Homocysteine, a cardiovascular disease risk factor? and which vitamins may help

Homocysteine, an essential amino acid necessary for protein synthesis and normal growth, has been implicated in a number of conditions, including alzheimer's disease and neural tube defects. However, it is the role that homocysteine plays in causing cardiovascular disease that has received the most attention.

High plasma homocysteine levels has long been suspected of causing increased risk to the development of coronary heart disease, ever since the observation that vitamin B6 depletion causes atherosclerosis and that the metabolism of homocysteine is blocked by deprivation of vitamin B6 leading to build up of high homocysteine levels.

The strength of evidence in favour of an important role of homocysteine in cardiovascular disease is growing. In the third National Health and Nutrition Examination Survey conducted in the US (Dec., 2000), researchers looked at the total serum homocysteine levels and the reported occurrence of heart attack or stroke.

The study excluded subjects with diabetes or those taking vitamin or mineral supplements, and found that past events were reported about 2.5 times more often by subjects with homocysteine levels greater than 12 micromol/L than those with lower homocysteine levels. These finding are consistent with a number of other finding for an association between homocysteine levels and cardiovascular disease. Although, there are some studies that do not provide evidence for a strong association. For example, a large follow-up study in Wales, U.K. , of men who developed coronary heart disease, could not find sufficient evidence for linking homocysteine as an independent risk factor for coronary heart disease. The researchers concluded that carefully controlled studies of the effects of homocysteine lowering treatments with , for example, folic acid are required to test the association between homocysteine and coronary heart disease. This brings us to the next area of discussion, which vitamins lower homocysteine levels.

A number of finding, including recent studies, suggest that vitamins B6, B12 and folate in particular do indeed lower homocysteine levels. These vitamins are involved in the metabolism of homocysteine. One example of a study that looked at vitamin intakes, found that in a group of over 300 men with atherosclerosis, taking vitamin supplements, the homocysteine levels were lower by 1.5 micromol/L than by non-vitamin takers. In another study , with younger and older women , low folate intakes were associated with high homocysteine levels and visa versa. Such findings are becoming fairly common-place.

There can be little doubt that vitamins B6, B12 and folate lowers homocysteine levels. However, can taking these vitamins protect against heart disease. A recent study that addressed this question showed that persons with lower folate levels had twice the risk of cardiovascular disease mortality than those with higher levels , which was not dependent on age or sex. It appears that the only uncertainty remaining is the strength of the causal relationship with cardiovascular disease. In other words, is it at least as important a risk factor as high cholesterol or only marginally important? One person that thinks it is more important than cholesterol in this regard is Kilmer McCully, MD, the person responsible for the initial discoveries. You can read a revealing transcript of an interview here with Dr. Mc Cully.


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Studies referred to in this article:
Arch Intern Med 2000 Nov 27;160(21):3258-62 Serum folate and cardiovascular disease mortality among US men and women.

Am J Clin Nutr 2000 Nov;72(5):1156-63 Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women.

J Nutr 2000 Dec;130(12):3073-6 Serum total homocysteine concentration is related to self-reported heart attack or stroke history among men and women in the NHANES III.

Heart 2001 Feb;85(2):153-8 Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up.

Ann Epidemiol 1997 May;7(4):285-93 Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults.

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