Supplements Provide No CVD Benefit in SEARCH Study

Patients who had experienced a heart attack and lowered their blood homocysteine levels with folic acid and vitamin B12 supplementation did not have an associated lower risk of heart attack, coronary death, or stroke, according to a study in The Journal of the American Medical Association. However, the researchers did find that folic acid supplementation did not increase the risk of cancer, which has been speculated.

Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal, according to background information in the article. A meta-analysis of prospective studies indicated that, after adjustment for known risk factors, a 25%-lower-than-usual homocysteine concentration was associated with an 11% lower risk of coronary heart disease and a 19% lower risk of stroke. “Daily supplementation with folic acid typically lowers homocysteine levels by about 25 percent, and the addition of vitamin B12 lowers it by a further 7 percent,” the authors wrote.

Jane M. Armitage, FRCP, of the University of Oxford in the United Kingdom, and colleagues with the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial assessed the effects of lowering homocysteine levels with folic acid plus vitamin B12 in 12,064 survivors of myocardial infarction in secondary-care hospitals in the United Kingdom between 1998 and 2008. Patients were randomized to receive either 2 mg of folic acid plus 1 mg of vitamin B12 daily or matching placebos. The primary outcomes measured included first major vascular event, defined as major coronary event (coronary death, heart attack, or coronary revascularization); fatal or nonfatal stroke; or noncoronary revascularization.

Patients who received the study vitamins reduced homocysteine by an average of 3.8 µmol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1,537 of 6,033 participants (25.5%) allocated folic acid plus vitamin B12 vs. 1,493 of 6,031 participants (24.8%) allocated placebo. “There was no evidence of any benefit beginning to emerge with more prolonged treatment and follow-up,” the authors wrote.

Receiving study vitamins also was not associated with a significant effect on any stroke (vitamins, 4.5% vs. placebo, 4.4%), noncoronary revascularizations (vitamins, 3% vs. placebo, 2.5%), or major coronary events (vitamins, 20.4% vs. placebo, 19.6%). There were no apparent differences in the numbers of deaths attributed to vascular causes or nonvascular causes.

New primary cancers (excluding nonmelanoma skin cancer) were diagnosed in 11.2% of the participants allocated folic acid plus vitamin B12 vs. 10.6% allocated placebo, with this difference not being significant.

“Taken together with the previous homocysteine-lowering trials, the results of SEARCH indicate that folic acid supplementation has no significant adverse effects on cancer or other major health outcomes, even if it also produces no beneficial effects on cardiovascular disease. In addition, these results highlight the importance of focusing on drug treatments (eg, aspirin, statins, and antihypertensive therapy) and lifestyle changes (in particular, stopping smoking and avoiding excessive weight gain) that are of proven benefit, rather than lowering homocysteine with folic acid-based vitamin supplements, for the prevention of cardiovascular disease,” the authors conclude.

Source: American Medical Association