Mixed
In older adults, resistance training combined with whey protein supplementation induces distinct skeletal muscle metabolic adaptations—specifically upregulation of tryptophan-indole metabolites, branched-chain amino acids (leucine, isoleucine, valine), and urea cycle intermediates—in individuals who exhibit high hypertrophic responsiveness (upper tertile).
For older adults seeking muscle growth, resistance training combined with adequate protein (whey) is effective, but results vary significantly. High responders exhibit specific metabolic adaptations, including increased levels of tryptophan, branched-chain amino acids, and urea cycle intermediates. This suggests that individual metabolic profiles play a key role in hypertrophic responsiveness, and those with lower responses may require different strategies or higher stimuli to achieve similar gains.
In the UPPER group, upregulation of tryptophan-indole metabolites and the kynurenine pathway suggests a potential role of gut function and anti-inflammatory effect on RT-induced hypertrophy. Also, leucine, isoleucine and valine were significantly upregulated in the absence of their catabolites. Enrichment of urea cycle/amino group metabolism alongside mitochondria-matrix metabolites in the UPPER group indicates improved amino acids and energy homeostasis.
Why this rating
The study uses a robust metabolomics platform (LC-MS) on a well-controlled clinical trial with clear grouping (UPPER vs LOWER), though it is observational regarding the metabolomic differences.
Source
Skeletal muscle metabolomic markers underlying the enhanced exercise-induced hypertrophy response to resistance training in older adults
Changhyun Lim et al. · GeroScience · 2026
DOI 10.1007/s11357-025-02074-x
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