Human Metabolism and Nutrition Guidelines
This research area, which forms part of the PRECINUT research group (Precision Nutrition in Obesity and Metabolic Syndrome), aims to address and integrate metabolic aspects related to nutrition, obesity and associated comorbidities. The metabolic analysis will be carried out before and after following different nutritional strategies focused in a personalized way to the improvement of these metabolic disturbances. Likewise, this area seeks to contribute to precision nutrition through the identification of metabolic biomarkers, as well as by means of the development of indexes and decision trees that allow the early diagnosis, follow-up and evolution of these pathologies.
This area of research has a multidisciplinary team that will carry out nutritional interventions and analyze the metabolic response, and will rely on the other lines of the Nutrition Research Center to achieve the expected results.
The specific objective is to design and develop nutritional intervention studies taking into account obesity and associated comorbidities (metabolic syndrome, non-alcoholic fatty liver, sarcopenia, etc.) as a central axis. The design of the dietary strategies is based on mechanisms underlying these pathologies and at the same time has an innovative component focused on precision nutrition (Mediterranean diet, high antioxidant capacity, satiating, anti-inflammatory, based on the frequency of intake, chrononutrition , with the presence of specific bioactive compounds, physical activity, etc.).
The specific objective is to evaluate the metabolic response of each participant in relation to the personalized nutritional strategy that has been assigned to them. For this, routine technology will be available, as well as innovative methodology in the field of human metabolism (imaging techniques, nutrigenetics, nutritional epigenetics, transcriptomics and regulation of gene expression, mRNA and miRNAs, intestinal microbiota, metabolomics, etc.). In addition, the evaluation will delve into factors that condition the metabolic response, such as dietary intake and factors of lifestyle, activity / physical exercise, behavioral aspects, depression, anxiety, etc.
The specific objective is to integrate the results obtained after individual metabolic response. The purpose is to contribute to the early diagnosis and evolution of nutritional metabolic alterations linked to adiposity. Currently, the research is focused on the search for biomarkers / scores that allow early non-invasive diagnosis of non-alcoholic fatty liver disease, as well as its evolution.
Referencia: PC082-083-084 EHGNA.
Entidad Financiadora: Departamento de Universidad, Innovación y Transformación Digital. Gobierno de Navarra. Ayudas a Centros tecnológicos y Organismos de investigación para la realización de proyectos de I+D colaborativos (convocatoria 2020).
Financiación: 193,350.23 euros
Investigador principal: Itziar Abete Goñi
Consorcio: CIMA; UNAV; UPNA
Duración: 2 años
Actualmente, se estima que 9 millones de españoles padecen enfermedad de hígado graso no alcohólico (EHGNA) y en torno a 1,1 millones de ellos desarrollarán esteatohepatitis. Es una enfermedad asociada a obesidad, diabetes y síndrome metabólico que, si no se detecta a tiempo, puede progresar a cirrosis y hepatocarcinoma. Estos datos de prevalencia e incidencia son aproximados debido a que la enfermedad es asintomática y el diagnóstico preciso sólo se puede realizar tras una biopsia hepática. Se estima que la esteatosis hepática no alcohólica se convertirá en las próximas décadas en un problema incluso mayor que la diabetes siendo la principal causa de trasplante de hígado, superando a la hepatitis y a la hepatopatía alcohólica. No existe tratamiento farmacológico específico para esta enfermedad, salvo la recomendación general de pérdida de peso.
El desarrollo de metodologías capaces de identificar la enfermedad y su estadío es clave para la investigación y necesario para la salud pública. Las tecnologías “omicas” entre las que se incluyen la metabolómica y epigenética entre otras, permiten un conocimiento profundo del organismo reflejando estados y perfiles de datos característicos capaces de identificar y detectar estados de enfermedad no detectables mediante las metodologías habituales. Así, la integración de toda la información procedente de metodología habitual y metodología más avanzada, mediante aplicación de inteligencia artificial, nos permitiría desarrollar un método de sub-diagnóstico alternativo a la biopsia capaz de describir de forma más precisa el estado de la enfermedad y su evolución, potenciando el diagnóstico precoz de pacientes que en la actualidad pasan desapercibidos y por tanto previniendo la evolución de la enfermedad hacia estadíos irreversibles.
En este sentido, el presente proyecto plantea identificar a partir de marcadores subrogados, y mediante la integración de datos aplicando inteligencia artificial, diferentes estadíos de la EHGNA, analizar su evolución tras el seguimiento de una intervención nutricional personalizada a largo plazo, con el fin último de desarrollar algoritmos de respuesta al tratamiento. Esto permitirá agilizar la identificación de la enfermedad y su grado de afectación, conocer su pronóstico evolutivo y prevenir la incidencia de estadíos crónicos irreversibles.
