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

该项目将研究将维生素E的抗氧化和细胞保护功能与巧克力多酚和体育活动的皮质醇降低作用相结合，是否有助于防止导致老年人肌肉萎缩的关键细胞功能的年龄依赖性下降。为了做到这一点，该联盟将首先与雀巢公司合作开发一种富含维生素E和多酚的黑巧克力。在为期6个月的试验中，研究人员将对有营养不良和体弱多病风险的老年人进行调查。试验对象最初将稳定在富含蛋白质的饮食（0.9-1.0克蛋白质/公斤理想体重/天）和体育锻炼计划（专门为这些受试者开发的高强度间歇训练）。然后将他们随机分为3组，每组25人。这些小组要么继续进行基线饮食和运动计划（A组），要么每天额外吃30克黑巧克力（含有超过500毫克的总多酚和100毫克的维生素E） （B组），要么额外吃不含额外维生素E的高多酚巧克力（C组）。干预时间为6个月。评估的主要结果将是受试者的肌肉质量，我们也将研究他们的神经认知状态和脆弱的生物分子指标。在研究开始和结束时，将对受试者进行肌肉活组织检查，以确定其收缩力的强度和关键的能量产生细胞器（称为线粒体）的活动。实验室测试将评估受试者遵守研究的程度，并检查干预措施在改变虚弱关键标志方面的有效性。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。改良巧克力成分的影响还将在细胞培养试验中进行检验，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，并使结果的后续应用个性化。

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.