HDHL- Combining vitamin E-functionalized chocolate with physical exercise to reduce the risk of protein-energy malnutrition in aged people (CHOKO-AGE)

Lead Research Organisation: University of Liverpool
Department Name: Musculoskeletal & Ageing Science

Abstract

This project will examine whether combining the antioxidant and cytoprotective functions of vitamin E with the cortisol lowering effect of chocolate polyphenols and physical activity will help prevent the age-dependent declines in key cellular functions that underpin the onset of muscle wasting in the elderly. In order to do this, the consortia will initially work with the Nestle company to develop a dark chocolate with high vitamin E content that is also rich in polyphenols. This will be investigated combined with physical activity in a 6-month trial examining a well-defined population of elderly subjects at risk of undernutrition and frailty. The test subjects will initially be stabilized on a protein rich diet (0.9-1.0 g protein/Kg ideal body weight/day) and a physical exercise program (High Intensity Interval Training specifically developed for these subjects). They will then be randomly allocated to 3 groups each containing 25 subjects. The groups will either continue on the baseline diet and exercise programme alone (Group A), or will additionally receive 30 g/day of dark chocolate (containing more than 500 mg total polyphenols and 100 mg vitamin E) (Group B), or will additionally receive the high polyphenol chocolate without the additional vitamin E (Group C). The duration of the intervention will be 6 months.

The main outcome that will be assessed will be the muscle mass of the subjects and we will also study their neurocognitive status and biomolecular indices of frailty. Muscle biopsies will be taken from the subjects at the beginning and end of the studies and examined to determine the strength of their contraction force and the activity of key energy-producing organelles, called mitochondria. Laboratory tests will assess how well the subjects have complied with the study and also examine markers of how effective the intervention has been in modifying key markers of frailty. These parameters will be investigated in muscle and blood cells by state-of-the-art "omics" techniques. The effects of the components of the modified chocolate will also be examined in tests of cell cultures including muscle cells, blood leukocytes and nerve cells. Finally, all of these data will be integrated in a new bioinformatics programme that will be developed with a company called Molecular Horizon Srl. This will allow us to interpret the responses to the nutritional intervention and to personalize the subsequent application of the results.

Technical Summary

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.

Publications

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