Insulin and Its Metabolic Effects (Part 2)

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July 14, 2001 | 43,977 views

Part 2 of 4 (Part1, Part 3, Part4)

By Ron Rosedale, M.D.

Presented at Designs for Health Institute's BoulderFestAugust 1999 Seminar

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

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

But most importantly, magnesium is also necessary for the actionof 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 thetissues, which makes them more insulin resistant, so the insulinlevels go up and you lose more magnesium. This is the vicious cyclethat begins even before you were born.

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

Worse yet, researchers have used sophisticated measurements andfound that if that fetus happens to be a female, the eggs of thatfetus are more insulin resistant. Does that mean it is genetic?No, you can be born with something and it doesn't mean that it isgenetic. Diabetes is not a genetic disease as such. You can havea 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 downor your blood vessels constrict you get high blood pressure. Insulinalso causes the retention of sodium, which causes the retentionof fluid, which causes high blood pressure and fluid retention:congestive heart failure.

One of the strongest stimulants of the sympathetic nervous systemis 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 showedthat heart attacks are two to three times more likely to happenafter a high-carbohydrate meal and are specifically NOT likely aftera high-fat meal.

Why is that?

Because the immediate effects of raising your blood sugar froma high-carbohydrate meal is a raise in insulin. This immediatelytriggers the sympathetic nervous system, which will cause arterialspasm, or constriction of the arteries. If you anyone is prone toa heart attack, this is when they are going to get it.

Blood Lipids

Insulin mediates blood lipids. For that patient mentioned earlierwho had a triglyceride level of 2200, one of the easiest thingswe can do is lower triglyceride levels. It is so simple. There wasjust an article in the Journal of the American Medical Association(JAMA) saying that the medical profession doesn't know how to reducetriglycerides dietarily, that drugs still need to be used.

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

The gentleman who had a triglyceride level of 2200 while on allthe drugs only had an insulin level of 14.7. That is only slightlyelevated, but it doesn't take much in some people. All we had todo was get his insulin level down to 8 initially and then it wentdown 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'sthe most oxidizable, and it’s the most able to actually fitthrough the small cracks in the endothelium. And this is the cholesterolthat insulin actually raises the most. When I say insulin, I shouldsay insulin resistance. It is insulin resistance that is causingthis.

Cells become insulin resistant because they are trying to protectthemselves from the toxic effects of high insulin. They down regulatetheir receptor activity and number of receptors so that they don'thave to listen to that noxious stimuli all the time. It is likehaving this loud, disgusting music played and you want to turn thevolume down.

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

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

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

That is a fasting insulin. I'm not sure how many people are familiarwith seeing fasting insulins, but if I drank all the glucose I couldpossibly drink my insulin would never go above probably 40. So shewas 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 listeningto insulin; she just has an exceptionally strong pancreas.

Her islet cells that produce insulin are extremely strong and areable to compensate for that insulin resistance by producing thirtytimes more insulin than what my fasting insulin is. And just bymass action her pancreas is yelling so loud that her cells are ableto listen, but they are not going to listen forever. Her pancreasis not going to be able keep up that production forever.

Once her production of insulin starts slowing down, or her resistancegoes up any more, then her blood sugar goes up and she becomes adiabetic. For many years, decades before that, her insulin levelshave been elevated but have never been checked.

That insulin resistance is associated with the hyperinsulinemiathat produces all of the so-called chronic diseases of aging, orat least contributes to them. As far as we know in many venues ofscience, 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 proliferationand cell division. If all of the cells were to become resistantto insulin we wouldn't have that much of a problem, but all of thecells don't become resistant.

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

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

The next tissue to become resistant is the muscle tissue. Whatis the action of insulin in muscles? It allows your muscles to burnsugar for one thing. So if your muscles become resistant to insulinit 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, andthis raises your blood sugar.

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

What is the action of insulin on your fat cells? To store thatfat. It takes sugar and it stores it as fat. So until your fat cellsbecome resistant you get fat. As people become more and more insulinresistant, 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 thefat cells protect themselves and become insulin resistant.

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

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

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

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

Insulin also causes the blood to clot too readily and causes theconversion of macrophages into foam cells, which are the cells thataccumulate the fatty deposits. Every step of the way, insulin iscausing cardiovascular disease. It fills the body with plaque, itconstricts 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 oxidein the endothelium. We know that helps mediate vasodilatation andconstriction, i.e. angina.

I mentioned that insulin increases cellular proliferation, whatdoes that
do to cancer? It increases it. And there are some pretty strongstudies that show that one of the strongest correlations to breastand 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 calciumthey 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 therebefore. So all the other hormones we have in our body were actuallybuilt upon insulin. In other words, insulin controls growth hormone.

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

Why are they called IgF's or insulin-like growth factors? Becausethey have an almost identical molecular structure to insulin. WhenI said that insulin promotes cellular proliferation, it is becauseit cross-reacts with IgF receptors. So somewhere in the evolutionarytree, IgFs diverged from insulin. Insulin can work very well byitself; it doesn't need growth hormone, but growth hormone can'tdo anything without insulin.


The thyroid produces mostly T4. T4 goes to mostly to the liverand is converted to T3. We are getting the idea that insulin controlsa lot of what goes on in the liver, and the liver is the primaryorgan that becomes insulin resistant.

When the liver can no longer listen to insulin, you can't convertT4 to T3 very well. In people who are hyperinsulinemic with a thyroidhormone that comes back totally normal, it is important to measuretheir T3. Just as often as not, their free T3 will be low, but gettheir insulin down and it comes back up.

Insulin helps control sex hormones estrogen, progesterone, andtestosterone as well. Insulin helps control the manufacture of cholesteroland where do all the sex hormones come from? All the stearic hormonesare originally derived from cholesterol, so that's one way. Dr Nestlerfrom the University of Virginia who has spent the last eight yearsdoing multiple studies to show that DHEA levels are directly correlatedwith 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, thatthe decline in DHEA is strictly due to the increase in insulin resistancewith age. If you reduce the insulin resistance, the DHEA rises.

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


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

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

Diseases are a result of a lack of communication. There are certainthings that your cells need to be healthy. If you learn nothingelse today, you should know that everything is at the cellular andmolecular level and we are nothing but a community of cells. Weare a commune of cells; a metropolis of cells that have been giveninstructions to cooperate.

When you have a large number of cells, like we have ten trillionor so, there must be proper communication so that there will beproper 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 liveall on its own. They each have a life of their own.

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

You can influence which part of that genetic library that everycell reads by the environment of that cell. The environment of thatcell is going to be very much dictated by hormones and what youeat. Eating is just internalizing the external environment. Thatis what you have circulation for, to bring that external environmentto 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 resistanceis not very good for you. So now let's talk about what causes insulinresistance.

What Causes Insulin Resistance?

Any time your cell is exposed to insulin it is going to becomemore insulin resistant. That is inevitable; we cannot stop that,but the rate we can control. An inevitable sign of aging is an increasein insulin resistance.

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

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

There is not a whole lot of middle ground. If you have a carbohydratethat is not a fiber it is going to be turned into a sugar, whetherit be glucose or not. It may be fructose and won't necessarily raiseyour blood glucose. Fructose is worse for you then glucose so ifyou just go by blood sugar, which is just glucose, it doesn't meanthat you are not raising your blood fructose, or your blood galactosewhich is the other half of lactose.

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

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

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