Lactulose is a semisynthetic disaccharide comprised of the sugars D-galactose and D-fructose. It is not found naturally. The sugars are joined by a beta glycosidic linkage making it resistant to hydrolysis by human digestive enzymes. There is no disaccharidase in the microvillus membrane of small intestine enterocytes that can hydrolyze lactulose; nor is the disaccharide absorbed from the small intestine. Lactulose is, however, fermented by a limited number of colonic bacteria. This can lead to changes in the colonic ecosystem in favor of some bacteria, such as lactobacilli and bifidobacteria, which may confer some health benefits. The chemical name for lactulose is 4-O-(beta)-D-Galactopyranosyl-D-fructofuranose. The molecular formula is C 12 H 22 O 11 . The molecular weight is 342.30. It is freely soluble in water.
Lactulose is used in the treatment of constipation and hepatic encephalopathy. The efficacy of lactulose in these conditions is based on its fermentation in the colon by certain bacteria and the increase of the biomass of these bacteria in the colon. The products of fermentation are mainly organic acids, such as lactic acid and small-chain fatty acids, which, by exerting a local osmotic effect in the colon, result in increased fecal bulk and stimulation of peristalsis. The higher doses used for hepatic encephalopathy lower the colonic pH, and ammonia, in the form of ammonium ions, is used by the bacteria for amino acid and protein synthesis. This lowers the serum ammonia levels and improves mental function.
Lactulose may promote the growth of favorable bacterial populations, such as bifidobacteria, in the colon. Bifidobacteria may inhibit the growth of pathogenic bacteria, such as Clostridium perfringens and diarrheogenic Escherichia coli. The stimulation of the growth of bacteria, such as bifidobacteria, may have other health benefits, such as protection against cancer of the colon. Lactulose is referred to as a bifidogenic factor. Substances such as lactulose that promote the growth of beneficial bacteria in the colon are called prebiotics. Prebiotics are typically nondigestible oligosaccharides. In addition to its uses in treatment of hepatic encephalopathy and constipation, lactulose is used in Japan in functional foods and as a nutritional supplement.
Lactulose may aid in lowering serum triglycerides in some. The mechanism of this possible effect is unclear. Decreased hepatocyte de novo synthesis of triglycerides is one hypothetical possibility. Lactulose may also lower total cholesterol and LDL-cholesterol levels in some. Again, the mechanism of this possible effect is unclear. Propionate, a product of lactulose fermentation in the colon, may inhibit HMG-CoA reductase, the rate-limiting step in cholesterol synthesis. The possible effects of lactulose on blood glucose may be explained in a few ways. Lactulose may delay gastric emptying and/or shorten small-intestinal tract transit time. This may be via the short-chain fatty acids produced from lactulose in the colon. Short-chain fatty acids may be involved in the so-called "ileocolonic brake," which refers to the inhibition of gastric emptying by nutrients reaching the ileo-colonic junction. Short-chain fatty acids may also stimulate contractions of the ileum and shorten ileal emptying. In addition, propionate may inhibit gluconeogenesis by its metabolic conversion to methylmalonyl-CoA and succinyl-CoA. These metabolites could inhibit pyruvate carboxylase. Propionate may also reduce plasma levels of free fatty acids. High levels of free fatty acids lower glucose utilization and induce insulin resistance. Finally, propionate may enhance glycolysis via depletion of citrate in hepatocytes. Citrate is an allosteric inhibitor of phosphofructokinase. Lactulose may bind/sequester such minerals as calcium and magnesium in the small intestine. The short-chain fatty acids formed from the bacterial fermentation of lactulose may facilitate the colonic absorption of calcium and, possibly, also magnesium ions. This could be beneficial in preventing osteoporosis and osteopenia.