Prospective evaluation of folic acid supplementation on plasma homocysteine concentrations during weight reduction: a randomized, double-blinded, placebo-controlled study in obese women

Elevated total homocysteine concentrations and obesity are both associated with an increased risk of cardiovascular disease. However, previous studies of weight reduction on serum homocysteine concentrations have obtained inconsistent reports. We investigated the effect of folic acid supplementation on serum homocysteine concentrations via a randomized, double-blinded, placebo-controlled study. Seventy-four obese women [age (mean ± SEM) 41 ± 1 years; body mass index, 29.6 ± 0.5 kgs/m2] completed a 12 weeks weight reduction program with dietary advice and light exercise. They were also randomized to take either folic acid supplementation (5 mg daily, n = 36) or placebo (n = 38) groups. This program led to a weight reduction of 7.7% and 8.9% of initial weight for folic acid supplementation and placebo groups, respectively. Serum folate concentrations increased for 3 folds (p < 0.001) in the folic acid group. In the folic acid group, there was a trend of lower fasting serum homocysteine concentratrions (7.6 ± 0.2 vs. 7.3 ± 0.3 μmol/L), but it did not reach statistical significance (p = 0.170). However, we found that serum homocysteine concentrations decreased significantly in those with higher baseline homocysteine concentrations (8.7 ± 1.3 vs. 7.8 ± 1.5 μmol/L, p = 0.004), while it did not change in those with lower baseline homocysteine concentrations (6.6 ± 0.6 vs. 6.8 ± 1.2 μmol/L, p = 0.334). Reduction of serum homocysteine concentrations did not correlate with elevation of serum folate concentrations (p = 0.646) in obese women with higher baseline homocysteine concentrations. In conclusion, serum homocysteine concentrations can be maintained in obese women during mild to moderate weight loss. Folic acid supplementation decreased serum homocysteine concentrations in those women who had higher serum homocysteine concentrations before participating in the weight reduction program.