Lactose intolerance

Lactose intolerance
Specialty	Endocrinology
Frequency	65%, 10%

Lactose intolerance^[1] is the condition in which lactase, an enzyme needed for proper metabolization of lactose (a sugar that is a constituent of milk and other dairy products), is not produced in adulthood. A lactose tolerance test, a hydrogen breath test, or a stool acidity test is required for a clinical diagnosis [2].

With lactose intolerance, the result of consuming too much lactose is excess gas production and often diarrhea. Most lactose-intolerant adults can drink about 250 ml (8 oz) of milk per day without severe symptoms (McGee 2004; Swagerty et al, 2002).^[2]

Most adults in the world are lactose-intolerant.^[3] The majority of humans stop producing significant amounts of lactase sometime between the ages of two and five. A relatively recent genetic change caused some populations, including many northern Europeans, to continue producing lactase into adulthood. However, these lactose-tolerant populations are in the minority. Lactose intolerance is an autosomal recessive trait, while lactase-persistence is the dominant allele.The Gene for the enzyme Lactase is a Dominant Allele. The gene is expressed and the enzyme synthesized if atleast one of the two genes are able to express properly. Only when both the gene expressions are affected, the lactase enzyme synthesis is reduced and because of reduced Lactase enzyme, lactose cannot be digested.

Biology

The normal mammalian condition is for the young of a species to lose the ability to digest milk sugar (lactose) effectively after the end of the weaning period (a species-specific length of time often equal to roughly 3% of lifespan). In humans, lactase production usually drops about 90% during the first four years of life, although the exact drop over time varies widely. However, certain human populations have undergone a mutation on chromosome 2 which results in a bypass of the common shutdown in lactase production, allowing members of these populations to continue consumption of fresh milk and other milk products throughout their lives.

There is some debate on exactly where and when the mutation(s) occurred. Some argue for separate mutation events in Sweden (which has one of the lowest levels of lactose intolerance in the world) and the Arabian Peninsula around 4000 BCE. However, others argue for a single mutation event in the Middle East at about 4500 BC which then subsequently radiated. Some sources suggest a third and more recent mutation in the East African Tutsi. Whatever the precise origin in time and place, most modern Western Europeans and people of Western European ancestry show the effects of this mutation (that is, they are able to safely consume milk products all their lives) while most modern East Asians, sub-Saharan Africans and native peoples of the Americas and Pacific Islands do not (making them lactose intolerant as adults)[3].

Lactose intolerance can also occur due to Coeliac disease, as coeliac disease damages the villi in the small intestine that produce lactase. This lactose intolerance is temporary. Lactose intolerance associated with coeliac disease ceases after the patient has been on a gluten-free diet long enough for the villi to recover.

It is interesting that many people who report problems with consuming lactose are not actually lactose intolerant. In a study of 323 Sicilian adults, Carroccio et al (1998) found only 4% were both lactose intolerant and lactose maldigesters, while 32.2% were lactose maldigesters but did not test as lactose intolerant. However, Burgio et al.(1984) found that 72% of 100 Sicilians were lactose intolerant in their study and 106 of 208 northern Italians (i.e., 51%) were lactose intolerant.

