Cholesterol is a peculiar molecule. It is often called a lipid or a fat. However, the chemical term for a molecule such as cholesterol is alcohol, although it doesn’t behave like alcohol. Its numerous carbon and hydrogen atoms are put together in an intricate three-dimensional network, impossible to dissolve in water. All living creatures use this indissolvability cleverly, incorporating cholesterol into their cell walls to make cells waterproof. This means that cells of living creatures can regulate their internal environment undisturbed by changes in their surroundings, a mechanism vital for proper function. The fact that cells are waterproof is especially critical for the normal functioning of nerves and nerve cells. Thus, the highest concentration of cholesterol in the body is found in the brain and other parts of the nervous system.
Because cholesterol is insoluble in water and thus also in blood, it is transported in our blood inside spheric particles composed of fats (lipids) and proteins, the so-called lipoproteins. Lipoproteins are easily dissolved in water because their outside is composed mainly of water-soluble proteins. The inside of the lipoproteins is composed of lipids, and here are room for water-insoluble molecules such as cholesterol. Like submarines, lipoproteins carry cholesterol from one place in the body to another.
The submarines, or lipoproteins, have various names according to their density. The best known are HDL (High Density Lipoprotein), and LDL (Low Density Lipoprotein). The main task of HDL is to carry cholesterol from the peripheral tissues, including the artery walls, to the liver. Here it is excreted with the bile, or used for other purposes, for instance as a starting point for the manufacture of important hormones. The LDL submarines mainly transport cholesterol in the opposite direction. They carry it from the liver, where most of our body’s cholesterol is produced, to the peripheral tissues, including the vascular walls. All cells can produce cholesterol, but if they need more than they are able to produce themselves, they call for the LDL submarines, which then deliver cholesterol into the interior of the cells. Most of the cholesterol in the blood, between 60 and 80 per cent, is transported by LDL and is called ”bad” cholesterol, for reasons that I shall explain soon. Only 15-20 percent is transported by HDL and is called ”good” cholesterol. A small part of the circulating cholesterol is transported by other lipoproteins.
You may ask why a natural substance in our blood with important biologic functions is called ”bad” when it is transported from the liver to the peripheral tissues by LDL, but ”good” when it is transported the other way by HDL. The reason is that a number of follow-up studies have shown that a lower-than-normal level of HDL-cholesterol and a higher than-normal level of LDL-cholesterol are associated with a greater risk of having a heart attack, and conversely, that a higher-than-normal level of HDL-cholesterol and a lower-than normal LDL-cholesterol are associated with a smaller risk. Or, said in another way, a low HDL/LDL ratio is a risk factor for coronary heart disease.
However, a risk factor is not necessarily the same as the cause. Something may provoke a heart attack and at the same time lower the HDL/LDL ratio. Many factors are known to influence this ratio.
What is good and what is bad? People who reduce their body weight, also reduce their cholesterol. In a review of 70 studies Dr. Anne Dattilo and Dr. P.M. Kris-Etherton concluded that, on average, weight reduction lowers cholesterol by about 10 per cent, depending on the degree of the reduction. Interestingly, it is only cholesterol transported by LDL that goes down; the small part transported by HDL goes up. In other words, weight reduction increases the ratio between HDL- and LDL-cholesterol. An increase of the HDL/LDL ratio is called ”favorable” by the diet-heart supporters; cholesterol is changed from ”bad” to ”good”. But is it the ratio or the weight reduction that is favorable? When we become fat, other harmful things occur to us. One is that our cells become less sensitive to insulin, so that some of us develop diabetes. And people with diabetes are much more likely to have a heart attack than people without diabetes, because atherosclerosis and other vascular damage occur very early in diabetics. In other words, overweight may increase the risk of a heart attack by mechanisms other than an “unfavorable” lipid pattern, while at the same time overweight lowers the HDL/LDL ratio.
Also smoking increases cholesterol a little. Again, it is LDL-cholesterol that increases, while HDL-cholesterol goes down, resulting in an ”unfavorable” HDL/LDL ratio. What is certainly unfavorable is the chronic exposure to the fumes from burning paper and tobacco leaves. Instead of considering the low HDL/LDL ratio as bad, it could simply be smoking itself that is bad. Smoking may provoke a heart attack and, at the same time, lower the HDL/LDL ratio.
