Folic acid supplements have no effect on cardiovascular disease events amongst people with existing vascular disease, says a meta-analysis of 12 randomised control trials.
However, the potentially more important question of whether increased folic acid/ folate intake could prevent the development of cardiovascular disease was not considered by the researchers behind the new study.
A range of studies has linked increased blood levels of the amino acid homocysteine to an increased risk of cardiovascular disease. It has been suggested that by lowering the levels of homocysteine in the blood with B-vitamins, people could cut the risk of CVD.
The meta-analysis, published in the high-profile Journal of the American Medical Association, included data for 16,958 participants from studies that compared folic acid supplementation with either placebo for a period of at least six months and a maximum follow-up of five years. Clinical cardiovascular disease events were reported as an end point.
The study focussed on people with pre-existing vascular disease.
The meta-analysis was warranted, said the researchers, because most of the trials did not have sufficient statistical power to fully elucidate a connection between folic acid and cardiovascular events, and many trials reported inconsistent findings.
"Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases among participants with prior history of vascular disease," wrote lead author Lydia Bazzano from Tulane University School of Public Health and Tropical Medicine, New Orleans.
When comparing folic acid supplementation groups and placebo the researchers reported that there was no significant difference between the groups for the number of events associated with CVD, CHD, stroke and all-cause mortality.
"The findings of this analysis suggest that folic acid supplementation is ineffective in the secondary prevention of CVD among persons with a history of vascular diseases. Therefore, it is important to focus on strategies of proven benefit in the secondary prevention of CVD, including smoking cessation, lipid reduction, treatment of hypertension and diabetes, maintenance of a healthy weight, and physical activity," the authors conclude.
While the results strengthen the notion that folic acid has no effect for people who have already developed some type of vascular disease, British experts claimed last month that there was sufficient evidence that folic acid could protect against heart disease in people with no CVD at baseline.
The authors of the British study, published in the British Medical Journal, acknowledged the null results from the various clinical trials, but stated: "If the only evidence available were the trial results, we would still be in the dark."
"Since folic acid reduces homocysteine concentrations, to an extent dependent on background folate levels, it follows that increasing folic acid consumption will reduce the risk of heart attack and stroke by an amount related to the homocysteine reduction achieved," wrote lead author David Wald in the BMJ.
Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence links has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.
This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.
Preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence. Parallel measures are being considered in some European countries; for instance, the UK this week moved into its final consultation stage, and expects to deliver advice to health ministers in May 2007. Source: Journal of the American Medical Association Volume 296, pages 2720-2726 "Effect of folic acid supplementation on risk of cardiovascular disease - A meta-analysis of randomised controlled trials"
Authors: L.A. Bazzano, K. Reynolds, K.N. Holder, J. He