Jianpi Qiangji granules improve muscle function in sarcopenia and reshape bile acid metabolism: A randomized double-blind positive-controlled trial

Background Jianpi Qiangji Granule (JQG), an in–hospital traditional Chinese medicine formulation developed at Shuguang Hospital, is clinically used for sarcopenia; however, high–quality evidence supporting its efficacy remains limited. Sarcopenia is an age–related condition characterized by progressive loss of skeletal muscle mass, strength, and physical function, substantially impairing quality of life in older adults. This exploratory trial aimed to evaluate the preliminary efficacy and safety of JQG in older patients with sarcopenia. Methods Eighty patients with sarcopenia were randomly assigned to receive JQG or calcitriol for 12 weeks under a double–blind, double–dummy, positive–controlled design. The primary outcome was the change in grip strength from baseline to week 12. Secondary outcomes included skeletal muscle index (SMI), 6–meter walking speed, and Sarcopenia Quality of Life (SarQoL) scores. Additional serum biomarkers, including IL–1β, IL–6, IL–10, TNF–α, growth hormone, testosterone, brain–derived neurotrophic factor ( BDNF ) , and growth differentiation factor 15 ( GDF15 ) were evaluated. To explore potential metabolic mechanisms, untargeted serum metabolomics was performed, followed by pathway enrichment analysis and targeted bile acid profiling. Safety assessments included vital signs, routine laboratory tests, serum electrolytes including calcium, and adverse events. Results In the intention–to–treat/full analysis set ( ITT/FAS ) analysis, JQG was associated with a greater improvement in the primary outcome, grip strength, than calcitriol after 12 weeks, with an adjusted between–group difference of 1.49 kg (95% CI : 0.24 to 2.75). For secondary outcomes, JQG showed greater improvements in 6–meter walking speed, with an adjusted between–group difference of 0.13 m/s (95% CI : 0.05 to 0.22), and SarQoL score, with an adjusted between–group difference of 8.13 points (95% CI : 4.15 to 12.11). The adjusted between–group difference in SMI was 0.03 kg/m 2 (95% CI : −0.13 to 0.19). Exploratory biomarker analyses suggested treatment–associated changes in inflammatory, hormonal, neurotrophic, and aging–related markers. Both interventions were well tolerated, and no clinically significant hypercalcemia or major safety concern was observed. Untargeted serum metabolomics suggested treatment–associated metabolic remodeling, with pathway enrichment highlighting bile acid–related metabolism. Targeted bile acid profiling further indicated changes in circulating bile acid composition, including alterations in free, conjugated, primary, and secondary bile acid species, accompanied by increased serum FGF19 levels. Conclusion In this exploratory randomized trial, JQG was associated with greater improvements in grip strength, physical performance, and sarcopenia–related quality of life than calcitriol over 12 weeks, with no major safety concerns observed. Exploratory biomarker and metabolomic findings suggest that inflammatory regulation, hormonal and neurotrophic modulation, and bile acid–related metabolic remodeling may be involved in the response to JQG. These findings are hypothesis–generating and warrant confirmation in larger, multicenter, adequately powered trials. Trial registration This trial was registered at the Chinese Clinical Trial Registry (ChiCTR) on October 21, 2024 (Registration No. ChiCTR2400091125).