Folic acid supplementation improves microvascular function in aged humans through nitric oxide-dependent mechanisms

Older adults have reduced vascular endothelial function, evidenced by attenuated nitric oxide (NO)-dependent cutaneous vasodilation. Folic acid and its metabolite 5-methyltetrahydrofolate (5-MTHF) are reported to improve vessel function. We hypothesized that (1) local 5-MTHF administration, and (2) chronic folic acid supplementation would improve cutaneous microvascular function in aging through NO-dependent mechanisms. Eleven young (Y:22±1yrs) and 11 older (O:71±3yrs) subjects participated in 2 separate studies. In both studies, two intradermal microdialysis fibers were placed in the forearm skin for local delivery of lactated Ringer’s with and without 5mM 5-MTHF. Red cell flux was measured by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC=LDF/MAP) was normalized as %CVCmax (28mM SNP, local 43°C). Study 1: After CVC plateaued during local heating, 20mM L-NAME was perfused at each site to quantify NO-dependent vasodilation. Local heating plateau (O:82±3 vs. Y:96±1%CVCmax; p=0.002) and NO-dependent vasodilation (O:26±6 vs. Y:49±5%CVCmax; p=0.03) were attenuated in older. 5-MTHF augmented overall (91±2%CVCmax; p=0.03) and NO-dependent (43±9%CVCmax; p=0.04) vasodilation in older but not young. Study 2: Subjects ingested folic acid (5mg/day) or placebo for 6wks in a randomized double-blind crossover design. A 1°C rise in oral temperature was induced using a water-perfused suit, body t...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research