Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function.
Level 4 - case-series / case-control
Two independent cross-sectional observational studies.
PubMed 38048992 · doi:10.1016/j.tjnut.2023.12.002
What was done
Researchers conducted two cross-sectional studies to evaluate associations among age, sex, vitamin D status, whole-body nitric oxide (NO) production, and endothelial function. Study 1 examined 40 healthy adults split into young (20–49 years) and older (50–75 years) male and female subgroups (10 participants each), assessing stable-isotope whole-body NO production, peripheral pulse wave velocity (PWV), blood pressure, and plasma 25(OH)D, nitrate, nitrite, and asymmetric dimethylarginine (ADMA). Study 2 assessed 80 overweight and obese postmenopausal women (age 61.2 ± 6.2 years, BMI 29.5 ± 4.4 kg/m²) for postocclusion reactive hyperemia (PORH), peripheral PWV, and biomarkers including 25(OH)D, nitrate, cGMP, 3-nitrotyrosine (3-NT), endothelin-1, VEGF, and ADMA.
What was found
In Study 1, whole-body NO production was significantly higher in young versus older adults (0.61 ± 0.30 vs. 0.39 ± 0.10 μmol·h⁻¹·kg⁻¹, P = 0.01), with no significant sex difference (P = 0.81). Plasma 25(OH)D showed no significant association with PWV (r = 0.18, P = 0.28) or NO production (r = -0.20, P = 0.22). Plasma ADMA correlated positively with age (r = 0.35, P = 0.03) and negatively with NO production (r = -0.33, P = 0.04). In Study 2, age correlated with reduced PORH (r = -0.28, P = 0.02) and elevated ADMA (r = 0.22, P = 0.04). 25(OH)D was inversely associated with 3-NT (r = -0.31, P = 0.004) but was not associated with NO production or endothelial function markers.
Why it matters
The findings demonstrate an age-related decline in human whole-body NO synthesis and worsening endothelial markers, but provide little support for a direct link between circulating vitamin D levels and NO-mediated vascular function.
Limits
The study design was entirely cross-sectional and observational, preventing causal conclusions. Sample sizes were small (n = 40 and n = 80), and Study 2 evaluated only overweight/obese postmenopausal females, limiting generalizability.
Cited by
- supports Endothelial production of nitric oxide in the human body significantly declines by approximately age 40.