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

CHOCKO-AGE - Combining vitamin E-functionalized CHOcolate with physical exercise to reduce the risK Of proteinenergy malnutrition in AGEd people. The world's population is getting older and is also becoming more physically inactive. Thus, the need for health care is dramatically increasing. Pre-dementia is the first of four stages of Alzheimer's disease, and individuals suffering this condition are particularly prone to frailty and impaired function. To counteract muscle loss and improve health in this population is of critical importance for the individual, their close family, and the society in general. Effective physical exercise in combination with better nutrition can be a solution to the challenge. Thus, this project investigates the effect of physical exercise combined with better nutrition on health and its potential to prevent malnutrition in the elderly. As part of the project, a new, innovative, nutritional product will be developed: Dark polyphenol-rich chocolate with vitamin E. In particular, the project will look at how the effect of these nutritional factors in dark chocolate can enhance the effect of strength and endurance training to improve muscle mass, muscle function and metabolism in pre-dementia elderly. The training, which will be carried out over a period of six months, has previously shown very good results in the elderly. The strength training will be performed applying high intensity in a leg press apparatus while the endurance training will be carried out as walking with relatively high intensity, in interval form, on a treadmill. In addition to helping this vulnerable group of the elderly, this project has the potential to increase the overall understanding of the effects of nutrition in combination with exercise. The clinical trial is now registered on ClinicalTrials.gov PRS system with the code NCT05343611 and was designed as Multicentric Blinded Randomized Control Trial. Ethical Approval has been obtained for the study. A total of 13 participants have been enrolled in the clinical trial in two of the four Centers, and 4 of them carried out the intervention and all the evaluation sessions planned. For recruiting participants, several local associations, that provide services for people affected by dementia and their family, have been contacted as well as neurologists and geriatricians. During these first months, the clinical trials showed the feasibility of evaluations and training modalities (Maximal Strength Training and High-Intensity Interval Training), chosen for the study, also in this kind of population.

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Antioxidant and cytoprotective functions of vitamin E combined with the cortisol- lowering effect of chocolate polyphenols and physical activity may help prevent the age-dependent decline of mitochondrial function and nutrient metabolism in skeletal muscle, key underpinning events in protein- energy malnutrition (PEM) and muscle wasting in the elderly. To test this hypothesis, a vitamin E- functionalized dark chocolate rich in polyphenols will be developed with the collaboration of Nestlè Company, and its effects will be investigated combined with physical activity in a 6-month randomized case-control trial on pre-dementia elderly patients, a well-defined population of subjects at risk of undernutrition and frailty. Subjects stabilized on protein rich diet (0.9-1.0 g protein/Kg ideal body weight/day) and physical exercise program (High Intensity Interval Training specifically developed for these subjects), will be randomized in 3 groups (n = 25 each): controls (Group A) will maintain the baseline diet and cases will receive either 30 g/day of dark chocolate containing 3500 mg total polyphenols (corresponding to 360 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (Group B) or the high polyphenol chocolate without additional vitamin E (Group C). Diet will be isocaloric and with the same intake of polyphenols and vitamin E in the 3 groups. Muscle mass will be the primary endpoint and other clinical endpoints will include neurocognitive status and previously identified biomolecular indices of frailty in pre-dementia patients. Laboratory endpoints will include the nutritional compliance to the proposed intervention (blood polyphenols and vitamin E status and metabolism), 24-h salivary cortisol, steroid hormones and IGF-1, and molecular indices of inflammation, oxidant stress, cell death and autophagy.