” And if there’s too much calcium, it would be like a thousand doorbells all ringing at once.

RON ROSEDALE

Or like a rock band playing inside the house, and the doorbell rings and it sounds like part of the music, and you have no idea that somebody’s at the door and you don’t answer it.

So all of these are reasons why it’s important to clear the calcium out after it’s done it’s job to get the doorbell rung?

RON ROSEDALE

Yeah. And cells have very interact ways to make sure that the calcium remains silent, a very low concentration of calcium, until it’s needed. So the two major mechanisms are, number one, we’re going to extrude calcium from the cell to keep the intracellular calcium really low, and the calcium that remains in the cell gets sequestered in a membrane complex called the endoplasmic reticulum, so that that calcium which isn’t excreted is sequestered so that the space inside the cell, the cytoplasm, has an extremely low calcium concentration. The intra- to extracellular calcium concentration, that gradient, is greater than any other mineral, any other chemical, really, in the body. It takes a lot of energy to maintain that gradient.

So our cells have a whole bunch of sump pumps that keep pumping the calcium out, because the cell says, “We don’t need too much calcium. We need to keep it cleared out of here.”

RON ROSEDALE

“We’re going to die if we don’t do that.” Exactly.

Here I see it, in these pictures of these bone cells. It looks like the calcium got spit out in a very organized way, and there’s this hole in the middle each time. We’ve been talking about seashells, but then we go to us, where our shells are not on the outside, they’re on the inside. That’s interesting because I gather that the ability to make bone concedes evolutionarily with the hormone leptin?

RON ROSEDALE

It apparently does. You can probably educate me a lot more on that, even, and why that might be so, because I’m not sure. I know that what occurred, and it had to do with fat-burning also, the ability to burn fat, which leptin is critical for, in taking our story a little further about shellfish and shelled organisms, in the ocean, you don’t have to withstand gravity. You’re pretty weightless. You don’t need rigidity. You need protection more than rigidity. The shells weren’t there to be necessarily rigid and to stand up against gravity. The shells there were protection almost entirely, some of them actually were used as weapons, spikes, also sometimes for protection, but also as weapons, to get prey.

Swordfish!

RON ROSEDALE

Yeah, swordfish and things like that, right. Teeth in general, which is kind of an offshoot of bone. But as we went from the oceans to land, as we sought different niches for different organisms and species, the environment changed quite a bit. Certainly one of the big changes as we left the ocean is that we encountered gravity. It’s always been a rule in evolution that bigness afford protection. It’s much easier to get eaten if you’re little than if you’re big. The big eat the little, not the other way around. For animals to grow on land, they had to become more rigid, and that distinction really has to be recognized between rigidity and strength. The two are not the same at all.

Internalizing our external shells, which is a relatively easy thing to do, we already had bone, sort of, and we were using it as shells on the exterior to make bone. We just had to bring it inside. That allowed us greater rigidity, so that we could then grow bigger and stand up and become mobile against gravity.

You’re making me think that perhaps our internal bones have a little different structure than shells, because shells can be just these hard, concrete-y things. But our bones have to be able to move with us. Most shelled creatures stay put, so their bones are dealing with weight and impact, they aren’t dealing with having to flex.

RON ROSEDALE

They basically weren’t dealing with having to be strong. They just had to be rigid.

And they didn’t even have to be alive. They were just the walls of the fortress.

RON ROSEDALE

Exactly. And that brings us into a philosophical argument or discussion of what life is, because all life, really, is mostly dead. [laughs] You can’t really distinguish between the two.

But our bones inside of us are a little bit more alive than the shells?

RON ROSEDALE

They’re definitely more alive than the shells we see in shellfish. The live part confers the strength, and that part doesn’t have to do with calcium.

There are some pictures in this book that show in some of those holes that go through bones, there are things called osteoclasts and osteoblasts, those kind of little scrubber things that are alive that go through and either chew up only bone or get room to make new bone cells they can spit out calcium again. There’s, like, these little Pac-Men going through the bones, scrubbing and cleaning it out. I don’t think that happens in seashells, but it happens in our bones.

RON ROSEDALE

You bet. We have living architects in our bones that model and remodel our bones, that make the bones the shape that they’re in so that they can be much more conducive to mobility, to joints and strength. So we have cells that actually eat up bone like a sculpture. You take a big lump of clay and then you take away some of that clay to make a shape. Those are the osteoclasts.

Clasts like “clear away.” C for clear away.

RON ROSEDALE

And then we have another type of cell that also make a sculpture, but by adding clay, you might say, in this case not clay, in this case, actually, it’s protein. So we have osteoblasts that make bone, but not by putting down calcium, but by putting down protein.

So osteoblasts B for “build” the bone.

RON ROSEDALE

The osteoclasts and the osteoblasts model the bone. They take a piece of clay and they make a sculpture out of it which we know as a femur or a humerus, a particular bone such that it can perform a particular function in the body, be an arm, a leg, have a joint so it can be mobile and convey strength.

What is protein doing in there? Why not just make it be calcium?

RON ROSEDALE

That’s a great question, and I think it’s a question that goes to the heart of the fallacy and myth of how we’re treating osteoporosis. One has to distinguish between rigidity and strength. They are not the same thing at all, and they’re mediated by totally different mechanisms. The strength is mediated more by flexibility, and the strength is mediated by the protein content of the bone, just like your muscles are strong. You can get nice strong muscles. Protein is what conveys strength and flexibility. So you have a green stem of a tree that’s bendable, and it’s going to survive a hurricane with a higher probability than an older, rigid oak tree that might be much thicker, and if you took an x-ray of it, you would say, “This is much thicker, that means it must be much stronger,” and the hurricane took it out like it was kindling.

I was hiking recently and saw some people fly-fishing. They do these wonderful bends of their rods. It’s just gorgeous to watch the string and the rod bend and flex. I think those rods are probably hollow, and I think they’re made of something that has some fibers that can bend and flex. I don’t think those rods are made strong because they’re made of thin pieces of stone. I think they wouldn’t work very well then.

RON ROSEDALE

No. If they were made rigid, they would crack with any type of pressure. So you’ll see all fishing rods being flexible, the more flexible the better, and that way they’re much stronger and they don’t fracture under pressure.

Fracture under pressure. That’s not what we want to have happen to any bone.

RON ROSEDALE

No, that’s not what we want to have happen, but that is what happens. It will happen even more, or to a greater extent, if you have more calcium than the bones should have and less protein. So you can have, for instance, a six-month-old, I remember we did this in medical school, we took a nice little six-month-old infant who at least did say we couldn’t do this, and the medical students were able to bend the forearm of this child, who, by the way, liked the attention, it doesn’t hurt, but you could very visually see that the forearm bent considerably. And it was a very strong bone. That six-month-old has stronger bones than I have, and I think I’ve got pretty strong bones. The reason was because of the flexibility. And yet if you did a test for osteoporosis—

You know, I just recently had one, because I’m at that age where I’m supposed to—

RON ROSEDALE

You measure the mineralization of the bone, is what they do. They measure the calcium content, not the protein content. They do not measure the protein content of the bone when you go for a test for osteoporosis and you have a bone scan. Calcium content, however, does not reflect on strength.

After I was done with my bone scan, I’ve got a very light frame, I don’t have very big bones, they said that I wasn’t osteoporotic but I was pretty close. I said, “Hmm, what would that mean? Is it because I have a light bone frame?” I was told, “No, you just don’t have that much calcium in your bones.” Now that I am at the age where I will probably be starting into menopause at some point, they said, “It’s going to get worse.”

RON ROSEDALE

And if they compared your bone to that of a six-month-old, they’d find it was much closer than if they compared somebody who had a so-called “good” bone scan study and had less osteoporosis, supposedly, to a six-month-old. Those bones would look much different. In other words, if you did a bone scan on a six-month-old, it would look like the worst case of osteoporosis ever recorded, because their bones haven’t classified very much, which is why they’re flexible and which is why they can actually maintain themselves with all the falling that six-month-olds are doing. They’re flexible. They’re not going to break. They’re much harder to break than somebody who had a perfect bone scan study.

If my bones ever get thin enough and lacking in calcium enough, I’ll be told to take a drug that’s called a bisphosphonate, like Fosamax, which is designed to make sure that my bones will look really good on a calcium bone scan.

RON ROSEDALE

Virtually all of the medical treatments right now for osteoporosis do so by inhibiting osteoclasts.

I’m looking at this picture here in this book which shows a very elegant hole in the middle of the bone and a little—it really does look like a little scrubber that you’d use on a pan to get the messy stuff off of a pan when you burn things, and it’s scrubbing away. These drugs take all of those little scrubbers and keep them from scrubbing.

RON ROSEDALE

Yeah. Gives you a very false sense of security. What you’re doing is, you’re inhibiting a very vital part of bone physiology, which is to get rid of old, damaged, brittle bone and replace it with new, flexible bone. That’s why we have both osteoclasts and osteoblasts that are active throughout our life, not just when the bone is being formed, as we’re a fetus, but after we’re alive up until so-called old age we have very active osteoblasts and very active osteoclasts, and we need both of them for healthy bone. We need the osteoclasts to break down our old bone so that it can be replaced with newer, fresher, stronger, more flexible bone.

And that means bone that isn’t just calcium, it has protein and other minerals in it, it has a live, active process, so it’s bendy.

RON ROSEDALE

So it’s bendy, and even the calcium has something to stick to. If you just have calcium, which is basically what they’re causing you to do by taking away osteoclasts and by not paying attention to the processes that allow protein to actually build up in bone, which is a totally separate story on how you get protein into your bone, if you are just concerned about calcium, like the medical profession right now, try taking calcium carbonate or calcium phosphate or any type of calcium you want and making a bone out of it. Take that dust and squeeze it together and make bone out of it. What happens when you let go? Whssst! It’s like sand.

And even if you could squeeze it together, I could just flick it with my finger and it would fracture all over the place. It would be like glass, very much like silica carbonate. X-ray technologists, radiologists will tell you that patients who are on these drugs who fracture their bones have a different structure of that fracture. It’s a much more severe fracture. No longer will you get a so-call “green stick” fracture, which looks just like that. If you take a green stick, the green twig we were talking about before, and you bend it enough that it breaks, it’s that little fine break in the middle, and you really don’t have to do anything to it. It’ll just heal itself. It won’t be in a bunch of pieces.

I have a friend who, her love Weimaraner dog is known with being clumsy. The dog’s name was Grace.

RON ROSEDALE

Good name for a clumsy dog. [laughs]

So Grace was following her down the stairs and got clumsy and walked in front of her and she fell down the last stair. Her ankle was shattered like if you dropped a teacup on a marble floor. It took a long time to heal a lot of pieces.

RON ROSEDALE

Right. And that’s what happens in the bone that doesn’t have the proper protein function, it doesn’t have proper osteoblastic functions, where you’ve inhibited the osteoblasts to get rid of that brittle bone. In other words, all medical treatment right now for osteoporosis, whether it be taking estrogen or Fosamax or any of the other—the injectable drugs that they’re giving that will last for six months that have all sorts of side effects that you can’t do anything about because it’s going to last in your body for six months once you’ve taken it, it costs $2,000 or some ridiculous amount of money that you’ll be out, they all work the same way, by inhibiting the osteoclastic activity so that you cannot reduce the brittleness of your bone. Your bones become thicker, they look great on an x-ray, but they’re extremely brittle, and if you do fracture them, they fracture like glass.

One thing that happens is that if somebody’s lost calcium in their bones, it is the case that they’re not able to carry as much weight on their bones. Pelvises and spines can start to compress because there isn’t enough stuff to make the bone be able to hold a steady pressure on it. I’ve heard that for somebody who has that kind of weakness, it does help to inject some kind of cement, some calcium in some way.

RON ROSEDALE

The cement, actually, is the protein. The calcium would be like the bricks.

That’s right. If you have a whole bunch of just the sandy stuff, it takes the glue to make it be concrete. You’re saying that the protein is kind of like the glue?

RON ROSEDALE

The protein actually has the glue. There are certain types of proteins called GLA proteins that essentially glue the calcium to it so the calcium has something to stick to. That’s what, for instance, vitamin K is necessary for, to increase the quantity of GLA proteins that allow calcium and magnesium and other minerals to actually stick to that bone.

But there’s heart disease, and everybody knows that vitamin K is a vitamin that if you’re losing a blood thinner, to have a lot of vitamin K in your blood—

RON ROSEDALE

That’s why they say that many heart patients and many people that are taking blood thinner, they’ll go to the extent not only to not take vitamin K, but to not eat green vegetables any more. “Don’t eat green vegetables, because we don’t want you to have vitamin K. That would be horrible.” Because they’ve got heart disease, and a lot of times they’ve got heart disease because they had too much calcium in their arteries, and they have too much calcium in their arteries, not because they’re taking too much calcium, but because the calcium doesn’t know where to go. You’ll find that those people who have lots of calcium in their arteries also have osteoporosis. It’s almost a one-to-one correlation.

So somebody could have calcium blockages in their arteries, they could have arthritis, all things with too much calcium in the wrong place, and they can still have thin bones?

RON ROSEDALE

They generally do. And they’ll be told, then, to take more calcium, even though the calcium is going in their arteries and in their gall bladder and in their kidneys and all the wrong places, they’re told to take at least two grams of calcium a day, even though it’s well documented that the calcium physiology is totally messed up, the body has no idea what to do with that calcium any more. More of it is going to go into their arteries, into the kidneys, into the gall bladder. Some of it, almost by default, is going to end up in your bones because that’s where we put excess calcium. That’s one of the reasons we put it there, because we’re trying to get it out of our cells and we have to put it somewhere. It’d be great if it could stick in our bones, because then we could take something that’s harmful, actually, to the cells and give it some use. The use isn’t, however, to make strong bones. That’s a misnomer, a misconception, I should say. The use is to give the bones rigidity. The strength, again, is conferred by the protein.

But if we only had protein, which would essentially be cartilage, if our bones were 100% made of cartilage, if we retained our six-month-old bones into adulthood, for instance, we’d still have really strong bones, maybe stronger than they are now, but we’d be like gummy dolls. As we tried to grow up and become five feet or six feet tall, we would just bend over. We wouldn’t have enough rigidity to withstand gravity. So we put minerals in our bones to make them more rigid, not to make them more strong, so that they’ll remain straight and allow us to walk upright.

Minerals like calcium, a little big of magnesium?

RON ROSEDALE

Boron, silicon. There’s a lot of minerals that go into our bone, not just calcium. But like anything else, health—I think we’ve talked about this in the past numerous times—health is not in the parts. It’s in the instructions given to the parts.

So in us talking here, you’ve answered my first two mysteries, and it sounds like it was no surprise to you that calcium supplements are now being associated with an increased risk of heart attacks. That’s more and more documented, it’s shown as a small risk, but there is a risk there. You’re saying, “Well, of course.”

RON ROSEDALE

There’s even a greater risk. It’s been shown, it was shown 15 years ago by Swedish researchers that people who had high normal serum calcium levels had a much higher rate of mortality. So if you really want to use, I think, a better index of health, which is mortality, your mortality goes up if your serum calcium goes up.

So there that is with calcium supplements, high levels of calcium in the blood are maybe not such a great thing. The other question you’ve answered is that drugs designed to strength bones in some cases lead to an increased risk of bone fractures, especially in the pelvis and the long bones of the legs. That would make some sense, because those are areas which need to flex, and if what’s happening is that the supplements are keeping the osteoclasts from clearing out the old bone—

RON ROSEDALE

The old dry, brittle bone. The medications being used right now for osteoporosis are inducing in people really dry, brittle bones, very, very susceptible to severe multiple fractures. As you mentioned, like glass or like a teacup breaking, in multiple pieces that are very difficult, certainly almost impossible for the body to heal itself. If it’s going to heal, it’s going to require surgery and multiple pins and most of the time it won’t be able to mend properly because the tools to mend bone and the ability to manufacture protein are being impaired by the treatment. So the treatment, once again, is actually becoming the disease.

let’s go through a quick list of the things that help bones and don’t, and then we’ll get to the cool stuff about how hormones influence the health of bones and how bones influence the health of hormones. The quick list would be, if somebody takes a nonsteroidal anti-inflammatory drug to reduce pain, will that improve bone strength or hurt it?

RON ROSEDALE

It’ll hurt it, for sure.

Taking calcium without the proper protein matrix won’t allow the calcium really to incorporate itself into the bone properly. It’s just there, so it looks good in an x-ray, but it really has no positive function as far as even rigidity is concerned. But the detriment is that as we age, cells have a harder and harder time keeping calcium out. As you mentioned, we have calcium sump pumps that constantly have to pump the calcium out. As we age, our ability to do that decreases. But then what they say is to take more calcium, which is like having the sump pump in the basement and making sure that it’s raining all the time. And as the sump pump is getting a bit older, and it’s really not as affective at keeping water or calcium out, and then you’re making sure that it’s raining all the time, you’re saying, “Make sure you take two grams of calcium a day,” which to your cell is like raining calcium, the ability to keep calcium out becomes much more difficult. Intracellular calcium rises, and when that happens, virtually all signaling processes in the cell, of all kinds of cells, not just bone-forming cells, we’re talking about heart cells, nerve cells, kidney cells, every cell that you’re made of this is relevant for. As calcium starts building up in cells and cells start losing signals because there’s too much static inside the cell, they can’t hear the right messages, everything becomes impaired, and you die. Which is why the Swedish study showed that mortality rate increases as serum calcium goes up.

The American Dairy Council is not going to like this interview.

RON ROSEDALE

Oh, nobody likes me. I’m not just focusing on them. I focus on everybody.

Although there is some evidence that taking calcium supplements is actually more problematic than eating foods that are higher in calcium. Perhaps that’s because if you take a supplement that has something that your body doesn’t need, it’s harder to get rid of it than when it’s packaged with other nutrients.

RON ROSEDALE

And it might not even probably get absorbed as well. There’s no way to get rid of it. It goes in and out.

Walt Willett is with the Harvard School of Nutrition, and he says, “If you really want strong bones, don’t milk your cow, take your cow for a walk.”

RON ROSEDALE

[laughs] That sounds good.

Walking and exercise really do help our bones, because it helps them flex, which makes them wake up and say, “Oh, my gosh, it’s time to—”

RON ROSEDALE

“We need more strength.”

“And we need to clear out some stuff that’s not flexing well and get those osteoblasts and osteoclasts going.” All of that works as long as you haven’t taken an anti-inflammatory that means that the bones don’t get the signal to be repairing themselves.

RON ROSEDALE

That’s exactly right. It’s like, if you want to build your muscle, you exercise your muscle. If you want to build the strength of your arms, you’ll do arm exercises. If you want to build the strength of your bone, you need to do bone exercise your bones.

I’ve got an idea. Since bones have protein in them, how about if people eat more protein?

RON ROSEDALE

It boils down to what we just said a little while ago. It’s not so much the parts that even make life, it’s how they’re integrated, it’s the organization of those parts. So if you have hormones that tell your protein what to do, if you have hormones that tell calcium where to go, then you’re going to be healthy. If you don’t, you can take all the calcium you want and there’s not going to be a homing pigeon attached to that calcium that tells it to go to your bone. The calcium has no idea if it’s supposed to go to your bone or your artery or your kidney or your gall bladder. It’s just calcium, it doesn’t have the knowledge. We have to give it the knowledge of what to do. Same with protein. You can’t just take protein and sit on a couch and watch television and expect your muscles to grow. That’s not going to happen. If you don’t have signals to build muscle, you won’t. If you don’t have signals to build the strength of the bone, essentially conferred by the protein content of the bone, then it’s not going to happen. You can take all the protein you want, it’s not going to end up in your bone. You’re going to end up burning it as fuel, and that’s going to be detrimental. Burning protein as a fuel source is highly unhealthy.

All right. That’s a quick primer in some things that can help your bones be stronger and some things that can interfere.

RON ROSEDALE

Eat your meat and vegetables and take very vitamin K. Don’t listen to your doctor.

How about the hormones that may influence healthy bones and the healthy bones that can influence hormones, such as insulin and leptin? Gerard Karsenty  gave one of the leading lectures at the American Association for Advancement of Science because of his remarkable research where he discovered that serotonin in the brain, the feel-good hormone, if it’s coming from the brain, send signals to strengthen bones. Lepton from the brain sends signals to strengthen bone. Serotonin created inside of our intestines, inside of our duodenum, which is just down below the stomach, if serotonin is being created there, it actually interferes and dampens down how much healthy bone the body will be making. What he has discovered is that these hormones, not only do they make a difference in how the body’s building bone, but it depends on where in the body the hormone comes from. This is very confusing. How would you unconfuse it?

