Diet and cholesterol gallstones

A group of 101 female patients with gallstones were compared to 101 agematched controls. The patients with gallstones had a statistically significant (p=0.0005) increased intake of calories, irrespective of dietary composition. Psychologic stresses were more frequent in patients with gallstones (p<0.001); the following factors were not significantly different in the two groups: body weight, working conditions, and physical exercise.     

Etiology of cholesterol gallstones.

Formation of pure cholesterol stones is initiated by an excessive intake of highly purified carbohydrates, a large intake of animal fats and a restricted intake of vegetable fibers. When the protein content of the lithogenic diet was reduced, mixed or combined stones were formed in golden hamsters. These experimentally, dietarily produced gallstones had compositions and fine structures similar to those of human gallstones. Some mentions were made on black stones which were found in the aged golden hamsters fed with lithogenic diets.     

Replacement of cholesterol gallstones by murideoxycholyl taurine gallstones in prairie dogs fed murideoxycholic acid

The effect of two hydrophilic bile acids, murideoxycholic acid (3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid) and ursodeoxycholic acid, on cholesterol and bile acid metabolism and hepatic pathology and gallstone composition was studied in the prairie dog. Cholesterol gallstones were induced by feeding a diet containing 1.2% cholesterol for 75 days. The animals were divided into six groups, and gallstone regression was studied as follows: groups 2 and 5, chow plus 0.2% cholesterol; groups 3 and 6, chow plus 0.2% cholesterol plus 0.15% ursodeoxycholic acid; groups 4 and 7, chow plus 0.2% cholesterol plus 0.15% murideoxycholic acid. Animals in groups 2 to 4 were killed after an additional 6 wk; animals in groups 5 to 7 were killed after an additional 12 wk. Gallstone dissolution did not occur in any group. The gallstones in groups 2, 3, 5 and 6 were typical cholesterol aggregates, as determined by polarized light microscopy and Fourier transform infrared spectrometry. The gallstones of the murideoxycholic acid group were large, solitary, dark stones that appeared radiopaque under 22 kVp x-ray examination. Scanning electron microscopy showed that in these stones the cholesterol crystals had been replaced by an amorphous material, both within the stone and on the stone surface. Chemical analysis indicated that at the end of 12 wk the calcium/sodium salt of the taurine conjugate of murideoxycholic acid (murideoxycholyl taurine) comprised 70% of the stones; protein, cholesterol and small amounts of other bile salts were also present. In vitro studies confirmed the insolubility of the sodium and calcium salts of murideoxycholyl taurine. These studies indicate that the hydrophilic bile acids, murideoxycholic acid and ursodeoxycholic acid, did not achieve gallstone dissolution under the conditions used. In the animals fed murideoxycholic acid, an insoluble calcium salt of murideoxycholyl taurine replaced cholesterol as the major constituent of gallbladder stones. This is the first example of an insoluble dihydroxy taurine-conjugated bile acid; administration of the unconjugated bile acid induced precipitation of a kind of gallstone not previously reported. The final result was transformation of cholesterol stones to bile salt stones.     

高胆固醇饮食对胆结石形成的研究

通过高胆固醇饮食对胆结石形成的动物试验 ,探讨高胆固醇饮食的成石原因和机理 ,为在饮食上预防胆结石的形成提供试验依据 ,为胆结石的临床治疗和病人的康复提出理论依据 ,并为今后胆固醇结石的研究提供适宜的动物模型。本研究以狗作为试验动物 ,用 0 3%的高胆固醇饲料进行试验喂养 ,连续喂养 6周 ,观察动物胆结石的形成 ,测定血中胆固醇和甘油三酯水平 ,分析胆汁中成分的改变。在试验四周内试验组动物形成胆结石 ,且成石率为 10 0 % ,结石直径为 1mm～ 11mm。试验组动物血清胆固醇和甘油三酯水平显著提高 (p <0 0 1) ,胆汁中胆固醇和胆固醇结晶显著升高 (p <0 0 1)。通过高胆固醇膳食 ,试验动物血清及胆固醇和甘油三酯水平增加 ,胆汁中胆固醇增加 ,成石性胆汁形成。提示胆固醇代谢的异常变化在胆囊结石中起作用。     

Prevention of cholesterol gallstones by lignin and lactulose in the hamster

The effect on prevention of cholesterol gallstones by a nonfermentable type of fiber, lignin, and a fermentable fiber analogue, lactulose, was studied in hamsters fed an essential fatty acid deficient diet. Control animals had a high incidence of cholesterol gallstones (21 of 24) and lithogenic bile (lithogenic index 1.08). Animals fed lignin had significantly fewer gallstones (11 of 25), improved cholesterol saturation of gallbladder bile, and increased fecal bile acid excretion. Lactulose-fed animals had significantly fewer gallstones (12 of 24) but no significant change in cholesterol saturation of gallbladder bile or in fecal bile acid excretion. Serum cholesterol concentration was reduced, however, and fecal neutral steroid excretion was increased. Gallstones were completely prevented in animals fed both lignin and lactulose (0 of 22), but gallbladder bile cholesterol saturation was not significantly different from the lignin-fed group. Gallbladder bile mucopolysaccharide concentrations did not differ among groups. Lignin appears to prevent cholesterol gallstones in this model by improving cholesterol saturation of bile. The mechanism of action of lactulose is not yet clear.     

