We hypothesize that the 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 a 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 = 34 each): controls (Group A) will maintain the baseline diet and cases will receive either 30 g/day of dark chocolate containing 500 mg total polyphenols (corresponding to 60 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. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. 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. These parameters will be investigated in muscle and blood cells by state-of-the-art omics techniques. Molecular and nutritional findings will also be confirmed in vitro using skeletal myotubes, blood leukocytes and neural cell lines. Clinical and laboratory results will be processed by a dedicated bioinformatics platform (developed with the external collaboration of the omics company Molecular Horizon Srl) to interpret the molecular response to the nutritional intervention and to personalize its application.
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Change in free-fat soft tissue mass (g)
Timeframe: Baseline (T00), Pre-intervention (T0) after 2-4 weeks, Mid-intervention (T1) after 3 months, Post-intervention (T2) after 3 months and Follow-up (T3) after 3 months