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

该项目将研究维生素E的抗氧化和细胞保护功能与巧克力多酚和体力活动的皮质醇降低作用相结合是否有助于防止关键细胞功能的年龄依赖性下降，这些功能是老年人肌肉萎缩的基础。为了做到这一点，财团将首先与雀巢公司合作，开发一种高维生素E含量的黑巧克力，这种黑巧克力也富含多酚。这将在一项为期6个月的试验中结合体力活动进行研究，该试验检查了一个明确定义的有营养不良和虚弱风险的老年受试者人群。受试者最初将稳定在富含蛋白质的饮食（0.9-1.0 g蛋白质/Kg理想体重/天）和体育锻炼计划（专为这些受试者开发的高强度间歇训练）。然后将其随机分配至3组，每组25例受试者。这些组将继续单独的基线饮食和锻炼计划（A组），或将另外接受30 g/天的黑巧克力（含有超过500 mg总多酚和100 mg维生素E）（B组），或将另外接受不含额外维生素E的高多酚巧克力（C组）。干预的持续时间将为6个月。评估的主要结果将是受试者的肌肉质量，我们还将研究他们的神经认知状态和虚弱的生物分子指数。肌肉活检将在研究开始和结束时从受试者身上采集，并进行检查，以确定其收缩力的强度和关键能量产生细胞器（称为线粒体）的活性。实验室测试将评估受试者遵守研究的情况，并检查干预措施在改变脆弱关键标志物方面的有效性。这些参数将通过最先进的“组学”技术在肌肉和血细胞中进行研究。改良巧克力的成分的效果也将在细胞培养试验中进行检查，包括肌肉细胞，血液白细胞和神经细胞。最后，所有这些数据将被整合到一个新的生物信息学项目中，该项目将由一家名为Molecular Horizon Srl的公司开发。这将使我们能够解释对营养干预的反应，并个性化随后对结果的应用。

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.