RON ROSEDALE

I’m not sure I can, particularly. The body is extremely interact in its information-disseminating orchestration. One of the keys to health is really how signals are orchestrated, not whether you have them or whether you don’t or how much you have or how much you don’t have, but how they’re orchestrated. An example would be antioxidants. Everybody wants to take antioxidants these days. The University of Colorado did a whole institute of antioxidant research. But I think they’re all missing the boat, in that it’s not how much antioxidant capacity you do. They do ORAC studies that measure how powerful the antioxidant capability is of a particular supplement, for instance, and if it has a really high ORAC score, it becomes promoted, pomegranate juice. Acai is really popular because it’s very high in antioxidants. You hear that all over the place.

It’s totally fallacious. It has nothing to do with health. We need oxidation. Breathing is oxidation. You can’t kill cancer without oxidation or viruses or bacteria. It’s not whether you have it or whether you don’t, it’s where, when, and how you have it. It has to be orchestrated. So you want it here and you don’t want it there. You want it now and you don’t want it then. The orchestration is through proper hormones, and those hormones more often than not have to do with nutrient availability and reproduction, because that’s what life is about. For life to perpetuate, you need to know when it’s the proper time to reproduce and what the nutrient availability is, because that’s necessary to reproduce. So the hormones that are essential in indicating nutrient availability and nutrient use and its integration with reproduction then have its fingers in everything else.

Gerard Karsenty I believe would agree with that when it comes to bone. He’s not talking about making lots of baby bone, but I guess in a way he is. We think about reproduction as babies and offspring, and with bone he is saying that it’s an energy-intensive process to make bone, so if the body doesn’t have enough resources, if it’s low on energy, it’s not a time to put into building and refreshing bone. If the energy resources are sending signals that there aren’t enough, then bone will get weaker, is part of what he’s saying, and that has to do with the signals from the brain that there’s enough of resources to make more bone. That’s one thing he’s saying. It’s very energy-intensive to make bone, and that’s one reason he thinks that leptin evolved at the same time as our internal bones did, because it was important to have an overall energy balance resource looking at this to say, when can we build bone?

RON ROSEDALE

Yeah. Leptin is really a crucial hormone having to do with virtually all facets of health disease. I’ve maintained for quite a few years that unless leptin is acting properly, if it’s not being signaled correctly, not necessarily high, not necessarily low, but signaled properly when to be high, when to be low, there is no other modality that one can do to be healthy. You have to get leptin right first, and then other things can help. And the only way you can get leptin right is to eat properly. That’s why proper dietary nutrition is so important to me, because it affects the hormones that are instrumental in indicating to the body and brain what the nutrient availability is and therefore, then, what the genetic expression is of maintenance, repair, or reproduction. All of that is extremely critical in all aspects of health.

For instance, if it’s deemed that the body has to live longer to be able to reproduce at a more opportune time, it’s probably going to want stronger bones. If you essentially have been given your opportunity to reproduce, then your body doesn’t care so much whether your bones are stronger and whether you have osteoporosis. Then we have to go essentially to what I would call unnatural modalities, not necessarily following nature, but seeing how nature gave us strong bones to begin with and then maintain it. It’s not that nature wants us to die after the reproductive age, it just doesn’t care whether we do or not. If we do, great. If we don’t, great. But we can use nature’s tricks to be able to live a very long, healthy, happy, post-reproductive lifespan if we follow what nature is telling us to do.

Maybe nature does want us to live a longer time even after reproduction, because we’re not like salmon. We don’t just get to the point where the male and female salmon work hard to swim upstream and they live just long enough to mate and lay the eggs.

RON ROSEDALE

There is parenting, so there is a certain post-reproductive span that might be necessary, even for grandparents. But we’re talking about even beyond that. Maybe we can live longer than what nature has thought we were necessary for.

And maybe if we do, maybe that will be an evolutionary advantage because of all of the wisdom that comes from experience if people are healthy. So maybe there’s a real benefit to society. So to get there, when it comes to our bones—

RON ROSEDALE

Mobility is certainly one of the sine qua nons of health. Mobility was definitely required for our evolutionary adaptation.

And for mobility, we need good bones. Leptin is an interesting detail, because there is evidence that very overweight people can have very strong bones. People who are very overweight often have very high levels of leptin. On the other hand, there’s also evidence that having very low levels of leptin, if a person’s cells are leptin-sensitive, it’s one of the best possibilities for building and strengthening bones that are too weak. So this is a paradox here?

RON ROSEDALE

Not so much a paradox. It’s important not to confuse a hormone level with the strength of the signal. So for instance, we know that in the vast majority of diabetics classified as type 2, they have high insulin, but the activity of insulin is very low. Actually, that’s not exactly correct. It’s low in the so-called blood glucose-controlling aspect of it, high in the ___ aspect. Actually, you lose the orchestration, which is what the problem of debates is. In other words, the high insulin generally means in the liver, the liver is not listening as well. It’s lost its hearing from noise exposure. It’s being exposed to so much noise you can’t hear it any more. The same happens in muscle tissue, the muscles can’t hear insulin properly, so they can’t burn sugar properly, since the liver is not listening to insulin properly, it makes too much sugar, all these contributing to high blood sugar, so a person becomes diabetic.

But the high insulin is not toned down in certain processes that instigate cell division, so the high insulin is then a risk for increased cancer.

So for our cells that multiply a lot, like our gut lining, and in women, breast tissue, linings of things, all of those epithelial cells, they’re more prone to cancer when insulin levels are high—

—prostate—

Prostate, because that has to do with tubes with linings of cells that never become insulin-resistant, so they’re just sittin’ ducks.

RON ROSEDALE

They’re sitting ducks. And even in the same cell now, we know that certain processes, like the metabolic processes of insulin, are toned down with insulin resistance, but other processes, the ___ process, which has to do with cell division, are not toned down. So even the same cells in the same organ have different processes. So it’s the orchestration that’s lost, and this is really kind of a sine qua non of ill health, what you’ll see. One must look way beyond just hormone levels. You have to look at the strength of the hormone signal and where. As you were saying, with serotonin, the strength of the hormone signaling in the intestines or the brain? Where is it going to?

If levels are high in people that are obese and their bones may be stronger, it’s hard to tell, because the high signal means that part of their body is leptin-resistant, it’s not understanding, it’s thinking it’s starving. It may be helping the bones, but if a signal of leptin is low and the cells are sensitive to the signal, that can be enough signal to tell the bones there’s enough energy to go ahead and build more bone, without all of the other mess that comes from being leptin-resistant.

RON ROSEDALE

And we know that there is a dichotomy in leptin signaling, just like insulin signaling, where high leptin generally indicates leptin resistance, and much of the end organs for leptin become resistant, and many of these end organs are in the brain. But the synthetic nervous system which is at least partially controlled by leptin doesn’t become resistant. And so the parts of the hypothalamus, for instance, that indicate or that regulate hunger and obesity become resistant to leptin, so you have high leptin, but the ___ nucleus and the hypothalamus is hearing low leptin, which would keep a person hungry and tell a person that they’re too skinny even though they’re fat and make a person make more fat and not burn what they have, which is one of the major causes, if not the major cause of obesity in the world. You have too much leptin, your body’s trying to tell your brain you’ve got too much fat, that you’re going to get eaten by a lion, you’re not going to be an effective hunter, you’re not going to be able to run away from a saber tooth tiger, you’d better lose some of that fat or you’re going to die.

But the brain is hearing a different message. The brain, then, at least that portion of the brain, the ___ nucleus, is hearing that you’re too skinny, you’re not going to be able to survive a famine, you’d better be hungry, you’d better make more fat, and you’d better conserve the fat that you’ve got. So there’s a disconnect.

Those two parts of the brain are sitting pretty much side by side and they’re hearing totally different messages?

RON ROSEDALE

And the worst part is, in any type of communication, what’s important is what you hear and not what’s being said. And so that portion of hearing that you have two little leptin, even though you have too much, is going to make you fatter until you make more and more and more leptin, so that it can scream then to the ___ nucleus, which gets the message that you’ve got enough fat. Not too much. You have 200 pounds of extra fat now, and the ___ nucleus is saying you’ve got just enough. But you’re producing massive amounts of leptin, which is telling other areas of your brain, that regulate the sympathetic nervous system, for instance, that your heart’s going to beat too fast, you’re going to have high blood pressure, and that’s going to increase your risk of cancer and diabetes and make you produce a lot more blood sugar through the vagus nerve that goes through the liver so that your liver produces way too much sugar. It then controls insulin in your thyroid and causes all sorts of reproductive problems.

Everything gets more extreme. Some of the feedback loops that rev things up rev up more. Some of the feedback loops that rev down rev things down more. It all gets out of balance.

RON ROSEDALE

It gets out of balance, and that out-of-balanceness is extremely complicated. Medical knowledge is nowhere close to the point where they could regulate all of those imbalances correctly.

Translated, you’re saying you don’t think a drug is going to solve this?

RON ROSEDALE

[laughs] Translated correctly. In fact, a drug is going to make it worse, almost for sure.

Serotonin is what most people think of when they think of antidepressants, that if your serotonin levels are low, supposedly, that’s what makes somebody feel depressed, even though there’s some data that says it’s not that they’re low, it’s that if your cells are resistant to the influence of serotonin, you can feel depressed. Whether or not it’s the signal or whether the signal is heard, there’s a debate about that. But most people know serotonin because of drugs that can make you have more serotonin in your body. Serotonin is also known as something that helps during labor for women, because it causes pretty strong muscle contractions. But serotonin causing better bone growth? It turns out that serotonin from the brain improves the likelihood of strong bones, but serotonin in the digestive tract reduces the chance of strong bones.

RON ROSEDALE

I don’t know what to say.

This is weird. Here’s some things that Gerard Karsenty I believe is saying, which I’d like to ask him about some day. I’m curious what you think about it. One is that when someone takes an antidepressant, it can actually interfere with bone strength. It’s a slight effect, but it’s there.

RON ROSEDALE

And I don’t doubt it. Nature is really thrifty. There are literally thousands of—in fact much more the rule than the exception, where a particular chemical or signal or hormone is used for a wide variety of different functions. It’s much easier to take something that’s already there and give it a new function than create something totally new. So having serotonin from the brain do one thing and serotonin from the intestines do something else would not be surprising in the least. And I think the rules of hormone resistance are universal in most cases. You could probably make a case that any hormone one can develop resistance to if it’s not used properly or if it’s overused, in particular.

So if you have constant high levels of estrogen, you’re going to become estrogen resistant. But that resistance isn’t going to be uniform. Some tissues are going to become more resistant than other tissues, and that’s really why it is impossible to treat medically, because you can’t then just take more estrogen or you can’t just take more insulin, because then you can’t orchestrate it. For instance, one of the problems in type 1 diabetics, they’ll say you can always take the insulin even though your body’s not producing it. Well, not exactly, because when your own body produces insulin, your pancreas will produce it, and there is a direction to where that insulin goes. So there’s a big bolus from the pancreas directly to the liver to shut out glucose production, and then from the liver it goes to the rest of the body. When you take insulin by shot, it’s going right under the skin, and you lose that direction first to the liver, so the liver gets no higher a dose than anywhere else.

The same is true for any type of hormone. It isn’t just how much you have, it’s where you have it. If it’s produced by the brain or if it’s produced by the intestines, there’s going to be a different direction of circulation, a different direction of where it goes and therefore what it does.

Let’s look at the serotonin paradox. I’ve wondered whether if it’s coming from the brain it’s a signal that has to do with telling the whole body to do something, but if it’s coming from the gut, I find myself wondering, why is the gut, why is part of the digestive tract producing serotonin? I’m wondering if it’s a stress signal, if the intestines produce serotonin when for some reason they’re stressed because there is a stress component to serotonin production, and maybe if the digestion is stressed, that’s a signal to the rest of the body, “We need to repair the digestion.” It’s not a time to allocate resources to building bones. That’s a guess.

RON ROSEDALE

And it’s a very good best. People have heard the adage, “I’ve got a feeling in my gut.” I think there was a book written a number of years ago that talks about the “gut’s brain,” your gut as having its own brain. So serotonin might be one of the brain neurotransmitters in the gut that allows it to have a gut feeling.

Maybe then that’s a question—if I were to dream of asking Gerard Karsenty some questions about these discoveries of his, maybe that would be one: why does the gut produce serotonin? What is the advantage to it of having this hormone produced? What kind of questions would you want to have him asked?

Why there would be a kind of an opposite action on bone. Why would serotonin from the gut produce a detriment in bone formation as opposed to serotonin from the brain  He’s wondering that, too. Having heard a speech that he gave, I believe that he said that to his knowledge, this is the first example of a hormone where its action is different when it’s produced in the brain versus when it’s produced below the brain. Does that mean that as we look, we’ll find no other hormone where this happens? Or does it mean that as people start looking for differences between brain and body hormones, that we will see more and more that have opposite actions?)

RON ROSEDALE

I think it’ll probably be more the rule than the exception, knowing how the body works. It’s just really interact, which is why it’s much easier to deal with it from it’s root than trying to get all the tentacles correct. That would just be impossible, I would think. That’s why drug therapy for this is really a hopeless cause.

If somebody wants to build bone, you would want them to eat a diet that has their hormone signals nice and clear without getting them resistant in any way, and exercise would be fine. Since serotonin is a stress hormone, maybe finding ways in addition to diet to reduce stress?

RON ROSEDALE

Going back to that, it even gets more complicated than we’re making it out. For instance, we know that serotonin and dopamine kind of work together, and that dopamine-to-serotonin ratios are important in the brain and I would assume elsewhere also. If you take so-called SSRI drugs like Prozac that raise serotonin by preventing their breakdown, one of the major problems with it is, number one, you develop resistant to serotonin, which makes it worse than when you started, and number two, you mess up the serotonin-to-dopamine ratios, which then messes up dopamine function, too. Dopamine is extremely important in all sorts of things, the pleasure center, getting enjoyment out of life, addictions. Until we can know what we’re doing with all aspects of the effects of all hormones, know basically how it’s affecting the entire orchestration of the music that our body is playing, we shouldn’t be messing with it, because we’re going to make it worse.

When I think about drugs that change the hormone ratios in the body, it’s interesting to me that our bodies work so hard just to use a little bit of these hormones and then clear them out as quickly as they can. They just send a puff of one of these hormones into the body, and then the body works very hard to clear it out. I don’t know if it’s whether too much is dangerous, or if it’s not good for the body to have stale hormones hanging around. If the hormones are in the bloodstream for very long, they get oxidized, they get dinged up, they may not act as well. So the body’s always working to put them in and then quickly take them out so that their half-lives are just a few minutes, quite often. It’s not like these hormones are there for hours on end. And antidepressants are often selective serotonin reuptake inhibitors, which means that they slow down how long those hormones are in the body. They make them be stale hormones. I don’t know whether that means that their actions can be messed up a bit because they’ve been there too long, or if they’re there very long, there are certain cells that start to burn out on them or get hurt by having too much of it there.

RON ROSEDALE

I’m sure that’s all correct, but it has to do, I think, with the language that the body speaks. We’re talking right now. The voice is determined as much by the silent areas as the noisy areas. So if I’m trying to say a wooooooooord [stretches it out] but I don’t shut it off and it just merges right into the next, we’re not going to be able to hear that sentence very well. In any type of language, it’s important to have a noise and then shut it off, have it here and not have it there. That’s what communication is.

You’re a fan of high-fat, low-carb diets. Do you think that kind of way to eat, high fat, low carb, adequate protein, what would that do to bones?

RON ROSEDALE

I think it does to bones what it can do everywhere else, and that is make them healthier. The reason for that is, I’ve measured thousands of leptin level and insulin levels and found that that sort of diet maximizes the accuracy of insulin and leptin signaling. Now we know that other signals pertaining to protein, such as ___, are going to be maximized also. And when I say “maximized,” I don’t mean levels. Actually, you’re lowering them. By lowering all three of them, you keep the signal and keep the communication. What that accuracy tells the body is to up-regulate genetic expression of maintenance and repair, which amounts then to longevity. The body will do what it can to live longer because it thinks it’s necessary. It gives the body what it deems to be a purpose to live longer, and strong bones are a part of that.

And that means that those osteoblasts and osteoclasts can get in there and do the job they’re meant to do.

RON ROSEDALE

Right. I think there’s very robust science now that shows how relevant leptin is in bone formation and strength. In the Journal of Science maybe eight or nine years ago, they showed that proper leptin signaling in the brain, meaning reduced leptin resistance, the way you reduce leptin resistance, if you have it, as indicated by high leptin, is by lowering the leptin, not by raising it more. As you lower it, you increase the leptin sensitivity of significant areas of the brain, which then through the central mechanism and through nerves, actually, stimulate osteoblastic activity so that bones make more protein, and that gives it more flexibility, which conveys strength and also allows the calcium to accumulate in the bone so that it doesn’t accumulate—and this is kind of a simplistic view—as much in the arteries.

Or in the joints—

RON ROSEDALE

—or elsewhere in the body.

Just as a hypothetical, every now and then there’s a child born who does not make bone very well. It’s somewhere of a genetic condition.

RON ROSEDALE

It’s called osteogenesis imperfecta, that’s the name of that condition. They get fractures very, very similar to the type of fractures that women are getting on all the osteoporosis drugs. Their bones are like glass.

So we can assume a child like that, they don’t make as good a protein matrix for the bone to build onto?

RON ROSEDALE

That’s what it is. It’s a specific genetic defect and an enzyme necessary to manufacture bony protein. Their condition is exactly like you would see in women taking osteoporotic drugs, where it’s great on x-rays, they have the minerals, but they don’t have the protein there to hold those minerals together, so their bones are almost like glass. They fracture their bones very repeatedly, which isn’t the bad part, but the kind of fractures that they get are bad, very difficult to heal, not a single fracture. They’re almost always multiple, compound fractures.

That sounds like one where the ideal solution would be to somehow get that child more of that enzyme?

RON ROSEDALE

In that particular case, that would be exactly what one would have to do, a genetic modification, increase the enzyme. But in the average person, it generally isn’t a defect in one’s ability—they didn’t inherit an inability to manufacture the enzyme. That enzyme is not getting the signal to become active.

Could that be also the case in these kids? If they ate differently, is there anything they could do to perhaps give them a little bit more margin for not breaking bones?

RON ROSEDALE

I would think that the would be the case, following the diet that you’re familiar with that I’ve recommended to improve leptin signaling. It improves testosterone signaling. Testosterone, by the way, is also very important in bone growth, and that’s one of the reasons why obese women, or men, have stronger bones. It has nothing to do, at least not totally, but also other hormones that leptin very much affects, such as estrogen, and if a person is fact, they make more estrogen, because the fat cells themselves make more estrogen, and that estrogen can turn into testosterone, which is good for the bone, but not so good for everything else. They increase their risk for certain cancers and things like that.

Again, you lose the orchestration, but not everything is bad. As a byproduct of some of the mess-up in hormone signaling, they get stronger bones, almost by luck, actually.

Better yet would be to have better hormone signaling and stronger bones. There may be a pathway for that.

RON ROSEDALE

That way you get thinner with stronger bones. You don’t have to be fat and produce all sorts of extraneous exogenous estrogen. That wouldn’t be so great.

The post Healthy Bones, the true story you are not being told. appeared first on Ron Rosedale, M.D..

This is an interview with Shelley Schlender, KGNU radio, Boulder, Colorado. Thank you Shelley for the article, graphics and the interview below. You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

From the FDA Press Release on September 23rd:  “The U.S. Food and Drug Administration announced that it will significantly restrict the use of the diabetes drug Avandia (rosiglitazone) to patients with Type 2 diabetes who cannot control their diabetes on other medications. These new restrictions are in response to data that suggest an elevated risk of cardiovascular events, such as heart attack and stroke, in patients treated with Avandia.”

Now, why doesn’t the FDA suggest something BETTER than medications to control their blood sugars?  And why does Avandia work in such a risky way?  To find out more, see these stories from our archives, from Ron Rosedale and from Eric Westman and Mary Vernon.

And for more detail about the FDA decision, and commentary about it, here’s a summary from David Mendosa.

The post FDA Slaps Major Restrictions onto Avandia appeared first on Ron Rosedale, M.D..

This is an interview with Shelley Schlender, KGNU radio, Boulder, Colorado.  Thank you Shelley for the article, graphics and the interview below.  You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

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Ron Rosedale
A long time ago, maybe 15 years ago, when I was in Asheville, North Carolina, before leptin was discovered, I was doing a lot of research on my patients about insulin, to see what lowered it, what raised it. I remember one boy who came in, brought in by really nice parents.  He was a rolly polly 11-year old.  They were both thin, and they were wondering why he was getting fat.

