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

Nitric Oxide. 2023 May 1:134-135:10-16. doi: 10.1016/j.niox.2023.02.003. Epub 2023 Mar 6.


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.

Keywords: Extracellular space; Interstitium; Intradermal microdialysis; Nitric oxide; Reduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Beta vulgaris*
  • Blood Pressure
  • Cross-Over Studies
  • Dialysis Solutions / pharmacology
  • Dietary Supplements
  • Double-Blind Method
  • Extracellular Fluid
  • Humans
  • Nitrates*
  • Nitrites
  • Nitrogen Dioxide
  • Young Adult


  • Nitrates
  • Nitrogen Dioxide
  • Nitrites
  • Dialysis Solutions