Lactose intolerance

Lactose Intolerance
Classification and external resources
Lactose (disaccharide of β-D-galactose & β-D-glucose) is normally split by lactase.
ICD-10	E73
ICD-9	271.3
OMIM	223100 150220
DiseasesDB	7238
MedlinePlus	000276
eMedicine	med/3429 ped/1270
MeSH	D007787

Lactose intolerance, also called lactase deficiency^[1] or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk. It is caused by a lack of lactase, the enzyme required to break down lactose in the digestive system, and results in symptoms including abdominal pain, bloating, flatulence, diarrhea, nausea and acid reflux.

Most mammals normally become lactose intolerant when they are young but some human populations have developed lactase persistence, in which lactase production continues into adulthood. It is estimated that 75% of adults worldwide show some decrease in lactase activity during adulthood.^[2] The frequency of decreased lactase activity ranges from 5% in northern Europe through 71% for Sicily to more than 90% in some African and Asian countries.^[3]

Terminology

"Lactose intolerance" primarily refers to a syndrome having one or more symptoms upon the consumption of food substances containing lactose. Individuals may be lactose intolerant to varying degrees, depending on the severity of these symptoms. "Lactose malabsorption" refers to the physiological concomitant of lactase deficiency (i.e. the body does not have sufficient lactase capacity to digest the amount of lactose ingested).^[4] A medical condition with similar symptoms is fructose malabsorption.

Lactase deficiency has a number of causes, and is therefore classified as one of three types:

• Primary lactase deficiency is genetic, only affects adults and is caused by the absence of a lactase persistence allele.^[4][5] It is the most common cause of lactose intolerance as a majority of the world's population lacks these alleles.^[6]
• Secondary lactase deficiency is caused by injury to the small intestine, usually in infancy, from acute gastroenteritis, diarrhea, chemotherapy, intestinal parasites or other environmental causes.^{[4][7][8][9][10]}
• Congenital lactase deficiency is a very rare, autosomal recessive genetic disorder that prevents lactase expression from birth.^[4] It is particularly common in Finland.^[11]

Symptoms

Nutritional implications

While dairy products, being rich in protein, calcium, and carbohydrates, can be a significant source of nutrients, there is no evidence that lactose intolerance has any adverse impact on health in populations where it is the norm amongst adults.^{[citation needed]} In dairy-consuming societies, however, dairy is often the main source of those nutrients and also, for lacto-vegetarians, the main source of vitamin B₁₂. Some countries require by law that milk be fortified with vitamin A and vitamin D.^{[citation needed]} In these societies individuals who reduce or eliminate consumption of dairy must obtain these nutrients elsewhere; calcium from fortified breakfast foods, for example, potassium and vitamin A from fruit and vegetables and B vitamins from meat and eggs. The human body produces some vitamin D from exposure to direct sunlight.

Congenital lactase deficiency (CLD), the inhibited production of lactase in infants as well as adults, can be dangerous in any society because of infants' nutritional reliance on breast milk. Before the 20th century those born with the condition were not expected to survive infancy^[4] but it can be mitigated using soybean-derived infant formulae and manufactured lactase-free dairy products.^[12][13] Beyond infancy individuals affected by CLD usually have the same nutritional concerns as other lactose-intolerant adults.

Causes

Lactose intolerance is a consequence of lactase deficiency, which may be either genetic or environmentally induced, depending on whether it is (primary, secondary, or congenital). In any case symptoms are caused by insufficient levels of the enzyme 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. Bacteria in the colon are able to 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 raises the osmotic pressure of the colon, resulting in an increased flow of water into the bowels (diarrhea).^[14]

Diagnosis

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 2 hours depending on other foods and activities.^[15] 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.

It is important to distinguish lactose intolerance from milk allergy, an abnormal immune response (usually) to milk proteins. This may be done in diagnosis by giving lactose-free milk, producing no symptoms in the case of lactose intolerance but the same reaction as to normal milk if it is a milk allergy. An intermediate result might suggest that the person has both conditions. Since lactose intolerance is normal state for most adults worldwide it is not considered a disease and a medical diagnosis is not normally required. However if confirmation is necessary four tests are available.

Hydrogen breath test

In a hydrogen breath test, after an overnight fast, 25 grams of lactose (in a solution with water) is 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 to 3 hours.

Blood test

In conjunction, measuring blood glucose level every 10 – 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 1 – 2 hours. However due to the need for frequent blood sampling this approach has been largely supplanted by breath testing.