He was starting to get ridiculed by his classmates and it was affecting him.  His fasting insulin was quite low.  So I said, well, let’s see what happens.  Let’s feed him half a piece of toast. I had done this to other people, too.  I knew that most people who have toast, it’ll cause their insulin to go from maybe a baseline of 5, which is quite good, to maybe the 30s or 40s, which is somewhat high.  (Note-This rise happens during a 2-hour test)  I measured his insulin level, after he ate a piece of toast, and his insulin levels went into the hundreds.

That is like the Dogrib Indians in Canada who were tested by Emoke Szathmary in the 1980s.  During a glucose tolerance test where she measured insulin levels, she noticed an extremely high rise in insulin response among a subgroup of the Dogrib who, over time, proved to be much more prone to develop diabetes when they’re eating the American diet. (When eating their traditional diet of fish and game meat, they did not get diabetes)

RON ROSEDALE

They just become hyperinsulinemic very easily.  People will say well, there are differences among people.  I say, well there are differences, but the direction is the same.  If you feed a piece of toast to anybody, their insulin will go up.  That’s the response to sugar.  Insulin will go up.  I don’t know any organism currently alive where they would eat sugar, glucose or anything starchy, where insulin goes down.  It goes up.  The genetic difference is how much insulin goes up.  Some become much more hyperinsulinemic than others.  They’re the ones who will become more rapidly insulin resistant.  Because they do have a high spike, and it’s going to stay high for a longer period of time.  It’s more extreme.  The response is in the same direction, but more extreme.

And the previous generation’s exposures to sugar may predispose the next generation to the more susceptible to having this extreme response.  That may be why one generation, such as thin parents, can drink sodas and eat french fries, and the next generation, which shows up as more overweight on the same food, is the one that has problems from those foods.

RON ROSDALE

One of the things scientists are finally coming to grip, hopefully sooner rather than later,  is the importance of genetics are not the genes you have but how they’re expressed, and genetic expression can change from meal to meal.  You don’t have to wait a hundred thousand years for your genes to change.  We need to concentrate on regulation on genetic expression and not paying so much attention to what genes a person has, which is where the focus has been for the last 50 years.

Editor’s note – The reason this post is interesting to me is that many diabetics, wisely, don’t like to do a 2-hour glucose tolerance test because the overall load of sugar is so high – around 80 grams of sugar all in one gulp.  In fact, it’s not a test that’s recommended for someone who’s diagnosed as diabetic.  It’s considered too harsh for a body that’s already stressed.  Additionally, most glucose tolerance tests are not done while measuring insulin, so a key variable is completely overlooked.  Ron Rosedale’s toast test seems an unorthodox, but informative alternative test for people who are curious about how they might fair, in terms of their blood sugars and insulin levels, with a glucose challenge.  After all, a piece of toast does have carbs, which will turn into sugar.  But it’s more like 25 grams of carb, so it’s not as brutal a hit to the body as a glucose tolerance test is.  By measuring insulin levels along with the glucose levels, it gives a clearer idea of how much insulin resistance is part of the picture.  The higher the insulin response to the toast, the more likely that insulin resistance is in play.  But it also might be a warning sign of someone whose body is more susceptible to high responses to sugar . . . which would be an early warning sign that this person is more likely to become insulin resistant from eating high carb foods, OR that this person’s pancreas works so hard in response to sugar, it might be more prone to burning out.  Or both.

The post The Toast Test – Ron Rosedale, M.D. interviewed by Shelley Schlender, KGNU appeared first on Ron Rosedale, M.D..

Interviewed by Shelley Schlender, KGNU radio, Boulder, Colorado.  Thank you Shelley for the article, graphics and the interview with Dr. Rosedale below.  You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

INTRODUCTION: Avandia is a drug that’s been used for over a decade to lower blood sugars in people with diabetes.  The reason that made Avandia important is that, in diabetics, blood sugars levels can go dangerously high.  They can hurt your heart, your kidneys, your eyes, every part of you.  High blood sugars can kill you.  And if you think this won’t ever happen to you, are you overweight? Do you wish you had more energy?  Do you need to urinate a lot — especially after eating something sweet?  How about high blood pressure?  Those all can be symptoms of diabetes.  And if a checkup reveals that your blood sugars are high, you might need to bring them down–with daily insulin shots.  Or exercise.  You could change your diet.   Or, how about taking a little pill?  Such as Avandia?

In 1999, the FDA approved this blood sugar lowering drug. It has earned billions of dollars for its maker, Glaxo Smith Klein.

Fast forward to 2010.  This summer, the FDA nearly banned Avandia, due to growing safety concerns.  Critics charge that during the last decade, Avandia caused 100,000 more heart attacks and deaths than the U-S would have experienced if Avandia had never been for sale.  Over 10,000 people have sued Glaxo charging that the big pharma company raked in profits while hid the dangers their drug, and hurting the people who swallowed it.  Sales of Avandia have slowed to a trickle.   Sales of a different sugar-lowering drug, Actos, have surged ahead.

Is Actos safer than Avandia?  Up next, we’ll hear some strong opinions on that topic — and more, by talking with Dr. Ron Rosedale.  Dr. Rosedale is an expert on reversing diabetes and other diseases of aging.  He recommends using a dietary approach to heal heart disease, arthritis and diabetes and more.  Dr. Rosedale is not a fan of Avandia.  For over ten years, he’s been warning people about its health risks.

RON ROSEDALE:  It’s old news.  The only new news is that they’re looking at it again, and that it took so long  The real story is why is it on the market, and why did it get on the market to begin with? And it goes much deeper than that, into the workings of the entire medical system.   The fact is there has not ever been a diabetic drug that doesn’t cause such significant side effects than it might be worse than the benefit of lowering the blood sugar.  Metformin might be an exception.  But every other drug, the sulfonylureas, the Troglitazone drug class that Avandia and Actos are in, the newer DDP-4 class, such as Januvia, the fact is, they probably cause more harm than they help.

Ron Rosedale says he figured out that Avandia was dangerous by studying how Avandia interacts with our body’s cells–and especially a special protein that carries instructions from our DNA.  This protein is called PPAR-gamma, and drugs such as Avandia work by forcing our cells to get a louder dose of instructions that come from  PPAR-gamma.  Ron Rosedale says it’s predictable that forcing a cell to take on more PPAR-gamma orders than it’s really able to handle can hurt the cell . . . . and also, hurt us.  He says the proof lies in what’s happened with this whole class of blood sugar lowering drugs, which are called – get ready for this, the Troglitazones.

RON ROSEDALE:  With the Troglitazones such as Avandia, if you actually just go into their mechanism of action, you could predict that they will kill people.  There was a drug that was withdrawn from the Market called Rezulin, prior to Avandia being approved..  Rezulin was the first of this class of diabetic medications that was on the market in 1997 and then later was taken off the market because it killed people.  The so-called PPAR gama agonists.  they stimulate a certain receptor on the nucleus of cells called PPAR Gama which is involved in fat metabolism.

Before it was even approved for market, I read up on PPAR gamma to see what it was.  At the time, it was a newly discovered receptor, a newly discovered part of our metabolism that certainly doctors had never heard of, and most researchers had just started doing experiments with.

Their experiments were showing that Avandia and similar drugs could push a body’s cells to take in more sugar, which did reduce blood sugars.   Because of this ability, Avanida became known as an insulin sensitizer.  So was it?  Is it?  Ron Rosedale:

RON ROSEDALE:  Well, Not really.  Not really.

Many other experts call Avandia an insulin sensitizer, including many scientists, the Journal of the American Medical Association, and the maker of Avandia — Glaxo-Smith Klein.  Ron Rosedale remains stubborn:

RON ROSEDALE:  That’s how it reads and that’s how the drug companies presented it to the community.  You have to understand, and people have to understand that drug companies are there to make money.  They’ll spin the information.  They’ll hire statisticians, PR departments.  The vast majority of money the drug companies spend has not to do with research but with very elaborate ways of marketing.

In case you’re wondering whether the words “insulin sensitizer” really even matter, imagine you’re a doctor, treating someone whose blood sugars are way too high.  Let’s make the doctor’s patient an insulin-resistant diabetic.  After all, most diabetics produce plenty of insulin.  That’s a hormone that is so powerful, usually, just a little insulin, easily get cells in our bodies to take in excess blood sugar . . . IF those cells are insulin sensitive.  But, most diabetics are insulin resistant, which means their cells don’t hear the message to take in more sugar.  So an insulin-resistant diabetic often has high insulin levels AND high blood sugars.

If you’re a doctor with an insulin resistant patient, wouldn’t you want their cells to be more insulin sensitive?  Wouldn’t you think that an insulin sensitizer might do the trick?  That’s a big reason why thousands of doctors prescribed Avandia . . . without realizing that in many cases, this so-called insulin sensitizer was doing more harm than good.

So, why did so many patients allow themselves to take so much Avandia, even though, today, we know this drug was causing many of them harm?  Looking back, it’s likely that their doctors told them that the drug would help them.  And for another thing, if you’re an insulin resistant diabetic–and most diabetics are–then you’re likely to be overweight — even obese.  You probably feel  drained of energy.  You may have a round belly and high blood pressure.  And because you’ve been told those conditions involve being insulin resistant, then wouldn’t you like to be more insulin sensitive?  And if you take a little pill that’s advertised as an insulin sensitizer, and you’re told it lowers the high blood sugars that cause so many problems . . . wouldn’t you expect that maybe that insulin sensitizer would also make it easier to lose the extra weight.  It’d be easier to have more energy.

The 2010 Congressional hearings have highlighted how much Avandia has NOT lived up to these expectations.  In reality, taking Avandia may have killed more people than it’s helped.  As for hopes of weight loss, people who take Avanida are more likely to gain weight.  And not only do they often feel more tired . . . in scientifically measurable ways, their body’s cells are more tired.  Their muscles may not work as well.  Their hearts might not pump as well.  So, how did so many doctors, and patients, overlook these potential problems with Avandia?  Dr Rosedale:

RON ROSEDALE:  People are very good at following, and that’s what the drug companies taught the doctors, and that’s what the doctors taught the patients.  It took me literally no more than five minutes back in 1996 to discover what the PPAR agonists do, like first Rezulin, then Avandia and Actos.

Ron Rosedale does not call these insulin sensitizers because they don’t give cells the room to be more insulin sensitive on their own.  For Dr. Rosedale, helping a cell be more insulin sensitive means creating the right conditions so that insulin levels in the body can naturally go down to just a tiny bit of insulin, while the cells become so sensitive to hearing insulin’s instructions that that tiny bit of insulin guides them to take sugar out of the blood and use it for things like making energy.  With the kind of insulin sensitivity that Dr. Rosedale recommends, excess fat does tend to melt away.  People generally do have more energy.  Their blood pressure often goes down naturally.  For Dr. Rosedale, a health change isn’t an insulin sensitizer unless it achieves all these things.  His issue with drugs such as Rezulin and Avandia and Actos is that they strong-arm a cell into taking in more sugar.  Dr. Rosedale says these drugs don’t make a cell more sensitive to insulin, and to taking in sugar.  They bludgeon cells into doing these things.

RON ROSEDALE:  And I spoke out against Rezulin before it ever came on the market.  And then it was withdrawn for safety reasons.  But they all work the same way.  Rezulin is the most powerful of the three.  It works has nothing to do with resensitizing the cells to insulin.  It does one thing only.  It causes cells to turn into fat cells.  it makes more fat cells.

Perhaps you’ve never thought of Avandia as a way to make a heart cell become less able to pump your blood — because it’s being forced to become more of a fat cell than a heart muscle cell.  Ron Rosedale says that Avandia can do this to any muscle cell.  It can make it take on more fat than it’s really designed by Nature to handle.  it can make liver cells store more fat than they’re designed to take.  As to your body’s fat cells–Avandia can make them fatter.  And that’s ironic.  You see, many doctors and health agencies blame diseases such as diabetes on people “letting themselves” get overweight.  So, why, for so many years, did so many of these health experts recommend a pill that would increase the chance of people getting fat?  Well, actually, what these former fans of Avandia might not have known is that the drug was basically putting into hyperdrive a natural sort of emergency choice that the body uses, on its own, for protecting itself from high blood sugars.  That protective action is called getting fat.  Here’s Ron Rosedale:

RON ROSEDALE:  It helps to understand a little more background about diabetes.  You can consider most people obesity to be the price one pays to keep people from becoming a diabetic.  As long as you can make fat out of the sugar, it keeps the sugar levels low.  If you simply define diabetes by blood sugar levels going high, which is how it’s done today by most doctors, then getting fat becomes a healthy event because it prevents our blood sugar from going too high.

Ron Rosedale says that cells in our bodies can take on excess sugar for a little while.  But they have other jobs, and our lives depend on them doing those jobs.  So over time, those cells start to resist the signal from insulin to take in even more sugar.  Dr. Rosedale says that muscle cells and liver cells tend to get insulin resistant first.  Over time, even fat cells will start to resist the taking excess sugar in.

RON ROSEDALE:  When fat cells get resistant to insulin, they can no longer make more fat out of the sugar, then blood sugars do start to go up, and that’s when someone is diagnosed as a diabetic.  That’s when it gets diagnosed, but in reality, the diabetes diagnosis was preceded the onset of the actual diagnosis of high blood sugar by decades.

Ron Rosedale says that before a baby is even born, it can be affected by high blood sugars.

RON ROSEDALE:  When you’re a fetus, you can start developing insulin resistance, which is really a disease, so if a mother eats a diet that largely turns into sugar, the fetus becomes insulin resistant.

While becoming insulin resistant does protect the inside of our cells from being as damaged by excess sugar, Dr. Rosedale says it also leads our bodies to become increasingly confused.  For instance, our livers have the natural ability to send out instructions to make sugar from our own body — by harvesting protein from our muscles and our bones then turning that protein into sugar.  This allows our bodies to make more sugar even when we aren’t eating foods that turn into sugar  . . . . but if a body’s insulin resistant, and blood sugars are already high, the liver can be so confused, it sometimes keeps making sugar.  It gets stuck in overdrive, dissolving muscles and bones to make MORE sugar, and in this way, making blood sugars even higher.

RON ROSEDALE:  As the liver becomes more insulin resistant, then insulin cannot do its job which is to put the breaks on the liver manufacture more sugar,  So the pancreas produces more insulin when the liver becomes resistant, there’s a disconnect.  Your liver can’t hear it and it starts making too much sugar.  That happens in almost all diabetics.  The liver produces too much sugar.  The muscles can burn some of that extra sugar.  So you’re still not being diagnosed as a diabetic because you’re burning off the excess sugar.  This is a kind of simplification.  Leptin regulates the ability of the body to do many things.  As does insulin.

As your muscles become more insulin resistant, they can no longer burn the sugar,  and they go to your fat cells.  And you become fatter, you still have a garbage can to put the excess sugar.  As your fat cells increase, you become 10, 20 100 pounds overweight, your fat cells will start to be insulin resistant, and the sugars will build up in your blood.

You actually became a diabetic when you were a fetus, but now you’re being diagnosed as a diabetic, and now you have nothing you can do with it.  And it starts accumulating and you’re diagnosed as a diabetic.  So they put you on Avandia.  Avandia stimulates PPAR receptors on cells.  It’s a chemical that was artificially manufactured to do that, period.  What PPAR gamma does is make fat cells.  So it doesn’t improve the receptors on cells that have anything to do with insulin.  it is not an insulin sensitizor– that has been a big fat lie, one of many that has been perpetrated by drug companies in their marketing efforts, and doctors believe this . . .. stuff.

Now, despite all these explanations, it may still be hard to swallow that a little pill that’s supposed to help people’s health can turn something as important as a heart cell into a fat storage cell.  But Ron Rosedale holds firm that this is what Avandia does.

RON ROSEDALE:  It causes them to turn into fat.  it causes liver cells to turn into fat cells.  It causes bone cells to turn into fat cells.  Those classes of drugs can multiply your risk of bone fracture.  it smothers your heart with fat and can turn your muscle cells into fat which can cause heart failure it turns liver cells into fat cells.  there’s a lot of adverse effects.  that’s the last thing you want as a diabetic.  The vast majority, because the underling disease is a metabolic disorder, not the least of which is the inability to properly burn fat.  The last thing they need is to become more obese.  The last thing they need is further dis-regulation in their fat metabolism, which is what Rezulin, and Avandia and Actos do.

Here’s more from Ron Rosedale about why it’s not beneficial to force the highly specialized cells in your body to take on the additional function of storing excess amounts of fat — which he says drugs such as Rezulin and Avandia and Actos make them do:

RON ROSEDALE:  They have trouble performing their job because heart cells stop performing like heart cells and they start performing like fat cells.  Bone cells stop performing like bone cells.  There’s a disorganization of the orchestration of division of labor in the body.  And it goes even further.

Up next, Ron Rosedale is going to talk about another problem with PPAR agonists such as Rezulin, Avandia and Actos.  That problem is that, in addition to pushing the body to store more sugar as fat, these drugs also reduce a body’s ability to burn the fat for energy.  Picture a vault full of gold bars that’s bursting at the seams, and contraption is still adding more gold to it.  Meanwhile, picture a desperate family that really needs some money to spend, but the vault is locked up tight.  Well, that’s similar to what happens in the body when the levels of instruction proteins, such as insulin and PPAR agonists go too high:  They push the body to store sugars as fat, and they lock up the ability to burn that stored fat as energy.  Ron Rosedale:

RON ROSEDALE:   There are studies from many years ago that shows the rate of aging in laboratory animals can be determined by the proportion of activity between PPAR gamma and alpha.  Alpha initiates the ability to burn fat.  Your body can burn sugar or fat and byproducts of fat called ketones.  Health is determined by which fuel you burn.  They more fat you burn the healthier you’ll be.  the rates of aging studies have concincingly shown that as you burn fat as your primary energy source, your rate of aging, and the symptoms of aging, will go down.  Avandia and Actos and Rezulin before them go exactly the opposite, and so it should be zero surprise that these actually increase the rate of death, which is what these studies are finding.

At this point, perhaps you’re thinking that drugs such as Avandia can be a bad idea.  Or, maybe you’re thinking that the mistakes made by our body’s cells are where the problem lies.  After all, if our cells would just take in blood sugars and burn them as energy in the first place, they wouldn’t end up being insulin resistant.  So, you might wonder, why are our bodies’ cells so stupid that they start to resist the signals sent by insulin?  Ron Rosedale:

RON ROSEDALE:  LAUGHTER  Well, actually, they’re probably not being stupid.  They’re probably protecting themselves.  They know that if there’s too much sugar inside the cells, it’ll cause damage within the cells.

You see, that’s the problem.  Yes, it hurts cells to have too much sugar touching their outer surfaces, burning and gumming them up what is basically, their “skin”.  But if high sugar levels can do this outside of a cell, think of how much more damage excess sugar could do if it was forced inside a cell, where everything is even more delicate.  Just what kind of damage can a little bit of sugar do?  Dr. Rosedale says sugar molecules really can gum things up – in a process known as glycation.

RON ROSEDALE:  Glycation enables sugar molecules to attach to other molecules such as proteins and DNA.  Proteins exist in a certain shape and it’s the shape that determines its information.  When sugars glycate a protein, they change its shape which prevents them from delivering the information they’re supposed to.  Glycation is one of the major damages that occurs in the body and this ultimately will accumulate and accrues and cause your death.

It’s well known in research but not as much in medical practice.  When cells glycate, when molecules glycate, they can form advanced glycated end products, and the acronym for that is ages, and they know it’s a measure player in the damages and rate of aging.  Therefore, having elevated blood sugars is not healthy.  But how you lower the blood sugars is very important.  We don’t want to substitute a worse evil than the elevated blood sugar.  If you’re lowering sugar by raising insulin, then you’re mimicking the conditions that cause diabetes in the first place.  When cells become insulin resistant, they’re not being stupid.  Cells become very smart because they let less sugar in.

That’s worth repeating.  The insides of cells are very delicate.  Yes, they need some sugar.  But not too much.  Look at it this way.  If you want a little bit of honey in your kitchen, maybe you store a little in a jar, so you can use it when you choose to use it.  Now think of what would happen if someone came to your front door with a fire hose and started blasting your kitchen full of honey.  Wouldn’t you want to protect yourself from getting way too much that way?  Wouldn’t you want to resist this strong-arming . . . this, basically, this assault?  Dr. Rosedale says it’s somewhat similar in cells.  Although, if you shut your front door and keep out the blast of honey . . . well, it would still cause problems.  Dr. Rosedale:

RON ROSEDALE:  By cells becoming insulin resistant, it keeps excess sugar out of those cells.  But the excess sugar outside the cells can cause problems to molecules external to the cells.  Thus kidney tubules becoming damaged,  nerves becoming damaged.

