|
1
|
Bin C, Zhang C. The association between vitamin D consumption and gallstones in US adults: A cross-sectional study from the national health and nutrition examination survey. J Formos Med Assoc 2025; 124:212-217. [PMID: 39261120 DOI: 10.1016/j.jfma.2024.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 05/13/2024] [Accepted: 09/06/2024] [Indexed: 09/13/2024] Open
Abstract
BACKGROUND Gallstone disease is common in the US and Europe. Gallstones are associated with factors such as age, sex, weight, and serum cholesterol levels. A complex relationship exists between vitamin D levels and cholesterol metabolism. However, the relationship between vitamin D level and gallstones remains unclear. This study aimed to investigate whether gallstones are associated with dietary vitamin D (D2+D3) consumption (VDC) in American adults. METHODS This cross-sectional study used data from people who participated in the National Health and Nutrition Examination Survey between March 2017 and March 2020. Multivariate logistic regression models were used to determine the association between vitamin D intake and the presence of gallstones. Stratified and interaction analyses were performed to determine whether the relationship was stable across different subgroups. RESULTS 6873 participants were included. VDC (per 1 SD) was positively associated with gallstones in the crude model (OR: 1.11, 95% Confidence Interval (CI): (1.05-1.17); p < 0.001), Further adjustment did not affect the results. When vitamin D was analyzed using quartiles, with increased quartile of VDC, the incidence of gallstones increased, and the OR of Q2 (OR: 1.08, 95% CI: 0.89-1.32, p = 0.436) and Q3 (OR: 1.55, 95% CI: 1.28-1.87, p < 0.001) was higher than that of Q1 in crude model. After adjusting for covariates, there is a positive association between VDC and incidence of gallstones without statistical significance. CONCLUSION VDC was positively associated with the incidence of gallstones, however, further studies are required to gather additional evidence.
Collapse
Affiliation(s)
- Chuxuan Bin
- Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Address: No. 1, Dongjiaomin Road, Dongcheng District, Beijing, China.
| | - Chuan Zhang
- Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Address: No. 1, Dongjiaomin Road, Dongcheng District, Beijing, China.
| |
Collapse
|
|
2
|
Wang H, So H, Ko SW, Jung SW, Bang SJ, Park EJ. Gallstone Is Associated with Metabolic Factors and Exercise in Korea. Healthcare (Basel) 2022; 10:healthcare10081372. [PMID: 35893194 PMCID: PMC9329956 DOI: 10.3390/healthcare10081372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/18/2022] [Accepted: 07/21/2022] [Indexed: 11/16/2022] Open
Abstract
Gallstone is a common health problem. Cholesterol stone accounts for 90% of stones in the United States and Europe, but East Asia has a high proportion of pigment stone. The aim of this study was to determine the relationship between modifiable metabolic factors and gallstone in a region with a high prevalence of pigment stone. Among 3159 participants who underwent health screening at Ulsan University Hospital from March 2014 to June 2019, 178 patients were diagnosed with gallstone using abdominal ultrasonography; 2860 participants were selected as a control group. Demographic and laboratory data, and a medical questionnaire were obtained. Hypertension and diabetes mellitus were more prevalent in the gallstone group. Age, waist circumference, systolic blood pressure (SBP) ≥ 140 mmHg, fasting blood glucose, HbA1c ≥ 6.5%, visceral fat index, normal-attenuated muscle area index, and engaging in vigorous exercise for ≥2 days per week were associated with gallstone by univariate analysis. Through multivariate logistic regression analysis, HbA1c ≥ 6.5% (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.31–2.98), and 2 or more days of vigorous exercise per week (OR 0.66, 95% CI 0.45–0.95) remained significant. The association persisted after adjusted analysis for age and sex. HbA1c ≥ 6.5% were positively associated with the gallstone. Vigorous exercise for at least 2 days weekly may be related to a lower risk of gallstone formation.
Collapse
Affiliation(s)
- Hoyoung Wang
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Hoonsub So
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea; (S.W.J.); (S.-J.B.)