Lactose intolerance by group

File:LacIntol-World.png

Human groups	Individuals Examined	Percent Intolerant	Allele frequency
Swedes	N/A	2%[4]	0.14
Europeans in Australia	160	4%[4]	0.20
White people of Northern European and Scandinavian descent	N/A	5%[5][6]	N/A
Danes	???	5%[7]	???
British	N/A	5–15%[8]	N/A
Swiss	N/A	10%[4]	0.316
White Americans	245	12%[4]	0.346
Tuareg	N/A	13%[8]	N/A
Germans	N/A	15%[8]	N/A
Austrians	N/A	15–20%[8]	N/A
Northern French	N/A	17%[8]	N/A
Finns	134	18%[4]	0.424
Central Italians	65	19%[9]	N/A
Indian Children	N/A	20%[5][6]	N/A
African Tutsi	N/A	20%[4]	0.447
African Fulani	N/A	23%[4]	0.48
Bedouins	N/A	25%[8]	N/A
Northern Indians	N/A	27%[10]	N/A
African American Children	N/A	45%[5]	N/A
Indian Adults	150	50%[5][6][11]	N/A
Southern Italians	51	41%[9]	N/A
Saami (in Russia and Finland)	???	25-60%[12]	???
Northern Italians	89	52%[9]	N/A
North American Hispanics	N/A	53%[8]	N/A
Balkans	N/A	55%[8]	N/A
Mexican American Males	N/A	55%[5][6]	N/A
Cretans	N/A	56%[5]	N/A
African Maasai	21	62%[13]	N/A
Southern French	N/A	65%[8]	N/A
Greek Cypriots	N/A	66%[5][6]	N/A
North American Jews	N/A	68.8%[5][6]	N/A
Southern Indians	N/A	70%[10]	N/A
Sicilians	100	71%[14][15]	N/A
South Americans	N/A	65–75%[8]	N/A
Rural Mexicans	N/A	73.8%[5][6]	N/A
African Americans	20	75%[4]	0.87
Lebanese	75	78%[16]	N/A
Central Asians	N/A	80%[8]	N/A
Alaskan Eskimo	N/A	80%[5][6]	N/A
Australian Aborigines	44	85%[4]	0.922
African Bantu	59	89%[4]	0.943
Asian Americans	N/A	90%[5][6]	N/A
Chinese	71	93%[4]	0.964
Southeast Asians	N/A	98%[5][6]	N/A
Thais	134	98%[4]	0.99
American Indians	24	100%[4]	1.00

The statistical significance varies greatly depending on number of people sampled.

Lactose intolerance increases with increasing age. At ages 2–3 y, 6 y, and 9–10 y, the amount of lactose intolerance is

• 0%, 0%, and 6% in white Americans
• 18%, 30%, and 47% in Mexican Americans
• 25%, 45%, and 60% in black South Africans
• approximately 30%, 80%, and 85% in Chinese and Japanese
• 30–55%, 90%, and >90% in Mestizos of Peru^{[17] [18]}

Chinese and Japanese people typically lose between 80 and 90 percent of their ability to digest lactose within three to four years of weaning. Ashkenazi Jews can keep 20-30 percent of their ability to digest lactose for many years.Cite error: A <ref> tag is missing the closing </ref> (see the help page).^[19] Of the 10% of the Northern European population that develops lactose intolerance, the development of lactose intolerance is a gradual process spread out over as many as 20 years.^[20]

Aetiology

Without lactase, the lactose in milk remains uncleaved and unabsorbed. Lactose cannot pass easily through the intestinal wall into the bloodstream, so it remains in the intestines. Soon, gut bacteria adapt to the relative abundance of lactose (relative to other sugars like glucose) and switch over to metabolizing lactose. Along the way they produce copious amounts of gas by fermentation.

The gas causes a range of unpleasant abdominal symptoms, including stomach cramps, bloating, flatulence and diarrhea. Like other unabsorbed sugars, e.g. mannitol, the lactose raises the osmotic pressure of the colon contents, preventing the colon from reabsorbing water and hence causing a laxative effect to add to the excessive gas production.

Diagnosis

Since the majority of northern Europeans and some Mediterranean Europeans have the mutation rendering them lactose-tolerant, lactose intolerance is widely regarded as a medical condition in Europe and North America. A fair proportion of patients with symptoms of irritable bowel syndrome actually have lactose intolerance without knowing it. ^{[citation needed]}

A simple test can clarify the issue: after an overnight fast, 50 grams of lactose (in a solution with water) are swallowed. If the lactose cannot be digested, enteric bacteria metabolize it and produce hydrogen. This can be detected in the air the patient exhales. The test takes about 2 to 3 hours. A medical condition with similar symptoms is fructose malabsorption.

Measuring the 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 an elevation of typically 50-100% within 1-2 hours.

A definitive diagnosis for research purposes can be obtained by analysis of an intestinal biopsy for lactase activity.

Although not as precise a test, an estimate of lactose intolerance can be made as follows: Drink two cups of milk on an empty stomach and watch for signs of intestinal discomfort over the next several hours. The following day, eat two ounces of hard cheese or drink two cups of lactose-free milk. If symptoms are experienced only on the first day, the individual may be lactose intolerant. If symptoms are experienced on both days, the individual may have an allergy to dairy products, which is unrelated to lactose intolerance.

