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水果和蔬菜中被称为类黄酮的成分的作用，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，一些类黄酮类和富含类黄酮的食物对血管壁具有直接保护作用，由于心血管疾病(CVD)和动脉僵硬是由于对血管壁的累积损伤造成的，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。当研究人员在我们食用富含黄酮类的食物后测量血液中任何一种类黄酮量时，它们的水平太低，无法解释观察到的心血管益处。因此，食用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的结果。因此，我们认为，食用类黄酮对健康的好处肯定是多种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食用它们时所发生的那样。在我们的血液和血管中发现了复杂的类黄酮化合物，这是因为人们食用了各种富含类黄酮的食物，如水果、蔬菜、巧克力、果汁、葡萄酒和茶。然而，尽管我们知道类黄酮是以化合物的混合物的形式摄入的，但到目前为止，研究人员已经孤立地研究了它们的影响，并使用了远远高于正常饮食所能获得的类黄酮水平。因此，这些现有的发现很可能是不准确的，因此很难利用这些发现来为摄入类黄酮对健康的好处提供饮食建议。我们计划研究摄入多种类黄酮对心血管的益处，就像在正常的英国饮食中一样，以提供更准确的数据，这些数据可以在未来用来为摄取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包括血管和免疫细胞的细胞培养模型来确定黄酮类化合物对心血管健康的有益影响是否是多种类型的黄酮类化合物共同作用的结果。我们还将在分离和组合两种情况下应用类黄酮及其代谢物，以提供更接近生物现实的模型。这些研究将利用国家饮食和营养调查的调查数据，探索在目前英国饮食中发现的丰度最高的类黄酮的活性。由于这项调查确定英国目前水果和蔬菜的平均摄入量约为每天3份(比建议摄入量低2份)，我们将测试相对于每天3、5和7份水果和蔬菜的摄入量的影响。影响：这项建议促进了一种营养战略，以改善心血管健康，使用一种‘天然’饮食方法，包括来自多种食物来源的类黄酮，这些食物与工业、农业和公众都有很强的相关性。该项目将提供证据，证明我们目前食用富含类黄酮类食物的饮食对健康的影响，与达到每天5次及以上的最佳水平有关；并将帮助设计未来旨在解决英国饮食变化以利于健康的喂养干预措施。该项目还将通过建立最佳的心血管终点、黄酮类化合物和剂量，为未来的类黄酮类干预试验的设计提供“概念证明”。最后，建立一些黄酮类化合物的共享和累积生物活性将有助于建立未来许多富含黄酮类化合物的产品的功能健康声明。

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.