Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype

Background: Folic acid reduces plasma homocysteine and may be an important therapy for preventing cardiovascular disease. A key mechanism may be the reduction of arterial stiffness. Objective: The effect of folic acid supplementation on blood pressure and large artery stiffness was examined in relation to methylenetetrahydrofolate reductase (MTHFR) genotype. Design: Forty-one asymptomatic men with normal or high-normal ambulatory blood pressure (systolic: > 130 to < 145 mm Hg; diastolic: > 80 to < 90 mm Hg) participated. The study had a randomized, placebo-controlled, double-blind, crossover design that incorporated 3-wk treatments with 5 mg folic acid/d or matching placebo; each treatment was separated by a 4-wk washout phase. Results: Folic acid reduced brachial pulse pressure by 4.7 +/- 1.6 mm Hg (P < 0.05) without changing mean arterial pressure. Systemic arterial compliance increased by 0.15 +/- 0.03 mL/mm Hg (P < 0.05) after folic acid treatment but did not change after placebo treatment. These responses did not significantly correlate with either homocysteine or folate plasma concentrations. MTHFR genotype CC homozygotes (without the 677C -> T polymorphism) with normal blood pressure had a larger reduction in homocysteine concentrations in response to folic acid than did T allele carriers. Blood pressure and arterial stiffness responses were independent of MTHFR genotype. Conclusion: Folic acid is a safe and effective supplement that targets large artery stiffness and may prevent isolated systolic hypertension.