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Low cholesterol increases cancer risk
Introduction
Countries with diets high in saturated fats tend to have high levels of colon cancer.
In 1974 a review of the Framingham data and those from Keys' 'Seven Countries' study was expected to show that the cancer could also be blamed on high blood cholesterol. However, the baffled researchers found the opposite; those with cancer had cholesterol levels which were lower than average.
In 1989, the Renfrew and Paisley Survey, which was studying the lowering of cholesterol levels to prevent heart disease, found that cases of cancer rose as cholesterol levels fell, such that any reduction in heart deaths was more than offset by an increase in cancers, mainly lung cancer.[1]
This was also the case in the World Health Organisation's Cooperative Trial of the cholesterol-lowering drug, clofibrate, which was published in the same year.
We should remember that cholesterol is a vital building block in cell membranes; it is essential for their integrity and stability. It is not, as seems to be suggested, an alien substance that must be reduced at all costs. Professor Michael Oliver pointed to the part that cholesterol played in the integrity of body cell membranes, saying:
'Normal cell activity depends . . . on membrane function and permeability. This is partly dependent on the balance . . . between cholesterol and saturated and polyunsaturated fatty acids. The possibility that normal membrane function is impaired when there is a disproportionate decrease in cholesterol, with resulting loss of resistance to cancerous change, has to remain on the agenda of the risk/benefits of lowering plasma cholesterol.'[2]
Studies confirm the cancer link with low cholesterol
Many epidemiological studies have shown consistently that cancer deaths rise in number as blood cholesterol levels fall.
A German study conducted at the Medizinische Universitätsklinik II, Tübingen, investigated blood cholesterol values at the time of diagnosis in patients with Hodgkin's lymphoma and found that they were significantly lower in these patients than in age- and sex-matched people without the disease. They also noted that patients with normal cholesterol values had a five-year survival rate which was two-and-a-half times higher than in patients with low blood cholesterol.[3]
Another study published in 1990 showed that colon cancer was preceded over a 10-year period by a fall in blood cholesterol levels. That doesn't mean the lower cholesterol caused the cancer; there are three possibilities:
- that the drop in cholesterol caused the cancers,
- that the drop in cholesterol was a result of the cancers
- or that the fall in cholesterol and the appearance of cancer at that time was merely a coincidence.
The scientists looked meticulously at these three possibilities and were able to rule two of them out: falling cholesterol they determined was the culprit.[4]
The figures are the interesting aspect of this study because the average level at diagnosis of cancer was 5.56 mmol/L (214 mg/dL), yet doctors are trying still to reduce population levels to below 5.0 mmol/L (192 mg/dL). Interestingly, this study also specifically attributed the cancers to low levels of LDL, which reinforces other evidence that the so-called 'bad' cholesterol is not bad after all.
Other cancers
Other cancers linked to low cholesterol levels include squamous cell and small cell lung cancers,[5] liver cancer,[6] multiple myeloma,[7] adrenal cancer,[8] blood cancers including lymphoma, acute leukaemia, chronic myeloid leukaemia, chronic myelomonocytic leukaemia, policytemia vera, myeloma, chronic lymphoid leukaemia,[9] hairy cell leukemia,[10] brain cancers,[11] and gastrointestinal cancers.[12]
What is a dangerously low cholesterol level?
So what is a dangerously low cholesterol level? Well, it's almost certainly higher than you think.
Scientists at the Department of Clinical and Experimental Medicine, University of Padua, Italy, analysed cancer deaths in 3282 elderly men and women aged 65 years or over taking part in the 12-year CASTEL (CArdiovascular STudy in the ELderly).[13] The study's analysis showed clearly an increase in cancers in people 'with very low cholesterol'.
'Very low' was defined as a level below 4.63 mmol/L (178 mg/dL). This level is similar to that found in a study of middle-aged men published four years earlier in which 'Serum cholesterol concentrations below 4.8 mmol/l [185mg/dL] were associated with the highest all cause mortality. . .'[14]
Incidentally, CASTEL showed that men whose Body Mass Index was 22.7 or lower — 22.7 is right in the middle of the 'healthy' weight range — also had an increased cancer risk.
