In the Forum
Low Dose Folic Acid for Homocysteine Reduction
Volume: 10 (22/10/2005)
Since cardiovascular disease was associated with high levels of homocysteine in the blood, numerous studies have concentrated on the homocysteine-lowering compounds. Folic acid was found to have a significant homocysteine-lowering effect, but then the question became "what dose of folic acid is necessary for a substantial reduction in homocysteine?"
The Homocysteine Lowering Trialists' Collaboration established, by meta-analyses, the homocysteine reduction achieved with different doses of folic acid. A first meta-analysis concluded that the homocysteine-lowering effect was comparable for doses of 0.5-1 mg/d, 1-3 mg/d, and doses higher than 3mg/d. The new meta-analysis compared doses of folic acid (0.2 mg/d vs. 0.4
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mg/d, 0.4 vs. 0.8) and reached the conclusion that there were no differences between 0.8 mg/d and the higher doses. The maximum reduction in plasma homocysteine was observed precisely with 0.8 g/d of folic acid.
A very important finding is that the response to 0.4 mg/d of folic acid is 90% of the maximum response, because 0.4mg/d is the amount usually included in multivitamin supplements.
Both meta-analyses have shown that the homocysteine-lowering effect is 7% greater when vitamin B12 is added to folic acid. However, no such effect was noted when vitamin B6 was added.
A finding that requires further study is that women are more responsive than men to the homocysteine-lowering effects of folic acid. It was previously suggested that sex modifies the relationship between homocysteine and cardiovascular disease as a matter of fact.
Scientists have also tried to find whether the reductions in homocysteine levels are sufficient to cause a reduction in the incidence of cardiovascular disease. Two other recent meta-analyses found that a 25% homocysteine reduction, the equivalent of the reduction effect produced by 0.8 mg/d of folic acid in the Homocysteine Lowering Trialists' Collaboration, was associated with a 11-16% decrease in the risk of ischemic heart disease and with a 19-22% reduction in the risk of stroke.
It is important to note though, that the results of these European meta-analyses are not applicable to studies performed in the United States and Canada, where the folic acid fortification of food has already caused a significant decrease in homocysteine concentrations.
A very important finding is that the response to 0.4 mg/d of folic acid is 90% of the maximum response, because 0.4mg/d is the amount usually included in multivitamin supplements.
Both meta-analyses have shown that the homocysteine-lowering effect is 7% greater when vitamin B12 is added to folic acid. However, no such effect was noted when vitamin B6 was added.
A finding that requires further study is that women are more responsive than men to the homocysteine-lowering effects of folic acid. It was previously suggested that sex modifies the relationship between homocysteine and cardiovascular disease as a matter of fact.
Scientists have also tried to find whether the reductions in homocysteine levels are sufficient to cause a reduction in the incidence of cardiovascular disease. Two other recent meta-analyses found that a 25% homocysteine reduction, the equivalent of the reduction effect produced by 0.8 mg/d of folic acid in the Homocysteine Lowering Trialists' Collaboration, was associated with a 11-16% decrease in the risk of ischemic heart disease and with a 19-22% reduction in the risk of stroke.
It is important to note though, that the results of these European meta-analyses are not applicable to studies performed in the United States and Canada, where the folic acid fortification of food has already caused a significant decrease in homocysteine concentrations.
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