Presence of Bile Acid in Alcohol Consumption

Skyline of Mexico City at night

There are important differences in gallstone disease (GD; gallstones or cholecystectomy) prevalence among populations. GD is one of the main diseases of North American Indians and those of Chile and Bolivia. High GD prevalence has also been reported in Mexican-Americans (23.2% for women, 7.2% for men)9. A. Diehl and M. Stern, Special health problems of Mexican-Americans. Obesity, gallbladder disease, diabetes mellitus, and cardiovascular disease. Adv Intern Med 34 (1989), p. 73. View Record in Scopus | Cited By in Scopus (74). In Mexico City, a study of necropsies at the General Hospital of Mexico shows a prevalence of GD of 20.4% for women and 8.4% for men over four decades (1953–1988). In a sample of subjects of low socioeconomic status in Mexico City, the prevalence of GD determined by ultrasound was 19.7% for women and 5.8 for men.

Among GD cases, gallstones can be symptomatic or asymptomatic. In some studies in which gallstones have been detected by ultrasound, prevalence of asymptomatic gallstones was defined as the non-presence of biliary pain or any epigastric area and/or hypochondrium pain lasting for more than 30 min; this type accounted for about 70% of the total gallstones.

Several risk factors for GD have been well documented and include the following: gender, age, obesity, number of pregnancies, oral contraceptive use, and non–insulin-dependent diabetes mellitus (NIDDM). In the Western World, cholesterol stones are the most common. In Mexico, 86.4% of stones are composed of cholesterol. It has been suggested that for cholesterol stones to develop, there must be an oversaturation of bile with cholesterol; there is a relationship between the metabolic pathway of plasmatic cholesterol with bile cholesterol and bile acid proportion. Bile is the principal way for excreting body cholesterol; therefore, an association between plasma lipid concentrations and GD has been suggested. Some studies that have evaluated this relationship have reported no differences in plasma cholesterol levels, or differences only in high density lipoprotein (HDL-C) concentration between subjects with and without GD. Other studies have reported an inverse association between GD and plasma cholesterol levels as well as low-density lipoprotein (LDL-C) concentrations that are lower among subjects with GD. Most studies reported a positive relationship between triglyceride concentration and GD, but others found no such a relationship.

Three basic elements are proposed as being responsible for the development of cholesterol gallstones, including the presence of bile oversaturated with cholesterol, the presence of nucleating factors in bile, and gallbladder hypomotility. It has been suggested that at least three defects could lead to cholesterol oversaturation of bile, these being cholesterol hypersecretion with normal bile acid secretion, normal cholesterol secretion with bile acid hyposecretion, or a combination of cholesterol hypersecretion and bile acid hyposecretion. Current evidence indicates that cholesterol hypersecretion with normal bile acid secretion is the dominant abnormality in the pathogenesis of cholesterol gallstones.

The conflicting results of studies on the association between plasma concentration of lipids and GD could be related to the method used to measure the outcome. Self-reports include symptomatic and cholecystectomy subjects, and ultrasound also includes asymptomatic subjects; therefore, not separating by disease phase can lead to conflicting results.

The main purpose of this article is to evaluate the association between the presence of GD: (a) separately by subjects with asymptomatic gallstones; (b) by subjects with a history of cholecystectomy, plasma cholesterol, triglycerides, and high-density lipoproteins (HDL-C) levels, after controlling for other risk factors.

The present study was carried out from August 1991 to August 1992 at a private health care facility in Mexico City that serves a middle- and upper-class population. Participating in this study were 2,089 subjects who visited a diagnostic unit for an annual physical examination. The subjects were at least 20 years of age and, if female, were not pregnant. At the time of their check-up, all participants were asymptomatic and apparently healthy. The subjects provided demographic data, obstetric-gynecologic histories, information on oral contraceptive use and their alcohol consumption rates and smoking habits, as well as previous diagnosis of NIDDM. Total cholesterol, triglycerides, and HDL-C concentrations were determined; liver and biliary tract ultrasounds were performed in all subjects.

GD cases were defined as the presence of at least one of the following criteria: (a) cholecystectomy history and the absence of the gallbladder, confirmed by ultrasonography; or (b) gallstones-vesicular lumen echoes, generating an acoustic shadow at the ultrasonography study. In all cases, recorded images of the gallbladder were reviewed by two radiologists.

Gallstones can be symptomatic or asymptomatic. In this study population, no one had or reported having biliary colic; therefore, we assume that all or at least the major cases were asymptomatic, as reported in similar studies.

The control group was made up only of subjects who had the ultrasound examination with a negative diagnosis of GD. Ultrasound studies were performed with a real-time 3.5 MHz transducer coupled to a Toshiba Sonolayer V Sal 38D echographer (Toshiba Tokyo, Japan).

Information regarding age, gender, alcohol consumption, smoking habits, previous diagnosis of NIDDM, and in women, number of pregnancies and oral contraceptive use, was obtained in face-to-face interviews. Alcohol consumption was categorized as positive for excessive alcohol consumption if the participant had drunk more than 40 g of alcohol per day during the last year, and negative if alcohol consumption was lower. A smoking habit was considered positive if tobacco consumption had exceeded 400 cigarettes during the last year. As part of the physical examination, anthropometric measurements of body weight and height were taken. Using this information, body mass index (BMI) was assessed and categorized as follows: <25 kg/m2 was considered normal; between 25–30 kg/m2 was considered overweight, and >30 kg/m2 was considered obese.

Blood specimens obtained after a minimum 12-h fast were analyzed for total plasma cholesterol and triglyceride concentration, and determined by means of colorimetry with a standard enzymatic assay. For high-density lipoprotein cholesterol (HDL-C), measurements were carried out with an enzymatic colorimetric assay after precipitating very low- and low-density lipoproteins (VLDL and LDL) with phosphotungstic acid in the presence of magnesium. An Abbott Spectrum Chemical Analyzer (Abbott Laboratories, Chicago, IL, USA) was used for all assays.