The Cholesterol Myth and Heart Disease....

I asked Dr. Carlos Braghini for permission to reproduce his excellent text on the cholesterol myth on my website, available at http://www.ecologiacelular.com.br/. I believe that reading this text not only provides quality information, but also a critical view that is essential for all of us, whether as patients or health professionals, and above all as human beings. As I often say in my social networks, lectures and other spaces, many people profit from the illness and misinformation of others: how long will this continue?

“The Cholesterol Myth and Heart Disease....

What is the standard medical treatment for someone with a cardiovascular problem?

First, check your blood pressure, and if it's high, start treatment with antihypertensive drugs. Then measure your blood cholesterol and, if it's high, start taking a special class of drugs to lower it - statins - and adopt a low-fat diet with margarine, skimmed milk and other light products. With a bit of luck, you may be recommended physical exercise.

Although standard, except for the exercises, these recommendations may have the opposite effect to what is expected. Prescribed by doctors all over the world as essential for lowering blood cholesterol, statins cause serious side effects, including muscle pain (the most common complaint), fatigue and generalized weakness, especially in the arms and legs. This is due to the destruction of the muscle cell, a process called rhabdomyolysis, but not only the peripheral muscles are affected: more recent studies show that statins worsen the clinical picture of congestive heart failure, a condition in which the heart muscle becomes weak to pump blood effectively. In addition, in the medium and long term, they can cause neurological damage (polyneuropathy), induce depression, worsen memory, cause pancreatitis and increase the incidence of cancer.

These serious side effects are explained by the mechanism of action of statins, which have a powerful cholesterol-reducing effect by inhibiting the action of an enzyme, HMG-CoA reductase (hydroxymethylglutarate coenzyme-A reductase). The process of cholesterol formation begins when three molecules of acetyl coenzyme-A (AcetylCoA) combine to form hydroxymethylglutaric acid (HMG), which in turn requires the action of the enzyme HMG-CoA reductase, which ultimately produces mevalonate. It is from mevalonate that a series of chemical reactions take place with the formation of a whole family of intermediate substances, many (if not all) of which have important biochemical functions. This is why, when we use statins, we prevent not only the formation of cholesterol, but also of two other fundamental molecules: coenzyme Q10 and dolichol.

Coenzyme Q10 (CoQ10) or ubiquinone is a biochemical compound needed to transfer energy from food to cells, i.e. what keeps us healthy and alive. It was unknown fifty years ago, but today some experts call it “vitamin 10” because it is an essential substance for cell function. It increases the cells' ability to use oxygen, optimizes energy production and prevents damage caused by free radical electrons. The heart requires large quantities of CoQ10, which is also present in all cell membranes and is essential for maintaining nerve impulse conduction and muscle integrity. In addition, CoQ10 plays an important role in the formation of collagen and elastin.

Dolichol also plays an extremely important role, since in cells it directs the manufacture of various proteins based on the information contained in DNA, ensuring that cells respond correctly to genetically programmed instructions.

The potent cholesterol-lowering effect of statins is due to this action on the so-called mevalonate chain, but it can lead to unpredictable chaos at cellular level. Consider the findings of pediatricians at the University of California, San Diego, who published a description of a child with a hereditary defect in mevalonate kinase, the enzyme that catalyzes the next step after HMG-CoA reductase. The child was born with a cataract, was mentally retarded, microcephalic (very small head), small for his age, profoundly anemic, acidotic and febrile. Predictably, her cholesterol was constantly low, between 70 and 79mg/dl. She died at the age of 24 months. This case, despite representing an extreme of cholesterol inhibition, sheds light on the possible consequences of using statins in high doses or for a prolonged period of time.

As for the practical results, the work shows that statins can indeed prevent some heart diseases in the short term, but not by inhibiting the production of cholesterol, but by blocking the creation of mevalonate, which seems to make the smooth muscle cells in blood vessels less active and leaves platelets less able to produce thromboxane. The clogging of arteries (atherosclerosis) begins with the growth of smooth muscle cells within the vessel wall and thromboxane is necessary for the blood to clot. However, the results, when analyzed in the medium and long term, are poor.

Below are the results of some of the main studies on statins:

1. MIRACL, 2001. It looked at the effects of high doses of Lipitor in 3,086 patients after angina or acute infarction. The results showed a reduction in reinfarctions requiring hospitalization in the first 16 weeks, but there was no difference in reinfarctions after this period or in mortality.

