Starch digestibility in vivo and in vitro.
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Biomedical subjects
Publications and source records attributed to W Scheppach.
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Short-chain fatty acid irrigation has been shown to ameliorate inflammation in diversion colitis. In this study the effect of butyrate enemas was tested in 10 patients with distal ulcerative colitis who had been unresponsive to or intolerant of standard therapy for 8 weeks. They were treated for 2 weeks with sodium butyrate (100 mmol/L) and 2 weeks with placebo in random order (single-blind trial). Before and after treatment, clinical symptoms were noted and the degree of inflammation was graded endoscopically and histologically. Rectal proliferation was assessed by autoradiography. After butyrate irrigation, stool frequency (n/day) decreased from 4.7 +/- 0.5 to 2.1 +/- 0.4 (P less than 0.01) and discharge of blood ceased in 9 of 10 patients. The endoscopic score fell from 6.5 +/- 0.4 to 3.8 +/- 0.8 (P less than 0.01). The histological degree of inflammation decreased from 2.4 +/- 0.3 to 1.5 +/- 0.3 (P less than 0.02). Overall crypt proliferation was unchanged, but the upper crypt-labeling index fell from 0.086 +/- 0.019 to 0.032 +/- 0.003 (P less than 0.03). On placebo, all of these parameters were unchanged. These data support the view that butyrate deficiency may play a role in the pathogenesis of distal ulcerative colitis and that butyrate irrigation ameliorates this condition.
Epidemiological and experimental studies indicate a strong association between an elevated colon cancer risk and increased fecal excretion of secondary bile acids, neutral sterols, and prolonged gastrointestinal transit time. Starch malabsorption, on the other hand, has been reported to be a possible protective factor in colon carcinogenesis. To study the impact of starch malabsorption on these parameters, 12 healthy volunteers consumed a diet rich in starch for two 4-week periods. During a double-blind crossover trial they received the alpha-glucosidase inhibitor acarbose (BAY g 5421) in one of the study periods and placebo in the other. During acarbose treatment stool wet weight increased by 68%, stool dry weight by 57%, and gastrointestinal mean transit time by 30%. Fecal concentrations (mg/g dry weight) of the neutral sterols coprostanol, coprostanone, campesterol, 4-cholesten-3-one, and beta-sitosterol decreased by 36.8, 48.7, 42.1, 34.6, and 39.4%, respectively, under acarbose. Concentrations of the major secondary bile acids, deoxycholic and lithocholic acid, decreased by 59.9 and 52.2%, respectively. In spite of an increased stool weight, also daily excretion (mg/day) of these two bile acids was lower under acarbose (47.9 and 36.6%, respectively) compared to placebo, whereas excretion of the main primary bile acid, cholic acid, rose from 22.58 mg/day to 379.80 mg/day during the acarbose period. The changes in fecal bile acid and neutral sterol excretion found during acarbose treatment may explain a protective effect of starch malabsorption on colon cancer development.
To estimate colonic carbohydrate fermentation following a potato meal, 13 healthy volunteers consumed 375 g potatoes containing 60 g starch on three different occasions in random order: (A) potatoes boiled and consumed fresh at 60 degrees C; (B) potatoes boiled, frozen, thawed and consumed at 20 degrees C; and (C) potatoes boiled, frozen, thawed, reheated to 90 degrees C, and consumed at 60 degrees C. End-expiratory breath hydrogen (H2) was measured every 15 min for 10-14 hr with a selective electrochemical cell. The extent of colonic carbohydrate fermentation (AUC = area under the breath H2 concentration vs time curve) in experiment B was significantly higher (+186%, P less than 0.002) than in experiment A. The breath hydrogen AUC in experiment C was higher than in experiment A (+48%, P less than 0.04) but lower than in experiment B (-94%, P less than 0.003). It is suggested that structural alterations of the starch molecule occur during freezing, thawing, and reheating and alter the availability of carbohydrates for fermentation by colonic anaerobes.
