Body fat and risk of all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies

Background/objectives We aimed to evaluate the relationships between body fat percentage (BF%), fat mass (FM), fat mass index (FMI) and visceral (VAT) and subcutaneous adipose tissue (SAT) with risk of all-cause mortality. Methods We did a systematic search in PubMed, Scopus, and Web of Science to June 2021. We selected prospective cohorts of the relationship between body fat with risk of all-cause mortality in the general population. We applied random-effects models to calculate the relative risks (RRs) and 95%CIs. Results A total of 35 prospective cohort studies with 923,295 participants and 68,389 deaths were identified. The HRs of all-cause mortality for a 10% increment in BF were 1.11 (95%CI: 1.02, 1.20; I-2 = 93%, n = 11) in the general adult populations, and 0.92 (95%CI: 0.79, 1.06; I-2 = 76%, n = 7) in adults older than 60 years. The HRs were 1.06 (95%CI: 1.01, 1.12; I-2 = 86%, n = 10) for a 5 kg increment in FM, 1.11 (95%CI: 1.06, 1.16; I-2 = 79%, n = 7) for a 2 kg/m(2) increment in FMI, and 1.17 (95%CI: 1.03, 1.33; I-2 = 72%, n = 8) and 0.81 (0.66, 0.99; I-2 = 59%, n = 6) for a 1-SD increment in VAT and SAT, respectively. There was a J shaped association between BF% and FM and all-cause mortality risk, with the lowest risk at BF% of 25% and FM of 20 kg. In subgroup analyses, although there was little evidence of between-subgroup heterogeneity, the observed positive associations were more pronounced in studies which had a longer duration, excluded participants with prevalent cardiovascular disease and cancer at baseline, with adjustment for smoking or restricted to never smokers, and less pronounced in studies which adjusted for potential intermediates, suggesting an impact of reverse causation, confounding and over-adjustment in some of the studies. Conclusions Higher body fat content was related to a higher risk of mortality in a J shaped manner. Any future studies should further assess the impact of reverse causation and residual confounding on these associations. Registration PROSPERO (CRD42021240743).