Tetrahydrobiopterin Supplementation Enhances Carotid Artery Compliance in Healthy Older Men: A Pilot Study

BACKGROUND We performed a pilot study to test the hypothesis that acute oral ingestion of tetrahydrobiopterin (BH4), a key cofactor modulating vascular nitric oxide (NO) synthase activity, improves large elastic artery stiffness with aging in men. METHODS Healthy older (63 +/- 2 years; n = 8) and young (age 25 +/- 1 years; n = 6) men were studied 3 h after ingestion of BH4 (10 mg.kg(-1) body weight) or placebo on separate days in a randomized, placebo-controlled, double-blind study. RESULTS Baseline carotid artery compliance was 37% lower (0.17 +/- 0.02 vs. 0.22 +/- 0.02 mm/mm Hg.10(-1)) and beta-stiffness was 42% higher (7.3 +/- 1.1 vs. 4.2 +/- 0.5 AU) in the older men (both P < 0.05). BH4 ingestion markedly increased circulating BH4 concentrations in both groups (17-19-fold, P < 0.05), but increased compliance (+39% to 0.23 +/- 0.02 mm/mm Hg.10(-1), P < 0.01) and decreased beta-stiffness index (-27% to 5.3 +/- 0.7 AU, P < 0.01) only in the older men. BH4 also reduced carotid systolic blood pressure (SBP) in the older men (P < 0.05). CONCLUSIONS These preliminary results support the possibility that limited BH4 bioavailability contributes to impaired carotid artery compliance in healthy older men. Further studies are needed to determine if increasing BH4 bioavailability though oral BH4 supplementation may have therapeutic efficacy for improving large elastic artery compliance and reducing central SBP with aging.