2. ALLHAT, 2002. Of the 5,170 people who received statins, 28% reduced LDL cholesterol significantly, while in the control group (5,185 people), without statins, 11% had a similar reduction; but both groups showed the same rates of death and heart attacks.

3. PROSPER, 2002. Studied the effect of pravastatin in groups of elderly people: 56% without evidence of coronary disease and 44% with coronary symptoms. There was no change in the mortality rate in either group, but the incidence of cancer increased in the treatment group.

4. J-LIT, 2002. This Japanese study involved 47,294 patients taking simvastatin for 6 years. The results showed no correlation between the amount of LDL reduction and the mortality rate. Some of them had no reduction in LDL levels while others had a moderate drop and others had larger reductions in LDL, but the groups that obtained the minimum cholesterol levels (between 160 and 170mg/dL) had more than double the mortality rates of those with 220 to 260mg/dL).

5. ASCOT-LLA, 2003. Evaluated the effect of atorvastatin versus placebo in hypertensive women with other coronary risk factors. The study was initially designed for 5 years, but was stopped at 3.3 years due to serious side effects. During the study period, the reduction in the rate of infarction was 1.2%; there was no significant difference in mortality.

6. Beth Israel Medical Center, USA, 2003. Examined coronary plaque in 182 patients taking statins, one group at high doses and the other at usual doses. Despite the reduction in LDL, contrary to expectations, there was an increase of around 9.2% in plaque in both groups.

7. REVERSAL, 2004. A study at the Cleveland Clinic, USA, showed that patients who received atorvastatin had a reduction in plaque size of around 0.4% after 18 months.

One study in particular is noteworthy because it brings home the concept of how the pharmaceutical industry uses statistics to its advantage. The PROVE-IT (PRvaastatin Or AtorVastatin Evaluation in Infection Study) 2004 introduced the concept that the lower the cholesterol, the better, and it was from this that doctors began to adopt the approach of increasing the dose of statins for those who were already using them and felt free to prevent them in people with no previous history of coronary disease.

In fact, what was the result of this study to generate such a stir? The study compared two drugs - Lipitor (Pfizer) and Pravacol (Bristol Meyers-Squibb); the latter funded the research. Half of the 4,162 patients with a previous heart attack or unstable angina took Lipitor and half took Pravacol. Those who took Lipitor had a greater reduction in LDL (32%) and 16% in all-cause mortality; these 16% were a reduction in relative/projected risk and not actual risk. In fact, the absolute reduction in the mortality rate in both groups was 1% - a drop from 3.2% to 2.2% in two years. In other words, the reduction in the absolute risk of death was exactly this: 0.5% per year. At the same time, it was not mentioned that 33% of patients had to discontinue treatment due to side effects.

In the best pro-statin study published to date, the WOSCOP Clinical Trial, LDL reduction meant a reduction in the mortality rate of 0.6% over 5 years, i.e. 165 healthy people would have to be treated for 5 years to extend the life of just 1 person for another 5 years.

And because of these “favorable” studies, statins are the best-selling class of drugs in the world, with annual sales of over 20 billion dollars. And it's because of these financial results that statistics are made up. Imagine two drugs, one that reduces the risk of cancer by 50% and another that eliminates cancer in one in a hundred people. Which would you choose? Most people would choose the first, but the point is that they both refer to the same drug. They are just two different ways of looking at the same statistic. One is called relative risk, while the other is called absolute risk.

Here's how it works: let's imagine that in a study involving 100 women, we would expect that, statistically, two would get breast cancer during the study, but when 100 women take an anti-cancer medication, only one develops cancer, which means that the breast cancer of one woman out of a hundred is reduced. So the pharmaceutical industry propagates the staggering result of a 50% reduction in cancer, because 1 is 50% of 2. And this result is propagated by the press, medical journals, the marketing departments of pharmaceutical companies and, finally, by doctors. And at the same time, the side effects are minimized, because while this medication may help one person in a hundred, its side effects create risks for all hundred people who take it.

To understand the relationship between this data and cholesterol, I would ask you to consider how cancer statistics are manipulated. The cancer industry has been busy for years making us believe that the cure for cancer is steadily advancing, but this is pure marketing. The area in which we are most advanced is diagnosis, and even then, to a lesser extent, in the types that are considered less important. Progress has been practically nil in curing the most serious types. These results are contradicted by the statistical data for many drugs in clinical trials, and I'll explain why.

