Flavonoids and polyphenols are the vast family of more than 8,000 distinct plant secondary metabolites that are responsible for the colours, the flavours, and the biological activities of fruits, vegetables, herbs, spices, tea, coffee, red wine, dark chocolate, and other plant-based foods. The flavonoids are characterised by a common three-ring C6-C3-C6 structure, and they are divided into subclasses — including the flavones (found in parsley, celery, and chamomile), the flavonols (found in onions, apples, berries, and Ginkgo biloba), the flavanones (found in citrus fruits), the flavanols (found in tea, cocoa, and grapes), the anthocyanins (found in berries, grapes, and red cabbage), and the isoflavones (found in soybeans and legumes). The polyphenols are a broader class that includes all plant phenolics, including the flavonoids and the non-flavonoid polyphenols such as resveratrol (from red wine and grapes), curcumin (from turmeric), and the hydroxycinnamates (found in coffee, fruits, and vegetables). Together, the flavonoids and polyphenols are the most abundant antioxidants in the human diet, and their regular consumption is associated with reduced risk of cardiovascular disease, cancer, neurodegenerative disease, and the chronic inflammatory conditions that are the pathological basis of the metabolic syndrome, type 2 diabetes, and the ageing process itself.
The Antioxidant Activity of Flavonoids
Flavonoids are the most effective dietary antioxidants that have been identified — they directly neutralise reactive oxygen species (ROS) and reactive nitrogen species (RNS) through their phenolic hydroxyl groups, which donate hydrogen atoms to the radical species and form stable flavonoid radicals that are relatively unreactive. The antioxidant activity of flavonoids is determined by the number and the position of the hydroxyl groups on the flavonoid molecule — the catechol group in the B-ring (which is present in the flavanols, the flavonols, and the anthocyanins) is particularly important for antioxidant activity, as is the 3,5-dihydroxylation of the A-ring and the 2,3-double bond in conjunction with the 4-carbonyl group in the C-ring. The structural requirements for antioxidant activity are met by the majority of the flavonoids that are found in plant-based foods, which explains why a diet that is rich in fruits and vegetables is consistently associated with higher antioxidant status and with reduced risk of the chronic inflammatory diseases that are driven by oxidative stress.
The clinical importance of dietary flavonoids for cardiovascular health is demonstrated by the consistent association between flavonoid intake and reduced cardiovascular risk in large prospective cohort studies. The Nurses Health Study and the Health Professionals Follow-Up Study found that the flavanone intake from citrus fruits was inversely associated with the risk of stroke, with an approximately 20% reduction in risk in the highest vs the lowest quintile of intake. The Zutphen Elderly Study found that the flavonoid intake from tea, fruits, vegetables, and wine was inversely associated with the risk of coronary heart disease, with an approximately 50% reduction in risk in the highest vs the lowest quartile of intake. These findings are consistent with the known biological activities of flavonoids — their antioxidant activity, their anti-inflammatory effects, their vasodilatory effects (through the stimulation of endothelial nitric oxide production), and their anti-platelet effects (through the inhibition of the cyclooxygenase and lipoxygenase enzymes).
Flavonoids and the Gut Microbiota
The flavonoids are also prebiotics — they are metabolised by the gut microbiota to produce a range of bioactive metabolites that may be responsible for some of the biological activities that are attributed to the parent flavonoid compounds. The gut microbiota can deglycosylate flavonoids (removing the sugar moiety that is attached to the flavonoid in plant-based foods), can cleave the flavonoid C-ring to produce phenolic acids, and can demethylate, dehydroxylate, and reduce the flavonoid skeleton to produce a range of metabolites that are absorbed into the bloodstream and that have biological activities that may differ from those of the parent compound. The gut microbiota of individuals differ in their capacity to metabolise flavonoids, and this interindividual variation in flavonoid metabolism is one of the factors that determine the variability in the biological responses to flavonoid supplementation that is observed in clinical trials.
Practical Application
For general flavonoid and polyphenol supplementation, the evidence-based approach is to consume a wide variety of plant-based foods — including fruits, vegetables, herbs, spices, tea, coffee, red wine (in moderation), and dark chocolate (with at least 70% cocoa content) — on a daily basis. The most evidence-based specific flavonoid supplements are the standardised extracts — including Ginkgo biloba extract (for cognitive function and cerebral blood flow), bilberry extract (for visual function and night vision), grape seed extract (for cardiovascular health), and the isoflavones from soy (for the management of menopausal symptoms and for cardiovascular health in postmenopausal women). For comprehensive antioxidant and anti-inflammatory support, flavonoids and polyphenols pair well with vitamin C (which regenerates the flavonoid radicals and extends the antioxidant activity of flavonoids), with vitamin E (which regenerates vitamin C at the lipid-water interface), with selenium (which is required for the glutathione peroxidase enzymes that work alongside flavonoids in the antioxidant defence system), and with the omega-3 fatty acids (which have complementary anti-inflammatory effects and which are particularly important for the resolution of chronic inflammation).
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