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Causes of lactose intolerance

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Lactose intolerance occurs when lactose isn’t absorbed properly – a result of lactase deficiency. Lactase is an enzyme that splits the milk sugar lactose to produce the sugars glucose and galactose.

The factors involved in lactase deficiency differ for the various types of lactose intolerance.

Primary lactose intolerance

Primary lactose intolerance is genetically determined. With this type of lactose intolerance, the production of lactase decreases after weaning because milk is slowly replaced with other foods.

It’s normal for lactase production to decrease with age. But in the case of lactose intolerance, the lactase production falls off sharply, making milk products difficult to digest. 

In dairy-farming populations, a protective genetic mutation developed to ensure that lactase is still available to digest lactose. This mutation is at position -13910 on the lactase gene. A cytosine (C = decrease in lactase production) is exchanged for a thymidine (T = persistent production of lactase) in the DNA.

Other genetic variants in the lactase gene that are linked to continued lactase production have also been discovered. These polymorphisms are -13907 C → G, -13913 C → T, -13914 G → A and -13915 T → G.

People who don’t carry these protective mutations experience a decrease in lactase production over the course of their lives. As a result, they’re lactose intolerant. 

Primary lactase deficiency usually begins after the age of two, when the body begins to produce less lactase. It develops over time, and symptoms generally appear in late adolescence or early adulthood.   

Secondary lactose intolerance

Secondary lactose intolerance occurs due to injury to the small intestine, resulting in a loss of lactase-containing epithelial cells at the tips of the villi. This condition is temporary and develops secondarily to another illness or disease. 

Illnesses such as a gastroenteritis or giardiasis (intestinal infections caused by a giardia parasite) can cause secondary lactose intolerance. Once the illness resolves, the lactase levels will be restored within 2-3 days. 

More serious illnesses such as celiac disease, Crohn’s disease and HIV cause inflammation in the gut wall, which may lead to a temporary decrease in lactase production. Treatment of these underlying conditions generally restores lactase levels, although this process can take time.

Certain medications and treatments (e.g. antibiotics, chemotherapy and radiation) can also cause secondary or temporary lactose intolerance.

Secondary lactose intolerance can occur at any age, but it’s most common in infants. Because primary lactose intolerance is rare in this age group, diseases causing secondary lactose intolerance should be considered. 

Infants with severe malnutrition may also develop intestinal atrophy, where the epithelial cells on the villi degenerate due to lack of nutrition. This leads to lactase deficiency and is commonly seen in developing countries. 

Developmental lactose intolerance

Developmental lactose intolerance occurs in babies who are born prematurely. Lactase is deficient in the small intestine until about the 34th week of pregnancy. At this point, lactase activity is only about 30% of what it is in full-term infants. Lactase maturation occurs predominantly in the third trimester. 

Therefore, infants that are born prematurely have lactase deficiency due to incomplete development. This usually improves quickly and lasts only for a short period of time after birth.

Congenital lactose intolerance

This refers to a genetic disorder in which no lactase is produced by the small intestine from birth. This is a very rare cause of lactose intolerance. 

The prevalence of lactose intolerance

The true prevalence of lactose intolerance is difficult to determine because of how lactose intolerance is defined and studied.

No studies have reported the prevalence based on the “gold standard” definition: gastrointestinal symptoms that are more severe after the ingestion of 50g of lactose as a single dose by a lactose-malabsorbing individual, where no symptoms are experienced when the individual receives a placebo.

Self-reported symptoms can be biased. Therefore, confirmation of lactose malabsorption is required to rule out other causes. In addition, lactose malabsorption doesn’t always result in symptoms, which means that the prevalence of lactose malabsorption could exceed the prevalence of lactose intolerance.

A systemic review and meta-analysis from 2017 estimated the global prevalence of lactose malabsorption as 68%, ranging from 28% in Western, Southern and Northern Europe to 70% in the Middle East.

Assessing the global prevalence of lactose intolerance using data from genetic studies, the estimate was 74%. With lactose tolerance and hydrogen breath tests, the prevalence was 55% and 57% respectively.

According to a study by Storhaug et.al, the prevalence of lactose intolerance in South Africa is 81%. Another source, Rediscoverdairy.co.za, reports that the prevalence of lactose intolerance is 11% in this country (although the prevalence of self-diagnosed lactose intolerance is much higher).

These inconsistencies in the data may be due to the ethnic differences seen with lactose intolerance.

Interestingly, in populations with a high diary intake, as little as 2% of the population have lactase deficiency. It also seems that the prevalence of lactose malabsorption in population groups that consume reasonable amounts of lactose may exceed the prevalence of lactose intolerance symptoms.

Different factors at play
Factors that affect the prevalence of lactose intolerance in population groups include the following:

Age
This is an important contributor to the prevalence rate of lactose malabsorption and intolerance. Every population group has lower rates of lactose intolerance in the youngest age groups, especially in individuals under the age of six.

In addition, the prevalence of lactose intolerance is very low in children of Northern European descent. In African American, Hispanic, Asian and American Indian populations, lactose intolerance rates are about 50% higher in childhood compared to rates observed among Caucasian children.

Ethnicity
The prevalence of lactose intolerance is far higher among Hispanic people (50-80%), black and Ashkenazi Jewish people (60-80%), and Asian and American Indian people (almost 100%) compared with Northern European people.

There’s a clear North-South divide when it comes to lactose intolerance. In the northern countries, almost 90% of the populations are able to digest lactose, while the rate is around 30% in the southern regions of Europe, and only 2% in regions closer to the equator.

It’s believed that Northern Europeans have evolved to produce lactase at a later age. This theory stems from the fact that there’s less sunlight in the north of Europe, which decreases the amount of vitamin D the body can make. Vitamin D is necessary for bone growth and regeneration through the absorption of calcium, and lactose can help with the absorption of this mineral. This evolution hasn’t been necessary in areas with abundant sunshine.

Culture
Cultural factors also play a role. The Japanese population originates from populations that were lactose intolerant, but Japanese people who have grown up in a society where drinking milk is normal are no longer affected by the digestive problem.

Similarly, the African Tuareg and Masai tribes, who farm cattle and have a high milk intake, are not lactose intolerant.

Reviewed by Kim Hofmann, registered dietitian, BSc Medical (Honours) Nutrition and Dietetics, BSc (Honours) Psychology. August 2018.

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