Some scholars say that one of the most commonly used methods is statistical manipulation. People are chosen from the groups to be used in the study: those with the best prognosis and health receive the drug and those with the least therapeutic possibilities receive the placebo. Thus, the results published in medical journals are not reproduced in practice. German epidemiologist Dieter Hoetzel, from the Clinical Center of the University of Munich (Germany), concluded in 2005 that in the last 25 years there has been no progress in survival from metastatic bowel, breast, lung and prostate cancers, which account for 80% of deaths. The harsh reality is that cancer patients die as quickly today as they did 25 years ago.

That said, we can understand why, even with all the pharmaceutical industry's efforts to link cholesterol to heart disease over the last 50 years, the evidence shows that this relationship is not true. A new Pfizer study was stopped in December 2006, after following 15,000 patients taking a new drug, torcetrapib: this drug, instead of reducing, increased the death rate. This drug increased the level of “good” cholesterol (HDL) and, despite this, atheroma plaques continued to be deposited on artery walls, the rate of heart attacks remained the same and the death rate increased.

No surprise there. It's exactly what studies have shown in recent years: lowering cholesterol doesn't save lives. On the contrary, several studies with large population groups show that lowering cholesterol to the recommended levels is linked to an increased risk of dying, especially from cancer.

Dr. Ron Rosendale, a critic of the demonization of cholesterol (for him the Darth Vader of medicine), has said categorically for more than 10 years: “Cholesterol is not primarily responsible for heart disease or any disease. In fact, cholesterol is transported to the tissues as part of the inflammatory response to repair damaged tissues. The real cause lies in the biochemical reaction of glycation (or glycosylation) that sugars such as glucose and fructose inflict on tissues, including the inner lining of arteries, causing chronic inflammation and the deposition of atheromatous plaque (atherosclerosis).”.

There is no such thing as good or bad cholesterol

The first theory was that fats in the blood were to blame and the responsibility fell on triglycerides, but what are triglycerides? Just medical terminology for fat. Someone with high triglyceride levels has a lot of fat circulating in their blood. When measured in the morning, on an empty stomach, if they're high, it shows that you're making too much and consuming (burning) too little; it shows that you're not being adept at spending it. And this brings us to a bigger problem: the inability to burn fat is behind the chronic diseases linked to ageing. And the main hormones responsible for what we know as ageing and for controlling our ability to burn and store fat are insulin and leptin.

The next step was to blame cholesterol, but eliminating it from the diet gave little result; cholesterol itself is not the problem. The next theory began to study its metabolism: it is produced in the liver to be released into the bile and form part of digestion, helping to digest fats, and must be absorbed back into the bloodstream to return to the liver. It has been discovered that certain carrier proteins are responsible for carrying cholesterol through the blood. Low-density lipoproteins (LDL) are responsible for transporting cholesterol to the cells, while high-density lipoproteins (HDL) are responsible for transporting it back to the liver. So, if you have a low LDL index and a high HDL index, this is good news. The Journal of the American Medical Association (JAMA) published a study in 2007 showing that HDL levels below 35mg/dL were associated with an eight times higher incidence of heart disease compared to those above 65 mg/dL. In addition, every 1mg/dL increase in HDL resulted in a 6% lower risk of death from a heart attack.

Note that LDL and HDL are lipoproteins - fats combined with proteins. There is no such thing as good or bad cholesterol; cholesterol is just cholesterol. It combines with other fats and proteins to be carried through the bloodstream, since fat and watery blood don't mix very well. Remember the school experience of trying to mix oil and water.

LDL and HDL are protein molecules and are far from being just cholesterol. In fact, there are several types of these protein and fat particles. LDL particles come in many sizes and the larger particles are not the problem. Only the so-called small, dense particles are potential problems, as they can clump together in small lesions in the artery wall, undergo oxidation and then cause inflammation. Also, some HDL particles are better than others. Knowing the level of total cholesterol therefore tells us very little. In reality, high cholesterol is the symptom that indicates that there are other problems.

So don't confuse cause with effect. There may even be a small correlation between cholesterol and heart disease, but this doesn't mean that cholesterol is the cause. Certainly, gray hair is related to aging; however, who would claim that it is gray hair that makes us age? Using a dye to darken your hair doesn't really make anyone younger; trying to reduce cholesterol works in the same way.

It is becoming increasingly clear that oxidized (damaged) cholesterol, whatever type of lipoprotein it is (LDL or HDL), is more likely to clog arteries. Normally, cholesterol is protected from oxidation by antioxidant nutrients. More recent findings indicate that the “problem” fat may actually be lipoprotein A orLp(a), a special combination of fat and protein that is used to repair damaged or leaking blood vessels, but ends up posing a risk of heart disease by building up deposits on the artery wall.

