Lactose intolerance pathophysiology

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Lactase Biology

The gene is expressed and the enzyme synthesized if at least one of the two genes are present. Only when both gene expressions are affected is lactase enzyme synthesis reduced, which in turn reduces lactose digestion.[1]. Lactose tolerance(lactase persistence) is the dominant allele. Lactose intolerance is an autosomal recessive trait.

The normal mammalian condition is for the young of a species to experience reduced lactose (milk sugar) production at the end of the weaning period (a species-specific length of time). In non dairy consuming societies, 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 a mutation on chromosome 2 which results in a bypass of the common shutdown in lactase production, making it possible for members of these populations to continue consumption of fresh milk and other dairy products throughout their lives.

Pathological lactose intolerance can occur due to Coeliac disease, which 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.

Certain 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

Lactose Intolerance by Region (African countries are only a rough guess)

Most Japanese can consume 200 ml (8 fl oz) of milk without severe symptoms (McGee 2004; Swagerty et al, 2002).[2]

Human groups Individuals Examined Percent Intolerant Allele frequency
Dutch N/A 1%[3] N/A
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 N/A 5%[7] N/A
British 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
Eastern Slavs (Russians, Belarusians, Ukrainians) N/A 15%[9] N/A
Northern French N/A 17%[8] N/A
Finns 134 18%[4] 0.424
Central Italians 65 19%[10] 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%[11] N/A
African American Children N/A 45%[5] N/A
Indian Adults 150 50%[5][6][12] N/A
Southern Italians 51 41%[10] N/A
Saami (in Russia and Finland) N/A 25–60%[13] N/A
Northern Italians 89 52%[10] 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%[14] 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%[11] N/A
Sicilians 100 71%[15][16] 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
Kazakhs from northwest Xinjiang 195 76.4% [17]
Lebanese 75 78%[18] 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
Inner Mongolians 198 87.9%[17]
African Bantu 59 89%[4] 0.943
Asian Americans N/A 90%[5][6] N/A
Northeastern Han Chinese 248 92.3%[17]
Chinese 71 93%[4] 0.964
Southeast Asians N/A 98%[5][6] N/A
Thais 134 98%[4] 0.99
Native Americans 24 100%[4] 1.00

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

Lactose intolerance levels also increase with age. At ages 2 - 3 yrs., 6 yrs., and 9 - 10 yrs., the amount of lactose intolerance is, respectively:

  • 6% to 15% in white Americans and northern Europeans
  • 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[19][20]

Chinese and Japanese populations 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. [21] 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.[22]

References

  1. [1] Soy Nutrition
  2. Studies on the etiology of milk intolerance in Japanese adults, Yoshida Y, Sasaki G, Goto S, Yanagiya S, Takashina K, Gastroenterol Jpn.;10(1):29–34, 1975
  3. Genetics of lactose digestion in humans., Flatz, G. , Advances in Human Genetics, 1987
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 Lactose and Lactase, Norman Kretchmer, Scientific American, October, 1972
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 Identification of a variant associated with adult-type hypolactasia, Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I, Nat Genet. 2002 Feb;30(2):233–7
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Lactose Intolerance: The Molecular Explanation, UC Davis Nutritional Genomics website
  7. Anne Charlotte Jäger, "Laktose-intolerans: Gentest for laktose-intolerans - hurtig og billig diagnostik", DSKB-NYT, no. 1, February 2006.
  8. 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 Michael de Vrese, Anna Stegelmann, Bernd Richter, Susanne Fenselau, Christiane Laue and Jürgen Schrezenmeir,"Probiotics—compensation for lactase insufficiency", American Journal of Clinical Nutrition, Vol. 73, No. 2, 421S-429s, February 2001.
  9. Prevalence of the lactase deficiency among the population of the northwestern region of Russia
  10. 10.0 10.1 10.2 Primary adult lactose malabsorption in Italy: regional differences in prevalence and relationship to lactose intolerance and milk consumption, LT Cavalli-Sforza, A Strata, A Barone and L Cucurachi, American Journal of Clinical Nutrition, Vol 45, 748–754, 1987
  11. 11.0 11.1 Lactose intolerance in North and South Indians, Tandon RK, Joshi YK, Singh DS, Narendranathan M, Balakrishnan V, Lal K., Am J Clin Nutr 1981;35:943–6, 1981.
  12. Lactose malabsorption in apparently healthy adults in northern India, assessed using lactose hydrogen breath test, Rana SV, Bhasin DK, Naik N, Indian Journal of Gastroenterology, Volume 23, Issue 2, p. 78, 2004
  13. A. Kozlov, D. Lisitsyn, "Hypolactasia in Saami subpopulations of Russia and Finland", Anthropologischer Anzeiger, 55(3-4):281–287, 1997.
  14. Lactose malabsorption among Masai children of East Africa, RT Jackson, MC Latham, Am J Clin Nutr. 1979 Apr;32(4):779–82.
  15. Prevalence of primary adult lactose malabsorption and awareness of milk intolerance in Italy, G Roberto Burgio, Gebhard Flatz, Cristiana Barbera, Rosario Patan, Attilio Boner, Cinzia Cajozzo, and Sibylle D Flaiz, The American Journal of Clinical Nutrition 39: pp 100–104, January 1984.
  16. Lactose Intolerance, Tuula H. Vesa, Philippe Marteau, and Riitta Korpela, Journal of the American College of Nutrition, Vol. 19, No. 90002, 165S-175S (2000)
  17. 17.0 17.1 17.2 Prevalence of primary adult lactose malabsorption in three populations of northern China, Wang YG, Yan YS, Xu JJ, Du RF, Flatz SD, Kühnau W, Flatz G., Hum Genet. 1984;67(1):103-6.
  18. Lactose intolerance in the Lebanese population and in “Mediterranean lymphoma”, Salah M. Nasrallah, The American Journal of Clinical Nutrition 32 , pp. 1994–1996, October, 1979.
  19. Genetics and epidemiology of adult-type hypolactasia, Sahi T., Scand J Gastroenterol Suppl ;29:202:7–20, 1994
  20. Lactose malabsorption in Mexican-American children, Woteki CE, Weser E, Young EA, Am J Clin Nutr;29:19–24, 1976
  21. Genetics of lactase persistence and lactose intolerance, Swallow DM., Annu Rev Genet ;37:197 - 219, 2003.
  22. Systemic lactose intolerance: a new perspective on an old problem, S B Matthews, J P Waud, A G Roberts and A K Campbell, Postgraduate Medical Journal;81:167 - 173, 2005.