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PubMed1983

Pulmonary hydrogen and methane and plasma ammonia after the administration of lactulose or sorbitol.

The gut microfloral metabolism of sorbitol and lactulose was investigated in 10 healthy control subjects and 10 patients with cirrhosis of the liver, by measuring the pulmonary excretion of the fermentational gases hydrogen and methane during 3 h. A possible acute effect on venous plasma ammonia after a single dose of sorbitol or lactulose was also investigated. No significant difference in fermentation gas excretion was found after ingestion of sorbitol compared with lactulose in healthy controls or cirrhotic patients (p greater than 0.05). Neither sorbitol nor lactulose had significant effect on plasma ammonia concentrations during the first 3 h after ingestion. These findings indicate that both sorbitol and lactulose are extensively fermented by the colonic flora and that the possibility of replacing lactulose with the much cheaper sorbitol in the treatment of portal-systemic encephalopathy ought to be investigated. The suggested acute gut-ammonia trapping effect of lactulose caused by acidification of the gut lumen from fermentative end-products was not supported by the present findings.

Adult↗
PubMed2005

Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study.

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p = 0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0 --> 4.2, p = 0.000); lactulose group (11.3 --> 5.0, p = 0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Female↗
PubMed1977

Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.

A randomized double blind clinical comparison of neomycin and lactulose was performed in 33 cirrhotic patients with chronic portal-systemic encephalopathy (PSE) at seven cooperating hospitals. In order to maintain double blindness, sorbitol syrup was used as a control solution along with neomycin and was compared with lactulose syrup and placebo tablets in a double drug protocol. Twenty-nine patients were studied in a crossover investigation in which each received both therapeutic regimens preceded and followed by control periods. Four additional patients received one or the other agent, but did not receive both. Serial, semiquantitative assessments were made in all patients of mental status, asterixis, and the trailmaking test (TMT) and electroencephalograms (EEG) and arterial ammonia levels. Both neomycin-sorbitol and lactulose were effective in the majority of patients (83 and 90%, respectively). Each of these parameters (mental state, asterixis, TMT, EEG, and NH3) was improved significantly by neomycin-sorbitol and lactulose. The post-treatment levels for each of these measures were similar in the neomycin and lactulose-treated groups. Mean stool pH was reduced by neomycinsorbitol to 6.1 and by lactulose to 5.5. This difference was highly significant statistically. Bowel activity was similar in the two groups. Both drugs were free of toxicity. These investigations demonstrate that both lactulose and neomycin-sorbitol are effective in the treatment of chronic portal-systemic encephalopathy.

Aged↗
PubMedDate not supplied

Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study.

Despite steady progress in therapeutics of liver disease, portal systemic encephalopathy remains to be a great challenge for clinicians because of the heterogeneity of neuropsychiatric symptoms, multiple risk factors and complexity on achieving a sustained response. We aimed to evaluate the efficacy of L-Ornithin, L-Aspartate versus lactulose in Mexican patients with hyperammonemic hepatic encephalopathy. A total of 20 patients were randomly allocated to receive either lactulose(n = 10) or L-ornithine - L-aspartate (n = 10) for 2 weeks. At baseline, patients of both groups were comparable in age (64 +/- 7 versus 60 +/- 6) and degree of hepatic failure according to the Child-Pugh scale (9.2 +/- 1.3 versus 9.2 +/- 1.1). A significant decrease in ammonia levels was observed both in the lactulose group (120.4 +/- 8.1 versus 91.4 +/- 10, p < 0.05) and in the LOLA group (141.6 +/- 9.1 versus 96.9 +/- 9.3, p < 0.05). Moreover, in patients who received LOLA a significant improvement was observed in mental status (1.0 +/- 0.14 versus 0.4 +/- 0.16, p < 0.05), Number Connection Test (184 +/- 43 versus 88 +/- 7, p < 0.05), asterixis (14.6 +/- 2.8 versus 6.7 +/- 1.5, p < 0.05), as well as EEG findings (6.8 +/- 0.6 versus 8.1 +/- 0.2 cycles per second, p < 0.05). Compliance with study medications was similar between the lactulose group (94%) and the LOLA group (100%). No serious adverse events were reported in the two groups; however, in the lactulose group an increase in the number of weekly defecations was reported, as well as a higher incidence of abdominal pain or flatulence. Finally, both patient groups reported an improvement in the Visual Analogue Scale for EuroQol index (51.1 +/- 24.1 versus 61.5 +/- 15.8, p < 0.05, in the lactulose group; 56.5 +/- 24.5 versus 70 +/- 19.4, p < 0.05, in the LOLA group). In conclusion, oral administration of lactulose or L-ornithine - L-aspartate to Mexican patients with cirrhosis and hyperammonemic encephalopathy significantly reduced serum ammonia levels in study groups and additionally improved mental status parameters, number connection test, asterixis scores, and EEG activity in the group receiving L-ornithine-L-aspartate.