Cholesterol-lowering drugs
Not surprisingly, there have been several reviews of the cholesterol-cancer connection.
This is of greater concern in cases where cholesterol has been lowered artificially with drug treatment as, in an increasingly litigious society, the person administering the drugs could be blamed and sued for causing the cancer.
Drs T.B. Newman and S.B. Hulley of the School of Medicine, University of California, San Francisco, reviewed the findings and implications of studies of cancer and cholesterol-lowering drugs in trials involving both rodents and humans, and list the drugs and types of tumour found. They note in their review that 'all members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed for humans.'
But they add that 'Evidence of carcinogenicity [cancer-causing properties] of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow up.'[15] Because the evidence here is sketchy, Newman and Hulley conclude that longer term surveillance needs to be carried out over the next few decades; in the meantime:
'the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.'You might like to consider this: while this surveillance is conducted, anyone taking cholesterol-lowering drugs is effectively being used as a guinea pig in an uncontrolled trial in which a likely outcome is an increased risk of cancer.
References
1. Isles CG, Hole DJ, Gillis CR, et al. Plasma cholesterol, coronary heart disease, and cancer in the Renfrew and Paisley survey. BMJ 1989; 298: 920-924
2. Oliver MF. Low cholesterol and increased risk. Lancet 1989; ii: 163.
3. Muller CP, Trilling B, Steinke B. The prognostic significance of total serum cholesterol in patients with Hodgkin's disease. Cancer 1992; 69: 1042-6.
4. Winawer SJ, Flehinger BJ, Buchalter J, et al. Declining Serum Cholesterol Prior to Diagnosis of Colon Cancer. JAMA 1990; 263: 2083-5
5. Siemianowicz K, Gminski J, Stajszczyk M, et al. Serum total cholesterol and triglycerides levels in patients with lung cancer. Int J Mol Med. 2000; 5: 201-5
6. Okamura T, Kadowaki T, Hayakawa T, et al. What cause of mortality can we predict by cholesterol screening in the Japanese general population? J Intern Med 2003; 253: 169-80.
7. Scolozzi R, Boccafogli A, Salmi R, et al. Hypocholesterolemia in multiple myeloma. Inverse relation to the component M and the clinical stage. Minerva Med 1983; 74: 2359-64.
8. Nakagawa T, Ueyama Y, Nozaki S, et al. Marked hypocholesterolemia in a case with adrenal adenoma-enhanced catabolism of low density lipoprotein (LDL) via the LDL receptors of tumor cells. J Clin Endocrinol Metab 1995; 80: 3391-2.
9. Aixala M, Sarandria CN, Speroni JG. Hypocholesterolemia in hematologic neoplasms. Sangre (Barc) 1997; 42: 7-10.
10. Pandolfino J, Hakimian D, Rademaker AW, Tallman MS. Hypocholesterolemia in hairy cell leukemia: a marker for proliferative activity. Am J Hematol 1997; 55:129-33.
11. Grieb P, Ryba MS, Jagielski J, et al. Serum cholesterol in cerebral malignancies. J Neurooncol 1999; 41:175-80.
12. Tomiki Y, Suda S, Tanaka M, et al. Reduced low-density-lipoprotein cholesterol causing low serum cholesterol levels in gastrointestinal cancer: a case control study. J Exp Clin Cancer Res 2004; 23: 233-40.
13. Mazza A, Casiglia E, Scarpa R, et al. Predictors of cancer mortality in elderly subjects. Eur J Epidemiol 1999; 15: 421-7.
14. Wannamethee G, Shaper AG, Whincup PH, Walker M. Low serum total cholesterol concentrations and mortality in middle aged British men. BMJ 1995;311: 409-13
15. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA 1996; 275: 55-60.
Last updated 1 December 2011
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