Insulin And Its Metabolic Effects               Print Version

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By Ron Rosedale, M.D.
Presented at Designs for Health Institute's BoulderFest, August 1999 Seminar
This article is essentially a transcription of a lecture given by Dr. Rosedale at BoulderFest in 1999.

Intracellular magnesium relaxes muscles. What happens when you can't store magnesium because the cell is resistant? You lose magnesium and your blood vessels constrict.

This causes an increase in blood pressure and a reduction in energy since intracellular magnesium is required for all energy producing reactions that take place in the cell.

But most importantly, magnesium is also necessary for the action of insulin and the manufacture of insulin. When you raise your insulin, you lose magnesium, and the cells become even more insulin resistant. Blood vessels constrict and glucose and insulin can't get to the tissues, which makes them more insulin resistant, so the insulin levels go up and you lose more magnesium. This is the vicious cycle that begins even before you were born.

Insulin sensitivity starts to be determined the moment the sperm combines with the egg. If a pregnant woman eats a high-carbohydrate diet, which turns into sugar, animal studies have shown that the fetus will become more insulin resistant.

Worse yet, researchers have used sophisticated measurements and found that if that fetus happens to be a female, the eggs of that fetus are more insulin resistant. Does that mean it is genetic? No, you can be born with something and it doesn't mean that it is genetic. Diabetes is not a genetic disease as such. You can have a genetic predisposition, but it should be an extremely rare disease.

Sodium Retention: Congestive Heart Failure
We mentioned high blood pressure; if your magnesium levels go down or your blood vessels constrict you get high blood pressure. Insulin also causes the retention of sodium, which causes the retention of fluid, which causes high blood pressure and fluid retention: congestive heart failure.

One of the strongest stimulants of the sympathetic nervous system is a high level of insulin. What does all of this do to the heart? Not very good things.

There was a solid study done a couple of years ago that showed that heart attacks are two to three times more likely to happen after a high-carbohydrate meal and are specifically NOT likely after a high-fat meal.

Why is that?

Because the immediate effects of raising your blood sugar from a high-carbohydrate meal is a raise in insulin. This immediately triggers the sympathetic nervous system, which will cause arterial spasm, or constriction of the arteries. If you or anyone is prone to a heart attack, this is when it is going to happen.

Blood Lipids
Insulin mediates blood lipids. For that patient mentioned earlier who had a triglyceride level of 2200, one of the easiest things we can do is lower triglyceride levels. It is so simple. There was just an article in the Journal of the American Medical Association (JAMA) saying that the medical profession doesn't know how to reduce triglycerides dietarily, that drugs still need to be used.

This is so ridiculous because you will find that it is the easiest thing to do. There is an almost direct correlation between triglyceride levels and insulin levels, though in some people more than others.

The gentleman who had a triglyceride level of 2200 while on all the drugs only had an insulin level of 14.7. That is only slightly elevated, but it doesn't take much in some people. All we had to do was get his insulin level down to 8 initially and then it went down to six and that got his triglycerides down to under 200.

The way you control blood lipids is by controlling insulin.
 

LDL cholesterol comes in several fractions, and it is the small, dense LDL that plays the largest role in initiating plaque, as it's the most oxidizable, and it’s the most able to actually fit through the small cracks in the endothelium. And this is the cholesterol that insulin actually raises the most. When I say insulin, I should say insulin resistance. It is insulin resistance that is causing this.

Cells become insulin resistant because they are trying to protect themselves from the toxic effects of high insulin. They down regulate their receptor activity and number of receptors so that they don't have to listen to that noxious stimuli all the time. It is like having this loud, disgusting music played and you want to turn the volume down.

You might think of insulin resistance as similar to sitting in a smelly room and pretty soon you don't smell it anymore because you get desensitized.
 

You can think about it, it’s not that you are not thinking about it anymore. But if you walk out of the room and then come back in, the smell is back, which means you get resensitized.

If your cells are exposed to insulin at all, they get a little bit more resistant to it. So the pancreas just puts out more insulin. I saw a patient today whose blood sugar was 102 and her insulin was 90! She wasn't sure if she was fasting or not, but I've seen other patients where their blood sugar was under 100 and their fasting insulin has been over 90.

That is a fasting insulin. I'm not sure how many people are familiar with seeing fasting insulins, but if I drank all the glucose I could possibly drink my insulin would never go above probably 40. So she was extremely insulin resistant.

What was happening was that she was controlling her blood sugar. Statistically she was not diabetic or even impaired glucose tolerant. Her glucose is supposedly totally normal. But her cells aren't listening to insulin; she just has an exceptionally strong pancreas.
 