Administration, Oral↗
PubMed1991

[Treatment of gut-derived endotoxemia with lactulose. An experimental study].

Endotoxemia plays an important role in the origination and development of many dangerous clinical diseases, for which there has been little medication so far. To determine whether lactulose has an effect on endotoxemia, we treated experimental, gut-derived endotoxemia using lactulose in vitro and in vivo. The results showed that 55 mg lactulose inactivated the activity of 0.01 mg endotoxin on limulus lysate in vitro, suggesting that lactulose may have a direct anti-endotoxin effect. In vivo study in rats showed that blood endotoxin level was significantly decreased from 78.61 +/- 6.54 pg/ml to 20.26 +/- 2.38 pg/ml (P less than 0.01), and liver damage significantly reduced after lactulose treatment. It is suggested that lactulose can prevent absorbtion of endotoxin from gut and may have an effect on gut-derived endotoxemia. The mechanism of lactulose for treating endotoxemia is discussed.

Animals↗
PubMed1990

[Effect of lactulose on ammonia metabolism during exercise].

In seven athletes, the effects of lactulose on ammonia metabolism during dynamic exercise were studied with a cycle ergometer. Each subject performed a graded incremental test with increases in work rate of 300 kpm/3 min until exhaustion set in, on two separate days, one without lactulose and one with 20 mg/day lactulose for 3 days. Without lactulose, maximal heart rate and peak oxygen uptake (VO2) were 193 beats/min and 4280 ml/min, respectively. LA was unchanged early in exercise, but elevated rapidly at work rates of 900 kpm (54% peak VO2) and thereafter. AMM increased even at rates as low as 600 kpm (40% peak VO2) and continued to rise attaining peak value at the termination of exercise. After exercise, AMM decreased rapidly. On the other hand, LA was still significantly above the basal level after 30 min of recovery. After lactulose, heart rate, duration of exercise or LA was not significantly different from the value without lactulose at the same work rate, however, AMM at low work rate was lower and VO2 at 1500 kpm was higher. Lactulose had small but significant effects on some parameters of graded exercise.

Adult↗
PubMed1996

The lactulose breath hydrogen test and small intestinal bacterial overgrowth.

OBJECTIVES: To i) document the sensitivity and specificity of a combined scintigraphic/lactulose breath hydrogen test for small intestinal bacterial overgrowth and ii) investigate the validity of currently accepted definitions of an abnormal lactulose breath hydrogen test based on "double peaks" in breath hydrogen concentrations. METHODS: Twenty-eight subjects were investigated with culture of proximal small intestinal aspirate and a 10-g lactulose breath hydrogen test combined with scintigraphy. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of overgrowth flora to ferment lactulose were determined. RESULTS: Sensitivity (16.7%) and specificity (70.0%) of the lactulose breath hydrogen test alone for small intestinal bacterial overgrowth were poor. Combination with scintigraphy resulted in 100% specificity, because double peaks in serial breath hydrogen concentrations may occur as a result of lactulose fermentation by cecal bacteria. Sensitivity increased to 38.9% with scintigraphy, because a single rise in breath hydrogen concentrations, commencing before the test meal reaches the cecum, may occur in this disorder. Sensitivity remained suboptimal irrespective of the definition of small intestinal bacterial overgrowth used, the nature of the overgrowth flora, favorable luminal pH, the presence of concurrent gastric bacterial overgrowth, or the in vitro ability of the overgrowth flora to ferment lactulose. CONCLUSIONS: Definitions of an abnormal lactulose breath hydrogen test based on the occurrence of double peaks in breath hydrogen concentrations are inappropriate. Not even the addition of scintigraphy renders this test a clinically useful alternative to culture of aspirate for diagnosing small intestinal bacterial overgrowth.

Bacterial Infections↗
PubMed2001

Lactulose-L-rhamnose intestinal permeability test in patients with liver cirrhosis.