Ron Rosedale says a deeper, more fundamental problem with being diabetic is confused instructions multiplying throughout the body.  And most of those confused instructions can’t be solved by taking a pill.

RON ROSEDALE:  The major problem in most diabetics, certainly Type 2 diabetics, is secondary to a hormonal regulation.  When a person becomes insulin resistant, it’s not a disease of blood sugar at all, it’s a disease of insulin signaling.  It produces too strong a signal in some cells, and that’s what causes the death and major problems,  And any drug has nothing to do with that.  it doesn’t treat the underlying cause of the disease.

Ron Rosedale adds that it’s impossible to really improve the body’s signaling instructions simply by adding more of the signaling instructions.  For instance, adding more insulin will generally just lead to greater insulin resistance . . . . meaning it takes more insulin to do what used to just take a little bit of insulin.  And all that extra signaling creates another problem.

RON ROSEDALE:  well it’s too noisy.  If I were to start screaming into the microphone here, not a whole lot of listeners would consider listening.  It’s how loud it’s being spoken, and if it’s being spoken too loud, your cells lose their hearing, just like you would, or I would.  You burn out, at least, temporarily.  the best way to treat it is to reduce the smell, not to increase it.  All you’re going to do is to perpetrate the cause of the disease in the first place.

He says that Rezulin, Avandia and Actos are one style of medication that doesn’t solve the underlying problems of diabetes and actually can make health worse.  Dr. Rosedale warns of problems with other diabetes drugs, such as Glipizide and Glimepriride, which are Sulfonylureas that push the pancreas to produce more insulin in a region of the pancreas known as the islet cells.  Some people have incredibly strong islet cells.  While a normal person who’s insulin sensitive may have islet cells that produce say, 15 units of insulin a day to keep their blood sugars normal, a person with a very strong pancreas, who’s insulin resistant, might be producing 1,000 units of insulin a day to keep their blood sugars at the same, “normal” level.  That incredibly high insulin level might be increasing the likelihood that person is overweight, or has high blood pressure, or heart disease, or cancer, or arthritis.  High insulin levels have been linked to all of these.  But, at least, their blood sugars will be normal, so they won’t be called a diabetic.  A person only gets called a diabetic by the medical community if their pancreas is so stressed, islet cells have been burning out.  They’ve been pushed so hard to make more insulin that they’ve been dying.  Then, blood sugars do start going up.  So, what happens Dr. Rosedale asks, when you give someone with a worn-out pancreas a drug that makes the pancreas work even harder?  He says they take an insulin resistant diabetic –called a Type II diabetic, and kill off enough of their pancreas that their bodies’ really can’t produce enough insulin period — a condition known as Type 1 diabetes.

RON ROSEDALE:  The Sulfonylureas cause the islet cells to make more insulin.  They took drugs that basically whipped a horse at the end of a race.  They whipped the islet cells to make more insulin and once the islet cells died, they needed more insulin.  They basically converted Type 2 diabetics into type 1 diabetics, and it’s due to how diabetes is being treated.  it’s an iatrogenic disease.

What I would call malpractice.

Speaking of malpractice, right now, over ten thousand patients are suing the makers of Avandia, Glaxo Smith-Klein.  These patients accuse Glaxo of fooling them into taking a dangerous drug.  Ron Rosedale has this to say about the lawsuit:

RON ROSEDALE:  The basis of the suit is not going to be that they took a drug that caused harm.  You could do that with virtually any drug.  what’s more alarming is the drug company got caught trying to cover up adverse side effects.  I could go after drug after drug, whereas if you just looked at the science behind them, you could have predicted the adverse side effect. Before the drug was ever approved, in 1999, they hid evidence that the drug Avandia causes heart disease.

Dr. Rosedale says the increase of heart disease was predictable because of how PPAR agonists such as Avandia stimulate any cell to take on more tasks of storing fat . . . including heart cells.  And he says that fat storage focus of drugs such as Avandia . . . and Rezulin . . . also made it predictable that these drugs would cause people to become more overweight.

RON ROSEDALE:  What I did . . . in the time of Rezulin, before it came on the market, so 1995, I calculated how much fat would have to be manufactured in order to lower the blood sugar.  If you took that amount, and you multiplied it by the number if liters in the body and the number of days, how much fat would be formed, and I calculated it would be 5 pounds, and that would account for the blood lowering effects of these drugs.  I asked the drug rep, because at that time I was praciticing conventional medicine and the drug reps were there every single day, when I was done seeing patients, to push drugs on me.  So I asked the drug rep, do these drugs cause weight gain, because theoretically by the way they work, they would have to, and she said, yes, about 5 pounds a year.

RON ROSEDALE:  Ron Rosedale goes on to say that if he predicted these problems about drugs such as Avandia, over a decade ago, why didn’t the FDA regulators?  Why did we have to wait until 2010 to have such strong warnings about Avandia?  And why not go further?  Why not ban it?

RON ROSEDALE:  They should never have been on the market.  There was a lot of evidence about its faults and its danger before it was ever accepted for distribution in 1999.  And Dr. Buse, I think, was threatened with a huge lawsuit.  the University of North Carolina was also threatened with a huge lawsuit that they could ill afford, and so they had to keep their mouths shut.

In terms of simple math, Ron Rosedale says you can accomplish the same benefits of taking Avandia, with fewer side effects, with a very simple dietary change:

RON ROSEDALE:  A person could eat one slice of bread less a day, and have a greater effect on blood sugar than every drug on the market.  If they stopped eating foods that are well known to turn into glucose, the diabetes can be reversed.  It’s an easy disease to reverse, without the use of drugs.  The drugs cause more harm than good.  They make my job harder, rather than easier.  I hate to say it, and it sounds like I’m way out in left field.  But if you look at the science behind them, that is the case.  Those people will have to take injections of insulin, if it can’t be reversed quickly.  Type II strictly by not eating foods that turn into sugar.

Ron Rosedale’s recommendation that people who are prone to diabetes NOT eat foods that turn into sugar goes against the grain of many well-respected health organizations.  The American Diabetes Association websites and the USDA food pyramid guidelines both recommend that the majority of calories in the American diet should come from sugars and starches such as bread, pasta, potatoes, cereal.

RON ROSEDALE:  And they’ve done a great job, and they’ve been extremely effective at reducing the number of diabetics, over the years, in this country.  The number of diabetics is accelerating and becoming far worse as people are adhering to the guideline of the American Diabetes Association.

Not only are more people becoming diabetic today . . . more people are getting diagnosed at much younger ages.  Because of this,  Ron Rosedale predicts that for the first time in our history, average lifespan may start going down.

RON ROSEDALE:   Children now are starting to behave as adults as far as disease is concerned.  So many children now are getting so called adult onset diabetes.  The insulin resistance that used to take decades to accrue is now occurring in a few years.

With all these problems happening through standard health recommendations and the use of drugs such as Avandia, Ron Rosedale says that it’s time to change:

RON ROSEDALE:  If we were a stupid mouse in a maze, and we’re trying to reach a goal which in this case, would be health, if you hit a wall, you at least go a different way.  what we’ve been doing isn’t right.  That is virtually proven, that people are getting worse.  The rate of diabetes is going up.  the rate of cancer certainly isn’t going down.  If we’re not doing something right, then we must do something different.

The key thing Ron Rosedale says to do differently is to eat differently.

RON ROSEDALE:  What you eat is going to determine your health more than anything else you’re going to do.  Well let’s eat something else  let’s do something different.

But we all know that it’s challenging for people to change what they eat.  So, why even try?  Ron Rosedale.

RON ROSEDALE:  Hmm.  Well, because it might not be a simple thing to do, it doesn’t mean we can’t start making some changes so it will be more simple in the future.  You could say the same thing about cigarette smoke.  It’s not easy to quit smoking cigarettes.  Cigarettes.  the incidence of cigarette smoking has gone down, as long as the government stood behind us.

Ron Rosedale warns that many groups have a vested interest in making money from rate of diabetes going up.  But as a nation, he says we can’t afford to let that happen.

RON ROSEDALE:  Yes.  It has to be done, and it has to be recognized that the forces that wish to prevent this are not concerned about the health of people.  They are afraid of their profits being lost.  billions, even trillions of dollars that are being spent on health care and wish it to stay the same, and they’ll make bogus studies, they’ll do whatever they can.  They’ll cover up information, they’ll publish wrong information, and they’ll spend lots of money on public relations and advertising.  I’m really happy that Some of this is being exposed, it’s the tiny tip of an iceberg, what’s going on with the Congressional Hearings that have to do with Avandia.

It has essentially dominated medical care for the last few decades.  The real problem is that real science is not being looked at.  the science is plain to see by anybody that has an open mind to science.  For a true scientist, the evidence is simple and clear, and the only thing clouding the picture are special interest groups that wish it to be hidden.

Now, so far, we’ve focused on Avandia as the drug that’s under fire for causing more harm to people’s health than benefit–especially to their hearts.  You see, a close analysis of the research studies involving Avandia have shown the it can increase the risk of heart attack and stroke.

Meanwhile, in this year when Avandia’s been under so much pressure, the makers of Actos have been running full page ads in newspapers, with headlines such as this: “Actos has been shown to lower blood sugar without increasing your risk of having a heart attack or stroke.”   Ron Rosedale says the key words to remember in this statement are “has been shown”

RON ROSEDALE:  It doesn’t mean it doesn’t do it.  It means the company wasn’t so audacious as to try and show its benefit, which might otherwise have revealed its detriment.  to show the 60% increase in risk of cardiac deaths.  That’s huge.  But it wouldn’t show with a single study.  What they’ve done with Actos is just not do studies.

Dr. Rosedale says his look at the biological workings of Actos makes him view it in the same way that he does Avandia.

RON ROSEDALE:  Metabolically, it’s virtually identical.  it is there specifically to stimulate PPR receptors, it’s in the same class of medication, it will do exactly the same thing, and over time as more data is gathered and looked at in an objective manner, that will come out, too.

And that means all the problems with Avandia, including cells being forced to take on more fat.  He adds that you really could get the same benefits by throwing away these pills and eating one less slice of bread.  And if a person wants to get even healthier, Ron Rosedale says eat even fewer foods that turn into sugar.

RON ROSEDALE:   Anybody can eat one slice of bread less a day.  If they want to have the benefit that they have on the drug, that’s all they have to do.  if they want to get rid of their diabetes, that would require a little more modification.  But when they do that, it modifies additions and desires and hunger.  You greatly improve the ability of leptin to work properly.  Leptin regulates the ability to sense sweetness.  Virtually everything changes for the better.  You’re allowed to burn fat.  You store less of it.  You’re not hungry.  Your desires and cravings to eat, and especially to eat carbohydrates  and that little bit of time can be just a few weeks.  All they have to do is make the attempt.  Even if they do it partially, they’ll still affect their body in a much more positive way than the medications would ever dream of doing.

Dr. Rosedale suspects that the current headlines about Avandia are not simply motivated by protecting consumer health.  He says they might be part of a carefully orchestrated marketing campaign that will clear the way for a new class of diabetes medications that will be sold in greater numbers very soon.  He suspects that big pharma agreed to the grilling regarding Avandia because of their future plans.

RON ROSEDALE:  It’s actually being allowed by the forces that be and the committees are on the payroll of the pharmaceutical industry.  Another drug, probably in the DPP4 antagonist class that can take its place, and I think that’s what’s happening, absolutely.  The DPP4, there’s like four or five of them now, Januvia was the first one.  They’re taking over now, and then it’ll take another ten years, or even longer, because the downside of them is that they will cause cancer.  DPP4 most of which have to do with inhibiting cancer.  It’s one of the major ways that your body identifies cancer cells.  You’re lowering your body’s ability to recognize cancer.  The drug companies are going ahead anyway, because the hardest disease to pin on something is cancer, and it’ll take five, ten years for people to start dying of cancer and another five to ten years of uncovering the truth.  Well, it can be a long time.

Rather than wait a long time to find out what the side effects, and harms, of the next group of diabetes drugs will be, Ron Rosedale says just change how you eat.  You can find his suggestions at his website:  drrosedale.com.  Or, at the very least, he says, beware taking drugs like Avanida.

RON ROSEDALE:  My biggest beef with all this is if they did nothing, they probably would be healthier, with the higher blood sugar.  I think the drugs are worse than their benefit in lowering the  sugar.

I’m Shelley Schlender.  Our guest has been Ron Rosedale.  Dr. Rosedale is not a fan of the diabetes drug, Avandia.  For over ten years, he’s been warning people about its health risks.  He recommends using a dietary approach to reverse problems such as heart disease, arthritis and diabetes.  You can find out more from his book, The Rosedale Diet.  Or check his website:  drrosedale.com.

The post Avandia Under Fire – with Dr. Ron Rosedale interviewed by Shelley Schlender appeared first on Ron Rosedale, M.D..

A day in the life as a patient visiting Dr. Rosedale for the first time.

Thank you Shelley Schlender for documenting this ‘checkup with Dr. Rosedale’ and for the work she has done on the article, graphics and the interview below.  You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com  

Magdalena had diabetes and congestive heart failure.  This is a true story, and this is a real transcript of a checkup that Magdalena and her family agreed for me to record, with Dr. Ron Rosedale in 2004.  We have changed some names to hide identities.  It’s a hard story to begin sharing because these are people I know and care about.  We share this interview in hopes that it will provide information useful to other people facing  challenging illnesses.

DR. ROSEDALE:  We are going to start with Magdalena . . .

MAGDALENA:  Mmhmm.

DR. ROSEDALE:  Right?

I’m Shelley Schlender.  We’re listening to Ron Rosedale in the summer of 2004, in his Denver office with 67-year old Magdalena.  She had diabetes and congestive heart failure.  That constant hiss is the sound of the oxygen that was sent from a small green tank into the tubes that sat in Magdalena’s nose, to feed her lungs with air.

DR. ROSEDALE:  And you’re how old?

Magdalena’s daughter, Carmen, translated this question into Spanish for her mother, and for a moment, Magdalena seemed to pause, confused, before she finally answered.

CARMEN:  67.

Seeing Magdalena’s hesitation, Dr. Rosedale grinned and asked his question another way.

DR. ROSEDALE:  How young?

A rapid exchange in Spanish followed between Carmen and her mother.  Magdalena’s weary face grew lively.  Her eyes twinkled, and her voice lilted with a teasing chuckle as she said something that made her daughter laugh.  Carmen translated for Dr. Rosedale.

CARMEN:  That’s why she didn’t understand the first time, and she’s 67.

In mid-July of 2004, Carmen was worried about her mom.  Magdalena had been in the hospital several times that year.  She had been in the Intensive Care Unit just two weeks before this visit to Ron Rosedale’s office.  At the ICU, hospital staff had taken Carmen aside and warned that, the way things were going, it was time to get her mom’s papers in order.  At that time, Carmen had been using Dr. Rosedale’s nutritional approach for over two months.  Dr. Rosedale had been leading the group for free, as part of a small community project that had invited him to help them, as they checked out his dietary ideas of low-carbohydrate, adequate protein, and high quality, high fat eating.  Carmen had seen a big improvement in the health of the entire group that was following Dr. Rosedale’s approach, including hers.  Because Ron Rosedale’s nutritional approach had been helping Carmen, she wondered if it would help her mother.  But Carmen’s mom had so many health problems going on, and was taking so many medications; Ron felt that she needed more attention than he could give if she simply attended the small community group.  And while the entire group had been urged to consult their doctors about their changes in diet, so they could have assistance in being monitored and adjusting medications, most of the community members had hesitated to actually talk with their doctors.  Of those who did, the responses from their regular physicians were not always helpful or encouraging.  Several people reported to the group that when the labs on their medical exams had shown big improvements in weight, cholesterol, blood pressure or other standard markers for health, their doctors had congratulated them on finally switching to a low-fat diet.  And most of the community participants, when told this by a doctor, didn’t explain that they were now doing a HIGH-fat diet.  In some cases, when one of the community members got up the courage to correct the doctor and explain what Dr. Rosedale’s diet is, their regular doctor said it was a bad idea.  Not always.  Sometimes the doctor had been enthusiastic, and those members of the little community group came back glowing from the praise and validation.  But that kind of response was the exception, rather than the norm.

So, Carmen had been uncertain that Magdalena’s doctors would be comfortable teaming up to help her change her diet to Dr. Rosedale’s approach.  And Dr. Rosedale was concerned that Magdalena would need some medical monitoring.  So that’s why she was here today.  Dr. Rosedale had agreed to see her in his office, as a special situation.

She had arrived there exhausted, using a walker, plus Carmen’s arm around her, so she could walk a few steps before resting again, her wheeled green oxygen tank trailing her, because of the problems in her lungs.  It had taken 15 minutes to go from the parking lot and up the elevator.  But now she was in Dr. Rosedale’s office for a checkup.

DR. ROSEDALE:  And the major reason you’re here, I understand, is because of congestive heart failure?

There was a moment of silence, as Magdalena looked with confusion at her daughter.

DR. ROSEDALE:  You don’t speak English very well?

MAGDALENA:  No

DR. ROSEDALE turned to Carmen:  You’re going to translate.

CARMEN:  Yes, I’ll translate.

DR. ROSEDALE:  Anyway, congestive heart failure is a major problem?

CARMEN:  Yes

Congestive heart failure happens when the heart loses the ability to pump blood properly.  This leads to many problems, including a very increased risk of heart attack, lack of oxygen, and fluid building up in the lungs.  That fluid can build up so much, a person basically drowns.  In the early 1970s, perhaps 2 million Americans suffered from congestive heart failure.  By 1994, that number had grown to nearly 5 million.

There are many possibilities as to why.  Diabetes is one of them.  Some medical researchers are concerned that the statin drugs that are given to reduce heart attacks might have a side effect of increasing the risk of congestive hearts.  But that’s a very controversial theory.  More commonly agreed is that diabetes increases the risk.  And, indeed, as diabetes increases in the United States, so does congestive heart failure.  Here we are in Ron Rosedale’s office, with, Magdalena, age of 67, one of these congestive heart failure statistics.

DR. ROSEDALE:  Blood pressure?  And has Magdalena had any heart attacks before?

CARMEN:  No.

DR. ROSEDALE:  No heart attacks.  Other than congestive heart failure, any other problems with her heart?  Do they know why it has congestive heart failure?  Sometimes there’s outside reasons.  Sometimes it can be lung disease that makes your heart have to work too hard.  Does Magdalena have lung disease?

CARMEN:  Yes

DR. ROSEDALE:  Emphysema?

CARMEN:  Yes.  She smoked.

DR. ROSEDALE:  You’ve heard the term in her medical records COPD, chronic obstructive pulmonary disease?

CARMEN:  Yes.

DR. ROSEDALE:  COPD.  So that’s probably what’s causing the congestive heart failure.  Now, there are two major divisions to the heart.  There’s kind of a left heart and a right heart.  Left ventricle and right ventricle.  Do you know which one is in failure?

Carmen and Magdalena didn’t know.  So Dr. Rosedale took a closer look at Magdalena.

DR. ROSEDALE:  Looks like fluid is building up in her belly.  Is that where the build up is?  In her belly or her lungs?

CARMEN:  They have never said anything about fluid in her tummy.  She has hernias in her tummy.  That’s one of the cause of her fluid.

DR. ROSEDALE:  It’s her left ventricle that would be failing if it’s her lungs that are filling up.  You’re not sure of that?  Do you have any of her old records?

CARMEN held up a thin beige manila folder:  No.  I have only a list of medications she’s been taking.

DR. ROSEDALE started writing on a doctor’s memo pad:  This is going to be a list of instructions.  One is going to be to have last hospital discharge summary and tests faxed to my office.  Okay?  That would be important.  The discharge summary in particular.  It will describe everything that went on in her last hospital admission.  What they did and all the medications she took and was left on and all that stuff.

CARMEN frowned slightly, as she thought about what the document that Dr. Rosedale was requesting:  That’s the summary that’s not usually given to the patient.  They gave us two sheets that is just the list of medications.

DR. ROSEDALE nodded:  So this is your followup stuff.  This is something you would get from the doctor or the hospital, and just have them fax it over here.  Okay?  And when did you get out of the hospital?

CARMEN translated, and MAGDALENA replied:  La semana pasada?

CARMEN:  Two weeks?