1. To test the hypothesis that the colon contributes significantly to venous plasma acetate concentrations, experiments were carried out in healthy volunteers and ileostomy patients. 2. Fasting plasma acetate levels were measured in 10 ileostomy patients and compared with those in 21 control subjects. Values in ileostomy patients (21.3 +/- 0.8 mumol/l) were significantly lower than in control subjects (48.0 +/- 4.2 mumol/l). 3. Plasma acetate concentration was estimated in eight healthy volunteers during 108 h of continuous fasting. Acetate concentrations rose significantly from 12 h (43.9 +/- 4.4 mumol/l) to 108 h of starvation (114.0 +/- 15.6 mumol/l) and fell back to normal fasting values on refeeding and another 12 h fast (44.3 +/- 4.7 mumol/l). 4. When colonic fermentation was stimulated after oral ingestion of 10 g of lactulose, the plasma acetate concentration increased significantly (from 44.0 +/- 7.4 to 114.4 +/- 16.2 mumol/l) in seven healthy control subjects. This rise was not affected by concomitant dosage of metronidazole. 5. These data suggest that there are at least two major sources of acetate in man, an endogenous source and the colon which probably becomes more important when fermentation of carbohydrate is occurring.
Carbohydrates from dietary fibre and starch are broken down by the anaerobic microflora to short-chain fatty acids (SCFA) in the caecum and ascending colon. In this study the adaptation of the remaining distal colon or ileum to resection of various lengths of the proximal colon was investigated. Faecal SCFA concentrations (mumol/g wet weight) were measured after right hemicolectomy (n = 10), subtotal colectomy (n = 3) and total colectomy (n = 8) and compared with SCFA in control subjects (n = 21). After right hemicolectomy faecal SCFA (48.7 +/- 5.6) were not different from values obtained in control subjects (47.8 +/- 4.0). SCFA levels after subtotal colectomy (14.5 +/- 0.8) and total colectomy (6.7 +/- 1.4) were significantly lower than after right hemicolectomy and in controls. It is concluded that, after right hemicolectomy, the remaining left colon offers conditions favourable to bacterial fermentation. After subtotal or total colectomy, however, postoperative conditions do not allow a normal fermentative activity. The consequences of a reduced SCFA production for sodium and fluid absorption are discussed.
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To study the impact of starch on colonic function and metabolism, 12 healthy volunteers consumed a controlled diet rich in starch for two 4-wk periods. In one of the study periods they received the glucosidase inhibitor acarbose (BAY g 5421) and placebo in the other. Stool wet weight increased by 68%, stool dry weight by 57%, fecal water content by 73%, and the mean transit time by 30% on acarbose. Breath hydrogen was significantly higher on acarbose, indicating stimulated carbohydrate fermentation in the colon. Fecal bacterial mass (+78%), total stool nitrogen (+53%), bacterial nitrogen (+200%), and stool fat (+56%) were higher in the acarbose than in the control period. The stimulation of fermentation in the human large intestine may be important in colonic and possibly other diseases.
1. Dietary fibre has a moderating impact on glucose metabolism. To test the hypothesis that this effect of fibre may be mediated by its breakdown product acetate, oral glucose tolerance tests were carried out in healthy volunteers with and without acetate. 2. Five subjects received 50 g of glucose orally while taking either acetate (15 mmol every 15 min) by mouth or chloride as control. Oral acetate made no detectable difference to glucose tolerance or to levels of free fatty acids, 3-hydroxybutyrate, lactate, insulin, glucagon and gastric inhibitory polypeptide. 3. The 50 g dose of glucose temporarily depressed acetate levels in blood. This was probably due to an interaction between glucose and acetate in the gastrointestinal lumen as the same effect was seen with 50 g of xylose in three subjects. 4. Plasma acetate concentrations were unaffected by 50 g of oral glucose in one subject when acetate was instilled into the sigmoid colon. 5. It is unlikely that the improvement of glucose tolerance by dietary fibre is mediated by acetate.
