The colon in carbohydrate malabsorption: short-chain fatty acids, pH, and osmotic diarrhoea.

Short-chain (C2-C6) fatty acids (SCFA) are the major anions in colonic contents and the result of anaerobic fermentation of mainly saccharides. The effects and regulation of saccharide fermentation were studied in vitro and in vivo. In vitro faecal incubation was used to study the effects of lactose, glucose, and galactose and of pH on SCFA formation. Changing the pH to below 5 or above 11 abolished SCFA formation in the faecal incubates; in the pH 5-9 interval SCFA production was high, with only minor pH dependence. Adding glucose, galactose, or lactose to the incubation system increased SCFA production, but at high saccharide concentrations (100-300 mmol/l) SCFA formation was inhibited by the pH change. In vivo disaccharide malabsorption with increasing doses of lactulose caused a decrease in faecal pH to less than 5, values inhibitory to fermentation, before the appearance of carbohydrate in faeces. In 6 of 12 volunteers diarrhoea occurred suddenly and was caused by malabsorbed non-fermented carbohydrate. The six other volunteers had a gradual increase in faecal output with lactulose dose and developed diarrhoea before the appearance of saccharide in faeces. The intake of lactulose tolerated before diarrhoea ensued varied between individuals, with the majority having diarrhoea of more than 11/day at 160 g lactulose per day. At this dose SCFA absorption was estimated to be in the range 550 to 1150 mmol/day.     

The influence of ispaghula husk and lactulose on the in vivo and the in vitro production capacity of short-chain fatty acids in humans

To evaluate factors influencing the short-chain fatty acid (SCFA) concentrations in stools, three different experiments were performed: faecal concentrations of SCFA at defecation were determined by gas liquid chromatography in nine healthy volunteers on a free diet. SCFAs were 114 +/- 15.0 mmol/l (means +/- SD). The coefficient of variation (CV) of the assay was 4-15%, the intraindividual CV 12-33%, and the interindividual CV 11-29%. On incubation of faeces at 37 degrees C concentrations of SCFA doubled in 6 h and rose fourfold in 72 h. In three volunteers the experiments were extended by adding ispaghula husk or lactulose to the diet for two 14-day periods each; no change in faecal SCFA concentrations was seen, either at defecation or after incubation. When ispaghula husk or lactulose was added to faeces in an in vitro incubation system, the concentrations of SCFA were five times higher than those of controls. We conclude that instant handling of faeces is essential for determinations of SCFA concentrations to obtain interpretable and comparable results; that determination of total SCFA output is of limited value; that addition of fibre to the diet does not influence faecal SCFA concentrations; and that the capacity for SCFA production in faeces is large provided a sufficient amount of substrate is available.     

Comparison of Diarrhea Induced by Ingestion of Fructooligosaccharide Idolax and Disaccharide Lactulose (Role of Osmolarity Versus Fermentation of Malabsorbed Carbohydrate)

