A close look at folate and homocysteine

Scientists believe that an elevated serum level of the amino acid by-product homocysteine is a marker for increased risk of ischemic heart disease. They've also noted an inverse association between serum folate and homocycteine levels. What is still under investigation, though, is how much folic acid-the form of the vitamin used in supplements-is needed to produce this homocysteine-lowering effect, an issue covered in a recent number of Archives of Internal Medicine.

Supplements show a significant effect

British researchers randomly divided 151 adults with ischemic heart disease to one of six treatment groups: supplemental folic acid at doses of 0.2, 0.4, 0.6, 0.8. or 1 mg per day or placebo. Fasting blood samples of folate and homocysteine were taken at the start and end of the 3-month trial period, as well as 3 months after the supplements were discontinued.

The researchers found a dose-dependent decrease in serum homocysteine levels up to a dose of 0.8 mg folic acid/day, with no additional decrease in serum homocysteine noted at the 1 mg/day intake level. Patients with the highest initial serum homocysteine levels saw the greatest reductions in response to folic acid supplementation; in fact a supplemental dose of 0.4 mg/day was enough to provide maximum homocysteine-lowering benefit in this highest risk group.

Blood tests done 3 months after the trial ended revealed that folic acid concentrations, for all but those at the 0.2 mg dose, did not return to pre-trial levels. Homocysteine levels, on the other hand, did return to near starting levels, with little evidence of a residual effect of 3 months of folic acid supplementation. This suggests that folic acid intake must be constant in order to have a lasting effect on homocysteine levels.

Study recommendations

The authors of this study believe that a nation-wide food fortification program, similar to the grain food fortification program in place in the US, is the best way to increase the folic acid intake of the general population.

But even a steady diet of folic acid-fortified foods, say the scientists, provides too little folic acid to offer maximum homocyteine-lowering benefits to those at high risk for ischemic heart disease. They believe that these patients would benefit from a daily supplemental dose of 0.8 mg of folic acid. This is several times the intake levels currently recommended in the US and the UK.

This recommendation, however, could resolve one problem only to create another. One argument against folic acid fortification of foods is that extended exposure to high amounts of folic acid may mask the symptoms of B12 deficiency, a potentially serious problem for older individuals. This is an issue that clearly needs more study. Pending further analyses, neither US nor UK heath guidelines currently advocate the prophylactic use of folic acid supplements to reduce the risk of heart disease.