Diet composition can affect genotype on a very large scale. This was established in a study conducted by an international team of scientists in 2016. Yeast cells were chosen as an object for experiments: they are easy to manipulate, at the same time, many genes in their composition are similar to genes in animals and humans. Therefore, the data obtained allow us to understand universal genetic and epigenetic mechanisms. As ‘agents of influence’ on the yeast genome, the experts used micro- and macronutrients: amino acids, fatty acids, sugars and vitamins. By introducing nutrients into the cell and correcting metabolism, the scientists recorded changes in the genes. By affecting cell metabolism through nutrition, the scientists were able to change the activity of nine out of ten genes. ‘The classical view is that genes control the breakdown of substances into molecules important to the cell,’ commented study leader Dr Markus Ralser on the results of the experiment. – But we have shown that the opposite is also true: the breakdown of nutrients affects the behaviour of genes’. According to the scientist, metabolic changes occurring in the cell under the influence of receipt and cleavage of certain food components, in many cases so strongly influenced the genome that some genes began to behave in a completely different way. Therefore, experts consider cellular biochemical reactions, the nature of which depends on the incoming nutrients, as the most important lever of gene control.

A study that showed that nutrition not only changes the way DNA works, but also causes inheritable transformations was conducted in 2003 at Duke University (USA). The objects for the experiment were so-called agouti mice. They differ from ordinary mice by the activity of a special gene responsible for the formation of agouti signal peptide. Under the influence of this protein, the animals are prone to obesity, the probability of tumour development increases, and a pigment is formed in the hair follicles, which gives the coat a yellow colour (instead of brown or black). In the study, female agouti mice were put on a special diet shortly before mating: their diet was rich in folic acid, vitamin B12, and the amino acids choline and methionine. This dietary style was maintained throughout the gestation and lactation periods. Most of the cubs were born with normal colouration and healthy metabolic processes, with no tendency towards obesity in adulthood. Moreover, the offspring, grandchildren and several other generations of mice born from the first offspring of agouti mice also showed no signs of agouti peptide activity, although they followed a standard diet. The experts found that the food components influenced the process of DNA methylation – the most studied to date mechanism of activation of some genes and suppression of others. It consists in attaching the methyl group CH3 to the nitrogenous base cytosine in the DNA molecule, which causes suppression of the activity of a particular gene. In order to trigger this process, a sufficient amount of methyl groups is needed: folic acid, methionine and vitamin B12 are the source of these groups (this is why pregnant women have such a high need for these micronutrients). Scientists explain the ability to transmit traits acquired under the influence of diet by incomplete erasure of epigenetic (methyl) marks on the surface of DNA: thanks to these marks, the same genes are activated and suppressed in offspring as in parents. Analysing the results obtained in the study, experts stress the importance of these data for humans. Scientists pay attention to the fact that the deficiency of folic acid, vitamin B12 (which is typical for vegetarians) during pregnancy leads to a violation of methylation processes. In this regard, at different stages of embryo development, disorders may occur, which have every chance to manifest themselves not only in this child, but also in his children, grandchildren and great-grandchildren.

The activation and suppression of genes is influenced not only by nutrition, but also by its absence – hunger. In the second half of the twentieth and early twenty-first centuries, scientists conducted a number of studies involving people who had experienced hunger in the womb. It is about the so-called ‘hungry winter’ in the Netherlands: in the period from November 1944 to May 1945 food supplies to this country were stopped. The caloric value of the daily ration of the Dutch inhabitants at the beginning of the ‘hunger winter’ was about 1000 kcal/day, and in the spring of 1944 it decreased to 500 kcal/day. Decades later, scientists became interested in the impact of the famine on the health of children born during the entire period of deprivation and several months after its end. Specialists studied medical documents relating to the parameters of infants at birth. A total of 2414 people took part in the research. It turned out that children who underwent intrauterine starvation in the first two trimesters of pregnancy were most often born with normal body weight. But the reduction in caloric content of the maternal diet in the last trimester ‘responded’ to the insufficient weight of the baby at birth – the average weight deficit was 300 grams. Within a year, the children’s weight indicators reached normal values. However, starvation at an early stage of intrauterine development affected the health of children in the future – this was confirmed by a study conducted in 1976. Its participants were conscripts born in the ‘hungry winter’: it turned out that men who experienced hunger in the early stages of foetal development (first-second trimester of pregnancy) by the age of 20 more often developed obesity than their peers. Scientists explained this by hormonal dysregulation that occurred under the influence of intrauterine hunger. According to experts, the lack of nutrients affects the maturation of hypothalamic centres that regulate food intake and growth processes. The purpose of the study, conducted in 1996, was to study the effect of intrauterine starvation on the risk of developing schizophrenia. It turned out that starvation suffered by the foetus in early pregnancy, doubles the risk of developing this mental illness. In a series of studies conducted in 1998, 1998, 1999, scientists have found that carried intrauterine hunger in adulthood significantly increased the risk of obesity, arterial hypertension, diabetes mellitus. In 2008, scientists conducted a study to examine the genetic characteristics of people who starved in the womb. The focus of attention of specialists was the IGF2 gene responsible for the production of insulin-like growth factor. This part of the genome, which plays a crucial role in the regulation of growth, development, and metabolism, is considered to be the most susceptible to epigenetic factors. It is proved that maternal epigenetic ‘imprint’ remains in this locus, which does not affect the genome structure, but contributes to the activation and suppression of certain genes. The study showed that in ‘children of hunger’ in comparison with their same-sex siblings who did not experience intrauterine hunger, there was more ‘low methylation’, i.e. fewer sites in the region of IGF2 gene location were marked with methyl tags. Moreover, such epigenetic changes affecting metabolic processes in the organism even in adulthood were detected only in those who underwent starvation at the early stages of intrauterine development, when changes in methylation processes have a pronounced effect on the process of fetal development. Children who had been starved shortly before birth had the same IGF2 methylation processes as siblings who had not experienced intrauterine starvation. In 2013, a new study was conducted involving the grandchildren of women whose children were intrauterine exposed to malnutrition during the Dutch ‘hunger winter’. A total of 360 people were examined, with an average age of 37 years. The control group included grandchildren of people born shortly before and shortly after the famine. It turned out that the participants in the main group had a higher body mass index compared to the control group. It also turned out that this situation was characteristic only for participants whose fathers had suffered starvation in utero – offspring born to girls born during and immediately after the ‘hunger winter’ had normal weight indices. This study shows that epigenetic changes associated with exposure to in utero starvation are not limited to a single generation, but can be passed on to grandchildren.

Not so long ago, it was thought that the foods we eat were merely a source of energy and substances needed to build our cells. Today, it is becoming apparent that its effects on our body are much more powerful. They influence whether the information encoded in the genes will be ‘manifested’ in our body or blocked. Nutrition during pregnancy is a powerful epigenetic factor. Deficiency of folic acid, found in plant foods, and vitamin B12, which is rich in meat, leads to suppression of the activity of many genes. As a result, the foetus develops various disorders that manifest themselves as diseases in adulthood. Epigenetic aspects of the impact of nutrition will still be studied, but there is no doubt that with a well-formed diet we can resist many diseases, including diabetes, cancer, obesity, hypertension and Alzheimer’s disease, and not only in themselves, but also in their descendants. Photo: endlessvacation.com