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

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 nonplacebo 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 meta-analyzing data from studies containing both placebo and nonplacebo 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% credible interval (CrI), 0.01-0.17)) improvement in the performance of placebo compared with 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, 0.20-0.56)). Expressed in relative terms, the placebo effect was equivalent to 25% (75% CrI, 16%-35%) and 59% (75% CrI, 34%-94%) of the total intervention effect for buffers and caffeine.

Conclusions: 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 use 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.