Abstract

The concept of lactose intolerance is based on evidence that intestinal lactase activity persist into later childhood and throughout life in only a minority of the world’s population. Lactose is the major carbohydrate found in mammalian milk, and lactose powder is widely used as an ingredient by the food industry. Lactose is hydrolyzed by lactase, an endo-enzyme present in the brush border membrane of the small intestine, which is encoded by LCT gene that maps on chromosome 2 (2q21). In most humans, lactase activity reaches a maximum in late pregnancy but declines after 2–3 years of age and reaches a stable low level at age 5–10 years (lactase non-persistence). Only about 35% of the human population can digest lactose beyond the age of about seven or eight, notably northern European-derived populations (lactase persistence). About two thirds of the world’s population undergoes a genetically programmed decrease in lactase synthesis after weaning. In Europe, the persistence or not persistence of the expression of lactase is predominantly associated with so-called point polymorphism C/T 13910. For many years, it was thought that lactase persistence (LP) in humans was the “wild-type” pattern but is now considered to be rather novel for humans and probably adaptative for particular circumstances, whereas the lactase non-persistence ((LNP) is the ancestral type. Lactase persistence is a recent human adaptation and its geographic distribution correlates with the importance of dairying in different human populations. The kinetics of the reduction and the amount of residual lactase has considerable variability between different ethnic groups and even between individuals.

Both, lactase persistence and non-persistence (leading to lactose malabsorbtion) are thus normal phenotypes. However, the reduction up to 50% of lactose is sufficient to ensure effective digestion of lactose. When the low lactase activity does not cause symptoms, it is called “lactose malabsorbtion”. Lactose intolerance occurs when the malabsorption causes symptoms.

Lactose is a key nutrient which provides about half of an infant’s energy needs, but is also a bifidogenic factor and may be involved in promoting innate immunity. The role of lactose in life-long human health may change with age, with key periods being infancy, growth and development, the reproductive years and later life. Nowadays milk and dairy products are often assumed to be the cause of gastrointestinal symptoms and inappropriate avoidance can lead to nutritional inadequacy, particularly for calcium intake and vitamin D status.

If the lactase enzyme activity is inadequate, the unabsorbed lactose is fermented by gut microflora with a production of short fatty acids (SCFA) and gases, thus increasing colonic distention and accelerating the oro-cecal transit time. The variable ability of the colonic microflora to ferment lactose in subjects with intolerance may explain why different subjects have different levels of tolerance. Fermentation of milk improves tolerance to lactose because of the presence of lactic acid bacteria (dairy foods in the form of cheese or yoghourt are better tolerated). Typical gastrointestinal complaints of individuals with the lactase non-persistence phenotype are diarrhoea, nausea, bloating, borborygmi and abdominal pain. Development of symptoms depends on several factors including diet, oro-cecal transit time, distribution and fermentation capacity of gut flora, sensitivity towards chemical and mechanical stimulation of the gut, psychological factors, presence of malnutrition, parasites, intestinal infections, alcoholism. Lactose intolerance is also responsible for many systemic symptoms, such as neurological symptoms (headaches, dizziness, short term memory impairment, vertigo), cardiac arrhythmia, muscle and joint pain, severe tiredness, oral ulcers, sore throat, various allergies and increased frequency of urination. When systemic complaints are present, it is important to exclude allergy to cow’s milk protein, which affects up to 20% of patients with symptoms suggestive of lactose intolerance. There is a wide variability of symptoms among patients, according to the amount of lactose ingested and the patient’s ability to digest it. Generally, foods with a high fat content and osmolarity decrease gastric emptying and reduce the severity of symptoms induced by lactose.

Lactase deficiency or hypolactasia exists in three different conditions: congenital, primary late onset and secondary. The congenital form is an extremely rare autosomal recessive condition in which lactase activity is low or even absent and is associated with a non-sense mRNA. It was a fatal condition before lactose free formulas were available.

The primary late onset hypolactasia is an autosomic recessive condition resulting from the physiological decline of lactase activity of intestinal cells, which does not occur before the age of two years. Mostly, constitutional lactase deficiency manifests itself after age of 5 to 6 years in white populations.

The secondary hypolactasia or temporary lactase deficiency occurs when a mucosal damage causes atrophy of the small bowel villi such as rotavirus infection, celiac disease, giardiasis, Crohn’s disease, radiation enteritis and other.

The gold standard of lactose malabsorption is the measurement of lactase in mucosal biopsies from the duodenum. Limitations are the patchy expressions of lactase and the invasiveness of the test. Measurement of the stool pH and/or the presence of reducing sugars in the stools are indirect indications of a carbohydrate malabsorption. The lactose hydrogen breath test depends upon the presence of colonic hydrogen producing bacteria flora. The lactose tolerance test is considered to be less sensitive than the lactose breath test. Most lactose tolerance tests (LTT) are with pure lactose, at the upper limit of what is an acceptable intake from food. It is therefore proposed that, for clinical purposes, Dairy Food Tolerance (DFT) tests replace LTT. Genetic tests establish lactase non-persistence and the 13910T genotype correlated with other tests for lactose malabsorption. A positive genetic test for lactase non-persistence indicates a decline in lactase activity but does not give information on actual patients symptoms. In children, genotyping could only be used as a rule out test since it does not tell anything about the age at which a child with homozygote CC genotype begins to decrease lactase expression. A new concept of lactose intolerance is based on the onset of gastrointestinal symptoms following a blinded, single-dose challenge of ingested lactose by an individual with lactose malabsorption. Some lactose maldigesters began to be adapted to tolerate lactose, and that with long term milk consumption their metabolic products of colonic microflora changed, as a result metabolic adaptations occurred. Treatment of lactose intolerance should not be primarily aimed at reducing malabsorption but rather improving gastrointestinal symptoms. Restriction of lactose intake (at least 12 g lactose – equivalent to 250 ml milk) may be associated with lactase supplementation and if typical abdominal symptoms persist with a trial of a diet low in FODMAPs.

Lactobacillus reuteri in standard dosage is an effective treatment option. Other strategies for management of lactose intolerance may include gut decontaminating agents such as rifaximin.

The restriction of dairy products may leads to a reduction of intake of substances such as calcium, phosphorus and vitamins.