Lactulose (ˈ) is a synthetic, non-digestible
sugarSugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
used in the treatment of chronic
constipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
and
hepatic encephalopathyHepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
, a complication of
liver diseaseLiver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
. It is a
disaccharideA disaccharide or biose is the carbohydrate formed when two monosaccharides undergo a condensation reaction which involves the elimination of a small molecule, such as water, from the functional groups only. Like monosaccharides, disaccharides form an aqueous solution when dissolved in water...
(double-sugar) formed from one molecule each of the simple sugars (
monosaccharideMonosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
s)
fructoseFructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...
and
galactoseGalactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
. It is produced commercially by isomerization of
lactoseLactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
.
Constipation
Lactulose is used in the treatment of chronic
constipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
. The metabolites of lactulose draw water into the bowel, causing a cathartic effect through osmotic action. It is safe for people of all ages, except for those in a very small percentage of the population that are
galactoseGalactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
intolerant. Dosage may have to be adjusted over time to produce the desired effect because the laxative effect can decline with daily treatment.
Lactulose works by increasing the water content and volume of the stools in the bowel, making them softer and easier to pass. Lactulose is made up of sugar molecules and is partly broken down by the bacteria that live in the lower part of the gut. This leads to the contents of the gut becoming more acidic because there are
carboxylic acidCarboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s among its
metaboliteMetabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
s, which are not absorbed from the lower bowel. That in turn causes
waterWater is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
to be retained in the lower bowel. This increases the amount of water in the stools, softening them and making them easier to pass. The added volume of gas and flatulence caused by
fermentationFermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...
of the lactulose adds to the volume of the fecal material, and makes it easier to expel. The slightly acidic condition of the colon caused by the presence of acids causes active
peristalsisPeristalsis is a radially symmetrical contraction and relaxation of muscles which propagates in a wave down the muscular tube, in an anterograde fashion. In humans, peristalsis is found in the contraction of smooth muscles to propel contents through the digestive tract. Earthworms use a similar...
. The combined effect of all of these processes relieves constipation in a very effective manner.
Lactulose is useful in treating people with chronic constipation due to forgetting or ignoring the need for
defecationDefecation is the final act of digestion by which organisms eliminate solid, semisolid or liquid waste material from the digestive tract via the anus. Waves of muscular contraction known as peristalsis in the walls of the colon move fecal matter through the digestive tract towards the rectum...
. The treatment is to start the dosage at a low amount and then gradually increase it over a period of weeks until the urgency is such that a daily bowel movement cannot possibly be ignored. After an efficacious dosage is determined, it is maintained indefinitely or increased as needed over time.
Lactulose is useful in treating people who abuse laxatives provided that they use lactulose as their only laxative drug, because it has very low toxicity yet produces powerful results.
Lactulose is useful for negating the constipating effects of opiates and opioids, as in individuals who are on narcotic pain medication, are opioid dependent, or are receiving Opioid Replacement Therapy such as with
methadoneMethadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
or
buprenorphineBuprenorphine is a semi-synthetic opioid that is used...
for a previous opioid dependency.
Lactulose is useful for treatment of hemorrhoids because it produces a soft bowel movement without any straining.
Lactulose is helpful for treating children who withhold their bowel movements out of fear because when taken in sufficient quantity and then withheld, it produces a very insistent, irresistible and powerful urge to defecate.
Lactulose is considered a prebiotic because it modulates the beneficial bacterial flora of the gut and is considered a digestive aid.
Lactulose has an overly sweet taste that can be completely masked by mixing it with fruit juice or desserts. It can take 24 to 48 hours to work, but generally produces results within 4 hours if taken on a daily basis. It is best taken at breakfast along with a bowl of
branBran is the hard outer layer of grain and consists of combined aleurone and pericarp. Along with germ, it is an integral part of whole grains, and is often produced as a by-product of milling in the production of refined grains. When bran is removed from grains, the grains lose a portion of their...
cereal.
For stubborn cases of constipation, lactulose is sometimes combined with
polyethylene glycolPolyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
3350Da, (sold as Miralax or Dulcolax Balance in the USA without prescription).
