The Human Nutrition Unit (HNU) is a highly productive, interdisciplinary and dynamic team with extensive experience and sufficient autonomy in developing epidemiological studies, clinical trials, and basic research. The scope of this research group is to evaluate the effect of dietary patterns or dietary compounds on obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), cardiovascular diseases (CVD), cognition and male fertility. We focus on the effect of dietary components and functional foods on energy balance, lipid profile, inflammation, oxidation and glucose metabolism, as well as on the effect of dietary patterns on the primary prevention of CVD and diabetes. In addition to classical epidemiology, the Research Unit possesses expertise in the use of omics sciences (especially genomics, transcriptomics, metabolomics, metagenomics and proteomics) to assess the effect of precision nutrition on health and disease.
The HNU also collaborates with well-recognized Spanish and international Universities and health research Institutes, demonstrating our commitment to the internationalization of Spanish research, drawing on strengths, leadership capability, and competence in technical and soft skills to effectively communicate and nurture sustainable partnerships with external organizations. The incorporation of expert multicultural researchers in different disciplines (medical doctors, dietitians, biologists, biotechnologists, food technologists, and psychologists), has provided the group with several skills related not only to the development and implementation of large clinical trials and cohort studies, but also with the capability of obtaining quantitative data; knowledge of data analysis techniques; ability to network and create contacts; creative ability, originality and innovation, and the ability to improvise and find ways to overcome any difficulties. Moreover, the group stands out for its capacity to obtain funding (public and private) and for its extensive scientific production.
The HNU's research facilities and equipment are primarily based at the Rovira i Virgili University. Our links with the Nutrition and Obesity Unit of the Sant Joan de Reus University Hospital enable us to integrate research into applied clinical care. The group is also affiliated with the Pere i Virgili Institute of Health Research, the CIBERobn - Instituto de Salud Carlos III that includes 23 state research groups in relation to Nutrition and Obesity, and the Catalan Nutrition Center of the Institute of Catalan Studies (CCNIEC), a research network center that brings together 27 research groups from Catalonia in relation to food and nutrition. These affiliations provide HNU extended access to their infrastructure and services.
The HNU is recognized as a consolidated group at regional (Generalitat de Catalunya in 2009), national (Instituto de Salud Carlos III in 2013) and International (European Association for the Study of Obesity in 2014) levels.
Over the last years, the group has led two large clinical trials for the primary prevention of cardiovascular disease (PREDIMED and PREDIMED-Plus) along with several other clinical trials (SATIN, PREDIGEN, EFINUT, EPIRDEM, FERTINUTS) and observational studies (CORALS, Led-Fertyl and NUTPOOL).
The PREDIMED study, http://www.predimed.es, is a large multi-center parallel clinical trial conducted in 7,447 participants at high CVD risk aiming to assess the effect of a Mediterranean diet supplemented with virgin olive oil or nuts in the context of primary prevention of CVD). PREDIMED which began in 2003 and was completed in 2009, demonstrated the beneficial effects of MedDiet on the incidence of CVD, T2D and other related outcomes. In this trial, our group has particularly focused on the study of inflammation, kidney function, T2D and its complications, and metabolic syndrome (MetS). PREDIMED has changed the current dietary recommendations for CVD and T2D worldwide, including the Dietary Guidelines for Americans. With the availability of a huge database, the HNU will continue to explore several hypotheses related to its research interests in the future. Currently, with the biological samples obtained from this study, several analyses have been conducted using different omics platforms (e.g., transcriptomics, genomics, metabolomics). These projects have been conducted in collaboration with the PREDIMED consortium and several other research groups, funded by the Spanish Ministry of Health, Fundació Marató TV3, Fundación Ramon Areces, and the US National Institutes of Health (NIH). As we are actively following this cohort, in the next 5-y, we will also test the long-term efficacy of the interventions on several other important outcomes.
