Does Lowering Homocysteine Prevent Cardiovascular Disease?

Stephen Barrett, M.D.
June 26, 2010

In 1969, a connection between homocysteine (a sulfur-containing amino acid) and cardiovascular disease was proposed when it was observed that people with a rare hereditary condition called homocystinuria are prone to develop severe cardiovascular disease in their teens and twenties. In this condition, an enzyme deficiency causes homocysteine to accumulate in the blood and to be excreted in the urine. Abnormal homocysteine elevation also occurs among people whose diet contains inadequate amounts of folic acid, vitamin B6, or vitamin B12. Regardless of the cause of the elevation, supplementation with one or more of these vitamins can lower plasma homocysteine levels.

Studies done in the 1980s and 1990s linked elevated blood levels of homocysteine to increased risk of premature coronary artery disease, stroke, and venous blood clots, even among people with normal cholesterol levels [1-8]. These studies led to speculations that high homocysteine levels could contribute to atherosclerosis in at least three ways: (a) a direct toxic effect that damages the cells lining the inside of the arteries, (b) interference with clotting factors, and (c) oxidation of low-density lipoproteins (LDL). Lowering the serum concentration of homocysteine has been proven to reduce the risk of adverse cardiovascular events among people with homocystinuria. Without clinical trials, however, it was impossible to know whether abnormal homocysteine levels among the general population cause atherosclerosis or are merely a “marker”—a non-causative finding that often occurs in people with atherosclerosis.

Unfortunately, large controlled studies have found that treatment with B-vitamins does not reduce the incidence of cardiovascular events despite significant lowering of homocysteine levels [10-14]. In fact, a 7-year study of women with kidney disease secondary to diabetes found that those who took the B-vitamin supplemnent more heart attacks and strokes than those who did not [15].

Enough study has been done to conclude with reasonable certainty that taking B-vitamins to lower homocysteine levels will not lower the incidence or heart attacks or strokes except for people with homocystinurea. Nor is it advisable to do routine screening for homocysteine levels [16].

References
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  14. SEARCH Collaborative Group. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardialinfarction survivors: A randomized trial. JAMA 303:2486-2494, 2010.
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This article was revised on June 26, 2010.