Cholesterol is our best friend! In 2016 we published a review in BMJ of 19 studies where the authors had followed more than 68,000 elderly people for several years after having measured their `bad` LDL-cholesterol. None of them found that LDL-cholesterol was bad; in fact, those with the highest values lived the longest; even longer than those on statin treatment.
In more than a hundred newspapers and magazines all over the world many statin advocates criticized our paper, but none of them was able to point at a study with the opposite result. Instead, three large industry-sponsored reviews were published, whose authors presented ´solid evidence´ for the benefits of statins.
It was easy for us to see that their evidence was far from solid. In a paper entitled LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature published in the journal Expert Review of Clinical Pharmacology, we presented the many ways by which the authors of the three reviews have mislead the world for many decades by misuse of statistics and by ignoring the many contradictory reports from independent researchers. In the following we shall mention the many assertions that have made the lipid hypothesis to the greatest and costliest medical scam ever.
High cholesterol does not cause atherosclerosis. The argument that atherosclerosis is caused by high cholesterol or high `bad` LDL-cholesterol has been repeated again and again since the start of the campaign. If true, people with high cholesterol should be more atherosclerotic than people with low cholesterol. However, more than a dozen studies, the first one published almost 80 years ago, have shown that those with low cholesterol become just as atherosclerotic as people with high cholesterol.
High cholesterol does not cause heart disease. Since the publication of the results from the Framingham study in the sixties, the world has been convinced that high cholesterol is also the main cause of heart disease. This argument was based on the finding that cholesterol of some of the Framingham participants who had died during the observation time from heart disease was slightly higher than normally. However, this finding was true only up to the age of 49. After that age they observed that ‘for each 1 mg/dl drop in total cholesterol per year, there was an eleven per cent increase in coronary and total mortality’.
Very few have heard about that because shortly afterwards, a report from the American Heart Association and the U.S. National Heart, Lung and Blood Institute published a joint summary concluding that ‘a one per cent reduction in an individual’s cholesterol results in an approximate two per cent reduction in CHD risk’, and here the authors fraudulently referred to the Framingham report.
Many studies have shown that a high level of total cholesterol is not a risk factor for elderly people, the age where most heart attacks occur, and, as mentioned above, this is also true for high levels of ´bad` LDL-cholesterol. That high cholesterol is associated with an increased risk for younger people may be because mental stress is more common among working people than among retired senior citizens, and stress is able to raise cholesterol by 30-40 per cent in the course of half an hour. However, association is not the same as causation. It may for instance be the body´s reaction to stress that causes a heart attack, not the high cholesterol.
If high LDL-cholesterol was the cause of heart disease, it should of course be higher among patients with acute myocardial infarction, but it is just the opposite. In an American study, including almost 140,000 patients with acute myocardial infarction, their LDL-cholesterol at the time of admission to hospital was lower than normal. In another study with the same finding, the authors decided to lower the patients’ LDL-cholesterol even more, but at a follow-up 3 years later, total mortality among those with the lowest LDL-cholesterol was twice as high compared to those with the highest LDL-cholesterol.
Cholesterol-lowering does not prevent heart disease. If high LDL-cholesterol was the cause of heart disease, lowering it should be able to reduce the risk. The more it becomes lowered, the more should the risk be lowered. This is called exposure-response, and it is also what the statin supporters claim has happened in the company sponsored statin trials.
According to a calculation of the outcome in 25 statin trials in the review by Michael G. Silverman and his eight co-authors from various American Universities, exposure-response was present. However, as we have shown in our paper in BMJ, they have excluded at least 11 unsuccessful trials with the opposite result, and if calculated together, no exposure-response is present.
In the review from the European Atherosclerosis Society Consensus Panel the 26 authors had analyzed the outcome in 30 statin trials and claimed presence of exposure-response as well. However, by analyzing their data we found that they have only used data from12 of these trials, and when we included data from the rest, no exposure-response was present
Furthermore, in most statin trials the outcome has been misleading because the authors have used relative risk reduction rather than absolute risk reduction. What´s the difference, you may ask? If, for instance, 2 of 100 participants in the control group of a trial suffer from heart disease but only 1 of 100 in the treatment group, the absolute risk reduction is only one per cent. However, the relative risk reduction is 50 per cent, because one is 50 per cent of two.
