Lactulose is also used to reduce the amount of ammonia in the blood of patients with liver disease. It works by drawing ammonia from the blood into the colon where it is removed from the body. [Source]

How is ammonia removed from the colon?

From the quote above it sounds like ammonia removal must be some other mechanism than absorbing it into the blood, correct?

  • 1
    $\begingroup$ I'd imagine it would be defecated out. $\endgroup$ – Rory M Jun 15 '13 at 19:15
  • $\begingroup$ @RoryM: Do you mean that ammonia would be dissolved in the liquid content of the stool? A stool with ammonia smell? $\endgroup$ – winerd Jun 15 '13 at 19:19
  • 1
    $\begingroup$ It's an interesting one, the BNF states that it "discourages the proliferation of ammonia-producing organisms" in the GI tract rather than pulling ammonia into the gut lumen, I'll perhaps write a full answer when my exams are out of the way :) $\endgroup$ – Rory M Jun 15 '13 at 19:29
  • 3
    $\begingroup$ and from MRHA "Lactulose is used to treat hepatic encephalopathy by reducing the pH of the colon causing ammonia to form in the colon, thereby reducing blood-ammonia concentrations." $\endgroup$ – Rory M Jun 15 '13 at 19:31
  • 1
    $\begingroup$ MRHA approval document though you can also just enter lactulose as a search term at mhra.gov.uk. $\endgroup$ – Rory M Jun 16 '13 at 10:48

Excess nitrogen must be excreted by the body and can come from nitrogen in the diet (e.g. amino groups from excess amino acids) or nitrogen-containing compounds produced by bacteria in the gastrointestinal tract (GI tract).

Normally the liver and kidneys are involved in excreting ammonia ($NH_3$) and ammonium ($NH_4^+$) from the body. Ammonia can be toxic in high concentrations, but the body can detoxify it through conversion to other nitrogen-containing substances (i.e. urea) or excrete the ammonia itself.

Ammonia in the blood is freely filtered at the kidney glomerulus and can be "trapped" in the urine flow by accepting a proton to become ammonium (i.e. $H^+ + NH_3 = NH_4^+$) . Because of the positive charge the ammonium ion is unable to passively diffuse back across the tubules into the blood. This is one mechanism that ammonia is excreted. In the liver, the Urea Cycle (see any basic or clinical biochemistry text for more information) is a set of enzymes that converts most of the excess nitrogen in the form of ammonia to urea, which is a non-toxic, water soluble organic compound that can also be excreted in the urine. The body uses these processes to dispose of excess nitrogen from amino acids as well as ammonia that is produced as a by-product of bacterial metabolism in the GI tract.

Some patients with significant liver disease (e.g. cirrhosis from either NAFLD, hepatitis or any other liver-damaging disease) have lost the ability to convert all the excess ammonia to urea. In these patients, an easy way to prevent excessive nitrogen uptake in the gastrointestinal tract is by treating them with lactulose. Lactulose is a carbohydrate that that is not digestible or absorbable by the body, but is osmotically active (pulls water into the intestinal lumen) and acts to speed up intestinal transit. Since lactulose works by speeding up GI transit it makes you stool more frequently (which is why it is very useful for constipation). For liver disease patients, however, the lactulose acidifies (i.e. decreases pH) the lumen of the intestines and ammonia is protonated to form ammonium, which effectively traps it in the intestinal lumen. A lot of the excess ammonium can then pass into the feces and decrease the amount of ammonia that the liver needs to process. This is similar to the mechanism of ammonium in the urine as mentioned above. Additionally, lactulose also decreases the amount of GI bugs that produce ammonia containing compounds as well, which also lessens the amount of ammonia for detoxification by the liver. (Lactulose can also be used for a treatment for small intestinal overgrowth). These GI bacteria metabolize dietary amino acids and other compounds in the gut for energy metabolism, which liberates nitrogen-containing compounds that can be absorbed by the intestines.

Edit: Here is a link for a great reference on NCBI that explains the mechanism of action of lactulose.

  • $\begingroup$ It is very difficult to see how lactulose (a carbohydrate) could by itself lower the pH. My understanding is that lactulose (which as you state is non-absorbed, but is also water-soluble) is metabolized by intestinal bacteria to short-chain fatty acids, including acetic acid, thus lowering the pH (and thereby causing ammonia to become protonated). $\endgroup$ – user1136 Jun 27 '20 at 21:11
  • $\begingroup$ This answer is good, but it could be still better with references. $\endgroup$ – Adhish Jun 28 '20 at 7:26
  • $\begingroup$ Reference: See "Mechanism of Action" - - ncbi.nlm.nih.gov/books/NBK536930 $\endgroup$ – Vance L Albaugh Jul 27 '20 at 20:11

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.