Abstract
BACKGROUND: Sarcopenia, characterized by progressive muscle loss, burdens aging populations. While bile acids (BAs) in skeletal muscle mass (SMM) are poorly understood, the role of amino acids (AAs) remains debated. This study investigated the associations between serum BAs, AAs, and low SMM in Chinese adults. METHODS: Among 2170 initially enrolled participants, 702 were finally analyzed. Participants were classified into low and normal SMM groups. Serum BAs and AAs were quantified by targeted LC-MS/MS. Nonlinear relationships were assessed using restricted cubic spline analysis. Mediation analysis was used to assess the mediating effects of metabolic factors. RESULTS: The prevalence of low SMM was 14.5% (females: 21.1% vs. males: 10.2%). Multivariable logistic regression identified that increased glycocholic acid (GCA, OR = 0.561, p = 0.030), glycolithocholic acid (GLCA, OR = 0.255, p < 0.001) and deoxycholic acid (DCA, OR = 0.444, p = 0.003) were independently associated with lower risk of low SMM in the fully adjusted model. Valine (OR = 0.646, p = 0.010) and leucine (OR = 0.680, p = 0.024) showed consistent protective effects against low SMM at physiological concentrations. Mediation analysis showed BMI mediated protective effects of GCA, valine and leucine (all p < 0.01), while creatinine/cystatin C ratio mediated leucine's effect (p = 0.030). Notably, GLCA exhibited direct protection independent of metabolic mediators (both p < 0.01). CONCLUSIONS: This study identified specific BAs and AAs significantly correlated with preserved SMM, suggesting that modulating BA metabolism (particularly elevating GLCA) and maintaining optimal BCAA levels may be effective strategies for low SMM. GLCA's direct protective effect supports exploring dietary or microbiota-targeted interventions. Individual metabolic profiles, such as BMI, should be incorporated into personalized sarcopenia management.