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PubMed2002

Economic impact of low dose polyethylene glycol 3350 plus electrolytes compared with lactulose in the management of idiopathic constipation in the UK.

OBJECTIVE: To estimate the economic impact of using low dose polyethyene glycol 3350 (PEG 3350) plus electrolytes (PEG+E) compared with lactulose in the treatment of idiopathic constipation in ambulant patients. DESIGN AND PERSPECTIVE: This was a decision analytic modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: The clinical outcomes from a previously reported single-blind, randomised, multicentre trial were used as the clinical basis for the analysis. These data were combined with resource utilisation estimates derived from a panel of six general practitioners (GPs) and four nurses enabling a decision model to be constructed depicting the management of idiopathic constipation with either PEG+E or lactulose over 3 months. The model was used to estimate the expected 3-monthly NHS cost of using either laxative to manage idiopathic constipation. MAIN OUTCOME MEASURES AND RESULTS: The expected 3-monthly NHS cost of using PEG+E or lactulose to manage idiopathic constipation was estimated to be 85 pound sterling and 96 pound sterling per patient, respectively (1999/2000 values). However, significantly more patients were successfully treated with PEG+E than lactulose (53% versus 24%; p < 0.001) at 3 months. GP visits were the primary cost driver for both PEG+E- and lactulose-treated patients, accounting for 56% (2.9 visits) and 73% (4.4 visits), respectively, of the expected NHS cost per patient at 3 months. Among PEG+E-treated patients, the acquisition cost of PEG+E was the secondary cost driver, accounting for 30% of the expected NHS cost per patient at 3 months, whereas the acquisition cost of lactulose accounted for only 11% of the expected NHS cost per lactulose-treated patient. District nurse domiciliary visits accounted for 4% and thyroid function tests for 2%. The costs of switched laxatives, concomitant laxatives, and gastroenterologist and colorectal surgeon visits collectively accounted for up to 9% of the total. CONCLUSIONS: The true cost of managing idiopathic constipation is impacted on by a broad range of resources and not only laxative acquisition costs. This study indicated that managing idiopathic constipation with PEG+E instead of lactulose reduces the expected 3-monthly NHS cost by 11 pound sterling per patient. Moreover, using PEG+E instead of lactulose is expected to double the percentage of patients successfully treated at 3 months. Hence, PEG+E is a dominant treatment compared with lactulose. This suggests that the decision to use either PEG+E or lactulose to treat idiopathic constipation should be based on efficacy, safety, patient preferences and total management costs, and not drug acquisition costs.

Adult↗

PubMed1997

Lactulose, lactic acid bacteria, intestinal microecology and mucosal protection.

During the fermentation of lactulose, short-chain fatty acids are formed with consequent lowering of the colon pH and modification of the microflora. Lactulose promotes the growth of lactic acid bacteria and bifidobacteria and, more specifically, Lactobacillus acidophilus in the colon. Lactulose and lactulose-containing products fermented with lactic acid bacteria lower colonic pH balancing intestinal microecology and normalizing intestinal transit. In animal studies, lactulose promotes a mainly Gram-positive faecal microflora, but large doses of lactulose may be associated with transient diarrhoea. Our studies indicate that lactulose with lactic acid bacteria effectively relieves constipation in human volunteers. Lactulose with lactic acid bacteria in a fermented diary product can balance and prevent radiotherapy-associated diarrhoea and intestinal side effects. Normalizing the intestinal flora and stabilizing mucosal integrity with lactulose has beneficial effects in intestinal disorders. Lactulose and lactic acid bacteria offer a promising ingredient combination for future functional and special dietary foods in treating intestinal disturbances.

Aged↗

PubMed2004

L-Rhamnose increases serum propionate after long-term supplementation, but lactulose does not raise serum acetate.

