Nonplacebo Controls to Determine the Magnitude of Ergogenic Interventions: A Systematic Review and Meta-analysis

Abstract

Introduction: Placebos are used as a control treatment that is meant to be indistinguishable from the active intervention. However, where substantive placebo effects may occur, studies that do not include a non-placebo control arm may underestimate the overall effect of the intervention (active plus placebo components). This study aimed to determine the relative magnitude of the placebo effect associated with nutritional supplements (caffeine and extracellular buffers) by metaanalysing data from studies containing both placebo and non-placebo control sessions. Methods:Bayesian multilevel meta-analysis models were used to estimate pooled effects and express the placebo effect as a percentage of the overall intervention effect. Results: Thirty-four studies were included, with the median pooled effect size (ES0.5) indicating a very small (ES0.5=0.09 [95%CrI:0.01 to 0.17]) improvement in performance of placebo compared to control. There was no moderating effect of exercise type (capacity or performance), exercise duration or training status. The comparison between active intervention and control indicated a small to medium effect (ES0.5=0.37 [95%CrI:0.20 to 0.56]). Expressed in relative terms, the placebo effect was equivalent to 25% [75%CrI:16 to 35%] and 59% [75%CrI:34 to 94%] of the total intervention effect for buffers and caffeine. Conclusion: These results demonstrate a very small, but potentially important placebo effect with nutritional supplementation studies. A substantive proportion of supplement effects may be due to placebo effects, with the relative proportion influenced by the magnitude of the overall ergogenic effect. Where feasible, intervention studies should employ nonplacebo control-arm comparators to identify the proportion of the effect estimated to come from placebo effects and avoid underestimating the overall benefits that the physiological plus psychobiological aspects associated with an intervention provide in the real world.

International Society of Sports Nutrition position stand: sodium bicarbonate and exercise performance

“…Indeed, there is considerable evidence to support placebo effects in sport and exercise nutrition, including sodium bicarbonate supplementation. In a recent meta-analysis, Marticorena et al [213] examined the effects of placebo ingestion compared to a nonplacebo control condition (no substance ingestion) on exercise performance in studies involving supplementation of caffeine and buffering agents (including sodium bicarbonate). In this meta-analysis, placebo ingestion was found to provide a small but ergogenic effect (Cohen's d = 0.09).…”

“…In this meta-analysis, placebo ingestion was found to provide a small but ergogenic effect (Cohen's d = 0.09). Additional analyses from this review showed that around 30% of the performance-enhancing benefits of buffering agents could be attributed to the placebo effect [213]. A double-blind crossover design, in which all participants receive both the active treatment and placebo prior to performing an exercise task, is the study design most used when investigating the effect of sodium bicarbonate supplementation on exercise outcomes.…”

Effects of Caffeine on Resistance Exercise: A Review of Recent Research

“…A recent meta-analysis explored the effects of placebo ingestion compared with a no-placebo control condition (i.e., no substance ingestion) [94]. This analysis reported that placebo ingestion provided a small but significant ergogenic effect (Cohen's d: 0.09) [94].…”

Individual Participant Data Meta-Analysis Provides No Evidence of Intervention Response Variation in Individuals Supplementing With Beta-Alanine

“…Collectively, these findings support consideration of more holistic approaches to intervention delivery. Factors that may influence an individual's response to intervention include nutritional status (both acute and chronic), physical activity levels, sleep, environmental conditions, and external sources of motivation (Mann et al, 2014) such as intervention expectancy (Marticorena et al, 2021). A logical next step for future research would be to attempt to parse out the relative influence of these factors on individual response variation, although this is undoubtedly challenging.…”