Some individuals are able to self-diagnose without intentionally testing themselves, simply by realizing in retrospect that their symptoms always correspond to prior lactose consumption. This, however, is the least reliable of the methods herein described, as peoples' memories are imperfect. In addition, it is harder to isolate one definite cause without a formal test.

Managing lactose intolerance

There is no "treatment" or "cure" to lactose intolerance. There have been some cases where the intolerance has somehow diminished with time; this has not been studied scientifically, however, and whether it is a case of desensitization remains to be seen. It should be remembered that lactose intolerance is not a binary (all-or-nothing) condition: the reduction in lactase production, and hence, amount of lactose that can be tolerated varies from person to person, and may change with age. The management of lactose intolerance involves avoiding lactose-containing products, use of alternative products or lactase enzyme medication (such as pills that are taken when eating or drinking a product containing lactose).

Acclimating the body to dairy products

A study by Purdue University found that people can acclimate themselves to dairy products. Consuming small quantities of dairy products several times a day over a couple of weeks will train bacteria in the large intestine to more effectively break down lactose.[4]

Avoiding lactose-containing products

Since each individual's tolerance to consumed lactose varies, according to the National Institute of Health, "Dietary control of lactose intolerance depends on people learning through trial and error how much lactose they can handle."[5]

Many people are more tolerant of yogurt than milk because it contains lactase produced by the bacterial cultures used to make the yogurt. Also, hard cheeses (e.g. Swiss) produce far less reaction than the equivalent amount of milk because the cheese making and ageing processes greatly reduce the amount of lactose. A typical Swiss or Cheddar might contain 5% of the lactose found in whole milk, while long-aged cheeses contain almost no lactose at all.[6]

It is important for lactose intolerant people to especially be careful in avoiding products that whilst not apparently dairy (or are dairy but normally contain low amounts of lactose) nonetheless contain lactose. Such products include commercial sausages (notably frankfurters), medications which may contain lactose as a filler, most meal replacement and protein bars, cottage cheese, and even yogurts containing carageenan or gelatin.

Kosher products labeled as Pareve do not contain any dairy products and are, therefore, lactose free.

Alternative products

Reduced or entirely lactose-free products (using milk substitutes, soy milk, almond milk, or rice milk) are available allowing lactose-intolerant people to maintain approximately the same diet as those who are tolerant, without having to purchase medication or significantly alter their eating habits.

The food industry has successfully managed to create high quality low-lactose or entirely lactose-free products to replace the regular items. Lactose-free milk can be produced by passing milk over lactase enzyme bound to an inert carrier: once the molecule is cleaved, there are no lactose ill-effects. Alternatively, a harmless bacterium such as L. acidophilus may be added, which affects the lactose in milk the same way it affects the lactose in yogurt (see above).

Finland has had "HYLA" (acronym for hydrolysed lactose) products available for many years, even though the number of lactose intolerant people there is relatively small. These low-lactose level cow's milk products, ranging from ice cream to cheese, use a Valio patented chromatographic separation method to remove lactose. The ultra-pasteurization process, combined with aseptic packaging ensures a long shelf-life. Recently, the range of low-lactose products available in Finland has been augmented with milk and other dairy products (including ice cream) that contain no lactose at all. The remaining about 20% of lactose in HYLA products is taken care of enzymatically. These typically cost 2-4 times more than equivalent products containing lactose. Valio also markets these products in Sweden.

Many countries have similar product lines, and new consumer products continue to become available. In America over recent years (1990–2000) there has been a notable increase of available lactose-reduced and lactose-free dairy products; examples being cottage cheese, American cheese and ice cream.

Lactase-enzyme medication

When lactose avoidance is not possible, or on occasions when a person chooses to consume such items, then lactase enzyme medicinal products may be used.^[21] This reduces symptoms and allows an "increase (in) the dairy consumption and promote health of people".^[22]

Milk may be preincubated with liquid lactase-enzyme drops but is of limited practicality as this must be prepared some hours before consumption. More commonly β-galactosidase is provided in tablet or capsule formulations which are taken with food. However the enzyme is inactivated by gastric acidity,^[23] making these both more expensive and less effective than prehydrolyzed milk. They are appropriate for use with solid dairy products.^[21]

Lactase-enzyme medication has an advantage over non-dairy products in that alternative provision must then be made for adequate calcium intake, especially in children.^[24]

Lactose levels in foods

The following are lactose levels in foods which commonly set off lactose-intolerance symptoms [7]. Reducing lactose intake, without cutting it out completely, is helpful for some sufferers.