DR. ROSEDALE:  Almost two weeks ago.  So the discharge summary should be done.  It’s done by the doctor in charge, and it should be ready by now.  That would be a good thing to look at, so I don’t have to start from square one.  Having the discharge summary will mean that I can see what they’ve prescribed, what tests have been done.  Right now I’m guessing a little bit as to what’s been happening.

But with the thin sheet of papers that Carmen had obtained, there was at least a short history of Magdalena’s past conditions.  Ron Rosedale looked it over now.

DR. ROSEDALE:  Congestive heart failure diagnosed seven years ago.  Diabetes.  How long have you had diabetes?  Thirty years?  Twenty years?

MAGDALENA:  Bente cinco . . .

Magdalena had said “twenty-five?” with a guessing sound.

DR. ROSEDALE:  Approximately . .  .Thirty years?  On insulin for 23 years.  And you’ve got . . . um . . . feet.

He tapped his pencil crisply, thinking of how to ask a medical question in a simple way.  What he would be asking about next was a condition known medically as “Intermittent Claudication.”  It’s a sort of angina of the legs.  According to the National Institutes of Health, “Angina,” also known as chest pain, is discomfort that occurs when an area of the heart muscle doesn’t get enough oxygen-rich blood.  This can be caused by plaque buildup or constricted vessels, meaning vessels that have narrowed or grown stiffer because they’re puffed up and inflamed.  While angina is a condition that doctors commonly check and monitor, there’s another place where constricted vessels can cause muscle pain—that condition known as “intermittent claudication.”

DR. ROSEDALE:  Do you have pain in your legs when you walk?

Carmen translated and her mother blinked at this question that wasn’t asked very often in a medical checkup.   The look on her face made it seem as though it had not occurred to her that a constant pain she lived with in her legs was something a doctor would want to talk about.

MAGDALENA:  Yeah

DR. ROSEDALE:  Where?  In your calf?

CARMEN translated, and her mother replied in Spanish, and Carmen then explained:  Her lower back legs.

DR. ROSEDALE:  That’s what hurts when you walk?

MAGDALENA:  Esto y aqui . . .en la noche . .

CARMEN:  The back of her knees, and at night her veins are altered.  Enlarged.

DR. ROSEDALE:  When she walks.  Let’s just talk about the pain when she walks right now.

CARMEN:  Quando caminas . . .

MAGDALENA explained in Spanish, then CARMEN said:  It’s the pain when she walks.

DR. ROSEDALE:  When it hurts after she walks, and she stops walking, does the pain go away?

CARMEN:  It gets a little better when she stops, but then she says that it affects her.  Her chest starts hurting when she stops walking and then her neck also hurts, and her arms feel very tired.

DR. ROSEDALE:  Does it go away when she stops?

MAGD.  Si . . .

CARMEN:  It goes a little bit away when she stops, and if she sits down she feels much much better.

DR. ROSEDALE was asking these questions as a detective might ask questions, trying to solve a case, and now, he seemed to relax and be pleased, as a detective might when they have a clue that was helpful.  Indeed, in other conversations, Dr. Rosedale had shared that sometimes, he’s seen patients where they’ve seen neurologists due to the pain in their legs.  They’ve seen physical therapists and other specialists.  They’ve had back surgery recommended, or pain killers in high doses, and yet the pain doesn’t go away.  But if he puts them on his diet, the pain in their legs goes away in less than a week, and usually, so does any angina – chest pain around the heart.  He didn’t say all these things at this moment, in this medical checkup with Magdalena.  He was still gathering information.  But he did look at the list of medications, and as he did, his face grew hard and angry.  He spoke crisply though, and kept his voice neutral:  Okay.  So she’s on these and these?  Two pages of drugs?

CARMEN:  Yes

DR. ROSEDALE:  Okay.  And these were done before the hospital admission.

CARMEN:  Yes, There’s one I think that was done in the hospital. There’s some the doctor wrote down.

Dr. Rosedale turned his attention from the list of medications and started writing on the notepad again, full of concentration as he combined steps for action with explanations about medical conditions that are often overlooked, such as diabetes caused by insulin resistance.  Insulin resistance happens when the body’s cells resist the signal of the hormone, insulin.  Insulin Resistance means, in a way, that a person’s basically eating a diet too high in sugar and carbohydrates, and their doctor is prescribing TOO MUCH insulin and medication for what their body would need if the person simply changed their diet.  The combination of the wrong diet and the high doses of medication often create a vicious cycle, and the insulin resistance gets worse and worse.  Now, that’s a description that’s contested by many standard doctors and diabetes experts.  They would argue that there’s no harm in giving a person extra insulin, to keep blood sugars lower.  But, that kind of “what’s the harm in more medication” overlooks a number of side effects.  That’s all background about what Dr. Rosedale may have been looking for in this checkup, and what he said to Carmen and Magdalena next.

DR. ROSEDALE:  This set of data was done in May.  OK.  There’s one lab that has not been done that we’re going to need, and I’ll write that on here.  Needs C-Peptide.  Serum.  Okay?  That needs to get done.  It has to do with her diabetes.  It lets us know how much insulin her own pancreas is still able to produce, if anything.  Okay?  And that’s very important.  We need to find out if she’s still capable of producing insulin on her own.  And if so, then the need for insulin by shot is much less important.  In fact it would be desirable not to take it.  If a person has too much insulin, most of the time diabetes, and I definitely suspect that in Magdalena’s case, this was the case, that her diabetes arose not because of too little insulin but because her cells weren’t listening to insulin.  And her pancreas was actually producing too much insulin.  The excess insulin causes fat to be stored around the arteries and makes asthma worse and all these other bad things.  Now she didn’t need that.  It didn’t make her smoke.  Smoking caused a lot of damage, and that certainly contributed to her congestive heart failure, but so did the high insulin.  And if we can get her off some of that insulin, it will help her a great deal.  High amounts of insulin that she’s giving herself and that she might be producing on her own causes fluid retention.  It causes excess fluid.  That’s why she had high blood pressure.  High blood pressure was actually caused by the insulin she was taking.  And the extra fluid puts a greater burden on her heart.  Got too much fluid floating around.  It makes it harder for your heart to handle all that fluid.  That also contributed to the congestive heart failure.  A lot of that fluid ends up in her lungs.  Now, she’s taking a bunch of diuretics to try and get rid of that fluid.  We can’t change that right now.  But the diuretics cause then further insulin resistance, and greater insulin requirements, which causes then fluid retention.  So then she’s in this horrible vicious cycle where basically driving with the accelerator and the brakes on at the same time.  And that’s not very good for her health.  We need to break that cycle.  We’re going to start breaking the cycle with diet.  And then we’re going to start working on some of these medications.   Because they’re getting in the way, more than they’re helping, actually.  They treat the symptom, but they make the underlying disease worse.  So you take one step forward, two steps backward.  Or three or four or five.  And we don’t have very far to step backwards, as you’re aware at this point.  We don’t have time to step very far backwards, so we need to make these changes as fast as we can.

Dr. Rosedale now turned his attention back to the long, two-page list of medications of Magdalena.  And now, his voice carried a tone of anger.

DR. ROSEDALE:  Some of the writing I can’t quite read.  Is that Glucophage?  No, Glucovance.  Okay.  That’s dumb.  Get off of that.  Lasix we have to be on right now.  Propranolol is a Beta blocker.  Predinisone. is that for her asthma?  Insulin 70/30, we’re going to change that, provided that Magdalena will adhere to the dietary changes.  It’s going to be really important, because otherwise we can’t change her insulin.  So we’re going to be making changes based on the assumption that she will be changing her diet.  Okay?

With a look of determination, Carmen nodded.  And since she had been eating the way that Dr. Rosedale recommended for over two months, she knew what he was talking about, when it came to how he’d recommend that her mother would eat.  Magdalena didn’t know yet what this diet was.  But watching her daughter, Magdalena nodded, too.  Dr. Rosedale continued looking down, and reading from the list, his face a mask, and yet, still seeming angrier the more he read.

DR. ROSEDALE:  Advair is for asthma.  Verapamil is another thing for blood pressure.  Calcium Blocker also makes her diabetes worse.  Next one, Trazidone, she takes for sleep.  The next one, I can’t quite make this last one.  Says for her stomach.  Preva?  I can’t quite read that.  Maybe you can.  Do you know what this is?

CARMEN:  Prevacid.

DR. ROSEDALE:  OK, that’s an acid blocker. Of course, the universal statin drug, which right now, she should probably get off of.  I’m going to go out on a limb on that one.

CARMEN:  Which?

DR. ROSEDALE:  Lovastain.  It’s a statin drug.  It makes it harder for her heart to beat. It’s the last thing she needs right now.  Okay?  They’re worried about long term cholesterol, which has nothing to do with her heart disease, number one.  But the immediate effect of it is that it weakens her heart.  She’s got heart failure.  We need as strong a heart as we can.  She’s got to get off of it.  Hydrazaine is another thing for her blood pressure.  Aspirin.  And Prozac.  So I’d say she’s taking her fair amount of drugs, making money for a lot of people.

He said that last statement with bitter humor.  At this point, I spoke up, saying,  “There’s a chance that the doctor involved might be receptive to talking with you.”  I said this with hope, not knowing that, like most other doctors who our community group had interacted with, Magdalena’s doctor was NOT going to be in favor of this change in diet.  Ron Rosedale, with years more experience explaining his unconventional diet to other medical professionals, sounded cynical as he responded to me.

DR. ROSEDALE:  Great.  I’d be happy to.

I caught the cynicism and decided to defend Magdalena’s regular doctors, who I was certain were well-intentioned, and wanted to see Magdalena healthier.  “My guess is that they’re following protocol.”

DR. ROSEDALE:  I’m sure.  They definitely are.  There’s no question that everybody gets put on statin drugs, but there’s a down side.  And right now, I’m just more concerned about, um, trying to save your life, really than I am about politics in medicine.  One of the things that Lovastain, the cholesterol drug does, is it depletes the body of something called Co-Enzyme Q 10, which is necessary for muscle function. Your heart is a muscle.  Probably the most important muscle.  We’re going to do the opposite.  We want to put her on a lot of Q 10.  So we don’t want to put her on something that something else is trying to get rid of.  That’s not really a good thing to do.  So, we’re going to have a supplement list of things we’re going to go on.  But the most important thing at this point is going to be diet.  And diet will allow her to lose more fluid than any of these drugs will.  And then I would say in a short period of time, we’re going to try and reduce that Lasix.  Lasix also gets rid of magnesium.  Magnesium is necessary for her cells to listen to insulin.  So, having low magnesium makes her diabetes worse, which makes her need more insulin, which causes fluid retention.  Which is what the Lasix is trying to get rid of.  So again, it works into this horrible, vicious cycle.  So we’re going to need to get as much magnesium into her as we can.  But there’s only a certain amount that your intestines can handle at a time, otherwise it gives you diarrhea.  We’ll spread it out and try and see if we can reduce that Lasix as soon as we can.

Dr. Rosedale was writing rapidly as he spoke, and soon he focused simply on looking at the medications and writing, and tapping his pencil furiously.  Watching as he concentrated, it was like watching a bomb specialist trying to sort through a tangle of wires that are connected to a ticking bomb.  To stop the bomb from going off, some of the wires had to be disconnected.  But if the wrong wires were taken off too soon, the bomb would explode, right there in his hands.  That image reminded me that right now, Magdalena’s congestive heart failure was a ticking bomb.  Her doctors had told Carmen to get Magdalena’s papers in order.  She was a half a step away from death at every moment.  By trying to help her, by trying to turn this whole situation into a healthier result, Dr. Rosedale was fencing with Death.

DR. ROSEDALE:  We’re going to have so see Magdalena again pretty soon because of all these changes.  Because of all the drugs that you’re on.  Okay?  And we’ll talk about diet first, but don’t let me forget to listen to her heart and lungs before she leaves.

DR ROSEDALE (turning to Magdalena):  Do you weigh yourself every day?

MAGDALENA:  No?

DR. ROSEDALE:  You need to.

CARMEN told her mother in Spanish, “You Have to”:  Necesitas hacer.

MAGDALENA:  OK

DR. ROSEDALE:  It’s one of the ways to know whether you’re accumulating fluid.  Initially when the weight comes down, most will be water, not so much fat.  But that’s good.  We want you to lose some of this excess fluid.  Reducing the excess fluid makes it easier on your heart.  But we want to do it without the diuretics as much as we can.  The diuretics will cause most of that fluid to come out of your bloodstream.  So it’s making your heartbeat fast.  Even though you have all this fluid in your tissues, you don’t have it inside your arteries.  And that’s not such a good thing.  Okay?  So I want you to weigh yourself every day.  And write it down.

CARMEN translated, and MAGDALENA said:  OK.

DR. ROSEDALE:  That’ll be good for your other doctor too.  When are you supposed to have another chest x-ray.

CARMEN translated, and MAGDALENA said:  Con Paula.

CARMEN:  She’s going to try to go to the doctor every Friday, because the doctor also told her to go there often.  She wants to keep an eye on her.

DR. ROSEDALE:  Good.  Okay.  Well, it will be something that’s difficult to listen to her lungs because of her emphysema.  And to be able to see how clear her lungs are, about the only way to do it will be with a chest x-ray.  I imagine she had a chest x-ray when she was discharged from the hospital.  I suspect they’ll want another one very soon.  Has Magdalena been on oxygen for a long time?

CARMEN:  It’s been probably a year.

MAGDALENA:  Poco menos.

CARMEN:  Less than a year.  Probably eight months.

DR. ROSEDALE:  Okay.  The diabetes we can certainly help, and we can certainly help the blood pressure without using all these medications and can help the congestive heart failure up to a point, because a lot of that is from the damage that’s occurred to her lungs.  The damage to her lungs can be reversed maybe a little bit but not very much.  It’s kind of a structural thing.  The tissue has kind of died, and we can’t reverse that too much, but we can make it a little bit better.  So that’s kind of what we’re dealing with.  And the blood pressure, we can, I think, certainly improve upon.  So those are our endeavors.  We want to help the diabetes and in that way we can reduce the blood pressure.  And get rid of some fluid without having to use these drugs which has some long-term side effects.  And even some circular side effects.  How often is Magdalena’s blood pressure taken?

CARMEN translated, and MAGDALENA said:  Quando voya.

CARMEN:  Every time she goes to the doctor, every week or two weeks.

DR. ROSEDALE:  She doesn’t take it herself.  Do you have a way to do that?

CARMEN:  Yeah.  We can get one of those.

DR. ROSEDALE:  Good.  That would be important, because blood pressure can change very rapidly within the week.  And then we need to reduce the blood pressure medications, or she’ll get very faint.  Now, How much insulin is she taking?
CARMEN:  She takes 24, 25 units in the morning, sometimes nothing at night because her sugars get very low during the night and she’s afraid.  Sometimes she just uses 4 or 5 at night.

DR. ROSEDALE:  And she’s using 70/30 insulin.  About 24 units in the AM and 0 to 5 units PM.  And that’s it?  Okay.  How often does Magdalena check her blood sugars?

Here, there came another issue that wasn’t clear to Dr. Rosedale at that time, and which Carmen and Magdalena didn’t mention.  You see, Magdalena was retired, and lived on a very tight budget.  She had a small apartment in low income housing, and she relied on government health care plans to pay her medical bills.  But the state’s computer system for government payments was not working properly, and so it was not paying for her regular healthcare needs, such as for the daily supplies needed for taking blood sugars.  Taking insulin shots, which Magdalena did, can cost at least a dollar a day.  Taking blood sugar measurements at least four times a day, which is a wise idea for someone like Magdalena, can cost two dollars a day.  And right now, Magdalena’s insurance wasn’t paying for any of this.  So she was “guessing” on the right amount of insulin to be taking, and she was saving her money by not checking blood sugars at all.  Magdalena didn’t explain all this at the moment, and at this time, Carmen may not have realized the extent of Magdalena’s medical payment problems either.  So Magdalena simply said she hadn’t been checking her blood sugars, and her daughter translated.  And so, in this exchange, it just sounded like Magdalena had gotten casual about checking her blood sugars.  It didn’t occur do Dr. Rosedale that finances were actually what stood in the way.  He was doing his part.  He was seeing Magdalena for free in this office visit.  It wasn’t obvious to him that other financial issues could still stand in the way.

CARMEN:  She hasn’t checked her blood sugars recently, or lately, like probably the last two days.

DR. ROSEDALE:  Does she have a blood sugar monitor?

CARMEN:  Yeah, she does.

DR. ROSEDALE:  And she knows how to check it?

CARMEN:  Yes.  We just need to get the strips.

DR. ROSEDALE:   Okay, so we need to . . . uh.  Okay.  Check blood pressure daily.  We’re going to be making some changes, and some of the changes will be fast.  So monitoring by her regular physician once a week, which I’m sure is all they could do.  That’s actually pretty good, and they’re not to be faulted for that.  But it’s not going to be enough.  So we need to do some self-monitoring everyday.  So that will be weight, blood pressure, blood sugar.  Check blood sugars every day, before breakfast and before bedtime.  Okay?  (WRITING ALL THIS DOWN)  I want you to keep chart of blood sugar, blood pressure and weight daily.  FAX to office every two days for now.  Okay?  You have a FAX machine?

CARMEN:  Yes

DR. ROSEDALE:  Because we’re going to have to make adjustments in the medications.  In the insulin.  In the blood pressure medications.  So we’ll have to stay in contact.  But we’ll give you a few guidelines right now.   If blood pressure goes low, do you have an idea of what it usually runs?

CARMEN:  Sometimes it’s .  . . . 140 over 90, or 68.  I just remember some of the numbers I saw at the hospital, and it went too high, like 220 over 60.  I don’t even remember, but it was too high, like 240, 220, and I think she’s always probably around 135.

MAGDALENA:  Siesta no recuerrdo quanto.  En la hospital, es la ultima, lo creo.

CARMEN:  She’s not sure, but she remembers 140 and 150.

DR. ROSEDALE:  (TAPPING PENCIL)  We’ll reduce the Verapimil.  That’ll be the first one, if the blood pressure goes low.  That means less than 110 over 70 for her.  If the blood pressure goes less than that, reduce the Veratimil . . . right now it’s 360 Milligrams.  If it’s low, reduce to ½ tablet.  If it stays low, stop altogether.  Okay?  If blood pressure—I’ll call it BP for blood pressure.  If blood pressure continues low, you’ll reduce something else.  Some of the blood pressure medications have dual roles.  So I think we’ll reduce the hydralazine to ½ dose, or altogether if you can.  Okay?  (Flipping page.)   My next thing I’m going to want to lower over time is going to be the Lasix.  But it doesn’t just lower blood pressure, they’re using it to get rid of the excess fluid.  That’s why it’s going to be very important to take daily weights.  Because when we start reducing that fluid buildup, I want to make sure the weight is not coming up, indicating that she might be retaining fluid.  Okay?  The Glocovance is a combination drug.  It has Glucophage and probably glyburide. . . I’d rather she just took the glucophage without the other half.  That’s all we can do to reduce the insulin for now.  It would be better to . . change insulin to MPH from 70/30.  We’re going to have to change the insulin.  OK?
CARMEN: OK

DR. ROSEDALE:  If she changes her diet, she won’t be able to stay on that insulin.  Her sugars will crash.  We need to go on a different kind of insulin.  Part of which, you’re already taking.  But it’s combined . . . The insulin Magdalena is taking a combination of fast acting and a slow acting.  We only want the slow acting.  The fast acting is to bring down spikes of sugar from eating carbohydrates.  If we’re not going to be eating the carbohydrates, we won’t be spiking the sugars.  And then, if you took that fast-acting inuslin, it would cause her sugars to go low.  She cannot take that.  So, how can you get insulin?

CARMEN:  She gets it from pharmacy in Boulder, and they give her a discount.

DR. ROSEDALE:  Do you have to pay for it?

CARMEN:  Yeah.  We have to pay for it.

DR. ROSEDALE now relaxed, now that he had an action plan in place.  And perhaps the fact that Magdalena was paying out of pocket for her insulin touched him in a way that connected him back to Magdalena and Carmen.  So in a light-hearted, friendly way, he explained:  The type I’m switching to is not a particularly expensive one.  So hopefully you won’t have to waste too much of what she’s already bought. But, before you leave, we need to get you a prescription for it.  Okay?  Or I probably should do it now.  Or I’ll forget!

After Ron Rosedale left the room to get the prescription ordered, Magdalena explained her hopes, with her daughter translating.

CARMEN:  She really wants to feel better, to feel well.  She’s willing to make the changes.  She says that the only thing that could happen is, if she gets ill and she has to go to the hospital, they will make changes and how will that work?  That’s a question that she has.