BACKGROUND: Acute ingestion of the unabsorbed sugar l-rhamnose in humans raises serum propionate, whereas acute ingestion of lactulose raises serum acetate. It is not known whether short-chain fatty acid concentrations in urine and feces reflect those in blood. OBJECTIVE: The objective was to test the effects of oral l-rhamnose and lactulose for 28 d on acetate and propionate concentrations in serum, urine, and feces. DESIGN: Eleven subjects ingested 25 g l-rhamnose, lactulose, or d-glucose (control) for 28 d in a partially randomized crossover design. One fecal sample, hourly blood samples, and all urine samples were collected over 12 h on the last day of each phase. RESULTS: The increase in serum propionate was greater after l-rhamnose than after lactulose (P < 0.05). The effect of lactulose on serum acetate was not significant, but lactulose raised the acetate:propionate ratio compared with d-glucose or l-rhamnose in serum (P < 0.005) and urine (P < 0.02). Flatulence was significantly greater after lactulose and l-rhamnose than after d-glucose (P < 0.0001), an effect that lasted 4 wk with lactulose but only 1 wk with l-rhamnose. CONCLUSIONS: This study confirmed that l-rhamnose ingestion over 28 d continues to selectively raise serum propionate in humans. Although serum acetate did not increase significantly after lactulose, the serum acetate:propionate ratio was significantly different after l-rhamnose and lactulose, which suggests that these substrates could be used to examine the role of colonic acetate and propionate production in the effect of dietary fiber on lipid metabolism. Changes in the ratio of urinary acetate to propionate reflected those in serum.

Acetates↗

PubMed1993

Intestinal calcium absorption in rats is stimulated by dietary lactulose and other resistant sugars.

Lactulose is a disaccharide analogue of lactose that is resistant to metabolism in the small intestine but not in the large intestine. The effects of lactulose and other sugars on intestinal Ca absorption were determined from the decrease in the 47Ca:47 Sc ratio between diet and feces after feeding male rats diets containing these sugars during a single night. Dietary lactulose was more potent than lactose in stimulating Ca absorption and was effective between 5 and 38 wk of age. The component sugars of lactulose, galactose and fructose, did not influence Ca absorption when provided together at concentrations equimolar to that of lactulose. The stimulation of Ca absorption by dietary lactulose increased as dietary Ca concentration was raised and was not influenced by prior injections of calcitriol. Lactulose must be present in the same meal as Ca to stimulate Ca absorption, but this stimulation was lost if the rats were fed lactulose continuously for 2 or 7 d prior to the test diet. Other sugars thought to be poorly absorbed in the small intestine (xylitol, lactobionate, arabinose, raffinose, pyroglutamate, sorbitol, gluconate and raftilose) stimulated Ca absorption to an identical extent as lactulose. Cecectomy did not influence the enhancement of Ca absorption by lactulose. These results indicate that sugars resistant to metabolism and absorption in the small intestine but not the large intestine stimulate Ca absorption in the small intestine.

Age Factors↗

PubMed1975

Lactulose therapy in Shigella carrier state and acute dysentery.

Antibiotic-resistant shigella are increasingly prevalent. Lactulose, a non-absorbable disaccharide, was investigated as an alternative therapy for shigella infection on the hypothesis that the short-chain fatty acids (inhibitory to shigella) resulting from metabolism of lactulose by normal colonic flora would diminish shigella excretion. A long-term antibiotic-refractory carrier (large bowel) excreting 10(4) to 10(7)Shigella sonnei/g of feces was given two courses of lactulose (of 24 and 16 days duration). During lactulose therapy, excretion of shigella was greatly diminished (24-day course) or suppressed below detectable levels (16-day course), but returned to pretreatment levels upon discontinuation of lactulose. The volunteers who developed induced shigellosis during an efficacy test of oral Shigella flexneri 2a vaccine were randomly given oral ampicillin, lactulose, or placebo in double-blind fashion. Daily rectal cultures were taken. After 4 days of therapy, cultures were still positive in four out of four men on lactulose, three of three on placebo and none of three on ampicillin. Mean stool pH of men receiving lactulose (6.1) was significantly lower than those getting ampicillin (7.4), P < 0.01, or placebo (7.0), P < 0.05. Only in the lactulose group was mean stool pH during therapy significantly decreased compared with the level off therapy (6.1 versus 7.1), P < 0.02. Lactulose shows promise for the treatment of shigella carriers but appears ineffective in treatment of acute shigellosis.