- Correspondence: (H.S.); (S.W.K.); Tel.: +82-2-3010-3194 (H.S.); +82-2-2030-4595 (S.W.K.); Fax: +82-2-2030-4641 (S.W.K.)
| | - Sung Woo Ko
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, Catholic University of Korea, Seoul 03312, Korea
- Correspondence: (H.S.); (S.W.K.); Tel.: +82-2-3010-3194 (H.S.); +82-2-2030-4595 (S.W.K.); Fax: +82-2-2030-4641 (S.W.K.)
| | - Seok Won Jung
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea; (S.W.J.); (S.-J.B.)
| | - Sung-Jo Bang
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea; (S.W.J.); (S.-J.B.)
| | - Eun Ji Park
- BigData Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea;
| |
Collapse
|
|
3
|
Retinol-binding protein 4 as a risk factor for cholesterol gallstone formation. Mol Cell Biochem 2013; 377:219-27. [DOI: 10.1007/s11010-013-1587-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 02/08/2013] [Indexed: 12/21/2022]
|
|
4
|
Richter D, Harsch S, Strohmeyer A, Hirobe-Jahn S, Schimmel S, Renner O, Müller O, Schäffeler E, Kratzer W, Schwab M, Stange EF. MALDI-TOF mass spectrometry screening of cholelithiasis risk markers in the gene of HNF1alpha. J Proteomics 2012; 75:3386-99. [DOI: 10.1016/j.jprot.2012.04.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2011] [Revised: 04/23/2012] [Accepted: 04/24/2012] [Indexed: 01/26/2023]
|
|
5
|
Jain R, L. Thiele D. Gastrointestinal and Hepatic Manifestations of Systemic Diseases. SLEISENGER AND FORDTRAN'S GASTROINTESTINAL AND LIVER DISEASE 2010:557-592.e11. [DOI: 10.1016/b978-1-4160-6189-2.00035-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
6
|
Abstract
PURPOSE OF REVIEW Hypertriglyceridemia (HTG) is a well recognized cause of acute pancreatitis accounting for approximately up to 10% of all cases and even up to 50% of all cases in pregnancy. Both primary and secondary disorders of lipoprotein metabolism may be associated with hypertriglyceridemic pancreatitis (HTGP). The purpose of this review is to provide an overview of the current studies on presentation and management of HTGP. RECENT FINDINGS/CONCLUSION Hydrolysis of triglycerides by pancreatic lipase and formation of free fatty acids that induce inflammatory changes are postulated to account for the development of HTGP, yet the exact pathophysiology remains unclear. The clinical features of patients with HTGP are generally not different from patients with acute pancreatitis of other causes, and there is some evidence that HTGP is associated with a higher severity or a higher complication rate. There is no clear evidence as to which HTG patients will develop pancreatitis. Several studies have evaluated the effect of apheresis, the benefit of insulin and/or heparin treatment and the use of different antihyperlipidemic agents in HTGP. Dietary modifications resemble the key features in the long-term management of HTG. Whether HTG may cause chronic pancreatitis in the long-term follow-up remains controversial.
Collapse
Affiliation(s)
- Nils Ewald
- Third Medical Department, University Hospital Giessen and Marburg, Giessen Site, Rodthohl 6, Giessen, Germany.
| | | | | |
Collapse
|
|
7
|
Abstract
Gallstone disease is one of the most prevalent gastrointestinal diseases with a substantial burden to health care systems that is supposed to increase in ageing populations at risk. Aetiology and pathogenesis of cholesterol gallstones still are not well defined, and strategies for prevention and efficient nonsurgical therapies are missing. This review summarizes current concepts on the pathogenesis of cholesterol gallstones with focus on the uptake and secretion of biliary lipids and special emphasis on recent studies into the genetic background.
Collapse
Affiliation(s)
- H-U Marschall
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
| | | |
Collapse
|
|
8
|
Jonkers IJAM, Smelt AHM, Princen HMG, Kuipers F, Romijn JA, Boverhof R, Masclee AAM, Stellaard F. Fish oil increases bile acid synthesis in male patients with hypertriglyceridemia. J Nutr 2006; 136:987-91. [PMID: 16549462 DOI: 10.1093/jn/136.4.987] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Fibrates are drugs of choice in patients with hypertriglyceridemia (HTG), but may increase the risk for gallstones by decreasing bile acid synthesis. Fish oil might be a therapeutic alternative, but its effect on bile acid metabolism in humans is unknown. We compared the effects of triglyceride-lowering therapy by fish oil or bezafibrate on cholesterol synthesis and bile acid metabolism in HTG. Cholesterol synthesis, bile acid pool sizes, and synthesis rates were compared between 9 male HTG patients and 10 normolipidemic controls matched for age, sex, and BMI. Effects of bezafibrate or fish oil were studied only in HTG patients in a randomized crossover trial. Patients had 14-fold higher serum triglyceride concentrations and greater cholesterol synthesis, as indicated by a 107% higher ratio of serum lathosterol to cholesterol (P < 0.01) than controls. The groups did not differ in bile acid metabolism. Both bezafibrate and fish oil reduced serum TG concentration (-68 and -51% vs. baseline, respectively). Compared with baseline, bezafibrate therapy was associated with reduced cholesterol synthesis (-25%, P = 0.009) without changes in bile acid synthesis rate and pool size. In contrast, fish oil increased bile acid synthesis (+31% vs. baseline, P = 0.07 and +53% vs. bezafibrate, P = 0.02) and altered bile acid distribution, as reflected by an increased ratio of the cholic acid (CA) synthesis rate to the chenodeoxycholic acid (CDCA) synthesis rate (+35% vs baseline, P = 0.05 and + 32% vs bezafibrate, P = 0.07) without effects on bile acid pool size or cholesterol synthesis. In conclusion, cholesterol synthesis is greater in HTG patients than in controls, whereas bile acid synthesis does not differ. Bezafibrate and fish oil have similar triglyceride-lowering capacities, but distinct effects on cholesterol synthesis. Bile acid synthesis is increased by fish oil, but not by bezafibrate therapy.
