Dose-structure-population interactions of protein supplementation combined with resistance training on body...

Protein supplementation is frequently utilized in conjunction with resistance training for the purpose of enhancing muscle mass and strength. Nevertheless, the efficacy of different protein types, dosing thresholds, and population-specific effects is debatable.

A systematic search was performed on PubMed, Web of Science, Scopus, SPORTDiscus, Cochrane CENTRAL, EMBASE databases through February 2026. RCTs comparing protein supplements (whey, casein, soy, pea, rice, milk, or blend) with placebo during supervised RT (≥6 weeks) were eligible. A Bayesian random-effects NMA was conducted using gemtc and JAGS. Dose-response curves were fitted with restricted cubic splines. The protocol was registered on PROSPERO (CRD420261340515).

Thirty-six RCTs (1,552 participants; 89 trial arms) formed a fully connected network of eight nodes. For LBM, whey protein ranked first (SUCRA = 0.91; MD vs. placebo: +1.24 kg, 95% CrI 0.61-1.87), followed by milk (SUCRA = 0.78; +1.18 kg) and casein (SUCRA = 0.72; +0.92 kg). The dose-response curve for whey indicated a plateau at 30-35 g/d. In older adults (≥65 years), the superiority of whey narrowed (SUCRA = 0.89 vs. 0.92 in younger adults), while casein's SUCRA increased from 0.68 in younger adults to 0.76 in older adults. However, this subgroup analysis was based on only nine trials, and the observed ranking changes may be unstable. Model convergence was satisfactory ( $\widehat{R^}$  = 1.01; ESS = 3,420), and node-splitting detected no significant inconsistency (all p > 0.10).

Among commonly available protein supplements, whey protein at approximately 30-35 g/d was associated with the largest gains in lean body mass when combined with RT, although this dose-response estimate is exploratory. Older adults may benefit from casein- or mixed-protein strategies as the advantage of whey is diminished in this population. Plant-based proteins showed smaller effect estimates than dairy-derived proteins, but the evidence certainty was low to very low and the credible intervals were wide, limiting firm conclusions.

Identifier: CRD420261340515.