Center of Excellence in Nutrition and Metabolism (CENM)

 

Research in the field of nutrition in Serbia began in 1947 with the establishment of the Institute for Nutrition at the Serbian Academy of Sciences; this institute served as one of the four focal points involved in the field of medical sciences, which were the foundation of the future Institute for Medical Research. In 2010, the research Group for Nutrition and Metabolism was nominated as the Center of Excellence in Nutrition and Metabolism (CENM). In terms of science, human resources and programs the Center is involved in basic research regarding the biological basis of the onset and development of human and animal diseases and the impact and effects of food ingredients and nutrition on these processes. However, the Center takes an equal interest in translational research, as a link between the results of fundamental research and their application in various fields of medicine, industry, the public sector and everyday practice. Based on the achieved results and experience, CENM has established and secured its place within the international scientific community in the field of food and nutrition research. Numerous international projects and fruitful collaborations with respectable scientific institutions resulted in further development and advancement of the CENM professional capacities, human resources, equipment, technology, and methodology. CENM cooperates with other educational and scientific institutions in the country and abroad, such as medical centers, industry, governmental and civic associations, via a range of activities which allow for the expansion of scientific knowledge, development of new products, and technologies based on scientific evidence. Such comprehensive research has been made possible by efficient networking and cooperation among multi-disciplinary research teams within the CENM and collaboration with competent researchers from other universities, clinics, and scientific institutions.

The human resources, scientific competence and openness for cooperation, but most of all previous experience and research achievements, provide a sustainable basis for the maintenance of the status of Center of Excellence in the field of nutrition. In addition, the Center has a developmental perspective which aims to meet the needs of the scientific community: to be the source of knowledge and an environment which nurtures the advancement of the scientific staff in the field of nutrition and biomedicine. This breadth and quality of activities has been achieved only by CENM in the country and in the Balkans region, while full harmonization with quality standards was accomplished mainly through research activities within European projects.

 

Three research directions are prominent in CENM: 1) biochemical research in the field of lipid metabolism and individual fa5y acids with the focus on polyunsaturated fa5y acids (PUFAs); 2) research in the field of public health and nutrition, and 3) studies on the effects of nutritive and non-nutritive bio-active components in food by application of various experimental model systems, ranging from cell culture, via animal models, to interventional clinical studies. The multidisciplinary character of the research team which currently consists of 23 researchers (of various backgrounds, including medical doctors, pharmacists, molecular biologists, biologists, technologists, mathematicians) and a broad range of expertise (internal medicine, clinical pharmacy, medical biochemistry, food chemistry, nutrition, public health, health protection, food safety, food technology, and state of the art cell cultivation and molecular biological techniques) represent the basis for the coverage of the broad field of nutrition science. 

 

Research activities conducted by CENM include assessment of complex interactions of nutrient intake-status-health effects, as well as the evaluation of the role of nutritive therapy in the prevention and treatment of non-communicable diseases. Long-term research has confirmed that assessment of the profile and quantity of fatty acids (FA) in serum and erythrocyte phospholipids is significant for both supplementation-interventional and nutritive – epidemiological studies. Alterations in distribution and profile of FA in phospholipids of serum/plasma have been found in various pathological conditions such as obesity, hyperlipidaemia, diabetes, various auto-immune diseases, cancer and terminal kidney failure. Acknowledging the fact that interventional dietary studies are essential in promotion of health, prevention, and therapy of diseases, CENM has been conducting such studies using food products enriched by essential PUFAs. It has been scientifically determined that a combination of sesame/pumpkin/flax seeds, added as a supplement to food, decreases the level of triglycerides and factors of inflammation, has an effect on glycaemia control, and improves the FA profile and pruritus symptoms among patients subjected to hemodialysis. Furthermore, through scientific and clinical collaboration, supplementation with n-3 FA has been carried out among patients subjected to hemodialysis, which showed favorable effects on the nutritive status, insulin resistance, and factors of inflammation. An interventional study in patients with hyper- lipidaemia indicated that AHA Step 1 diet and / or fibrate therapy results in a deficit in the levels of n-3 FA as compared to the healthy population before treatment, but also significantly improves the lipid profile and FA in serum and erythrocyte phospholipids. The level of serum triglycerides was negatively correlated with the main n-3 fractions in serum phospholipids. This agrees with published results which point out the deficit of n-3 FA in hypertriglyceridaemia and justifies the recommendation for a greater intake of oily fish rich in n-3 FA. We have determined that the best effect in reducing the atherogenic FA is accomplished by a combination of the AHA-Step 1 diet and statin therapy. This is in concordance with scientific evidence which indicates that, although statins when compared with other lipid lowering medicines, have the most powerful effect on cholesterol levels, lead to deficiency of n-3 FA.