Collapse
Affiliation(s)
- Iris J A M Jonkers
- Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Walcher T, Haenle MM, Kron M, Hay B, Mason RA, von Schmiesing AFA, Imhof A, Koenig W, Kern P, Boehm BO, Kratzer W. Pregnancy is not a risk factor for gallstone disease: Results of a randomly selected population sample. World J Gastroenterol 2005; 11:6800-6. [PMID: 16425387 PMCID: PMC4725038 DOI: 10.3748/wjg.v11.i43.6800] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence, risk factors, and selection of the study population for cholecystolithiasis in an urban population in Germany, in relation to our own findings and to the results in the international literature.
METHODS: A total of 2 147 persons (1 111 females, age 42.8 ± 12.7 years; 1 036 males, age 42.3 ± 13.1 years) participating in an investigation on the prevalence of Echinococcus multilocularis were studied for risk factors and prevalence of gallbladder stone disease. Risk factors were assessed by means of a standardized interview and calculation of body mass index (BMI). A diagnostic ultrasound examination of the gallbladder was performed. Data were analyzed by multiple logistic regression, using the SAS statistical software package.
RESULTS: Gallbladder stones were detected in 171 study participants (8.0%, n = 2 147). Risk factors for the development of gallbladder stone disease included age, sex, BMI, and positive family history. In a separate analysis of female study participants, pregnancy (yes/no) and number of pregnancies did not exert any influence.
CONCLUSION: Findings of the present study confirm that age, female sex, BMI, and positive family history are risk factors for the development of gallbladder stone disease. Pregnancy and the number of pregnancies, however, could not be shown to be risk factors. There seem to be no differences in the respective prevalence for gallbladder stone disease in urban and rural populations.
Collapse
Affiliation(s)
- Thomas Walcher
- University Hospital Ulm, Department of Internal Medicine I, Robert-Koch-Str. 8, D-89081 Ulm, Germany
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
10
|
Fraquelli M, Pagliarulo M, Colucci A, Paggi S, Conte D. Gallbladder motility in obesity, diabetes mellitus and coeliac disease. Dig Liver Dis 2003; 35 Suppl 3:S12-S16. [PMID: 12974503 DOI: 10.1016/s1590-8658(03)00087-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
We reviewed data on gallbladder motility in obesity, diabetes and coeliac disease. In obesity, a condition characterised by increased risk of gallstone(s), decreased gallbladder motility has heterogeneously been reported as a consequence of the different type of meals used to induce gallbladder contraction, characteristics of the population studied, technique used, and proportion of patients with hyperinsulinaemia. Moreover, recent studies have evaluated the effect of dietary restriction on gallbladder motility in obese patients. A two- to three-fold increase in the risk of cholesterol gallstone(s) has been reported in diabetic patients, mainly in relation to obesity and hypertriglyceridaemia. Furthermore, decreased gallbladder motility has been described and attributed to other factors, including underlying autonomic neuropathy, reduced gallbladder sensitivity to cholecystokinin and/or reduced number of cholecystokinin receptors on the gallbladder wall. Impaired gallbladder motility has been reported also in patients with coeliac disease in relation to reduced secretion of enteric hormones and/or decreased gallbladder sensitivity to them. In particular, untreated coeliacs, when compared to controls, showed low postprandial cholecystokinin and increased fasting somatostatin levels. Interestingly, the correlation between fasting somatostatin levels and gallbladder size has clearly been confirmed in patients affected by somatostatinoma or treated with somatostatin or its analogues. Gallbladder motility can be affected by various clinical conditions, such as obesity, diabetes mellitus and coeliac disease.