A lactulose-L-rhamnose intestinal permeability test was conducted on 35 patients with liver cirrhosis and six normal controls. Gas chromatography was used to measure lactulose and L-rhamnose concentrations in blood and urine specimens. The excretion of each molecule was expressed as the percentage of the orally administrated dose and the lactulose-L-rhamnose ratio as the ratio of the percentage of each probe molecule excreted. The mean 8-h lactulose excretion ratios were 0.56 and 0.16% in patients with liver cirrhosis and the control subjects, respectively (P<0.05), whereas the corresponding excretion ratios for L-rhamnose were 4.40 and 3.49%. The mean lactulose-L-rhamnose excretion ratios in patients with liver cirrhosis and the control subjects were 0.124 and 0.049, respectively (P<0.05). The lactulose-L-rhamnose excretion ratio increased in patients with liver cirrhosis complicated by large intestinal vascular ectasia of the large intestine or rectal varices, which were used as parameters for evaluating the effects of portal hypertension on the lower digestive tract. These results suggest that an increase in lactulose intestinal permeability in patients with liver cirrhosis proves the effects of portal hypertension extending to the lower digestive tract.

Journal Article↗
PubMed1986

Experimental and clinical study of lactulose in obstructive jaundice.

The role of lactulose in preventing endotoxaemia in obstructive jaundice has been investigated. A prospective study was performed on 24 consecutive patients with obstructive jaundice undergoing surgery. Twelve patients were given oral lactulose before operation and were compared with twelve controls. Endotoxaemia was reduced in peroperative portal (P less than 0.05) and postoperative systemic (P less than 0.05) blood samples in the lactulose treated group, and a significant fall (P less than 0.05) occurred in the postoperative 24 h creatinine clearances in controls compared with the lactulose treated group. Results from animal experiments in which oral lactulose reduced endotoxin related mortality in obstructive jaundice (P less than 0.05), and the in vitro demonstration of a direct anti-endotoxic action of lactulose suggest that its beneficial action is due in part to an inactivation of endotoxin.

Acute Kidney Injury↗
PubMedDate not supplied

Galactosamine hepatitis, endotoxemia, and lactulose.

Studies by Liehr et al. suggest that endotoxins are important in the pathogenesis of galactosamine hepatitis (Gal-N hepatitis) in rats. Lactulose (9.1 gm per kg per day) prevents hepatic lesions induced by Gal-N; an antiendotoxin effect of lactulose is postulated. However, commercial preparations of lactulose are contaminated with galactose, which shows a competitive action to Gal-N. To analyze the effect of galactose, male Wistar rats were pretreated with lactulose (Duphalac, 9.1 gm per kg per day) and given Gal-N (375 mg per kg i.p.). After 24 hr, serum was analyzed for glutamic pyruvate transaminase, glutamate dehydrogenase, and sorbitol dehydrogenase activities. Pretreatment with Duphalac, even 1 hr before Gal-N, abolished toxicity. Duphalac contains 10 gm galactose per 100 ml. Galactose was given in a similar concentration and similar inhibition occurred. Pretreatment with purified lactulose (9.1 gm per kg for 5 days) diminished the effects of Gal-N but did not normalize enzyme concentrations. Because small doses of galactose (80 and 300 mg per kg) showed similar inhibitory effects, we conclude that the protective effect of commercial lactulose preparations is mainly due to galactose contamination and not to an antiendotoxin effect.

Animals↗
PubMedDate not supplied

Lactitol vs. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial.

Lactitol (beta-galactosido-sorbitol) is a nonabsorbable disaccharide available as a powder which, in open comparison, is as effective as lactulose in the treatment of chronic hepatic encephalopathy, but is better tolerated. Twenty-five cirrhotic patients experiencing 28 episodes of acute hepatic encephalopathy were randomized blindly to treatment with either lactitol (n = 15) or lactulose (n = 13). The sugars were dispensed in solutions identical in appearance, taste and pH and of similar osmolarity, which contained either 66.7 gm per 100 ml lactitol or 66.7 ml (44.5 gm) per 100 ml lactulose syrup. The initial dose of 0.75 ml per kg was adjusted to produce two semisoft stools per day. Patients were assessed every 12 hr for 5 days. There were no significant differences in sex ratio, age, body weight, clinical status, duration and extent of coma, etiology of liver disease or of hepatic encephalopathy between the two groups of patients on entry to the trial. An adequate catharsis was obtained with an equivalent mean (+/- 1 S.D.) daily dose of 26 +/- 5 gm lactitol or 31 +/- 7 ml (21 +/- 5 gm) lactulose syrup. During the trial, significant improvements occurred in clinical status and psychometric performance and in the electroencephalogram mean cycle frequencies in the majority of patients in both groups. At the end of the trial, 67% of the patients in the lactitol group and 69% of the lactulose group were clinically normal. However, patients treated with lactitol responded significantly more quickly than patients treated with lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The effects of lactulose-sweetened yoghurt on the rate of gastric emptying and intestinal transit in healthy human volunteers.

