NANA LAHOZA personalized diet can balance the functioning of genes and reduce natural propensities to certain genetic-based diseases, such as diabetes. In fact, as yet it cannot, but some researchers believe that with adequate funding and coordinated efforts, in about a decade nutrigenomics will be a reality. It is as part of this concerted effort that about 600 researchers will be gathering in Guaruja, on the coast of São Paulo, between the 26th and 29th of this month for the International Conference on Nutrigenomics.
One strand of nutrigenomics is investigating how nutrients directly affect the action of genes. Such is the case with the action of fats, or fatty acids, on genes that control immune system cells, which is being studied by pharmacist Renata Gorjão, from the Cruzeiro do Sul University, in collaboration with the group coordinated by Rui Curi, from the Institute of Biomedical Sciences at the University of São Paulo (ICB-USP). They have discovered that DHA and EPA – the two commonest types of omega-3, a common fat in the oil of fish from cold water – reduce the activity of genes involved in the proliferation of lymphocytes, cells that act as the immune system’s memory. “If these cells multiply too much, the result is an inflammatory disease,” says Renata. Hence the need to ration the consumption of omega-3 according to individual needs.
The effect of fat seems to be widespread. The German Hannelore Daniel, from the Technical University of Munich, one of the leading guests at the congress, has been showing in mice that diets with different levels of carbohydrates and fats affect the expression of genes in several organs and tissues.
Nutritionist Sophie Deram, from the School of Medicine, at USP, tracks another strand of nutrigenomics, nutrigenetics, which examines how the genetic makeup of each person interacts with food in terms of propensity to disease. The researcher who was born in France, but who already considers herself to be Brazilian, is studying children who arrive at the child obesity clinic at Hospital das Clínicas. She discovered that variations in the gene of the perilipin (Plin), a protein from fat cells, affect the tendency to obesity. Children with the Plin-4 variant, if they become overweight, are more at risk of developing the metabolic syndrome: insulin resistance, increased blood pressure and low levels of HDL cholesterol, the one that is of more benefit to the body.
“The curious thing,” explains Sophie, “is that Plin-4 accelerates the breakdown of fats and, therefore, is considered to protect against obesity.” This is an eloquent reminder that genes work jointly with the environment: children with Plin-4 who have a very inappropriate diet end up having problems precisely because of the large number of fragments of free fat in the blood, with toxic effect. Sophie also saw that children with the Plin-6 variant respond very well to treatment with diet and exercise.
This approach has also been promising in the fight against cancer, the theme of the International Conference on Mechanisms of Antimutagenesis and Anticarcinogenesis, which is taking place at the same time as that of nutrigenomics. Pharmaceutical biochemist Thomas Ong, from the Faculty of Pharmaceutical Sciences, at USP, has been showing, in a study coordinated by Dr. Fernando Moreno from the same laboratory, that a molecule that is common in honey and dairy products, tributyrin, can help prevent liver cancer. In experiments with rats, the group showed that treatment with tributyrin reduces pre-cancerous lesions in the liver. It modifies the chromatin, a structure that packages the DNA, and as a result, activates genes related to cell death. Therefore, the treated rats developed fewer lesions in the liver and those that appeared were smaller than in the untreated rats. “These studies show how epigenetic processes that modulate gene expression without altering the DNA sequence can be important tools against cancer,” says Ong.
Joint effort
Research like this is an important initiative, but in order to put it into practice it is necessary to join forces. “Science is becoming so complex that it’s simply impossible to do it alone,” comments Chris Evel, head of the Bioinformatics Department at the University of Maastricht, in the Netherlands. “Much of the genomics and genetics on a large scale is, in fact, very new and we”re learning how to apply these tools,” he adds, which makes bioinformatics central in the current stage of research. It is, therefore, essential to have initiatives from international networks, like the European Nutrigenomics Network, coordinated by Dutchman Ben van Ommen, which sets up collaboration agreements with several countries outside Europe, including Brazil.
Most of the researchers who are at the forefront of nutrigenomics are keen to stress that the knowledge is still insufficient to generate practical applications. As nutrigenomics requires knowledge of genetic variation in the entire population, a Brazilian group led by biologist Carlos Menck from the ICB-USP, is now looking to lay the groundwork for a human varioma project.
“The nutritional recommendations that come on food and supplement packaging are based on American and European studies,” says biologist Lucia Ribeiro, from the Paulista State University (Unesp) in Botucatu. She is the coordinator of the Brazilian Network and Latin American Network of Nutrigenomics and chairs the organizing committee of the International Conference on Nutrigenomics. She is at the forefront of studies on vitamin D and is preparing to start work on vitamin A, which is important for growth, eyesight and embryonic development. “Some people are able to transform beta-carotene from their diet into vitamin A, while others need direct supplementation,” she explains. This depends on genes, hence the need to understand the genetic characteristics of the Brazilian population in order to arrive at appropriate recommendations.
The work is just beginning. “In my opinion, personalized nutrition is still a long way off and will not be widely used for a long time,” argues John Hesketh, coordinator of the International Micronutrient Genomics Project, of which Lucia forms part. Among other things he has been studying how the consumption of selenium affects genes that may interfere with the development of bowel cancer.
For Jim Kaput, director of the Division of Nutrition and Personalized Medicine, of the Food and Drug Administration (FDA), in the United States, nutrigenomics’ great achievement so far has been to emphasize the importance of analyzing genes and nutrient intake in the same experiment. He says the field, driven by the results of the Human Genome Project, in fact has ancient roots. “We often quote Hippocrates, from 2500 years ago: ‘Let food be your medicine and medicine your food’.”
