The collective bioactivity of dietary flavonoids: importance of specific structural characteristics for cardiovascular benefits

大量摄入水果和蔬菜可以降低患心脏病的风险，但提供这些保护作用的水果和蔬菜的成分尚不清楚。越来越多的证据支持被称为类黄酮的水果和蔬菜成分的作用，研究表明，摄入大量富含类黄酮的食物的人可以改善心血管健康。特别是，研究表明，一些类黄酮和富含类黄酮的食物对血管壁有直接的保护作用，由于心血管疾病（CVD），特别是动脉硬化是由血管壁的累积损伤引起的，这些数据表明，类黄酮可以帮助恢复和优化血管功能；从而降低心血管疾病的风险。当研究人员在我们吃了富含类黄酮的食物后测量血液中任何一种类黄酮的含量时，它们的水平太低，无法解释观察到的心血管益处。因此，摄入类黄酮的健康益处很可能是同时摄入多种类黄酮的集体效应。因此，我们相信，摄入类黄酮对健康的好处一定是许多不同类型的类黄酮共同作用的结果，就像我们在正常饮食中摄入它们一样。在我们的血液和血管中发现了复杂的类黄酮组合，这是食用多种富含类黄酮的食物的结果，如水果、蔬菜、巧克力、果汁、葡萄酒和茶。然而，尽管我们知道黄酮类化合物是作为化合物的混合物被食用的，但迄今为止，研究人员已经单独研究了它们的影响，并使用了远高于正常饮食所能获得的黄酮类化合物水平。因此，这些现有的研究结果很可能是不准确的，因此很难利用这些发现为摄入类黄酮的健康益处提供饮食建议。我们计划研究在正常的英国饮食中摄入多种类黄酮对心血管的益处，以提供更准确的数据，这些数据可以在未来用于为摄入类黄酮的真正健康益处提供建议。目的和目的：我们的目标是使用一种先进的细胞培养模型，包括血管细胞和免疫细胞，以确定黄酮类化合物对心血管健康的有益作用是否是多种黄酮类化合物共同作用的结果。我们还将应用黄酮类化合物及其代谢物分离和组合，以提供一个更现实的生物学模型。这些研究将探索目前英国饮食中含量最高的类黄酮的活性，这些类黄酮是根据国家饮食和营养调查的调查数据建立的。由于这项调查确定了目前英国人每天平均食用3份水果和蔬菜（比推荐摄入量低2份），我们将测试每天食用3份、5份和7份水果和蔬菜的影响。启示：该建议提倡一种利用“天然”饮食方法改善心血管健康的营养策略，其中包括来自多种食物来源的类黄酮，这些类黄酮具有很强的工业、农业和公共相关性。该项目将为我们目前饮食中富含类黄酮的食物对健康的影响提供证据，以达到每天5种及以上的最佳水平；并将有助于设计未来的喂养干预措施，旨在解决英国的饮食变化，以促进健康。该项目还将通过建立最佳心血管终点、类黄酮和剂量，为未来类黄酮干预试验的设计提供“概念证明”。最后，建立一些类黄酮的共享和累积生物活性将有助于建立许多高类黄酮产品的未来功能性健康声明。

A high intake of fruits and vegetables reduces heart disease risk, but the components of the fruits and vegetables that provide these protective effects remains unclear. Growing evidence supports a role of fruit and vegetable components called flavonoids and research shows that people who consume high intakes of flavonoid-rich foods have improved cardiovascular health. In particular, research shows that some flavonoids and flavonoid-rich foods exert direct protective effects on blood vessel walls, and since cardiovascular diseases (CVD) and specifically stiffness of the arteries results from accumulated damage to blood vessel walls, these data suggest that flavonoids can help restore and optimise vessel function; therefore reducing CVD risk. When researchers measure the amount of any one type of flavonoid in the blood after we eat flavonoid-rich foods, their levels are too low to explain the observed cardiovascular benefit. Therefore, it is likely that the health benefits of flavonoid consumption results from the collective effects of consuming multiple types of flavonoids at the same time. We therefore believe that the health benefits resulting from flavonoid consumption must be the result of many different types of flavonoids working together, as happens when we eat them in our normal diet. Complex combinations of flavonoids are found in our blood and vessels as a result of the consumption of a diversity of flavonoid-rich foods, such as fruits, vegetables, chocolate, juice, wine, and tea. However, although we know that flavonoids are consumed as mixtures of compounds, to date, researchers have studied their impacts in isolation and using levels of flavonoids that are well above that which could be obtained through eating a normal diet. These existing findings are therefore likely to be inaccurate, making it difficult to use these findings to provide dietary advice for the health benefits of flavonoid consumption. We plan to study the cardiovascular benefits of consuming multiple flavonoids as would be consumed in the normal UK diet to provide more accurate data which could be used in the future to provide advice on the true health benefits of flavonoid consumption. Aims and objectives: We aim to use an advanced cell culture model involving both vascular and immune cells to establish if the beneficial effects of flavonoids on cardiovascular health are the result of many types of flavonoid working together. We will also apply flavonoids and their metabolites in both isolation and in combination to provide a more biologically realistic model. These studies will explore the activities of the flavonoids found in the highest abundance in the present UK diet as established using survey data from the National Diet and Nutrition Survey. As this survey established the current UK consumption of fruits and vegetables to be around 3 portions per day on average (and 2 portions below recommended intake levels), we will test the effects of consuming doses relative to 3, 5 and 7 servings of fruits and vegetables per day. Implications: This proposal promotes a nutritional strategy to improve cardiovascular health using a 'natural' dietary approach, involving flavonoids from multiple food sources which hold strong industrial, agricultural and public relevance. This project will provide evidence of the health impact of our current dietary consumption of flavonoid-rich foods, in relation to reaching optimal levels of 5-a-day and above; and will aid in the design of future feeding interventions directed at addressing dietary change in the UK for health benefit. This project will also provide 'proof of concept' for the design of future flavonoid intervention trials by establishing optimal cardiovascular endpoints, flavonoids and doses. Lastly, establishing a shared and cumulative bioactivity of a number of flavonoids will aid in establishing future functional health claims for many products high in flavonoids.