Collapse
|
|
11
|
Abstract
Accumulating evidence indicates that hypertriglyceridemia (HTG) is a risk factor for cardiovascular disease. This increased risk is probably substantially mediated through the metabolic interrelationships between serum triglyceride (TG) levels and other risk factors, such as the atherogenic lipid profile (low high density lipoprotein-cholesterol levels and elevated small dense low density lipoprotein levels), insulin resistance, a prothrombotic propensity and low grade systemic inflammation. TG-lowering strategy in patients with HTG encompasses dietary modification and pharmacological agents, such as fibric acid derivatives, fish-oil and hydroxymethylglutaryl coenzyme A reductase inhibitors, which have, besides their known effects on the atherogenic lipid profile, beneficial effects on other determinants of cardiovascular disease. However, in spite of data from trials investigating fibric acid derivative-induced reduction in coronary events in patients with distinct types of hyperlipidemia, no specific trials have been performed that investigated this risk reduction in patients with HTG, in whom other cardiovascular risk factors are clustered as well. Small-scale studies on determinants of cardiovascular disease in patients with HTG and post-hoc analyses of the Helsinki Heart, Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial and Bezafibrate Infarction Prevention trials in patients with high serum TG levels suggest a drug-induced reduction in cardiovascular events. However, a specific trial should be conducted to investigate the effects of lipid-lowering therapy on clinical end-points in patients with HTG of defined types.
Collapse
Affiliation(s)
- I J Jonkers
- Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
| | | | | |
Collapse
|
|
12
|
Abstract
Dietary intake and plasma lipids were estimated in 200 patients with gallstones and 98 control subjects from a hospital in Northern India and were matched for age, sex, and social class. The intake of total calories and carbohydrates and the plasma triglyceride values were higher in all gallstone patients as compared with controls (p < 0.05 and p < 0.01, respectively). The dietary intake of refined carbohydrates was higher than in controls, but only in the female patients with gallstones (35.6 +/- 32.9 g/day compared with 24.5 +/- 11.8 g/day; p < 0.001). By contrast, the male patients with gallstones had an increased intake of fat (patients 79.0 +/- 38.1 g/day vs. controls 60.2 +/- 24.3 g/day; p < 0.05) and had increased plasma cholesterol values (patients 166.4 +/- 54.2 mg/dl vs. controls 140.3 +/- 32.8 mg/dl; p < 0.01). Such sex differences in the dietary intake and plasma lipid values may form a special feature of gallstone disease in Northern India and should be studied further.
Collapse
Affiliation(s)
- R K Tandon
- Department of Gastroenterology and Surgery, All India Institute of Medical Sciences, New Delhi
| | | | | | | |
Collapse
|
|
13
|
Yang H, Petersen GM, Roth MP, Schoenfield LJ, Marks JW. Risk factors for gallstone formation during rapid loss of weight. Dig Dis Sci 1992; 37:912-8. [PMID: 1587196 DOI: 10.1007/bf01300390] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Risk factors for the development of gallstones during rapid weight loss were assessed in 457 subjects who entered a weight control program (520 kcal/day). Absence of gallstones in these subjects was documented by ultrasonography prior to entry into the study. Ultrasonography was performed again at 16 weeks on the subjects who remained in the study (N = 248). The incidence of gallstones by 16 weeks of rapid weight loss was 10.9% (27/248). Most factors associated with gallstones in the general population, eg, older age, female gender, parity, positive family history, etc, were not associated with gallstones in this population. The risk factors for developing gallstones included increased initial body mass index [weight (kg)/height (m)2], amount of body mass index loss, and serum triglyceride levels. The positive predictive value of these risk factors was 75%, but the sensitivity was only 12%. These observations indicate that risk factors for the development of gallstones during rapid weight loss are probably different from those in the general population. The factors identified by this study are useful in predicting patients at high risk for gallstones. However, since only a minority of gallstones that form can be predicted, further study is needed to identify additional factors that will improve our ability to predict gallstone formation.
