{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:48:28Z","timestamp":1790632108604,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Buddhist Tzu Chi General Hospital","award":["TCRD-I9605-02"],"award-info":[{"award-number":["TCRD-I9605-02"]}]},{"name":"Tzu Chi Medical Foundation","award":["TCMMP104-08-02"],"award-info":[{"award-number":["TCMMP104-08-02"]}]},{"name":"Tzu Chi Medical Foundation","award":["TCMMP105-13-05"],"award-info":[{"award-number":["TCMMP105-13-05"]}]},{"name":"Tzu Chi Medical Foundation","award":["TCMMP106-04-01"],"award-info":[{"award-number":["TCMMP106-04-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vegetarian diets may lower symptomatic gallstone disease via cholesterol lowering. This study aimed to examine the risk of symptomatic gallstone disease (GSD) in Taiwanese vegetarians vs. nonvegetarians in a prospective cohort and to explore if this association is related to cholesterol concentration. We prospectively followed 4839 participants, and in the 29,295 person-years of follow-up, 104 new incident GSD cases were confirmed. Diet was assessed through a validated food frequency questionnaire. Symptomatic GSD was ascertained through linkage to the Taiwan National Health Insurance Research Database. Blood cholesterol profiles were measured at recruitment. Cox regression was applied to assess the effect of diet on symptomatic GSD, adjusting for age, education, smoking, alcohol, physical activities, diabetes, kidney diseases, body mass index, lipid-lowering medication, and hypercholesterolemia. Vegetarian diet was associated with a decreased risk of symptomatic GSD compared with nonvegetarian diet in women (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28\u20130.96) but not in men. In women, nonvegetarians with hypercholesterolemia had 3.8 times the risk of GSD compared with vegetarians with normal cholesterol (HR, 3.81, 95% CI, 1.61\u20139.01). A vegetarian diet may therefore protect against GSD independent of baseline hypercholesterolemia. A nonvegetarian diet and hypercholesterolemia may have an additive effect in increasing GSD risk in women.<\/jats:p>","DOI":"10.3390\/nu11020335","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T11:31:07Z","timestamp":1549366267000},"page":"335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Plant-Based Diet, Cholesterol, and Risk of Gallstone Disease: A Prospective Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Chun-Ming","family":"Chang","sequence":"first","affiliation":[{"name":"Department of General Surgery, Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"},{"name":"College of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina H. T.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science, Fu-Jen Catholic University, Taipei 242, Taiwan"},{"name":"Department of Nutrition Therapy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 622, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 622, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Nan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 622, Taiwan"},{"name":"Department of Family Medicine, College of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Lon","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 622, Taiwan"},{"name":"Department of Internal Medicine, College of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1111\/j.1440-1746.2006.04381.x","article-title":"Prevalence and risk factors of gallstone disease in an adult population of Taiwan: An epidemiological survey","volume":"21","author":"Chen","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0140-6736(06)69044-2","article-title":"Cholesterol gallstone disease","volume":"368","author":"Portincasa","year":"2006","journal-title":"Lancet (Lond. Engl.)"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chen, Y.C., Chiou, C., Lin, M.N., and Lin, C.L. (2014). The prevalence and risk factors for gallstone disease in Taiwanese vegetarians. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115145"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/MOG.0000000000000423","article-title":"An update on the pathogenesis of cholesterol gallstone disease","volume":"34","author":"Wang","year":"2018","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1111\/j.1572-0241.2004.30153.x","article-title":"Long-term intake of dietary fiber and decreased risk of cholecystectomy in women","volume":"99","author":"Tsai","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1038\/ajg.2017.216","article-title":"Diet and Risk of Cholecystectomy: A Prospective Study Based on the French E3N Cohort","volume":"112","author":"Barre","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00394-016-1298-6","article-title":"Fruit and vegetable consumption and risk of cholecystectomy: A prospective cohort study of women and men","volume":"57","author":"Nordenvall","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ypmed.2016.03.016","article-title":"Vegetable protein intake is associated with lower gallbladder disease risk: Findings from the Women\u2019s Health Initiative prospective cohort","volume":"88","author":"Lander","year":"2016","journal-title":"Prev. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/ejcn.2016.252","article-title":"Vegetarian diet as a risk factor for symptomatic gallstone disease","volume":"71","author":"McConnell","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e002408","DOI":"10.1161\/JAHA.115.002408","article-title":"Effects of Vegetarian Diets on Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"4","author":"Wang","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1017\/S0007114515002937","article-title":"Cross-sectional and longitudinal comparisons of metabolic profiles between vegetarian and non-vegetarian subjects: A matched cohort study","volume":"114","author":"Chiu","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1093\/nutrit\/nux030","article-title":"Association between plant-based diets and plasma lipids: A systematic review and meta-analysis","volume":"75","author":"Yokoyama","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1001\/jamainternmed.2013.6473","article-title":"Vegetarian dietary patterns and mortality in Adventist Health Study 2","volume":"173","author":"Orlich","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Crowe, F.L., Appleby, P.N., Allen, N.E., and Key, T.J. (2011). Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): Prospective study of British vegetarians and non-vegetarians. BMJ (Clin. Res. Ed.), d4131.","DOI":"10.1136\/bmj.d4131"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1001\/jamainternmed.2015.59","article-title":"Vegetarian dietary patterns and the risk of colorectal cancers","volume":"175","author":"Orlich","year":"2015","journal-title":"JAMA Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41387-018-0022-4","article-title":"Vegetarian diet, change in dietary patterns, and diabetes risk: A prospective study","volume":"8","author":"Chiu","year":"2018","journal-title":"Nutr. Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1001\/jamainternmed.2013.14547","article-title":"Vegetarian diets and blood pressure: A meta-analysis","volume":"174","author":"Yokoyama","year":"2014","journal-title":"JAMA Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1017\/S1368980013001560","article-title":"Relative validity and reproducibility of a quantitative FFQ for assessing nutrient intakes of vegetarians in Taiwan","volume":"17","author":"Chiu","year":"2014","journal-title":"Public Health Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1467-789X.2005.00175.x","article-title":"Prevalence of obesity in Taiwan","volume":"6","author":"Chu","year":"2005","journal-title":"Obes. Rev. Off. J. Int. Assoc. Study Obes."},{"key":"ref_20","unstructured":"(2015, January 20). National Health Insurance Administration, Ministry of Health and Welfare, Taiwan. Available online: http:\/\/www.nhi.gov.tw\/webdata\/webdata.aspx?menu=17&menu_id=1023&WD_ID=1023&webdata_id=815."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Li, S.S., Blanco Mejia, S., Lytvyn, L., Stewart, S.E., Viguiliouk, E., Ha, V., de Souza, R.J., Leiter, L.A., Kendall, C.W.C., and Jenkins, D.J.A. (2017). Effect of Plant Protein on Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Am. Heart Assoc., 6.","DOI":"10.1161\/JAHA.117.006659"},{"key":"ref_22","first-page":"24","article-title":"Effect of hypolipidemic treatment on the composition of bile and the risk or cholesterol gallstone disease","volume":"146","author":"Zak","year":"2007","journal-title":"Cas. Lek. Ceskych"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1172\/JCI107321","article-title":"Cholesterol solubility in bile. Evidence that supersaturated bile is frequent in healthy man","volume":"52","author":"Holzbach","year":"1973","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0002-9610(05)80932-8","article-title":"Pathogenesis of gallstones","volume":"165","author":"Carey","year":"1993","journal-title":"Am. J. Surg."},{"key":"ref_25","first-page":"656","article-title":"The relationship between serum lipids, apolipoproteins level and bile lipids level, chemical type of stone","volume":"75","author":"Fu","year":"1995","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_26","first-page":"187","article-title":"The effects of serum cholesterol, LDL, and HDL levels on gallstone cholesterol concentration","volume":"29","author":"Atamanalp","year":"2013","journal-title":"Pak. J. Med Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Weerakoon, H.T., Ranasinghe, S., Navaratne, A., Sivakanesan, R., Galketiya, K.B., and Rosairo, S. (2014). Serum lipid concentrations in patients with cholesterol and pigment gallstones. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-548"},{"key":"ref_28","first-page":"308","article-title":"A comparative study of serum lipid profile and gallstone disease","volume":"50","author":"Aulakh","year":"2007","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1464-5491.2010.03209.x","article-title":"Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes","volume":"28","author":"Kahleova","year":"2011","journal-title":"Diabet. Med. A J. Br. Diabet. Assoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11606-015-3390-7","article-title":"Vegetarian Diets and Weight Reduction: A Meta-Analysis of Randomized Controlled Trials","volume":"31","author":"Huang","year":"2016","journal-title":"J. Gen. Intern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.numecd.2011.07.004","article-title":"Vegetarian diets and incidence of diabetes in the Adventist Health Study-2","volume":"23","author":"Tonstad","year":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis. NMCD"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.bbalip.2009.06.006","article-title":"New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation","volume":"1791","author":"Wang","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/S1665-2681(19)30975-5","article-title":"Cholesterol cholelithiasis in pregnant women: Pathogenesis, prevention and treatment","volume":"13","author":"Wang","year":"2014","journal-title":"Ann. