How Much Folic Acid Is Enough?

Summarized by Robert W. Griffith, MD
January 2, 2006

Introduction

Raised blood homocysteine levels are linked to an increased risk of cardiovascular disease, and folic acid taken by mouth lowers homocysteine levels. So it's natural to ask: "How much folic acid should I take?" A collaborative analysis of published studies to determine this was undertaken 6 years ago; the results were not conclusive. However, a second analysis by the same investigators has now been published¹ and is the subject of a review in the American Journal of Clinical Nutrition.

The 1998 Analysis

The first analysis showed that the dose of folic acid had little effect. A 25% lowering of homocysteine levels was achieved with doses grouped into three classes - 0.5 to 1.0 mg/day, 1 to 3 mg/day, and over 3 mg/day.

The 2005 Analysis

This new meta-analysis found that there was indeed dose-dependence for lower folic acid doses. At the lowest dose (0.2 mg/day) there was some decrease in homocysteine levels, which was greater with 0.4 mg/day and still greater with 0.8 mg/day. But there was no improvement in homocysteine-lowering effect with doses above 0.8 mg/day, and the maximum reduction achieved (with 0.8 mg/day and above) was only 23%.

Most multivitamin supplements contain 0.4 mg, which, as a daily dose, achieved 90% of the benefit shown by 0.8 mg/day or more.

Regional Differences

Cereals and breads are routinely fortified with folic acid in North America, and this procedure results in considerably higher blood folate levels and lower homocysteine levels, compared with European values. Adding 0.8 mg/day in North America is, therefore, much less effective in lowering blood homocysteine.

Adding Vitamin B-12

Both the1998 and 2005 analyses showed that adding vitamin B-12 to oral folic acid results in a 7% greater decrease in homocysteine levels. (Adding vitamin B-6 has no such effect.) A clinical study has demonstrated that the frequency of high homocysteine levels in older people fell from 13% to 3% when they were given a supplement containing 0.44 mg folic acid, 0.048 mg vitamin B-12, and 1.8 mg vitamin B-6. This suggests that future food fortification programs should include vitamin B-12 along with folic acid, especially those in countries where low blood vitamin B-12 levels are common.

Gender Differences?

The recent analysis showed that women are more responsive than men to the homocysteine-lowering effects of folic acid. And women have a stronger link between homocysteine levels and cardiovascular disease than men do, according to earlier studies. So evaluation of homocysteine levels and possible additional folic acid-vitamin B-12 supplementation may be more useful in women than in men.

Is a 25% Reduction in Homocysteine Worthwhile?

Two recent studies have shown that a 25% reduction in homocysteine level (i.e. down to about 3 micromol/L) is associated with an 11% to 16% reduction in the risk of coronary heart disease, and a 19% to 22% reduction in the risk of stroke. As we have seen, this effect could be produced by a dose of 0.8 mg/day of oral folic acid.

Should Everyone Take Folic Acid (and Vitamin B-12)?

The answer to this may well be: "It depends where you live". People living in countries where cereals and other foods are fortified with folic acid and vitamin B-12 will get little benefit from additional supplements of these substances, unless they are shown to have clear-cut homocysteine overload. People in countries where there is no such fortification will benefit considerably more from folic acid supplements. They should be advised of the benefits of taking 0.4 or (better) 0.8 mg of folic acid daily. Ongoing studies in different countries should reveal the closer link between folic acid intake and less heart attacks and strokes.

Source

• Do low doses of folic acid result in maximum lowering of homocysteine? L. Bailey, Editorial. Am J Clin Nutr, 2005, vol. 82, pp. 717--718

Footnotes
1. Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of randomized trials. Am J Clin Nutr 2005;82:806-812

Related Links
Folate Part of a Heart Healthy Diet
Folate May Lower Stroke Risk
Amino-Acid Tied to Alzheimer's Risk

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