Nitric Oxide. 2026 Jan 17:S1089-8603(26)00009-1. doi: 10.1016/j.niox.2026.01.001. Online ahead of print.
ABSTRACT
BACKGROUND: Nitric oxide (NO) is involved in the regulation of vascular, immune and metabolic functions. Physiological modelling of stable isotope tracers provides an accurate method to measure whole-body NO production in humans. A systematic review and meta-analysis of studies using stable isotope methods was conducted to measure in vivo NO production in healthy individuals and patients with various disease conditions, characterise production rates across different populations and assess methodological factors contributing to measurement variability.
METHODS: PubMed/MEDLINE, Embase, Scopus and Web of Science databases were searched from inception to April 2025. Random-effect models were used to estimate of NO production. Risk of bias was assessed using the BIOCROSS scale for biomarker studies. Publication bias was evaluated by Funnel Plots and Egger's regression test.
RESULTS: 58 studies were included in the systematic review, and 42 had valid data to be included in the meta-analysis. Mean NO production in healthy adults was 0.74 (95%CI 0.47, 1.00) μmol·kg-1·hour-1 and ranged from 0.73 to 4.89 μmol·kg-1·hour-1 depending on methodology and population characteristics. NO production in cardiovascular diseases [0.19 (95%CI 0.11, 0.28) μmol·kg-1·hour-1] and metabolic diseases [0.43 (95%CI 0.21, 0.64) μmol·kg-1·hour-1] was associated with lower physiological NO production. Conversely, chronic kidney disease [5.42 (95%CI 2.04, 8.81) μmol·kg-1·hour-1] and inflammatory conditions [1.35 (95%CI 0.78, 1.92) μmol·kg-1·hour-1] were associated with increased NO production.
CONCLUSIONS: Chronic metabolic and cardiovascular diseases were overall characterised by a lower NO production. Standardisation of stable isotope protocols and reference ranges are needed to improve clinical utility for monitoring and therapy.
PMID:41554399 | DOI:10.1016/j.niox.2026.01.001