Dairy product	Lactose Content
Yogurt, plain, low-fat, 240 mL (1 cup)	5 g
Milk, reduced fat, 240 mL	11 g
Swiss cheese, 28 g (1 oz.)	1 g
Ice cream, 120 mL (½ cup)	6 g
Cottage cheese, 120 mL	2-3 g

History of diagnosis

Lactose intolerance was recognized by Hippocrates (460-370 B.C.).^[25]Hippocrates noted gastrointestinal upset and skin problems in some who consumed milk. However it was only in the last few decades that the syndrome was more widely described by modern medical science.

The condition was first recognized in the 1950s and 1960s when various organizations like the United Nations began to engage in systematic famine-relief efforts in countries outside Europe for the first time. Holzel et al (1959) and Durand (1959) produced two of the earliest studies of lactose intolerance. As anecdotes of embarrassing dairy-induced discomfort piled up, the First World donor countries could no longer ascribe the reports to spoilage in transit or inappropriate food preparation at the recipient end in the Third World.

Since the first nations to industrialise and develop modern scientific medicine were dominated by people of Western and Northern European descent, adult dairy consumption was long taken for granted. Westerners for some time did not recognize that the majority of the human ethnogenetic groups could not consume dairy during adulthood. Although there had been regular contact between Europeans and non-Europeans throughout history, the notion that large-scale medical studies should be representative of the ethnic diversity of the human populations (as well as all genders and ages) did not become well-established until after the American Civil Rights Movement.

Since then, the relationship between lactase and lactose has been thoroughly investigated in food science due to the growing market for dairy products among non-Europeans.

Originally it was hypothesised that gut bacteria such as E. coli produced the lactase enzyme needed to cleave lactose into its constituent monosaccharides and thus become metabolisable and digestible by humans. Some form of human-bacteria symbiosis was proposed as a means of producing lactase in the human digestive tract. Genetics and protein analysis techniques by the early 1970s revealed this to be untrue; humans produce their own lactase enzyme natively in intestine cells.

Approximately 70% of the global population cannot tolerate lactose in adulthood.^{[citation needed]} Thus, some argue that the terminology should be reversed, lactose intolerance should be seen as the norm, and the minority groups should be labelled as having lactase persistence. A counter argument to this is that the cultures that don't generally consume unmodified milk products have little need to discuss their intolerance to it, leaving the cultures for which lactose intolerance is a significant dietary issue to define its terminology.

History of genetic prevalence

Lactose intolerance has been studied as an aid in understanding ancient diets and population movement in prehistoric societies. Milking an animal vastly increases the efficiency of raising it in regards to the calories that can be extracted compared to consumption of its meat alone. It is not surprising then, that consuming milk products became an important part of the agricultural way of life in the Neolithic. Given that at this time the majority of the population was lactose intolerant, it is believed that most of the milk was used to make mature cheeses, which lose most of the lactose and can be safe to eat.

However, cheese takes a long time to produce and one of the theories for the prevalence of lactose tolerance in northern Europe and certain parts of the near east is that, at a time of famine, it became advantageous to consume the milk directly, without having to wait for it to mature. A small number of others believe that the practical advantages of the mutation have been over emphasised and that it is no more than chance that this gene was allowed to flourish in certain societies.^{[citation needed]}

In Europe, Roman sources attest that milk was often used as a purgative (to induce vomiting and diarrhea), and horse milk is suggested as the best, with goat's milk as the worst. This corresponds to the amount of lactose in the milk; horse milk has a great deal of lactose, and goat's milk not very much. Roman authors also remark that the people of northern Europe, particularly Britain and Germany drank unprocessed milk (as opposed to the Romans who made cheese).^{[citation needed]} This corresponds very closely with modern European distributions of lactose intolerance, where the people of Britain, Germany and Scandinavia have a good tolerance, and those of southern Europe, especially Italy, have a poorer tolerance.[8]

In east Asia, historical sources also attest that the Chinese did not consume milk, whereas the nomads that lived on the borders did. Again, this reflects modern distributions of intolerance. China is particularly notable as a place of poor tolerance, whereas in Mongolia and the Asian steppes horse milk is drunk regularly. Here they even make an alcoholic beverage, called Kumis, from horse milk (although the fermentation process reduces the amount of lactose present). This tolerance is thought to be advantageous as the nomads do not settle down long enough to process mature cheese or may find themselves regularly going through brief periods of starvation; and given that their prime source of income is generated through horses, to ignore their milk as a source of calories would be greatly detrimental.

