Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms.
Older adults have reduced vascular endothelial function, evidenced by attenuated nitric oxide (NO)-dependent cutaneous vasodilatation. Folic acid and its metabolite, 5-methyltetrahydrofolate (5-MTHF), are reported to improve vessel function. We hypothesized that (i) local 5-MTHF administration and (ii) chronic folic acid supplementation would improve cutaneous microvascular function in ageing through NO-dependent mechanisms. There were two separate studies in which there were 11 young (Y: 22 ± 1 years) and 11 older (O: 71 ± 3 years) participants. In both studies, two intradermal microdialysis fibres were placed in the forearm skin for local delivery of lactated Ringer's solution with or without 5 mM 5-MTHF. Red cell flux was measured by laser-Doppler flowmetry. Cutaneous vascular conductance [CVC=red cell flux/mean arterial pressure] was normalized as percentage maximum CVC (%CVCmax) (28 mM sodium nitroprusside, local temperature 43°C). In study 1 after CVC plateaued during local heating, 20 mM NG-nitro-L-arginine methyl ester (L-NAME) was perfused at each site to quantify NO-dependent vasodilatation. The local heating plateau (%CVCmax: O = 82 ± 3 vs Y = 96 ± 1, P = 0.002) and NO-dependent vasodilatation (%CVCmax: O = 26 ± 6% vs Y = 49 ± 5, P = 0.03) were attenuated in older participants. 5-MTHF augmented the overall (%CVCmax = 91 ± 2, P = 0.03) and NO-dependent (%CVCmax = 43 ± 9%, P = 0.04) vasodilatation in older but not young participants. In study 2 the participants ingested folic acid (5 mg/day) or placebo for 6 weeks in a randomized, double-blind, crossover design. A rise in oral temperature of 1°C was induced using a water-perfused suit, body temperature was held and 20 mM L-NAME was perfused at each site. Older participants had attenuated reflex (%CVCmax: O = 31 ± 8 vs Y = 44 ± 5, P = 0.001) and NO-dependent (%CVCmax: O = 9 ± 2 vs Y = 21 ± 2, P = 0.003) vasodilatation. Folic acid increased CVC (%CVCmax = 47 ± 5%, P = 0.001) and NO-dependent vasodilatation (20 ± 3%, P = 0.003) in the older but not the young participants. Both local perfusion of 5-MTHF and supplementation with folic acid increase vasodilatation in ageing individuals through NO-dependent mechanisms.
*Department of Kinesiology, Noll Laboratory, Pennsylvania State University, University Park, PA, U.S.A.
Anna E
AE
Stanhewicz
*Department of Kinesiology, Noll Laboratory, Pennsylvania State University, University Park, PA, U.S.A.
Lacy M
LM
Alexander
*Department of Kinesiology, Noll Laboratory, Pennsylvania State University, University Park, PA, U.S.A.
W Larry
WL
Kenney
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D001783:Blood Flow Velocity; D001831:Body Temperature; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D017551:Microdialysis; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D010414:Pennsylvania; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*; D055815:Young Adult
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005492:Folic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III