Collapse
Affiliation(s)
- H Yang
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048
| | | | | | | | | |
Collapse
|
|
14
|
Odman B, Ericsson S, Lindmark M, Berglund L, Angelin B. Gemfibrozil in familial combined hyperlipidaemia: effect of added low-dose cholestyramine on plasma and biliary lipids. Eur J Clin Invest 1991; 21:344-9. [PMID: 1909637 DOI: 10.1111/j.1365-2362.1991.tb01380.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Gemfibrozil is frequently used for lipid-lowering in familial combined hyperlipidaemia (FCHL) and in other forms of combined hyperlipidaemia. This therapy increases biliary cholesterol saturation, enhancing the risk for gallstone formation. Furthermore, in hypertriglyceridaemia, LDL cholesterol levels often tend to rise. We have explored the possibility that addition of a low dose of cholestyramine to gemfibrozil therapy obliterates these phenomena. Eighteen gallstone-free patients with definite (n = 5) or probable (n = 10) FCHL, or combined hyperlipoproteinaemia (n = 3) were randomized to a 6 week treatment with gemfibrozil, 600 mg b.i.d., or gemfibrozil 600 mg b.i.d. plus 4 g cholestyramine o.d. After 6 weeks the patients were crossed over to the alternative treatment. Plasma lipoproteins and biliary lipids were determined at baseline and at the end of each period. Institution of gemfibrozil treatment resulted in a decrease in plasma cholesterol by 15% (P less than 0.05) and in plasma triglycerides by 47% (P less than 0.05); HDL cholesterol increased by 18% (P less than 0.05). Addition of cholestyramine further decreased plasma and LDL total cholesterol by 9% (P less than 0.05). Total triglycerides and HDL cholesterol did not change. Gemfibrozil treatment was associated with a rise in the relative biliary concentration of cholesterol from 5.6 +/- 0.4 to 6.9 +/- 0.5 molar percent (P less than 0.01), and a parallel decrease in the relative concentration of bile acids, resulting in an increased cholesterol saturation of the bile, from 77 +/- 5 to 90 +/- 6% (P less than 0.05). This change was not observed during the combined therapy (mean cholesterol saturation, 82 +/- 4%).(ABSTRACT TRUNCATED AT 250 WORDS)
Collapse
Affiliation(s)
- B Odman
- Department of Medicine, Karolinska Institute, Huddinge University Hospital, Sweden
| | | | | | | | | |
Collapse
|
|
15
|
Abstract
The role of serum lipids in the etiology of cholesterol gallstones and pigment gallstones was assessed in a case-control study. The study included 250 cases with surgically or ultrasonographically confirmed cholecystolithiasis and 526 hospital control patients. The highest gallstone risk was found at low high-density cholesterol levels and high triglyceride levels. An additional weakly negative association was found between total cholesterol level and gallstone risk. These findings were similar for cholesterol gallstones and pigment gallstones. The association between body mass index and gallstone risk disappeared after adjustment for serum lipids in a multivariate analysis. This study confirms previous reports on the association between gallstone risk and serum lipids. The similarity between cholesterol and pigment gallstones with regard to their association with serum lipids indicates that these types of gallstones share more causal factors than previously suggested. The absence of an effect of body mass index independent from serum lipids (as shown by the multivariate analysis) suggests that serum lipids are more closely linked to the pathogenesis of gallstones than obesity.
Collapse
Affiliation(s)
- C Thijs
- Department of Epidemiology/Health Care Research, Rijksuniversiteit Limburg, Maastricht, The Netherlands
| | | | | |
Collapse
|
|
16
|
Abstract
Biliary lipid composition and plasma lipoprotein levels were determined in nine gallstone-free male patients with familial combined hyperlipidaemia (FCHL). In the basal situation, stimulated fasting duodenal bile from the patients contained a higher relative concentration of cholesterol than bile obtained from age- and sex-matched normal controls (n = 22), 6.5 +/- 0.3 (SEM) vs. 4.7 +/- 0.2 mol % (P less than 0.01). This resulted in a higher cholesterol saturation of bile from FCHL patients, 85 +/- 6 vs. 70 +/- 2% (P less than 0.05). After 6 weeks of treatment with acipimox, 750 mg day-1, total plasma triglycerides were lowered from 7.5 +/- 1.5 to 4.6 +/- 0.7 mmol l-1 (P less than 0.05) and plasma cholesterol decreased from 8.0 +/- 0.1 to 7.1 +/- 0.3 mmol l-1 (P less than 0.05) in the FCHL patients. These changes were mainly due to a decrease in very low density lipoprotein concentrations while low density lipoprotein levels remained unaltered. The relative proportion of cholesterol in stimulated fasting duodenal bile was reduced from 6.5 +/- 0.3 to 4.3 +/- 0.5 mol % (P less than 0.01), resulting in 'normalization' of biliary cholesterol saturation, from 85 +/- 6 to 58 +/- 6% (P less than 0.005). No correlations between the changes in biliary lipid composition and those in plasma lipoprotein levels were observed. The results indicate that treatment with acipimox in patients with FCHL, a disorder commonly associated with supersaturated bile, does not increase biliary cholesterol, and presumably not the risk for gallstone formation.