Cholesterol is the Hero, not the Villain

Cholesterol is a vital component of the membrane of every cell. This also means that it cannot be bad on its own. How else can we explain the fact that breast milk is rich in cholesterol? In fact, we can't live without it.

Cholesterol is responsible for the structural integrity of the cell membrane, is a precursor of steroid hormones (estrogen, testosterone and cortisone) and vitamin D, participates in the production of bile salts, is an antioxidant and protects the intestinal mucosa. It also makes serotonin receptors more sensitive to serotonin, which is why people who take statins are more prone to depression - and end up adding another drug to the pharmacy budget: antidepressants.

Because it is so important, we have developed a powerful mechanism for producing cholesterol. So much so that only 30% of it comes from our diet; the other 70% is produced by various tissues in the body, mainly the liver, although some of the cholesterol released by the bile returns to the bloodstream after being absorbed in the intestine.

And as well as producing cholesterol, our bodies have developed mechanisms to preserve it and prevent it from being eliminated unnecessarily. Remember that HDL is responsible for taking cholesterol back to the liver so that it can be recycled, released again and taken to the tissues and cells that need it.

It is cholesterol that prevents the cell membrane from breaking down; we can think of it as “cell glue”, a necessary ingredient for cell repair. So instead of fighting cholesterol, we have to learn to protect it, because the damage to the artery wall that causes inflammation oxidizes cholesterol and causes lipoprotein deposition in the artery wall.

Inflammation

Think about what happened the last time you cut your finger. Some cells ruptured and, in a split second, chemicals that were inside those cells leaked out and came into contact with the receptors that inform you about harmful stimuli, the nociceptors. This is the main reason why pain is felt. At the same time, other chemical substances initiate what we call an inflammatory reaction.

Inflammation is what allowed his small cut to heal and stopped him from bleeding to death. The cut blood vessels contract, preventing too much blood loss, and the blood thickens to flow more slowly and “plug” - clot - the lesions. Cells of the immune system are alerted and head for the injured area to prevent intruders, such as viruses and bacteria, from invading your body. Other cells are stimulated to multiply to repair and replace the injured cells. After a few days, your finger will be ready to work again, and if the cut is extensive enough, you are likely to show a scar; it's your body's way of telling you to be more careful next time.

These same events take place in the artery wall. When damage occurs, chemicals are released to start the inflammatory process. Vessels constrict, flow slows down, blood becomes more prone to clotting, leukocytes arrive to fight off potential invaders, other defense cells arrive to “clean up” and “eat” the dead cells and others are stimulated to reproduce. And in the end, inside the arteries, scars form: plaques. Fat is deposited in these plaques.

And how does cholesterol play a part in this process? Cholesterol is being distributed by the blood to inflamed tissues to help repair the tissue damage and keep it alive. If the damage is extensive, extra cholesterol needs to be distributed through the bloodstream. If measured, the level of cholesterol in the blood will be high. Therefore, simply reducing cholesterol and forgetting why it's high doesn't seem to be the best course of action. Cholesterol rises when there is inflammation; if this is chronic, it is chronically increased. This deserves special attention.

There are several causes of chronic inflammation, the most important of which is sugar metabolism and its influence on insulin and leptin.

Hundreds of excellent scientific articles show the link between insulin resistance (and more recently leptin resistance) and heart disease. Insulin and leptin are at least partly responsible for abnormalities in cholesterol metabolism.

The link between cholesterol metabolism and sugar metabolism is manifested in the metabolic conditions called insulin resistance and leptin resistance. Insulin and leptin resistance result in an increase in the number of small, dense LDL cholesterol particles that concentrate in the junctions of the endothelium, the inner wall of the arteries, oxidize and harden, causing a local inflammatory reaction and the formation of fatty plaques.

According to this concept, cholesterol is not the cause of heart disease, but rather inadequate cholesterol metabolism. Removing cholesterol will not remove the cause of the disease, which lies in the inadequate metabolic communication caused by insulin and leptin.

Author: Dr. Carlos Braghini - http://www.ecologiacelular.com.br/

The text above was kindly provided by the author Dr. Carlos Braghini and is part of the book Cellular Ecology - The Role of Food and the Environment in Aging and Longevity. The book was launched in 2008 and has invaluable content for those who want to improve their health by changing their relationship with food and the environment.