 

Evaluation of the health effects of functional foods has been conducted by the Center in cooperation with the industry. Two open-label controlled interventional studies were carried out to investigate potential hypolipidemic effects of dietary supplements based on soy proteins and lecithin (LeciVita and LeciVita D), among subjects affected by hyperlipidaemia, and patients with type 2 diabetes. In the experimental group, a significant improvement of the lipid status as well as a more favorable serum and erythrocyte phospholipid FA profile were observed. Another line of research has been aimed at studying alterations of lipid and FA composition of serum phospholipids in premature infants throughout neonatal life, with the focus on newborn infants born with intrauterine growth restriction. In addition, special attention has been paid towards the provision of adequate dietary recommendations to women in reproductive age, children and adolescents.

 

In recent years, researchers of CENM have developed several new research directions, which focus on examining the interaction of food rich in n-3 FA and food of vegetable origin rich in polyphenols/antioxidants with the lipid and FA profile of phospholipids of plasma and tissue (erythrocytes), as well as the activity of antioxidant enzymes and the level of cytokines in different pathological conditions. A particular area of interest is the examination of lipid metabolism and redox balance among professional athletes and persons exposed to increased oxidative stress. Such studies explore the mode of action and effects of fruit juices (pomegranate and aronia - chokeberries) on alterations of lipid composition of cell membranes and the increase in membrane fluidity. Previous research in this area focused on dietary-based interventional studies with the objective to determine the effects of non-nutritive, biologically active food components on the reduction of risk factors for cardiovascular diseases. These studies involved measurement of relevant biomarkers and evaluation of risk factors including anthropometric and biochemical parameters, blood pressure, parameters of oxidative stress, and lipid composition and antioxidant status of erythrocyte membranes (using gas-liquid chromatography). The most significant result of the above-mentioned studies was a positive effect of food rich in polyphenols, concerning the level of oxidative stress, mediated by improvement of the FA profile of the erythrocyte membrane. The interventional nutritive study of supplementation with the native juice of Aronia melanocarpa has shown a beneficial effect on metabolic syndrome biomarkers, anthropometric parameters and FA profiles, by reducing the oxidative stress parameters, exhibiting a hypotensive effect and improving antioxidant protection in postmenopausal women affected with the metabolic syndrome. Furthermore, within the FP7 BACCHUS project, the research activities included the assessment of markers of platelet activation and aggregation using an advanced method of flow cytometry. Except for interventional studies, the effect of isolated bioactive components and their gastrointestinal tract metabolites on the function of thrombocytes has also been measured in in vitro conditions, using the blood of healthy donors and individuals at an increased risk of cardiovascular diseases.

 

In the food and metabolism research domain, in addition to interventional nutritive clinical trials, the mechanism of action of various active food components has been studied in animal models, with the purpose of determining the mechanism of development and prevention of diverse diseases. The models included young and old rats, mice, and working dogs, and CENM team members explored the effect of cod-liver oil, polyphenols and a wide variety of foods on the oxidative stress level and alterations in the FA metabolism. Studies conducted in experimental models (Wistar rats) were based on supplementation with various active substances or ready-made products, such as cod-liver oil and aronia juice, and the assessment of their effects on the composition of phospholipids in the membranes, both in the plasma and erythrocytes as well as in the tissues, mostly the liver. Another research interest involved ageing as a biologically spontaneous and obligate process and certain alterations of phospholipid fatty acids profile  have been recorded (an increase in n-6 fatty acids as well as an increase in n-6/n-3 ratio). The tissue specificity has been observed in the changes of fatty acids composition caused by supplementation and by ageing. In order to enable parallel testing of gender-specific response to supplementation with essential fatty acids, animals of both sexes were used in these studies. Research in the field of lipid metabolism and biological effects has revealed the dependence of fatty acids upon the hormone status as well as  upon sexual maturity pointing out that estradiol hormone causes the increase of anti-inflammatory n-3 PUFA and the reduction of the pro-inflammatory n-6 PUFA in animal model of cerebral ischemia. In recent years, in addition to experimental model of the rats and mice, model of working / police dogs has been introduced for the purpose of research in the field of everyday stress and preventive actions of essential fatty acids. These studies were conducted in cooperation with the Faculty of Veterinary Medicine.

