Randomized clinical trial of folate supplementation in patients with peripheral arterial disease

Background: The aim was to determine whether folate supplementation improved arterial function in patients with peripheral arterial disease (PAD). Methods: Individuals with PAD were randomly assigned to receive 400 mu g folic acid (45 patients) or 5-methyltetrahydrofolate (5-MTHF (48) daily, or placebo (40) for 16 weeks. Primary endpoints were changes in plasma total homocysteine (tHcy), ankle: brachial pressure index (ABPI) and pulse wave velocity (PWV). Secondary outcomes were changes in plasma inflammatory markers. Results: Plasma tHcy was significantly reduced in folic acid and 5-MTHF groups compared with controls: median difference: -2.12 (95 per cent confidence interval -3.70 to -0.75) mu mol/l (P = 0.002) and -2.07 (-3.48 to -0.54) mu mol/l (P = 0.007) respectively. ABPI improved significantly: median difference 0.07 (0.04 to 0.11) (P < 0.001) and 0.05 (0.01 to 0.10) (P = 0.009) respectively. Brachial-knee PWV (bk-PWV) decreased significantly in individuals receiving 5-MTHF and tended to be reduced in those taking folic acid compared with controls: median difference: -1.10 (-2.20 to -0.20) m/s (P = 0.011) and -0.90 (-2.10 to 0.00) m/s (P = 0.051) respectively. Plasma levels of inflammatory markers were not affected. Conclusion: Folate administration reduced plasma homocysteine, and slightly improved ABPI and bk-PWV.