With the completion of PREDIMED, in 2014, the HNU began another multi-center RCT, PREDIMED-Plus (https://www.predimedplus.com), to study the effects of a 6-y lifestyle modification program for weight loss. The PREDIMED-Plus clinical trial has become the biggest milestone in nutrition investigation accomplished in Spain, investigating the effect of an energy-restricted MedDiet and physical activity on 1) CVD incidence and mortality; weight loss; 2) incidence of other related chronic diseases; 3) changes in CVD risk factors and other intermediate outcomes. The recruitment of this study (n= 6,874) was finished in 2016. Vast amounts of data and biological samples (plasma, serum, DNA, urine, stools) collected according to protocol will be utilized for further studies. As coordinator of this study involving 23 recruiting research groups and 6 lab centres, the group has received an array of National, European and USA grants. With all of these projects and collaborations, we have also developed skills in the area of precision medicine using different approaches such as OMICs (proteomics, metagenomics, meta-metabolomics, metabolomics), which we are now applying in epidemiologic and clinical studies.
Another important target of the Unit related to PREDIMED and PREDIMED-Plus is to work on the predictability of T2D, chronic kidney disease (CKD), and CVD using metabolome profiling and genetic polymorphisms. The close collaboration with other international research groups facilitates the validation of our findings in other international cohorts (the Health Professionals Follow-up Study, Nurse's Health Study, MESA, DPP, and EPIC studies). Over the last 5 years, we have identified several metabolites, genetic polymorphisms, and pathways implicated in the risk of CVD, diabetes, heart failure, atrial fibrillation, and peripheral artery disease. We have also tested the mediating effect of the interventions on CVD, diabetes, heart failure or atrial fibrillation risk on genetic and plasma metabolome variations. Recently, we also assessed the effect of our interventions and diabetes status on impulsivity, compulsivity, cognition and the mediating effect of the gut microbiota, metabolomics and proteomics on these end-points. For this purpose, we have had two National grants (two from the ISCII) and 3 European grants as Co-investigators (Eat2BeNice; https://eat2benice.eu, STOP; http://www.stopchildobesity.eu; and PRIME; https://prime-study.eu), and a Canadian grant PI from the Canadian Institutes of Health Research (CIHR). Moreover, with a project granted by the Fundación Francisco Soria Melguizo, we study the risk factors for COVID-19 infection and their impact on quality of life, mood and cognitive function in the PREDIMED-Plus study participants.
Our group has participated in different NIH-funded projects in collaboration with Navarra University, Harvard University, Broad Institute, and other groups belonging to the PREDIMED study. Prof. Salas-Salvadó is co-PI of 5 NIH projects: 1) Dietary Interventions, Metabolites, and Risk of Type 2 Diabetes; 2014-2018), 2) Circulating plasma metabolites, diet, and risk of type 2 diabetes; 2018-2021), 3) Lifestyle Interventions, Metabolites, Microbiome, and Diabetes Risk; 2020-2023), and co-investigator of the project Mediterranean diet, Metabolites, and cardiovascular disease; 2013-2021 and 2022-2026). Research on those projects has explored the association between specific metabolites related to key pathways such as glycolysis/gluconeogenesis, tricarboxylic acid cycle, lysine, arginine, tryptophan, glutamate, branched chain/aromatic amino acids, choline, acylcarnitines, ceramides, lipidomic profile, and T2D and/or CVD. Moreover, the consortium has also published manuscripts in reputable journals unravelling metabolites associated with the Mediterranean diet pattern as a whole and also certain key food groups defining the Mediterranean diet, such as red wine, coffee, protein, walnuts, nuts, and dairy products. In 2024, the group as Co-PI, received another research grant from the USA-NIH entitled: The Microbiome-Gut-Brain Axis and Personalized Mediterranean Diet Interventions for Alzheimer's Dementia Prevention conducted in 650 PREDIMED-Plus participants using metagenomics, metabolomics and transcriptomics techniques).
Additionally, in collaboration with Toronto University (Canada), the Human Nutrition Unit is contributing to a novel and transformative research paradigm via the multicenter CHEAP trial funded by the Canadian Institutes of Health Research to study the use of technology in improving personal, public, and planetary health. In collaboration with Toronto University and as co-applicants we are participating in two other projects granted by Diabetes Canada and the Almond Board of California.