After an overnight fast blood is drawn and then 50 grams of lactose (in aqueous solution) is swallowed. Blood is then drawn again at the 30 minute, 1 hour, 2 hour, and 3 hour mark. If the lactose cannot be digested blood glucose levels will rise by less than 20 mg/dL.^[16]

Stool acidity test

This test can be used to diagnose lactose intolerance in infants, for whom other forms of testing are risky or impractical.^[17] The infant is given lactose to drink. If the individual is tolerant, the lactose is digested and absorbed in the small intestine, otherwise it is not digested and absorbed and it reaches the colon. The bacteria in the colon, mixed with the lactose, cause acidity in stools. Stools passed after the ingestion of the lactose are tested for level of acidity. If the stools are acidic, the infant is intolerant to lactose.^[18]

Intestinal biopsy

An intestinal biopsy can confirm lactase deficiency following discovery of elevated hydrogen in the hydrogen breath test.^[19] Modern techniques have enabled a test to be performed at the patient's bedside identifying the presence/absence of the lactase enzyme in conjunction with upper gastrointestinal endoscopy.^[20] However, for research applications such as mRNA measurements a specialist laboratory is required.

Management

Lactose intolerance is not considered a condition that requires treatment in societies where the diet contains relatively little dairy. However those living among societies that are largely lactose-tolerant may find lactose intolerance troublesome. Although there are still no methodologies to reinstate lactase production, some individuals have reported that their intolerance varies over time depending on health status and pregnancy^[21]).

Lactose intolerance is not usually an absolute condition: the reduction in lactase production, and the amount of lactose that can therefore be tolerated, varies from person to person. Since lactose intolerance poses no further threat to a person's health, the condition is managed by minimizing the occurrence and severity of symptoms. Berdanier and Hargrove recognise four general principles; avoidance of dietary lactose, substitution to maintain nutrient intake, regulation of calcium intake and use of enzyme substitute.^[19]

Avoiding lactose-containing products

Since each individual's tolerance to lactose varies, according to the US National Institute of Health, "Dietary control of lactose intolerance depends on people learning through trial and error how much lactose they can handle."^[1] Label reading is essential, as commercial terminology varies according to language and region.^[19]

Lactose is present in two large food categories: conventional dairy products, and as a food additive (in dairy and non dairy products).

Dairy products

Lactose is a water-soluble molecule. Therefore fat percentage and the curdling process affect tolerance of foods. After the curdling process lactose is found in the water portion (along with whey and casein) but not in the fat portion. Dairy products that are "fat reduced" or "fat free" generally have a slightly higher lactose percentage. Low fat dairy foods, additionally, often have various dairy derivatives such as milk solids added to them to enhance sweetness, increasing the lactose content.

Milk. Human milk has the highest lactose percentage at around 9%. Unprocessed cow milk has 4.7% lactose. Unprocessed milk from other bovids contains similar lactose percentages (goat milk 4.7%,^[22] buffalo 4.86%,^[23] yak 4.93%,^[24] sheep milk 4.6%)

Butter. The butter-making process separates the majority of milk's water components from the fat components. Lactose, being a water soluble molecule, will largely be removed, but will still be present in small quantities in the butter unless it is also fermented to produce cultured butter. Clarified butter, however, has extremely low concentrations of lactose and is safe for most LI patients.

Yogurt, Frozen Yogurt and kefir. People can be more tolerant of traditionally made yogurt than milk because it contains lactase produced by the bacterial cultures used to make the yogurt. Frozen yogurt, if cultured similarly to its unfrozen counterpart, will contain similarly reduced lactose levels. However many commercial brands contain milk solids^{[citation needed]}, increasing the lactose content.

Cheeses. Traditionally made hard cheese (such as Emmental) and soft ripened cheeses may create less reaction than the equivalent amount of milk because of the processes involved. Fermentation and higher fat content contribute to lesser amounts of lactose. Traditionally made Emmental or Cheddar might contain 10% of the lactose found in whole milk. In addition, the traditional aging methods of cheese (over 2 years) reduces their lactose content to practically nothing.^[25] Commercial cheese brands, however, are generally manufactured by modern processes that do not have the same lactose reducing properties, and as no regulations mandate what qualifies as an "aged" cheese, this description does not provide any indication of whether the process used significantly reduced lactose.

Sour cream if made in the traditional way, may be tolerable, but most modern brands add milk solids. Consult labels.^[26]

Examples of lactose levels in foods. As scientific consensus has not been reached concerning lactose percentage analysis methods ^[27] (non-hydrated form or the mono-hydrated form), and considering that dairy content varies greatly according to labeling practices, geography and manufacturing processes, lactose numbers may not be very reliable. The following are examples of lactose levels in foods which commonly set off symptoms.^[28] These quantities are to be treated as guidelines only.

