Factors that Moderate the Effect of Nitrate Ingestion on Exercise Performance in Adults: A Systematic Review with Meta-Analyses and Meta-Regressions

Abstract

To identify how variables such as exercise condition, supplementation strategy, participant characteristics and demographics, and practices that control oral microbiota diversity could modify the effect of inorganic nitrate ingestion (as nitrate salt supplements, beetroot juice, and nitrate-rich vegetables) on exercise performance, we conducted a systematic review with meta-analysis. Studies were identified in PubMed, Embase, and Cochrane databases. Eligibility criteria included randomized controlled trials assessing the effect of inorganic nitrate on exercise performance in healthy adults. To assess the variation in effect size, we used meta-regression models for continuous variables and subgroup analysis for categorical variables. A total of 123 studies were included in this meta-analysis, comprising 1705 participants. Nitrate was effective for improving exercise performance (standardized mean difference [SMD]: 0.101; 95% CI: 0.051, 0.151, P <0.001, I2 = 0%), although nitrate salts supplementation was not as effective (P = 0.629) as ingestion via beetroot juice (P <0.001) or a high-nitrate diet (P = 0.005). Practices that control oral microbiota diversity influenced the nitrate effect, with practices harmful to oral bacteria decreasing the ergogenic effect of nitrate. The ingestion of nitrate was most effective for exercise lasting between 2 and 10 min (P <0.001). An inverse dose-response relation between the fraction of inspired oxygen and the effect size (coefficient: -0.045, 95% CI: -0.085, -0.005, P = 0.028) suggests that nitrate was more effective in increasingly hypoxic conditions. There was a dose-response relation for acute administration (P = 0.049). The most effective acute dose was between 5 and 14.9 mmol provided ≥150 min prior to exercise (P <0.001). An inverse dose-response for protocols ≥2 d was observed (P = 0.025), with the optimal dose between 5 and 9.9 mmol·d-1 (P <0.001). Nitrate, via beetroot juice or a high-nitrate diet, improved exercise performance, in particular, in sessions lasting between 2 and 10 min. Ingestion of 5-14.9 mmol⋅d-1 taken ≥150 min prior to exercise appears optimal for performance gains and athletes should be aware that practices controlling oral microbiota diversity may decrease the effect of nitrate.

Keywords: exercise; hypoxia; nitrate supplementation; nitric oxide; oral microbiota.