Lactose intolerance is caused by a lessened ability or a complete inability to digest lactose, a sugar found in dairy products. Humans vary in the amount of lactose they can tolerate before symptoms develop. Symptoms may include abdominal pain, bloating, diarrhea, flatulence, and nausea. These symptoms typically start thirty minutes to two hours after eating
Medical conditionLactose intolerance is caused by a lessened ability or a complete inability to digest lactose, a sugar found in dairy products.[1] Humans vary in the amount of lactose they can tolerate before symptoms develop.[1] Symptoms may include abdominal pain, bloating, diarrhea, flatulence, and nausea.[1] These symptoms typically start thirty minutes to two hours after eating or drinking something containing lactose,[1] with the severity typically depending on the amount consumed.[1] Lactose intolerance does not cause damage to the gastrointestinal tract.[2]
Lactose intolerance is due to the lack of the enzyme lactase in the small intestines to break lactose down into glucose and galactose.[3] There are four types: primary, secondary, developmental, and congenital.[1] Primary lactose intolerance occurs as the amount of lactase declines as people grow up.[1] Secondary lactose intolerance is due to injury to the small intestine. Such injury could be the result of infection, celiac disease, inflammatory bowel disease, or other diseases.[1][4] Developmental lactose intolerance may occur in premature babies and usually improves over a short period of time.[1] Congenital lactose intolerance is an extremely rare genetic disorder in which little or no lactase is made from birth.[1] The reduction of lactase production starts typically in late childhood or early adulthood,[1] and prevalence increases with age.
Diagnosis may be confirmed if symptoms resolve following eliminating lactose from the diet.[1] Other supporting tests include a hydrogen breath test and a stool acidity test.[1] Other conditions that may produce similar symptoms include irritable bowel syndrome, celiac disease, and inflammatory bowel disease.[1] Lactose intolerance is different from a milk allergy.[1] Management is typically by decreasing the amount of lactose in the diet, taking lactase supplements (the amount of supplements should be based on the amount of lactose consumed), or treating the underlying disease.[1][5] People are typically able to drink at least one cup of milk without developing symptoms, with greater amounts tolerated if drunk with a meal or throughout the day.[1][6]
Worldwide, around 65% of adults are affected by lactose malabsorption.[7] Other mammals usually lose the ability to digest lactose after weaning. Lactose intolerance is the ancestral state of all humans before the recent evolution of lactase persistence in some populations, which extends lactose tolerance into adulthood.[8] Lactase persistence evolved in several populations independently, probably as an adaptation to the domestication of dairy animals around 10,000 years ago.[9][10] Today the prevalence of lactose tolerance varies widely between regions and ethnic groups. The ability to digest lactose is most common in people of Northern European descent, and to a lesser extent in some parts of Central Asia, the Middle East and Africa.[7]
Lactose intolerance is most common among people of East Asian descent (with 90% lactose intolerance), people of Jewish descent, people in African and Arab countries, and among some people of Southern European descent. Traditional food cultures reflect local variations in tolerance and historically many societies have adapted to low levels of tolerance by making dairy products that contain less lactose than fresh milk.[11] One ethnographic example of this is kumis, a fermented milk product that contains little to no lactose, which is the main source of dairy nutrition in Mongolia.[12]
The medicalization of lactose intolerance as a disorder has been attributed to biases in research history, since most early studies were conducted amongst populations which are normally tolerant,[8] as well as the cultural and economic importance and impact of milk in countries such as the United States.[13]
Terminology
Lactose intolerance primarily refers to a syndrome with one or more symptoms upon the consumption of food substances containing lactose sugar. Individuals may be lactose intolerant to varying degrees, depending on the severity of these symptoms.
Hypolactasia is the term specifically for the small intestine producing little or no lactase enzyme.[14] If a person with hypolactasia consumes lactose sugar, it results in lactose malabsorption.[2] The digestive system is unable to process the lactose sugar, and the unprocessed sugars in the gut produce the symptoms of lactose intolerance.
