Oat bran rapidly increases bile acid excretion and bile acid synthesis
Correspondence: Dr L Elleg Department of Air Max 2015 Clinical Nutrition, The Sahlgrenska Academy at the University of G Sahlgrenska University Hospital, SE 405 30 G Sweden.
Results: Native oat bran increased median excretion of bile acids by 144% (P=0.008). Cholesterol excretion remained unchanged, cholesterol absorption decreased by 19% (P=0.013), whereas the sum of bile acid and cholesterol excretion increased by 40% (P=0.008) compared with hydrolysed oat bran. 7 HC reflecting bile acid synthesis increased by 57% (P=0.008) within 24 h of consumption, whereas serum lathosterol concentration reflecting cholesterol synthesis increased by 12% (P=0.015).
Conclusions: Oat bran with native glucans increases bile acid excretion within 24 h of consumption and this increase can also be detected by rising serum concentrations of 7 HC. Thus, 7 HC could be used for rapid detection of dietary effects on bile acid metabolism. These effects could possibly be explained by entrapment of whole micelles in the gut owing to higher viscosity.
Keywords: oat bran, glucans, dietary fibre, bile acid excretion, cholesterol absorption, ileostomy
Top of pageIntroductionCholesterol metabolism is determined by diet, genetic factors, cholesterol absorption, sterol synthesis and sterol excretion. Serum cholesterol concentration is influenced by dietary cholesterol intake, but even more by dietary fatty acids and dietary fibre intake. Cholesterol uptake is usually about 50%, but recent studies have shown that there are large individual variations and an uptake of 30 has been reported (Bosner et al., 1999). In addition, genetic factors such as apoprotein E phenotype affect cholesterol absorption (Kes et al., 1987). Cholesterol is synthesized mainly in the liver and in the intestine, and is used in all cells as an essential element in the cell membranes, and as a precursor in the hepatic synthesis of bile acids, the adrenal and gonadal synthesis of steroid hormones and the dermal synthesis of vitamin D (Dietschy et al., 1993). The synthesis and excretion of bile acids is the major pathway for elimination of cholesterol. Primary bile acids are synthesized from cholesterol in the liver, and cholesterol 7 hydroxylase is considered to catalyse the rate limiting step in the biosynthesis process (Cohen, 1999). Hepatic bile acid synthesis is controlled in the liver through negative and positive feedback mechanisms. The bile acids recirculating to the liver in the enterohepatic circulation regulate their own synthesis by influencing the activity of 7 hydroxylase (Reihn et al., 1989). Thus, increased bile acid excretion promotes bile acid synthesis from cholesterol through decreased feedback inhibition of bile acids on 7 hydroxylase (Grundy et al., 1971; Marlett et al., 1994). The consequences of increased bile acid excretion are stimulated cholesterol uptake from the circulation followed by a decreased serum cholesterol concentration (Grundy et al., 1971).
The human body has no enzymes capable of breaking down the sterol ring structure of the cholesterol molecule, and therefore, cholesterol can only be eliminated from the body by faecal excretion. Sterol balance studies have been performed to evaluate the effects of the composition of the diet on sterol excretion (Connor et al., 1969; Grundy and Ahrens, 1969; Nestel et al., 1975). These metabolic ward investigations were elaborate, but owing to variations in bacterial degradation of the sterol ring structure in the large intestine, and variations in colonic transit time, precision was insufficient to settle the question of the effects of different diets on sterol excretion (Andersson and Bosaeus, 1993).
We have readdressed the question of evaluating the effects of the composition of the diet on sterol excretion by studying ileostomy subjects without resection of the small intestine (Sandberg et al., 1981). With this approach, diets with potential to reduce serum cholesterol concentrations have been shown to increase sterol excretion from the small bowel, either as bile acids or as cholesterol within 2 days in carefully controlled dietary studies. This has been shown with diets low in fat, or high in polyunsaturated fat (Bosaeus and Andersson, 1987), high in monounsaturated fat (Bosaeus et al., 1992), with pectin (Bosaeus et al., 1986) and with oat bran (Lia et al., 1995). We have also reported increased cholesterol excretion, in spite of an identical cholesterol intake, from a ‘prudent’ diet, that is, a diet in accordance with contemporary dietary guidelines of less saturated fat and more fibre rich foods compared with the average contemporary Swedish diet (Elleg and Bosaeus, 1991). This combination of low saturated fat and high fibre reduces cholesterol absorption, and increases cholesterol and sterol excretion from the small intestine (Elleg et al., 2000).
