Viktor Oskarsson,1 Caroline Nordenvall,2 and Alicja Wolk1

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No association of fruit and vegetable consumption with risk of cholecystectomy Viktor Oskarsson,1 Caroline Nordenvall,2 and Alicja Wolk1 1Institute of Environmental Medicine and 2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Fig. 1. Age-sex-adjusted (A) and multivariable-adjusted (B) hazard ratios and 95% confidence intervals of cholecystectomy according to sex-specific quartiles of fruit and vegetable consumption*† Conclusion Results In this prospective study, after adjustment for potential confounders, there was no association of fruit and vegetable consumption with risk of cholecystectomy. Future studies are needed to establish the true nature of this association. During 14 years of follow-up (944,179 person-years), we identified 2129 cases of cholecystectomy (1002 in men and 1127 in women). In age- and sex-adjusted analysis, FV consumption was inversely associated with risk of cholecystectomy (Ptrend=0.018) (figure 1A). However, after adjustment for potential confounders, particularly for education, physical activity, and energy intake, the inverse association disappeared (Ptrend=0.29). The multivariable-adjusted HR was 0.92 (95% confidence interval [CI], 0.81–1.05) for the highest compared with the lowest quartile of FV consumption (figure 1B). The association between FV consumption and risk of cholecystectomy was unchanged after adjustment for possible mediators (HR, 0.93; 95% CI, 0.82–1.06), and it did not differ by sex (Pinteraction=0.79). Likewise, neither fruit consumption (Ptrend=0.72) nor vegetable consumption (Ptrend=0.58) were associated with cholecystectomy as separate exposures. A Background Although gallstone disease is common in the Western world, the epidemiologic data on its association with fruit and vegetable (FV) consumption are sparse. In the only large prospective study, which was performed among US women, it was observed that high-consumers of FVs had a reduced risk of cholecystectomy (as a proxy for symptomatic gallstone disease). Our objective was to examine the association between FV consumption and risk of cholecystectomy in a prospective setting. B Appendix Separate results for men and women, as well as baseline characteristics by fruit and vegetable consumption, can be viewed via the QR code below. In addition, details on (a) prior literature on the exposure-outcome association, (b) study population, (c) assessment of exposure and co-variables, (d) case ascertainment, and (e) statistical analyses are available. Methods We used data from 74,953 men and women (born 1914–1952), enrolled in the Cohort of Swedish Men and the Swedish Mammography Cohort, who at baseline had no history of cholecystectomy and had completed a food-frequency questionnaire. Follow-up was conducted from 1998 through 2011 by linkage to national health registries. We obtained hazard ratios (HRs) according to sex-specific quartiles of FV consumption with the use of Cox models. P values for trend were calculated by modeling the quartiles as a continuous variable. Multivariable models were adjusted for potential confounders (figure 1, footnotes). In a separate model, we further adjusted for possible mediators (ie, body mass index, diabetes, and hyperlipidemia). *Median consumption in quartile 1 was 1.5 (men) and 2.3 (women) servings/d; in quartile 4, it was 6.2 (men) and 7.8 (women) servings/d. †Multivariable models were adjusted for age (time-scale), sex, education, smoking status, alcohol intake, physical activity, aspirin use, coffee consumption, and energy intake. Karolinska Institutet Viktor Oskarsson, MD Institute of Environmental Medicine Nobels väg 13 • Box 210, 171 77 Stockholm E-mail: viktor.oskarsson@ki.se Telephone: +46 8 524 87 394 Web site: ki.se/en/people/vikosk