Acute Disease↗

PubMed2002

Effects of lactulose on the intestinal microflora of periparturient sows and their piglets.

The periparturient period of animals (and humans) is very stressful and influenced by the microecosystem of the gastrointestinal tract (GIT). Performance and productivity of animal husbandry depend on the health of animal mothers and their offspring. We investigated the influence of prebiotic amounts of lactulose in sows and their piglets. Two experimental trial sows received daily 30 ml lactulose, 71 field trial sows received daily 45 ml lactulose during their periparturient period (10 days before until 10 days after parturison). The weaners of trial sows received 15 ml lactulose per 1 kg baby food 10 days before and 10 days after weaning.The effect of lactulose was recorded by performance parameters like number of piglet born alive, losses until weaning, body mass of piglets, daily weight gain of weaners until 35 days after weaning. The effect of lactulose on GIT microflora was estimated by bacterial counts of faeces of sows (total aerobic bacteria, Gram-negative bacteria, Clostridium (C.) perfringens). In order to show a previously unknown effect of lactulose we investigated the levels of antibodies to phospholipase C (PLC) of C. perfringens in plasma of experimental sows and in colostral and ripe milk of field sows. Lactulose influenced the performance parameters of sows in a non-significant way. In case of weaners we recorded significant daily weight gains. Lactulose significantly influenced total aerobic bacterial counts, C. perfringens counts in faeces of sows 20 days after parturison. Under experimental conditions it was shown that trial sows and their piglets had higher IgG-antibody levels to C. perfringens PLCs than the control animals. Similar results were found under field conditions. Trial sows had significant higher IgG-anti LPS (J5) antibodies in milk 10 days after birth.

Animal Feed↗

PubMed2002

Diminished efficacy of colonic adaptation to lactulose occurs in patients with inflammatory bowel disease in remission.

Lactulose has been proposed to be beneficial in treating inflammatory bowel disease (IBD). The hypothesis is based on the prebiotic potential of lactulose. A practical approach to testing its usefulness is to determine colonic adaptation to tolerable doses in patients with IBD. Our objective was to determine if a 3-week course of lactulose will decrease BH2 and symptoms in response to an acute lactulose challenge test in control subjects and IBD patients. The design was a prospective cohort study. Subjects were given a 30-g lactulose challenge test (test 1), and then ingested 10 g of lactulose twice a day for 3 weeks before being retested (Test 2). A third test was given after a further 5-week washout period. The main outcomes were the change in 4-hr sum of BH2 (sum(4HrBH2)) values obtained every 30 min, peak BH2, and 4-hr sum of symptom score (sum(4HrSS)) during the lactulose challenge test. In addition, we also report the change in self-reported symptoms and diarrhea during the 3-week administration of lactulose. In controls, sum(4HrBH2) decreased from test 1 (380.5 +/- 56.6 ppm) to test 2 (288.6 +/- 57.4 ppm) (P < 0.05), and returned toward test 1 levels by test 3 (307.5 +/- 53.1, P > 0.5). Unlike controls, the sum(4HrBH2) in patients failed to achieve significance between test 1 (444.5 +/- 55.8 ppm), test 2 (366.5 +/- 80.7 ppm, P > 0.2) or test 3 (411.6 +/- 62.5 ppm, P > 0.2). Sum(4HrSS) results in controls followed a pattern similar to sum(4HrBH2), achieving significance only in test 2 (P < 0.02). Symptoms during the intertest periods decreased by the third week in controls (P < 0.05), but not in patients (P > 0.5). Symptoms were lower in patients and varied insignificantly both in challenges and intertest periods. In conclusion, although controls adapt to a 3-week period of lactulose ingestion, IBD patients fail to meet the criteria for adaptation. However, longer studies may be needed to establish whether IBD patients are slower to adapt.