1. The effect of acetate absorbed from the gut on glucose turnover has been determined in four healthy subjects during both fasting and an intravenous glucose infusion by using [U-13C]glucose. 2. In the first part of the study, after an overnight fast, a tracer dose of [U-13C]glucose was infused at a constant rate along with an infusion of saline for 7 h. In the second part the saline infusion was replaced by glucose at 4.25 mg min-1 kg-1. In both studies 15 mmol of sodium acetate was given by mouth at 15 min intervals from the fourth to the sixth hour. Glucose turnover, respiratory quotient, metabolic rate and blood levels of acetate, 3-hydroxybutyrate, lactate, insulin, glucagon and gastric inhibitory polypeptide were measured. 3. Glucose turnover rates (means +/- SEM) were 1.88 +/- 0.1 mg min-1 kg-1 during fasting and 4.0 +/- 0.08 mg min-1 kg-1 during glucose infusion. Acetate had no effect on glucose turnover, insulin, glucagon and gastric inhibitory polypeptide levels, but temporarily halted the rise in free fatty acids seen during the fasting study. No changes in oxygen consumption or carbon dioxide output occurred, in keeping with previous observations that acetate substitutes for lipid oxidation during metabolism and has no direct effect on glucose turnover.
Breath methane and hydrogen, plasma acetate, serum selenium, vitamin A and beta-carotene were measured in 47 patients from whom colonic polyps had been removed by endoscopic polypectomy between 3 months and 2 years previously. Patients were compared with 39 control subjects in whom no abnormality was detected during colonoscopy. The proportion of methane exhalers was significantly (p less than 0.0005) higher in patients after polypectomy (66.0%) than in controls (28.2%). Mean plasma acetate was lower (p less than 0.025) in post-polypectomy patients (70.5 microM) than in control subjects (97.1 microM) while breath hydrogen was similar in both groups. The serum concentrations of the antioxidants selenium and beta-carotene showed no differences between the groups whereas vitamin A was higher (p less than 0.01) in serum samples of patients after polypectomy than of controls. These findings indicate that the colonic environment in post-polypectomy patients exhibits certain characteristics which may be related to the formation of benign tumors and possibly colon cancer.
To study the impact of starch malabsorption on fecal short-chain fatty acid concentrations, 11 healthy volunteers consumed a controlled diet rich in starch for 2 4-week periods. They received the glucosidase inhibitor acarbose (Bay g 5421) in one of the study periods and placebo in the other. Stool wet weight increased by 68% and stool dry weight by 57% with acarbose. The fecal concentration (mumol/g wet weight) of n-butyrate (+58%) rose significantly when acarbose was added to the diet. The fecal excretion (mmol/day) of total short-chain fatty acids (+95%) and of their constituents acetate (+97%) and n-butyrate (+182%) was significantly higher when starch malabsorption was induced by acarbose.
The utilization of acetate and its effects on acid-base balance and on free fatty acid metabolism were investigated during regular hemodialysis (HD). Fourteen patients with chronic renal failure were studied during two successive dialysis treatments for which either acetate or bicarbonate were used as a buffer anion in the dialysate. In the acetate studies the mean plasma acetate concentration in the arterial line rose from 0.16 mM to 4.67 mM, while it rose from 0.17 mM to 0.62 mM during bicarbonate dialysis. There was a linear relationship between acetate utilization and the acetate concentration in the venous line. The increase of the blood pH during bicarbonate HD was due to an immediate increase of HCO3, whereas acetate caused a smaller HCO3 rise and a pronounced fall of the pCO2. The heart rate was higher during acetate than during bicarbonate HD. During both types of dialysis there was a twofold rise of total FFA as well as the individual fatty acids palmitate, palmitoleate, oleate, stearate and linoleate which was of similar magnitude when acetate or bicarbonate were used. The postulated antilipolytic effect of the short-chain fatty acid acetate could not be demonstrated under the circumstances of routine hemodialysis. Pre-dialysis dopamine was elevated in 7 of the 11 patients and remained high during both types of HD; other hormones were normal during acetate and bicarbonate HD.
