Folate Fortification and Supplementation Do Not Provide Vascular Health Benefits in Type 1 Diabetes

ObjectiveTo evaluate the lowest effective dose-response of folic acid on endothelial function in children with type 1 diabetes.Study designA randomized, double-blind, crossover, placebo-controlled trial was conducted in 20 children with type 1 diabetes (age range 10-18 years) after mandatory folate fortification in Australia. Each child received orally 4 interventions (1 per month)—3 folic acid doses (0.5, 2, and 5 mg) and 1 placebo dose—in random order. The primary outcome was 2-hour postintervention change in endothelial function measured with flow-mediated dilatation (FMD). Thirty-five children with type 1 diabetes from our folic acid interventional trial before folate fortification were used for comparison.ResultsAll children completed the study. There were no differences in baseline FMD or folate status between the visits. Folic acid supplementation increased serum folate (P = .0001) and red cell folate (P < .0001), but none of the doses improved FMD (P = .96). Baseline serum folate and red cell folate levels and FMD and glyceryl trinitrate–mediated dilatation were significantly higher in these children compared with children from our trial before mandatory folate fortification (P = .0001, .0001, .014, and .04, respectively).ConclusionsFolate status and vascular function have improved in children with type 1 diabetes since the introduction of mandatory folate fortification, but the beneficial endothelial effects of additional folic acid are no longer present.