Homocysteine, Folate Keys to Heart Disease?

LONDONAn academic team including epidemiologists and a cardiologist report a review of existing trials shows folic acid can lower the increased homocysteine levels associated with in increased risk of heart attack and stroke. Published in the Nov. 25 British Medical Journal (2006, 333:114-17), their findings represent a meta-analysis of cohort studies, past reviews and randomized, controlled trials (RCTs).

The cohort studies showed significant positive associations between serum homocysteine concentrations and ischemic heart disease eventsfatal and non-fatal myocardial infarction and sudden cardiac deathand stroke; just 0.8 mg/d folate can lower risk of heart attack by 15 percent and stroke by 24 percent.

Homocysteine levels can rise moderately (25-percent higher than normal) in cases of a mutation in the methylenetetrahydrofolate reductase (MTFR) gene, pushing risk of cardiac events up from 14 percent to 25 percent in groups not treated with folic acid. They noted publication bias was not likely to explain the conclusions of studies on this area of CVD.

As further evidence, in studies on people with homocystinuria, a metabolic disorder that can be caused by MTFR mutation and can result in abnormal homocysteine accumulation, risk of vascular events was 50 percent without folate intervention, but almost no vascular events were recorded after intervention. The reviewers noted despite the lack of randomized trials in this area, selection bias could not explain the results.

With the bulk of RCTs on homocysteine, folate and heart disease still underway, the researchers reported folate intervention is expected to reduce cardiovascular disease (CVD) events by only about 10 percent to 15 percent. They stated most RCTs on the subject lack statistical power, and reports from individual studies tend to inappropriately interpret non-significant effects as evidence of no effect. They added the results are unfortunately consistent with not only both a 12-percent reduction in heart attacks and a 22-percent reduction in stroke, but also with no reduction at all.

They concluded homocysteine is a cause of CVD explains the observations from all the different types of study, even if the results from one type of study are, on their own, insufficient to reach that conclusion. Thus, increasing folic acid consumption will reduce the risk of heart attack and stroke by an amount related to the homocysteine reduction achieved. They reasoned the evidence is now sufficient to justify action on lowering homocysteine concentrations, although the position should be reviewed as evidence from ongoing clinical trials emerges.