Low Cholesterol Levels Increase Mortality

Proponents of the cholesterol theory of cardiovascular disease claim that dietary cholesterol and saturated fat cause elevations in plasma cholesterol. This they claim is the cause of atherosclerosis which increases risk of cardiovascular disease. However, this line of reasoning is provably false, and the contention that dietary lipids can affect plasma cholesterol has fallen into disfavour within the nutritional sciences. Irrespective of the cause of elevated levels of plasma cholesterol, there is some evidence that they are associated with cardiovascular disease. However, confusion surrounds this association between plasma cholesterol levels and cardiovascular disease because it is often perceived as cause and effect when there is no evidence to determine the causative agent. In addition, the plasma lipoprotein biochemistry has been greatly oversimplified to allow the development of clinical testing, and this over simplification has created obfuscation with regard the roll played by cholesterol.

Originally research measured the total cholesterol carried in the plasma in order to determine cardiovascular risk. However, this is only very weakly associated with cardiovascular disease, which suggests that a confounding variable exists or that cholesterol is not associated with cardiovascular disease in some sub-groups of the population. Division of the total cholesterol into low density lipoprotein (LDL) and high density lipoprotein cholesterol (HDL) fractions improves the association because elevated HDL is not associated with cardiovascular disease. Low density lipoprotein carries cholesterol to the peripheral tissue for deposition, where it is suggested that it can accumulate in the endothelial lining of the arteries causing atherosclerosis. However, HDL carries cholesterol back to the liver where it is metabolised and excreted, and may actually be protective. Therefore the ratio of LDL to HDL may be a better cardiovascular disease risk predictor than total cholesterol.

The HDL to LDL ratio measurement is the basis of the test that is used today in the clinical setting. The medical establishment recommendation is therefore to reduce levels of LDL cholesterol to improve the ratio, which they attempt to do through use of pharmacological intervention using statin drugs. However, the HDL to LDL ratio is an oversimplified model that poorly reflects lipoprotein metabolism in humans. For example, another particle called lipoprotein(a) exists that is identical to the normal LDL particle but contains an extra protein fragment. Lipoprotein(a) is highly atherogenic and is not distinguished from LDL in clinical testing. In addition, LDL exists as both a small dense particle and a large buoyant particle, and only the former is associated with increase cardiovascular risk. Therefore the HDL to LDL measurement is of questionable use to accurately predict cardiovascular risk because it is oversimplified.

In addition, the use of cholesterol testing is problematic because certain sub-groups of the population actually have lower mortality with higher levels of plasma cholesterol, and very low levels of plasma cholesterol are known to increase total mortality.  The use of pharmaceutical drugs and sterol therapy to lower plasma concentrations might therefore be dangerous. This explains the increase in mortality seen in some trials investigating the effects of statin drugs. In such trials the statins appear to decrease mortality from cardiovascular events, but at the same time the fall in plasma cholesterol levels increase mortality from other causes such as suicide, accident and violence. The need of the brain for adequate cholesterol might explain the rise in these other causes of death. Some studies have investigated the effects of plasma cholesterol on total mortality, and confirmed that low levels of plasma cholesterol do increase mortality.

For example, research published in the British Medical Journal in 19801, investigated the association between plasma cholesterol and mortality in 630 New Zealand Maoris over the course of around 10 years. Plasma cholesterol levels were taken at baseline and after 11 years medical records were used to determine the cause of mortality in those that had died. Using survival analysis statistics, the researchers reported that cholesterol plasma levels were inversely associated with all cause mortality, including cardiovascular disease, cancer and other disease. The odds ratio of mortality between the low cholesterol group and the high cholesterol group was 2.3 and 1.9 for men and women, respectively. The risk ratio of total mortality at a serum cholesterol level of 4.14 mmol/L as compared to a serum concentration of 6.73 mmol/L was 1.7 and 1.4 for men and women, respectively.

This supports data from statin studies that show that lowering plasma cholesterol increases mortality from non-cardiovascular related causes significantly. Ironically, the data reported here is also supported by many of the studies used by some to argue that cholesterol is the causative factor in cardiovascular disease. For example, the Framingham study, one of the most referenced papers used to support the cholesterol theory of cardiovascular disease actually reported an increase in mortality with decreasing plasma levels of cholesterol in men. Lowering cholesterol with pharmaceuticals is therefore potentially dangerous. However, many of the proponents of the cholesterol theory of cardiovascular disease have become wealthy off testing, treating and researching cholesterol as a causative factor in atherosclerosis. The vested interest in this cholesterol industry will therefore defend their own position, so the emphasis is on the individual to educate themselves regarding these issues.

RdB

1Beaglehole, R., Foulkes, M A., Prior, I. A. M.  and Eyles, E. F 1980. Cholesterol and mortality in New Zealand Maoris. British Medical Journal. 280: 285-287

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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