Combining vitamin E-functionalized CHOcolate with physical exercise to reduce the risK Of protein-energy malnutrition in pre-dementia AGEd people

Combining vitamin E-functionalized CHOcolate with physical exercise to reduce the risK Of protein-energy malnutrition in pre-dementia AGEd people
Francesco Galli
University of Perugia


Partner Organization Partner Country
University of Perugia, Department of Pharmaceutical SciencesItaly
University of Verona, Department of Neurological and Movement SciencesItaly
Norwegian University of Science and Technology, Department of Circulation and Medical ImagingNorway
University of Liverpool Department of Musculoskeletal Biology II, Institute of Ageing and Chronic DiseaseUnited Kingdom
Aging and Physical Exercise Research Group. INCLIVA Biomedical Research InstituteSpain
Nestlé Italiana SpAItaly
Molecular Horizon SrlItaly

1. Overall project description

1.1 Summary

The CHOKO-AGE project starts from the assumption that nutrition and physical exercise can support each other to prevent protein-energy malnutrition (PEM) and muscle wasting in the elderly at risk of frailty and disability. Age-dependent PEM is associated with specific alterations of endocrine factors, such as cortisol and insulin, and with a reduced competence of tissues, including the muscle, to utilize dietary nutrients to prevent and eventually repair the lesions deriving from the exposure to cellular stressors, such as reactive metabolites of molecular oxygen produced during metabolic processes, mechanical stresses, etc. The control of cortisol levels and the protection of mitochondrial function and membrane integrity in muscle cells, are key targets in PEM.
Our experimental hypothesis is that physical activity and chocolate polyphenols can combine their cortisol lowering effect with the antioxidant and cytoprotection function of vitamin E, to prevent the age-dependent decline of mitochondrial function and nutrient metabolism in skeletal muscle. Positive effects are also expected on immune cells and in the homeostatic control of inflammatory pathways and tissue repair mechanisms.
To test this hypothesis, a vitamin E-functionalized dark chocolate rich in polyphenols will be developed in collaboration with Perugina, Nestlè company, and its effects will be investigated combined with a high-intensity interval physical training in a 6-month randomized case-control trial in elderly dementia patients. This is a well-defined population of subjects at risk of PEM and frailty. Muscle mass will be the primary endpoint in this intervention study, whereas metabolomics and proteomics data on muscle metabolism, together with cortisol levels and clinical and laboratory indices of neurological and immuno-inflammatory functions, will represent secondary end-points. The latter will be important to interpret molecular and mechanistic aspects standing behind the response to nutrition and physical activity treatment.
To summarize, the fundamental aim of this project is to develop a nutritionally-enhanced and palatable food to support physical activity in preventing PEM in the elderly.
The CHOKO-AGE project involves a consortium of 5 university partners located in Italy, Norway, United Kingdom, and Spain, and of two external collaborators: “Perugina, NestlèItaliana, Spa” and “Molecular Horizon Srl”.

1.2 Highlights

● the CHOKO-AGE project will develop a new vitamin E-functionalized dark chocolate food product
● content and type of the functional agents present in the innovative food product will be verified and their biological activity will be investigated in cell models,
● a high-intensity interval physical training program tailored to elderly subjects at risk of malnutrition and frailty will be designed,
● the effects of the innovative food product and physical activity on indices of protein-energy malnutrition will be verified in a randomized clinical trial,
● molecular and functional data of muscle tissue metabolism and immuno-inflammatory pathways will be gathered and evaluated for interpretation with state-of-the-art bioinformatics tools,
● study outcomes will be utilized to develop models of personalized nutrition and physical activity in the aged at risk of malnutrition and frailty,
● results will be available for the scientific community, national and local health systems, and the general public.

