Eating disorders (TCA) are significantly frequent in people with disabilitydue to factors such as social isolationlow self-esteem and awareness of their limitations physical or mental. These factors may increase the risk of developing anorexia either bulimiaalso making its early diagnosis difficult. In this context, mastering metabolomics is crucial, since it allows a precise evaluation of the nutritional deficiencies and metabolic in these patients, offering essential data to personalize treatments and improve their quality of life in the long term.
A recent study launched by the HM Nens Hospital and the Vall d’Hebron Hospital has evaluated the metabolomic-nutritional status and the risk cardiovascular in adolescents with anorexia nervosa and underweight. With the first results in hand, the researchers have highlighted that the food restriction Severe disease negatively affects metabolism and cardiovascular markers, which can have serious long-term consequences if not intervened early. Thus, the analysis highlights the need to quick treatment to avoid complicationsespecially at a critical time of development like adolescence.
To find out all the details of the study, we spoke with the Dr. José Manuel Siuranahead of the Cardiology Service at HM Nens Hospital and professional who has led the metabolomics study in Eating Disorders.
What was the main motivation for starting this study on metabolomics in eating disorders in children and adolescents?In 2018, at the HM Nens Hospital, together with the Vall d’Hebron Hospital, we began a line of research to study cardiovascular risk in pediatrics. We began by studying cardiovascular changes in adolescents with obesity and went deeper into the search for advanced indicators of cardiovascular risk for the study of cholesterol, studying the distribution of lipoproteins and plasma lipids, parameters related to the formation of atheroma plaques in the arteries.
Later, in 2020, with the COVID-19 pandemic and the sharp increase in cases of Eating Disorders such as anorexia nervosa in adolescents, we decided to expand our project to study the risk in these patients, since their levels of plasma cholesterol are even higher than in obesity. In addition, we added the determination of precursors of the Krebs cycle, which is the way in which cells are able to generate energy. A curiosity about conventional analyzes of patients with anorexia nervosa is that most macronutrients, such as triglycerides, glucose or proteins, have normal values.
What advantage does metabolomics provide over conventional analytical tests in the diagnosis of eating disorders?Metabolomics allows us to determine what is happening in our patients’ bodies at the current moment, unlike other omics sciences, such as genomics or epigenomics, which predict what could happen. Therefore, for the doctor, it is a more useful tool for managing the patient’s current physical condition. Through metabolomics, various types of micronutrients can be determined, such as essential amino acids or polyunsaturated fatty acids such as omegas. Furthermore, metabolomics allows us to study the size and composition of lipoproteins, which are the main molecules for the transport of cholesterol in the blood and those responsible for the initiation of the formation of atheromatous plaques in the arterial wall. In pediatrics, these determinations are of great help because, given the youth of our patients, in most cases only early changes in metabolism can be observed that are not determined with conventional analysis.
Preliminary results show a significant deficit in certain nutrients. What nutrients would you highlight as the most critical in these patients?In adolescents with obesity, the most notable is the decrease in cardioprotective fatty acids such as omega 3 and the increase in small LDL lipoproteins, which previous studies have already shown to have a relationship with cardiovascular pathologies such as myocardial infarction or arteriosclerosis. While in adolescents with anorexia nervosa, the generalized decrease in precursors of cellular nutrition has caught our attention, especially some important amino acids such as alanine, branched chain amino acids (BCAA) or glutamate.
How does this nutritional deficit affect the risk of cardiovascular complications in young people with low weight?We have not found cardiovascular complications in young people with low weight. At the cardiovascular level, we have detected metabolic changes that generate a higher risk in adolescents with obesity.
How does reduced glutamate impact the brain of patients and what role does it play in the development of mental health disorders?Glutamate is the most abundant neurotransmitter in the central nervous system (CNS) and the main excitatory neurotransmitter. The greater amount of glucose that reaches the brain will be used to generate glutamate. Its decrease in the CNS has been related to depressive symptoms. However, it is advisable to be cautious at this point because it has not yet been proven that there is a relationship between blood glutamate levels and levels in the cerebrospinal fluid. In our group we believe that since glutamate synthesis depends on blood glucose, it is feasible to hypothesize that if blood levels are decreased, something similar may occur at the brain level. It must be kept in mind that depression and anxiety symptoms are very important in patients with anorexia nervosa, so if there is a possibility of improving them through diet, it could be a relevant advance for the management of these patients.
Are there specific metabolic markers that can predict the chronification of anorexia nervosa in pediatric patients?We have no data on this. In a second part of the project, we want to do metabolomic monitoring of these patients to detect which profiles have had the best evolution.
In terms of treatment, how could metabolomics guide future more personalized therapies for these patients?Metabolomics allows us to have something like a metabolic fingerprint of our patients and know what deficits we must correct or excesses we must limit, since each individual is unique, processes nutrients differently or their genetics predispose them to generate them. internally. It is very useful for targeted management in patients with eating disorders.
What role have collaborating centers, such as the Vall d’Hebron Hospital, the Sant Joan Hospital in Reus, the Institut Pere Mata or the ITA centers, played in the development and execution of this study?We started the project together with the Vall d’Hebron Hospital, where Dr. Diego Yeste’s team has experience in the management of adolescents with obesity, and the Biosfer Teslab advanced metabolomics laboratory of Dr. Núria Amigó, who are experts in molecular diagnosis. Subsequently, to develop the anorexia nervosa project, the Hospital Sant Joan (Dr. Albert Feliu) and the Institut Pere Mata (Dr. Vanessa Sánchez) of Reus joined forces, which care for a significant number of patients with anorexia nervosa in the south. of Catalonia.
The ITA mental health centers collaborate with our hospital and have extensive experience in caring for adolescents with this pathology. Our project is a multicenter public-private collaboration that has been possible thanks to the excellence of the professionals who are working in the different centers and the funding received through competitive grants from the Spanish Society of Arteriosclerosis, the Spanish Society of Pediatric Cardiology and Congenital Heart Disease and the Spanish Society of Pediatric Endocrinology.
How accessible is metabolomics testing technology currently in daily clinical practice for pediatricians and specialists?Only a blood sample is necessary, but it depends on access to a specialized laboratory. Only a handful of laboratories around the world can perform the technique that we use and we are lucky that one of them is in Catalonia. At the HM Hospitales centers in Catalonia, in collaboration with Biosfer Teslab, we offer metabolomic analysis both for eating disorders and for the advanced study of the nutritional status of athletes.
Looking to the future, what next steps or research are proposed to consolidate metabolomics as a diagnostic tool in eating disorders?We have been surprised by the clinical applicability of this technique, which is why we plan to expand our studies with the incorporation of adolescent athletes with high rates of physical exercise, since it is a population that is very susceptible to presenting nutritional alterations and who They would benefit from having knowledge of their metabolomic profile, both to improve their performance and to detect nutritional alterations.