RON (RETURNING WITH PRESCRIPTION)  Okay.  That’s for the new “old” insulin.    And you have to kind of monitor . . . you need to monitor your blood sugars.  Are you going to be involved in her care?

CARMEN:  I can be with her in the morning and also in the afternoon.  During the day my daughter is with her.  And I can talk with her.  She’ll be able to help.

DR. ROSEDALE:  That would be great.  She might need help with changing her insulin requirements.  I’m going to change the glucovance into glucophage.  That will lower her insulin production.  One of the components of the glucovance causes her own pancreas to produce more insulin.  But in so doing, it stresses out the cells that make the insulin and causes them to die over time.  We don’t want that.  Long-term it’s not good.  And that certainly would be one way to lower her insulin.  Although it won’t be apparent in the insulin she’s taking.  Her total insulin is determined by how much her own pancreas is producing and how much she’d taking by shot.  I don’t want her to take the kind that is trying her to whip her own pancreas into producing more insulin.  That is stressful to the pancreas.  She doesn’t need any more of that.  So we’re going to take off one of the components of the drug that she’s taking and use the other component.  Similar to what we’re doing with the 70 30 insulin.  We’re just going to use the 70 portion and not the 30.  And the glucovance, we’re going to use the glucophage portion and not the glyburide.  Okay, you’re going to use a whole bunch of Co-Q10.  You’ll stop the lovastatin for now. Okay?  I said for two months.  I’m being politically correct, then we’ll reevaluate it.  Right now, we want her heart to beat as powerfully as it can, and the lovastatin’s getting in the way of that.  OK.  We’re going to change glucovance to glucophage.  Oh, wait a second here.  Her creatine’s doing pretty good?  Let’s see.  I would need updated laboratory work.  I need the laboratory work that they did in the hospital.  The only laboratory data here from the hospital is her blood count, but not the chemistry.  Basically what I need here is the creatine.  For now.  Okay, the glucophage, one, 1 three times per day with meals.  So you have to stop the glucovance.  I’m going to circle it.  So you’ll know.  And we’re changing the insulin, too.  That’s what we’re changing right now.  And then you might change, I’ll put a square around verapamil, and I’ll put a square around hydralaine.  Those are the two blood pressures you might have to lower, depending on what happens with her blood pressure.

CARMEN:  So if her blood pressure goes low, then we are going to lower both at the same time.

DR. ROSEDALE:  You’re going to do first the Veratamil.  I wrote it down.  And then the Hydralazine.

CARMEN:  If we go to that pharmacy, she gets a discount, and I think she was referred by her regular clinic, so I think it will work with any prescription it brings and we will get the discount.

DR. ROSEDALE:  It’s really important that she does not take the glucovance and glucophage together.  Okay?  That would be a bad mistake.  Okay, now Magdalena’s going to have to change her diet.  You already know what to eat.

CARMEN knew this question was for her.  And she answered with confidence:  Yes.

DR. ROSEDALE now turned to Magdalena, as her doctor translated his next question:  OK.  What would be a typical breakfast?

MAGDALENA:  Una tortilla, triga.

CARMEN:  One egg, some cereal, and one wheat flour tortilla, and the milk with the cereal.

DR. ROSEDALE:  Okay.  Anything to drink?

MAGDALENA:  Agua.
CARMEN:  Just water.

DR. ROSEDALE:  Okay.  That’s good.  That’s the one good thing.  Egg not so bad.  How’s the egg cooked?

CARMEN:  Poached egg with very little grease, and she uses canola oil.

DR. ROSEDALE:  Okay.  The tortillas she uses, you’re going to switch tortillas.  To La Tortilla tortillas. You can get them at Vitamin Cottage. Those are the only ones that Magdalena can use.  Are you familiar with those kind.

CARMEN nodded, thinking of the low carb tortillas that didn’t taste as good as regular tortillas, but at least were shaped like them:  Ah, yes.

DR. ROSEDALE:  Do you use them?

CARMEN:  I don’t use them, because I don’t like them.

DR. ROSEDALE:  But you know what they are?

CARMEN:  Yes.

DR. ROSEDALE:  Those are the only ones that Magdalena can use.

CARMEN translated, then when Magdalena nodded, looking confused but trusting of her daughter, DR. ROSEDALE said this:  And only half a tortilla at a time.

As Carmen translated this dietary restriction, along with others to bring her carbohydrates much, much lower, Magdalena started laughing . . . as sound that transcended language barriers as “You have GOT to be kidding me!”

DR. ROSEDALE:  For Magdalena, We have to go to more extreme measures here.

CARMEN translated, and in disbelief, MAGDALENA SAID:  And no puedo comer la fruita . . .

CARMEN:  She’s asking about fruit and jello, because she knows I was not eating fruit.

DR. ROSEDALE nodded, adding:  She cannot eat cereals.   She can eat two eggs and half a tortilla.  That would be a breakfast.  Okay?

CARMEN:  That was one of her questions.  Since the beginning when I told her about the diet.  She says if her sugar level goes too low, what should she drink to bring it up.  Because she usually uses orange juice.

DR. ROSEDALE:  We will be trying to prevent high and low blood sugars.  It will be less likely by changing the type of insulin we’re using and changing the diet.  But if it does happen, two swallows of orange juice.

CARMEN:  She says just not getting to that level of . . . but she says, it’s fine.  If she’s not going to require a lot of the juice, and her sugars are not going to go that low, because she feels really bad when that happens.

DR. ROSEDALE:  OKAY.  Then after we change the diet, we’re already reducing her total insulin by changing from the glucovance to the glucophage.  She might still need to take less insulin.  Now the insulin we’re changing her to is a long-acting insulin.  I’m going to hope that she can get off of it totally over the next month or two.  We’re just going to have to wait and see.  So, if her sugars are running low all day long, then the next day she should take less.  There should be a gradual decline in her blood sugars, in which case, you can reduce her insulin requirement.   I’m going to say start with the same you’re using now, 24 units of NPH insulin.  Reduce, depending on how low her sugars might go, reduce insulin if sugars . . . now when Magdalena gets a sugar reaction, when it goes low. . . how low does it go?

CARMEN:  52, and I remember one, 74.  Sometimes, she’s 29.

DR. ROSEDALE:  Okay, 74 wouldn’t be so bad, unless she gets symptoms.  If you’re healthy your sugars will run 74 anyway.  I’m going to say, reduce insulin if the sugars go under 80.  And then reduce by 5 units at a time.  If it’s staying low, you might have to reduce.  You might have to go off of it.  Great!  How fast is hard to guess.  So you just have to check the blood sugars and see what happens.  Do we have her weight recorded today?

CARMEN:  175 and some ounces.

DR. ROSEDALE looked again at Magdalena, who is just barely five feet tall, and he calculated her likely lean body protein mass:  No more than 50 grams of protein per day, and not more, and remember, it’s not a high protein diet.  No more than 15 grams protein per meal.  That would be about the size of a deck of cards for a piece of meat.  So half of a half of a chicken breast.  Does she like nuts?

CARMEN:  Yes

DR. ROSEDALE wrote more instructions on the pad:  Good.  If hungry, she can snack on a few nuts.  Almonds, walnuts, pecans.  Not peanuts.  She can eat some cashews, but not many cashews.  Not peanuts, not cashews.  Other nuts are fine.  Nuts are not the same as seeds, so don’t eat seeds such as sunflower seeds.  I don’t care where she gets her protein.  I prefer she doesn’t eat a lot of red meat until I see her other laboratory level and we see how much iron she’s been storing.  If we know how much iron she’s storing, we’ll know whether she needs to reduce iron-containing foods.  If she hasn’t had a ferritin level checked, we need to check it.

CARMEN explained all this for Magdalena, and then explained that her last check showed normal ferritin levels.

DR. ROSEDALE:  Oh, good.  So her ferritin is probably not a problem.  So no . . . and I capitalized, DO NOT EAT TORTILLA OR STARCHES.  So do not eat sugar or starches, and I capitalized it.  Other than La Tortillas.  That is her only bread like product.  No rice.  No cereal.  No potatoes.

CARMEN:  But oatmeal.  She loves oatmeal.

DR. ROSEDALE:  No oatmeal.  It all turns to sugar.  Really quickly.  If she eliminates that stuff, we might get her off the insulin totally.  And getting her off the insulin totally, her fluids are going to come down.  And then we can get her off the Lasix.  And that’ll help her heart beat harder.  And then we can start reversing these vicious cycles that are taking place in her right now.  Take a medication for one thing then it ends up causing something else that she need to take a medication for.  It’s gone on now for a long time and therefore you have lots of medications.  We can start reversing that.  Ideally, when we’re all set and done, maybe a little for her lungs, and I don’t know if we’ll need anything for blood pressure or not.  If we do, maybe the Imdur and that might be it.  It helps to dilate the arteries of her heart a little bit. But other than that, I’d like to see her off of almost everything else.  Now we’ll see how close we can come to that accomplishment.  I don’t know.  Now, certainly, we can help the diabetes, and diabetes underlies a lot of everything else.  Her numb feet will get better over time.  But will take a long time.  Probably several months or a year even.  But that’ll get better too.  A lot of things are going to get better.  She can pick up her energy a little bit.  And then there’s some supplements she’s going to be taking.  You know the diet pretty well.  We’ll give you, see if they have that done yet, and we’ll copy these instructions to pin on your refrigerator or wherever you want.  And, make sure that you do that chart of blood sugars, blood pressure and weight and fax it over.  Make sure that you replace the glucovance.  if you don’t take the glucophage, I don’t care that much, but do not take the two of them together.  That would be a severe problem.

Carmen nodded as Dr. Rosedale told her all this.  Her look of determination said she was going to work to make this happen.

DR. ROSEDALE:  Change the insulin today.  Probably do that today.  She’s already had her shot this morning.  If she starts the diet today, she won’t need a shot tonight.  The changes take place rapidly if you don’t eat sugar.  Obviously if you don’t eat sugar, the sugars go down.  Also, we just got through breakfast.  What would be a typical lunch?

CARMEN:  Chicken, salad.  She’s eating a little because she doesn’t have good appetite since she left the hospital.  So she just eats a piece of chicken and a salad.

DR. ROSEDALE:  And how about dinner?

CARMEN:  Sometimes the same thing she ate for lunch.

DR. ROSEDALE: Those will be fine.  Chicken, chicken salad. Teach her what to eat, and we’ll give a list of food that she can and can’t eat.

CARMEN:  For a snack she eats a yogurt and crackers.

DR. ROSEDALE:  We’re going to change that.  That’s gone.  OK?  No yogurt, no crackers.

CARMEN:  For her tea she uses the sweetener, Nutrasweet.  Can she continue taking that.

DR. ROSEDALE:  I would not use sweeteners.  She’ll crave the sweets more and that’s when she’ll want the yogurt, that’s when she’ll want to fruit.  I would just stay away from sweets for now, and then it’s easier.  If you’re not constantly reminded of sweets, you won’t miss it.

MAGDALENA as this was translated, again gave that almost-panicked laugh of disbelief, her voice registering, “You’re kidding?!?”

DR. ROSEDALE:  It’s very important that she doesn’t cheat.  Especially not for the first three weeks.  After three weeks it becomes a lot easier to follow the diet if you’ve been strict from the very start.

CARMEN translated.

DR. ROSEDALE:  Keep some almonds around.  Either dry roasted or raw.

MAGDALENA:  Okay

DR. ROSEDALE:  Does she like guacamole?

CARMEN—Yes she does.

DR. ROSEDALE:  Some people cut the la tortilla into smaller segments and then bake it in the oven to make kind of crackers to dip into the guacamole.

Carmen and Magdalena talked about this, and Magdalena seemed to like the idea.

DR. ROSEDALE:  OK.  We do have a ferritin of 25.  Good.  Now we will write down a list of supplements.  One, I will be sorry to inform you will be expensive and long term.  We’ll see what we can do short term, but it is something she’ll need to stay on it indefinitely. That’ll be Co-Q10.  The raw price at the factory that makes it in Japan has gone way up. They are starting to charge a lot more because they can.  There are only two factories that make it.  Unfortunately.  But that doesn’t change the fact that she needs it.  Whereas you and I take one, she’s going to take 6 a day.  And if it weren’t so expensive, I’d have her do twice that.  It’s vital to her health right now.  Two at breakfast, two at lunch and two at dinner.  She’ll take Diabest.  Arginine.

CARMEN:  TRANSLATES

DR. ROSEDALE:  Okay.  This is what she will need, for right now, and that’s actually keeping it as simple as I can.  And on here, right here is what she should be taking, and this will say something else on the bottle, so I’ll write that here.  Thiacid, I think.  Take Co-Q10 2 at breakfast, 2 lunch, 2 dinner.  Diabest.  Arginine.  That means empty stomach.  Thiacide, Lipoic acid.  Acetl Carnitine.  Potassium.  Ascorbic Palmitate, a form of Vitamin C.  Vitamin E.  For 6 weeks.  Okay?

DR. ROSEDALE:  Now, the Lasix, is Magdalena also taking Potassium?

CARMEN:  Yes

DR. ROSEDALE:  Even so, I’m putting her on other potassium with magnesium also.  And that’s not a mistake.  In addition to the potassium she’s taking for the Lasix, she’ll take this other for 6 weeks, and I am hopeful that in a couple of weeks, we’re going to start getting her off that Lasix, or at least greatly lowering the dose.  Okay?  So, we need to, let’s find out if she’s going to have another chest x-ray and see how clear that looks.  If there’s no fluid in her lungs, we can start weaning her off the Lasix.  I don’t need to see the actual x-ray.  I’ll take the radiologist’s word for it.  Thanks.

DR. ROSEDALE:  Copy those  . . .

This ends Magdalena’s first appointment with Dr. Ron Rosedale, two weeks after she left the Intensive Care Unit congestive heart failure that was getting worse each time she ended up being hospitalized.

Carmen and Magdalena talked with Dr. Rosedale about how to connect up with her regular doctor.  Magdalena said that she would talk about all this at her next regular appointment, depending on if she could get a car ride to it, since she doesn’t have a car.  Checking blood pressure, we would later find out, was also somewhat complicated, since the nearest blood pressure checking place was at an Albertson’s supermarket several blocks from where she lived, and she didn’t have a  car, and she had hardly the energy to walk from her bedroom to the bathroom.   And, there was the new diet.  Many, many things to see about and do.  But at least, there was a new possibility.  Magdalena left, talking about how if she got better, she’d be able to teach other people about how to be healthy as well.  The key would be HER getting healthy first.

This concludes this special program about Magdalena—part 1.  There are other episodes to follow.  Always remember to consult with your physician before changing your medications, and also tell your doctor about dietary and supplement changes you make.

The post Medicine for Magdalena – Checkup with Ron Rosedale appeared first on Ron Rosedale, M.D..

This is an interview with Shelley Schlender, KGNU radio, Boulder, Colorado. Thank you Shelley for the article, graphics and the interview below. You can learn more about Shelley and her passion for exposing the truth in health at her website, www.meandmydiabetes.com

Ron Rosedale says to keep your cells sensitive to leptin, insulin and other hormones for better health.

He gave this talk at the American Society of Bariatric Physicians (ASBP) meeting Oct 31, 2006.  They’re medical experts who work to reduce obesity.  As part of the 2006 presentations, the ASBP included a special segment that featured low-carb diets, researchers and scientists who are connected to the  Nutrition and Metabolism Society.  Special thanks to Instatapes for recording this presentation.

Listen to or download Ron Rosedale speech (60 minutes)

Listen to or download Ron Rosedale speech (60 minutes)

SPEAKER’S INTRODUCTION:  Dr. Ronald Rosedale is an internationally renowned expert on the biology of aging. He was at the International Conference on Aging Medicine at Rio de Janiero, and the first European Conference on Longevity Medicine and many more. He is the author of The Rosedale Diet: Insulin and its metabolic effects. He will be speaking to us this morning on the detrimental effects of too much protein. Please welcome Dr. Ronald Rosedale.

We might give a different view on protein intake and nutrition and actually health in general. First, you hear a lot about paleolithic nutrition, the idea being that ancient man can tell us how to be healthy. That we need to go back to our ancient roots and eat like they did, and then we’ll be healthy. But you have to go back even further and understand what Nature is after. And there are two prime prerogatives of all life, since the beginning of life. And they both involve making more life.

How do you make more life? Reproduce. What do you do to reproduce? You have to eat. You have to eat and reproduce. It’s all life does, and we evolved with those dictums.

We can’t use Paleolithic Man. We evolved with a diet to not allow a man to live a long healthy life.

Nature does not care about us living a long healthy life, or any life, for that matter.  Nature wants “Life” to live.

It’s like, you don’t care if there’s a little cell on your hand that dies, as long as the whole remains. Nature doesn’t care if you or I dies, or if all mankind dies. Nature wants life to live. The diet that ancient man grew up with was to maximize reproductive sense. Not necessarily the life of each individual.

We do know, there is a powerful connection between energy stores, reproduction and longevity. Certainly, we know that it takes a lot of energy to make babies. And if there was not a lot of energy around, Nature would put off reproduction, and it is that trick that we want to use. It puts off reproduction by allowing the organism to live longer. It appears that all organisms have genetic mechanisms to delay aging, to delay dying so that the organism can reproduce at a future more opportune time. And generally this is genetically controlled, and it’s controlled by the availability of nutrients, whether it’s good to reproduce now or put off reproduction into the future.

Because of this, we know now that there are nutrient sensors that tell the body and tell the genetics how much nutrition is available right now, and it is a liaison between nutrient stores and genetic expression that determines whether the body will move toward reproduction or maintenance and repair. This is on an organism level and on a cellular level. On a cellular level, increasing reproduction might not be such a good thing because when you push growth and reproduction too far, you stimulate cancer.

We’ll talk a little about diabetes because it’s the quintessential disease of nutrient stores. Ask anyone what is diabetes, and they’ll say it’s a disease of blood sugar. Diabetes is not a disease of blood sugar. If you get nothing else out of this talk today, realize that diabetes is not a disease of blood sugar. It is a disease of insulin signaling. What we have hear is a failure to communicate. Insulin tells the body a very vital message. Not how much sugar to have. The real purpose of insulin has to do with being a switch, a nutrient sensor, that is one of the pathways that will dictate whether a cell reproduces or whether it lives.

Caloric restriction, metabolism, IGF and insulin are integrated into this longevity pathway, and this pathway appears to be conserved through all of evolution.

It’s found in yeast and flies and worms. Everything down to yeast. Not bacteria. Bacteria has a different definition of life. In fact, it never dies. It just keeps reproducing. So you can’t throw bacteria in there. But yeast, flies, worms, rodents, primates, and certainly humans, it appears. Since the discovery of insulin, most studies have focused on the role of insulin in the metabolism of glucose, however a failure of insulin signaling is certainly associated with a shorter lifespan. What we’re seeing over the last decade is a central role of insulin signaling in lifespan. The discoveries indicate that aging is a programmed and well controlled process regulated by the same pathways that affect growth, metabolism and lifespan. It is an evolutionarily conserved process, so you can extrapolate, it appears, to humans, since it appears ubiquitous.

Calorie restriction also appears to ubiquitously extend lifespan in laboratory animals, and so far, it appears to extend lifespan in humans, too. It extends lifespan in yeast, flies, fish, worms, mice, rats, monkeys, and perhaps humans. Some common, consistent effects of caloric restriction include lower fat mass, particularly visceral fat–remember that–lower circulating insulin and IGF concentrations, increased insulin sensitivity, lower body temperature. Flowers live longer if you keep them cooler. It appears to be a universal truth. Lower fat free mass. Lower sedentary energy expenditure. Decreased levels of thyroid hormone and decreased oxidative stress. Reduced metabolism and therefore free radical production is another possible explanation. And there Other effects such as lower body temperature, decreased insulin, decreased IGF, decreased sympathetic nervous system activity, altered gene expression have all been suggested as mechanisms that explain the extended lifespan associated with calorie restriction.

There’s also a connection between calorie restriction and chromatin structure. Genes are wrapped around chromatin, and their expression is often dictated by how well they’re wrapped. Basically, you uncover the genes to read them. Genetic expression is really the importance of genetics. It’s not the genes you have. Every cell in your body other than your sperm and eggs have the same genes. What makes a heart cell a heart cell and a kidney cell a kidney cell depends on which genes are read. That depends on chromatin structure and other molecular mechanisms such as methylation and acetylation and things like that.