胆固醇与胆结石的关系

目的:探讨胆固醇与胆结石的关系.方法:对某高校3 905名教职员工进行健康检查,采用彩超进行肝胆检查,全自动生化分析仪进行血总胆固醇测定,分析他们二者的关系.结果:3905名教职员工健康检查发现胆结石189例,其中胆固醇增高(>5.17 mmol/L)68例(35.98%),胆固醇正常偏高(4.67-5.16mmol/L)40例(21.16%),胆固醇正常(<5.17mmol/L)81例(42.86%),胆固醇正常偏高和增高与胆固醇正常相比,其胆结石发病率明显增高(均P<0.01).结论:胆结石与高胆固醇增高有一定关系,在胆结石保守治疗时,应注意降低胆固醇.     

Composition of pigmented centers of cholesterol gallstones

Most cholesterol gallstones have visually pigmented centers, but it is unclear whether this represents simple co-precipitation of pigment with cholesterol during stone nidation or nidation on a true pigment stone center. To clarify this issue, we selected from among 67 sets of cholesterol gallstones, 12 sets with the most conspicuously pigmented centers. The composition of the centers and the peripheries of these 12 stones was analyzed using infrared spectroscopy and compared with that of 10 black pigment gallstones. The pigmented centers of cholesterol stones contained 80.1 +/- 7.9% (mean +/- S.E.) cholesterol, 6.2 +/- 3.4% calcium bilirubinate (only 4 of the 12 centers had measurable calcium bilirubinate), trace amounts of calcium phosphate and no calcium carbonate or calcium palmitate. The peripheral areas of the cholesterol stones contained 91.6 +/- 2.3% cholesterol and no detectable calcium salts. For comparison, the composition of the centers of 10 black pigment gallstones was 13.5 +/- 2.2% cholesterol, 28.2 +/- 5.3% calcium bilirubinate, 5.5 +/- 2.4% calcium phosphate and 10.6 +/- 5.8% calcium carbonate. The composition of only one cholesterol stone center (15.8% cholesterol, 26.8% calcium bilirubinate) resembled that of a pigment stone, but even this center differed from that of a typical pigment stone in that it contained only a trace amount of calcium phosphate and no calcium carbonate. Thus, the chemical composition of pigmented centers of cholesterol gallstones is quantitatively different from that of black pigment stones, suggesting that cholesterol gallstones do not form on a pigment stone nidus.     

Mucus glycoprotein content of human cholesterol gallstones

Cholesterol gallstones were obtained from patients undergoing cholecystectomy and the mucus glycoprotein extracted. The biliary mucus glycoprotein was separated from other contaminants by Sepharose 4B gel filtration and the PAS staining excluded volume used to estimate mucus glycoprotein content of the gallstones. Hexosamine and sialic acid analysis of the glycoprotein indicated it was compositionally similar to the human mucus glycoprotein from bile. The mucus glycoprotein content of the nine stones analysed individually varied between 0.75 and 2.3 mg (a 3-fold variation) (1.27 +/- 0.16 mg, mean +/- SEM), whereas stone weight varied between 0.076 and 5.885 g (a 77-fold variation) (1.27 +/- 0.63 g, mean +/- SEM). When a pool of smaller stones, average weight 47 mg, was extracted, only 1.73 mg of glycoprotein was isolated, an average of 0.01 mg/stone. Analysis of the mucus glycoprotein by gel filtration on Sepharose 2B showed the majority of the glycoprotein was excluded as is the case with the mucus glycoprotein in bile. These results are consistent with biliary mucus glycoprotein being involved in the initial stages of gallstone formation but not in subsequent growth.     

Diet and cholesterol gallstones. A further study

In a first study, a population of 1,045 women from 20 to 61 years old has been studies. 24 (2.3%) were known to have gallstones. After excluding these 24 cases, 214 were drawn from the same population and accepted an oral cholecystography. 11 cases of stones (5.1%) were discovered. The diet of these 11 patients and of the 202 women without gallstones was not significantly different. In a second study, the diet of 50 patients with known gallstones and the diet of 50 matched controls have been compared. No significant difference between the two groups can be demonstrated for calories, protein, fat or carbohydrates intake. These results are compared to previous results which showed overconsumption of food in gallstone patients. The method for all studies being similiar, it seems that the dietetic factors are now less important in cholesterol stones pathogenesis than during the period which followed the second world war starvation in southeast France. The assumption that undernutrition diminishes the chance for a women to develop gallstones is proposed.     