Whether carbohydrate malabsorption causesdiarrhea probably depends on the balance between theosmotic force of the carbohydrate and the compensatorycapacity of the colon to dispose of the carbohydrate by bacterial fermentation. The present studyevaluated the specific role of the osmolarity bycomparing the severity of diarrhea after ingestion oftwo nonabsorbable carbohydrates, thefructooligosaccharide Idolax and the disaccharide lactulose. Bothcarbohydrates are readily fermented by the colonic florabut differ in osmolarity, the osmotic force being twiceas high for lactulose as for Idolax. Twelve subjects were given increasing doses (0, 20, 40, 80, 160g/d) of Idolax and lactulose in a crossover design.Every dose level was administered for three days withintervals of one week. Stools were collected on the third day to determine 24-hr volume,concentrations of short-chain fatty acids, L- andD-lactate, residues of Idolax or lactulose, sodium,potassium, pH, osmolarity, and in vitro productions oforganic acids. Measured by short-chain fatty acid andlactate formation in a fecal incubation system, thefermentation of Idolax and lactulose was identical andvery rapid compared with a range of referencecarbohydrates. A laxative effect of both Idolax and lactulosewas demonstrated. The increment in fecal volume as afunction of the dose administered was twice as high forlactulose (slope of the regression line = 7.3, r = 0.64, P < 10^-5) as for Idolax(slope = 3.7, r = 0.51, P < 10^-3), i.e.,isosmolar doses of lactulose and Idolax had the sameeffect on fecal volume. The variation in fecal volumewas substantial (lactulose 80 g/day: 110-1360 g/day; Idolax 160g/day: 130-1440 g/day). High responders had earlier andlarger fecal excretions of the saccharide compared withlow-responders. Fecal volume in carbohydrate-induced diarrhea is proportional to the osmotic forceof the malabsorbed saccharide, even though all or themajority of the saccharide is degraded by colonicbacteria. The capacity to modify the diarrhea varies considerably from person to person and isassociated with colonic saccharide disposal, whereas thevariation in response to isosmolar amounts of differentsaccharides is small within the sameindividual.     

Lactate and pH in faeces from patients with colonic adenomas or cancer.

Earlier studies have reported that faecal pH is more alkaline in patients with colonic cancer, indicating a reduction in colonic carbohydrate fermentation to organic acids. The pH of faeces from 11 pre and 14 postoperative, selected colonic cancer patients without intestinal obstruction, major loss of appetite or weight, not treated with antibiotics, and without signs of dissemination or recurrence of the cancer, did not differ, however, from faecal pH in 17 patients with previous colonic adenomas removed by polypectomy and faecal pH in 17 age matched (mean 61 years) healthy controls (mean (SE) 7.03 (0.10), 7.15 (0.11), 7.20 (0.12), 7.11 (0.12) respectively; p = 0.82). Faecal pH in 20 younger (mean 32 years) healthy controls tended to be lower (6.89 (0.07) compared with the older age matched control group (p < 0.06). Faecal concentrations of D-, L- or total D+L-lactate did not differ between the patients with present or previous colonic cancer, adenomas, and the healthy controls (D+L-lactate mean (SE) 3.2 (0.5), 3.1 (0.3), 3.5 (0.7), 4.1 (1.0) mmol/l respectively; p = 0.72), and the production pattern of lactate from different carbohydrates (glucose and dietary fibre) in 16.6% faecal homogenates was similar in all the three groups of patients and the healthy controls. Faecal pH was changed within days by modifications of the diet. An enteral diet free of fibre, starch, and lactose increased faecal pH within three days, whereas pH decreased when the colonic load of carbohydrates was increased by lactulose. Therefore, the reported alkaline faecal pH in patients with colonic cancer may reflect short term reduction in dietary intake and colonic fermentation secondary to the presence of the cancer, especially in patients with advanced disease, rather than long term differences in the precancer dietary habits.     

Lactose tolerance in lambs with rotavirus diarrhoea.

It has been suggested that lactose malabsorption is an important factor in producing the diarrhoea of acute rotavirus infection. Accordingly, the lactose tolerance of gnotobiotic newborn lambs, infected with lamb rotavirus, has been investigated by clinical studies and tissue enzyme assays. Although lactase activity is low in affected areas of the small intestine, rotavirus infected lambs are not lactose intolerant as assessed by the measurement of reducing substances in the faeces, or by the clinical effects and blood glucose levels after a 5.8 mmol (2 g)/kg lactose load on the second day post-infection. Lactose intolerance could be demonstrated by using extremely high (29.2 mmol (10 g)/kg) doses of lactose, three or four times the normal dietary lactose intake. These experiments suggest that lactose-containing feeds (such as maternal milk) are not necessarily contraindicated in patients or animals with rotavirus diarrhoea.     