Lactose intolerance is not an allergy, because it is not an immune response, but rather a sensitivity to dairy caused by a deficiency of lactase enzyme. Milk allergy, occurring in about 2% of the population, is a separate condition, with distinct symptoms that occur when the presence of milk protein, whey, triggers an immune reaction.[15] A milk allergy most often appears in the first year of life, while lactose intolerance typically appears later in life.[16]
Signs and symptoms
The principal manifestation of lactose intolerance is an adverse reaction to products containing lactose (primarily milk), including abdominal bloating and cramps, flatulence, diarrhea, nausea, borborygmi, and vomiting (particularly in adolescents). These appear thirty minutes to two hours after consumption.[1] The severity of these signs and symptoms typically increases with the amount of lactose consumed; most lactose-intolerant people can tolerate a certain level of lactose in their diets without ill effects.[17][18]
Because lactose intolerance is not an allergy, it does not produce allergy symptoms (such as itching, hives, or anaphylaxis).
Causes
Lactose intolerance is a consequence of lactase deficiency, which may be genetic (primary hypolactasia and primary congenital alactasia) or environmentally induced (secondary or acquired hypolactasia). In either case, symptoms are caused by insufficient levels of lactase in the lining of the duodenum. Lactose, a disaccharide molecule found in milk and dairy products, cannot be directly absorbed through the wall of the small intestine into the bloodstream, so, in the absence of lactase, passes intact into the colon.[citation needed] Bacteria in the colon can metabolise lactose, and the resulting fermentation produces copious amounts of gas (a mixture of hydrogen, carbon dioxide, and methane) that causes the various abdominal symptoms. The unabsorbed sugars and fermentation products also raise the osmotic pressure of the colon, causing an increased flow of water into the bowels (diarrhea).[19][8]
Lactose intolerance in infants (congenital lactase deficiency) is caused by mutations in the LCT gene. The LCT gene provides the instructions for making lactase. Mutations are believed to interfere with the function of lactase, causing affected infants to have a severely impaired ability to digest lactose in breast milk or formula.[20] Lactose intolerance in adulthood is a result of gradually decreasing activity (expression) of the LCT gene after infancy, which occurs in most humans. The specific DNA sequence in the MCM6 gene helps control whether the LCT gene is turned on or off.[21] At least several thousand years ago, some humans developed a mutation in the MCM6 gene that keeps the LCT gene turned on even after breast feeding is stopped.[22] Populations that are lactose intolerant lack this mutation. The LCT and MCM6 genes are both located on the long arm (q) of chromosome 2 in region 21. The locus can be expressed as 2q21.[22] The lactase deficiency also could be linked to certain heritages and varies widely. A 2016 study of over 60,000 participants from 89 countries found regional prevalence of lactose malabsorption was "64% (54–74) in Asia (except Middle East), 47% (33–61) in eastern Europe, Russia, and former Soviet Republics, 38% (CI 18–57) in Latin America, 70% (57–83) in the Middle East, 66% (45–88) in northern Africa, 42% (13–71) in northern America, 45% (19–71) in Oceania, 63% (54–72) in sub-Saharan Africa, and 28% (19–37) in northern, southern and western Europe." According to Johns Hopkins Medicine, in the United States lactose intolerance is more common in Asian Americans, African Americans, Mexican Americans, and Native Americans.[23] Analysis of the DNA of 94 ancient skeletons in Europe and Russia concluded that the mutation for lactose tolerance appeared about 4,300 years ago and spread throughout the European population.[24]
Some human populations have developed lactase persistence, in which lactase production continues into adulthood probably as a response to the benefits of being able to digest milk from farm animals. Some have argued that this links intolerance to natural selection favoring lactase-persistent individuals, but it is also consistent with a physiological response to decrease lactase production when it is not needed in cultures in which dairy products are not an available food source.[25] Although populations in Europe, India, Arabia, and Africa were first thought to have high rates of lactase persistence because of a single mutation, lactase persistence has been traced to a number of mutations that occurred independently.[10] Different alleles for lactase persistence have developed at least three times in East African populations, with persistence extending from 26% in Tanzania to 88% in the Beja pastoralist population in Sudan.[26]
