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.
Bitter solutions may not be effective in improving functional performance in older adults. Lack of significant findings could be due to 1) inappropriately low dosages of caffeine to produce an ergogenic effect 2) caffeine is not as effective quinine in stimulating oral receptors in the mouth 3) decreased chemosensitivity and oral receptor function due to age related changes. Further research is needed to assess the effects of bitter solution mouthwashes in older adults as a way to effect acutely change performance measures. PURPOSE: Cannabidiol (CBD) may exert physiological and psychological effects that benefit athletes (e.g. protect against neurological damage; reduce inflammation, anxiety and pain) (McCartney et al. 2020). This pilot study investigated the effects of CBD on physiological responses to exercise to determine its practical utility within the sporting context. METHODS: On two occasions, nine endurance-trained males (VO2max: 57.4±4.0 mL•min -1 •kg -1 ) ran for 60 mins at a fixed, moderate-intensity (70% VO2max) (RUN 1) before completing an incremental run to exhaustion (RUN 2) on an indoor treadmill (21.4±0.4°C). Participants received an oral dose of CBD (300 mg) or placebo 1.5 hrs prior to exercise in a randomised, doubleblind, crossover design. Respiratory gases were sampled continuously between 24-32, 37-45 and 50-58 mins of submaximal exercise; heart rate (HR), ratings of perceived exertion (RPEs), ratings of pleasure-displeasure, blood glucose (BG) and lactate (BL) concentrations were measured at 20-min intervals. Blood was drawn at baseline, pre-and post-RUN 1, post-RUN 2 and 1 hr post-RUN 2. RESULTS: CBD tended to increase submaximal oxygen consumption (+24±13 mL•min -1 , p=0.094). No differences in HR, RPE, BG, BL, or respiratory exchange ratio were observed during submaximal exercise (p's>0.10); VO2max (CBD: 3987±462; Placebo: 3868±577 mL•min -1 ; p=0.121) and time to exhaustion (CBD: 1286±150; Placebo: 1246±197 sec; p=0.204) were also similar during the incremental run. CBD tended to increase ratings of pleasure at 20-(p=0.050) and 40-mins (p=0.065) of submaximal exercise. Serum interleukin (IL)-6, IL-1β, tumor necrosis factor-α, lipopolysaccharide and myoglobin concentrations increased from baseline with exercise (i.e., post-RUN 1, post-RUN 2 and/or 1 hr post-RUN 2, p's<0.05); however, the change was too small to reliably evaluate the effect of CBD. Plasma CBD concentrations were 0±0, 3±2, 77±18, 164±35 and 99±26 ng.mL -1 at each respective time point. CONCLUSIONS: These preliminary findings suggest that CBD has potential to alter physiological responses during exercise. Further research involving a larger participant sample is required to confirm and better understand these effects.
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