Short-chain fatty acids and the irritable bowel syndrome: the effect of wheat bran

Short-chain fatty acids (SCFA) in faeces were examined in 18 patients with the irritable bowel syndrome (IBS) during treatment with wheat bran or placebo. In the placebo period, the patients could be classified in accordance with the faecal concentrations of SCFA into one group with low concentrations (mean, 40 mmol/l; range, 19-77 mmol/l; 10 patients) and another with high concentrations (mean, 168 mmol/l; range, 145-187 mmol/l; 8 patients). The concentrations of SCFA differed (P less than 0.001) in both groups from concentrations found in faeces from a reference group of nine normal individuals (mean, 114 mmol/l; range, 93-155 mmol/l). Patients with low levels of SCFA had lower (P less than 0.001) mean stool mass and longer (P less than 0.05) transit times than those with high concentrations of SCFA in faeces. Ingestion of bran, although a precursor of SCFA, did not change faecal concentrations of SCFA. Abdominal pain, distension, and rumbling were not correlated to low or high concentrations of SCFA in faeces, nor did bran improve these symptoms when compared to placebo. The level of SCFA was rather constant intraindividually and independent of the variability of the daily faecal mass. It is concluded that patients with IBS apparently have continuously abnormal concentrations of SCFA in faeces, either high or low, which are unaffected by the treatment with bran and which hypothetically may be of pathophysiologic importance.     

Coincidental Malabsorption of Lactose, Fructose, and Sorbitol Ingested at Low Doses Is Not Common in Normal Adults

Normal subjects may incompletely absorb either lactose, fructose, or sorbitol and may therefore have abdominal symptoms. The frequency of coincidental malabsorption of these sugars is not known. This is clinically important, since we often ingest them during the same day and malabsorption may cause abdominal symptoms. To shed light on this issue we studied 32 normal subjects. Volunteers drank in random order the following solutions: 20 g lactulose, 50 g sucrose, 50 and 25 g lactose, 50 and 25 g fructose, 20 and 10 g sorbitol. Semiquantitative carbohydrate malabsorption was estimated with lactulose standards. Frequency of 50-g lactose (69%), 50-g fructose (81%), and 20-g sorbitol (84%) malabsorption was not significantly different (P = 0.3). The estimated median fraction of the ingested high dose malabsorbed was 42, 19, and 68% for lactose, fructose, and sorbitol, respectively. At low challenging doses, 63% of the volunteers absorbed two of three or all three sugars, and 88% were asymptomatic to two or all three sugars. In conclusion, the frequency of coincidental malabsorption of lactose, fructose, and sorbitol and intolerance to these sugars is not common, when normal adults ingest them at low doses.     

Increasing the intestinal resistance of rats to the invasive pathogen Salmonella enteritidis: additive effects of dietary lactulose and calcium.

BACKGROUND AND AIMS: Lactulose fermentation by the intestinal microflora acidifies the gut contents, resulting in an increased resistance to colonisation by acid sensitive pathogens. The extent of fermentation should be controlled to prevent acid induced epithelial cell damage. Considering the buffering capacity of calcium phosphate and its intestinal cytoprotective effects, whether supplemental calcium phosphate adds to the increased resistance to intestinal infections by lactulose fermentations was studied. METHODS: In a strictly controlled experiment, rats were fed a purified low calcium control diet, a low calcium/lactulose diet, or a high calcium/lactulose diet, and subsequently infected orally with Salmonella enteritidis. RESULTS: Lactulose fermentation lowered the pH and increased the lactic acid concentration of the intestinal contents, which significantly reduced excretion of this pathogen in faeces; thus it improved the resistance to colonisation. This agreed with the high sensitivity of S enteritidis to lactic acid (main metabolite of lactulose fermentation) in vitro. Calcium phosphate decreased translocation of S enteritidis to the systemic circulation, an effect independent of lactulose. The unfavourable increased cytotoxicity of faecal water caused by lactulose fermentation was more than counteracted by supplemental calcium phosphate. Moreover, calcium phosphate stimulated lactulose fermentation, as judged by the reduced lactulose excretion in faeces and increased lactic acid, ammonia, and faecal nitrogen excretion. CONCLUSION: Extra calcium phosphate added to a lactulose diet improves the resistance to colonisation and translocation of S enteritidis. This is probably mediated by a calcium induced stimulation of lactulose fermentation by the intestinal microflora and reversion of the lactulose mediated increased luminal cytotoxicity, which reduces damage inflicted on the intestinal mucosa.     