Significant segment of biochemical studies of metabolism and the role of fatty acids refer to the research directed toward the exploration of the changes in reactivity of the thiol group of Cys34 human serum albumin due to the binding of non-esterified fatty acids (NEFAs), polyphenols, and their metabolites. It is known, based on the literature data that the binding of non-esterified fatty acids to the human serum albumin brings to significant changes in reactivity of its free thiol group. In the same time, the literature lacks data on the binding of significant metabolites of polyphenols, enterolaktones, and enterodiols for human serum albumin. Our test results have shown the presence of an interaction between enterolactone and enterodiol with the human serum albumin in the sub-domain IIIA of moderate intensity, as well as the competition between their binding and the binding of non-esterified fatty acids. In addition, the research concerning binding ligands and an effect on the reactivity of free thiol group of albumin have shown for the first time that the binding of enterolactones and enterodiols, except non-esterified fatty acids, may result in the reactivity change of the group Cys34 human serum albumin. The importance of these results is reflected in the revelation of the fact that dietary intake of food rich in polyphenols may affect the anti-oxidative activity of human serum albumin, which has an important role in anti-oxidative defense of the organism.  In addition to this research, individual FAs have been examined as biomarkers in the occurrence or prevention of the development of increased blood pressure and metabolic syndrome. In collaboration with other research centers in the country, nutrigenetics methods were employed to assess the association between the FA status and parameters of cardiovascular health.

 

In the field of public health nutrition, the Center works intensively on capacity building, development and management of a food composition database for Serbia and the Balkan region, harmonization of nutritional recommendations on micronutrient intake and creation of soware applications with an objective of validating the scientific methods intended for application in dietary assessment. The focus is particularly on the development and improvement of the methodology used for evaluation of food consumption and diet quality on both the individual and population level. Through participation in a number of FP6 and FP7 projects, the Center has created (in collaboration with computer programmers) the first electronic Serbian Food Composition Database, which is harmonized with the databases of other European countries. One achievement of particular importance is the creation of an electronic platform with several programs for food consumption data collection, comprehensive dietary assessment and nutrition planning. CENM researchers have contributed to the pan-European harmonization of micronutrient recommendations intended for diverse population groups within the frame of the FP7 EURECA project. By participation in international projects, CENM researchers have become familiar with the systematic literature review process and meta-analysis with an objective to collect relevant information concerning various micronutrients and their status (iodine, folate, iron, zinc, and Vitamin D) and to explore the complex relationship between dietary intake, nutritional status and health among different population groups. Through activities of the FP7 CHANCE project and numerous advanced trainings in the country and abroad, CENM researchers have developed methods of modeling and simulation of the food fortification effect on the diet quality. Furthermore, they have improved their knowledge and skills in the field of data analysis by applying advanced statistical programs (SPSS, R, STATA, and SAS). From 2013 onwards, CENM researchers have established a doctoral studies module at the Faculty of Biology, University of Belgrade, named Integrated Nutrition Sciences, as the first postgraduate program in the field of nutrition in Serbia but also in the Balkan region. The module involves a number of CENM researchers as accredited lecturers, doctoral candidate mentors and research supervisors.  

 

