Abstracts
Amino acids & gallstones
Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved.
Measured the effect of giving rapid intravenous infusions of amino acid solutions in 8 normal subjects.
Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of amino acid infusion.
Rapid infusion of 125 mL of an amino acid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction.
Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.
Zoli G et al., Promotion of gallbladder emptying by intravenous amino acids. Lancet, 1993 May 15, 341:8855, 1240-1.
Antioxidants & gallstones
Antioxidant intake (1)
Whereas macronutrient intake has been extensively investigated in an attempt to unravel the pathogenesis of human cholesterol gallstones, theoretical considerations and animal models suggest that deficits in micronutrient antioxidants may be more relevant.
Analysis of data for the 9 pairs involving patients on their normal diets showed no differences in the intakes of energy macronutrients, and cholesterol, but the patients ingested lower amounts of 10 among 16 antioxidants (P < 0.05 for methionine, alpha-tocopherol, manganese, and vitamin D; 0.05 < P < 0.10 for cysteine, beta-carotene, vitamin C, selenium, zinc, and phosphorus).
Both subsets of patients ingested lower amounts of linoleic acid (diet unchanged P = 0.009, changed P = 0.026) and several essential amino acids than did matched controls.
Institution of a low-fat diet caused the expected fall in intakes of energy and saturated fatty acids such that the deficit in alpha-tocopherol was amplified, but substitution of fruit and vegetables by the patients resulted in a fortuitous increase in vitamin C, beta-carotene, and manganese intake.
Results support the hypothesis that insufficiency of dietary antioxidants, particularly alpha-tocopherol, may be germane to human gallstone disease; also, low intakes of linoleic acid and essential amino acids may be relevant.
Worthington HV et al., A pilot study of antioxidant intake in patients with cholesterol gallstones. Nutrition, 1997 Feb, 13:2, 118-27.
Carotenoids and tocopherols (2)
Compared the plasma and biliary concentrations of carotenoids, retinoids and tocopherols among controls and patients with biliary and pancreatic diseases, these compounds were measured by high performance liquid chromatography in bile collected during 41 endoscopic retrograde cholangiopancreatographies.
In 13 patients in whom bile duct stones impaired biliary excretion (as reflected by raised serum bilirubin), beta-carotene was significantly decreased in both plasma (199.6 +/- 35.5 nmol/l) and bile (9.4 +/- 2.0 nmol/l), with a similar trend for other carotenoids.
In 3 subjects with complete biliary obstruction, plasma beta-carotene (35.8 +/- 20.2 nmol/l) decreased even more, probably reflecting malabsorption.
Indeed, for the entire group (n = 41), the correlation between plasma and bile or red blood cell beta-carotene was highly significant, whereas plasma/red blood cell ratios remained unchanged.
Similar findings were observed for alpha-tocopherol, with 8.4 +/- 0.9 mumol/l in control bile (vs. 23.2 +/- 1.7 mumol/l in plasma), and no significant change in the various groups.
1. Carotenoids and tocopherols undergo biliary excretion in man.
2. Biliary concentrations reflect plasma levels in both normal and pathologic states.
3. Decreased biliary excretion of carotenoids does not increase plasma concentrations.
Leo MA et al., Carotenoids and tocopherols in various hepatobiliary conditions. J Hepatol, 1995 Nov, 23:5, 550-6.
Cholelithiasis
Implementing a 605 kcal very low calorie diet, 179 obese patients with a mean body mass index of 36.3 were retrospectively evaluated for the development of gallstones. Nine percent of the patients had preexisting gallstones, and 11% of the patients developed gallstones either during or within 6 months of completing the diet. Six percent had subsequent cholecystectomies. Ursodeoxycholic acid administered to 1 patient resulted in spontaneous stone dissolution, whereas natural spontaneous dissolution occurred in 3 patients. A similar incidence of gallstones was observed in 3 other programs using the same diet. Rapid weight loss associated with the use of very low calorie diets can result in a significant incidence of gallstone formation.
"Cholelithiasis in Patients Treated With a Very Low Calorie Diet", Kamrath, Richard O., et al, American Journal of Clinical Nutrition, 1992;56:255S-7S.
Coffee & gallstones
Normal consumption of either regular coffee, or decaffeinated coffee without additives, cream or sugar, is capable of inducing gallbladder contractions and may be responsible for gallbladder attacks in certain patients. Suggest symptomatic gallstone formers avoid drinking coffee.