Ecological studies on intestinal microbial flora of Kenyan children with diarrhoea

The intestinal microflora was analysed together with short-chain fatty acids (SCFA) and bile acids in faeces from nine children with acute diarrhoeal disease in Lari, Kenya. Enteric pathogens such as enteroinvasive E. coli, enteropathogenic E. coli, Yersinia enterocolitica, rotavirus, Giardia lamblia and Entamoeba histolytica were isolated either singly or in combination from diarrhoeal faecal specimens. The most striking finding in these patients was a marked reduction of anaerobes. Analysis of the SCFA revealed a significantly higher quantity of the volatile fatty acids (VFA) such as acetic, propionic, and butyric acid in recovery period faeces in comparison to diarrhoeal faeces, although no significant difference was seen in the quantity of non-volatile fatty acids. On analysing bile acids in faeces, conjugated primary bile acids were detected from all cases in diarrhoea whereas the free form of secondary bile acids was seen only in recovery. The pH of recovery faecal specimens was significantly lower than that in diarrhoeal faecal specimens. There was a parallel between the decrease in number of anaerobes and fluctuation in the amount of SCFA, showing that the drastic reduction of VFA accompanying decrease of anaerobes during the diarrhoeal state, and the rise in pH thought to arise from these facts, result in an increase of water content.     

Breath testing to evaluate lactose intolerance in irritable bowel syndrome correlates with lactulose testing and may not reflect true lactose malabsorption

OBJECTIVES: An increased prevalence of lactose intolerance is seen in irritable bowel syndrome (IBS). Recently, we demonstrated a high prevalence of abnormal lactulose breath test results in IBS suggesting bacterial overgrowth. Because symptoms of lactose intolerance result from bacterial fermentation, the purpose of this study was to determine whether an abnormal lactose breath test is reflective of malabsorption or early presentation to bacteria. METHODS: Subjects with diarrhea-predominant IBS were enrolled. On day 1, subjects underwent a lactulose breath test after an overnight fast. Within 1 wk, subjects returned after fasting for a lactose breath test with simultaneous blood glucose measurements every 15 min to complete a lactose tolerance test (LTT). Symptoms were evaluated 3 h after lactose administration. RESULTS: Twenty subjects completed the study. One subject inadvertently received dextrose through the intravenous and was excluded. Of the remaining 19 subjects, three (16%) had an abnormal LTT suggesting malabsorption. In all, 10 subjects (53%) had an abnormal lactose breath test, 14 (74%) had an abnormal lactulose breath test, and 11 (58%) had symptoms after lactose administration. The agreement with symptoms was moderate (kappa = 0.47) and fair (kappa = 0.24) when compared to the lactose breath test and LTT, respectively. There was a fair correlation between lactose breath test and LTT (kappa = 0.29). However, lactose breath test hydrogen levels >166 ppm were universally predictive of abnormal LTT. Finally, a significant correlation was seen between the hydrogen production on lactose and lactulose breath test (r = 0.56, p = 0.01). CONCLUSIONS: Lactose breath testing in IBS subjects does not seem to reflect malabsorption; it may be an indicator of abnormal lactulose breath test, suggesting bacterial overgrowth.     

