While cholesterol remain possibly the most vilified natural and essential body constituent, and we are encouraged to put constant downward pressure on our cholesterol levels, it should perhaps not be forgotten that low levels of cholesterol are associated with enhanced risk of death. Low cholesterol is associated with an enhanced risk of specific health issues including haemorrhagic stroke (stroke caused by bleeding of rather than blockage in blood vessels) and cancer. This last association has been quite consistently found in studies [1-3].
Recently, the American College of Cardiology held a scientific meeting during which data relating to cholesterol levels and cancer was presented. The research assessed LDL-cholesterol levels and risk of cancer for an average period of almost 19 years prior to a diagnosis of cancer being made. The researchers found that throughout the course of the study (even many years before cancer was detected), lower levels of LDL-cholesterol were associated with enhanced risk of cancer.
Just because low cholesterol and cancer are associated does not mean low cholesterol causes cancer. Some scientists have suggested that the relationship is the other way round and the result of what is known as ‘reverse causality’ i.e. that chronic conditions such as cancer can cause lowered cholesterol, rather than the other way round. This idea is sometimes referred to as ‘Iribarren’s hypothesis’.
However, the long length of the study referred to above and the fact that low cholesterol appeared to predict cancer risk many years in advance of the disease appearing points against reverse causality. And it’s not the only evidence which does this.
A previous study found that individuals with a low serum cholesterol maintained over a 20-year period had the worst outlook in terms of overall risk of death . The authors of this study wrote: “Our present analysis suggests that this [Iribarren’s] hypothesis is implausible and is unlikely to account for the adverse effects of low cholesterol levels over twenty years.” In other words, according to these authors, it’s more likely that low cholesterol causes chronic disease than the other way round.
If low cholesterol were to increase the risk of cancer, how might it do this? One explanation might be that cholesterol is the basic building block of vitamin D – a substance which appears to have potent anti-cancer properties.
There is some other evidence that low-cholesterol might cause cancer in the form of studies which found the combination of two cholesterol-reducing drugs (simvastatin and ezetimibe) over four years was associated with a significantly increased risk of cancer . The pooling of the results of three relevant studies found that this drug combination raised risk of death from cancer was raised by 45 per cent.
Oddly, this result was put down by prominent scientists as likely to be due to ‘chance’, when the statistics showed that it was statistically significant and therefore highly unlikely to be due to chance. You can read more about this here.
So, in fact, there is more than a little evidence that low cholesterol levels might cause cancer, and we should perhaps be cautious about driving cholesterol levels to ever-lower levels.
1. Alawi A, et al. Statins, Low-Density Lipoprotein Cholesterol, and Risk of Cancer. Journal of the American College of Cardiologists 2008;52(14):1141-7
2. Yang X, et al. Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus. Canadian Medical Association Journal 2008;179(5):427-437
3. Schatzkin A, et al. Serum cholesterol and cancer in the NHANES I epidemiologic followup study. National Health and Nutrition Examination Survey. Lancet 1987;2:298-301
4. Schatz IJ, et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001;358(9279):351-5
5. Peto R, et al. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008;359(13):1357-66