Adaptation, Physiological↗

PubMed1998

Comparison of diarrhea induced by ingestion of fructooligosaccharide Idolax and disaccharide lactulose: role of osmolarity versus fermentation of malabsorbed carbohydrate.

Whether carbohydrate malabsorption causes diarrhea probably depends on the balance between the osmotic force of the carbohydrate and the compensatory capacity of the colon to dispose of the carbohydrate by bacterial fermentation. The present study evaluated the specific role of the osmolarity by comparing the severity of diarrhea after ingestion of two nonabsorbable carbohydrates, the fructooligosaccharide Idolax and the disaccharide lactulose. Both carbohydrates are readily fermented by the colonic flora but differ in osmolarity, the osmotic force being twice as high for lactulose as for Idolax. Twelve subjects were given increasing doses (0, 20, 40, 80, 160 g/d) of Idolax and lactulose in a crossover design. Every dose level was administered for three days with intervals of one week. Stools were collected on the third day to determine 24-hr volume, concentrations of short-chain fatty acids, L- and D-lactate, residues of Idolax or lactulose, sodium, potassium, pH, osmolarity, and in vitro productions of organic acids. Measured by short-chain fatty acid and lactate formation in a fecal incubation system, the fermentation of Idolax and lactulose was identical and very rapid compared with a range of reference carbohydrates. A laxative effect of both Idolax and lactulose was demonstrated. The increment in fecal volume as a function of the dose administered was twice as high for lactulose (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 same effect on fecal volume. The variation in fecal volume was substantial (lactulose 80 g/day: 110-1360 g/day; Idolax 160 g/day: 130-1440 g/day). High responders had earlier and larger fecal excretions of the saccharide compared with low-responders. Fecal volume in carbohydrate-induced diarrhea is proportional to the osmotic force of the malabsorbed saccharide, even though all or the majority of the saccharide is degraded by colonic bacteria. The capacity to modify the diarrhea varies considerably from person to person and is associated with colonic saccharide disposal, whereas the variation in response to isosmolar amounts of different saccharides is small within the same individual.

Adult↗

PubMed2004

Lactulose ingestion increases faecal bifidobacterial counts: a randomised double-blind study in healthy humans.

OBJECTIVE: Faecal bifidobacteria and lactobacilli, perceived as exerting health-promoting properties, may be increased by ingestion of high-dose lactulose in humans. The effects of low and well-tolerated doses of lactulose are not well known. The aim of the study was to assess the effects of prolonged low-dose lactulose administration on faecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis. SUBJECTS AND METHODS: In all, 16 healthy volunteers were included in this controlled, randomised, double-blind, parallel group trial. Participants ingested lactulose or placebo (sucrose) at a dose of 5 g b.i.d. for 6 weeks. Stools were regularly collected at baseline (d0), and after 3 (d21) and 6 (d42) weeks of sugar ingestion. Tolerance was evaluated using a daily chart. RESULTS: Faecal bifidobacterial counts were higher in lactulose than in sucrose group (P=0.03). Lactulose ingestion led to a significant increase in faecal bifidobacteria counts from d0 to d21 and d42 ((m+/-s.e.m.) 8.25+/-0.53, 8.96+/-0.40 and 9.54+/-0.28 log colony-forming units/g wet wt (CFU/g), respectively (P=0.048)). Placebo ingestion did not lead to any faecal bifidobacterial count change. Total anaerobes, Lactobacillus and pH were not significantly changed throughout the study in the two groups. Neither faecal bile acids nor neutral sterols were modified by lactulose. Excess flatus was more common in the lactulose group (P=0.03), but was very mild. Bloating and borborygmi did not differ between both the groups. CONCLUSIONS: A measure of 10 g lactulose/day increases faecal bifidobacterial counts, and lactulose fulfils the criteria requested to be considered as a prebiotic.

Adult↗

PubMed1998

Acid production from lactulose by dental plaque bacteria.

