Association Between Fat-Free Mass and Mortality: A Systematic Review and Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of prospective observational cohort studies.
PubMed 42430205 · doi:10.1002/jcsm.70331
What was done
A PRISMA-guided systematic review and meta-analysis (PROSPERO: 321722) was conducted to evaluate the association between fat-free mass and all-cause mortality in community-dwelling adults. Searches were performed across PubMed, Web of Science, and Embase through mid-to-late 2025. Studies assessing fat-free mass by computed tomography, dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), or anthropometry were included, while studies of hospitalized participants were excluded. Maximally adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using random-effects models, with publication bias assessed via trim-and-fill, robustness assessed with leave-one-out sensitivity analyses, and potential unmeasured confounding quantified with E-values.
What was found
In total, 49 cohort studies met inclusion criteria, comprising 1,149,807 participants and 83,798 deaths. Low versus high fat-free mass was associated with increased all-cause mortality (RR: 1.42, 95% CI: 1.30-1.55). Trim-and-fill adjustment for publication bias yielded an adjusted RR of 1.31 (95% CI: 1.20-1.44). Sensitivity analyses showed robustness across leave-one-out iterations (RR range: 1.39-1.43) with an E-value of 2.19. Associations remained consistent across age (p = 0.133), geographic region (p = 0.983), and cause of death (cardiovascular disease p = 0.240; cancer p = 0.136). The association was stronger in men (RR: 1.56, 95% CI: 1.32-1.85) than in women (RR: 1.25, 95% CI: 1.11-1.39; p < 0.0001). By measurement method, associations were strongest for calf circumference (RR: 2.19, 95% CI: 1.50-3.20), moderate for DXA (RR: 1.52, 95% CI: 1.29-1.79), and weakest for BIA (RR: 1.23, 95% CI: 1.07-1.41).
Why it matters
This meta-analysis demonstrates that low fat-free mass independently predicts higher all-cause mortality in community-dwelling adults. It highlights the prognostic utility of body composition assessment beyond total body mass for identifying high-risk individuals.
Limits
The findings rely entirely on observational cohort data, precluding causal conclusions. Statistical evidence of publication bias was identified, and effect sizes showed substantial variation depending on the body composition measurement modality employed. Findings cannot be generalized to hospitalized or institutionalized populations.
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