Effect Of Lactulose Research Articles

The effect of lactulose on colonic ammonia and SCFA

The effect of lactulose on colonic ammonia and SCFA

Effects of lactulose and lactitol on protein digestion and metabolism in conventional and germ free animal models: relevance of the results to their use in the treatment of portosystemic encephalopathy.

Protein digestion and metabolism have been studied in laboratory rats and miniature pigs to investigate the mechanisms of action of lactulose and lactitol when used in the treatment of patients with portosystemic encephalopathy. Lactulose (beta-D-galactopyranosyl-(1----4)-beta-D-fructofuranose) and lactitol (beta-D-galactopyranosyl-(1----4)-D-glucitol) increased the excretion of nitrogenous material in the faeces and decreased nitrogen excretion in the urine in a similar degree to that reported for human patients. In studies with germ free rats given lactulose no such effect was observed, suggesting that, for lactulose at least, these effects are mediated by the gut flora. Measurement of the alpha-, epsilon-diaminopimelic acid content of the faeces confirmed that the enhancement of faecal nitrogen was due to an increased contribution from bacteria. The similarity in the results for lactulose and lactitol suggests that, from the perspective of protein metabolism, lactitol acts in a similar way to lactulose in the treatment of portosystemic encephalopathy.

Effect of lactulose on the metabolism of short-chain fatty acids

Short-chain (C2C5) fatty acids account for 60%–70% of the anions in the colon. Acetate (C2) is nontoxic in contrast to C(3)4C5 fatty acids (propionate, butyrate, isobutyrate, valerate, and isovalerate), which induce coma in animals and may be important in the pathogenesis of hepatic coma in humans. An in-vitro fecal incubation system was used to map out short-chain fatty acid production in the presence of lactulose, amino acids, albumin, or blood. Albumin and blood increased production of all C2C5 fatty acids. In contrast, lactulose was converted to acetate only and increased fecal acidity. The degradation of amino acids, albumin, and blood to short-chain fatty acids was completely inhibited by 10–25 mM lactulose. This was caused mainly by the acidifying effect of lactulose. pH-independent inhibition of blood and amino acid degradation to short-chain fatty acids required concentrations of lactulose exceeding 50–100 mM. Thus, the effect of lactulose in the treatment of hepatic coma may be related to its rapid fermentation into organic acids at rates exceeding colonic buffering capacity. This probably reduces formation of toxic fatty acids and ammonia from amino acids, polypeptides, and blood in the colon.

The effect of lactulose, pectin, arabinogalactan and cellulose on the production of organic acids and metabolism of ammonia by intestinal bacteria in a faecal incubation system

An in vitro faecal incubation system was used to study the metabolism of complex carbohydrates by intestinal bacteria. Homogenates of human faeces were incubated anaerobically with added lactulose, pectin, the hemicellulose arabinogalactan, and cellulose, both before and after subjects had been pre-fed each carbohydrate. Fermentation of added substrate was assessed by the production of short-chain fatty acids (SCFA) and suppression of net ammonia generation over 48 h of incubation. Control faecal homogenates to which carbohydrate was not added yielded an average increment of SCFA of 43 mmol/l, equivalent to 172 mmol/kg in the original stool. The addition of lactulose, pectin and arabinogalactan each increased the yield of SCFA by a similar amount, averaging 6.5 mmol/g carbohydrate or 1.05 mol/mol hexose equivalent; organic acid yield was not increased by pre-feeding these substances for up to 2 weeks. Acetate was the major SCFA in all samples at all times and, after pre-feeding with extra carbohydrate, butyrate concentrations exceeded propionate in all samples. Faecal homogenates incubated with cellulose showed no greater SCFA production than controls over the first 48 h, but there was a slight increase when samples from two subjects pre-fed cellulose were incubated for 14 d. Net ammonia generation was markedly suppressed by addition of lactulose to faecal incubates with an initial period of net bacterial uptake of ammonia. Pectin and arabinogalactan also decreased ammonia generation, but the reductions were not significant unless subjects were pre-fed these materials; cellulose had no effect on ammonia generation.

Lactulose detoxifies in vitro short-chain fatty acid production in colonic contents induced by blood: Implications for hepatic coma

Short-chain (C2–C6) fatty acids constitute the major anions of colonic contents. Acetate is nontoxic in contrast to C(3)4–C6 fatty acids, which induce coma in animals and have been reported to be of importance in the development of hepatic coma in humans. An in vitro fecal incubation system was used to demonstrate how blood, hemoglobin, albumin, lactulose, galactose, fructose, and glucose influence short-chain fatty acid production in the colon. Blood, hemoglobin, and albumin caused increased production of all C2–C6 fatty acids, with the most pronounced increase (fourfold) in C4–C6 fatty acids. Lactulose was converted to acetate only, as were its monosaccharide components, d-galactose and d-fructose. In assays incubated with blood, the production of C4–C6 fatty acids was completely inhibited by lactulose, d-galactose, d-fructose, and d-glucose, respectively, whereas the production of acetate was increased. Lactulose thus “detoxified” the profile of short-chain fatty acids produced in the presence of blood and proteins, indicating that colonic fermentative bacteria prefer lactulose to blood when both substrates are available. The effect of lactulose in the treatment of hepatic coma caused by episodes of gastrointestinal bleeding may therefore be due to a shift in bacterial metabolism from blood or proteins, or both, to lactulose in the colon, resulting in a simultaneous reduction in toxic nitrogenous and organic acid products.