Representative strains of oral streptococci, lactobacilli and bifidobacteria were incubated overnight with lactulose or other carbohydrates and the final pH recorded. Most bacteria tested were able to metabolize lactulose with the exception of strains of Streptococcus salivarius, Lactobacillus acidophilus and Lact. fermentum. Streptococcus mutans produced most acid overnight but the initial rate of acid production from lactulose by uninduced cultures was very low. Plaque pH was monitored in 12 volunteers following rinsing the mouth with lactulose, sucrose or sorbitol or Lactulose BP. These studies in vivo showed both lactulose and Lactulose BP to exhibit low acidogenic potential. Thus, although plaque bacteria are capable of fermenting lactulose, the results suggest that lactulose is likely to pose a small acidogenic challenge to teeth under normal conditions of use.

Bifidobacterium↗

PubMed2004

Physiological effects of lactulose and inulin in the caecum of rats.

A model experiment was performed on rats to evaluate the effect of partial or total substitution of saccharose (S) and cellulose (C) by preparations of lactulose and inulin on the development and metabolism of the caecum. In the experimental diets given to rats for 4 weeks, the examined preparations were administered either with an equivalent amount of cellulose (each at 4% of the diet) or as sole source of dietary fibre at 8% of the diet. Compared to the saccharose group cellulose had no effect, and low doses of lactulose and inulin in the diet increased to a medium extent the weight of the caecum wall and caecal digesta. The addition of lactulose and inulin at 8% increased significantly the content of caecal digesta (4.62 and 4.11 g/100g BW, respectively) and the weight of the caecal wall (1.10 and 0.86 g/100g BW, respectively), compared to the groups with saccharose and cellulose (0.73, 0.90 and 0.24, 0.28 g/100g BW, respectively). Cellulose and cellulose partially-substituted with lactulose and inulin caused an increase in the dry matter content of caecal digesta (26.5-27.5%), compared to other groups (21.8-22.8%). The administration of lactulose and inulin preparations was accompanied by a significant drop in pH (5.47-5.81), compared to the groups with cellulose or saccharose (6.83-6.91), and a decrease in the ammonia concentration in the caecal digesta, compared to the cellulose control (0.27-0.40 and 0.62 mg/g, respectively). The group with 8% lactulose was characterized by the highest activities of microbiological alpha- and beta-galactosidase and beta-glucosidase in the caecal digesta. Cellulose and both preparations significantly decreased the activity of beta-glucuronidase, compared to the saccharose group (0.39-0.89 and 1.52 U/g, respectively). The highest concentration of VFA in the caecal digesta was observed in the saccharose group (89.2 micromol/g), and the lowest concentration in the group where cellulose was totally substituted by lactulose and inulin (55.1 and 57.5 micromol/g, respectively). The total production of VFA in the caecum was fourfold higher with 8 % lactulose and inulin (254.7 and 236.4 micromol/100g BW, respectively) than in both controls groups (65.1 and 67.8 micromol/100g BW, respectively). The high dose of inulin and lactulose increased the share of propionic acid in the VFA profile (C2:C3:C4) compared to both control groups. When 4% inulin was added to the diet a significant increase of butyrate concentration in the caecum was observed.

Animals↗

PubMed2006

Low-dose lactulose produces a tonic contraction in the human colon.

Lactulose (10-20 g day(-1)) is used to treat constipation. At this therapeutic dose, its effects on colonic motility remain unknown. Twenty-two healthy subjects swallowed a probe with an infusion catheter, six perfused catheters and a balloon connected to a barostat. Colonic phasic and tonic motor activity was recorded in fasting state. In group 1, four volunteers ingested 15 g lactulose and motility was recorded for 5 h after entry of lactulose into the caecum; in group 2, motility was recorded during (3 h) and 2 h after intracolonic infusion of isoosmotic and isovolumetric solutions containing sodium chloride alone (n = 9) or with 15 g lactulose (n = 9). In a last group of volunteers, isotopic colonic transit after ingestion of lactulose (10 g,n = 9) was assessed and compared with a control group (n = 17). Ingestion or intracolonic infusion of 15 g lactulose significantly decreased barostat bag volume (maximal decrease: 45 +/- 12% and 35 +/- 9% of basal value respectively). Phasic contractions remained unchanged. Tonic and phasic motility was unchanged by the isotonic and isovolumetric infusion of saline. Ingestion of lactulose significantly accelerated isotopic colonic transit time compared with the control group. We conclude that in healthy humans, 10-15 g ingestion or intracaecal infusion of lactulose produces a prolonged tonic contraction that may be involved in the laxative effect of lactulose.

