Folic acid improves endothelial function in children and adolescents with type 1 diabetes

Objective To evaluate the effect of folate supplementation on endothelial function in children and adolescents with type 1 diabetes. Study design Thirty-six subjects with type 1 diabetes age 13.6 +/- 2.6 years completed a randomized, double-blind, placebo-controlled crossover trial. Each subject received 8 weeks of oral folic acid (5 mg/d) and 8 weeks of placebo, with an 8-week washout period. Before and after each intervention, we assessed endothelial function by using brachial artery responses to flow (flow-mediated dilatation [FMD]) and glyceryl trinitrate, von Willebrand factor, glucose, hemoglobin Alc, total plasma homocyst(e)ine (tHcy), vitamin B-12, serum folate, and red cell folate (RCF). Results Folic acid increased FMD by 2.58 (3.1-5.7)% (95% confidence interval, 1.28-3.88), whereas placebo did not change FMD (-0.42%; 95% confidence interval, -1.67 to 0.83; P < .001). Folic acid increased serum folate by 14 nmol/L (6.2 ng/mL, P < .001) and RCF by 467.2 nmol/L (206 ng/mL, P < .001). Change in FMD was related to change in serum folate (r = 0.46, P = .005) and RCF (r = 0.39, P = .02). Glyceryl trinitrate responses, von Willebrand factor, tHcy, and hemoglobin Alc were not affected by the intervention. Conclusions Short-term high-dose folic acid improves endothelial function in children and adolescents with type 1 diabetes and normal folate status independently of tHcy.