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Impaired Absorption of Cholesterol and Bile Acids in Patients with an Ileoanal Anastomosis Gut: First Published As 10.1136/Gut.41.6.771 on 1 December 1997

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Impaired Absorption of Cholesterol and Bile Acids in Patients with an Ileoanal Anastomosis Gut: First Published As 10.1136/Gut.41.6.771 on 1 December 1997 Gut 1997; 41: 771–777 771 Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis Gut: first published as 10.1136/gut.41.6.771 on 1 December 1997. Downloaded from K Hakala, M Vuoristo, P Luukkonen, H J Järvinen, T A Miettinen Abstract infer that cholesterol absorption, dependent Background—No data exist on cholesterol on micellar solubilisation with bile acids and absorption in patients with an ileoanal fatty acids,10 11 may also be disturbed and anastomosis (IAA). markedly influence serum and biliary lipids in Aims—To study cholesterol absorption patients with an ileoanal anastomosis. How- and its eVects on cholesterol and bile acid ever, to our best knowledge, no data are yet metabolism in patients with an IAA. available on cholesterol absorption and syn- Patients and methods—Cholesterol ab- thesis in this condition. Therefore, in the sorption, and serum, biliary, and faecal present study we explored absorption, elimi- lipids were studied in 24 patients with an nation, and synthesis of cholesterol, biliary IAA and 20 controls. lipids, faecal bile acids, and serum lipoproteins Results—Fractional cholesterol absorp- in 24 patients with ileoanal anastomosis and in tion was significantly lower in the patients 20 control subjects. (36% versus 47% in controls). Surpris- ingly, the calculated intestinal influx of Methods endogenous cholesterol was reduced so SUBJECTS that the absolute absorption of cholesterol The series consisted of 24 patients with was decreased; elimination of cholesterol ulcerative colitis who had undergone an as faecal neutral steroids remained nor- ileoanal anastomosis with a double limb J mal. Thus, the slightly increased shaped pouch. In construction of the pouch, cholesterol synthesis was mainly due to any resection of the terminal ileum was increased faecal bile acid excretion, avoided, and it was 1–3 cm at most. Liver which, in turn, was associated with re- function tests (serum albumin, alanine ami- duced absorption and biliary secretion of notransferase, alkaline phosphatase) were nor- bile acids. Serum total and low density mal in all patients, and none was using consti- http://gut.bmj.com/ lipoprotein (LDL) cholesterol and LDL pating drugs. Six had a history of pouchitis, triglycerides were lower in the patients. but each had been without symptoms of pou- Molar percentage and saturation index of chitis and oV antibiotics for at least three biliary cholesterol were slightly higher in months. patients with an IAA. Proportions of The control subjects comprised 20 men secondary bile acids in bile and faeces selected from a random 50 year old male were diminished, and faecal unidentified population of Helsinki on the basis that their bile acids were higher in patients. body mass index (BMI, kg/m2) range fell within on September 27, 2021 by guest. Protected copyright. Conclusions—Cholesterol absorption is that of the patients with ileoanal anastomosis significantly impaired in patients with an (mean (2SD)). However, because mean body IAA, and is closely related to changes in weight was slightly higher in the controls, serum and biliary lipids observed in these where appropriate, the data are expressed per patients. kg of body weight. Department of (Gut 1997; 41: 771–777) Medicine, Division of All subjects were informed of the nature and purpose of the studies, and the study protocol Internal Medicine and Keywords: cholesterol absorption; cholesterol synthesis; Geriatrics faecal bile acids; inflammatory bowel disease was approved by the Ethics Committee of the K Hakala hospital. M Vuoristo T A Miettinen Since the invention of the ileoanal pouch PROCEDURES 1 Department of anastomosis in 1978 by Parks and Nicholls, All patients were hospitalised and placed on a Surgery, University of its use with various modifications in patients standardised solid food diet of 300 mg of Helsinki with ulcerative colitis has markedly increased. cholesterol and 100 g of fat per day. Daily P Luukkonen Earlier studies showed that proctocolectomy energy content was adjusted to maintain H J Järvinen with conventional ileostomy does not aVect constant body weight. For determination of 23 12 Correspondence to: bile acid metabolism, whereas the ileoanal cholesterol absorption, faecal fat, and faecal Dr M Vuoristo, Department anastomosis may disturb absorption of bile steroids, each patient received a capsule of Medicine, Division of 4–6 14 acids or vitamin B12, both of which are containing C-cholesterol (0.15 µCi/day) and Internal Medicine and 3 Geriatrics, University of absorbed in the ileum. Bile acid malabsorption H-â-sitosterol (0.80 µCi/day) three times a day Helsinki, Haartmaninkatu 4, has actually been suggested as being responsi- with the main meals for seven days. At the end FIN-00290, Helsinki, ble for the lithogenic bile in these patients in of this period, a three day stool collection was Finland. some studies78 but not in all.9 Interestingly, performed. Then, after overnight fasting, a Accepted for publication steatorrhoea may also occur in some patients blood sample was taken and the patients 24 June 1997 with ileoanal anastomosis.4 Thus, one can received intravenously a bolus (1 IDU of body 772 Hakala, Vuoristo, Luukkonen, Järvinen, Miettinen weight up to 100 IDU) of cholecystokinin (VLDL), low density lipoprotein (LDL), and (Cholecystokinin, Ferring Pharmaceuticals, high density lipoprotein (HDL) were quanti- Malmö, Sweden) to make the gall bladder con- fied according to the Lipid Research Clinic’s Gut: first published as 10.1136/gut.41.6.771 on 1 December 1997. Downloaded from tract, in order to allow aspiration of a duodenal manual.17 Biliary and faecal sterols of bile sample through a gastroscope. The bile cholesterol origin were determined by gas samples were placed in a water bath at 70°C for liquid chromatography18 19 on a 50 m SE-30 five minutes to destroy lipase activity and then capillary column,19 and biliary phospholipids stored at –20°C until analysed. The total intesti- were determined as described by Bartlett.20 nal transit time was measured by determination Faecal fat was determined acccording to van de of time between ingestion of carmine red (1 g in Kamer et al21 and chromic oxide by the method 200 ml of water) and first appearance of the dye of Bolin et al.22 Faecal radioactivities were in the faeces. Small bowel transit time was determined with a liquid scintillation counter measured with the lactulose hydrogen breath with 0.5% 2,5-diphenyloxazole in toluene test, carried out by administration of 20 g of lac- (Wallac Rackbeta Scintillation; Model 1215). tulose, and thereafter by collection of breath Because equal recoveries for 3H-â-sitosterol samples at 10–15 minute intervals up to 120 and chromic oxide in faecal samples disclosed minutes. Appearance of peak concentration of no marked degradation of the sterol nucleus, breath hydrogen (a rise 50% above the baseline faecal data were calculated in relation to chro- value) was regarded as small bowel transit mic oxide (Cr2O3). 13 time. Absorption of vitamin B12 with intrinsic factor was measured according to Bayly et al.14 The control subjects were studied at our CALCULATIONS outpatient clinic. All subjects were asked to The percentage absorption of cholesterol was continue their customary home diet and to calculated from the 14C:3H ratios in the keep a dietary record for seven days, with mean capsules administered and in the faecal daily intake of cholesterol and fat being samples collected.12 The intestinal cholesterol computed from these records.15 16 Daily analy- influx, consisting of dietary, biliary, and sis of the control data disclosed that intake of mucosal cholesterol, was determined by an cholesterol and fat (4.9 (0.4) mg/kg/day and indirect method23 assuming that exogenous 1.3 (0.1) g/kg/day, respectively) very closely and endogenous cholesterol were similarly corresponded to intake in the patients (4.6 absorbed.24 The average intestinal influx of (0.2) mg/kg/day and 1.5 (0.1) g/kg/day, respec- cholesterol was calculated from the absorption tively). During the seven day period, percentage of cholesterol and faecal neutral cholesterol absorption, faecal steroids, faecal steroids, and biliary cholesterol secretion was fat, blood, and bile sampling were carried out calculated by subtraction of cholesterol intake as described above. from intestinal cholesterol influx. The biliary secretion rates for cholesterol and bile acids http://gut.bmj.com/ MEASUREMENTS obtained with this indirect calculation have Serum total cholesterol and triglycerides, and been similar to those measured by the intesti- their content of very low density lipoprotein nal perfusion technique.24 Biliary bile acid TABLE 1 Clinical data and absorption, elimination, and synthesis of cholesterol in 24 patients with an ileoanal anastomosis and 20 control subjects Absorption Faecal steroids (mg/day) Postoperative Intestinal of vitamin Cholesterol Cholesterol Sex Body BMI period transit B12 (% of Faecal fat absorption Neutral synthesis on September 27, 2021 by guest. Protected copyright. Case no Age (y) (F/M) weight (kg) (kg/m2) (months) time (h) dose/24 h) (g/day) (%) Bile acids steroids (mg/day) 1 27 F 55 19.0 6 6.3 16.9 1.9 48.6 342 352 394 2 35 F 55 19.5 13 2.8 16.5 3.0 21.8 356 601 657 3 36 F 61 24.4 14 4.2 17.5 2.7 36.3 375 346 421 4 48 F 86 34.9 4 4.0 22.4 2.0 30.8 471 538 709 5 30 F 69 26.3 5 2.8 17.9 6.5 51.6 1525 561 1786 6 42 F 66 26.4 25 1.8 16.5 6.9 44.7 1357 778 1835 7 37 F 64 22.4 5 3.7 11.7 2.8 34.2 473 581 754 8 38 M 71 21.4 6 7.3 25.5
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