Dairy product	Serving size	Lactose content
Milk, regular	250 ml	12 g
Milk, reduced fat	250 ml	13 g
Yogurt, plain, regular	200 g	9 g
Yogurt, plain, low-fat	200 g	12 g
Cheddar cheese	30 g	0.02 g
Cottage cheese	30 g	0.1 g
Butter	1 tsp	0.03 g
Ice cream	50 g	3 g

Lactose in non-dairy products

Lactose (also present when labels state lactoserum, whey, milk solids, modified milk ingredients, etc.) is a commercial food additive used for its texture, flavour and adhesive qualities, and is found in foods such as processed meats^[29] (sausages/hot dogs, sliced meats, pâtés), gravy stock powder, margarines,^[30] sliced breads,^[31][32] breakfast cereals, potato chips,^[33] processed foods, medications, pre-prepared meals, meal replacement (powders and bars), protein supplements (powders and bars) and even beers in the milk stout style. Some barbecue sauces and liquid cheeses used in fast-food restaurants may also contain lactose.

Kosher products labeled pareve or fleishig are free of milk. However, if a "D" (for "Dairy") is present next to the circled "K", "U", or other hechsher, the food likely contains milk solids^[29] (although it may also simply indicate that the product was produced on equipment shared with other products containing milk derivatives).

Alternative products

Plant-based milks and derivatives are inherently lactose free: soy milk, rice milk, almond milk, hazelnut milk, oat milk, hemp milk, peanut milk, horchata.

Main article: Milk#Reduction_or_elimination_of_lactose

The dairy industry has created low-lactose or lactose-free products to replace regular dairy.

Lactase supplementation

When lactose avoidance is not possible, or on occasions when a person chooses to consume such items, then enzymatic lactase supplements may be used.^[34][35]

Lactase enzymes similar to those produced in the small intestines of humans are produced industrially by fungi of the genus Aspergillus. The enzyme, β-galactosidase, is available in tablet form in a variety of doses, in many countries without a prescription. It functions well only in high-acid environments, such as that found in the human gut due to the addition of gastric juices from the stomach. Unfortunately, too much acid can denature it,^[36] and it therefore should not be taken on an empty stomach. Also, the enzyme is ineffective if it does not reach the small intestine by the time the problematic food does. Lactose-sensitive individuals can experiment with both timing and dosage to fit their particular needs.

While essentially the same process as normal intestinal lactose digestion, direct treatment of milk employs a different variety of industrially produced lactase. This enzyme, produced by yeast from the genus Kluyveromyces, takes much longer to act, must be thoroughly mixed throughout the product, and is destroyed by even mildly acidic environments. Its main use is in producing the lactose-free or lactose-reduced dairy products sold in supermarkets.

Enzymatic lactase supplementation may have an advantage over avoiding dairy products, in that alternative provision does not need to be made to provide sufficient calcium intake, especially in children.^[37]

Rehabituation to dairy products

For healthy individuals with secondary lactose intolerance, it may be possible in some cases for the bacteria in the large intestine to adapt to an altered diet and break down small quantities of lactose more effectively^[38] by habitually consuming small amounts of dairy products several times a day over a period of time. Reintroducing dairy in this way to people who have an underlying or chronic illness, however, is not recommended, as certain illnesses damage the intestinal tract in a way which prevents the lactase enzyme from being expressed.

Some studies indicate that environmental factors (more specifically, the consumption of lactose) may "play a more important role than genetic factors in the etio-pathogenesis of milk intolerance",^[39] but some other publications suggest that lactase production does not seem to be induced by dairy/lactose consumption.^[40]

Lactase persistence

Main article: Lactase persistence

Lactase persistence is the phenotype associated with various autosomal dominant alleles prolonging the activity of lactase beyond infancy; conversely, lactase non-persistence is the phenotype associated with primary lactase deficiency (see above). Among mammals, lactase persistence is unique to humans – it evolved relatively recently (in the last 10,000 years) among some populations, and the majority of people worldwide remain lactase non-persistent.^[6] For this reason lactase persistence is of some interest to the fields of anthropology and human genetics, which typically use the genetically-derived persistence/non-persistence terminology.

Recognition of the extent and genetic basis of lactose intolerance is also relatively recent. Though the symptoms were recognised as early as Hippocrates (460-370 B.C.),^[41] until at least the 1960s the prevailing assumption in the medical community was that tolerance was the normal condition and intolerance either the result of milk allergy, an intestinal pathogen, or else was psychosomatic (it being recognised that some cultures did not practice dairying, and people from those cultures often reacted badly to consuming milk).^[42][43] Many people are still surprised or disbelieving that, from a cross-cultural and evolutionary perspective, lactose tolerance is the "abnormal" condition. There are two reasons for this perception. Firstly Western countries, as a result of their mostly European heritage, have particularly low frequences of lactose intolerance,^[44] and an extensive cultural history of dairying, so tolerance actually was the norm in most of the societies sampled by medical researchers. Secondly, in such societies lactose intolerance tended to be under-reported: genetically lactase non-persistent individuals can tolerate varying quantities of lactose before showing symptoms, and their symptoms differ in severity. Most are able to digest a small quantity of milk, for example in tea or coffee, without suffering any adverse effects.^[45] Fermented dairy products, such as cheese, also contain dramatically less lactose than plain milk. Therefore in societies where tolerance is the norm many people who consume only small amounts of dairy, or have only mild symptoms, may be unaware that they cannot digest lactose. Eventually, however, it was recognised that in the United States lactose intolerance was closely linked to race.^[46][47][48] Subsequent research revealed that intolerance was the worldwide norm,^{[49][50][51][52][53]} and that the variation was genetic.^[43][54] However, as yet there is no comprehensive understanding of either the global distribution of lactase persistence, the number of alleles that cause it, or the reasons for its recent selection.^[6]

