Plant Natural Products and Health
Polyphenols and Health
Primary Objectives
- Studying the bioavailability and metabolism of dietary polyphenols in humans.
- Understanding the chemical and biological activity of polyphenols and their human metabolites.
- Development of foods with enhanced levels of polyphenols.
Polyphenols are secondary metabolites that are present in the majority of plants and plant foods. The flavonoids are the dominant class of dietary polyphenols and have received considerable attention due to their potent antioxidant activities and their potential to protect against cell / tissue damage and inhibit disease progression in animal models. Examples of flavonoid-rich foods are cocoa / dark chocolate and tea (flavan-3-ols), berry fruits (anthocyanins), onions (flavonols), citrus (flavanones), soy (isoflavones) and apples / red wine (mixed flavonoids). Epidemiological studies provide evidence that diets rich in polyphenols such as flavonoids protect against vascular dysfunction, promote vascular health and reduce CVD risk.
Over the past decade a growing body of evidence from human intervention studies has indicated that specific flavonoids and flavonoid-rich foods can beneficially affect markers related to vascular function and cardiovascular disease risk. However, elucidating the underlying mechanisms has proven a major challenge. Current postulated mechanisms are based on observations from animal and cultured cell models where high doses of hydrophobic aglycones are required to elicit responses, and these are not representative of dietary exposure. The conjugates are unlikely to enter cells because they are too hydrophilic, such as conjugated metabolites, or too large, such as procyanidins. Little is known of the biological activities of flavonoid conjugates largely because these compounds are not available commercially and their synthesis represents a significant technical challenge.
IFR has made a major contribution to this field by focussing on mechanisms that are relevant to polyphenols in the diet, with a particular emphasis on linking human metabolism with biological activities. Currently, we are focussed on understanding, in relation to cardiovascular function, (i) the biological activities of flavonoid phase-2 conjugates produced through human metabolism, (ii) the production and properties of phenolic acid catabolites produced by colonic (microbial) metabolism, and (iii) the absorption and properties of flavan-3-ol oligomers which appear to escape human metabolism.
Previous research at IFR, supported by the BBSRC and the EU, has shown that, during absorption, dietary polyphenols are extensively metabolised and catabolised such that it is predominantly metabolites and catabolites of the food polyphenols that reach the blood and tissues beyond the gut. We have shown that the gut is highly efficient at phase-II metabolism of polyphenols such as flavonoids and, as a result, flavonoids in plasma are present predominantly or exclusively as sulfated and glucuronidated metabolites of the parent flavonoid or their methylated derivatives. The concentrations of flavonoid metabolites in blood and tissues are significantly lower that those frequently used in studies with cell and animal models. We have developed synthetic routes to a number of flavonoid conjugates and are in a position to determine the ability of conjugates to elicit relevant biological responses.
A large portion of ingested flavonoids and other polyphenols reach the colon where they become substrates for the microflora. Research at IFR and with EU partners has shown that the major products are phenolic acids (benzoic, phenyl-acetic and phenyl proprionic acid derivatives) which are absorbed and may be subject to further transformation.
Flavan-3-ols are major dietary flavonoids and the predominant forms in the diet are oligomers and polymers. The most consistent evidence available from controlled intervention trials with flavonoids supports a vascular-protective effect for flavan-3-ols, evidence which is further supported by epidemiologic associations. Since 2005, we have investigated the biological activities of monomeric and oligomeric procyanidins from fruits such as apples and grapes. These studies have shown that whereas oligomeric procyanidins are potent in altering gene expression (assessed using global and gene-specific techniques), protein expression, enzyme activities and cytokine levels, monomeric flavan-3-ols were almost inactive. Although procyanidins have been considered poorly bioavailable with published plasma concentrations <0.1μM, a recent report indicated that traditional extraction methods lead to very poor procyanidin recoveries from plasma, and demonstrated up to 10μM procyanidin in rat plasma. Taken together, these observations support further research to establish the extent to which procyanidins reach the human vascular system and the biological consequences.
We will focus on elucidating mechanisms that are congruent with dietary exposure and with low levels of metabolised polyphenols in vivo. We will provide evidence which is appropriate for underpinning dietary advice and which will serve as a basis for developing foods with enhanced levels of polyphenols that deliver enhanced levels of bioactive metabolites.
Fax: +44(0)1603 507723 