Her islet cells that produce insulin are extremely strong and are able to compensate for that insulin resistance by producing thirty times more insulin than what my fasting insulin is. And just by mass action her pancreas is yelling so loud that her cells are able to listen, but they are not going to listen forever. Her pancreas is not going to be able keep up that production forever.
Once her production of insulin starts slowing down, or her resistance goes up any more, then her blood sugar goes up and she becomes a diabetic. For many years, decades before that, her insulin levels have been elevated but have never been checked.

That insulin resistance is associated with the hyperinsulinemia that produces all of the so-called chronic diseases of aging, or at least contributes to them. As far as we know in many venues of science, this is the main cause of aging in virtually all life.

Insulin is that important.

So controlling insulin sensitivity is extremely important.

Insulin and Cardiovascular Disease
Insulin is a so-called mytogenic hormone. It stimulates cell proliferation and cell division. If all of the cells were to become resistant to insulin we wouldn't have that much of a problem, but all of the cells don't become resistant.

Some cells are incapable of becoming very resistant. The liver becomes resistant first, then the muscle tissue, then the fat. When the liver becomes resistant it suppresses the production of sugar.

The sugar floating around in your body at any one time is the result of two things, the sugar that you have eaten and how much sugar your liver has made. When you wake up in the morning it is more of a reflection of how much sugar your liver has made. If your liver is listening to insulin properly it won't make much sugar in the middle of the night. If your liver is resistant, those brakes are lifted and your liver starts making a bunch of sugar, so you wake up with a bunch of sugar.
 

The next tissue to become resistant is the muscle tissue. What is the action of insulin in muscles? It allows your muscles to burn sugar for one thing. So if your muscles become resistant to insulin it can't burn that sugar that was just manufactured by the liver. So the liver is producing too much, the muscles can't burn it, and this raises your blood sugar.

Well the fat cells become resistant, but not for a while as it takes them longer. So for a while your fat cells retain their sensitivity.

What is the action of insulin on your fat cells? To store that fat. It takes sugar and it stores it as fat. So until your fat cells become resistant you get fat. As people become more and more insulin resistant, their weight goes up and up.

But eventually they plateau. They might plateau at 300 pounds, 220 pounds, 150 pounds, but they will eventually plateau as the fat cells protect themselves and become insulin resistant.

As all these major tissues, your liver, muscles and fat, become resistant your pancreas is putting out more insulin to compensate, so you are hyperinsulinemic and you've got insulin floating around all the time, 90 units or more.

But there are certain tissues that aren't becoming resistant such as your endothelium; the lining of the arteries doesn’t become resistant very readily, so all that insulin is affecting the lining of your arteries.
 

If you drip insulin into the femoral artery of a dog, there was a Dr. Cruz who did this in the early 70s by accident, the artery will become almost totally occluded with plaque after about three months.

The contra lateral side was totally clear, just contact of insulin in the artery caused it to fill up with plaque. That has been known since the 70s and has been repeated in chickens and in dogs; it is really a well-known fact that insulin floating around in the blood causes a plaque build-up. They didn't know why, but we know that insulin causes endothelial proliferation. This is the first step as it causes a tumor, an endothelial tumor.
 

Insulin also causes the blood to clot too readily and causes the conversion of macrophages into foam cells, which are the cells that accumulate the fatty deposits. Every step of the way, insulin is causing cardiovascular disease. It fills the body with plaque, it constricts the arteries, it stimulates the sympathetic nervous system, it increases platelet adhesiveness and coaguability of the blood.

Insulin is a part of any known cause of cardiovascular disease. It influences nitric oxide synthase; you produce less nitric oxide in the endothelium. We know that helps mediate vasodilatation and constriction, i.e. angina.

I mentioned that insulin increases cellular proliferation, what does that do to cancer? It increases it. And there are some pretty strong studies that show that one of the strongest correlations to breast and colon cancers are levels of insulin.

Hyperinsulinemia causes the excretion of magnesium in the urine. What other big mineral does it cause the excretion of? Calcium. People walking around with hyperinsulinemia can take all the calcium they want by mouth and it's all going to go out in their urine.

Insulin-like Growth Factors (IgFs)
Insulin is one of the first hormones that any organism ever developed, and as I mentioned in genetics, things are built upon what was there before. So all the other hormones we have in our body were actually built upon insulin. In other words, insulin controls growth hormone.
 

The pituitary produces growth hormone, and then it goes to the liver and the liver produces what are called IgF 1 thru 4, there are probably more. What does IgF stand for? Insulin-like growth factor. They are the active ingredients. Growth hormone has some small effects on its own, but the major growth factors are the IgFs that then circulate throughout the body.

Why are they called IgF's or insulin-like growth factors? Because they have an almost identical molecular structure to insulin. When I said that insulin promotes cellular proliferation, it is because it cross-reacts with IgF receptors. So somewhere in the evolutionary tree, IgFs diverged from insulin. Insulin can work very well by itself; it doesn't need growth hormone, but growth hormone can't do anything without insulin.