The Centre organizes epidemiological studies using state-of-the-art methodological approaches to explore the nutritive status and metabolic functions of diverse population groups in Serbia. The CENM members evaluate the dietary intake, metabolic status and the role of various micronutrients, with emphasis on folates and vitamin D. Folates are essential micronutrients that cannot be synthesized de novo in the mammalian body and therefore, an adequate amount of these compounds, which play a critical role in numerous biochemical processes, has to be provided through food and/or supplementation. Although important for all population groups, an adequate folate intake and status is of particular significance for women of reproductive age. Since reliable and objective nutritional assessment is a prerequisite for successful coping with the challenges associated with achieving adequate levels of essential nutrients, CENM researchers have developed and validated a Food Frequency Questionnaire for folate intake assessment (F-FFQ). In the absence of mandatory fortification of staple foods with folic acid and limited availability of voluntarily fortified products, public health campaigns and educational programs aimed at promoting periconceptual care and improving social awareness concerning importance of folates for health, are of exceptional significance. Acknowledging the potential role and responsibility of health care professionals, in particular pharmacists and pharmacy technicians, for the promotion of folic acid supplementation and health education of reproductive age women, special efforts and activities have been directed towards the strengthening of their professional capacities, knowledge, skills and motivation. Dietary intake, nutritional and metabolic status, and the status of vitamin D, have been studied in Serbia in vulnerable population groups such as pregnant and lactating women, and miners. The Center is also engaged in studying the impact of occupational stress on overall health as well as on temporary and/or permanent working disability among Serbian workers. These studies have pointed out the necessity of active education and counseling of both lay public and health professionals on the importance of proper intake of vitamin D, folates and PUFAs.

 

Further activities of the CENM team include education on the importance of physical activity essential for maintaining an ideal body weight, prevention and treatment of obesity as well as enhancing the overall quality of life. Moreover, CENM researchers are involved in the creation of physical activity programs tailored for different population groups with an objective to reduce the main risk factors for the development of chronic non-communicable diseases by improving the aerobic capacity, metabolic and immune functions, increasing fibrinolytic activity, decreasing platelet adherence and increasing energy expenditure. CENM has carried out several studies exploring the joint effects of physical activity and supplementation with fruit and fruit products rich in polyphenols. Young, physically inactive girls were recruited for the study with an aim to evaluate the effect of aerobic physical activity, alone or in combination with aronia berry juice supplementation, on stress factors and their physical and mental status. The combined treatment showed significantly more favorable effects. Another study has examined the effect of aronia berry juice consumption immediately prior to a simulation of a half-marathon race on the oxidative status, platelet function and biochemical parameters of recreational and long-distance runners. As intense physical activity may cause oxidative damage and an increase in thrombocyte aggregation, the results of this study, which indicated that intake of juice rich in polyphenols reduced oxidative stress factors and thereby decreased the negative effects of intensive physical activity, are very important.

 

In recent years, research on trans fatty acids (TFAs) has been intensified and studies conducted in the Center have revealed that the Serbian population is exposed to foodstuffs of a high risk for cardiovascular diseases, as the average content of TFAs in the most frequently consumed foodstuffs exceed, by several fold, the recommended limit of 2% of the total fat content. Of all the analyzed foods, the worst results concerning TFA were obtained for almost all margarines available on the Serbian market. CENM researchers have organized a number of lectures on this issue and actively participated in the public debate held in the National Assembly of the Republic of Serbia, and strongly support, by providing scientific justification, the initiative for passing legislation and establishment of a legal limit for TFA content in foodstuffs in Serbia.

 

RESEARCHERS

 

Marija Glibetić, PhD , Professor of Research (Head of Group)

Mirjana Gurinović, MD/PhD , Professor of Research

Vesna Vučić, PhD , Professor of Research

Danijela Ristić-Medić, MD/PhD, Associate Professor of Research

Aleksandra Arsić, PhD, Associate Professor of Research

Tamara Popović, PhD, Associate Professor of Research

Snježana Petrović, PhD, Associate Professor of Research

Gordana Petrović-Oggiano, MD/PhD, Assistant Professor of Research

Jasmina Debeljak-Martačić, PhD, Assistant Professor of Research

Nevena Vidović (ex. Kardum), PhD, Assistant Professor of Research

Ivana Šarac, MD/PhD, Assistant Professor of Research

Aleksandra Konić-Ristić, PhD, Assistant Professor of Research

Marija Takić, PhD, Assistant Professor of Research

Marija Ranić, PhD, Assistant Professor of Research

Manja Zec, PhD, Assistant Professor of Research

Vuk Stevanović, PhD, Assistant Professor of Research

Milica Kojadinović, PhD student

Milica Zeković, PhD student

Marina Nikolić, PhD student

Jelena Milešević, PhD student

Slavica Ranković, PhD student

Biljana Pokimica, PhD student

Ana Jelenković, PhD student

Irena Krga, PhD student

 

Пројекти