Some authorities recommend lactulose twice a day. However, an evening dosage can be problematic. When taken on a regular basis, it tends to work in about four hours. If given to small children who are in diapers, this is not a problem. However, for older children and adults, there is the ever present danger of voluminous
defecationDefecation is the final act of digestion by which organisms eliminate solid, semisolid or liquid waste material from the digestive tract via the anus. Waves of muscular contraction known as peristalsis in the walls of the colon move fecal matter through the digestive tract towards the rectum...
during sleep or being awake for hours on the toilet with a feeling of imminent expulsion. A juvenile or
adult diaperAn adult diaper is a diaper made to be worn by a person with a body larger than that of an infant or toddler. Diapers become necessary for adults with various conditions, such as incontinence, mobility impairment, or dementia...
is recommended along with protective
plastic pantsPlastic pants are devices worn over a diaper for the purpose of containing liquid or solid waste that may otherwise leak through the fabric. Today, "plastic pants" are usually made out of polyvinyl chloride or polyurethane though, in some instances, the traditional latex rubber is still used...
. This is especially true if a sleeping pill is taken.
In common with other osmotic laxatives, lactulose can cause electrolytic imbalances in sensitive individuals (see side effects below). However, it tends to do this less because it does not rely on mineral salts to draw fluid into the intestinal tract and also because it relies on nonosmotic modes of action: It stimulates peristalsis through acidification and gas and increases feeling of urgency through enlarging the volume of the bowel contents.
Lactulose is sold over the counter (without prescription) in most countries in the world. In the United States and Austria, it requires a prescription over unfounded fears that it could be dangerous to diabetics. However, it is an indigestible sugar and has been proved to be safe even for them.
Hepatic encephalopathy
In treating
hepatic encephalopathyHepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
, lactulose helps "draw out"
ammoniaAmmonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
(NH
3) from the body.
Lactulose is metabolized in the
colonThe colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
by
bacterial floraThe bacterial flora is the community of bacteria that exists on or in the body but which are not part of the body and so exists in its own biochemical environment:*Exogenous bacteria*Flora *Gut flora*Human flora*mouth flora*Skin flora...
to short chain fatty acids including the production of the lactic acid and acetic acid. This partially dissociates, acidifying the colonic contents (increasing the H
+ concentration in the gut).
This favors the formation of the nonabsorbable NH
4+ from NH
3, trapping NH
3 in the colon and effectively reducing plasma NH
3 concentrations.
The effectiveness of lactulose in treating hepatic encephalopathy is somewhat controversial.
However, lactulose can effectively be used as secondary prohylaxis of hepatic encephalopathy in patients with cirrhosis.
Moreover, recent studies showed improved cognitive functions of cirrhotic patients with minimal hepatic encephalopathy treated with lactulose.
Lactulose, also an osmotic laxative, is not absorbed, does not affect the absorption of spironolactone and may be used by diabetics. It is used in patients with cirrhosis/hepatic encephalopathy to limit the proliferation of ammonia forming gut organisms and increase the clearance of protein load in the gut.
Lactulose for hepatic encephalopathy generally requires oral dosage three or four times a day with diarrhea and constant flatulence almost a certain side effect.
Lactulose Breath Test
Lactulose is used as a test of small intestine bacterial overgrowth syndrome (SIBO). Recently the reliability of it for diagnosing SIBO has been seriously questioned. A large amount of it is given with subsequent testing of molecular
hydrogen gas in the breathA hydrogen breath test is used as a clinical medical diagnosis for people with irritable bowel syndrome, and common food intolerances. The test is simple, non-invasive, and is performed after a short period of fasting . Even though the test is normally known as a "Hydrogen Breath Test" some...
. The test is positive if an increase in exhaled hydrogen occurs before that which would be expected by normal
colonocyteGut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....
digestion. An earlier result has been hypothesized to indicate digestion occurring within the small intestine. An alternate explanation for differences in results is the variance in small bowel transit time among tested subjects.
Side effects
Common side effects of lactulose are abdominal cramping,
borborygmusBorborygmus also known as stomach growling, rumbling, gurgling, grumbling or wambling, is the rumbling sound produced by the contraction of muscles in the stomach and intestines of animals, including humans...
, gas and pungent
flatulenceFlatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
that some people find difficult to control in social situations. Excessively high dosage can cause explosive and uncontrollable
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
. In normal individuals, overdose is considered uncomfortable, but not life threatening. Uncommon normal side effects are
nauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
.
In sensitive individuals, such as the elderly or people with reduced
kidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
function, excess lactulose dosage can result in
dehydrationIn physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
and electrolytic disturbances such as
high sodium levelsHypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body...
.
Although lactulose has less potential to cause
dental cariesDental caries, also known as tooth decay or a cavity, is an irreversible infection usually bacterial in origin that causes demineralization of the hard tissues and destruction of the organic matter of the tooth, usually by production of acid by hydrolysis of the food debris accumulated on the...
than sucrose, there is a minimal potential because it is a sugar. This should be taken into consideration when taken by people with a high susceptibility to this condition.
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