Influence of Oral Intake of Seven Different Antibiotics on Faecal Short-Chain Fatty Acid Excretion in Healthy Subjects

Faecal excretion of short-chain fatty acids (SCFAs) has been measured by gas chromatography in groups of six or seven healthy subjects before, during, and after they received the antibiotics bacitracin, co-trimoxazol, doxycycline, erythromycin, nalidixic acid, ofloxazin, or vancomycin orally for 6 days. Intake of bacitracin and vancomycin had pronounced effects on faecal SCFAs excretion and reduced median total concentration of SCFAs from 105.4 mmol/kg to 21.8mmol/kg and from 69.3 mmol/kg to 19.4 mmol/kg, respectively (p < 0.05). Erythromycin had moderate effects on the faecal SCFAs excretion, whereas small or no changes were seen during intake of co-trimoxazol, doxycycline, nalidixic acid, and ofloxacin. 2-Methylbutyric acid, a SCFA not previously seen in human faeces, was found in the faeces of all subjects (median concentration before intake of antibiotic, 1.3 mmol/kg). Bacitracin, erythromycin, nalidixic acid, and vancomycin were detected in high concentrations in faeces during therapy, whereas trimethoprim, doxycycline, and ofloxacin were found in relatively low concentrations. In conclusion, some, but not all, peroral antimicrobials induce changes in faecal SCFAs, most likely reflecting changes in the colonic ecosystem.     

Acidic colonic microclimate--possible reason for false negative hydrogen breath tests.

About 5% of normal subjects fail to produce increased hydrogen breath concentration after ingestion of the non-digestible carbohydrate lactulose (low hydrogen producers). The existence of low hydrogen producers limits the diagnostic use of hydrogen (H2) breath tests. We studied the effects of lactulose and of magnesium sulphate (MgSO4) pretreatment on stool-pH and on hydrogen exhalation after oral loading with lactulose or lactose in 17 hydrogen producers and 12 low hydrogen producers. In seven hydrogen producers acidification of stool pH by lactulose pretreatment (20 g tid) decreased hydrogen exhalation and three of seven (43%) became low hydrogen producers. In contrast, after pretreatment of eight low hydrogen producers with magnesium sulphate (5 g twice daily) all eight produced hydrogen after a lactulose load. Similarly four lactose intolerant low hydrogen producers had abnormal lactose hydrogen breath tests after MgSO4 pretreatment. MgSO4 pretreatment neither resulted in false positive lactose hydrogen breath tests in five lactose tolerant hydrogen producers, nor increased the hydrogen exhalation in five additional hydrogen producing controls after ingestion of lactulose. The results of these studies confirm that hydrogen production from lactulose decreases when the colonic pH is lower (lactulose pretreatment), and increases when colonic pH is higher (MgSO4 pretreatment). In low hydrogen producers the lacking increase of H2 exhalation after ingestion of non-digestible carbohydrates can be overcome by MgSO4 pretreatment, thus increasing the sensitivity of the test by avoiding false negative hydrogen breath tests in low hydrogen producers with disaccharide malabsorption or maldigestion. The underlying mechanism of this remarkable effect of MgSO4 pretreatment warrants further investigation.     

Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects

Faecal excretion of short-chain fatty acids (SCFAs) has been measured by gas chromatography in groups of six or seven healthy subjects before, during, and after they received the antibiotics bacitracin, co-trimoxazol, doxycycline, erythromycin, nalidixic acid, ofloxazin, or vancomycin orally for 6 days. Intake of bacitracin and vancomycin had pronounced effects on faecal SCFAs excretion and reduced median total concentration of SCFAs from 105.4 mmol/kg to 21.8 mmol/kg and from 69.3 mmol/kg to 19.4 mmol/kg, respectively (p less than 0.05). Erythromycin had moderate effects on the faecal SCFAs excretion, whereas small or no changes were seen during intake of co-trimoxazol, doxycycline, nalidixic acid, and ofloxacin. 2-Methylbutyric acid, a SCFA not previously seen in human faeces, was found in the faeces of all subjects (median concentration before intake of antibiotic, 1.3 mmol/kg). Bacitracin, erythromycin, nalidixic acid, and vancomycin were detected in high concentrations in faeces during therapy, whereas trimethoprim, doxycycline, and ofloxacin were found in relatively low concentrations. In conclusion, some, but not all, peroral antimicrobials induce changes in faecal SCFAs, most likely reflecting changes in the colonic ecosystem.     

