Milking Our Genes: Lactose Intolerance Explained

Lactose intolerance is still common throughout the world but the development of dairy farming in Northern Europe led to the evolution of individuals who can digest milk.

Most people cannot drink milk as adults, despite its importance as a cheap and nutritious food source. Scientists have shown that the gene which enables adults to digest milk appeared, and became predominant in Northern Europe, as dairy farming took off. The rapid spread of the lactase gene is an example of the power of natural selection to select for a gene with strong evolutionary advantages.

Symptoms of Lactose Intolerance

Symptoms usually appear 30 minutes to 2 hours after consumption of milk or milk-rich products. These can vary quite significantly in their intensity; commonly, symptoms include nausea, cramps, bloating, diarrhoea and flatulence.

Lactose intolerance is not the same as milk allergies; these are an immune response to milk proteins.

There is no known treatment for lactose intolerance. Unlike milk allergies, intolerant individuals cannot become tolerant by exposure to small, then increasing quantities of lactose. However, lactose intolerance is easily managed by avoiding lactose, particularly as lactose-free milk is available in most supermarkets.

Many of the symptoms are dose-related so avoiding dairy products completely is not usually necessary. Lactose intolerant people can still eat yoghurts and small amounts of hard cheeses to ensure regular consumption of calcium and other essential nutrients.

What Causes Lactose Intolerance?

Milk is a rich source of protein and the carbohydrate lactose, a major source of energy for babies and young children. Lactose cannot be absorbed intact in the gut: the enzyme lactase breaks it down into its component sugars, glucose and galactose, which are easily transported across the gut wall.

Most lactose intolerance in adults is caused by an absence of the lactase enzyme. This is a developmental adaptation. All mammals, including humans, have high levels of expression of lactase in early life when their sole source of food is milk. As weaning takes place, the gene for lactase is gradually switched off and lactase expression decreases. This begins at 2-3 years of age and is generally complete by 5-10 years old. This inability to produce lactase to digest milk is often termed lactase non-persistence.

Lactase non-persistence is seen in the majority of the world’s population, including most of Asia and Africa. For example, in non-pastoral communities, such as the Chinese, only 1% produces lactase into adulthood. Conversely in Northern Europe, particularly Scandinavia, and in some nomadic tribes of the Middle East and Africa, lactase persistence is much more common.

Genes Involved in Milk Digestion

The genetic ability to digest milk can be seen as an example of evolution in action. Domestication of dairy animals and the increasing availability of a nutritious and clean food source led to the selection of the genes for lactase persistence. This gave some early Europeans a huge survival advantage.

Analysis of DNA from skeletons of Neolithic Europeans (between 5800 BC and 5000BC) revealed that the lactase gene was absent. Despite the fact that these were some of the earliest farming communities in Europe, these Europeans would not have been tolerant to milk. Scientists believe that the lactase gene, allowing the digestion of milk, emerged after dairy farming really took hold, such that over 90% of northern Europeans now have the lactase gene.

As the human genome project revealed the complexity of human genetic inheritance and evolution, scientists are studying the genetic variants of the lactase gene. New variants have been discovered in pastoral communities in East Africa which may have evolved independently from and more recently than the European lactase gene.

Attention is now focused on whether persistence of the lactase gene is associated with rising obesity and associated diabetes in Western countries or whether in some cases it is protective. The jury is still out on the long term effects of lactase persistence but, with increasing use of large scale genomic studies, the answer is likely to emerge soon.

Genetic profile affects age of menopause

The average age of menopause in the UK is 51 years. This is partly determined by your lifestyle but recent scientific research is revealing the genes that account for a 50% link with your mother’s age of menopause.

The onset of menopause is associated with various health risks, such as cardiovascular disease, osteoporosis and breast cancer, increasingly important as the population ages. In 1900 the life expectancy for a women in the UK was 50, so many women would not have reached menopause before they died. In 2017, the life expectancy for a women is in the late 80s, at least 35 years after the onset of menopause.

Women are born with a finite number of eggs in their ovaries. During the monthly menstrual cycle, an egg is realised from the ovaries. If no fertilisation takes place, the lining of the uterus is shed in the monthly period. As the levels of fertility hormones change with increasing age, egg production and monthly periods gradually cease, often with accompanying symptoms such as hot flushes.

Menopause is said to have occurred when a woman has not had a period in the preceding 12 months. Natural menopause happens between the age of 40 and 60, with the average at 51 years. Premature menopause, occurring before the age of 40, is also of concern as women have children later in life. It is estimated that 1-5% of women have a premature menopause; in some cases, this is associated with surgery and/or the treatment of cancer. Studies of populations who use no birth control have also shown that fertility wanes significantly about 10 years before menopause occurs.

If you smoke around the time of the menopause, it will hasten its onset by 2 years. This only appears to apply if you smoke 14 or more cigarettes a day; the association does not hold up if you’re a light smoker or smoked in the past.

Although the evidence is clear cut with smoking, the jury is still out on other environmental influences. These include: race, education, BMI, number of children, age of first menstrual cycle, oral contraceptive use, breast feeding, alcohol consumption, altitude and even exposure to sunlight.  Reports are conflicting, partly because of the difficulties of studying menopause, which is defined retrospectively.

The age at which your mother or sister had their last period plays a large part in the timing of your menopause. Studies in twins and in mothers and daughters have revealed that approximately 50% of the timing of your last period is governed by your genetic inheritance. A Danish research team found that women whose mothers had an early menopause had significantly fewer eggs in their ovaries than those whose mothers had a later menopause.

Now scientists are beginning to dissect the genes involved. One gene which has emerged is carried on the X sex chromosome (women have two X chromosomes and men an X and a Y chromosome). Men who carry a particular form of this gene develop Fragile X syndrome with severe learning difficulties. Female relatives of Fragile X individuals do not tend to have developmental problems, but are at a 25% risk of menopause before the age of 40.

With the latest technologies techniques that scan the entire genome, containing all our genes, large numbers of people can be studied. Similar research has been done for genetic markers of obesity for example. “One thing that intrigues scientists is whether different genes act at different ages to explain the huge range in natural age of menopause,” says Dr Anna Murray (Lecturer in Human Genetics, Peninsula University Medical School, Exeter, UK). In the latest research, published in Nature Genetics, 56 genetic variants were identified from a cohort of 70,000 women. These variants were enriched in genes involved in repairing damaged DNA and in genes linked to delayed puberty, suggesting potential molecular links between the onset and end of the female reproductive lifespan. In addition, the study also found evidence that genetic variants leading to later menopause also increase breast cancer risk.

Understanding the genes that influence the age of menopause, and how defective DNA repair mechanisms affect the quality and release of eggs, may help the treatment of infertility and influence treatments for heart disease and breast cancer. This will be increasingly relevant as, with an ageing population, women can except to live approximately 40% of their lives after the menopause.