"Coffee Stimulation of Cholecystokinin Release and Gallbladder Contraction in Humans", Douglas, Bruce R., et al, American Journal of Clinical Nutrition, 1990;52:553-6.
Gallstones in children
Fifty children (21 boys and 29 girls) and adolescents were found to have gallstones at Children's Hospital of Buffalo (NY) during a period of 10 years.
The majority of patients could be categorized into four groups:
· hemolytic disease (18 patients),
· parenteral nutrition (eight patients),
· adolescent pregnancy (seven patients), and
· idiopathic (10 patients),
· while seven patients had a variety of other etiologies.
Right upper quadrant pain was the most common symptom (32 patients), followed by jaundice (15 patients), vomiting (13 patients), and nonspecific abdominal complaints (13 patients).
Ultrasonography was the mode of diagnosis in 48 patients. Cholecystectomy was performed in 36 patients.
In contrast to gallstones in adults, after exclusion of the patients with adolescent pregnancy, there was no female predominance. Pancreatitis was the most common complication, occurring in 8% of the patients; cholecystitis and cholangitis were absent.
Reif S et al., Gallstones in children. Characterization by age, etiology, and outcome [see comments]. Am J Dis Child, 1991 Jan, 145:1, 105-8.
Hispanics & gallstones
The 1982-1984 Hispanic Health and Nutrition Examination Survey used ultrasonography to investigate risk factors for gallstone disease (gallstones or cholecystectomy). Mexican American, Cuban American, and Puerto Rican men (n = 968) and women (n = 1,325) aged 20-74 years were selected from household samples in nine states.
Among men, the risk of gallstone disease increased with age, education, and subscapular skinfold thickness.
Among women, the risk of gallstone disease increased with age, body mass index, four skinfold measures, diabetes, impaired glucose tolerance, and oral contraceptive usage, but not with parity.
Women currently using oral contraceptives were also found to be at increased risk of current gallstones. Menopause was a risk factor for gallstone disease and cholecystectomy. Alcohol consumption was negatively related to the risk of gallstone disease.
In men, the cholesterol/high density lipoprotein cholesterol ratio was positively related to gallstone disease and, in women, this ratio was negatively related. Gender was highly significant. Mexican Americans are at increased risk of gallstone disease.
Maurer KR et al., Risk factors for gallstone disease in the Hispanic populations of the United States. Am J Epidemiol, 1990 May, 131:5, 836-44.
Middle-aged Men & gallstones
Studied the relation between the intake of energy, nutrients, and foods and the 25-year incidence of clinically diagnosed gallstones was.
Information on the presence of gallstones was obtained by self-report and verified through medical records after death. Of 860 men, 54 developed symptomatic gallstones, yielding an incidence rate of 3.1/1000 person-years.
Provide a comprehensive picture of dietary risk factors for clinically diagnosed gallstones based on a long-term follow-up.
Calcium intake was inversely associated with gallstone incidence.
A positive association with sugars (monosaccharides and disaccharides) appeared after the introduction of age, body mass index, calcium intake, and the intake of energy from nutrients other than sugars into the model.
Calcium may alter the composition of bile by preventing the reabsorption of secondary bile acids in the colon, whereas sugars may influence bile composition through lipoprotein metabolism.
Moerman CJ et al., Dietary risk factors for clinically diagnosed gallstones in middle-aged men. A 25-year follow-up study (the Zutphen Study). Ann Epidemiol, 1994 May, 4:3, 248-54.
Obesity & gallstones
Obesity (1)
Experts agree that overweight and obesity pose a significant public health problem in the United States. Obesity is considered to be a complex, multifactorial disease involving genetics, physiology, psychology, and environment, and is influenced by cultural messages.
Comorbidities linked to obesity include coronary heart disease, stroke, hypertension, diabetes mellitus, gout, dyslipidemias, cholecystitis, and gallstones.
Pharmacists can help patients with dietary goals by understanding sound principles of weight management.
Wood OB & Popovich NG: Nonpharmacologic treatment of obesity. J Am Pharm Assoc (Wash), 1996 Nov, NS36:11, 636-50.
Obesity (2)
Overnutrition manifested by obesity has emerged as a major health problem in affluent countries. In spite of increased interest in fitness, obesity is on the increase in the United States. This is particularly so among children and adolescents. Although obesity is associated with many risk factors for diseases, the mechanisms whereby it enhances disease risk are not fully understood.
