Comparative efficacy of different interventions on circulating factors in sarcopenia individuals: a systematic review and network meta-analysis

BACKGROUND: Age-related circulating factors are recognized as major contributors to the progression of sarcopenia. This network meta-analysis (NMA) aimed to compare the effects of various interventions on circulating factor responses among individuals with sarcopenia. METHODS: PubMed, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, and Chinese National Knowledge Infrastructure (CNKI) were searched from inception through April 2025 and updated in October 2025. Randomized clinical trials (RCTs) involving healthy individuals with sarcopenia were included if they reported circulating factors related to exercise, nutrition, or a combination of both interventions. Effect sizes were calculated as standardized mean difference (SMD) with 95% confidence interval (CI) using a frequentist NMA framework. The rank order of competing interventions was determined using the surface under the cumulative ranking curve (SUCRA). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was employed to evaluate the quality of evidence supporting each network estimate. RESULTS: A total of 24 RCTs involving 1,779 sarcopenia individuals were included. Seven distinct intervention strategies and control group were involved in this study. The C-reactive protein (CRP) network included 12 direct comparisons, while the insulin-like growth factor-1 (IGF-1) network encompassed 9 studies (n = 996 participants). Combined exercise (SMD = -2.24, 95%CI: -3.67 to -0.81) and Nutrition (SMD = 0.45, 95%CI: 0.04 to 0.86) were the most effective interventions for reducing CRP and improving the IGF-1 response in patients with sarcopenia, respectively. The certainty of evidence, on average, ranged from low to moderate in this study. CONCLUSION: The findings suggest that Combined exercise may be optimal for CRP reduction in patients with sarcopenia, whereas Nutrition appears to be effective in improving IGF-1 response. These findings need to be validated and addressed in future large-scale, high-quality RCTs.