Abstract

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 and muscle wasting in the elderly. A vitamin E functionalized dark chocolate rich in polyphenols will be developed with Nestle, and its effects will be investigated combined with physical activity in a 6-month randomized case-control trial on pre-dementia elderly patients at risk of undernutrition and frailty. Subjects stabilized on protein rich diet and physical exercise program will be randomized in 3 groups (n = 25 each): Group A – baseline diet. Group B will receive 30 g/day of chocolate containing >500 mg polyphenols and 100 mg RRR-alpha-tocopherol. Group C will receive the high polyphenol chocolate without additional vitamin E. Diet will be isocaloric with the same basal intake of polyphenols and vitamin E in all groups. Muscle mass will be the primary endpoint. Other endpoints will include neurocognitive status and biomolecular indices of frailty. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Laboratory endpoints will assess compliance to the intervention (blood polyphenols and vitamin E status), 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 Molecular Horizon Srl) to interpret the molecular responses to the intervention and to personalize its application.