Collapse
Affiliation(s)
- S Ericsson
- Department of Medicine, Karolinska Institute, Huddinge University Hospital, Sweden
| | | | | |
Collapse
|
|
17
|
Angelin B, Holmquist L, Leijd B, Einarsson K. Bile acid metabolism in familial dysbetalipoproteinaemia: studies in subjects with the apolipoprotein E-2/2 phenotype. Eur J Clin Invest 1990; 20:143-9. [PMID: 2112478 DOI: 10.1111/j.1365-2362.1990.tb02261.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Bile acid kinetics and biliary lipid composition were determined in seven subjects with primary dysbetalipoproteinaemia. They were all homozygous for the apolipoprotein E isoform E-2 and six of them were hyperlipidaemic (type III hyperlipoproteinaemia). With or without hyperlipidaemia, the apo E-2/2 phenotype was associated with increased bile acid formation (mean increase compared with 32 normolipidaemic controls, 43%; P less than 0.025). The biliary lipid composition was not different from that seen in the controls. The results indicate that the uptake by the liver of apo E-containing remnant particles is of importance for the regulation of hepatic cholesterol metabolism in man. It is suggested that hepatic cholesterol synthesis is stimulated in dysbetalipoproteinaemia, and that this leads to a compensatory increase in bile acid synthesis.
Collapse
Affiliation(s)
- B Angelin
- Department of Medicine, Huddinge University Hospital, Sweden
| | | | | | | |
Collapse
|
|
18
|
Henriksson P, Einarsson K, Eriksson A, Kelter U, Angelin B. Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma. J Clin Invest 1989; 84:811-6. [PMID: 2760214 PMCID: PMC329723 DOI: 10.1172/jci114240] [Citation(s) in RCA: 76] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
To assess if and by which mechanisms pharmacological estrogen treatment induces gallstone disease, we examined patients with recently diagnosed prostatic cancer randomly allocated to estrogen therapy (n = 37) or orchidectomy (n = 35). According to gallbladder ultrasonography, after 1 yr new gallstones had developed in 5 of 28 estrogen-treated patients, compared with 0 of 26 orchidectomized patients (P = 0.03). Estrogen therapy for 3 mo increased the relative concentration of cholesterol and cholesterol saturation of bile by approximately 30% (n = 10). Serum LDL cholesterol was reduced by approximately 40%, and its relative change related inversely to that of bile cholesterol (Rs = -0.77). There were no changes in biliary or serum lipids after orchidectomy (n = 9). Secretion rates of biliary lipids were measured with a duodenal perfusion technique. Patients on chronic estrogen therapy (n = 5) had approximately 40% higher biliary excretion rates of cholesterol than age-matched controls (n = 7). Phospholipid secretion was also higher, but no difference in bile acid secretion was found. We conclude that an increased hepatic secretion of cholesterol results in increased cholesterol saturation of bile and an enhanced rate of gallstone formation during estrogen treatment. The changes in bile cholesterol seem to be related to the induced changes in serum lipoprotein metabolism.
