Ergogenic effects of supplement combinations on endurance performance: a systematic review and meta-analysis of randomized controlled trials

Background Supplements such as caffeine and sodium bicarbonate have been found to exert ergogenic effects on endurance performance. However, little is known about the effects of supplementary combinations on performance parameters. This review and meta-analysis aimed to summarize and analyze studies that investigated the effects of performance-enhancing supplements in combination and isolation on endurance (>35 s).Methods A structured search was conducted in accordance with the PRISMA® statement and PICOS guidelines in the PubMed, Scopus and Dimensions databases in January 2024 without restriction to specific years. Sixteen studies that compared isolated and combined supplementation with placebo in an identical situation and tested their effects on endurance performance (time, distance, power) were included. The studies were all blinded, randomized controlled crossover studies that showed some concerns about risk of bias. Meta-analyses could be calculated for the supplement combinations caffeine (CAF) with sodium bicarbonate (SB) and CAF with beetroot juice (BJ), as sufficient studies were available for these two combinations. For the comparisons of the trials (e.g. placebo (PLA) vs. CAF; PLA vs. BJ; PLA vs. CAF-BJ; CAF-BJ vs. CAF; CAF-BJ vs. BJ), five studies each were included in the meta-analyses. A random-effects model and pooled standardized mean differences (SMD) according to Hedges’ g were used for the ergogenic effect.Results The results showed no significant differences for either the isolated (CAF/PLA [CAF+SB studies]: SMD = 0.30, 95% CI [−0.12, 0.73], p = 0.16; SB/PLA: SMD = 0.31, 95% CI [−0.18, 0.80], p = 0.22; CAF/PLA [CAF+BJ studies]: SMD = 0.28, 95% CI [−0.08, 0.63], p = 0.13; BJ/PLA: SMD = 0.02, 95% CI [−0.33, 0.38], p = 0.90) or the combined supplement intake (CAF-SB/PLA: SMD = 0.43, 95% CI [−0.05, 0.91], p = 0.08; CAF-BJ/PLA: SMD = 0.33, 95% CI [−0.03, 0.69], p = 0.07) compared with the PLA trial. The subgroup analysis “test protocols” showed a borderline significance for cycling tests for the comparison of CAF-BJ with PLA (SMD = 0.39, 95% CI [−0.00, 0.78], p = 0.05). In addition, no significant differences were found between the isolated supplements and the co-ingestion (CAF-SB/CAF: SMD = 0.12, 95% CI [−0.30, 0.54], p = 0.57; CAF-SB/SB: SMD = 0.12, 95% CI [−0.29, 0.54], p = 0.56; CAF-BJ/CAF: SMD = 0.06, 95% CI [−0.30, 0.41], p = 0.76; CAF-BJ/BJ: SMD = 0.28, 95% CI [−0.08, 0.64], p = 0.13). According to the I2 statistics (0–22%), there was no or a low heterogeneity in the studies.Conclusions In summary, it can be stated that the current state of research with few small studies and different methodological approaches (e.g. different types of sport, test protocols) only allows a limited reliable statement to be made about the combined effect of supplements. Although not statistically significant, trends observed in the forest plots suggest a potential advantage of combined supplement intake. Athletes should therefore test a possible benefit under their competition conditions. Further studies with a homogeneous design are required in the future in order to obtain more clarity about the tendencies of a combined ergogenic effect.