A systematic analysis of 8 large trials concluded that use of folic acid supplements does not appear to be linked to reduced rates of cardiovascular events, despite having been shown to lower blood levels of homocysteine, an amino acid thought to be a risk factor for diseases of the heart and blood vessels.
You can read how Dr Robert Clarke of the University of Oxford in the UK, and colleagues in the B-Vitamin Treatment Trialists’ Collaboration arrived at this finding online in the 11 October 1 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Homocysteine is an amino acid created by the body, usually as a byproduct of digesting consumed meat.
The researchers wrote in their background information that studies of cardiovascular diseases in children with homocystinuria, a rare genetic disorder that results in extremely high levels of homocysteine in the blood, has led researchers to propose that high blood levels of the amino acid in the general population may have the same result, and to suggest it is a risk factor for coronary heart disease, stroke and other blocked blood vessel diseases.
In fact, trials with B vitamin supplements, and folic acid in particular, have resulted in lower blood homocysteine levels and reduced risk of cardiovascular disease risk among patients with homocystinuria, but several trials involving people without the condition have been inconclusive.
Thus the effects on cardiovascular disease in the general population of taking folic acid supplements to lower plasma homocysteine levels are somewhat uncertain, said the authors.
That is why in 2004, the investigators on 8 large trials decided to collaborate on conducting a meta-analysis “based on individual participant data from all large randomized trials of folic acid-based B-vitamin supplementation intended to lower plasma homocysteine levels for the prevention of cardiovascular disease,” they wrote.
For the study, Clarke and colleagues pooled the results of 8 large randomized, placebo-controlled trials of folic acid supplementation involving nearly 37,485 participants at increased risk of cardiovascular disease. The last trial completed in 2009.
Altogether, 18,723 of the participants were randomly assigned to take a daily dose of folic acid ranging from 0.8 milligrams per day to 40 milligrams, while the other 18,762 took placebo or an equivalently small dose of folic acid.
The trials lasted for a median of 5 years.
The results showed that:
- 9,326 participants had a major vascular event during the treatment period; 3,010 developed cancer; and 5,125 died.
- Overall, those in the active folic acid groups experienced an average 25 per cent reduction in homocysteine levels.
- Over a median follow-up of 5 years, there was little difference between the active folic acid and placebo participants’ rates of major vascular events (rate ratio RR was 1.01, with 95 per cent confidence interval CI ranging from 0.97 to 1.05).
- Similarly, there was little difference between active folic acid and placebo in the rates of major coronary events and stroke (RR 1.03, CI 0.97-1.10 for coronary; RR 0.96, CI 0.87-1.06 for stroke).
- There were also no significant differences between active folic acid and placebo for overall vascular mortality, overall cancer incidence, cancer mortality, or deaths from all causes, either during the whole scheduled treatment period or during the later period of it.