Suggest that overnutrition produces clinical diseases only in individuals who already possess a metabolic weakness or "defect" in a given system. In the absence of such underlying defects, overnutrition, or obesity, is well tolerated.
One of the most common consequences of obesity is dyslipidemia, that is, elevations of very low-density lipoprotein (VLDL) triglycerides and low-density lipoprotein (LDL) cholesterol and low concentrations of high-density lipoprotein (HDL) cholesterol. The major effect of overnutrition on lipoprotein metabolism is to stimulate the production of VLDL. For patients who have an underlying defect in lypolysis of VLDL triglycerides, hypertriglyceridemia will develop in the obese state.
For those who have defective clearance of LDL, obesity will accentuate hypercholesterolemia. Both of these effects can be explained by overproduction of VLDL, due to obesity, combined with a genetic defect in clearance of VLDL or LDL.
The mechanism whereby obesity causes a lowering of HDL cholesterol is uncertain, although it could enhance removal of HDL by an excess of adipose tissue.
Another disease associated with obesity is cholesterol gallstones. The presence of obesity more than doubles the risk for gallstones. Two underlying factors increase the danger for gallstones: a deficiency of hepatic secretion of bile acids and a tendency for formation of cholesterol crystals in bile. Overnutrition promotes the synthesis of whole-body cholesterol, and the only route for excretion of this excess cholesterol is through the biliary tree.
Grundy SM & Barnett JP: Metabolic and health complications of obesity. Dis Mon, 1990 Dec, 36:12, 641-731.
Pigmented gallstones
Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct.
Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition.
Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones.
Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease.
The pathogenesis of black stones is probably related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates.
Brown pigment stones are formed in bile infected with enteric bacteria that elaborate hydrolytic enzymes: beta-glucuronidase, phospholipase A, and conjugated bile acid hydrolase. The resulting anions of bilirubin and fatty acids form insoluble calcium salts.
Trotman BW: Pigment gallstone disease. Gastroenterol Clin North Am, 1991 Mar, 20:1, 111-26.
Women & gallstones
Dietary risk factors for the development of gallstones have not been clearly established.
Evaluated the role of dietary constituents, fasting, and dieting on subsequent hospitalization with gallstone disease among 4,730 women, ages 25 to 74 years, who participated in the first follow-up of the first National Health and Nutrition Examination Survey.
Baseline dietary variables were established through a 24-hour dietary recall and a medical history.
The hazard rate of hospitalization with gallstone disease increased with increasing overnight fasting period and with dieting. Intake of fiber showed a small protective effect. The effect of energy intake was significant only among women younger than age 50 years at baseline. Results were not affected by adjustment for known risk factors for gallstone disease or other dietary factors.
A long overnight fasting period, dieting, and low fiber intake may increase the risk of hospitalization with gallstone disease.
Sichieri R et al., A prospective study of hospitalization with gallstone disease among women: role of dietary factors, fasting period, and dieting. Am J Public Health, 1991 Jul, 81:7, 880-4.
The Young & gallstones
Infants, children and adolescents
Cholecystitis and cholelithiasis are being recognized with increasing frequency in infancy, childhood, and adolescence. Hematologic disorders account for a large proportion of cases; however, in most cases the etiology is uncertain.
Infants and children are noted with stones in association with total parenteral nutrition, prolonged fasting, or ileal resection. Biliary dyskinesia, a disorder of impaired gallbladder contractility, is being recognized with increased frequency in late childhood and teenage years.
Spontaneous stone resolution is frequently noted in infancy, and a period of observation is appropriate in the absence of symptoms. Laparoscopic cholecystectomy is the procedure of choice for symptomatic cholelithiasis and biliary dyskinesia. Common bile duct stones are unusual in children, occurring in 2% to 6% of children with cholelithiasis, often in association with obstructive jaundice and pancreatitis.
Rescorla FJ: Cholelithiasis, cholecystitis, and common bile duct stones. Curr Opin Pediatr, 1997 Jun, 9:3, 276-82.
Exercise & gallstones
Exercise
An 8-year study of over 45,800 men between 40 and 75 years of age found that men who exercised the most had a 37% lower risk of developing gallstone pain than men who reported the least amount of physical activity. Men who regularly ran, jogged, walked briskly, or played racquet sports had the lowest rate of gallstone problems.
Exercise May Help Prevent Gallstone Symptoms, Medical Tribune, April 16, 1998;21/Annals of Internal Medicine, 1998;128:417-425.
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