Thyroid
The thyroid produces mostly T4. T4 goes to mostly to the liver and is converted to T3. We are getting the idea that insulin controls a lot of what goes on in the liver, and the liver is the primary organ that becomes insulin resistant.

When the liver can no longer listen to insulin, you can't convert T4 to T3 very well. In people who are hyperinsulinemic with a thyroid hormone that comes back totally normal, it is important to measure their T3. Just as often as not, their free T3 will be low, but get their insulin down and it comes back up.

Insulin helps control sex hormones estrogen, progesterone, and testosterone as well. Insulin helps control the manufacture of cholesterol and where do all the sex hormones come from? All the stearic hormones are originally derived from cholesterol, so that's one way. Dr Nestler from the University of Virginia who has spent the last eight years doing multiple studies to show that DHEA levels are directly correlated with insulin levels, or I should say insulin resistance.

The more insulin resistant you are, the lower your DHEA levels. He firmly believes, and has a lot of studies to back it up, that the decline in DHEA is strictly due to the increase in insulin resistance with age. If you reduce the insulin resistance, the DHEA rises.

And how are these sex hormones carried around the body? Something called sex hormone binding globulins. The more that is bound, the less free, active hormone you have. Sex hormone binding globulin is controlled by what? Insulin. There is not a hormone in the body that insulin doesn't affect, if not directly control.

Osteoporosis
You take a bunch of calcium. The medical profession just assumes that it has a homing device and it knows to go into your bone. What happens if you have high levels of insulin and you take a bunch of calcium? Number one, most of it is just going to go out in your urine. You would be lucky if that were the case because that part that doesn't does not have the instructions to go to your bone because the anabolic hormones aren't working.

This is first of all because of insulin, then because of the IGFs from growth hormone, also testosterone and progesterone. They are all controlled by insulin and when they are insulin resistant they can't listen to any of the anabolic hormones. Your body doesn't know how to build tissue anymore so while some of the calcium may end up in your bone, a good deal of it will end up everywhere else--leading to metastatic calcifications, including in your arteries.

Diseases are a result of a lack of communication. There are certain things that your cells need to be healthy. If you learn nothing else today, you should know that everything is at the cellular and molecular level and we are nothing but a community of cells. We are a commune of cells; a metropolis of cells that have been given instructions to cooperate.

When you have a large number of cells, like we have ten trillion or so, there must be proper communication so that there will be proper division of labor. You can take most any cell in your body, put it in a petrie dish and under the right conditions it can live all on its own. They each have a life of their own.

You can manipulate the genetics of a cell, and we've now made a blood cell into a nerve cell. Pretty soon we are going to be able to take any cell we want and make it into any other cell, because every cell in your body has the identical genetics, all derived from that egg and that sperm that came together. Why is one cell different from another? Because they are reading different parts of the same library.

You can influence which part of that genetic library that every cell reads by the environment of that cell. The environment of that cell is going to be very much dictated by hormones and what you eat. Eating is just internalizing the external environment. That is what you have circulation for, to bring that external environment to each and every one of those cells that is inside of you.

I hope that by now you have gotten the idea that high insulin resistance is not very good for you. So now let's talk about what causes insulin resistance.

What Causes Insulin Resistance?
Any time your cell is exposed to insulin it is going to become more insulin resistant. That is inevitable; we cannot stop that, but the rate we can control. An inevitable sign of aging is an increase in insulin resistance.

That rate is the variable. If you can slow down that rate, you can become a centenarian, a healthy one. You can slow the rate of aging. Not even just the rate of disease, but the actual rate of aging itself can be modulated by insulin. We talked about some of the lower animals and there is some pretty good evidence that even in humans we still retain the capacity to control lifespan at least partially. We should be living to be 130 to 140 years old routinely.

Let's talk about carbohydrates. We talk about simple and complex carbohydrates, this is totally irrelevant, it means absolutely nothing. Carbohydrates are fiber or non-fiber. Few things in life are as clear-cut as this. Fiber is good for you, and a non-fiber carb is bad for you. You can bank on that.

There is not a whole lot of middle ground. If you have a carbohydrate that is not a fiber it is going to be turned into a sugar, whether it be glucose or not. It may be fructose and won't necessarily raise your blood glucose. Fructose is worse for you then glucose so if you just go by blood sugar, which is just glucose, it doesn't mean that you are not raising your blood fructose, or your blood galactose which is the other half of lactose.

All of those sugars are as bad or worse for you than glucose. You can't just go by so-called blood sugar because we just don't measure blood fructose or blood galactose, but they are all bad for you.

Why are they bad? Well number one we know that it provokes insulin and every time you provoke insulin it exposes your body to more insulin and just like walking in a smelly room your body is going to become more resistant to insulin.

So every time you have a surge of sugar and you have a surge of insulin, you get more and more insulin resistant and risk all of the problems we've talked about.
 

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