Four weeks of vitamin D supplementation improves nitric oxide-mediated microvascular function in college-aged African Americans

Am J Physiol Heart Circ Physiol. 2020 Oct 1;319(4):H906-H914. doi: 10.1152/ajpheart.00631.2020. Epub 2020 Aug 28.


Reduced nitric oxide (NO)-mediated cutaneous vasodilation, secondary to increased oxidative stress, presents in young African American (AA) compared with European American (EA) adults and may be modulated by vitamin D status. We assessed cutaneous microvascular function in 18 young, healthy (21 ± 2 yr; 9 men, 9 women) subjects before (pre, 8 AA, 10 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation and in 13 subjects after (post, 7 AA, 6 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation. Serum vitamin D concentrations [25(OH)D] were measured at each visit. Three intradermal microdialysis fibers placed in the ventral forearm were randomized for treatment with 10 μM Tempol, 100 μM apocynin, or lactated Ringer's solution (control). Local heating (39°C) induced cutaneous vasodilation; red cell flux was measured at each site (laser-Doppler flowmetry), and cutaneous vascular conductance (CVC = flux/MAP) was expressed as a percentage of maximum (28 mM sodium nitroprusside, +43°C) for each phase of local heating. After stable elevated blood flow was attained, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) was perfused at all sites to quantify the NO contribution to cutaneous vasodilation (%NO), calculated as the difference between local heating and l-NAME plateaus. Serum [25(OH)D], the magnitude of the local heating response, and %NO were all lower in AAs versus EAs (P < 0.01). Tempol (P = 0.01), but not apocynin (P ≥ 0.19), improved the local heating response and %NO. Four weeks of supplementation improved serum [25(OH)D], the local heating response, and %NO in AAs (P ≤ 0.04) but not in EAs (P ≥ 0.41). Vitamin D supplementation mitigated endothelial dysfunction, an antecedent to overt cardiovascular disease (CVD), in otherwise healthy, young AA adults.NEW & NOTEWORTHY Endothelial dysfunction, an antecedent to overt cardiovascular disease (CVD), is observed earlier and more frequently in otherwise healthy African Americans (AAs) when compared with other ethnic groups. Vitamin D may modulate endothelial function, and darkened skin pigmentation increases risk of vitamin D deficiency. We show that 4 wk of 2,000 IU/day vitamin D supplementation improves microvascular responses to local heating in AAs. Ensuring adequate vitamin D status may mitigate development of cardiovascular dysfunction in this at-risk population.

Keywords: microvascular function; nitric oxide; vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Black or African American*
  • Dietary Supplements* / adverse effects
  • Female
  • Humans
  • Male
  • Microvessels / drug effects*
  • Microvessels / metabolism
  • Microvessels / physiopathology
  • Nitric Oxide / metabolism*
  • Skin / blood supply*
  • Time Factors
  • Treatment Outcome
  • Vasodilation / drug effects*
  • Vitamin D / administration & dosage*
  • Vitamin D / adverse effects
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy*
  • Vitamin D Deficiency / ethnology
  • Vitamin D Deficiency / physiopathology
  • Young Adult


  • Vitamin D
  • Nitric Oxide
  • 25-hydroxyvitamin D