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Homocysteine-Lowering with B Vitamins: No Benefit

Vitamin B supplementation did not improve outcomes among patients at high risk for vascular events.

Blood homocysteine levels are associated with increased cardiovascular risk, and intake of several B vitamins lowers homocysteine levels. Thus, we can logically ask whether vitamin B supplements reduce risk for adverse cardiovascular events. In two new studies, researchers address this question.

An international randomized trial involved 5522 patients with histories of documented vascular disease (coronary, cerebrovascular, or peripheral) or with diabetes plus another risk factor. Patients received either a combination pill (containing folic acid [2.5 mg], vitamin B₆ [50 mg], and vitamin B₁₂ [1 mg]) or placebo daily. After 5 years, mean homocysteine levels were about 25% lower in the vitamin group than in the placebo group. However, no significant difference was found between groups in the primary endpoint of myocardial infarction, stroke, or cardiovascular death (18.8% vs. 19.8%; P=0.41) or in various secondary outcomes. Importantly, vitamin B supplementation did not benefit patients with the highest baseline homocysteine levels or patients from countries without mandatory folate fortification of food.

In a secondary prevention randomized trial from Norway, 3749 patients with MI during the preceding 7 days received vitamin B supplements or placebo. During an average follow-up of 3 years, vitamin supplementation conferred no benefit for any clinical outcome.

Comment: These studies join several previously published trials in showing that vitamin B supplementation does not improve outcomes among patients at high risk for vascular events who have relatively normal baseline homocysteine levels (Journal Watch Feb 17 2004 and Journal Watch Aug 15 2003). An editorialist concludes firmly that supplemental folic acid and vitamins B₆ and B₁₂ are not beneficial for patients with established vascular disease. What remains unclear is whether homocysteine is merely a marker for other atherogenic factors or whether adverse effects of the vitamins themselves offset the theoretical benefits of homocysteine-lowering. Finally, it remains possible that B vitamins confer cardiovascular benefit in the unusual patient with extremely elevated homocysteine levels.

— Allan S. Brett, MD

Published in Journal Watch General Medicine March 28, 2006

Citation(s):

The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006 Apr 13; 354:1567-77. (http://dx.doi.org/10.1056/NEJMoa060900)

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Bønaa KH et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006 Apr 13; 354:1578-88. (http://dx.doi.org/10.1056/NEJMoa055227)

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• Medline abstract (Free)

Loscalzo J. Homocysteine trials — Clear outcomes for complex reasons. N Engl J Med 2006 Apr 13; 354:1629-32. (http://dx.doi.org/10.1056/NEJMe068060)

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• Medline abstract (Free)