Diet and cholesterol gallstones. A multicenter study

In France, changes in the incidence of gallstones during the 20 years following World War II paralleled the changes in total calories, protein and lipid of the diet. The incidence of gallstones in autopsy statistics has been compared to the diets in different countries: France, India, Japan, Portugal, South Africa, Sweden and Uganda. Low calorie, low protein, low lipid intake and vegetable diet are associated with a low incidence of gallstones. A positive correlation between calorie intake and gallstones incidence was found at necropsy for calorie intakes lower than 3,000 kcal. In countries with high calorie, high protein and high lipid intakes, such a correlation was not found. These results suggest that a hypocaloric diet associated with a low intake of fat and protein mostly of vegetable origin, is protective against cholelithiasis.     

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones

In Japan the composition of gallstones is changing rapidly from the once-predominant brownpigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 ±10 vs. 146 ±8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 α-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 α-hydroxy-4-cholesten-3-one 12 α-hydroxylase (12 α-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 α-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 α-hydroxylase and 12 α-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis. This study was supported in part by a Grant-in-Aid for Scientific Research (No. 02454226) from the Ministry of Education, Science and Culture of Japan, and a grant from University of Tsukuba Project Research.     

Measurement of apolipoprotein A1 in cholesterol gallstones and gallbladder bile of patients with gallstones

Biliary apolipoprotein A1 in bile inhibits the nucleation of cholesterol crystals from bile supersaturated with cholesterol. In the present study, using an enzyme-linked immunosorbent assay of apolipoprotein Al, we determined the content of apolipoprotein Al in cholesterol gallstones and samples of gallbladder bile collected simultaneously from 23 patients during cholecystectomy. Protein content in cholesterol gallstones ranged from 50 to 5700 g/g, with median, quartile, and three quartile values being 250, 111, and 740; apolipoprotein A1 content ranged from 9 to 9000 ng/g (200, 41, 647). The gallbladder bile samples contained protein at concentrations of 0.4-9.0 mg/ml (2.0, 1.1, 3.2), while apolipoprotein A1 was present at concentrations of 2.0-136.0 g/ml (30.0, 10.0, 90.0). A notable finding was that the A1/total protein (TP) values for gallbladder bile, which ranged from 0.13% to 6.80% (1.62, 0.89, 3.34), were several times higher than those determined for gallstone samples, which ranged from 0.01% to 1.2%, 2% (0.06, 0.02, 0.25). The results of sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the protein profile in cholesterol gallstones was similar to that in gallbladder bile. It was concluded that: (1) the protein contained in gallstones may originate from bile, (2) the content of apolipoprotein A1 in cholesterol gallstones is only a trace amount, compared with that in gallbladder bile, and (3) biliary apolipoprotein A1 may be retained in a soluble phase in gallbladder bile, with minimal precipitation onto the surfaces of gallstones.     

Regression of preestablished cholesterol gallstones by dietary garlic and onion in experimental mice

We have recently reported the health beneficial potential of dietary garlic and onion in reducing the incidence and severity of cholesterol gallstone (CGS) during its experimental induction in mice. In the current study, the efficacy of dietary garlic and onion in regressing preestablished CGS was investigated in experimental mice. After inducing CGS in mice with a lithogenic diet for 10 weeks, they were maintained on basal diets containing 0.6% dehydrated garlic or 2% dehydrated onion for a further 10 weeks. Dietary garlic and onion, either raw or heat processed, regressed preformed CGS in mice up to 53% to 59%, whereas the regression in the basal control diet group was only 10%. The antilithogenic potency of garlic was decreased by its heat processing, but not in the case of onion. Biliary cholesterol was significantly decreased in garlic- and onion-fed animals. Biliary cholesterol saturation index and hydrophobicity index were significantly lowered by dietary garlic and onion. Serum and liver cholesterol levels were decreased by feeding these spices during post-CGS induction period. Hepatic hydroxymethylglutaryl-coenzyme A reductase activity was increased after feeding garlic and onion, whereas activities of the cholesterol-degrading enzymes cholesterol-7α-hydroxylase and sterol-27-hydroxylase were increased in spice-fed groups. These results indicate that feeding garlic and onion effectively accelerates the regression of preformed CGS by promoting cholesterol desaturation in bile. This observation is significant in the context of evolving dietary intervention strategy to address regression of existing CGS and stopping the possible recurrence.