According to the review by Sir Rory Collins from the University of Oxford and his 25 co-authors, lowering LDL-cholesterol will lower the relative risk of cardiovascular events by 45 per cent per year, and here they referred to a previous analysis of 27 statin trials performed by the Cholesterol Treatment Trialists. However, according to that analysis the absolute risk reduction of cardiovascular events was only 0.8 per cent and the absolute reduction of total mortality was only 0.4 per cent.
Usually, the benefit from statin treatment is reported as the lowering of the number of cardiovascular events, a term that may include mild, non-fatal diseases and all kinds of harmless interventions. We are confident that most people use statins because they want to prolong their life. A better way to calculate the benefit of statin treatment would therefore be to compare the reduction of mortality with the degree of cholesterol-lowering. Silverman and co-workers also did that in their review by using the results from 26 statin trials. However, we found that they had excluded at least 11 trials with the inverse result.
Statin treatment may cause many serious side effects
Even if the benefit from statin treatment is small, such treatment should be acceptable if it was harmless, and this is also what the trial directors have reported. However, in almost all statin trials the directors have tested the drug on all participants in a short run-in period before the start and excluded those who suffered from side effects. The results from two trials without a run-in period and where a high statin dose was compared with a low dose demonstrated that this is an effective way to minimize the number of reported side effects, because in one of them serious side effects were recorded in about 20 per cent in both groups, and in the other one the number was about 40 per cent. Furthermore, some of the most serious adverse effects do not appear immediately; it may take several months or years before they arrive, and most doctors and patients may therefore think that they are due to increasing age.
The commonest side effect is muscular damage. According to the drug companies it occurs in less than 0.01 per cent, but muscular damage has only been recorded if the blood level of creatine, a molecule that reflects muscular damage, becomes ten times higher than normal. Independent researchers have reported that muscular symptoms occur in more than 20%, and microscopic examinations of the muscles of statin-treated patients with muscular symptoms and with normal creatine have shown muscular damage that disappeared together with the muscular symptoms when the patients stopped treatment. Independent researchers have also documented that statin treatment may cause heart failure, diabetes, cataract, hearing loss, impotency, memory loss, cognitive impairments, depression, suicidal ideation, Parkinson´s disease, and cancer.
High cholesterol is beneficial. The reason for the broad spectrum of adverse effects is easy to understand because cholesterol is one of our most important molecules. All cell walls and nerve fibres are built by cholesterol and all cells are renewed regularly, and to build new cells demands much cholesterol; particular in the brain, the cholesterol-richest organ in the body. Furthermore, cholesterol is used for the creation of the stress and sex hormones; the sun converts cholesterol in the skin to vitamin D, and to absorb fat-soluble vitamins from the gut we need bile, another cholesterol-product. And there are more benefits. What is little known but what has been documented by at least a dozen research groups is that LDL, the molecular submarine that transports cholesterol around in the blood, partake in the immune system by adhering to and inactivating almost all types of microorganisms and their toxic products. This fact may explain why people with low cholesterol suffer more often from infections than people with high cholesterol and also why people with high LDL-cholesterol live the longest.
Inherited high cholesterol is beneficial as well. It is a general view that the increased risk of heart disease among people with inherited high cholesterol (familial hypercholesterolemia) is caused by their high cholesterol. However, it has been shown that on average, people with this abnormality live just as long as other people. Only very few die early from a heart attack, and after the age of sixty the survivors live longer than other people because they are protected against cancer and infectious diseases. Several studies have shown that the few who die early from a heart attack have also inherited abnormally high levels of various types of coagulation factors.
Are the trial directors honest? For some years, many researchers have questioned the results from statin trials because they have been denied access to the primary data. In 2004–2005, health authorities in Europe and the United States introduced New Clinical Trial Regulations which specified that all trial data had to be made public. Since 2005, no statin trial has been successful.
Conclusion. Our conclusion is that the statements from the supporters of the cholesterol campaign and the drug companies are invalid, compromised by misleading statistics, excluding unsuccessful trials, minimizing the side effects of cholesterol lowering, and ignoring contradictory observations from independent investigators.
PS. After the publication of our paper in BMJ, 19 more follow-up studies including more than six million patients and healthy people had resulted in similar findings.