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Physical Activity and the Risk of Gallstone Disease: A Systematic Review and Meta-analysis. BACKGROUND: The role of physical activity in preventing gallstone disease independent of its effect on the body weight has not been well established. We performed a systematic review and meta-analysis of cohort and case-control studies to analyze this potential association. METHODS: We searched PubMed and EMBASE to identify all published studies in English through April 2016. We pooled the relative risks (RRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) from individual studies using a random-effects model to investigate associations between physical activity and the risk of gallstone disease. RESULTS: A total of 16 studies comprising 19 independent reports of approximately 260,000 participants met the inclusion criteria, including 6 case-control studies and 13 cohort studies. In a pooled analysis of cohort studies, physical activity (in a comparison of the highest-level and the lowest-level groups) was associated with a reduced risk of gallstone disease (RR=0.85; 95% CI, 0.78-0.92; I=79.5%). For men, the RR was 0.76 (95% CI, 0.60-0.97), and for women, the RR was similar (RR=0.77; 95% CI, 0.66-0.91). In a dose-response analysis, the RR of gallstone disease was 0.87 (95% CI, 0.83-0.92; I=1.0%) per 20 metabolic equivalent-hours of recreational physical per week. In comparison, case-control studies yielded a stronger significant risk reduction for gallstone disease (OR=0.64; 95% CI, 0.46-0.90; I=76.6%). CONCLUSIONS: This study suggests an inverse association between physical activity and gallstone disease in both men and women; however, these findings should be interpreted cautiously because of study heterogeneity.