Cholesterol is Our Best Friend

Introduction
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 Expert Review of Clinical Pharmacology, we have 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 beenrepeated 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 lowerthan 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 is 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, 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 analysed the outcome in 30 statin trials and claimed presence of exposure-response as well. However, by analysing 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 LDL-C 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 may be beneficial
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.