Ergogenic Effect of Nitrate Supplementation in Clinical Populations: A Systematic Review and Meta-Analysis

Background/Objectives: Inorganic nitrate (NO₃^-) supplementation, via its conversion to nitric oxide (NO), has been purported to be ergogenic in healthy individuals. Many disease states are characterized by reduced NO bioavailability and are expected to derive a benefit from NO₃^-. This systematic review and meta-analysis evaluate the current literature on the ergogenic effect of NO₃^- supplementation in individuals with cardiopulmonary and metabolic diseases (CPMD). Methods: Relevant databases were searched up to December 2023 for randomized, placebo-controlled crossover trials for aerobic exercise outcome variables with CPMD. Results: Twenty-two studies were included, and 46% reported ergogenic benefits of inorganic nitrate supplementation. NO₃^- supplementation had no effect on aerobic performance with respect to maximal (SMD = 0.11, 95% CI: -0.12 to 0.34, p = 0.34) and submaximal (SMD = 0.16, 95% CI: -0.13 to 0.46, p = 0.27) TTE, VO_2peak (SMD = 0.002, 95% CI: -0.37 to 0.38, p = 0.99), or 6MW (SMD = 0.01, 95% CI: -0.29 to 0.28, p = 0.96). When the studies were limited to only cardiovascular disease conditions, NO₃^- supplementation had trivial effects on aerobic performance with respect to Timed Trials (SMD = 0.14, 95% CI: -0.04 to 0.33, p = 0.13), VO₂ (SMD = -0.02, 95% CI: -0.32 to 0.27, p = 0.87), and small effects on Distance Trials (SMD = 0.25, 95% CI: -0.18 to 0.69, p = 0.25). Sunset funnel plots revealed low statistical power in all trials. Conclusions: The results of this systematic review revealed that 46% of the individual studies showed a positive benefit from inorganic nitrate supplementation. However, the meta-analysis revealed a trivial effect on physical function in CPMD populations. This is likely due to the large heterogeneity and small sample sizes in the current literature.