This is talking about an important part of genetic expression dictated by a gene called SIR-2 which in the humans, the homologue is SIRT-1, and research at MIT and Harvard has looked and determined this pathway is NAD and NAHD dependent, meaning energy stores, and when SIRT-1 in humans and SIRT 2 in so called lower forms of animals goes up, animals tend to live longer, and it appears it does this by turning off detrimental pathways that can accelerate aging and turns on maintenance and repair pathways that extend lifespan, and at least partially, you can up-regulate SIRT expression and therefore, by suggestion, lifespan, by amino acid restriction.

Interestingly also, SIRT-1 protein binds to and represses genes controlled by the fat regulator PPR. Where have you heard that before? That’s Avandia, Actos. The first one was Rezulun but they had to take it off the market because it killed too many people. They still kept the other drugs on the market. These are supposedly insulin sensitizers. They are NOT insulin sensitizers. That’s just marketing hype. These PPR agonist drugs such as Actos and Avandia actually work by increasing fat mass. They multiply fat cells. They give you a bigger dumping ground to put sugar. So yes, it lowers blood sugar. Only because you turn it into fat. But is that a healthy thing to do?

Okay? You have to ask the right questions.

Is reducing kidney disease a healthy thing to do?

If I could snap my fingers and create a pill that cuts heart disease in half. Is that a healthy thing to do? Well not necessarily if it increases cancer. You have to look at mortality rate. What is the end result?

If you dig deeper into the answers, you always end up face to face with the biology of aging. Because it will give you the answers. If you slow the again process, and that doesn’t mean getting older, longer. that means staying younger longer, it’s probably a good thing to do, and then you’re going to repress the symptoms of aging. You’re going to repress diabetes and obesity and osteoporosis and cancer and arthritis. The diseases and symptoms we associated with aging. The only way we can really make a dent in that is to treat the underlying disease. And that is aging and that is a disease. In laboratory animals we can manipulate the process of aging to step back in time to a time when it no longer had diabetes. So it isn’t just to prevent disease. You treat disease this way.

Insulin/IGF represents a family of growth factors that regulate metabolism, growth, cell differentiation and survival. It links insulin action to the map-kinase pathway of cell division. Here’s a very important gene, one of the first genes that was discovered that can extend lifespan is DAF-2 discovered by Cynthia Kenyon at University of California in San Francisco that amazed everyone. They didn’t know at the time what it did, but they did know that DAF-2 mutants can live four times longer. They found a moderate decrease in insulin IGF-1 signaling has been shown to extend lifespan in mice. It’s associated with lower levels of insulin, and it’s similar to the improved insulin sensitivity that you see in caloric restriction.

In mouse models, decreased food intake can extend lifespan, and there’s a special role for insulin signaling in fat in the longevity process. Reduced fat tends to lower insulin and protects you from diabetes. They found, by testing various tissues that if you just reduce fat levels, and you enhance insulin sensitivity while reducing fat levels in fat tissue, you extend lifespan. So it doesn’t have to be all over. Fat tissue is a particularly important part of this process. Just a moderate decrease in insulin and IGF signaling has been shown to extend lifespan in mice. This was done by a friend of mine, Andre Bartke and he’s done a lot of studies in mice and shows that if you down regulate insulin and IGF signaling, and you increase insulin sensitivity, you can increase lifespan in mice. A couple of years ago he won the Methusula award. It’s given to the researcher who can extend the life of a mouse the longest. I think he’s extended lifespan about six years now in mice. The normal lifespan is two years. What they’re doing in these laboratories is amazing. They’re tripling lifespan. They’re doing it by the same pathways of genetics that we have in humans. They’re going into the genetics of it, which we can’t quite do in humans yet. The genetics are altered by nutritional stores and nutrient sensors. We do have a way to dig into these genes. Maybe not with pliers yet, but by what we put in our mouths.

Centenarians, people who live to be 100 or older, have lower insulin and IGF levels. One of the nice ways to study aging in humans is on centenarians. Centenarians, they’ve been showing now for quite a few years that there are differences among centenarians. They eat different diets, they smoke and have different personalities. There are not a lot of similarities between centenarians. But they universally have lower IGF, lower insulin, lower temperature and lower thyroid levels. Those go together.

Conclusions: Strong similarities exist between insulin and IGF systems. Maybe linked to oxidative stress, lifespan. It suggests that the Insulin-IGF system arose early in evolution and it is an essential component of anti-aging systems which is conserved from yeast to humans.

Now let’s look at a slightly different view on how insulin works. The typical thinking is that the most important organs that will determine whether a person will become diabetic is how insulin sensitive the muscles, fat and liver are. But that doesn’t seem to be the case. In mice, they turned on and off genes of insulin receptors in different tissues of the body. They determined that the two organs most important by far in determining whether an organism will be diabetic or not are whether it has insulin sensitivity in the brain and liver. Two big keys in determining health and diabetes. These researchers say that we’ve overestimated how important insulin is in muscle and fat and underestimated its importance in other tissues.

This is where we get to leptin.

How many people have heard of leptin? Unfortunately there hasn’t been as much publicity on leptin as there probably should because there aren’t yet any drugs to control it. But leptin is very critical to your health. We’re going to spend time talking about it and its connection to the diseases of aging and actually aging itself. It has a key role in regulating glucose. We get to the brain-liver circuit, which regulates glucose. Brain will tell the liver how much sugar to make. About half the sugar you have floating around in your body on a day to day period depends on how much your liver manufactures. The other half is how much sugar you put in your mouth. I agree with Mike and Mary Dan Eades and many other people about the importance of not putting a bunch of sugar in your mouth. If you want to keep your insulin and sugar low, it doesn’t take an Einstein to figure out, just don’t eat it. You want to keep low the amount of sugar you put in your mouth. That means all the foods that turn into sugar, even rice, potatoes, cereal, pasta, bread. Those are just other names for sugar. Bread is just a slice of sugar, potatoes are just a lump of sugar. Within minutes after swallowing it you just digest these foods into sugar. Fastest way to up-regulate IGF and insulin and sugar and accelerate aging and all the diseases associated with aging is by eating sugar. We’re not going to go there. The mountains of evidence that show that a high carbohydrate diet is bad could fill this room. We’re going to assume we’re on common ground, that eating sugar is bad for you. One of the reasons is because of the up-regulation of insulin and IGF which accelerates aging. One of the ways you up-regulate sugar is that your brain takes signals and tells your liver to manufacture a bunch of sugar. That’s why diabetics can wake up and find their sugars are higher than when they went to bed. They haven’t eaten for twelve hours and their sugars are high, sometimes higher than when they went to bed. It’s because the liver is pumping out glucose. The major control of the liver is the brain. What controls the brain? The hypothalamus. There is cross talk between the brain and liver that couples central nutrient sensing to peripheral nutrient production, ie, glucose. Disruption may lead to hyperglycemia, and that crosstalk between the brain and liver, and the central nutrient pathway involves leptin, your fat. Leptin modulates the meal regulated food intake. It leads to Increased vagal outflow to the liver which produces more sugar. Your fat speaks to the brain via leptin, and is supposed to tell it how much sugar to produce.

We go back to the beginning.

What we have here is a failure to communicate. That’s how you get sick.

We’re ten trillion cells. They have to communicate with one a other. We think of ourselves as a single individual. Well, we’re not. We’re more like a beehive or an ant colony. There has to be constant and really harmonious signals hitting each and every cell, all the time, and when the communication goes awry, you get sick. That’s the difference between life and death. If I died right now, I’d have the same parts. But they wouldn’t be speaking to each other properly.

Leptin modulates glucose by acting as an insulin-sensitizing factor in most insulin-target tissues. Leptin can modulate, in an inhibitory manner, insulin sensitivity, Directly as an autocrine signal and indirectly through neuroendocrine pathways. These pathways may be relevant to conditions caused by hyperleptinemia, such as in aging. As we get older, and as indicated in accelerated aging, and in people who are older chronologically, they have higher levels of leptin, due to leptin resistance. Almost all fat people have high levels of leptin. Fat is associated with diseases of aging. Leptin is a pro-aging hormone. You want to keep it down. Not up.

Are people here familiar, cause I’m skipping over and assuming people are familiar with what leptin usually does.

Here’s a very brief review. Leptin was discovered about ten years ago. Produced by fat. It’s supposed to tell your hypothalamus how much fat you’ve got and whether to produce more fat. And whether you should keep eating to produce more fat or get rid of some excess. In our evolutionary history, it was good to store some fat. All of our ancestors encountered a famine. You needed to have a good energy source. Fat’s a good, efficient energy source, but it wasn’t good to be too fat, because if you were too fat, you were going to end up as a meal for another organism. Because if you are running from a lion in a group of people, which one is it going to catch? If you got too fat, the lion catches you, because you can’t run up a tree. And those genes would have been eliminated from the gene pool. Leptin tells the brain how much fat there is, and whether you should get more fat or you shouldn’t..

Which means, leptin controls whether or not you’re hungry.

It, leptin, knows people are only going to do what they feel like doing. The only way to get people to lose weight is, which means to lose fat, is to get people to not eat too much. That means they can’t be hungry. Trying to not eat in the face of hunger is an impoosibility, it’s bound to fail. That’s why you see this yo yo dieting. If you’re hungry, ultimately, you’re going to eat. It’s like holding onto a cliff. You look down two miles, and you know if you let go, you’re going to die. Gravity is unrelenting. So is hunger.

Therefore, there are signals to the brain that will tell you how hungry you are. These are the same things that will control, also fat storage. The same master signal that controls hunger also controls your ability to store and burn fat. It also controls how much sugar is available. It also controls through the nutrient sensing pathways, the rate of aging, and therefore the diseases associated with aging.

I can’t stress how important that is, because no drugs control it. You can control it by what you eat. Very important, because you dig right into the same genes that are regulating all these aging process in all these laboratory animals.

If you inject leptin into the brain, right into the hypothalamus, you increase glucose uptake. All those people who are hyper-leptinemic, they have high levels of leptin because their brains can’t listen to leptin. If your hypothalamus can’t hear the leptin signal. If you’re a fat slob, and the fat signal’s trying to yell, quit eating, and the brain can’t hear the signal, it’s getting a whisper, and it’s not hearing the signal to stop being hungry. It’s hearing that you’re too skinny and there’s a famine and you need to eat more fat, and so that’s what you’ll do. There’s a disconnect. A failure to communicate. So you make more fat, you make more leptin, until finally the volume goes high enough that your hypothalamus can hear it, but in the meantime, you’ve increased your set point for how much leptin it takes, and how much fat you have,df before your hypothalamus can hear the signal. You’ve got much more fat than you should have had, if your thalamus had better hearing. You have to restore that hearing.

It appears that with insulin resistance, that’s because your cells can’t listen to insulin, so your pancreas produces more insulin so your pancreas can yell at your cells. Because speaking normally wasn’t getting the message through, so your pancreas has to yell. That’s not a good thing because you raise insulin and accelerate aging.

Same thing appears to happen with leptin. Hypothalamus can’t listen to leptin. You have to yell at it. Well, Increasing leptin so it can be heard has detrimental effects. One of the things is increased glucose.

Leptin prevents triglyceride accumulation, provided it can be heard. Well, fat regulates insulin sensitivity. Leptin also regulates glucose homeostasis independent of energy balance. Leptin has a direct effect in promoting glycemic control. It acts directly on insulin production by the pancreatic beta cells, apparently through signals sent through the vagus nerve. Leptin goes up, you make more sugar.

Just remember, your fat apparently is in charge of your brain.

We kind of thing of the brain as being in control. Fat influences your brain. It’s not just an ugly energy storage tissue you’ve got to get rid of. With the discovery about ten years ago that fat is an endocrine organ that produces hormones that regulate lots of important processes in the body, we now know that your brain listens to fat. When I say we’re ten trillion cells that need to listen to communication signals, it’s kind of like the military. You’ve got generals and colonels and lieutenants and captains. It appears from what we know thus far, that leptin is a four-star general. I put insulin as a three star general. Reproductive hormones and insulin listen to leptin. Thyroid listens to leptin. And ovarian hormones. They listen to instructions from above. Leptin appears to integrate everything, including aging. Your lifespan will be determined by the communication of hormones, primarily insulin and leptin.

Hypothalamic arcuate nucleus . . . Leptin signaling in the arcuate nucleus is an affect on glucose. The restoration of leptin signaling remarkably improves the homeostasis of the mouse. Eight weeks after treatment blood glucose levels fell.

Deficits of leptin activity in certain regions of the central nervous system might underlie type 2 diabetes. We think of diabetes being a disease of blood sugar. No. Insulin signaling? That’s what I thought. Now, It appears that leptin might actually supercede insulin in causing or treating diabetes.

Here’s a study that raised eyebrows. After you’re born, everybody thought your brain had fixed neuron connections and they showed that leptin actually changes nerve endings in the brain to do its bidding. If it wants to make you hungry, it doesn’t just do it by neurotransmitters. The “fat brain” actually changes the anatomy of the brain, and leptin is a crucial regulator, including synaptic plasticity and axon guidance within the hypothalamus. Links between nutrition and adipocyte driven instructions from leptin . . . leptin makes you hungry, it actually changes the anatomy of the brain. It’s talking about the fat brain accesses a new dimension in the journal science. Axon guidance within the hypothalamus.

Very important clinical implications. Leptin controls not only how fat your are, but where you’re fat. For a long time we’ve heard about the apple shape versus the pear shape. The apple shape is associated with much more detrimental physiological processes. The pear shape might look ugly, but it’s not particularly unhealthy. It’s visceral fat versus subcutaneous fat. Visceral fat is a totally different organ than subcutaneous fat. It produces different hormones. Visceral fat is really bad for you. If you’ve got visceral fat, it’s because of leptin resistance.

Islets within the pancreas can get fat. We think of ourselves as a single individual. We have to think that we’re 10 trillion cells, and cells can get too fat. Just as getting fat is not good for us, being fat is not good for cells. Beta cells in the pancreas can get fat, and when they do, they can’t produce insulin properly. That’s another way that leptin controls glucose and determines whether you’re a diabetic or not. Whether the cells are getting fat or not is being proposed to be caused by leptin. We propose the signal is leptin and its function is to create for adipocytes a monopoly on fat storage, to maintain a constancy of intracellular triglycerides and adipocytes. So when things are working properly, you store fat in fat cells. When the signals or getting messed up, you start storing fat in other places,and it’s when you start storing fats in other places you get really unhealthy.

Bears get really fat prior to hibernating. But bears don’t get heart disease, because their fat is stored almost all in subcutaneous fat, not in visceral tissues. So being fat doesn’t make you sick. Being fat in the viscera makes you sick. Being fat in places other than the subcutaneous tissue makes you sick. And that’s determined by leptin.

The other tissue that’s very importantly regulated by leptin is the liver, via the vagal nerve from the hypothalamus, but it also determines how fat the liver is, and a few studies here talk about non-alcoholic fatty liver disease. Fatty liver is grossly under-diagnosed. It affects at least two thirds of obese people, perhaps more, and also some people who are not obese. It almost totally parallels the incidence of the so-called metabolic syndrome, and many people believe that metabolic syndrome is actually caused by fatty liver. Which is determined by leptin.

Fatty liver disease is strongly associated with diabetes. High cholesterol. Hypertension. The process starts when there’s so much dietary fat in the blood it can no longer be stored in normal places such as fat cells.

Leptin treatment decreased visceral fat specifically, supporting the role of leptin in determining fat distribution. That’s a very important role of leptin. Determining not only whether you’re fat, but where you’re fat. Perhaps more important.

We’re talking about cardiovascular disease now. There’s a link between insulin action and cardiovascular disease. And Insulin resistance in the development of diabetes can be reduced by preventing the age-dependant accumulation of visceral fat.

When you do liposuction, it doesn’t really help health by taking out subcutaneous fat. It didn’t really help diabetics. But if they took out the omentum in mice, they could totally reverse diabetes in mice. So they’re starting to do this in humans, at Vanderbilt. Leptin activity increases aromatase activity, in visceral fat (not subcutaneous), which converts testosterone and estrogen, which is why you see all these overweight men with breasts. That’s because of an increase in aromatase, and that’s not good because it’s also a powerful increaser of cancer, particularly prostate cancer.

Leptin is linked to autoimmune diseases.

Some of this has to do with how it promotes hypoandrogenicity. Leptin is also a powerful pro-inflammatory agent. You’ve heard of the link between chronic inflammation and cardiovascular disease. Leptin is itself an inflammatory cytokine. But it also dictates the production of interleukins and TNF alfa, Which are pro-inflammatory agents linked to heart disease and diabetes.

Leptin is a novel independent risk factor for coronary heart disease. Leptin enhances the calcification of vascular cells. This was new to people. Leptin also helps control osteoporosis. It helps control where you put calcium. We think of osteoporosis, and women are being given the dictum to take a bunch of calcium. As if osteroporosis is caused by a lack of calcium. That is ridiculous. That’s like saying, I’m going to put a bunch of bricks on an empty lot, and stand back and watch a house be built. I could take a cup calcium carbonate or coral calcium, any type of calcium you want, and dissolve it in a bucket of your blood and stand back and watch for the better part of eternity and I would never see a bone form. And you won’t see a bone form. It won’t happen. You have to have the right signals to make bone. And there’s a powerful correlation between ostereoporosis and calcium buildup and plaque in arteries. You’ve got the calcium but you’re putting it in the wrong place. Just as you can end up with fat in the wrong place, with calcium, whether it’s put in the right place or the wrong place, lot of it is apparantly controlled by leptin. Leptin kind of dictates where you put calcium.

How can one hormone make a difference in all these different things? It has to do with leptin’s ability to control the rate of aging. Aging, or the lack of it, is determined by proper communication. When that communication goes awry, all kinds of things go wrong.

They have shown leptin inhibits bone formation.

Leptin controls osteoblastic activity in bones and vascular cells. High leptin inhibits bone formation via the hypothalmus. And the arterial wall may be an inportant target for leptin action. All the treatment for osteoporosis has to do with osteoclastic activity. Osteoclasts break down bone. They want to prevent the breakdown of bone. The drug treatments don’t make new bones.

But bone strength is determined by the protein content, not the calcium content of bone. It’s the flexibility of bone, which has nothing to do with bone density. It’s the protein content of bones. You want to have protein, you need protein, but you want it in the right places, and you want it in the right amount. High leptin levels are a potent inhibitor of bone formation.

Life is not in the parts. We’re all made of the same stuff. it’s what you, or more accurately, your hormones, do with the parts, that will will determine whether you’re healthy or not. That’s really the way to think.

By changing leptin sensitivity, the Hypothalamic set point can be reversed. In regards to leptin levels, there’s a Possible role of protein.

You know, leptin controls sweetness. I’m just recognizing that this is my next talk.

It doesn’t matter. The problem was, they’re both so linked. You got off easy. I really blast protein in the next one!

I just talked about leptin regulating inflammatory responses. So this is a talk about hormones and aging. The next talk is going to go into problems with proteins and aging. And we’ll go a bit deeply, through a pathway called the M-TOR pathway.

How many people have heard of M-TOR? A couple of people. Not too many. It’s extremely important. It’s another nutrient sensing pathway. You have insulin that senses sugar stores, and leptin that senses fat stores. M-TOR senses the amount of amino acids available and also regulates aging similar to insulin but using amino acids as the key to energy stores. The two major sources of nutrition that determine whether an organism will reproduce or live longer, you have to have fuel available and you have to have parts available. The fuel early on was glucose and not fat. These signals arose in evolution was very long ago. It’s a very ancient mechanism when there wasn’t oxygen in the atmosphere. Life had to flourish before there was oxygen in the atmosphere. Plants had to flourish before they put out oxygen, so these pathways arose with glucose as the fuel availability, and amino acids for the parts availability, and those are the two things you need to make more cells.

So the next talk, we’re going to talk about the MTOR pathway that dictates the amino acid availability and how it plays into the aging process.

Getting back to hormones — Reduced leptin concentrations lead to reduced temperature. You live longer. Temperature kills. You heat something up and it disrupts molecules. It denatures proteins. If you’re going to live longer, one of the ways is by toning down the temperature. In dietary restriction, there may be diverse mechanisms, often known as calorie restriction.

How many people have heard of caloric restriction as a way to enhance lifespan. The dictum has been that it’s strictly a reduction of calories. It doesn’t matter where they come from. As long as you restrict them, you’ll live longer. What they’re showing in more recent studies is that is not true. There are specific nutrients that you can restrict that mediate the effects of dietary restriction. In this particular study by Linda Partridge in London, who’s done a lot of work with aging, the reduction of either dietary yeast or sugar can reduce mortality and extend lifespan by an amount that’s unrelated to the calorie content of the food, with yeast having a much greater effect per calorie than sugar. Get that. Yeast having a much greater effect per calorie than does sugar. Yeast was the form of protein they were feeding these animals. So when you reduce protein, you live longer.