Administration, Oral↗

PubMed1999

Lactulose stimulates calcium absorption in postmenopausal women.

Animal studies have indicated that calcium absorption is increased by lactulose, a synthetic disaccharide. Therefore, the influence of lactulose on calcium absorption was measured in postmenopausal women who may benefit from the possible enhancing effect of lactulose on calcium absorption. Twelve postmenopausal women drank 100 ml of water containing 5 or 10 g of lactulose or a reference substance at breakfast for 9 days. The three treatments were given according to a randomized, double-blind, cross-over design, separated by two 19-day wash-out periods. On the 8th day of each treatment period, 44Ca dissolved in orange juice was drunk immediately after the solution with the study substance and just before a standard breakfast with 162 mg of carrier calcium. Within half an hour, 48Ca was given intravenously. Based on isotope ratios measured in urine collected before and until 36 h after isotope administration, true fractional calcium absorption was calculated. Calcium absorption during the treatments with the reference substance, 5 g and 10 g of lactulose was (mean +/- SD) 27.7 +/- 7.7, 30.0 +/- 7.6, and 32.2 +/- 7.0, respectively. A significant difference in calcium absorption was found between the highest dose of lactulose and the reference treatment (p < 0.01). A significant linear trend was found between the dose of lactulose and its positive effect on calcium absorption. In conclusion, in postmenopausal women a 9-day consumption of lactulose increases calcium absorption in a dose-response way. More research is warranted to explore how lactulose stimulates calcium absorption and whether it is able to improve calcium balance and/or to attenuate the rate of aging bone loss.

Calcium↗

PubMed1990

Lactulose in the treatment of symptomatic diverticular disease: a comparative study with high-fibre diet.

OBJECTIVE: To compare the efficacy and tolerance of lactulose (Duphalac) and high-fibre diet in the treatment of symptomatic diverticular disease. DESIGN: Prospectively randomised, parallel groups study over 12 weeks. Patients were seen by their clinician for an initial assessment and then at weeks 4, 8 and 12. SETTING: Hospital out-patients in the United Kingdom. PATIENTS: Forty-three patients with a confirmed diagnosis of diverticular disease were entered into the study. INTERVENTION: Patients were prospectively randomised to receive lactulose (15 ml bd) or high-fibre diet (30-40 g daily) for 12 weeks. MEASUREMENTS AND RESULTS: Data were collected using diary cards and physicians' assessments. Bowel frequency and stool consistency improved similarly with both treatments. Pain on bowel movement improved with both treatments in respect of frequency (lactulose: P = 0.017, fibre: P = 0.084) and severity (lactulose: P = 0.028, fibre: P = 0.043). Abdominal pain also improved with both treatments in respect of frequency (lactulose: P = 0.0015, fibre: P = 0.022) and severity (lactulose: P = 0.009, fibre: P = 0.028). Nine patients on lactulose and 12 on fibre reported treatment-emergent symptoms, of which none was serious. CONCLUSIONS: Lactulose and high-fibre diet were both shown to be effective in the treatment of diverticular disease, with some differences in favour of lactulose.

Adult↗

PubMed1982

Effects of lactulose and neomycin on urea metabolism in cirrhotic subjects.

