Lactulose: (Introduction, Structure, Source, Production, Medical uses, Mechanism)

Lactulose

(Synthetic disaccharide)

Introduction:

• Lactulose is a synthetic sugar used in the treatment of constipation and liver disease
• Lactulose was first made in 1929, and has been used medically since the 1950s
• It is a disaccharide (double-sugar) formed from one molecule each of the simple sugars (monosaccharides) fructose and galactose.
• Not hydrolysed by intestinal enzymes, but fermented by intestinal bacteria.
• It is used clinically in medicine as an osmotice laxative.

Structure:

• It is β-D-galctopyranosyl-(1→4)-β-D-fructofuranose
• The molecular weight is 342.30. It is freely soluble in water.

Source:

• Heated milk (small amounts). Mainly obtained synthetically.
• Each 15 mL of Lactulose solution contains 10 grams Lactulose (and less than 1.6 grams galactose, less than 1.2 grams lactose, and 0.1 grams or less of fructose)

Production:

• Lactulose is made from the milk sugar lactose, which is composed of two simple sugars, galactose and glucose.
• Lactulose is not normally present in raw milk but is a product of heat-processes:the greater the heat, the greater amount of this substance (from 3.5 mg/L in low temperature  pasteurized milk to 744 mg/L in in-container sterilized milk). 
• It is produced commercially, by isomerization of lactose.

Medical uses:

• Constipation: Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment
• Hyperammonemia: Lactulose is useful in treating high blood ammonia, which can lead to hepatic encephalopathy. Lactulose helps trap the ammonia (NH₃) in the colon and bind to it.

Mechanism:

• Lactulose is not absorbed in the small intestine nor broken down by human enzymes, thus stays in the digestive bolus through most of its course, causing retention of water through osmosis leading to softer, easier to pass stool. 
• In the colon, lactulose is broken down primarily to lactic acid, and also to small amounts of formic and acetic acids, by the action of via evolved-beta galactosidase from colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents.
• This in turn causes an increase in stool water content and softens the stool.
•  lactic acid and acetic acid partially dissociate, acidifying the colonic contents (increasing the H⁺ concentration in the gut).
• 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.

References:

• https://medlineplus.gov/druginfo/meds/a682338.html
• https://www.drugs.com/pro/lactulose.html
• https://en.wikipedia.org/wiki/Lactulose
• https://www.geneticsfacts.com/lactulose/