Nature is full of accidents and injustices – just take the common bee. From birth, all their larvae are almost identical and have the same genes, with which they can perfectly develop into queen bees. Except that in most bees the enzyme DNMT3A gradually blocks all the royal genes, and they turn into boring worker-bees. Others are much luckier (or less lucky?): chosen by blind fate to be future queen bees, these individuals receive not ordinary food, but royal jelly – a high-quality nutrient mixture, the active ingredients of which ‘switch off’ DNMT3A and unblock the royal genes. This story with bees is probably the most striking example of the influence of food on the functions of a living organism through its epigenome – a set of reversible chemical modifications of the DNA structure that do not affect the hereditary information itself, but determine which of the many instructions for assembling the organism should be applied in different conditions and at different times. Epigenetics decides which genes should be activated and which should be repressed, thus helping twin cells with identical genomes to form different organs and tissues. The cell’s epigenetic mechanisms for controlling genes are many. Most of them are tied to regulating the intensity of transcription, the process by which RNA is synthesised on the DNA matrix. For example, the aforementioned DNA methyltransferase DNMT3A represses the promoter regions that usually start the transcription of each gene. For this purpose, it ‘hinges’ methyl groups on these sites – after that, it becomes much more difficult for protein complexes conducting transcription to get close to DNA, and as a result, RNA synthesis for these methylated genes slows down or stops altogether.

‘Methylation is the most studied mechanism of food influence on the epigenome,’ says Professor Tatiana Tatarinova. – The same methyl groups -CH3, of course, do not arise in the body from nowhere, and therefore the cellular process of their production from various raw materials is very important for maintaining the process of epigenetic regulation’. One of the most important players in the methyl group production chain is vitamin B9, or folic acid, which not only all pregnant women have probably heard of, but also people within a two to three handshake radius of them. At the moment of conception and in the first months of pregnancy, folic acid deficiency can lead to miscarriages, premature births and serious abnormalities of the child’s nervous system. At the same time, 10% of people on Earth have genes that make it difficult to obtain folic acid from ordinary food (significant amounts of B9 are found in citrus fruits and various greens). Therefore, this vitamin is now prescribed as an essential supplement for almost all expectant mothers. The detailed mechanism of folic acid during pregnancy is still unclear, but there are indications that it is tied, among other things, to epigenomics. For example, there are papers showing that sufficient amounts of B9 increase methylation of the IGF2 (insulin-like growth factor 2) gene, which regulates fetal growth and development. However, it is unethical to experiment with the diet of pregnant women, and so scientists are turning to rodents in search of deeper explanations and reliable evidence. For example, one experiment examined pregnant mice with a mutant ‘tail curl’ phenotype that predisposes their offspring to defects. There were two groups of mutant mice in the study. One received normal food and the other received food enriched with folic acid and other sources of methyl groups. As a result, the mother mice in the first group had sickly offspring with neural tube defects, while the lucky mice in the second group had healthy mice. Apparently, the mutant gene causing the painful abnormalities was methylated and switched off in rodent embryos while still in utero. Another biologically significant element closely related to epigenomics is vitamin B12, which is involved not only in carbohydrate metabolism and hydrogen transfer, but also in the processes of methylation and methionine synthesis. Normally, vitamin B12 comes to us with food – most of it is found in fish, seafood and meat. This is why vegetarian diets can lead to serious health problems, including those associated with hypomethylation (insufficient methylation) of genes, and even the development of cancer. That is why vegetarians are recommended to compensate for the lack of B12, if not with the help of biologically active supplements, then at least abundant portions of seaweed, soya, hops and other plant products relatively rich in this vitamin. Nearly 60% of meat haters need vitamin B12 supplementation, especially the elderly and pregnant women. However, as is always the case in matters of diet and nutrition, there are opposing views. ‘It doesn’t make sense to be mindlessly addicted to vitamin B12 and stuff yourself full of it,’ says Tatarinova. – Many cancer patients, for example, have elevated levels of vitamin B12. What’s more, there is some indirect evidence that overeating folic acid, B12 or other recommended supplements can trigger the growth of existing but undiagnosed tumours. This is because cancer can involve both hypomethylation of oncogenes that are normally inactive in a healthy cell and hypermethylation of genes that inhibit tumour development.’ In addition, a later study found no link between B12 deficiency and altered gene methylation. Such contradictions within the nutrigenomics of even the simplest epigenetic mechanism are quite common for a young field trying to understand the intricacies of nutrients, cycles, and genes in our bodies, which are forced to spend their entire lives not only fuelled by imperfect and contradictory food from the outside, but also constantly tormented by the fact that they are doing it completely wrong. It eats at the wrong time, not as much as it needs, and in general completely wrong.

Another epigenetic change that can be triggered by food is various modifications of histones, the bulky protein molecules on which DNA strands are wound within chromosomes. By slightly altering the chemical structure of histones, it is possible to rearrange the spatial structure of DNA and its stacking within chromosomes, for example making it easier to unwind from the histone coil during transcription. Research has shown that histone acetylation (this is one of the most common epigenetic modifications of histones – the attachment of acetyl groups to them, resulting in improved transcription) can increase in the presence of isothiocyanates, organic substances found in broccoli, cabbage and other cruciferous plants. Scientists have already unravelled dozens of such plots involving the devious effects of different nutrients and foods on epigenetics, and are even tempted by personalised diets with epigenome-matched diets. But in practice, the evidence is still too patchy and contradictory to improve health. ‘Individualised diets are certainly necessary,’ says Tatarinova. – Often they can help get rid of a host of problems – from flatulence to migraines, or even curb tumour development. But a good selection of diet on epigenome – this is still a fantasy.’ Oh, and in general, any strict unbalanced diet is an extreme that can lead to disorders, even though the human body has flexible and stable self-regulation. ‘That’s why I believe that the best diet for humans is an ancestral diet. Here our ancestors in the middle zone of Russia ate some food, survived on it, left healthy offspring, so this diet is likely to be good for us too.’ For example, there are a lot of second-generation Chinese and Japanese in the United States who are obese. Their ancestors’ diets were rich in seafood and vegetables, but when they came to America, these ethnic Japanese and Chinese quickly “Americanised” – they switched to burgers and crisps, which were not familiar to their bodies, and as a result they got nice rounded shapes. At the same time, the Scots, who have been eating fatty haggis for generations, remain quite thin and healthy even after switching to burgers. On the other hand, our daily diet, if not entirely, then to a large extent shaped by the dietary habits of our distant ancestors, may in turn influence the tastes of our descendants. Some epigenetic changes are not only inherited from parents to children, but are also capable of becoming entrenched in the population over time as gene variants selected by selection. ‘Under the influence of dietary habits, the genome changes very slowly: it usually takes 150-400 generations,’ says Tatarinova. – If we fantasise about how Western European and American food culture will affect our descendants, we conclude that they are likely to develop an adaptation to high-calorie processed food, just as the Maasai gradually developed an adaptation to a diet rich in fat. The descendants of modern Europeans will be able to digest fast food on the fly and not get fat at all. But, really, I still hope that we won’t be eating substandard fast food for another 150 generations. Or at least eat less of it than we do now. This I tell you as a convinced vegetarian and supporter of a healthy lifestyle with 35 years of experience!’ Source