Effect of lactulose on renal function in liver cirrhosis with and without ascites

Effect of lactulose on renal function in liver cirrhosis with and without ascites

The effect of lactulose and neomycin treatment on systemic and portal ammonia and amino acid levels in conscious pigs with a normal nitrogen intake

The effect of lactulose and neomycin treatment on systemic and portal ammonia and amino acid levels in conscious pigs with a normal nitrogen intake

Effect of lactulose on biliary lipid composition

It has been reported that lactulose can reduce biliary secondary bile acid (deoxycholate) composition and by this action can decrease biliary cholesterol saturation in patients with supersaturated bile. We tried to confirm this by feeding 60 g of lactulose per day during a period of 12 weeks to 8 healthy females with colonic adenomatous polyps and slightly elevated biliary cholesterol saturation. Although a 38% reduction of biliary deoxycholate was noted--38% after 4 weeks, and 32% after 12 weeks of lactulose feeding (P less than 0.01)--at the expense of a rise in both primary bile acids, cholate and chenodeoxycholate, no significant change in biliary cholesterol saturation was found after 4 nor after 12 weeks of lactulose feeding. These results do not support the concept that colonic bacterial metabolites of bile acids play a major role in the production of supersaturated bile and cholesterol gallstone formation.

Constipation in long-stay elderly patients: its treatment and prevention by lactulose, poloxalkol-dihydroxyanthroquinolone and phosphate enemas.

37 long-stay geriatric patients were studied. All had 80% transit time (TT) in excess of 6 days. Only an average of 23% of markers were passed by day 6 and 30% of patients still had markers in situ after 2 weeks. Three daily enemas had no effect on TT and three daily enemas together with a laxative for 6 days normalized TT in 40% only. A further 3 weeks of laxatives did not prevent constipation from getting worse. The effectiveness of lactulose and poloxalkol-dihydroxyanthroquinolone, respectively, were the same and better than no treatment.

Comparative effects of lactulose and magnesium sulfate on urea metabolism and nitrogen excretion in cirrhotic subjects

In previous studies with cirrhotic subjects administration of oral lactulose caused a reduction in the urea production rate associated with an increase in fecal nitrogen excretion. The change in the urea production rate in response to lactulose therapy was an indirect measure of a reduction in total gut ammonia production. In this study, the effect of magnesium sulfate administration was compared with lactulose therapy in 5 cirrhotic subjects to determine whether the effects of lactulose on nitrogen metabolism might be attributed to a nonspecific, cathartic effect. Both magnesium sulfate (5–15 g/day) and lactulose (40–80 g/day) caused significant and comparable increases in stool weight, solids, and total nitrogen. Only lactulose caused a reduction in fecal pH. Magnesium sulfate had no significant effect on the urea production rate or urinary nitrogen excretion, whereas lactulose caused a 25% reduction in the urea production rate and an 18% reduction in urinary nitrogen excretion. The latter was accounted for by a fall in urinary urea. Nitrogen balance was more negative during magnesium sulfate than during control or lactulose periods since magnesium sulfate increased fecal nitrogen without altering urinary nitrogen excretion. These data demonstrated that the effects of lactulose on nitrogen excretion and urea metabolism were not duplicated by equivalent cathartic doses of magnesium sulfate.

The effect of lactulose on urea metabolism and nitrogen excretion in cirrhotic patients

The mechanism of action of lactulose is not known, although in vitro evidence suggests that lactulose may increase ammonia utilization and decrease ammonia production by gut flora. If these changes occur in patients, they should be reflected in altered urea metabolism and nitrogen excretion. In seven studies conducted in 6 cirrhotic patients, the effects of lactulose on the kinetics of urea metabolism and nitrogen excretion were determined. Lactulose caused a fall in urea production (−24%, P < 0.005) that was reflected in a decrease in both urea degradation and urinary urea excretion. Likewise, lactulose caused a decrease in the total body urea pool. The fall in urinary urea was accompanied by a large (two- to threefold) increase in stool nitrogen that was of a similar magnitude of the fall in urinary urea. Although urea degradation fell after lactulose, the intestinal (extrarenal) clearance of urea did not, indicating that the fall in urea degradation was due to the observed fall in the urea pool. The results indicate that: (a) Lactulose decreases urea production by increasing the fecal output of nitrogen, a finding compatible with altered ammonia metabolism by gut flora, (b) Lactulose decreases urea degradation, although this effect is primarily the result of a fall in the urea pool and connot be attributed to an inhibition of urea of breakdown in the gut lumen.

