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Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms
Journal article   Open access   Peer reviewed

Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms

Anna E Stanhewicz, Lacy M Alexander and W Larry Kenney
Clinical science (1979), Vol.129(2), pp.159-167
07/2015
DOI: 10.1042/CS20140821
PMCID: PMC8080301
PMID: 25748442
url
https://www.ncbi.nlm.nih.gov/pmc/articles/8080301View
Open Access

Abstract

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.
 Administration, Cutaneous Administration, Oral Age Factors Aged Blood Flow Velocity Body Temperature Cross-Over Studies Dietary Supplements Double-Blind Method Enzyme Inhibitors - pharmacology Female Folic Acid - administration & dosage Folic Acid - analogs & derivatives Humans Hypothermia, Induced Male Microcirculation - drug effects Microdialysis Microvessels - drug effects Microvessels - metabolism Nitric Oxide - metabolism Nitric Oxide Synthase Type III - antagonists & inhibitors Nitric Oxide Synthase Type III - metabolism Pennsylvania Regional Blood Flow Skin - blood supply Vasodilation - drug effects Vasodilator Agents - administration & dosage Young Adult

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