See also

• Dairy allergy
• Food allergy
• Gastroenterology
• Gluten intolerance
• Soy cheese
• Soy milk and Plant milk
• Sucrose intolerance

Notes

1. ^ ^{a b} National Digestive Diseases Information Clearinghouse (March 2006). "Lactose Intolerance". National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. http://digestive.niddk.nih.gov/ddiseases/pubs/lactoseintolerance/. 
2. ^ "Improved lactose digestion and intolerance among African-American adolescent girls fed a dairy-rich diet". Journal of the American Dietetic Association 100 (5): 524–8; quiz 529–30. 2000. doi:10.1016/S0002-8223(00)00162-0. PMID 10812376. http://www.accessmylibrary.com/coms2/summary_0286-27939567_ITM. Retrieved 2009-02-03. "Approximately 75% of the world's population loses the ability to completely digest a physiological dose of lactose after infancy" 
3. ^ Bulhões, A.C.; Goldani, H.A.S.; Oliveira, F.S.; Matte, U.S.; Mazzuca, R.B.; Silveira, T.R. (2007). "Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia". Brazilian Journal of Medical and Biological Research 40 (11): 1441–6. doi:10.1590/S0100-879X2007001100004. PMID 17934640. 
4. ^ ^{a b c d e} Heyman, M. B.; Committee On, N. (2006). "Lactose Intolerance in Infants, Children, and Adolescents". Pediatrics 118 (3): 1279–1286. doi:10.1542/peds.2006-1721. PMID 16951027.  edit
5. ^ Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I (2002). "Identification of a variant associated with adult-type hypolactasia". Nat. Genet. 30 (2): 233–7. doi:10.1038/ng826. PMID 11788828. 
6. ^ ^{a b c} Swallow, D. M. (2003). "Genetics Oflactasepersistence Andlactoseintolerance". Annual Review of Genetics 37: 197–219. doi:10.1146/annurev.genet.37.110801.143820. PMID 14616060.  edit
7. ^ Mark Wiser (August 30, 2007). "Intestinal Protozoa". Tulane University. http://www.tulane.edu/~wiser/protozoology/notes/intes.html. Retrieved 2008-01-31. 
8. ^ Giardiasis at eMedicine Andre Pennardt February 22, 2006
9. ^ Swagerty DL, Walling AD, Klein RM (2002). "Lactose intolerance". Am Fam Physician 65 (9): 1845–50. PMID 12018807. http://www.aafp.org/afp/20020501/1845.html. 
10. ^ Colic and lactose intolerance
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12. ^ Cite error: Invalid <ref> tag; no text was provided for refs named Sinden.2C_A.A_1991; see Help:Cite errors/Cite error references no text
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14. ^ Lactose intolerance~overview at eMedicine
15. ^ R. Bowen (December 28, 2006). "Lactose Intolerance (Lactase Non-Persistence)". Pathophysiology of the Digestive System. Colorado State University. http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/lactose_intol.html. 
16. ^ "Lactose tolerance tests". 3-May-2011. http://www.nlm.nih.gov/medlineplus/ency/article/003500.htm. 
17. ^ National Digestive Diseases Information Clearinghouse (March 2006). "Lactose Intolerance -- How is lactose intolerance diagnosed?". National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. http://digestive.niddk.nih.gov/ddiseases/pubs/lactoseintolerance/#diagnosed. 
18. ^ "Stool Acidity Test". Jay W. Marks, M.D.. http://www.medicinenet.com/stool_acidity_test/article.htm#stool. Retrieved 20/5/2011. 
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21. ^ Lactose Intolerance at eMedicine Roy, Barakat, Nwakakwa, Shojamanesh, Khurana, July 5, 2006 - About 44% of lactose intolerant women regain the ability to digest lactose during pregnancy. This might be caused by slow intestinal transit and intestinal flora changes during pregnancy.
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38. ^ Lactose intolerant? Drink more milk Steve Tally
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40. ^ Prevalence, Age & Genetics of Lactose Intolerance - foodreactions.org
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References

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