Benefits
Supports regular bowel movements and softer stool
At 10 to 20 g a day, lactulose holds water in the colon and softens stool, and the US label notes it can take 24 to 48 hours to work. An independent systematic review of adult trials rated the evidence for it as moderate, and EU rules let a food carrying 10 g per serving say it contributes to faster intestinal transit.
Outperformed by polyethylene glycol for constipation
An independent pooled analysis of ten head-to-head trials found polyethylene glycol (PEG) beat lactulose on stool frequency, stool form, abdominal pain relief and the need for extra laxatives. A separate pooled analysis in children found the same pattern: 18% of children on PEG needed another laxative versus 31% on lactulose.
Raises gut bifidobacteria at low prebiotic doses
In small placebo-controlled trials, 2 to 10 g a day raised bifidobacteria in stool over two to six weeks, and in one trial the rise faded within a week of stopping. The recent low-dose trials were run by researchers at Morinaga Milk, which makes lactulose, and EU regulators judged a claimed gut flora benefit, fewer potentially harmful microbes, as not established.
Slightly more frequent bowel movements at 2 g a day
In a crossover trial analyzing 52 healthy Japanese women who had two to four bowel movements a week, two weeks of 2 g a day gave about 4.3 bowel movements a week versus 3.8 on placebo, slightly softer stool and no increase in flatulence. That is a small change, from a manufacturer-run trial, in people without diagnosed constipation.
May support calcium absorption, from one small study
In twelve postmenopausal women, 10 g of lactulose a day for nine days gave measured calcium absorption of about 32% versus 28% on a reference drink, with 5 g in between. The study did not measure bone, and its authors called for research on whether the effect changes calcium balance or age-related bone loss.
Prescription role in advanced liver disease, not a supplement use
US drug labels list portal-systemic encephalopathy, a brain complication of cirrhosis, as a prescription indication at 20 to 30 g three or four times a day. That use needs a physician, dose titration and electrolyte monitoring. It is summarized under clinical trials for context, not as a reason to self-dose.
Mechanism of action
Reaches the colon essentially intact
Lactulose is not split or absorbed to any real extent in the small intestine. The US label reports that only small amounts reach the blood, with 3% or less excreted in urine within 24 hours, so almost the whole dose arrives in the colon unchanged, which is where it acts.
Osmotic water retention and bacterial fermentation
In the colon, bacteria ferment lactulose mainly to lactic acid, with smaller amounts of formic and acetic acids. The unabsorbed sugar and these acids hold water in the bowel, raising stool water and softening stool, which is the basis of its use as an osmotic laxative.
Colonic acidification and ammonia trapping
The acids lower colonic pH, which converts ammonia into the ammonium ion and traps it in the bowel so less is absorbed. Lowering blood ammonia is the rationale for its prescription use in cirrhosis, where ammonia is linked to brain dysfunction.
Selective growth of bifidobacteria
Below laxative doses, the main measurable effect is on which bacteria grow. Trials of 2 to 10 g a day raised stool bifidobacteria, and in the 10 g trial total anaerobes and lactobacilli stayed level, consistent with bifidobacteria being efficient users of the sugar.
Hydrogen gas production
Fermentation also releases hydrogen gas. That explains the flatulence and bloating many users notice at first, and it is why the label warns that hydrogen buildup could, in theory, ignite during electrocautery at colonoscopy unless the bowel is cleansed with a non-fermentable solution.
Clinical trials
Cochrane systematic review and meta-analysis of all ten randomized trials comparing lactulose with polyethylene glycol for chronic constipation or fecal impaction (Lee-Robichaud H, Thomas K, Morgan J, Nelson RL 2010, Cochrane Database Syst Rev 2010(7):CD007570, PMID 20614462).
Adults and children with chronic constipation across ten randomized controlled trials.
Polyethylene glycol was better than lactulose for weekly stool frequency, stool form, relief of abdominal pain and the need for additional products. On subgroup analysis the advantage held in both adults and children, except for abdominal pain relief. The reviewers concluded polyethylene glycol should be used in preference to lactulose for chronic constipation.
Cochrane systematic review of randomized trials of lactulose or lactitol versus placebo or no intervention, and of lactulose versus lactitol (Gluud LL, Vilstrup H, Morgan MY 2016, Cochrane Database Syst Rev 2016(5):CD003044, PMID 27153247).
1,828 people with cirrhosis in 38 randomized trials covering prevention and treatment of hepatic encephalopathy.
Compared with placebo or no intervention, the disaccharides were associated with lower mortality (RR 0.59; 24 trials, 1,487 participants) and less hepatic encephalopathy (RR 0.58; 22 trials, 1,415 participants), both graded moderate quality. Only eight trials had a low risk of bias for mortality, and all had a high risk of bias for other outcomes. Lactulose and lactitol did not differ. One author disclosed speaker payments from Norgine. This is prescription drug use in liver disease.
Open-label randomized controlled trial of lactulose versus placebo after recovery from an episode of hepatic encephalopathy (Sharma BC, Sharma P, Agrawal A, Sarin SK 2009, Gastroenterology 137(3):885-91, 891.e1, PMID 19501587).
140 patients with cirrhosis enrolled after recovering from hepatic encephalopathy; 125 analyzed over a median follow-up of 14 months.
Overt encephalopathy recurred in 12 of 61 patients (19.6%) on lactulose versus 30 of 64 (46.8%) on placebo (P = .001). Deaths (5 versus 11) and readmissions for other causes did not differ significantly. Because the trial was open-label, patients and doctors knew the assignment, which adds some risk of bias.
Randomized, double-blind, placebo-controlled crossover trial of 2 g/day lactulose for two weeks (Sakai Y, Seki N, Hamano K, Ochi H, Abe F, Masuda K, Iino H 2019, Benef Microbes 10(6):629-639, PMID 31131617). Five of the seven authors are employees of Morinaga Milk Industry, a lactulose manufacturer.
60 healthy Japanese women with two to four bowel movements a week; 52 analyzed, with a three-week washout between periods.
Bowel movement frequency was 4.28 a week on lactulose versus 3.83 on placebo, with slightly softer stools, larger stool volume and less straining. Bifidobacteria made up 25.3% of stool bacteria on lactulose versus 18.2% on placebo. Flatulence did not differ. The effects are small and each treatment period lasted only two weeks.
Randomized, double-blind, parallel-group trial of lactulose 5 g twice daily versus sucrose for six weeks (Bouhnik Y, Attar A, Joly FA, Riottot M, Dyard F, Flourié B 2004, Eur J Clin Nutr 58(3):462-6, PMID 14985684).
16 healthy volunteers.
Fecal bifidobacteria were higher on lactulose than on sucrose (P=0.03), while total anaerobes, lactobacilli, stool pH, fecal bile acids and neutral sterols did not change. Excess flatus was more common on lactulose but very mild, and bloating did not differ. With 16 participants, this is a small trial.