4. Impact

4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf
Cristina Mas-Bargues , Consuelo Escrivá , Mar Dromant , Consuelo Borrás *, José Viña *Lipid peroxidation as measured by chromatographic determination of malondialdehyde. Human plasma reference values in health and disease2021, Volume 709, 1089414
De La Rosa, A., Olaso-Gonzalez, G., Garcia-Dominguez, E., Mastaloudis, A., Hester, S. N., Wood, S. M., Gomez-Cabrera, M. C., & Vina, J.* Glucosamine Supplementation Improves Physical Performance in Trained Mice. 2022, 54(3), 466-474. 4
Esteve, D., Molina-Navarro, M. M., Giraldo, E., Martinez-Varea, N., Blanco-Gandia, M. C., Rodriguez-Arias, M., Garcia-Verdugo, J. M., Vina, J.*, & Lloret, A. Adult Neural Stem Cell Migration Is Impaired in a Mouse Model of Alzheimer's Disease. 2022, 59(2), 1168-1182.4
Garcia-Gimenez, J. L., Mena-Molla, S., Tarazona-Santabalbina, F. J., Vina, J.*, Gomez-Cabrera, M. C., & Pallardo, F. V. Implementing Precision Medicine in Human Frailty through Epigenetic Biomarkers. 2021,18(4).4
Gomez-Cabrera, M. C., Carretero, A., Millan-Domingo, F., Garcia-Dominguez, E., Correas, A. G., Olaso-Gonzalez, G., & Vina, J.*Redox-related biomarkers in physical exercise. 2021, 42, 101956. 4
Ingles, M., Belenguer-Varea, A., Serna, E., Mas-Bargues, C., Tarazona-Santabalbina, F. J., Borras, C.*, & Vina, J. * Functional transcriptomic analysis of centenarians' offspring reveals a specific genetic footprint that may explain that they are less frail than age-matched non-centenarians' offspring. 20224
Marques, P., Fernandez-Presa, L., Carretero, A., Gomez-Cabrera, M. C., Vina, J.*, Signes-Costa, J., & Sanz, M. J. The radiographic assessment of lung edema score of lung edema severity correlates with inflammatory parameters in patients with coronavirus disease 2019-Potential new admission biomarkers to predict coronavirus disease 2019 worsening. 2022, 9, 871714. 4
Mas-Bargues, C., Borras, C.*, & Vina, J.* Genistein, a tool for geroscience. 2022a, 204, 111665. 4
Mas-Bargues, C., Borras, C.*, & Vina, J. *The multimodal action of genistein in Alzheimer's and other age-related diseases. 2022b,183, 127-137. 4
Mas-Bargues, C., Escriva, C., Dromant, M., Borras, C.*, & Vina, J.*Lipid peroxidation as measured by chromatographic determination of malondialdehyde. Human plasma reference values in health and disease. 2021, 709, 108941. 4
Monllor, P., Giraldo, E., Badia, M. C., de la Asuncion, J. G., Alonso, M. D., Lloret, A., & Vina, J. * Serum Levels of Clusterin, PKR, and RAGE Correlate with Amyloid Burden in Alzheimer's Disease.2021, 80(3), 1067-1077.4
Bartolini D*, Marinelli R, Stabile AM*, Frammartino T, Guerrini A, Garetto S, Lucci J, Migni A, Zatini L, Marcantonini G, Rende M*, Galli F. *Wheat germ oil vitamin E cytoprotective effect and its nutrigenomics signature in human hepatocyte lipotoxicity. 2022, 8(9):e10748. 1 10.1016/j.heliyon.2022.e10748.Download

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Online General Public awarenessUnit Coordinator and all partners.Project website: LinkDownload
General PublicAll the partners of the Consortium; Kick-off meeting , online event, 09/07/2021live-streaming of the kick-off eventLink
scientific community Unit Coordinator and P3, 100 Years of Vitamin E: 3rd Vitamin E (VEES3) Satellite Symposium, Ghent, Belgium, 23 of August, 2022.Oral presentations and posters, Conference proceedings.Link

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf


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