Lactose Intolerance Etiology

Pathogenesis (development of disease)

Lactose is normally broken down in the small intestine by the lactose-splitting enzyme lactase (ß-galactosidase). When this enzyme is not adequately produced or is absent, maldigestion (inadequate breakdown of food components) occurs in affected individuals. As a result, the accumulation of lactose, in an osmotically active form, in deeper sections of the small and large intestine, as well as its increased microbial degradation, whereby methane, carbon dioxide, hydrogen, etc. are produced, leads to abdominal complaints of varying degrees. Flatulence (flatulence) and diarrhea (diarrhea), among other symptoms, may result. The various forms of lactose intolerance include primary lactase deficiency (subdivided into hereditary/congenital (congenital) and acquired lactase deficiency) and secondary lactase deficiency (disease-related lactase deficiency). Hereditary lactase deficiency is extremely rare and causes diarrhea (diarrhea) even in infants. The cause of hereditary lactase deficiency is a genetic defect, whereby the enzyme lactase is absent from birth or can only be produced to a very low degree (alactasia). Only a dozen cases of this disease have been described worldwide. Acquired lactase deficiency (primary lactase deficiency) is the most common form of lactose intolerance. The prevalence (disease incidence) is 7-22% (in Germany). Lactase activity decreases continuously with increasing age. The causes of this are still largely unknown. It is suspected that age-related changes in the intestinal mucosa surface (surface of the intestinal mucosa) impair the activity of lactase. Furthermore, damage to the mucosa of the small intestine (small intestinal mucosa) due to viral infections is discussed. In approx. 70% of the world population, the activity of lactase drops to 10% of the original activity after weaning and represents the most frequent reason for an enzyme deficiency. In countries with a high prevalence of lactose intolerance (such as Asia or Africa), this occurs as early as 2 to 3 years of age, whereas in Germany enzyme activity does not decline until adolescence. Secondary lactase deficiency can be the result of a primary intestinal disease. Lactose intolerance often occurs in celiac disease (gluten-induced enteropathy). With complete abstinence from the specific food components, the primary disease heals and the secondary deficiency regresses. Lactase deficiency also develops in many cases after gastric resection (partial stomach removal) or after antibiotic therapy due to the non-physiological load on the small intestine (dysbiosis). Notice. The individually tolerated amounts of lactose vary greatly. Usually, people with lactose intolerance tolerate meals with amounts of up to 12,000 mg of lactose without showing symptoms of lactose intolerance! In a few isolated cases, amounts of 3,000 mg or more of lactose trigger symptoms. (EFSA, 2010). In addition, there is a small group of people who have a disorder in galactose metabolism (so-called galactosemia) and have to eat a diet practically free of galactose and thus also free of lactose. In addition to lactose intolerance, glucose–galactose malabsorption (poor “absorption” of glucose and galactose) can also be the cause of gastrointestinal symptoms (complaints of the gastrointestinal tract) after intake of lactose, since lactose is hydrolytically cleaved into galactose and glucose before it is absorbed. Glucose-galactose malabsorption is a rare autosomal recessive disorder in which the transport of glucose and galactose into the intestinal mucosa cells (mucosal cells of the intestine) is impaired. The unabsorbed monosaccharides cause an osmotic influx of water into the intestinal lumen (bowel), which can lead to diarrhea (diarrhea), sometimes severe. The symptoms of glucose-galactose malabsorption can be controlled by a fructose-based diet that is free or low in glucose, galactose, lactose, and sucrose.

Etiology (Causes)

Biographic causes

  • Genetic burden
    • Genetic risk depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: MCM6
        • SNP: rs4988235 in the gene MCM6
          • Allele constellation: CT (20% are lactose intolerant).
          • Allele constellation: CC (77% are lactose intolerant).
  • Ethnic origin
    • Differential frequency of lactase deficiency in different ethnic populations:
      • Asia 80-100%
      • Africa 70-95 %
      • USA 15-80 %
      • Europe 15-70 %
      • Germany about 15%
  • Skin type – dark-skinned (lactase deficiency).

Behavioral causes

  • Consumption of stimulants
    • Chronic alcohol abuse

Causes related to disease

Other causes

  • Gastrectomy (complete removal of the stomach) or gastric resection (partial removal of the stomach).
  • Chemotherapy
  • Radiatio (radiotherapy)