Oat bran has been shown to increase faecal excretion of bile acids, and also to increase bile acid synthesis, but without data on cholesterol absorption or excretion (Marlett et al., 1994). Oat bran glucan has also been shown to increase ileal bile acid excretion (Lia et al., 1995), to decrease serum cholesterol (Brown et al., 1999), and recently to increase serum concentrations of 7 hydroxy 4 cholesten 3 one (7 HC) (Andersson et al., 2002). Serum concentrations of 7 HC strongly correlate with the activity of the key enzyme cholesterol 7 hydroxylase (Bj et al., 1987), and 7 HC is considered to be a reliable marker for bile acid synthesis in hu Air Max 2015 mans (Sauter et al., 1996). Thus, this study was designed to investigate the effects of oat bran glucans on bile acid and cholesterol excretion and cholesterol absorption by the addition of native or hydrolysed glucans to a controlled basal diet in subjects with conventional ileostomies. In addition, our objective was to analyse simultaneously serum concentrations of 7 HC as a marker for bile acid synthesis, together with lathosterol as a marker for cholesterol synthesis.
Top of pageSubjects, materials and methodsSubjectsNine persons (three female, six male) volunteered for the study. Clinical data on the subjects are presented in Table 1. All subjects had previously undergone proctocolectomy for ulcerative colitis (n=7) or Crohn’s disease (n=2) and had well functioning ileostomies for at least 2 years. No additional small bowel resections had been performed in any of the subjects. Seven of the nine subjects used some medication (listed in Table 1), but these medications were unchanged during the study. Subjects using thyroxin had normal serum thyroxin concentrations. One male subject was overweight, and had elevated serum glucose twice during the study, and thus was diagnosed as diabetic. Data from this subject were included in the analyses because the results did not differ from those of the other volunteers. No subjects had any signs of anaemia, inflammation, hepatic or renal disease as judged by history, hospital records and standard laboratory tests, except subject no. 1 who had slightly elevated C reactive protein concentrations because of arthritis. All subjects had stable bowel function at the time of the study. There was a washout period of at least 4 days between the dietary periods. The order of the diets was randomized for each subject, and the diets were blinded both for the laboratory staff, the investigators and for the subjects.
The first day (24 h from 0800 to 0800) of each period was used for adaptation and to minimize any carry over effects from the habitual diets of the participants. Serum samples for analyses specific to the study (lathosterol, cholesterol, plant sterols and 7 HC) were collected on the second day after overnight fast, but before breakfast with either native or hydrolysed glucan cereals at 08.00 and 10 h later just before supper at 18.00.
On day 2 of study, isotopic cholesterol and sitosterol were added at breakfast, lunch and dinner, in three divided doses. Ileostomy excretion was accumulated for 24 h (0800 to 0800) on days 2 and 3 for determination of sterol excretion and cholesterol absorption.
Informed consent was obtained from each participant. The study protocol was approved by the Ethics Committee of Sahlgrenska University Hospital.
MaterialsDiets The basal menu (Table 2) was composed of common food items and was identical in both 3 day periods. All food except beverages and fresh vegetables was prepared in advance in a metabolic ward kitchen from ingredients taken from the same batches and meticulously measured, and the servings were weighted to nearest 0.1 g. At 0800 h was served 75 g of breakfast cereals based on extruded oat bran concentrate with either native or hydrolysed glucans. The only difference between the two experimental diets was the differently treated oat bran cereals served for breakfast. Th Air Max 2015 e compositions of the resulting experimental diets with native or hydrolysed glucans, given in Table 3, were calculated from Swedish food composition tables (Swedish National Food Administration, 2001) and from analyses of energy, glucans, plant sterols and cholesterol of duplicate portions of the diets and oat bran cereal. To meet energy demands, one subject (no. 7) was served portions 50% larger than normal of all items on the menu, except for the breakfast cereals. The bags were immediately frozen on dry ice in Dewar vessels, which the subjects kept at home. Each morning the bags were delivered to the metabolic ward, freeze dried and pooled for two 24 h outputs to collect enough material for subsequent chemical analysis. The analyses were performed in duplicate on the ileostomy output from the second day of the study, ranging from 0800 h at day 2 to 0800 h at day 3, whereas the output from day 3 was collected as a security measures for back up.
Chemical analyses Wet weight and dry weight of ileostomy effluent were determined as described previously (Sandberg et al., 1981). Energy of the diets was determined by combustion in a Gallenkamp bomb calorimeter (Loughborough, Leicestershire, UK). Determinations of cholesterol and plant sterols in the basal diet and in native and hydrolysed oat bran glucan cereals, as well as cholesterol, bile acids and plant sterols in the ileostomy contents were made by gas liquid chromatography as described previously (Bosaeus and Andersson, 1987). Coefficients of variation (CV) in duplicate samples from food and ileostomy excreta were 3.6% for cholesterol and 3.4% for bile acids.
Analysis of glucans in the oat bran cereals was c Air Max 2015 arried out by the manufacturer (Finn Cereal Ltd, Vantaa, Finland), according to the AOAC method 995.16 (McCleary and Mugford, 1997). To correct for the amount of glucan hydrolysed to glucose monomer during the processing or enzymatic hydrolysing step, glucose content of the final product was determined according to the same procedure but omitting the lichenase hydrolysis step, and the values obtained subtracted from the results of the analyses where lichenase was used.