Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid

Acute dietary nitrate (NO₃^-) supplementation can increase [NO₃^-], but not nitrite ([NO₂^-]), in human skeletal muscle, though its effect on [NO₃^-] and [NO₂^-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO₃^--rich beetroot juice (BR; 9.6 mmol NO₃^-), and 6 young adults ingested 140 mL of a NO₃^--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO₃^-] and [NO₂^-]. The relative recovery rate of NO₃^- and NO₂^- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO₃^-] and [NO₂^-]. Baseline [NO₃^-] was lower, whereas baseline [NO₂^-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO₃^-] and [NO₂^-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 μM for Δ[NO₃^-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO₂^-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO₂^-] post BR ingestion was higher, whereas [NO₃^-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO₃^- and NO₂^- distribution at rest and indicate that acute BR supplementation increases [NO₃^-] and [NO₂^-] in human skin interstitial fluid.