The accumulation of epigenetic factors, primarily DNA methylation, in the extended LCT region, including the gene enhancer located in the MCM6 gene near C/T-13910 SNP, may also contribute to the onset of lactose intolerance in adults.[27][28] Age-dependent expression of LCT in mice intestinal epithelium has been linked to DNA methylation in the gene enhancer.[28]
Lactose intolerance is classified according to its causes as:
Primary hypolactasia Primary hypolactasia, or primary lactase deficiency, is genetic, develops in childhood at various ages, and is caused by the absence of a lactase persistence allele. In individuals without the lactase persistence allele, less lactase is produced by the body over time, leading to hypolactasia in adulthood.[2][29] The frequency of lactase persistence, which allows lactose tolerance, varies enormously worldwide, with the highest prevalence in Northwestern Europe, declines across southern Europe and the Middle East and is low in Asia and most of Africa, although it is common in pastoralist populations from Africa.[8] Secondary hypolactasia Secondary hypolactasia or secondary lactase deficiency, also called acquired hypolactasia or acquired lactase deficiency, is caused by an injury to the small intestine. This form of lactose intolerance can occur in both infants and lactase persistent adults and is generally reversible.[30] It may be caused by acute gastroenteritis, coeliac disease, Crohn's disease, ulcerative colitis,[31] chemotherapy, intestinal parasites (such as giardia), or other environmental causes.[2][32][33][34] Primary congenital alactasia Primary congenital alactasia, also called congenital lactase deficiency, is an extremely rare, autosomal recessive enzyme defect that prevents lactase expression from birth.[2] People with congenital lactase deficiency cannot digest lactose from birth, so cannot digest breast milk. This genetic defect is characterized by a complete lack of lactase (alactasia). About 40 cases have been reported worldwide, mainly limited to Finland. Before the 20th century, babies born with congenital lactase deficiency often did not survive,[2] but death rates decreased with soybean-derived infant formulas and manufactured lactose-free dairy products.[35]Diagnosis
In order to assess lactose intolerance, intestinal function is challenged by ingesting more dairy products than can be readily digested. Clinical symptoms typically appear within 30 minutes, but may take up to two hours, depending on other foods and activities.[36] Substantial variability in response (symptoms of nausea, cramping, bloating, diarrhea, and flatulence) is to be expected, as the extent and severity of lactose intolerance varies among individuals.[37]
The next step is to determine whether it is due to primary lactase deficiency or an underlying disease that causes secondary lactase deficiency.[2] Physicians should investigate the presence of undiagnosed coeliac disease, Crohn's disease, or other enteropathies when secondary lactase deficiency is suspected and infectious gastroenteritis has been ruled out.[2]
Lactose intolerance is distinct from milk allergy, an immune response to cow's milk proteins. They may be distinguished in diagnosis by giving lactose-free milk, producing no symptoms in the case of lactose intolerance, but the same reaction as to normal milk in the presence of a milk allergy. A person can have both conditions. If positive confirmation is necessary, four tests are available.[38]
Hydrogen breath test
In a hydrogen breath test, the most accurate lactose intolerance test, after an overnight fast, 25 grams of lactose (in a solution with water) are swallowed. If the lactose cannot be digested, enteric bacteria metabolize it and produce hydrogen, which, along with methane, if produced, can be detected on the patient's breath by a clinical gas chromatograph or compact solid-state detector. The test takes about 2.5 hours to complete. If the hydrogen levels in the patient's breath are high, they may have lactose intolerance. This test is not usually done on babies and very young children, because it can cause severe diarrhea.[39]
Lactose tolerance test
In conjunction, measuring blood glucose level every 10 to 15 minutes after ingestion will show a "flat curve" in individuals with lactose malabsorption, while the lactase persistent will have a significant "top", with a typical elevation of 50% to 100%, within one to two hours. However, due to the need for frequent blood sampling, this approach has been largely replaced by breath testing.[40]
After an overnight fast, blood is drawn and then 50 grams of lactose (in aqueous solution) are swallowed. Blood is then drawn again at the 30-minute, 1-hour, 2-hour, and 3-hour marks. If the lactose cannot be digested, blood glucose levels will rise by less than 20 mg/dl.[41]
