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<p>Leucine-enriched supplementation is a primary intervention for sarcopenia, yet individual responses vary. We integrated <sup>1</sup>H-NMR metabolomics with clinical assessments in 47 older adults at high sarcopenia risk to identify metabotypes associated with improvements in muscle mass and strength. Following a 12-week intervention, distinct metabolic trajectories emerged between responders and non-responders. Notably, urinary levels of the gut-derived metabolite trimethylamine (TMA) and phenylpyruvic acid exhibited divergent trends across outcome-defined groups. Elevated TMA was associated with a blunted muscle mass response to leucine supplementation and with impaired myogenic differentiation and compromised myotube integrity in vitro, supporting a potential role in limiting myogenic capacity. These findings highlight the gut-muscle axis as a key modulator of heterogeneous responses to nutritional intervention and provide a metabolic framework for stratifying individuals in sarcopenia prevention strategies.</p>

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Elevated trimethylamine levels characterize impaired muscle mass response to leucine-enriched protein supplementation in older adults at risk of sarcopenia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月4日

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  • Hsiang-Yu Tang,
  • Chi-Jen Lo,
  • Hung-Yao Ho,
  • Cheng-Hung Yang,
  • Chen-Yu Chang,
  • Yu-Hsuan Ho,
  • Ji-Tseng Fang,
  • Chih-Ming Lin,
  • Mei-Ling Cheng

摘要

Leucine-enriched supplementation is a primary intervention for sarcopenia, yet individual responses vary. We integrated 1H-NMR metabolomics with clinical assessments in 47 older adults at high sarcopenia risk to identify metabotypes associated with improvements in muscle mass and strength. Following a 12-week intervention, distinct metabolic trajectories emerged between responders and non-responders. Notably, urinary levels of the gut-derived metabolite trimethylamine (TMA) and phenylpyruvic acid exhibited divergent trends across outcome-defined groups. Elevated TMA was associated with a blunted muscle mass response to leucine supplementation and with impaired myogenic differentiation and compromised myotube integrity in vitro, supporting a potential role in limiting myogenic capacity. These findings highlight the gut-muscle axis as a key modulator of heterogeneous responses to nutritional intervention and provide a metabolic framework for stratifying individuals in sarcopenia prevention strategies.