Acronym: FLIO (Fatty Liver in Obesity)
Funding body: Dpto de Salud del Gobierno de Navarra
Lead researcher: Mª Ángeles Zulet Alzórriz.
This project falls within the "Promotion of health and lifestyles" research area, with an emphasis on hepatic alterations connected to excess weight/obesity. It aims to contribute to a more integrated treatment of NAFLD (non-alcoholic fatty liver disease) to ensure that the nutritional strategies/lifestyle habits contribute to a more rational use of current therapies (a reduction in the cost of pharmacological treatment, hospitalisation, liver transplants). At the same time, the variables/techniques applied will contribute to advancing early diagnosis, helping to identify non-invasive biomarkers for early diagnosis of hepatic steatosis, for use in future patients. To this end, it proposes a personalised nutritional intervention based on two strategies: 1) Conventional, in accordance with the current proposal by the AASLD (American Association for the Study of Liver Diseases) and 2) RESMENA, based on a project subsidised by the nutrition group at the University of Navarra (Dept Health-GN/48/2009) and whose objective was to “REducir Síndrome MEtabólico en Navarra (Reduce Metabolic Syndrome in Navarra): RESMENA”. After two months of monitoring, it was determined to be as effective at reducing metabolic syndrome criteria as the AHA (American Heart Association) proposal and even more effective after six months' monitoring, particularly in obese subjects with altered glucose values, significantly reducing oxidized LDL in RESMENA. For this reason, the application of this strategy in NAFLD is a result of the profile of individuals suffering this disease: obese, with insulin resistance and cardiovascular disease; as well as the mechanisms involved in NAFLD. It also mentions oxidative stress and inflammation; issues that were considered in the dietary design. Both strategies focus on personalised education to teach the patient to adopt a wholesale modification of their behaviour, both nutritional and lifestyle habits, that respects the strategy designed for each case.
This approach it was supported by the Nutrition Group at the University of Navarra, and proposes synergy with the Liver Transplant and Cirrhosis Complications group at the Hepatology Unit at the Clínica Universidad de Navarra-CUN and the Digestive Service at the Hospital Complex of Navarra as well as the Hepatic Oncology and Radiology group at CUN. All the groups are part of the Metabolic and Digestive Illnesses area at IdiSNA, Instituto De Investigación Sanitaria de Navarra, (Healthcare Research Institute of Navarre).
1) considers obesity and fatty liver as well as indirect factors for cardiovascular risk and insulin resistance/diabetes;
2) combines multidisciplinary/multicentric, scientific/clinical knowledge;
3) addresses personalised strategies with scientific support, with no additional costs for the patient;
4) provides health education and promotes healthy lifestyles;
5) is reproducible and applicable to "Health Promotion and Lifestyles."
All with the aim of:
1) shedding more light on the influence of personalised nutritional strategies on NAFLD;
2) contributing to a more comprehensive treatment, as a contributing factor in the reduction of hepatic conditions and its associated healthcare burden;
3) further advancing early diagnosis;
4) contributing to the transfer of knowledge about obesity/NAFLD to the healthcare and scientific community for the benefit of public health.
Funding body: Institute of Health Carlos III (ISCIII) and the European Regional Development Fund (FEDER)
Reference: PI17/00926. Proyecto de Investigación en Salud (FIS)
Lead researcher: Mª Ángeles Zulet Alzórriz (2018-2020)
Lead researcher: Itziar Abete Goñi (2021-2023)
Substantiation of therapeutic strategies that are applicable in routine clinical practice is a priority to reduce the health burden associated with type 2 diabetes mellitus (T2DM). Interventions seeking changes in lifestyle including weight loss or aiming at the promotion of a Mediterranean Dietary (MedDiet) pattern have been shown effective in the prevention of T2DM. However, no clinical trial has been conducted up to date in which both strategies have been combined for the prevention of T2DM in overweight or obese individuals at high risk for the disease. The PREDIMED+DM study was designed to address the primary aim of comparing the incidence of T2DM of an intensive weight loss intervention based on a traditional hypocaloric Mediterranean Diet, physical activity and behavioral therapy, as compared to dietary advice based on a MedDiet in the context of usual health care. The proposed methodology was that of a randomized, multicenter, clinical trial with parallel groups and at least 3 years follow up of a total of 3600 males and females, aged 55 to 75 years, with overweight/obesity, without T2DM but with the metabolic syndrome (MetSd). We proposed to evaluate potential underlying mechanisms and safety aspects of the intervention. In this context, this proposal is an extension of funding of the PREDIMED+DM trial, in which 4958 subjects without T2DM but with the MetSd had been enrolled at completion of recruitment. The PREDIMED+DM study is impinged in the PREDIMED-PLUS study, a randomized clinical trial evaluating the effect of same therapeutic strategies used in our study but on primary prevention of cardiovascular disease in overweight/obese subjects with the MetSd. Thus, the multicenter PREDIMED+DM study should be viewed in the broader sense of the evaluation of strategies aiming at the prevention of cardiovascular disease in our country. Coordinated project (12 centers, among them our group from the University of Navarra). Coordinator: Josep Vidal Cortada, Instituto de Investigaciones Biomédicas August Pi i Sunyer (Barcelona).
