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Metabolites in biofluids can serve as biomarkers for diagnosing diseases and monitoring body conditions. Among the available biofluids, interstitial fluid (ISF) in the skin has garnered considerable attention owing to its advantages, which include inability to clot, easy access to the skin, and possibility of incorporating wearable devices. However, the scientific understanding of skin ISF composition is limited. In this study, we aimed to compare metabolites between skin dialysate containing metabolites from the skin ISF and venous blood (plasma) samples, both collected under resting states. We collected forearm skin dialysate using intradermal microdialysis alongside venous blood (plasma) samples from 12 healthy young adults. We analyzed these samples using capillary electrophoresis–fourier transform mass spectrometry–based metabolomics (CE–FTMS). Significant positive correlations were observed in 39 metabolites between the skin dialysate and plasma, including creatine (a mitochondrial disease biomarker), 1-methyladenosine (an early detection of cancer biomarker), and trimethylamine N-oxide (a posterior predictor of heart failure biomarker). Based on the Human Metabolome Technologies database, we identified 12 metabolites unique to forearm skin dialysate including nucleic acids, benzoate acids, fatty acids, amino acids, ascorbic acid, 3-methoxy-4-hydroxyphenylethyleneglycol (an Alzheimer's disease biomarker), and cysteic acid (an acute myocardial infarction biomarker). We show that some venous blood biomarkers may be predicted from skin dialysate or skin ISF, and that these fluids may serve as diagnostic and monitoring tools for health and clinical conditions. • Skin interstitial fluid offers non-clotting, easy access from the skin surface. • Identified 12 key metabolites in skin dialysate by using CE–FTMS–based metabolomics. • Skin dialysate positively correlates with plasma in 39 metabolites. [ABSTRACT FROM AUTHOR]

Acute dietary nitrate (NO 3 −) supplementation can increase [NO 3 −], but not nitrite ([NO 2 −]), in human skeletal muscle, though its effect on [NO 3 −] and [NO 2 −] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO 3 −-rich beetroot juice (BR; 9.6 mmol NO 3 −), and 6 young adults ingested 140 mL of a NO 3 −-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 [NO 3 −] and [NO 2 −]. The relative recovery rate of NO 3 − and NO 2 − through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO 3 −] and [NO 2 −]. Baseline [NO 3 −] was lower, whereas baseline [NO 2 −] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO 3 −] and [NO 2 −] 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[NO 3 −] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO 2 −] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO 2 −] post BR ingestion was higher, whereas [NO 3 −] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO 3 − and NO 2 − distribution at rest and indicate that acute BR supplementation increases [NO 3 −] and [NO 2 −] in human skin interstitial fluid. • [NO 3 −] and [NO 2 −] in skin interstitial fluid was assessed using microdialysis. • Basal [NO 3 −] is lower in skin interstitial fluid relative to plasma. • Basal [NO 2 −] is higher in skin interstitial fluid compared with plasma. • Dietary nitrate (NO 3 −) increases [NO 3 −] and [NO 2 −] in skin interstitial fluid. [ABSTRACT FROM AUTHOR]