Here, they’re showing that a fall in leptin is one of things that mediates dietary restriction. If leptin doesn’t fall, you’re not going to live longer. In normal men, a fall in leptin in fasting may be both a necessary and sufficient physiological adaptation of these axes, which has to do with hypthalaumus, pituitary, gonads, IGF, thyroid. You have to drop leptin, or dietary restriction is not going to help.

Dietary restriction explained from an evolutionary viewpoint is an adaptive response by the neuroendocrine and metabolic response systems to maximize survival during times of food shortage. Adipose tissue is recognized as an endocrine organ, and leptin secreted by the adipocytes seems to be an especially important factor for the adaptive response to fasting and neuroendocrine response under caloric restriction.

The one known way to extend lifespan of every species studied since 1933 has been to reduce calories. Since that time, the emphasis has been to figure out why. Ten years ago, they discovered a gene that can control aging, Age-1 gene, discoered by Tom Johnson at the university of Colorado, and Cynthia Kenyon with DAF-2 expanded on this. These all link to nutrient sensors and it all links into a pathway that governs maintenance and repair or growth. They’re all linked to nutrient receptors, and it appears that in mammals, leptin plays a key role, and those animals that use fat as a prime energy store, leptin plays a key role in the aging process.

Prior to leptin, and it appears that they’re cousins, it was Insulin and IGF. Insulin and IGF in ancient organisms, insulin and Insulin like Growth factor were the same. Over time they evolved to have separate duties. Now insulin is more metabolic, and IGF is more anabolic.

Leptin has been proposed as a potential candidate for the adaptive response to Caloric restriction.

This was a longer talk than the other one.

So we’ll have to hurry.

A hypothesis for interpreting the extension of life from caloric restriction posits that normal food intake is geared toward optimizing the internal milieu for reproduction. That’s what Nature is after. Not after health. Nature doesn’t care whether you’re healthy or not. We have to use this trick, however. Nature wants us to live long if it thinks we can reproduce better in the future.

In our ancient life, that was dictated by fuel availability. We can use the science to regulate the nutrient sensing pathways to improve our lifespan and our health.

Here it’s showing that leptin is very much involved in reproduction.

Skinny women, women marathon runners stop ovulating. Inject them with leptin and they’ll start ovuating again. Reproduction and eating are the two main endeavors or all life, and they’re both controlled by leptin.

DAF-16, I don’t have the time. Here, it’s showing that Daf-16 is one of the genetic components that mediates caloric restriction. They’re finding that just activity in the intestines — In C-elegans, the intestines is where it stores fat. DAF-16 in fat, Determines lifespan in the worm.

Signals from fat regulate genetic expression.

Here again, talking about the importance of fat tissue in longevity. Leptin controls whether you’re satiated or not. It also has to do with life extension. With PPAR alpha. Not PPAR gamma. PPAR gamma is what people are taking drugs for. PPAR gamma accelerates life and reduces lifespon. PPR Alpha enhances lifespan. Exactly the opposite. Leptin modulates this through the PPR system because PPR gamma influences a lot of what happens in fat.

Failure of leptin suggests leptin plays a major role in dietary restriction. There’s a link between leptin concentration, with higher levels linked to telemere shortening, which is another theory for aging, that shorter telomeres reduces lifespan, and telomere shortening is controlled by leptin. Waist-to-hip ratio correlates with leptin levels. Centenarians have lower waist to hip ratio. Longer lifespan was predicted by lower levels of leptin. Here, they’re showing that a bunch of amino acids stimulated leptin production.

One of the ways that leptin is elevated that causes hyperleptinemia is caused by high levels of amino acids.

Whereas a high fat diet is associated with low leptin.

In membrane composition, insulin and leptin regulate the types of fat found in membranes.

Talking about IGF again and membranes, that omega three fatty acids improve leptin sensitivity.

This is a study that hasn’t been published yet, that is a collaboration between myself and Eric Westman and John Konhilas. What we’re showing is that a high fat, adequate protein, low carbohydrate diet with nutritional supplements in an outpatient setting, resulted correlates of aging. There were reductions in body weight, triglycerides, insulin, glucose, leptin, free T3 The same things you see with caloric restriction. But we were not restricting calories. The reduction in insulin and leptin levels was strongly correlated with reduction in weight, but the reduction in leptin levels was far greater than the initial weight loss. In other words, leptin is not dictated by how fat you are. It’s dictated by what you eat. Sugar increases leptin output, and amino acids increase leptin output.

You don’t have to have any sugar, but you have to have some protein. But you don’t want too much. Too much protein raises leptin and accelerates aging.

Your brain is a servant of your fat, your brain is what fat uses to do its bidding, and your fat’s bidding will determine your lifespan.

Special thanks to Greg and April at Instatapes for helping to track down the audio of this talk, and to Ron for permission to post the audio, transcript and PDF of the citations used in the talk.

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Drug companies are increasingly obliged to publish details of payments to doctors. The United States is leading the charge, but are we getting the full story in Europe? Andrew Jack reports..

When the drug company Cephalon took  13 British doctors to the European pain congress in Lisbon in September 2009, the expenses it provided did not stop with travel, fees, and accommodation—and its presentations were not limited to a balanced scientific explanation of its products at a day time satellite meeting. An internal feedback document circulated to the sales team at the company (now owned by Teva) described one evening’s festivities that it funded for staff and doctors: “Dinner was fantastic . . . we then went to a few bars and to a club till 3am. All the customers were really looked after and spoke positively about Effentora [fentanyl]—let’s make sure they start Rxg [prescribing] now!”

It was a complaint from a former Cephalon sales representative that triggered an inquiry by the Prescription Medicines Code of Practice Authority, the self regulatory arm of the Association of the British Pharmaceutical Industry. That led to a sharp public rebuke for the company, while providing a rare public insight into the tactics and motivations behind corporate links to doctors. Such incidents—and many far more troubling and extensive ones exposed and penalized through lawsuits in the US in recent years—have led to increasingly tough codes of conduct being introduced by drug companies around the world, and to calls by politicians and regulators for far greater “sunshine” to highlight their activities.

Similar pressures are now building in Europe. Since 2008, Denmark has required companies to disclose to the Medicines Agency any payments they make to doctors, and even details of extensive “unpaid involvement” such as unremunerated work on advisory boards.1 There have been calls for a similar approach in the Netherlands, and politicians in France recently drafted legislation that requires companies to release details of payments to doctors, drafted in response to concerns over the marketing tactics of Servier that were exemplified by the scandal around its drug benfluorex.2

“I think sunshine in Europe is both desirable and inevitable,” says Richard Bergstrom, head of the European Federation of Pharmaceutical Industries and Associations, the Brussels based industry trade body that represents companies across the EU. But he stresses the need to take into account the varied approaches and interactions between doctors and companies in different countries.

US LEAD
With widespread direct to consumer television advertising of medicines, free product samples, and extensive support of continuing medical education, the US has led the world in the aggressive marketing of pharmaceuticals. Not coincidentally, it is now also leading the way in the provision of information about such activities. Twelve drug companies have recently begun publishing details on their websites of the payments they make to physicians in the US, declaring payments or expenses incurred for meals, travel, consulting, and research to each of thousands of named doctors. While far from complete and difficult to compare, the records are starting to reveal the extent of the links between the two, and shifting practices as a result.

According to an analysis by the Financial Times, conducted with the US based consultancy PharmaShine, in the first quarter of this year alone payments amounted to more than $110m (£71m; €84m).3 Last year, they totaled $437m, paid to 262 000 doctors across the country. Some doctors received more than $100 000 each in 2010, and one got $234 000, most of which was speaker fees from Cephalon.

The companies often claim they are championing an ethical stance in releasing the data, and all stress that such links with the medical profession are essential for the development and uptake of innovative drugs to improve patient outcomes. In practice, most have been forced to provide the information because of legal settlements, often “corporate integrity agreements” imposed by the Department of Justice. Some of the drug companies are yet to provide the data in the US, including Shire, Sanofi, and Bayer. They point to the enormous complexity and cost of compiling all the information from a wide range of internal computer systems and the lack of any legal obligation to do so. Yet companies will soon have no choice. As part of President Barack Obama’s healthcare reforms, putting “sunshine” on physician payments—fueled by public pressure and exposure of past practices—becomes compulsory in 2013.

The new regulations may provide some much needed consistency. Currently, each company has published different types of data in different ways, making the information hard to access or compare. The differences may reflect particular legal requirements in each case reached in negotiations with prosecutors, but they leave the impression that the companies are doing their best to make the information as inaccessible as possible.

Few allow their data to be easily searched, ranked, or extracted for analysis. Each has different thresholds below which they do not provide information. Some publish only ranges of support rather than providing specific figures. Some companies’ figures are inflated by the sums they provide in research funding to prescriber’s academic institutions, while others are limited to personal payments to doctors.

The result has been periodic and labor intensive efforts by external organizations to make comparisons from the data. ProPublica, a US nonprofit journalism organization, has recently updated its analysis of the figures, “Dollars for Docs,” which allows anyone to search by company, state, or doctor.4

The project, and the sunshine data on which it draws, has met with mixed reviews. “Our once proud profession has been totally corrupted by the insurance cartel and PhARMA [the US industry association],” wrote one retired doctor on the ProPublica site. “No longer is the Hippocratic Oath the ethical basis of medical care . . . by [and] large making money has become the ideal.”

Yet others—both doctors and drug companies—defend the financial connections, stressing that the payments to most physicians are modest; that they can legitimately provide information without distorting prescribing practice; and that connections are essential between top disease specialists and companies developing new drugs. Eli Lilly said in a statement: “Lilly is committed to ensuring that our relationships with healthcare providers are conducted in a manner that complies with applicable legal and ethical standards. Our collaboration with healthcare providers is essential to our ability to provide innovative medicines, improve health education, better understand patients’ needs and improve individual patient outcomes.”

BEHAVIOR CHANGE
It is difficult to tell what impact sunshine has had on drug industry practices. Though the data remain incomplete and the timescales are still short, some companies seem to be providing less support than in the past. But the entire sector is also under broader financial pressure to save costs by cutting back on marketing expenses, reducing the number of sales staff they employ in the US and cutting support to prescriber’s. Following recent legal settlements, drug companies have also introduced tougher ethical codes. Travel and entertainment expenses have been pared back and the maximum value of gifts sharply reduced.

GlaxoSmithKline this year removed any direct bonus for its sales staff linked to the volumes of prescriptions by the doctors they target. AstraZeneca has introduced a ban on paying doctors’ travel expenses to international medical conferences.

Allan Coukell, head of the Pew Prescription Project, a US drug safety watchdog, says: “Sunshine has certainly heightened awareness of the concerns. Many individual companies have changed this or that practice. I don’t think we have data yet that really lets us say there are measurable trends.”

But there are already some indications of the impact of the public data. With more information on the totals paid by companies to physicians some have since set—or made public—annual caps. Others have ceased payments to doctors whom ProPublica has highlighted were the object of disciplinary action George Dunston, founder of PharmaShine, which sells its own constantly updated database derived from the disclosures, says his clients include academic and medical institutions that are keen to see whether the figures provided by industry tally with the declarations made directly by their staff.

For now, the pressures for greater disclosure in the UK and much of the rest of Europe have been more limited. The principles to limit conflict are clear, but the evidence of abuse is limited. In its 2009 report Innovating for Health, a working party convened by the Royal College of Physicians concluded that there was mistrust in the relationship between industry and doctors and called for changes, including the elimination of drug company funding of medical education.5

So far, progress has been modest. Article 74 of the General Medical Council’s good medical practice guidelines states: “You must act in your patients’ best interests when making referrals and when providing or arranging treatment or care. You must not ask for or accept any inducement, gift or hospitality which may affect or be seen to affect the way you prescribe for, treat or refer patients. You must not offer such inducements to colleagues.”6 The body says it has no record of any recent action against a doctor for violating this clause.

The UK’s Prescription Medicines Code of Practice Authority, which polices a code of conduct that has been tightened considerably in recent years, does periodically clamp down on abuses, from Cephalon’s conference entertainment to Abbott’s excesses in hiring lap dancers during an evening for prescribers. It relies on tip-offs, which often come from rival drug companies or former employees as well as prescribers. It has limited powers of investigation, largely relying on cooperation and honesty from those it questions.

In Scotland, doctors working for the health service are already required to declare any conflicts of interest with drug companies, although accessing—let alone policing—the information is difficult. A parallel requirement by companies to disclose what they are paying to prescribers would allow government officials, health service administrators, patients, journalists, and prosecutors the chance to compare the two sets of data.

Meanwhile, the external scrutiny of industry support for doctors is stepping up. US investigators are now increasingly looking to pursue cases under the Foreign Corrupt Practices Act that take place beyond its own shores, including a $70m settlement against Johnson & Johnson reached earlier this year. The UK’s Corruption Act also scrutinies bribery within and beyond the UK.

Vivienne Nathanson, head of science and ethics at the British Medical Association, points to her organization endorsement of the industry code and stresses the importance of “making sure there is as much declaration of interest as you can possibly make.” She adds that she would “not object to more statutory declarations, but given there’s already so much bureaucracy, so much already declared, people want to make sure it is useful and does not just cloud the issue.”

Companies seem resigned to greater transparency ahead, while also cautioning about the costs of disclosure. David Brennan, head of AstraZeneca, which has released data for the US (showing payments of $32m last year) but not so far for Europe, says: “We’re not afraid to be transparent. The difficulty is our ability as a company to systematically capture that data across multiple physicians and markets.” Up till now, transparency has normally been a result of legal actions rather than voluntarily introduced by companies or doctors. Sunshine alone cannot in any case guarantee honesty. But in the current climate of suspicion, pressure for greater disclosure seems likely to grow.

NOTES
Cite this as: BMJ 2011;343:d6459
Previous Section Next Section

FOOTNOTES
         •      Competing interests: The author has completed the ICJME unified disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares no support from any organization for the submitted work; no financial relationships with any organization that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
         •      Provenance and peer review: Commissioned; not externally peer reviewed.

REFERENCES
         1.      Danish Medicines Agency. Guideline on notification of information about doctors, dentists or pharmacists associated with a pharmaceutical company. 2010.http://laegemiddelstyrelsen.dk/en/ service-menu/legislation/doctors,-dentists-and-proprietary-pharma–alcompany/ companies-notification/guideline-on-notification-ofinformation– al-company#3.

         2.      Arie S. France is set to radically overhaul its drug regulatory system. BMJ2011;343:d4979. [FREE Full text]

         3.      Jack A. Big pharma opts to publish funding of doctors. Financial Times 2011 Aug 29. www.ft.com/cms/s/0/991bdf68- d181-11e0-89c0-00144feab49a.html#axzz1a090uSAL.

         4.      ProPublica. Dollars for docs. 2011. http:// projects.propublica.org/docdollars.

         5.      Royal College of Physicians. Put patients at centre of pharmaceutical innovation. Press release, 4 Feb 2009. www.rcplondon.ac.uk/news-media/press-releases/put-patients-centrepharmaceutical- innovation.

         6.      General Medical Council. Good medical practice: conflicts of interest. www.gmc-uk.org/guidance/good_medical_practice/ probity_conflicts_of_interest.asp. via bmj.com

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Amazing low carb New York Ricotta cheesecake.

Light, super creamy, delicious.. with treats like this the Rosedale lifestyle is a pleasure! 

Ingredients:

• If you prefer a lighter cheese cake, then using Ricotta is perfect.  If you want a heavier NY dense style cheese cake then add more cream cheese and pass on the ricotta.
• 24 ounces cream cheese, softened
• 1 cup extra-fine whole milk ricotta cheese (to refine, process in a food processor for 1 minute)
• 1/2 cup sour cream
• 1 1/2 cups sugar substitute, or a little less depending on your sweetness desires (recommended: xylotol)
• 1/3 cup heavy cream
• 1 tablespoon no sugar added vanilla extract
• 2 tablespoon fresh lemon juice (some people like to add a little zest as well)
• 2 eggs
• 3 egg yolks
• 1 teaspoon of Nutmeg (if you like nutmeg)
• 1/8th teaspoon salt
• Special Equipment: 1 (8-inch) springform cake pan

Crust Ingredients:

 Can also be made without a crust.

• 1/4 cup Finely Chopped pecans
• 1/4 cup Finely Chopped almonds
• 1/4 cup Finely Chopped walnuts
• 3/4 cup almond meal (almond flour)
• 2 Tablespoons butter (melt in microwave)
• Depending on your sweetness desires, some might add a little bit of sugar substitue to the base.

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Creamy, tasty smoothie ~ the perfect breakfast to start your day off with the correct amount of protein and fat. 

Ingredients:

• 1 scoop whey protein powder (or 15 grams of protein) – comes in all kinds of great flavors – check the label that there are no hidden unnecessary ingredients. Also keep in mind your protein requirements for the day, so if the scoop size is for 30 grams of protein then use half a scoop only.
• ½ avacado
• 8 oz. water, or some ice if desired.

• 1-2 Tbs. almond or cashew butter or 10-15 raw nuts.
• 1/3 cup (fresh) frozen berries (strawberries, raspberries, blueberries, etc.) Add the fruit for a treat, we would have this everyday without the fruit.  Pass on this option if you are diabetic.
• For a treat if you can add some whipped cream on top sweetened with xylotol.

Directions:

            Mix in a blender, pour in a nice glass and drink slowly, enjoy.

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Amazing muffins, and the same recipe for the cookie with slight adjustments listed below.  We often take these on trips, easy snack, tasty treat, very filling.  Add a few blueberries on the top and even more delicious!

Ingredients:

• 2 cups almond flour
• 1/2 cup xylotol (or sugar substitute you like) you can reduce this to 1/4 cup as you like.
• 1/2 cup coconut oil or butter (half stick of butter)
• Pinch of salt
• Pinch of baking soda
• 1 teaspoon vanilla extract
• 1 teaspoon almond extract
• 1/4 full fat cream (or little less for more of a cookie, it also works without it)
• Sprinkle of nutmeg and cinnamon to your liking. I use about a teaspoon of each.
• 2 eggs (if you like them a little more dry, cut it back to one, or more muffin like add 3 or 4 eggs)
• Other options..
• We always throw in a half cup of almond chunks for crunch, half cup of coconut unsweetened flakes, spoonful of almond butter.  Another option is to put 3-5 blueberries on the top just before they go in the oven.  Whey protein is something else you can add as well, or 78% sugar free cocoa/chocolate chips.  Once you have the base down, you can get really creative here.

Directions:

1. Preheat the oven at 400.
2. In two separate bowls, mix all the dry stuff together, and then all the wet stuff together.  If you are going to add some of the almond butter, heat it a little so it mixes easier with the wet stuff bowl.  If the mixture is a little runny then use a muffin tray, or you can add a little more almond meal to thicken it up a little.  Melt the coconut oil or butter first so that it all mixes well.
3. Then pour the wet stuff in to the dry stuff, and keep stirring till it is all mixed pretty well.
4. Grease with butter the cookie sheet or muffin tray.  My mixture is always a little runny so a muffin tray works great and I fill each pod about 3/4 full.  If you opt for the thicker mix, then use a table spoon and dollop the mix leaving some space around, on a try you should be able to get about 12 cookies, unless you want to make mini cookies.
5. Cook for about 15 minutes, keep and eye depending on how big your cookies/muffins are, small will need less time, larger a little more.  Light golden brown on top.  This time is with a convection oven.
6. Will make around 12 nice sized muffin/cookies.  I am guessing around 6-7 grams of protein, and with great fats, and really low carbs .

We love Honeyville almond flour in a 5lb bag which is a lot cheaper than what we have found at the store.

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Deviled eggs make a nice starter or perfect at a buffet or party.

You can add your own flavors, curried deviled eggs are especially nice and the curry flavor goes really well with the egg taste. You can add a bit of sweet relish or chopped mushrooms, sun dried tomatoes, the options are endless. You might also want to add a couple of drops of Tabasco sauce or a bit of Dijon mustard to spice your deviled eggs recipe up. If you prefer plain deviled eggs then this is the base recipe below.

Using a piping bag to pipe the egg yolk filling back into the egg whites will give your deviled eggs a more professional finish.

Tip:  The best way to hard-boil your eggs is to simmer them for seventeen minutes, then put them in a bowl of ice water. This shrinks the egg away from the shell. Put them back in simmering water for ten seconds to expand the shell from the egg, then chill them in the fridge. They are easier to peel when they are cold.

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