In our previous studies of cirrhotic subjects lactulose caused a 25% decrease in the urea production rate associated with a decrease in urinary urea excretion and an increase in stool nitrogen. The decrease in the rate of urea production was an indirect measure of reduction in gut ammonia production. The present study was designed to determined if the poorly adsorbed antibiotic neomycin had an additive effect in reducing ammonia production when administered in combination with lactulose. Six stable cirrhotic subjects received isonitrogenous diets during separate lactulose and lactulose + neomycin treatment periods. The addition of neomycin to a lactulose regimen caused a 17% reduction in the urea production rate that was quantitatively accounted for by a 70% reduction in the urea degradation rate. The intestinal urea clearance rate demonstrated a parallel reduction, indicating an inhibition of bacterial ureolysis. There was no evidence that neomycin altered the effects of lactulose since urinary urea excretion did not rise, fecal nitrogen remained high, and stools remained acidic. These results demonstrate that neomycin inhibited bacterial ureolysis when administered with lactulose while lactulose itself was metabolized and its individual effect on nitrogen metabolism persisted. Lactulose and neomycin, when administered together, had an additive effect in reducing gut ammonia production in cirrhotic subjects.

Aged↗

PubMed1981

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 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.

Disaccharides↗

PubMed1997

Lactulose--a multifaceted substance.

Lactulose is therapeutically used in hepatic encephalopathy, constipation, and salmonellosis. This semisynthetic disaccharide is neither metabolized nor absorbed in the normal small intestines. Comparable to plant-polysaccharides lactulose is bacterially fermented in the colon to short chain fatty acids and gases. Major consequences are a drop in pH and a change in composition and metabolic activity of the colonic flora. These and other potential effects suggest complex mechanisms of action of lactulose, with the potential for additional indications in diagnosis and therapy. The use of lactulose as substrate for the H2-breath-test is well known as a means for the measurement of oroeceal transit time and as test for small intestinal bacterial overgrowth. An extension of the diagnostic potential is given by the assessment of the permeability in diffuse intestinal disease with combined disaccharide/monosaccharide test solutions, especially in Crohn's disease. Explanations for positive effects in the prophylaxis of cholesterol-gallstones, in the therapy of hypercholesterolemia and in the prevention of colorectal adenoma and carcinoma can be found in changes in lipid- and bile acid metabolism found after lactulose ingestion. Lactulose may lead to an improved glucose-tolerance in parallel to fibre and acarbose effects which involve several mechanisms of carbohydrate metabolism. Lactulose presumably reduces pathogenic bacteria in favor of the health promoting bifidusflora; also, production and absorption of endotoxines may be reduced; this suggests that lactulose may have therapeutic effects on both infectious and idiopathic inflammatory bowel diseases. Numerous studies with interesting but not as yet convincingly documented clinical relevance suggest that the many effects of lactulose may be interesting subjects for future research.

Gastrointestinal Diseases↗

PubMed1992

Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis.

Lactitol (beta-galactosido-sorbitol) has been recently compared with lactulose for the treatment of chronic hepatic encephalopathy in a few studies, each comprising a small number of patients. The results are controversial. We studied the efficiency and tolerance of both compounds by using a meta-analysis on the basis of published controlled trials. Our study only included controlled or randomized trials comprising cirrhotic patients with chronic hepatic encephalopathy. Analyzed parameters were the portosystemic encephalopathy index of Conn after treatment, the percentage of improved patients and the percentage of patients who had ill effects related to the treatment (flatulence, diarrhea). Bibliographical screening revealed five studies comparing the effects of lactitol and lactulose in chronic hepatic encephalopathy. Four crossover studies were done that included 48 patients and one parallel study that included 29 patients. The duration of the treatment ranged from 3 to 6 mo. All studies found a similar efficiency with both drugs. However, they exhibited some discrepancies in the relative frequency of adverse reactions (flatulence). Meta-analysis showed no statistical differences in the portosystemic encephalopathy index after lactitol or lactulose treatment. The percentage of improved patients after lactitol or lactulose was similar. In contrast, the analysis revealed a higher frequency (p less than 0.01) of flatulence in patients treated with lactulose compared with those treated with lactitol. In conclusion, this meta-analysis shows no statistical difference between therapeutic effects of lactitol and lactulose, but it does show a higher frequency of flatulence with lactulose. This suggests that lactitol should be preferred to lactulose for the treatment of chronic hepatic encephalopathy.

Chronic Disease↗