What is the effect of lactulose?

From the Guidelines

Lactulose is a synthetic sugar that works as an osmotic laxative to treat constipation and hepatic encephalopathy by reducing ammonia levels in the blood and promoting bowel movements. When taken orally, lactulose passes undigested through the small intestine and reaches the colon, where it draws water into the intestines, softening stool and promoting bowel movements 1. For constipation, typical dosing is 15-30 ml once or twice daily, while hepatic encephalopathy may require higher doses of 30-45 ml three to four times daily, adjusted to produce 2-3 soft bowel movements per day 1.

Key Mechanisms of Action

• Lactulose creates an acidic environment in the colon that converts ammonia to ammonium, which cannot be absorbed back into the bloodstream, thereby reducing the neurotoxic effects of ammonia on the brain 1.
• It also increases the count of lactobacillus, which do not produce ammonia, and produces an osmotic laxative effect that flushes the ammonia out 1.

Dosage and Administration

• The dose should be titrated to achieve two to three soft stools per day 1.
• If patients are unable to take medications orally, administration via nasogastric tube might be tried 1.
• For severe hepatic encephalopathy, an enema of 300 mL lactulose and 700 mL water can be performed 3–4 times per day until clinical improvement is noted 1.

Side Effects and Precautions

• Common side effects include bloating, gas, abdominal cramps, and diarrhea if the dose is too high 1.
• Patients should drink plenty of water when taking lactulose and be aware that it may take 24-48 hours to produce a bowel movement.
• Bloating and flatulence are dose-dependent and common side effects, which may limit its use in clinical practice 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Lactulose causes a decrease in blood ammonia concentration and reduces the degree of portal-systemic encephalopathy. These actions are considered to be results of the following: Bacterial degradation of lactulose in the colon acidifies the colonic contents. This acidification of colonic contents results in the retention of ammonia in the colon as the ammonium ion Since the colonic contents are then more acid that the blood, ammonia can be expected to migrate from the blood into the colon to from the ammonium ion. The acid colonic contents converts NH3 to the ammonium ion (NH4)+,trapping it and preventing its absorption. The laxative action of the metabolites of lactulose then expels the trapped ammonium ion from the colon

Lactulose reduces blood ammonia concentration and decreases portal-systemic encephalopathy by:

• Acidifying colonic contents through bacterial degradation
• Trapping ammonia in the colon as the ammonium ion
• Expelling the trapped ammonium ion from the colon through its laxative action 2

From the Research

Mechanism of Action

• Lactulose is a synthetic disaccharide that is not absorbed from the small intestine and is fermented by colonic bacterial flora, producing short-chain fatty acids and gases 3.
• The fermentation of lactulose by gastrointestinal tract bacteria produces a considerable amount of hydrogen, which has antioxidant effects and can reduce oxidative stress 4.
• Lactulose acts as a prebiotic, increasing the abundance of short-chain fatty acid-producing bacteria, such as Lactobacillus and Bifidobacterium, and suppressing potentially pathogenic bacteria 5.

Therapeutic Effects

• Lactulose is used to treat constipation and hepatic encephalopathy due to its efficacy and good safety profile 3.
• Lactulose may have a role in the management and prevention of type 2 diabetes by influencing gut metabolism and modifying the gut microbiota 5.
• Lactulose has been shown to have benefits in patients with chronic renal insufficiency by reducing nitrogen-related products in serum 6.

Pharmacokinetics and Safety

• The effects of lactulose on human microbiota composition are both patient- and dose-dependent 7.
• Lactulose is well-tolerated, with mild adverse effects such as diarrhea observed in some cases 6.
• The removal rate of lactulose by dialysis is approximately 83.6%, and no plasma accumulation is expected when coordinating with dialysis 6.