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

Abstract

Nitric oxide (NO)-mediated endothelial dysfunction, secondary to increased oxidative stress, presents in young African American (AA) compared to 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 M, 9 F) subjects before (pre: 8 AA, 10 EA) and 13 subjects after (post: 7 AA, 6 EA) four weeks 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 (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 (28mM sodium nitroprusside+43°C) for each phase of the local heating response. After attaining stable elevated blood flow, 15mM 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 AA versus EA (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 AA (p≤0.04), but not EA (p≥0.41). Vitamin D supplementation mitigated endothelial dysfunction, an antecedent to overt CVD, in otherwise healthy, young AA adults.

Vitamin D and Its Role in the Lipid Metabolism and the Development of Atherosclerosis

“…Similarly, in one 2018 meta-analysis evaluating endothelial function indirectly through FMD, PWV, or AI in response to vitamin D supplementation in approximately 1800 patients with metabolic syndrome or related conditions, a statistically significant correlation only in FMD improvement without affecting PWV or AI was found [ 60 ]. Additional data comes from a small population RCT from 2020, where 4 weeks of 2000 IU/day vitamin D supplementation in an African American cohort significantly reduced oxidative stress and increased endothelial nitric oxide production and bioavailability [ 63 ]. These two mechanisms are known to give rise to atherosclerotic disease [ 57 ].…”

Serum of limb remote ischemic postconditioning inhibits fMLP-triggered activation and reactive oxygen species releasing of rat neutrophils

“…200 μL cell suspension was inoculated into the 96-well culture plate coated with 0.1% gelatin, then cultured at 37 °C under 95% O 2 and 5% CO 2 . 24 h later, p38 MAPK inhibitor SB (10 μM, DMSO) [ 10 ] and NADPH oxidase inhibitor APO (100 μM, DMSO) [ 11 ] were added into SB and APO groups, respectively, then SB group was cultured for 30 min and APO group for 15 min, followed by stimulation with fMLP (10 μM, DMSO) [ 12 ] for 10 min. After carefully transferred into 96-well plate and gently washed with PBS, the culture medium was added with 100 μL of 2, 7 dichlorofluorescein diacetate (DCFH-DA) diluted (1:1000) to PBS, then incubated at 37°C for 25 min.…”

The evolution of human skin pigmentation involved the interactions of genetic, environmental, and cultural variables

“…Vitamin D serves many critical functions in the body, and deficiency in the vitamin increases susceptibility to a range of developmental, chronic, and infectious diseases via its effects on the epigenome and on the expression of many genes on nearly all organs and tissue types in the body (Bora & Cantorna, 2017 ; Bustamante et al., 2020 ; Caccamo et al., 2018 ; Carlberg, 2019 ; Sassi et al., 2018 ). The recognition that vitamin D improves endothelial function by signaling for the transcription of endothelial nitric oxide synthase (eNOS) and thereby acting to preserve production of NO and healthy peripheral vascular function augments our understanding of the vitamin's consummate importance in human physiology and has potentially great consequences for our understanding of the evolution of skin pigmentation (Wolf et al., 2020 ; Wolf & Kenney, 2019 ). Vitamin D is produced in the upper epidermis through UVB‐induced catalysis of 7‐DHC into pre‐D, and it is required in the dermis to preserve NO production required for healthy vasodilation.…”

“…This important function of vitamin D probably accounts for the intriguing finding of reduced all‐cause mortality in a large cohort of lightly pigmented Scandinavian women reported by Lindqvist and colleagues (Lindqvist et al., 2020 ). The role of vitamin D’s role in eNOS signaling, control of vasodilation, and regulation of blood pressure warrants further investigation in an evolutionary context with respect to the evolution of skin pigmentation under low UVR conditions (Wolf et al., 2020 ). It is also of potentially great relevance in clinical contexts with respect to the importance of low and carefully controlled doses of natural UVR sufficient to produce vitamin D and maintain healthy vasodilation and blood pressure (Alfredsson et al., 2020 ; Wolf et al., 2020 ).…”

“…The role of vitamin D’s role in eNOS signaling, control of vasodilation, and regulation of blood pressure warrants further investigation in an evolutionary context with respect to the evolution of skin pigmentation under low UVR conditions (Wolf et al., 2020 ). It is also of potentially great relevance in clinical contexts with respect to the importance of low and carefully controlled doses of natural UVR sufficient to produce vitamin D and maintain healthy vasodilation and blood pressure (Alfredsson et al., 2020 ; Wolf et al., 2020 ). This consideration is of particular concern in habitually indoor‐dwelling people, older people with attenuated cutaneous vitamin D production abilities, and darkly pigmented people living in low UVR environments.…”