The effect of lactulose on urea and nitrogen metabolism in cirrhotic patients

The effect of lactulose on urea and nitrogen metabolism in cirrhotic patients

Effect of lactulose (L), neomycin (N) and antacid (A) on colonic pH

Effect of lactulose (L), neomycin (N) and antacid (A) on colonic pH

Effect of lactulose on ammonia production in a fecal incubation system

An in vitro fecal incubation system was used to demonstrate how lactulose influences ammonia metabolism in the colon. Lactulose and other fermentable substrates (glucose, mannitol, and sorbitol), pH, and organic acid were varied independently so that their different effects could be determined. Fermentable substrate caused a fall in ammonia concentration during the period of fermentation. Acidification to pH 5.0 or less, with hydrochloric acid or a lactic-acetic acid mixture, significantly reduced ammonia generation, but unlike fermentable substrates, did not lower the existing ammonia concentration. The lactic-acetic acid mixture did not reduce ammonia generation significantly below that found with acidification by hydrochloric acid. The effect of lactulose in reducing ammonia concentration is attributed to its role as a bacterial substrate in either increasing bacterial assimilation of ammonia or reducing deamination of nitrogenous compounds. The effect of low pH in reducing generation of ammonia appears to be part of a general reduction in bacterial metabolism.

The Effect of Lactulose on Ammonia Production in a Faecal Incubation System

An in vitro fecal incubation system was used to demonstrate how lactulose influences ammonia metabolism in the colon. Lactulose and other fermentable substrates (glucose, mannitol, and sorbitol), pH, and organic acid were varied independently so that their different effects could be determined. Fermentable substrate caused a fall in ammonia concentration during the period of fermentation. Acidification to pH 5.0 or less, with hydrochloric acid or a lactic-acetic acid mixture, significantly reduced ammonia generation, but unlike fermentable substrates, did not lower the existing ammonia concentration. The lactic-acetic acid mixture did not reduce ammonia generation significantly below that found with acidification by hydrochloric acid. The effect of lactulose in reducing ammonia concentration is attributed to its role as a bacterial substrate in either increasing bacterial assimilation of ammonia or reducing deamination of nitrogenous compounds. The effect of low pH in reducing generation of ammonia appears to be part of a general reduction in bacterial metabolism.

An Explanation of the Effect of Lactulose in the Treatment of Hepatic Encephalopathy?

An Explanation of the Effect of Lactulose in the Treatment of Hepatic Encephalopathy?

The effect of lactulose on the faecal flora of patients with hepatic encephalopathy.

SUMMARY The changes that occurred in the faecal flora during the separate administration of lactulose and magnesium sulphate were studied in five patients with hepatic encephalopathy. Lactulose therapy produced significant increases in lactobacillus counts in three patients, and two of these patients showed clinical improvement. No systematic change occurred in the counts of other organisms during either treatment; in particular it was not possible to correlate clinical improvement with a reduction in the count of the two groups of organisms- enterobacteria and Bacteroides spp.-that are considered to be most active in the production of ammonia.

Faecal ammonia and pH during lactulose administration in man: comparison with other cathartics.

The effect of lactulose on faecal pH and ammonia has been studied in three normal subjects with the aid of dialysis of faeces in vivo. Observations were also made with sodium sulphate and the two hexahydric alcohols, mannitol and sorbitol, given in doses sufficient to cause a similar increase in stool weight. All four cathartics rendered the stool more acid, but there was no increase in the concentration of faecal ammonia. Lactulose, despite increasing faecal volume, did not cause an increase in the absolute amount of ammonia lost in the faeces, but the other purgatives did show a modest rise. The results are inconsistent with the theory that lactulose benefits the clinical picture of portosystemic encephalopathy by trapping ammonia in an acid stool. An alternative suggestion is advanced, namely, that any cathartic (including lactulose) reduces ammonia absorption from the colon by decreasing colonic transit time, and so reducing the amount of ammonia generated by autolysis of colonic bacteria.

The many effects of lactulose: a rational approach to its therapeutic use.

The many effects of lactulose: a rational approach to its therapeutic use.

Effect of lactulose on cerebral metabolism in patients with chronic portosystemic encephalopathy.

Cerebral blood flow and cerebral metabolism were studied in six patients with moderately severe portosystemic encephalopathy before and after a 10-day course of lactulose. As a result of therapy there was a mean increase in cerebral oxygen utilization but no changes in either mean glucose consumption or in mean cerebral blood flow. It appears therefore that the abnormalities in cerebral metabolism that have been previously described in patients with hepatic encephalopathy can be improved by the oral administration of lactulose.