The African Fulani have a nomadic origin and their culture once completely revolved around cow, goat, and sheep herding. Dairy products were once a large source of nutrition for them. As might be expected if lactase persistence evolved in response to dairy product consumption, they are particularly tolerant to lactose (about 77% of the population). Many Fulani still live in Guinea-Conakry, Burkina Faso, Mali, Nigeria, Niger, Cameroon, and Chad.

Additional information

• 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.^[26]
• Many global cat breeds (Asian breeds in particular) share the mammalian lactose sensitivity, unlike many European breeds that have a mutation similar to the European human mutation.
• Interestingly, although many Maasai are found by standard tests to have substantial amounts of lactose intolerance, they are able to consume large amounts of dairy products including milk without exhibiting any symptoms.

See also

• Gastroenterology
• Sucrose intolerance

References

• HOLZEL, A., V. SCHWARZ AND K. W. SUTCLIFFE, "Defective lactose absorption causing malnutrition in infancy", The Lancet 1: 1126, 1959.
• DURAND, P. "Lactosurie et saccharosurie", In: BibI. Paediat. IV. Carbohydrate Metabolism in Children, edited by E. Rossi, E. Gautier, and J. W. Weber. Basel: S. Karger, 1959, pp. 496-502.
• BAYLESS, T. M., AND N. S. ROSENSWEIG. "A racial difference in incidence of lactase deficiency", Journal of the American Medical Association, 197: 968, 1966.
• CUATRECASAS, P., D. H. LOCKWOOD AND J. R. CALDWELL, "Lactase deficiency in the adult", The Lancet 1: 14, 1965.
• HUANG, S. S., AND T. M. BAYLESS, "Milk and lactose intolerance in healthy orientals", Science, 160:83, 1968.
• GILAT T., R. KUHN, E. GELMAN, ET AL. "Lactase deficiency in Jewish communities in Israel". Am. J. Digest. Diseases, 15: 895, 1970.
• A. Carroccio, G. Montalto, G. Cavera, A. Notarbatolo (1998). "Lactose Intolerance and Self-Reported Milk Intolerance: Relationship with Lactose Maldigestion and Nutrient Intake". Journal of the American College of Nutrition. 17 (6): 631–636.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• McGee, Harold (2004). "Milk after infancy: dealing with lactose". On Food and Cooking (Revised Edition). Scribner. pp. pp 14–15. ISBN 0-684-80001-2. {{cite book}}: |pages= has extra text (help)
• Huang S-S, Bayless T M (1968). "Milk and Lactose Intolerance in Healthy Orientals". Science. 160: 83–84. PMID 5694356.
• Patel YT, Minocha A (2000). "Lactose intolerance: diagnosis and management". Compr Ther. 26 (4): 246–50. PMID 11126094.
• Rusynyk RA, Still CD (2001). "Lactose intolerance" (PDF). J Am Osteopath Assoc. 101 (4 Suppl Pt 1): S10-2. PMID 11392211.
• Swagerty DL Jr, Walling AD, Klein RM (2002). "Lactose intolerance". Am Fam Physician. 65 (9): 1845–50. PMID 12018807.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Swallow DM (2003). "Genetics of lactase persistence and lactose intolerance". Annu Rev Genet. 37: 197–219. PMID 14616060.
• Vesa TH, Marteau P, Korpela R (2000). "Lactose intolerance". J Am Coll Nutr. 19 (2 Suppl): 165S–175S. PMID 10759141.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Footnotes

External links

• United States National Institutes of Health page regarding lactose intolerance
• Types, symptoms, causes, treatments, and prevalence of Lactose Intolerance
• Study Detects Recent Instance of Human Evolution (Finding that lactose tolerance is a recent change)
• Scientific American: African Adaptation to Digesting Milk Is "Strongest Signal of Selection Ever" (East African cattle herding communities rapidly and independently evolved ability to digest lactose)
• University of Alabama powerpoint slides of Dr. Bindon for Nutritional Anthropology course; includes a global map of lactose intolerance