A non-invasive, radioisotopic method was utilised to study the effects of a lactulose-sweetened yoghurt product on gastric emptying and intestinal transit. Healthy human volunteers were given 99mtechnetium-DTPA-labelled lactulose yoghurt before and after adaptation to the product. A control group received a similarly labelled glucose solution. Gastric emptying and intestinal transit were evaluated by scintigraphy. The mean half-time for gastric emptying for glucose was 39.8 +/- 3.4 min and for lactulose yoghurt, 31.3 +/- 11.0 min. After 10 days' adaptation, the corresponding value for lactulose yoghurt was 25.2 +/- 8.2 min. Intestinal transit time was faster after lactulose yoghurt than after glucose solution and did not change during adaptation. The observed effects indicate that lactulose yoghurt may be beneficial in the treatment or chronic constipation using dietary methods.

Adult↗
PubMed1990

The degradation of amino acids, proteins, and blood to short-chain fatty acids in colon is prevented by lactulose.

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.

Albumins↗
PubMed1992

Scintigraphic demonstration of lactulose-induced accelerated proximal colon transit.

Although lactulose, a widely used cathartic, is known to increase stool frequency, details of its site of action in the colon are obscure. In the present study a noninvasive scintigraphic technique was used to closely follow the movements of proximal colonic contents. Lactulose, 10-20 mL three times daily, significantly accelerated mean transit through the ascending colon from 12.9 +/- 3.7 to 7.0 +/- 2.5 hours (n = 11; P less than 0.01). This was associated with the occurrence of mass movements, with six such events seen during lactulose treatment whereas only one was seen during the control study (P less than 0.05). Lactulose also accelerated movement through the rest of the colon so that at 24 hours after dosing the geometric center of the isotope bolus was distal to that seen during the control study (6.6 +/- 1.2 vs. 4.7 +/- 1.3; n = 11, P less than 0.001). This model of diarrhea in otherwise normal subjects was subsequently used to study the effects of viscous gels in diarrhea. The viscous and relatively poorly fermented gel ispaghula, 3.5 g three times daily, abolished mass movements and was associated with a small but significant increase in proximal colonic transit time, which increased from 6.1 +/- 2.1 to 7.7 +/- 1.5 hours (n = 8; P less than 0.05). By contrast, the viscous but readily fermentable gelling agent guar gum, 5 g three times daily, further accelerated the cathartic effect of lactulose, with the mean transit time decreasing from 6.4 +/- 2.3 to 4.7 +/- 1.7 hours (n = 8; P less than 0.05). The acceleration of proximal colonic transit by lactulose may be a useful model to study diarrhea and its modification by therapy.

Adolescent↗
PubMed1989

Lowered prevalence of infection with lactulose therapy in patients in long-term hospital care.

Over a 6-month, retrospective study period, regular lactulose therapy resulted in a significant reduction in the prevalence of UTIs when compared to a control group receiving no lactulose (P less than 0.005). The overall number of patients contracting infections was also reduced (P less than 0.25). There was a parallel reduction in the prescription of antibiotics (P less than 0.05) and in the number of patients requiring antibiotic therapy (P less than 0.005). There was no alteration in faecal continence with lactulose therapy and no urinary catheters were used in either group. In two additional groups of patients, low dose lactulose therapy for 6 months and a shorter duration of lactulose therapy for under 2 months, had no significant effect on the prevalence of UTIs. This study was retrospective and the results were both unexpected and do not explain the mode of action of lactulose. A controlled prospective study involving larger patient numbers is required before any realistic therapeutic recommendations can be made.

Aged↗
PubMed1999

Method development for the quantitative determination of lactulose in heat-treated milks by HPAEC with pulsed amperometric detection.

