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

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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.