Why warning of the heart risks associated with high cholesterol doesn’t tell the full story

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The idea that high levels of cholesterol in the bloodstream puts us in mortal danger is perhaps one of the most firmly entrenched medical ‘facts’ of our time. Repeatedly, consistently and frequently we are warned that the cholesterol in our blood will bung up are arteries and increase our risk of heart disease. Another reminder came this week on the publication of review in the Journal of the American Association [1]. The review was really a revisiting of a previous study which found that in a group of more than 360,000 men, the higher the level of cholesterol, the greater the risk of heart disease was found to be [2]. This original study is known as the MR FIT study (an acronym that comes from the title ‘Multiple Risk Factor Intervention Trial’). The paper puts the original study in the context of other evidence which supports the concept that cholesterol is killing people and is a beast that needs taming.

While studies do indeed show that raised cholesterol levels are associated with an increased risk of heart disease, it does make sense to take a wider view if at all possible. Recently I have reported on a couple of studies which link lower cholesterol levels with an increased risk of cancer. One of these studies found lower cholesterol levels were associated with an increased risk of death too. You can read about there studies here and here. The bottom line is that focusing only on heart disease can give us a somewhat skewed impression of the association between cholesterol and health.

The thing is, though, we don’t need to look beyond the MR FIT study itself to find similar data. In a study published in 1992, the participants of the MR FIT study were assessed for the relationship between a number of conditions [3]. The positive association between cholesterol levels and heart disease was once again noted. However, lower cholesterol levels were found to be associated with an increased risk of bleeding into the brain (intracranial haemhorrage). Here are some other findings from this study: A serum cholesterol level less than 4.14 mmol/L (less than 160 mg/dL) was also associated with a significantly increased risk of death from cancer of the liver and pancreas; digestive diseases, particularly hepatic cirrhosis; suicide; and alcohol dependence syndrome. In addition, significant inverse graded associations were found between serum cholesterol level and cancers of the lung, lymphatic, and hematopoietic systems, and chronic obstructive pulmonary disease.

So, according to this data, the low cholesterol levels are associated with increased risk of, among other things, several forms of cancer. The authors of this week’s JAMA article were also authors of this study revealing the apparent hazards of low cholesterol. But this week’s JAMA article makes no mention of these findings.

However, let us not led also this epidemiological data (which is good only for showing us associations between things) blind us to what the MR FIT study was really about. The clue is in the title: The study took thousands of men and randomised them to undergo multiple interventions in an effort to reduce their risk of heart disease. One of the interventions was intensive counselling on the reduction of fat and cholesterol in their diets. The participants in the active group were also given blood-pressure lowering medication and encouraged to stop smoking. The results over time were compared to individuals who had not undergone these interventions [4].

The result? The interventions did not bring a statistically significant reduction in risk of death from heart disease nor overall risk of death either. This dismal result was not mentioned in this week’s JAMA paper either. We can’t judge from this study whether taking dietary steps to reduce cholesterol is worthwhile or not, because of multifactorial nature of this trial. However, one thing is for certain: the results of the original MR FIT study in no way support the notion that reducing fat and cholesterol is beneficial to health.

What about other evidence? Well, in one meta-analysis taking dietary steps to reduce cholesterol was not found to bring statistically significant benefits in terms of overall risk of death [5]. It’s this sort of data that the JAMA and other medical journals should be drawing our attention to, I reckon.


1. Stamler J, et al. The Multiple Risk Factor Intervention Trial (MRFIT)”Importance Then and Now. JAMA 2008;300(11):1343-1345.

2. Stamler J, et al. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? JAMA. 1986;256(20):2823-2828.

3. Neaton JD, et al. Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med 1992;152(7):1490-500

4. [No authors listed] Multiple risk factor intervention trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group. JAMA. 1982;248(12):1465-77.

5. Studer M, et al. Effect of different antilipidemic agents and diets on mortality. Archives of Internal Medicine. 2005;165:725-730

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