CORALS (http://www.corals.es), is a multicentric, long-term (10-year follow-up) large (n=2200) observational prospective pediatric cohort study that allows us to explore in the future the association between lifestyle and other determinants of adiposity, cognition, and CVD risk factors. This observational ongoing study started four years ago and we are collecting a large amount of information and biological samples (plasma, serum, buffy coat, urine, and stools. CORALS has included in a European grant entitled: "Zero_HiddenHunger_EU: Tackling micronutrient malnutrition and hidden hunger to improve health in the EU.
Another subject of interest of the group is male infertility, an important public health problem in the last few decades. In particular, we have been interested in the effect of obesity, food, and food patterns on semen quality. FERTINUTS was an international randomized clinical trial conducted by our group to assess the effects of chronic nut consumption on semen quality and functionality in a cohort of healthy males and described several potential mechanisms. Recently, we have started a cross-sectional cohort study (LED-FERTYL; https://ledfertyl.eu/) to explore the potential lifestyle and environmental determinants of male fertility that has been expanded to other investigators´ groups (Poland, Spain, and the UK).
Our group is also very interested in analyzing the beneficial effects of fat-rich food on several outcomes. Using epidemiological approaches and clinical trials (EFINUT, EPIRDEM), we explored the effect of the consumption of nuts on several intermediate outcomes using our developed and acquired methodological techniques in collaboration with national and international (India and USA) research groups. Recently, we have begun work on the NUTPOOL project; https://nutpool.eu/, as Co-PI in close collaboration with the University of Copenhagen (PI) that aims to analyze the association between nut consumption and several chronic disease outcomes using data from different cohorts around the world (granted by the International Nut and Dried Fruit Foundation).
THE MULTIDISCIPLINARY RESEARCH GROUP:
Prof. J. Salas-Salvadó is the Director of the HNU, the Coordinator of the PREDIMED-Plus study, Co-PI on the NUTPOOL project, a member of the steering committee of PREDIMED, the director of the URV Chair in nuts, and CIBERobn PI and coordinator of its nutrition program. He has extensive experience in studying the relationship between food, food components or dietary food patterns in obesity and other cardiovascular risk factors. A medical doctor by training, he has been both a successful leader and collaborator in several large nutritional and pharmacological trials for the management of obesity. His research in recent years has also focused on the modulation of circulating metabolome, microbiome, and several epigenetic tags including microRNAs and their potential role in obesity. Dr. N. Babio, Co-PI of the HNU, is a dietitian-nutritionist and has participated in most of the clinical trials that have been conducted in our unit. Dr. Babio currently leads the CORALS and Led-Fertyl studies. Dr. JF. García-Gavilan is an epidemiologist specializing in nutritional epidemiology and metabolomics and is the PREDIMED-Plus project manager. Dr. SK. Nishi is a postdoctoral researcher from Canada and is a dietitian and expert in conducting clinical trials, epidemiology, and meta-analyses assessing the impact of diet and dietary factors on cardiometabolic and cognitive health. Dr. MA. Martinez-Rodriguez is a researcher with a large background in molecular biology and specialized in endocrine disruptors and metagenomics. She is responsible for our laboratory and is skilled in all of the molecular analysis techniques required (i.e. metagenomics and telomere analysis). Dr. A. Atzeni is a postdoctoral researcher with biomedical laboratory technique expertise, specifically in the field of gut microbiota and metabolomics, machine learning and bioinformatics, in Italy. Dr. I. Paz-Graniel is a postdoctoral researcher and nutritionist with extensive epidemiological research experience in the field of dietary factors, especially the area of beverages, and cardiometabolic and mental health as well as metabolomics and proteomics applied to cognition and cardiovascular disease. Dr. S. Shyam is a senior postdoctoral researcher with expertise in conducting and reporting nutrition trials. She has 9 years of teaching experience at the International Medical University in Malaysia prior to joining the HNU team.
Cumulatively, the Human Nutrition Unit is well-versed in conducting robust scientific research given the team's background in basic sciences and expertise in clinical research. This guarantees the translationally of their research.