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 △[NO₃-] from baseline and 155±190 vs. 217±204 nM for △[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.