The specific objectives of our group are the following:
1. Evaluate the effect of the intervention on body composition.
2. Analyze the evolution of liver damage by non-invasive techniques, as well as the lipid profile as a criterion of metabolic syndrome.
3. Evaluate the inflammatory state, as a mechanism linked to adiposity, hepatic steatosis and depression.
4. Evaluate the psychological state and relate it to body composition, inflammation and liver damage.
5. Epigenetic analysis of candidate genes linked to the inflammatory process, steatosis and depression.
Funding body: The Centre for the Development of Industrial Technology (CDTI) and the European Regional Development Fund (FEDER)
Reference: IDI-20160734. Programa I+D+I CIEN del CDTI.
The increase in the prevalence of chronic noncommunicable diseases such as obesity and related comorbidities (diabetes mellitus type 2, cardiovascular disease, non-alcoholic fatty liver, etc.), present a major public health challenge worldwide. At the same time, between 2015 and 2050, the percentage of individuals aged 60 or over will almost double, increasing from 12% to 22%, which involves a clear aging of the population.
The present situation is giving rise to the development of nutritional strategies aimed at establishing a balanced diet and a healthy lifestyle in the elderly. However, it is important to personalize the nutritional treatment to the individual requirements of each person. This task is being addressed by the "Precision Nutrition", a new operative concept, whose ultimate objective is to provide a proper and characteristic nutrition for each individual, considering relevant personal and clinical information, age and phenotypic and genotypic features. In this context, the number of investigations focused on the search for healthy and functional foods is increasing. Thus, the development of new food products could be interesting in the design of precision nutritional models that allow the individualization of the nutritional treatment in order to improve the response to treatment and ultimately, their health situation.
Within the framework of the NUTRIPRECISIÓN project, the objective is to design precision nutritional strategies that will help in the prevention of diseases associated with aging in the pre-senior and senior population. For this, the precision nutritional intervention will be based on the inclusion of functional foods.
In this sense, the project comprises two main phases:
Phase I: Postprandial studies
The design of functional foods will be carried out through the companies participating in the project. After the preparation of precision foods, the UNAV Nutrition group will perform postprandial, cross-over, double-blind studies in adult men and women, in which the efficacy of the designed food will be evaluated compared to its original unmodified food.
Phase II: Precision nutritional intervention
After completing the postprandial studies, the global intervention study will be addressed. In this sense, the nutritional intervention of precision will be a prospective, randomized study where the effectiveness of different nutritional strategies on the overall health status of senior and / or pre-senior population with metabolic alterations will be analysed.
1) considers aging and associated metabolic diseases (obesity, insulin resistance, cardiovascular disease, etc);
2) combines scientific and business knowledge;
3) addresses precision personalized nutritional strategies with scientific support;
4) provides health education and promotes healthy lifestyles adapted to the specific needs of each individual;
5) is reproducible and applicable in "Promotion of Health and lifestyles".
All with the purpose of:
1) shedding more light on the influence of personalized nutritional strategies in aging and associated pathologies;
2) providing a proper and characteristic nutrition for each individual, considering relevant personal and clinical information, age and phenotypic and genotypic characteristics
3) contributing to the increase of knowledge about precision nutrition to the health and scientific community for the benefit of Public Health.
Development of specific nutritional guidelines for pathologies associated with the metabolic syndrome, particularly personalized advice related to the prevention and progression of non-alcoholic fatty liver.
Development of indexes/scores that allow diagnosis and progression of nutritional metabolic alterations, particularly linked to adiposity, including non- alcoholic fatty liver.
Development of indexes/scores that allow offer a precision nutrition according to a specific metabolic complication or focused in the prevention of its onset. This area of the Center will address on the management of non-alcoholic fatty liver disease.