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/00365521.2013.858180","article-title":"Postmenopausal hormone replacement therapy and risk of cholecystectomy: A prospective cohort study","volume":"49","author":"Nordenvall","year":"2014","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1503\/cmaj.121490","article-title":"Menopausal hormone therapy and risk of cholecystectomy: A prospective study based on the French E3N cohort","volume":"185","author":"Racine","year":"2013","journal-title":"CMAJ"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1002\/cncr.11735","article-title":"The effects of a low-fat\/high-fiber diet on sex hormone levels and menstrual cycling in premenopausal women: A 12-month randomized trial (the diet and hormone study)","volume":"98","author":"Gann","year":"2003","journal-title":"Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/bjc.1997.348","article-title":"Effects of a low-fat high-carbohydrate diet on plasma sex hormones in premenopausal women: Results from a randomized controlled trial. Canadian Diet and Breast Cancer Prevention Study Group","volume":"76","author":"Boyd","year":"1997","journal-title":"Br. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1002\/1097-0142(19951215)76:12<2491::AID-CNCR2820761213>3.0.CO;2-R","article-title":"Effects of a very low fat, high fiber diet on serum hormones and menstrual function. Implications for breast cancer prevention","volume":"76","author":"Bagga","year":"1995","journal-title":"Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1017\/S1368980013002553","article-title":"Oestrogen levels in serum and urine of premenopausal women eating low and high amounts of meat","volume":"17","author":"Harmon","year":"2014","journal-title":"Public Health Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ijc.22728","article-title":"Dietary patterns, the Alternate Healthy Eating Index and plasma sex hormone concentrations in postmenopausal women","volume":"121","author":"Fung","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1017\/S0007114510000619","article-title":"Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women","volume":"104","author":"Karelis","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/sj.bjc.6690546","article-title":"Oestradiol and sex hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans","volume":"80","author":"Thomas","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/MCG.0b013e3182a14fba","article-title":"Prolonged orocecal transit time enhances serum bile acids through bacterial overgrowth, contributing factor to gallstone disease","volume":"48","author":"Kaur","year":"2014","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/0140-6736(93)92479-D","article-title":"An explanation for gallstones in normal-weight women: Slow intestinal transit","volume":"341","author":"Heaton","year":"1993","journal-title":"Lancet (Lond. Engl.)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1365-2982.1995.tb00231.x","article-title":"Influence of age, gender, hormonal status and smoking habits on colonic transit time","volume":"7","author":"Meier","year":"1995","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1113\/jphysiol.2011.224717","article-title":"Augmented cholesterol absorption and sarcolemmal sterol enrichment slow small intestinal transit in mice, contributing to cholesterol cholelithogenesis","volume":"590","author":"Xie","year":"2012","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1542\/peds.96.5.997","article-title":"An overview of the effects of dietary fiber on gastrointestinal transit","volume":"96","author":"Hillemeier","year":"1995","journal-title":"Pediatrics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1053\/j.gastro.2015.09.002","article-title":"A Prediction Rule for Risk Stratification of Incidentally Discovered Gallstones: Results From a Large Cohort Study","volume":"150","author":"Shabanzadeh","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/bjs.4547","article-title":"Development of symptoms and complications in individuals with asymptomatic gallstones","volume":"91","author":"Halldestam","year":"2004","journal-title":"Br. J. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3949\/ccjm.85a.17035","article-title":"Gallstones: Watch and wait, or intervene?","volume":"85","author":"Ibrahim","year":"2018","journal-title":"Clevel. Clin. J. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/2\/335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:31:00Z","timestamp":1760185860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/2\/335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,4]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["nu11020335"],"URL":"https:\/\/doi.org\/10.3390\/nu11020335","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,4]]}}}