A lthough folic acid supplementation has proven benefts- most notably, preventing birth defects-hopes it might protect against cardiovascular disease and cancer were disappointed by a major new meta-analysis.
Folic acid seemed especially promising for cardiovas- cular protection because it lowers levels of an amino acid, homocysteine, associated with greater risk of heart disease and stroke. And, indeed, the supplements (ranging from 0.8 milligrams/day to 5 milligrams/day, often in combination with vitamins B6 and B12) did succeed in bringing down homocys- teine levels by an average 25%. But that didnt translate into clinical benefts, the review concluded.
Robert Clarke, MD, of Oxford University in England, and colleagues analyzed eight randomized trials of folic-acid supplementation totaling 37,485 patients, average age 65, who suffered various underlying conditions including heart disease, diabetes, prior stroke and kidney disease. Two-thirds were men.
Across all eight trials, among patients randomly assigned to folic-acid supplements, 24.9% suffered a major vascular event and 11.4% experienced a major coronary event. Those rates were almost identical to the results for those getting a placebo instead (24.8% and 11.1%, respectively). No signifcant differences were seen for other outcomes including stroke, artery revascularization and coronary revasculariza- tion. Even in trials with the largest homocysteine reductions and those with the longest durations, the folic-acid groups showed no signifcant beneft.
Dr. Clarke and colleagues also looked at cancer risk in seven trials totaling 35,603 participants. Overall cancer incidence among those assigned to folic-acid supplements was essentially the same as those getting placebos-8.7% versus 8.2%.
In a commentary that accompanied the fndings in Archives of Internal Medicine, Jeffrey A. Tice, MD, of the University of California-San Francisco wrote, This is a cau- tionary tale for all who are searching for therapies to prevent disease in the general population. He added, We should recommend therapies to prevent disease in healthy patients only when randomized trials unequivocally demonstrate that net benefts outweigh net harms, and we should continue to emphasize the importance of a nutritious diet, regular physi- cal activity, and no smoking as the best ways to optimize health.
The one positive note from the meta-analysis is that it may help assuage concerns that folic-acid fortifcation of food, designed to prevent spina bifda and other neural-tube birth defects, might somehow prove harmful to the general population. Since 1998, grain products in the US and Canada have been fortifed with folic acid, which is the synthetic form of folate.
Dr. Clarke and colleagues noted, Although the lack of any other benefts is disappointing (albeit fairly defnitive), the lack of any signifcant adverse effects on vascular events, cancer incidence, cancer mortality and overall mortality provides reassurance about the safety of population-wide folic-acid fortifcation. Archives of Internal Medicine, Oct. 11, 2010; abstract at <archinte.ama-assn.org/cgi/content/abstract/170/18/1622>