Ergogenic Effect of Nitrate Supplementation: A Systematic Review and Meta-analysis

Jonathon W Senefeld, Chad C Wiggins, Riley J Regimbal, Paolo B Dominelli, Sarah E Baker, Michael J Joyner, Jonathon W Senefeld, Chad C Wiggins, Riley J Regimbal, Paolo B Dominelli, Sarah E Baker, Michael J Joyner

Abstract

Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO3) supplementation in young, healthy men and women, it is unclear if participant and environmental factors modulate the well-described ergogenic effects-particularly relevant factors include biological sex, aerobic fitness, and fraction of inspired oxygen (FiO2) during exercise. To address this limitation, the literature was systematically reviewed for randomized, crossover, placebo-controlled studies reporting exercise performance outcome metrics with NO3 supplementation in young, healthy adults. Of the 2033 articles identified, 80 were eligible for inclusion in the meta-analysis. Random-effects meta-analysis demonstrated that exercise performance improved with NO3 supplementation compared with placebo (d = 0.174; 95% confidence interval (CI), 0.120-0.229; P < 0.001). Subgroup analyses conducted on biological sex, aerobic fitness, and FiO2 demonstrated that the ergogenic effect of NO3 supplementation was as follows: 1) not observed in studies with only women (n = 6; d = 0.116; 95% CI, -0.126 to 0.358; P = 0.347), 2) not observed in well-trained endurance athletes (≥65 mL·kg·min; n = 26; d = 0.021; 95% CI, -0.103 to 0.144; P = 0.745), and 3) not modulated by FiO2 (hypoxia vs normoxia). Together, the meta-analyses demonstrated a clear ergogenic effect of NO3 supplementation in recreationally active, young, healthy men across different exercise paradigms and NO3 supplementation parameters; however, the effect size of NO3 supplementation was objectively small (d = 0.174). NO3 supplementation has more limited utility as an ergogenic aid in participants with excellent aerobic fitness that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects (e.g., women) are needed to advance the study of NO3 supplementation; however, additional descriptive studies of young, healthy men may have limited utility.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study selection.
FIGURE 2
FIGURE 2
Forest plot displaying random-effects meta-analysis of exercise performance after placebo or NO3− supplementation. The vertical line represents the mean overall effect. Symbol size reflects weight of the effect for each individual study. Symbols on the left of the continuous black line at 0 show better exercise performance after placebo supplementation, whereas studies on the right of the black line demonstrate better exercise performance after NO3− supplementation.
FIGURE 3
FIGURE 3
Subgroup analysis of biological sex and aerobic fitness. SMD of NO3− supplementation compared with placebo for biological sex of included participants (A) and V˙O2peak (B) calculated used random-effects meta-analyses. * denotes better performance after NO3− supplementation compared with placebo, P < 0.05.
FIGURE 4
FIGURE 4
Subgroup analysis of exercise parameters. SMD of NO3− supplementation compared with placebo for FiO2 (normoxia vs hypoxia; A), mean exercise time (B), and exercise type (C) calculated used random-effects meta-analyses. * denotes better performance after NO3− supplementation compared with placebo, P < 0.05.
FIGURE 5
FIGURE 5
Subgroup analysis of NO3− supplementation parameters. SMD of NO3− supplementation compared with placebo for different daily concentrations of NO3− supplementation (A), different number of days of NO3− supplementation (B), and different timing of NO3− supplementation relative to commencement of exercise (C) calculated used random-effects meta-analyses. * denotes better performance after NO3− supplementation compared with placebo, P < 0.05.
FIGURE 6
FIGURE 6
Funnel plot of the SE and standardized effect for each study. The angled lines define the area including the 95% CI of the SMD, and the vertical line defines the middle of the funnel at the mean SMD. Visual inspection of the funnel plot shows that three studies fall below 95% CI and three studies are above 95% CI.

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