Mechanism of Action of Lactulose
Lactulose is a synthetic disaccharide that works primarily as an osmotic laxative by drawing water into the intestinal lumen and promoting peristalsis, while also being metabolized by colonic bacteria to produce short-chain fatty acids that acidify the colon. 1, 2
Primary Mechanisms of Action
- Lactulose is a β-galactosido-fructose synthetic disaccharide that is not digested in the small intestine and reaches the colon essentially unchanged 1, 2
- It exerts an osmotic laxative effect by drawing water into the intestinal lumen, which hydrates and softens stool, promoting peristalsis 1
- When lactulose reaches the colon, it is metabolized by colonic bacteria to produce short-chain fatty acids, primarily acetic and lactic acids, which lower colonic pH 3, 2
- The acidification of colonic contents further stimulates colonic motility and facilitates bowel movements 3
Therapeutic Applications
For Constipation:
- Lactulose increases stool water content through its osmotic properties, improving stool consistency and frequency 1
- It is FDA-approved for constipation treatment at a dose of 10-20g daily, which may be increased to 40g daily if needed 1
- Common side effects include bloating and flatulence, which are dose-dependent and may limit its use in some patients 1
For Hepatic Encephalopathy:
- The acidification of colonic contents converts ammonia (NH3) to ammonium ions (NH4+), which cannot be absorbed across the colonic mucosa 2
- This trapping of ammonia in the colon prevents its absorption into the bloodstream 2
- The laxative effect then expels the trapped ammonium ions from the colon 2
- Lactulose increases fecal bacterial mass, which incorporates nitrogen and is excreted, further removing potential neurotoxins 4
- For hepatic encephalopathy, higher doses are typically used to achieve the desired therapeutic effect 3
Additional Effects
- At lower doses, lactulose can function as a prebiotic, stimulating the growth of beneficial bacteria like Bifidobacterium and Lactobacillus species 5
- It may enhance mineral absorption, particularly calcium and magnesium, which could have implications for bone health 5
- Lactulose creates intestinal conditions that favor beneficial bacteria while inhibiting potentially harmful bacteria like Salmonella and Shigella 6
- Some evidence suggests lactulose may have anti-inflammatory properties by reducing endotoxin absorption and increasing hydrogen production, which acts as an antioxidant 7
Clinical Considerations
- Lactulose is poorly absorbed systemically, with only small amounts reaching the bloodstream and approximately 3% or less excreted in urine 2
- The effectiveness of lactulose for constipation has been demonstrated in clinical trials, though older studies had significant limitations 1
- Bloating and flatulence are common side effects that may limit patient adherence 1
- Generic lactulose is generally low cost, making it an accessible treatment option 1
Lactulose's dual mechanism of osmotic action and bacterial metabolism makes it effective for both constipation and hepatic encephalopathy, with its therapeutic effects directly related to its unique pharmacological properties in the colon.