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Atherosclerosis and folic acid

AMSTERDAM, THE NETHERLANDS. A high blood level of homocysteine (a sulfur-containing amino acid derived from methionine) has been associated with the development of atherosclerosis. High homocysteine levels can be reduced by supplementation with folic acid; however, it is still uncertain whether this reduction actually lowers the risk of atherosclerosis. Now researchers at the University Hospital Vrije Universiteit report evidence that supplementation with folic acid and vitamin B6 is associated with a decreased occurrence of abnormal exercise electrocardiographs - important markers for atherosclerosis. The study involved 158 siblings of 167 patients with premature atherothrombotic disease. The study participants (siblings) had no signs of arterial disease when entering the study, but were obviously at greater risk of developing atherosclerosis than normal. The participants underwent a methionine-loading test at the start of the study and were subsequently divided into two groups. One group of 104 had high homocysteine levels after the methionine-loading test while the second group of 54 siblings had normal levels. Each group was subsequently randomized to receive either 5 mg folic acid plus 250 mg vitamin B6 daily for a two-year period while the other group received a placebo.

At the end of two years all participants had an electrocardiogram, an ultrasound measurement of the carotid and femoral arteries, and a determination of their ankle-brachial pressure index at rest and after exercise. As expected, the vitamin treatment was associated with a significant drop in both fasting homocysteine concentration and postmethionine homocysteine concentration. Blood plasma content of folic acid increased 13-fold and that of vitamin-B6 9- fold in the supplement group. There was no apparent effect of vitamin treatment on ankle-brachial pressure indices or ultrasound measurements; however, the incidence of new abnormal exercise electrocardiograms was much lower in the vitamin group (6 versus 14 in the placebo group). The researchers conclude that vitamin therapy lowers the risk of an abnormal exercise electrocardiogram by 60 per cent independent of other risk factors such as age, sex, baseline level of postmethionine homocysteine, cholesterol levels, smoking habits, and the presence of hypertension or diabetes. Although the trial involved participants at high risk for atherosclerosis the researchers see no reason why the results should not be applicable to healthy individuals.
Vermeulen, E.G.J., et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. The Lancet, Vol. 355, February 12, 2000, pp. 517-22

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