What is the mechanism of action of lactulose?

How Lactulose Works

Lactulose is an osmotic laxative that draws water into the intestinal lumen to hydrate and soften stool, while also being metabolized by colonic bacteria to produce short-chain fatty acids that lower colonic pH and promote peristalsis. 1

Primary Mechanism of Action

Lactulose functions through two complementary pathways:

Osmotic Effect

• Lactulose is a non-absorbed synthetic disaccharide that draws water into the intestinal lumen through osmosis, increasing stool water content and promoting bowel movements. 2
• The drug is poorly absorbed from the gastrointestinal tract, with urinary excretion of only 3% or less, meaning it reaches the colon essentially unchanged. 3
• This osmotic action hydrates and softens the stool, making it easier to pass. 1

Bacterial Metabolism and Acidification

• Once in the colon, lactulose is metabolized by colonic bacteria to produce short-chain fatty acids, primarily acetic and lactic acids. 2
• This bacterial fermentation lowers the colonic pH, which promotes colonic peristalsis and accelerates transit. 2
• The acidic environment created by these metabolites is crucial for lactulose's therapeutic effects. 3

Additional Mechanisms in Hepatic Encephalopathy

When used for hepatic encephalopathy (a different indication than simple constipation), lactulose has additional mechanisms:

• The acidification of colonic contents converts ammonia (NH₃) to ammonium ions (NH₄⁺), which cannot be absorbed across the colonic mucosa, effectively trapping ammonia in the colon. 2, 3
• The laxative effect then expels these trapped ammonium ions from the body. 2, 3
• Lactulose increases fecal bacterial mass, which incorporates nitrogen and removes potential neurotoxins through excretion. 2

Effects on Intestinal Flora

• Lactulose promotes the growth of beneficial lactic acid bacteria (such as Lactobacillus acidophilus) while inhibiting pathogenic bacteria including coliforms, bacteroides, Salmonella, and Shigella. 4
• This prebiotic effect contributes to its overall therapeutic benefit beyond simple laxation. 4

Clinical Dosing Context

• For constipation, the American Gastroenterological Association recommends starting at 10-20 g (15-30 mL) daily, which can be increased to 40 g (60 mL) daily if needed. 5, 2
• The drug should be taken as a single evening dose to optimize compliance and minimize dose-dependent gastrointestinal side effects like bloating and flatulence, which occur in approximately 20% of patients. 5, 6

Common Pitfalls

• Bloating and flatulence are very common, dose-dependent side effects that may limit lactulose's use in clinical practice. 5
• Starting with lower doses and titrating upward as tolerated helps minimize these gastrointestinal adverse effects. 5, 6
• Excessive dosing can lead to diarrhea with potential complications including hypokalemia and hypernatremia. 5