Collapse
Affiliation(s)
- P Henriksson
- Department of Medicine, Karolinska Institute, Huddinge, Sweden
| | | | | | | | | |
Collapse
|
|
19
|
The epidemiology of gallstone disease in Rome, Italy. Part II. Factors associated with the disease. The Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO). Hepatology 1988; 8:907-913. [PMID: 3391520 DOI: 10.1002/hep.1840080434] [Citation(s) in RCA: 111] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The epidemiological associations of gallstone disease were evaluated in a population of 2,325 civil servants (1,244 men and 1,081 women) in Rome, Italy, which was enrolled in a cross-sectional survey on cholelithiasis. Participants were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire on family and personal history and underwent a physical examination and blood chemistry. Statistically significant associations were established by univariate analysis of the age-standardized data and by step-wise multiple logistic regression. At univariate analysis, increasing age, serum triglycerides and number of cigarettes smoked per day, and decreasing high-density lipoprotein-cholesterol were the conditions associated with the presence of gallstones in men. Age and parity were the correspondent associations in women. After controlling by multiple logistic regression, a different pattern of associated conditions emerged. In men, only age and serum triglycerides showed a significant positive association with gallstones, which was independent of other variables. In women, the presence of gallstones was independently associated with increasing age, number of pregnancies, body mass index and serum triglycerides, and with decreasing total (and low-density lipoprotein) cholesterol. The latter association was curvilinear in shape. The conditions associated with a history of cholecystectomy differed from those observed in subjects with gallstones, with the exceptions of age, in both sexes, and high serum triglycerides, in women. Fasting blood glucose levels were higher in women with a history of cholecystectomy than in those with or without gallstones, both at univariate and multiple logistic regression analyses.(ABSTRACT TRUNCATED AT 250 WORDS)
Collapse
|
|
20
|
Einarsson K, Nilsell K, Leijd B, Angelin B. Influence of age on secretion of cholesterol and synthesis of bile acids by the liver. N Engl J Med 1985; 313:277-82. [PMID: 4010739 DOI: 10.1056/nejm198508013130501] [Citation(s) in RCA: 170] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Supersaturation of bile with cholesterol predisposes to the development of cholesterol gallstones. To identify the factors determining cholesterol saturation of bile, we analyzed the lipid composition of stimulated duodenal bile in 60 healthy subjects of various ages (31 men and 29 women) who were not obese and were free of gallstones. A positive correlation between age and cholesterol saturation of bile was found (P less than 0.001). To analyze the relation between age and cholesterol saturation, we studied the rates of hepatic secretion of biliary lipids and the kinetics of cholic acid and chenodeoxycholic acid in 22 and 18 of the subjects, respectively. Age was positively correlated with the cholesterol secretion rate (r = 0.48) and negatively correlated with bile acid synthesis (r = -0.60) and the size of the cholic acid pool (r = -0.54). We conclude that cholesterol saturation of bile increases with age as a consequence of enhanced hepatic secretion of cholesterol and decreased bile acid synthesis. These findings may explain why age is a risk factor for the development of cholesterol gallstones.
Collapse
|
|
21
|
|
|
22
|
|
|
23
|
Abstract
Twelve subjects with radiolucent gall stones and bile supersaturated with cholesterol were studied after six weeks each on diets which contained 112 g and 16 g respectively of refined (fibre depleted) sucrose but which allowed free access to other foods. Energy intake was 24.5% higher on the high sugar diet and body weight ended 1.4 kg higher than on the low sugar diet. Biliary secretion rates of cholesterol, phospholipid and bile acid, measured by a perfusion technique, were similar on the two diets, as were the bile acid pool sizes measured by isotope dilution. Cholesterol saturation index of fasting 'gall bladder' bile was 1.30 +/- 0.11 and 1.37 +/- 0.14 on high and low sugar respectively (NS). Plasma triglycerides were 36% higher and plasma high density lipoprotein cholesterol concentrations were 9% lower on the high sugar diet. These findings indicate that over a six week period refined sugar in normally consumed amounts does not adversely affect the lipid composition of bile.
Collapse
|
|
24
|
Leiss O, von Bergmann K. [Relation between serum lipoprotein metabolism and biliary lipid metabolism]. KLINISCHE WOCHENSCHRIFT 1983; 61:579-92. [PMID: 6876687 DOI: 10.1007/bf01487336] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
This review concern with recent results regarding interrelationships between serum lipoprotein and bile acid metabolism. First, changes in bile acid metabolism in primary hyperlipoproteinaemia type II and type IV are described. In addition, influences of lipid-lowering drugs such as sitosterol, cholestyramine/colestipol, neomycin, nicotinic acid, clofibrate and thyroxin on serum lipoproteins and biliary lipid metabolism are discussed. Changes in lipoprotein metabolism in disorders of bile acid metabolism and effects of primary and secundary bile acids on lipoprotein metabolism, hepatic cholesterol metabolism and intestinal cholesterol absorption are described. In the final discussion interrelationships between very low density lipoprotein - triglycerides and cholic acid metabolism as well as low density lipoprotein and chenodeoxycholic acid metabolism are stressed. The positive correlation between serum triglycerides and lithogenicity of bile is underlined and the possible significance of high density lipoprotein-cholesterol as precursor of biliary cholesterol is discussed.
Collapse
|
|
25
|
Abstract
Nine slightly obese patients with hyperlipoproteinemia type IV were studied, before and after a mean weight reduction of about 15 kg, with respect to bile acid kinetics, cholesterol balance and biliary lipid composition. The bile acid pool size was not consistently changed. The synthesis of cholic acid and chenodeoxycholic acid was decreased by about 65% and 50%, respectively. The net steroid balance, calculated as bile acid synthesis plus fecal excretion of neutral steroids minus dietary cholesterol intake, was reduced by about 50%. In all but one of the patients bile was supersaturated with cholesterol but weight reduction was not associated with any change in cholesterol saturation. The results indicate that hyperlipoproteinemia type IV may be associated with some metabolic defects which are not corrected for by weight reduction.
