Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study . Am J Clin Nutr 2003;77:658–62.
For a decade, many countries have fortified food with folic acid because of its importance for pregnant women and cardiovascular disease prevention through reducing cellular and blood homocysteine. This supplementation can mask vitamin B12 deficiency. The researchers argue that folate is safer because its effect on B12 deficiency symptoms is minor.
Folate activity in cells depends on a methyl molecule donated by cobalamin (B12), so their activities are interdependent. Widespread folic acid fortification may cause B12 deficiencies. Folic acid acts differently from folate: it is inactive in the body and, after intestinal absorption, must be adapted by the liver for activity within cells. The claim that folic acid is preferable to natural folate was examined in the following study.
A randomized placebo-controlled study published in The American Journal of Clinical Nutrition examined folate versus folic acid effects on homocysteine in 167 healthy participants over 24 weeks.
Participants were divided into three groups: A (52) received 100 μg folic acid, B (35) received 113 μg folate, and C (50) received placebo as controls.
Blood homocysteine was measured at weeks 8, 16 and 24.
Study results:
Homocysteine decreased in the supplemented groups compared with placebo: by 14.6% with folate and 9.3% with folic acid.
Serum folate increased by 34% and folic acid by 52% compared with baseline. In red blood cells, increases were 23% in the folate group and 31% in the folic acid group.
Researchers’ conclusion:
Low-dose folate is as effective as synthetic folic acid in reducing homocysteine and maintaining normal blood folate.
The findings refute earlier claims. First, folate’s intestinal absorption and bioavailability are similar to those of synthetic folic acid. Folate floods the blood and cells less than folic acid, giving it a more moderate action.
Folate reduced homocysteine more effectively than folic acid. It does not flood the blood and cells, so its activity requires less B12. The reduction in homocysteine, which requires both folate and B12, is evidence of this. Folic acid use depletes body B12, leading to higher homocysteine.
The study clearly presents long-term natural folate use as effective, safe, well absorbed and non-disruptive to cellular metabolic activities.