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

Naoto Fujii, Shin Omori, Yufuko Kataoka, Gulinu Maimaituxun, Stephen J. Bailey, Alex B. Lloyd, Josh T. Arnold, Tatsuro Amano, Yoko Tanabe, Naomi Omi, Koichi Watanabe, Takeshi Nishiyasu

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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.
Original languageEnglish
Pages (from-to)10-16
Number of pages7
JournalNitric Oxide
Early online date6 Mar 2023
Publication statusPublished - 1 May 2023


  • Extracellular space
  • Interstitium
  • Intradermal microdialysis
  • Nitric oxide
  • Reduction

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