In 15 patients with cirrhosis of the liver and 10 control subjects, 7.5 mmol sodium propionate and 7.5 mmol sodium acetate were instilled endoscopically into the duodenum. Venous concentrations of propionate and acetate were measured for 90 min after administration of the enteral dose by gas-liquid chromatography. In patients with liver cirrhosis, propionate rose from a basal value of 6.1 +/- 4.7 (SD) microM to a peak concentration of 50.1 +/- 25.6 microM, whereas, in controls, it rose only from 1.4 +/- 1.6 to 10.3 +/- 7.6 microM. The oral propionate clearance was significantly lower in patients with cirrhosis (4.51 +/- 1.63 L/min) than in controls (118.47 +/- 154.79 L/min). Acetate went up from 39.5 +/- 16.3 to 134.1 +/- 62.7 microM in patients with cirrhosis and from 60.9 +/- 19.0 to 102.0 +/- 44.0 microM in controls. The oral acetate clearance was lower in patients with liver cirrhosis (2.80 +/- 2.17 L/min) than in control persons (10.86 +2- 5.72 L/min). The differences between the groups were more striking for propionate than for acetate values. It is concluded that the systemic availability of propionate and acetate is higher in patients with liver cirrhosis than in controls. This may be due to portosystemic shunting and/or diminished hepatic and extrahepatic extraction of the acids.
PURPOSE: Vena cava filter (VCF) application is the method of choice to prevent recurrent pulmonary embolism in patients with deep venous thrombosis. Because of the reported complications after VCF placement we summarize our long-term follow-up results with the LGM and Titanium Greenfield (TG) devices. METHODS: Eighty-seven LGM VCF and 17 TG VCF were placed in 104 patients (average age 64 years). The follow-up examinations were performed by color-coded duplex sonography, plain radiographs, cavography, and computed tomography (CT). The maximum observation time was 81 months. RESULTS: Filter migration occurred in 11% (8/76) of the LGM VCF and 15% (2/13) of the TG VCF. Vena cava thrombosis was seen in 17% (13/76) of the patients with an LGM VCF and in 31% (4/13) of those with a TG VCF. The patency rate was 95% (72/76) for the LGM VCF and 92% (12/13) for the TG VCF. Pulmonary embolism was noted in 3 patients after LGM VCF insertion and in no patient after TG VCF insertion. CONCLUSION: A VCF should only be inserted in a patient after pulmonary embolism and when there is strict proof of the indication.
Short-chain fatty acids (SCFAs: acetate, propionate, n-butyrate) arising in the large bowel during bacterial fermentation of dietary fibre and starch have paradoxical effects on colonic epithelial proliferation. While the three major SCFAs stimulate proliferation of normal crypt cells, n-butyrate and, to a lesser degree, propionate inhibit growth of colon cancer cell lines. At the molecular level, n-butyrate causes histone acetylation, favours differentiation, induces apoptosis and regulates the expression of various oncogenes. To understand the complex effects of SCFAs on carcinogenesis, it is important to study the intermediate stages of the adenoma-carcinoma sequence where a "switch" from stimulation to suppression of cell proliferation must occur.
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Dietary fiber defined as nonstarch polysaccharides (NSP) has been added to liquid formula diets in order to approach a more physiological state of nutrition. There are interesting experimental data supporting a role for fiber in artificial enteral feeding: NSP components have been shown to increase fecal bacterial mass, to favor colonic sodium and water absorption, to stimulate colonic crypt proliferation and to delay small intestinal glucose absorption. The number of controlled studies testing the effects of fiber added to liquid formulas is, however, small. Thus, there is no firm basis for the routine use of fiber-enriched formulas although these products are commercially available and in widespread clinical use. Research in this important field of digestive physiology is encouraged as many experimental data are in favor of supplementing formula diets with fiber.