Modification of Colonic Fermentation by Bifidobacteria and pH In Vitro (Impact on Lactose Metabolism, Short-Chain Fatty Acid, and Lactate Production)

Colonic fermentation plays an important role inthe prevention of lactose intolerance and intestinaldisorders. The objectives of this study were to evaluatewhether supplementation with bifidobacteria modify colonic fermentation of lactose andshort-chain fatty acid production and to assessinfluence of the pH in an in vitro continuous culturesystem. There was a significantly greater reduction inlactose concentrations at pH 6.7 than that at either pH6.2 or pH 5.7, accompanied by the highest-galactosidase activity and D-lactate production.Bifidus supplementation reduced lactose and D-lactateconcentrations and increased acetate production at pH 6.7. Thestudy demonstrates that lactose is rapidly metabolizedby colonic bacteria and lactose fermentation in vitro ispH dependent with a maximum rate at pH 6.7. Bifidobacteria supplementation may have thepotential to improve lactose fermentation and tomanipulate SCFA and lactate production.     

Colonic dysfunction in acute diarrhoea: the role of luminal short chain fatty acids.

Faecal concentrations and output of short chain fatty acids (SCFA) were assessed on successive days by gas-liquid chromatography in 24 patients with acute watery diarrhoea. Absorption of water and sodium from the rectum was also measured by a dialysis technique in 17 of these patients and in nine normal subjects in the presence and absence of luminal SCFA. Faecal SCFA concentrations were low on the first day of diarrhoea (mean (SEM) 9.9 (5.8) mmol/kg) and increased to 94.8 (16.4) mmol/kg by the fifth day. Faecal output of SCFA corresponded to these figures. Net water absorption, in the absence of luminal SCFA, was stopped in patients with acute diarrhoea (-59 (81) nl/cm2/min) compared with healthy controls (+322 (63) nl/cm2/min) (p < 0.01). Luminal SCFA restored net water absorption to +184 (67) nl/cm2/min in patients with acute diarrhoea (p < 0.01). Net absorption of sodium decreased in patients with acute diarrhoea in the absence of luminal SCFA, but returned to normal with luminal SCFA. Net secretion of potassium increased in acute diarrhoea, and did not change in the presence of SCFA. Defective absorption from the rectum in acute diarrhoea is reversed by luminal SCFA. The reduction of luminal SCFA in acute diarrhoea treated conventionally may be a factor contributing to colonic dysfunction.     

Pilot study on the effect of reducing dietary FODMAP intake on bowel function in patients without a colon

BACKGROUND: Poorly absorbed short-chain carbohydrates (FODMAPs) in the diet should, by virtue of their osmotic effects, increase fecal output following colectomy and ileal pouch formation or ileorectal anastomosis (IRA). The aim was to perform a proof-of-concept evaluation of this hypothesis. METHODS: Fifteen patients (13 pouch, 2 IRA) had dietary and symptomatic evaluation before and during a low FODMAP diet. Carbohydrate malabsorption was evaluated by breath tests. Pouchitis was assessed clinically/endoscopically or by fecal lactoferrin. RESULTS: Of 8 patients with a breath hydrogen response to lactulose, 7 had fructose malabsorption, 3 with lactose malabsorption, and 1 had lactose malabsorption alone. Five of 7 studied retrospectively improved stool frequency (from median 8 to 4 per day; P = 0.02), this being sustained over 0.5-3 years of follow-up. Five of 8 patients completed a prospective arm of the study. One patient had sustained improvement in stool frequency and 1 had reduced wind production. Overall, none of 8 patients who had pouchitis improved. In contrast, median daily stool frequency fell from 8 to 4 (P = 0.001) in the 7 without pouchitis. The degree of change in FODMAP intake also predicted response. There was a tendency for pouchitis to be associated with low baseline FODMAP intake. CONCLUSIONS: There is a high prevalence of carbohydrate malabsorption in these patients. Reduction of the intake of FODMAPs may be efficacious in reducing stool frequency in patients without pouchitis, depending on dietary adherence and baseline diet.     

