Lactulose is a non-absorbable

sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...

used in the treatment of

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

and

hepatic encephalopathy Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages ...

. It is used by mouth for constipation and either by mouth or in the rectum for

. It generally begins working after 8–12 hours, but may take up to 2 days to improve constipation. Common

side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

include abdominal

bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, press ...

and cramps. A potential exists for

electrolyte problems Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...

as a result of the

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

it produces. No evidence of harm to the baby has been found when used during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

. It is generally regarded as safe during breastfeeding. It is classified as an

osmotic laxative Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubri ...

. Lactulose was first made in 1929, and has been used medically since the 1950s. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. It is available as a

generic Generic or generics may refer to: In business * Generic term, a common name used for a range or class of similar things not protected by trademark * Generic brand, a brand for a product that does not have an associated brand or trademark, other ...

and brand-name product. Lactulose is made from the milk sugar

lactose Lactose is a disaccharide sugar synthesized by galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from ' (gen. '), the Latin word for milk, plus the suffix '' - ...

, which is composed of two simple sugars,

galactose Galactose (, '' galacto-'' + '' -ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molec ...

and

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

History

In 1957, Peitele discovered that lactulose is a ''bifidobacterium'' proliferation factor. In 1964, Hoffman found that only ''bifidobacteria'', ''Lactobacillus'' and ''Streptococcus'' could metabolise lactulose into lactic acid and acetic acid. In 1966, Baicier found that lactulose can promote the growth of basophilic gram-positive bacteria lacking urease (e.g. ''Escherichia coli'') and reduce ammonia production. It has been proven that lactulose reduces blood ammonia, and it has been successfully used in the treatment of hepatic encephalopathy. In 1979, Nianmoleyou treated viral hepatitis with lactulose and he found that lactulose has the effect of reducing plasma endotoxin. From 1980 to 1981, Leicier found that the limulus test agglutination reaction of lactulose inhibits endotoxin in vitro, alleviating the liver injury of rats induced by D-amino galactose. He believed that lactulose had anti-endotoxin activity, meaning that and it can be used in the treatment of liver and kidney syndrome.

Medical uses

Constipation

Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment. The dosage of lactulose for chronic idiopathic constipation is adjusted depending on the constipation severity and desired effect, from a mild stool softener to causing diarrhea. Lactulose is contraindicated in case of

galactosemia Galactosemia (British galactosaemia, from Greek γαλακτόζη + αίμα, meaning galactose + blood, accumulation of galactose in blood) is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galacto ...

, as most preparations contain the monosaccharide galactose due to its synthesis process. Lactulose may be used to counter the constipating effects of

opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

, and in the symptomatic treatment of

hemorrhoids Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''hemo ...

as a stool softener. Lactulose is commonly prescribed for children who develop fear of their bowel movements and are withholders. This is because lactulose, when dosed in the proper amount, causes a bowel movement that is impossible to retain for very long. Lactulose is also used for the elderly because of its gentle and consistent results.

Hyperammonemia

Lactulose is useful in treating

hyperammonemia Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammonia is a substance that contains nitrogen. It i ...

(high blood ammonia), which can lead to

. Lactulose helps trap the

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

(NH₃) in the colon and bind to it. It does this by using gut flora to acidify the colon, transforming the freely diffusible ammonia into

ammonium The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary a ...

ions (), which can no longer diffuse back into the blood. It is also useful for preventing hyperammonemia caused as a side effect of administration of

valproic acid Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...

Small intestine bacterial overgrowth

Lactulose is used as a test of

small intestine bacterial overgrowth Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is ...

(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 breath. The test is positive if an increase in exhaled hydrogen occurs before that which would be expected by normal digestion by the normal

gut flora Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut mi ...

in the colon. 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.

Pregnancy

No evidence of harm to the baby has been found when used during

. It is generally regarded as safe during breastfeeding.

Side effects

Common side effects of lactulose are abdominal cramping,

borborygmus A stomach rumble, also known as a bowel sound, peristaltic sound, abdominal sound, bubble gut or borborygmus (pronounced ; plural borborygmi), is a rumbling, growling or gurgling noise produced by movement of the contents of the gastro-intestinal ...

, and

flatulence Flatulence, in humans, is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed environm ...

. In normal individuals, overdose is considered uncomfortable, but not life-threatening. Uncommon side effects are

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

. In sensitive individuals, such as the elderly or people with reduced

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

function, excess lactulose dosage can result in

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

and electrolyte disturbances such as low magnesium levels. Ingestion of lactulose does not cause a weight gain because it is not digestible, with no nutritional value. Although lactulose is less likely to cause

dental caries Tooth decay, also known as cavities or caries, is the breakdown of teeth due to acids produced by bacteria. The cavities may be a number of different colors from yellow to black. Symptoms may include pain and difficulty with eating. Complicatio ...

than sucrose, as a sugar, a potential for this exists. This should be taken into consideration when taken by people with a high susceptibility to this condition.

Mechanism of action

It is a

disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar formed when two monosaccharides are joined by glycosidic linkage. Like monosaccharides, disaccharides are simple sugars soluble in water. Three common examples are sucrose, lact ...

formed from one molecule each of the

simple sugars Monosaccharides (from Greek ''monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. They are usually colorless, water-solub ...

(

monosaccharide Monosaccharides (from Greek ''monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. They are usually colorless, water-solub ...

fructose Fructose, or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galacto ...

and

. 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 Pasteurization American and British English spelling differences#-ise, -ize (-isation, -ization), or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mi ...

milk to 744 mg/L in in-container sterilized milk). It is produced commercially by

isomerization In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...

of lactose. Lactulose is not absorbed in the

small intestine The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...

nor broken down by human enzymes, thus stays in the digestive bolus through most of its course, causing retention of water through

osmosis Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...

leading to softer, easier-to-pass stool. It has a secondary laxative effect in the colon, where it is

fermented Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...

by the

, producing

metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

which have osmotic powers and

peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, which ...

-stimulating effects (such as

acetate An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...

), but also

methane Methane ( , ) is a chemical compound with the chemical formula (one carbon atom bonded to four hydrogen atoms). It is a group-14 hydride, the simplest alkane, and the main constituent of natural gas. The relative abundance of methane on Eart ...

associated with

. Lactulose is metabolized in the colon by bacterial flora into short-chain fatty acids, including

lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natu ...

and

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...

. These partially dissociate, acidifying the colonic contents (increasing the H⁺ concentration in the gut). This favors the formation of the nonabsorbable from NH₃, trapping NH₃ in the colon and effectively reducing plasma NH₃ concentrations. Lactulose is therefore effective in treating hepatic encephalopathy. Specifically, it is effective as secondary prevention of hepatic encephalopathy in people with cirrhosis. Moreover, research showed improved cognitive functions and health-related quality of life in people with cirrhosis with minimal hepatic encephalopathy treated with lactulose.

Society and culture

Name

Lactulose is its international nonproprietary name (INN). It is sold under various brand names.

Availability

Lactulose is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. It is available without prescription in most countries, but a prescription is required in the United States and Austria.

Food additive

In some countries where lactulose may be obtained without a prescription, lactulose is commonly used as a

food additive Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (salt ...

to improve taste and promote intestinal transit.

Veterinary use

Lactulose is used in veterinary medicine.

References

External links

* {{Laxatives Carbohydrates Disaccharides Gastroenterology Laxatives Wikipedia medicine articles ready to translate World Health Organization essential medicines