The prevalence of cholesterol gallstones is high in Western populations, while pigment gallstones are common in Asian populations. Dietary factors are suggested to be associated with gallstone risk, but their relationship with gallstone type has not been evaluated. This study investigated the association between diet and risk of cholesterol gallstone or pigment gallstone in a Korean population whose dietary pattern and type of gallstone were changed during the last 30 years.
Patients with cholesterol (n = 40) and pigment (n = 59) gallstones were recruited after laparoscopic cholecystectomy and were compared with those of age- and sex-matched controls without gallstones (n = 99). Dietary intakes were assessed by trained dietitians using a semi-quantitative food frequency questionnaire. Multinomial logistic regression analysis was performed to calculate odds ratios and 95% confidence intervals to examine the associations between diet and risk for type of gallstones adjusted by potential confounders.
Patients with cholesterol gallstone consumed more lipid, animal lipid, beef, pork, and fried food than those with pigment gallstones and control, while patients with pigment gallstone consumed more carbohydrate and noodles than patients with cholesterol gallstone and control. In multinomial logistic regression analysis using control as reference group, dietary pattern with high consumption of beef, pork, and fried food was associated with risk of cholesterol gallstones, while there was no association between the risk of pigment gallstone and dietary pattern. In addition, control consumed more alcohol than patients with cholesterol and pigment gallstones.
The present study suggested consumption of fat from meat and fried foods increased the risk of cholesterol gallstone, and intake of carbohydrate from noodles increased the risk of pigment gallstone.
Gallstone disease is one of the most prevalent gastrointestinal disorders . Its incidence has increased around the world, including in Korea, over the past 30 years . Gallstones are mostly classified as cholesterol and pigment gallstones; the prevalence of cholesterol gallstones is higher and the prevalence of pigment gallstones is lower in Western populations compared to Asian populations . Development of cholesterol gallstones is related to saturation of cholesterol in bile, cholesterol crystallization and gallbladder stasis . On the other hand, pigment gallstones develop from the release of β-glucuronidase from bacterial infections; this produces calcium salts of unconjugated bilirubin .
It has been shown that age, sex, ethnicity, obesity, and family history of gallstone disease are risk factors for gallstone, and diet is a major modifiable risk factor . Previous studies reported that risk of gallstone was positively associated with intake of meat, energy, fat and saturated fat, but negatively associated with intake of vegetable and fiber in Western and Asian population [6,7,8,9,10,11,12,13,14,15]. In particular, high meat intake was associated with risk of gallstone disease , since consumption of red meat inhibited bile acid transporters by trimethylamine which induced cholesterol gallstone . In addition, previously studies reported that risk of gallstone was positively intake of margarine, cooking oil, trans fatty acids, and refined sugars, but negatively associated with moderate intake of alcohol and coffee in Western population and Japanese [7, 13, 17,18,19]. The risk of gallstone was also negatively associated with a healthy dietary pattern in Iranian women  and a traditional Mexican diet pattern in Mexican-American men . However, none of the above studies differentiated type of gallstones.
A few animal studies reported that intake of high carbohydrate led to formation of pigment gallstone in prairie dogs  and hamsters . However, there has been no human study to compared diet and the risk of pigment gallstones.
Pigment gallstones were predominant in Korean people, but the proportion of cholesterol gallstones has been increased > 50% since the late 1990s . The dietary pattern in Korea has become more westernized with more fat and less fiber during the past a few decades . With the change in dietary pattern, the incidence of cholesterol gallstones has increased and pigment gallstones have decreased in Korea . This finding suggests that Koreans may be a good representative population for analyzing the association between diet and gallstone type. Thus, the purpose of present study was to investigate the hypothesis that westernized diet with more meat rich in fat and less fiber was associated with risk of cholesterol gallstones, while carbohydrate rich diet was associated with risk of pigment gallstones.
This study was performed from April 2014 to May 2015 at the general surgery clinic, HYU Hospital, Seoul, Korea with gallstone patients (n = 135) who underwent laparoscopic cholecystectomy after diagnosed with gallstones. The presence of gallstones was determined by ultrasonography or computed tomography. Removed gallstones were classified into cholesterol gallstone (n = 40), pigment gallstone (n = 59), and mixed gallstone (n = 36) based on external appearance of the gallstone determined by two independent general surgeons. Patients (cases) were excluded if they had following conditions: underwent open cholecystectomy or biliary drainage procedure; serious comorbidity that required long-term hospitalization; and diagnosed mixed gallstones. Age- and sex-matched controls (n = 99) with similar demographic characteristics but without gallstones were recruited from same hospital.
This study protocol was conducted according to the guidelines laid out in the Declaration of Helsinki and was approved by the Institutional Review Board of HYU (HYI-14-001-2). Written informed consent was obtained from all participants.
Information obtained from participants by trained interviewers included age, sex, family history, medical history, regular exercise, smoking, drinking, and taking supplements. Height and weight were obtained from medical records and body mass index (BMI) was calculated. All women were asked about parity, oral contraceptive use, and hormone replacement therapy.
Dietary intake was assessed by registered dietitian using a semi-quantitative food frequency questionnaire (FFQ) of 63 food items commonly consumed by Koreans Health and Nutrition Examination Survey . Frequency of food intake was classified into 10 categories: one, two, or three times per day; four to six times per week; two to three times per week; once per week; two to three times per month; once per month; six to 11 times per year; never or seldom. Dietary intake was analyzed with CAN-pro 4.0 software (Computer Aided Nutritional Analysis Program for professionals, Korean Nutrition Society, Seoul, Korea).
Data were expressed as mean ± SD and a P value < 0.05 was considered statistically significant. All data were analyzed using SPSS version 21.0 (Statistical Package for Social Science, Inc., Chicago, IL, USA). Categorical variables were analyzed using chi-square test, and continuous variables were analyzed using ANOVA after adjusting for potential confounders.
Principal component factor analysis was used to generate dietary patterns based on 25 food groups. Factor scores were rotated using orthogonal (varimax) rotation. To identify the characteristics of the factors, the collection of food groups with factor loadings > 0.4 was used. The factor score for each pattern was calculated by summing intake of food by their factor loadings . After obtained factor scores, multinomial logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to examine the associations between dietary patterns and risk for cholesterol and pigment gallstones after adjusting for potential confounders such as energy intake, family history of gallstone disease, and drinking, which were significantly different factors among three groups. In addition, energy intake was added as potential confounders for analyzing association between risk of gallstone and intake of nutrients and foods .
Baseline characteristics of subjects
Patients with cholesterol and pigment gallstones had significantly higher family history of gallstone disease as compared to controls, while controls consumed more alcohol than patients with cholesterol and pigment gallstones (Table 1). However, there were no significantly differences in age, sex, pregnancy experience, oral contraceptive use, hormone replacement therapy, height, weight, body mass index (BMI), medical history, exercise, smoking, and supplement use among three groups.