Sex-stratified handgrip strength and adipose-derived inflammatory biomarkers in sarcopenia – a systematic review and meta-analysis

Abstract

Background: Sarcopenia involves a progressive loss of muscle function, with inflammation regarded as a potential contributing factor. The sex-specific relationship between adipose-derived inflammatory biomarkers and muscle function outcomes remains unclear. Methods: We searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library (2015–2024) with no language restrictions for observational studies reporting handgrip strength (HGS), gait speed (GS), and circulating TNF-α, IL-6, CRP, IL-8, or IL-10 in adults with and without sarcopenia. Random-effects models (R version 4.4.2, meta package) pooled mean differences for HGS and GS and standardised mean differences for biomarkers. Heterogeneity (I², τ², prediction intervals) was explored through subgroup analyses, meta-regression, sensitivity and influence diagnostics, and funnel/contour-enhanced plots. Certainty of evidence was assessed with GRADE. Results: Thirty-six studies (n ≈ 8,200; predominantly cross-sectional) were included. Sarcopenia was associated with lower HGS (MD − 3.97 kg; 95% CI − 6.95 to − 1.00; I² = 93%), while GS showed no significant difference (MD − 0.15 m/s; 95% CI − 0.41 to 0.11; I² = 97.9%). In sex-stratified analyses of HGS (exploratory; k = 2 per stratum), women and men each showed directionally lower strength, but estimates were imprecise and not statistically significant. Among circulating biomarkers, TNF-α was directionally higher in pooled analyses but did not reach statistical significance, and between-study heterogeneity was substantial (SMD 0.40; 95% CI − 0.35 to 1.15; I² = 98.5%). CRP, IL-6, IL-8, and IL-10 showed no consistent between-group differences. Conclusions: Sex-stratified handgrip strength may aid sarcopenia screening and risk stratification, with larger deficits observed in women in cross-sectional data. Pooled analyses showed a slight, imprecise elevation of TNF-α in sarcopenia, while CRP, IL-6, IL-8 and IL-10 showed no consistent differences. These findings support sex-aware assessment but do not permit causal inferences or treatment recommendations.