Saturday, July 7, 2012

Do Low Cholesterol Levels Cause Cancer?

Do Low Cholesterol Levels Cause Cancer?

March 26, 2012
We live in a world where a high cholesterol is now considered to be virtually the most terrible and dangerous thing known to man. Everything possible must be done to bring the level down, or else you are going to die of a stroke or heart attack.

The anti-cholesterol propaganda has been so successful that six million people in the UK now take statins each and every day to reduce their risk of heart disease. Something which, I strongly believe, future generations will look back on in amazement. ‘Did they not know that cholesterol is essential for human health….what on earth did they think they were doing?’

Can it really be true that a chemical compound, so important that the liver synthesises at least five times as much as you consume in food, can be disastrous to our health. All cell membranes need it, our brains need it, almost all of our hormones are made out of it, and it is used to make vitamin D in our skin. It has always seemed to me that having too little cholesterol is just as likely to be damaging as having too much – probably more so.

One area I have particular concerns about is cancer. For many years it has been noticed that people with low cholesterol levels are more likely to die of cancer. This has been a consistent finding, for many years, from studies done all around the world1-9.

The statin ‘zealots,’ as I shall call them, are well aware of the association between low cholesterol and cancer, and they have gone out of their way to dismiss the possibility that low cholesterol may cause cancer.

The primary argument they have used is known as reverse causality. This ‘reverse-causality’ hypothesis suggests that depressed LDL-cholesterol levels are the result of subclinical cancer (not the other way round). This idea has been put forward with absolutely no evidence to support it. Despite this, it has been accepted without question.

It is true that if you have advanced cancer, your cholesterol levels fall. This happens for a number of interconnected reasons, including the fact that large tumours use a lot of cholesterol to divide and grow.

However, the idea that a cancer so small, that it cannot not yet be detected, is using up so much cholesterol that it lowers the total cholesterol level throughout the body, is stretching the boundaries of possibility. I would say breaking the bounds of possibility.

The second argument put forward, which is not really an argument, is the ‘how can a low cholesterol level cause cancer anyway.’ It should always be remembered that a great deal of medical research consists of bumping into effects, without understanding how it could happen in the first place – see under penicillin. See more recently under aspirin protecting against cancer. A finding as yet, without any clearly defined mechanism of action.

In short, just because you can’t easily see a mechanism of action, does not mean that it doesn’t exist. In fact, several possible ways that cholesterol, or to be more accurate lipoproteins, could protect against cancer have been researched in some detail10.

Anyway, as I have always known must happen, the ‘reverse causality’ hypothesis has finally been laid to rest. A recent analysis of the longest running heart disease research project in the world (the Framingham Study) has shown that low cholesterol levels predate cancer diagnosis by many, many, years. And, to quote:

“Based on these data, it would suggest that lower cholesterol predated the development of cancer by quite a long time. Now, that doesn’t necessarily speak to [low cholesterol] causing the cancer; it could have been related to something else altogether, but it’s not supportive of the hypothesis that cancer caused the low levels of LDL cholesterol. We don’t know why it predates cancer, but it would be premature to attribute it to the cancer itself.” 11

In short, it must now be accepted that cancer doesn’t cause low cholesterol levels. Which leaves the possibility that low cholesterol levels might cause cancer. This, inevitably, leads to the next question. If low levels of cholesterol precede cancer, can statins cause cancer?

The evidence is not conclusive, and I would not claim that it was. But there have been some significant warning signs from statin studies. Just to mention three. In the CARE trial12, twelve women in the statin group had breast cancer at follow up, compared on only one in the placebo group. In the PROSPER study13 there were forty six more cases of cancer in the statin group than the placebo group.

Possibly the most worrying figures come from a Japanese study which looked at nearly fifty thousand people taking statins over six years. They found that the number of cancer deaths was more than three times higher in patients whose total cholesterol was less than 4.0mmol/l at follow-up, compared with those whose cholesterol was normal or high:

The patients with an exceptionally low TC (total cholesterol) concentration, the so-called ‘hyper-responders’ to simvastatin, had a higher relative risk of death from malignancy than in the other patient groups.’

The authors then went on to warn:
Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC (cholesterol) and LDL-C (Low Density Lipoprotein ‘bad cholesterol’) concentrations with low-dose statin.’14

This is not proof of causation, but these are warning signs. Armed with the Framingham data, I believe that the medical profession has to face up to the painful reality that low cholesterol levels could be a cause of cancer, and this needs to be properly researched. We must remember that it took Richard Peto more than thirty years to prove that smoking caused lung cancer, and no statin trial has lasted longer than six.

1. Williams RR, Sorlie PD, Feinleib M, McNamara PM, Kannel WB, Dawber TR. Cancer incidence by levels of cholesterol. JAMA 1981; 245:247–52.
2. Salmond CE, Beaglehole R, Prior IA. Are low cholesterol lvalues associated with excess mortality? BMJ 1985;290:422–4.
3. Schatzkin A, Hoover RN, Taylor PR, Ziegler RG, Carter CL,Larson DB, et al. Serum cholesterol and cancer inthe NHANES I epidemiologic followup study. NationalHealth and Nutrition Examination Survey. Lancet 1987;2:298–301.
4. To¨rnberg SA, Holm LE, Carstensen JM, Eklund GA. Cancer
incidence and cancer mortality in relation to serum cholesterol. J Natl Cancer Inst 1989; 81:1917–21.
5. Isles CG, Hole DJ, Gillis CR, Hawthorne VM, Lever AF.Plasma cholesterol, coronary heart disease, and cancer inthe Renfrew and Paisley survey. BMJ 1989; 298:920–4.
6. Kreger BE, Anderson KM, Schatzkin A, Splansky GL. Serum cholesterol level, body mass index, and the risk of coloncancer. The Framingham Study. Cancer 1992; 70:1038–43.
7. Schuit AJ, Van Dijk CE, Dekker JM, Schouten EG, Kok FJ.Inverse association between serum total cholesterol andcancer mortality in Dutch civil servants. Am J Epidemiol1993; 137:966–76.
8. Chang AK, Barrett-Connor E, Edelstein S. Low plasma cholesterol predicts an increased risk of lung cancer in elderlywomen. Prev Med 1995; 24:557–62.
9. Steenland K, Nowlin S, Palu S. Cancer incidencein the National Health and Nutrition Survey I. Follow-updata: diabetes, cholesterol, pulse and physical activity.Cancer Epidemiol Biomarkers Prev 1995; 4:807–11
10: http://qjmed.oxfordjournals.org/content/early/2011/12/08/qjmed.hcr243.full.pdf?keytype=ref&ijkey=kZGZxqVjYWEOtoc
11: http://www.theheart.org/article/1375049.do?utm_campaign=newsletter&utm_medium=email&utm_source=20120325_ACC_dimanche_2
12: Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD,Cole TG, et al. Effect of pravastatin on cardiovascular eventsin women after myocardial infarction: the cholesterol and recurrent events (CARE) trial. N Engl J Med 1996;335:1001–9
13: Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM,Cobbe SM, et al. Pravastatin in elderly individuals at risk ofvascular disease (PROSPER): a randomised controlled trial.Lancet 2002; 360:1623–30.
14: . Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N,Oikawa S, et al. Japan Lipid Intervention Trial. Large scalecohort study of the relationship between serum cholesterol lconcentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia. Circ J 2002; 66:1087–95.
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