Gallstone formation is the result of a complex interaction between genetic and nongenetic factors. We searched and reviewed the available literature to define how the primary prevention of gallstones (cholesterol gallstones in particular) could be applied in general practice. Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case–controlled studies were analyzed and graded for evidence quality. The epidemiological data confirmed that genetic factors are estimated to account for only approximately 25% of the overall risk of gallstones, while metabolic/environmental factors are at least partially modifiable in stone-free risk groups, and are thus modifiable by primary prevention measures related to diet, lifestyle, and environmental factors (i.e., rapid weight loss, bariatric surgery, somatostatin or analogues therapy, transient gallbladder stasis, and hormone therapy). There is no specific recommendation for the secondary prevention of recurrent gallstones. Family physicians can contribute to preventing gallstones due to their capability to identify and effectively manage several risk factors discussed in this study. Although further studies are needed to better elucidate the involvement of epigenetic factors that may regulate the effect of environment and lifestyle on gene expression in the primary prevention of gallstone formation, preventive interventions are feasible and advisable in the general practice setting.
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