Collapse
|
|
26
|
Greco AV, Mingrone G, Passi S. Bile acid content of gallbladder bile and stones in type IIb and IV hyperlipoproteinemia. Clin Chim Acta 1981; 116:81-9. [PMID: 7318176 DOI: 10.1016/0009-8981(81)90171-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
We examined the bile acid composition of gallbladder bile using reversed-phase high performance liquid chromatography (HPLC), in normolipemic and hyperlipidemic (types IIb and IV) patients with cholelithiasis and compared them with normal subjects. Similarly, bile acid composition was determined n the gallstones of these patients. No free bile acids were found in any of the samples examined. We observed that gallbladder bile and gallstones of patients with type IV hyperlipidemia showed a significant increase in the percentage of glyco-conjugated bile acids and reduction in taurine conjugates. Based on this finding we postulate that in addition to biliary lipid composition bile acid composition may also play a role in the pathogenesis of cholesterol gallstone formation.
Collapse
|
|
27
|
Maton PN, Murphy GM, Dowling RH. Lack of response to chenodeoxycholic acid in obese and non-obese patients. Role of cholesterol synthesis and possible response to ursodeoxycholic acid. Gut 1980; 21:1082-6. [PMID: 7461467 PMCID: PMC1419396 DOI: 10.1136/gut.21.12.1082] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
This paper describes seven patients with radiolucent gallstones in functioning gallbladders who did not respond to chenodeoxycholic acid (CDCA). Despite large doses (greater than or equal to 19 mg CDCA/kg/day), CDCA-rich bile (CDCA conjugates 70-97% of total biliary bile acids) and greater than or equal to one year's treatment, their fasting duodenal bile remained supersaturated with cholesterol and their gallstones did not dissolve. Five patients came to cholecystectomy, gallstone analysis and liver biopsy for measurement of hepatic cholesterogenesis (HMGCoAR activity). In three who stopped CDCA before surgery, the mean HMGCoAR (pmol/mg microsomal protein/min) of 50.2 was higher than in our untreated gallstone controls (32.2 +/- SEM 2.0; P less than 0.05). Two patients who took CDCA until surgery had a mean HMGCoAR of 33.5--more than twice that in CDCA-treated gallstone controls. These findings suggest that non-response to CDCA may be related to high or unsuppressed hepatic cholesterogenesis. In one patient who did not respond to CDCA, treatment with 19 mg ursodeoxycholic acid/kg/day did desaturate his bile.
Collapse
|
|
28
|
Danzinger RG, Kurtas TK, Torchia MG. Low-dose chenodeoxycholic acid for gallstone dissolution: a randomized trial in poor operative risk patients. Dig Dis Sci 1980; 25:785-9. [PMID: 7000476 DOI: 10.1007/bf01345300] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Thirty-five patients, with minimally symptomatic radiolucent gallstones in well opacifying gallbladders who had an unusually high risk of operative mortality, were randomized, double blind, into three groups: group 1, placebo; group 2,250 mg chenodeoycholic acid (CDC)/day; group 3,375 mg CDC/day. Every six months, oral cholecystograms and duodenal bile were obtained. Serum was collected at 0, 1, 2, 3, and 6 months, then at 6-month intervals. After 6 months, all placebo patients were assigned to 375 mg CDC/day (group 3b). No changes occurred in group 1 (N = 15). Gallstones dissolution: group 2, 2/10; 1 complete (C), 1 partial (P); group 3, 4/10, 1C, 3P; group 3b, 2/12, 2C. Lowest dose with complete dissolution was 3 mg/k/day (actual body wt). Lithogenic index of bile only improved with 375 mg/day (1.27 +/- 0.13 vs 0.88 +/- 0.05; mean +/- SDM), P < 0.01. No diarrhea or serum biochemical changes occurred; however, three patients died of their other medical illness. Low fixed doses of CDC, although not optimal, dissolved stones without toxicity in very ill patients.
Collapse
|
|
29
|
|
|
30
|
Angelin B, Leijd B. Effects of cholic acid on the metabolism of endogenous plasma triglyceride and on biliary lipid composition in hyperlipoproteinemia. J Lipid Res 1980. [DOI: 10.1016/s0022-2275(20)39834-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
|