Background The evidence about the synergy of combining caffeine (CAF) and nitrates on exercise performance has not been summarized, although there is a possibility of additive/synergistic effects of the co-ingestion of these substances given their different mechanisms of action in central (CAF) and peripheral tissues (nitrates). Objectives The aim was to analyze the effects of co-supplementation of CAF and nitrates on sports performance in comparison to the isolated ingestion of these substances. Methods The databases of PubMed, Web of Science, Medline, CiNAHL and SPORTDiscus were used until June 2024 following PRISMA guidelines. Randomized controlled trials, at least one single-blind trial, conducted in adults were considered. A meta-analysis was performed using the random effects model to calculate the standardized mean difference estimated by Hedges` g and 95% confidence intervals (CIs) for studies with four arms. Results Six studies were included (N = 95). The meta-analysis revealed that caffeine and nitrates supplementation (CAF+nitrates) did not enhance performance in time trials (TTs) over the CAF alone (g = -0.06; 95% CI = -0.46 to 0.35; p = 0.78) or nitrates alone (g = 0.29; 95% CI = -0.12 to 0.70; p = 0.17). CAF+nitrates did not affect heart rate during submaximal exercise trials over CAF alone (g = 0.04; 95% CI = -0.31 to 0.40; p = 0.80) or nitrates alone (g = -0.15; 95% CI = -0.50 to 0.20; p = 0.40). Likewise, CAF+nitrates did not affect oxygen uptake during submaximal exercise trials over CAF alone (g = -0.04; 95% CI = -0.45 to 0.37; p = 0.84) or nitrates alone (g = -0.29; 95% CI = -0.70 to 0.12; p = 0.16). Conclusions CAF+nitrates did not offer further benefits on exercise performance or physiological variables from the isolated intake of CAF and nitrates.
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