A robust, rapid, and sensitive high-performance anion-exchange chromatographic method for the separation and quantitative determination of lactulose in heated milks, along with other common milk carbohydrates, has been developed. Complete separation of galactose, glucose, N-acetylgalactosamine, lactose, lactulose, and epilactose was isocratically accomplished in about 22 min by an anion-exchange column eluted with 10 mM NaOH spiked with 2 mM Ba(OAc)2. The within-day repeatability was lower than 2.1% for 10 repetitive injections. Under optimized conditions, there was no need either of post-column addition of strong bases to the eluent for enhancing detection sensitivity or, even more important, for column regeneration between chromatographic runs. Upon 100-fold sample dilution, the amperometric response of lactulose in milk samples was found to be linear up to 100 microM (r = 0.99935) with a limit of detection equal to 1.2 microM (S/N = 3). The lactulose content in ultrahigh-temperature (UHT) and sterilized milks was evaluated by a calibration graph using 2-deoxyglucose as the internal standard, making the proposed method very useful in discriminating among heat-treated milks. Whereas the mean value of lactulose in skimmed, partially skimmed, and whole UHT milks ranged from 10 to 90 mg/100 mL, lactulose content in bottle-sterilized whole milk (two samples) was higher than 140 mg/100 mL. The presence of epilactose, which is another isomer of lactose, was also ascertained in sterilized milk.

Animals↗
PubMed2004

Enzymatic production and complete nuclear magnetic resonance assignment of the sugar lactulose.

The enzymatic transgalactosylation from lactose to fructose leading to the prebiotic disaccharide lactulose was investigated using the beta-galactosidase from Aspergillus oryzae and the hyperthermostable beta-glycosidase from Pyrococcus furiosus (CelB). The conditions for highest lactulose yields relative to the initial lactose concentration were established on a 1 mL scale. Dependent on the initial molar ratio of lactose to fructose, more or fewer oligosaccharides other than lactulose were generated. Bioconversions on a 30 mL scale in a stirred glass reactor were performed, and lactulose yields of 46 mmol/L (44% relative to lactose) for CelB and 30 mmol/L (30% relative to lactose) for A. oryzae beta-galactosidase were achieved. Only <5% of other oligosaccharides were detectable. The corresponding productivities were 24 and 16 mmol/L/h, respectively. The molecular structure of lactulose was investigated in detail and confirmed after purification of the reaction solution by LC-MS and 1D and 2D NMR. Lactulose (4-O-beta-D-galactopyranosyl-D-fructose) was unambiguously proved to be the major transglycosylation disaccharide.

Aspergillus oryzae↗
PubMed1999

Measurement of small intestinal permeability markers, lactulose, and mannitol in serum: results in celiac disease.

To date, tests of small intestinal passive permeability have involved the ingestion of test molecules whose permeation is assessed indirectly by measuring their urinary recovery. Excretion ratios of marker molecules (eg, lactulose-to-mannitol excretion ratio, LMER) are useful clinically. Measurement of permeability markers in serum would improve the convenience of the tests. Our aim was to assess small intestinal permeability in celiac patients using serum lactulose and mannitol levels with calculation of lactulose to mannitol serum ratios (LMSR) and to compare the results with the standard methods using urinary recoveries. Twenty-four newly diagnosed celiacs and 10 control subjects were studied; 10 celiacs were restudied while established on a gluten-free diet. Test subjects and patients ingested 10 g lactulose and 2.5 g mannitol in 50 ml water. In 10 untreated celiacs and the controls, blood was taken from 0 to 120 min and all urine was collected for 6 hr. The remaining 14 untreated and the 10 treated celiacs had a single serum sample taken 60 min after ingestion of the test solution. At 1 hr after ingestion, the mean mannitol level in normals (0.156 mmol/liter) was significantly higher than in untreated celiacs (0.06 mmol/liter). The 1-hr mean serum lactulose level in normals (0.125 micromol/liter) was significantly lower than in untreated celiacs (0.56 micromol/liter). The median 1-hr LMSR in untreated celiacs was 0.42 compared with 0.039 in normals and 0.08 in treated celiacs. There was a significant correlation between LMSR and LMER. Permeability testing using serum measurements of lactulose and mannitol gave comparable results in celiac patients to the tests using urinary recovery of the permeability markers and may prove to be more convenient, especially in pediatric patients.

Adolescent↗