Preventing Heart Disease with Folic Acid — How Much Is Enough?
By Steve Austin, ND

Healthnotes Newswire —Many cardiologists and researchers believe that lowering homocysteine, a piece of protein manufactured within the body, will reduce the risk of heart disease. And while folic acid is the most important vitamin needed by the body to convert homocysteine into other substances, the optimal dose of folic acid has been unknown. But, according to the findings of a double-blind trial from England, published in the current issue of Archives of Internal Medicine,1 that optimal dosage is 800 micrograms of supplemental folic acid per day. The other nutrients required to convert homocysteine into harmless substances—vitamins B6 and B12—were not used in the current trial. The effects might well have been greater if they had been. Until the publication of this report, evidence suggested that the optimal amount was at or below 1,000 mcg per day.

In the new trial, 151 adults with a history of heart disease were given 200, 400, 600, 800, or 1,000 mcg of folic acid or placebo per day for three months. Homocysteine levels were measured at the beginning of the trial, immediately following three months of supplementation, and three months after supplementation was discontinued. At the end of the supplement period, homocysteine levels had fallen in all groups receiving folic acid. The decrease was proportionate to the dose of folic acid up to—but not beyond—800 mcg per day. The group receiving the 800-mcg dose experienced a 23% greater drop in homocysteine than that observed in the placebo group.

More is Not Always Better

The fact that a higher dose of folic acid was not more effective than the 800-mcg level of supplementation dovetails with the findings of an analysis of previous trials. In that analysis, much higher doses of folic acid—up to 5,000 mcg per day—produced approximately the same drop in homocysteine as that just reported in people given 800 mcg or more in the new report.2 The findings of that analysis reveal that taking 5,000 mcg per day of folic acid is no more effective than using 1,000 mcg per day. The effect of doses less than 1,000 mcg per day was not considered in that analysis of previous trials.

If 5,000 mcg produces no better effect than does 1,000 mcg, the question then becomes, how much less than 1,000 mcg of folic acid per day could still achieve the maximum possible reduction in homocysteine levels? The data from the new report strongly suggest that the amount of folic acid supplementation needed to optimally reduce homocysteine levels is approximately 800 mcg per day.

How Much Folic Acid Should Americans Take?

The American food supply is fortified with 140 mcg of folic acid per 100 grams (approximately three and a half ounces) of flour, as mandated by the U.S. Food and Drug Administration (FDA). At this level of fortification, the average person receives approximately 100 mcg of folic acid per day beyond the level found naturally in the diet. Aside from the 100-mcg amount that results from food fortification, Americans consume approximately the same amount of natural folates from food as do the English. As a result, the findings of the current report suggest that Americans would benefit optimally from supplementation with 700 mcg per day of folic acid, or 100 mcg per day less than the optimal English level of supplementation. The authors of the new report acknowledge, “Current U.S. food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.”

According to the findings of a previous report published in the Archives of Internal Medicine,3 the 23% drop in homocysteine levels reported in the current trial is likely to lead to an approximate 15% decrease in the incidence of heart disease. As a result, the authors of the new report conclude, “It would be reasonable for clinicians to consider advising patients with ischemic heart disease to take 0.8 mg [800 mcg] of folic acid each day.” However, as this level of folic acid supplementation costs only a few cents per day and would be accompanied by virtually no toxicity, and as heart disease is the leading cause of death in the United States, these findings suggest that most people should be supplementing with folic acid in addition to the folic acid they receive as a result of the FDA fortification program. Moreover, these findings suggest that the amount of folic acid found in a one-day supply of many B-complex vitamins and multivitamins—400 mcg—is not high enough to provide maximum protection against heart disease.

In the new report, three months after folic acid supplementation ceased, homocysteine levels had rebounded to approximately the same levels observed before supplementation had begun, suggesting that folic acid supplementation needs to be ongoing in order to continually control blood levels of homocysteine.

Why Not Give Folic Acid to Only Those Who Need It?

The current trial reported that homocysteine readings varied greatly over time within the same person, suggesting that measurement of homocysteine in one individual can often be inaccurate. As a result, measuring homocysteine only once or twice would not necessarily provide accurate information about whose level will need to be lowered.

So far, research findings have suggested that the lower the level of homocysteine, the lower the risk of heart disease. The current report found that even people with relatively low levels of homocysteine responded somewhat to folic acid. These findings suggest that most people are likely to reduce their risk of heart disease by supplementation with higher levels of folic acid than those found in many supplements.

For previous reports on folic acid supplementation and homocysteine levels, click on the following:

FDA Attempt at Restricting Folic Acid Labeling Ruled Unconstitutional

1. Wald DS, Bishop L, Wald NJ, et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med 2001;161:695–700.
2. Homocysteine Lower Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ 1998;316:894–8.
3. Wald NJ, Watt HC, Law MR, et al. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med 1998;158:862–7.

Steve Austin, ND, is the Chief Science Officer for Healthnotes, Inc. He is a former Professor of Nutrition at the National College of Naturopathic Medicine in Portland, Oregon. Dr. Austin has also headed the nutrition department at Bastyr University.