Faecal Short-Chain Fatty Acids in Patients with Antibiotic-Associated Diarrhoea,before and after Faecal Enema Treatment

Background: Antibiotic-associated diarrhoea (AAD) may range from mild disturbances to severe pseudomembranous colitis. Many antibiotics affect several intestinal microflora-associated characteristics, such as short-chain fatty acid (SCFA) pattern. In the present study we investigated SCFAs in 31 patients on admittance to the hospital for severe AAD. Nine patients were followed up more extensively after they had received an enema containing faecal microflora from a healthy person on a Western diet. Methods: Faecal SCFAs were determined by gas chromatography. The enema was characterized before use. Results: AAD patients showed significant disturbances in faecal SCFA pattern. Clinically, most enema-treated patients recovered within days and had no relapses within 18 months. Conclusions: Intestinal microflora showed great disturbances, and the amounts of SCFAs were reduced, although the diarrhoea was not related to total amount SCFAs. Administration of a faecal enema resulted in the clinical recovery of most patients with severe diarrhoea within 4 days.     

Blood glucose response after oral intake of lactulose in healthy volunteers: A randomized,controlled, cross-over study

AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars(e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L(mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations(P 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities(1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.     

Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect?

Background—Uncontrolled studies of lactoseintolerant subjects have shown that symptom severity decreases afterchronic lactose consumption. Adaptation of the colonic flora mightexplain this improvement.
Aims—To compare the effects of regularadministration of either lactose or sucrose on clinical tolerance andbacterial adaptation to lactose.
Methods—Forty six lactose intolerant subjectsunderwent two 50 g lactose challenges on days 1 and 15. Between thesedays they were given 34 g of lactose or sucrose per day, in a doubleblind protocol. Stool samples were obtained on days 0 and 14, tomeasure faecal β-galactosidase and pH. Symptoms, breathH₂ excretion, faecal weight and electrolytes, and orofaecaltransit time were assessed.
Results—Except for faecal weight, symptomswere significantly milder during the second challenge in both groups,and covariance analysis showed no statistical difference between them.In the lactose group, but not in the sucrose group, faecalβ-galactosidase activity increased, pH dropped, and breathH₂ excretion decreased.
Conclusion—Bacterial adaptation occurredwhen lactose intolerant subjects ingested lactose for 13 days, and allsymptoms except diarrhoea regressed. Clinical improvement was alsoobserved in the control group which displayed no signs of metabolicadaptation. This suggests that improved clinical tolerance may be justa placebo effect.

     

Absorption of Wheat Starch in Patients Resected for Left-Sided Colonic Cancer

Bacterial fermentation of carbohydrate in the colon, producing short-chain fatty acids (SCFA)–and especially butyrate–has been shown possibly to impede cell proliferation and regulate cell differentiation of colonocytes. In patients with diverticular disease or benign polyps in the colon a hyperabsorption of potato starch in the small intestine has been found. We have investigated the absorption of wheat starch in 15 patients radically resected for cancer in the descending or sigmoid colon, and the results were compared with those of 15 healthy controls. The starch malabsorption was quantified by the hydrogen breath test. The patients malabsorbed 2-14 g (median, 8g) of 100 g wheat starch ingested, and the control group malabsorbed 3-11 g (median, 6 g) (P > 0.1). Mouth-to-cecum transit time for wheat starch and lactulose and the hydrogen production capacity after the lactulose standards were also similar in patients and controls. The results do not support the theory that hyperabsorption of starch is characteristic of patients with malignant disease in the large intestine