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Background: The long-term effect of repeated intentional weight loss and weight regain on the risk of gallstone disease in men is not clear.

Methods: Participants in the Health Professionals Follow-up Study provided information on intentional weight loss during the previous 4 years in 1992. Weight cyclers were men who had intentional weight loss and weight regain. Men free of gallstone disease at baseline were followed from 1992 to 2002. On biennial questionnaires the participants reported newly diagnosed gallstone disease.

Results: During 264 760 person-years of follow-up we ascertained 1222 cases of symptomatic gallstones. We examined the effect of weight cycling on the risk of gallstone disease. The multivariate relative risk of weight cyclers, compared with weight maintainers, after adjusting for potential confounding variables, including body mass index, was 1.11 (95% confidence interval [CI], 0.94-1.31) in light cyclers, 1.18 (95% CI, 0.97-1.43) in moderate cyclers, and 1.42 (95% CI, 1.11-1.81) in severe cyclers. We further examined the effect of number of cycling episodes. Among weight cyclers, the relative risk associated with having more than 1 weight cycle, compared with weight maintainers, was 1.10 (95% CI, 0.88-1.37) in light cyclers, 1.28 (95% CI, 1.03-1.59) in moderate cyclers, and 1.51 (95% CI, 1.13-2.02) in severe cyclers.

Conclusions: Our findings suggest that weight cycling, independent of body mass index, may increase the risk of gallstone disease in men. Larger weight fluctuation and more weight cycles are associated with greater risk.

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