Flavonoid
Flavonoids are a class of polyphenolic secondary metabolites found in plants. Blackberry, black currant, chokeberry, and red cabbage are examples of plants with rich contents of flavonoids. In plant biology, flavonoids fulfill diverse functions, including attraction of pollinating insects, antioxidant protection against ultraviolet light, deterrence of environmental stresses and pathogens, and regulation of cell growth.
Although commonly consumed in human and animal plant foods and in dietary supplements, flavonoids are not considered to be nutrients or biological antioxidants essential to body functions, and have no established effects on human health or prevention of diseases.
Chemically, flavonoids have the general structure of a 15-carbon skeleton consisting of two phenyl rings and a heterocyclic ring. This carbon structure can be abbreviated C6-C3-C6. According to the IUPAC nomenclature, they can be classified into flavonoids or bioflavonoids, isoflavonoids, derived from 3-phenylchromen-4-one structure, and neoflavonoids, derived from 4-phenylcoumarin structure.
As ketone-containing compounds, the three flavonoid classes are grouped as anthoxanthins. This class was the first to be termed bioflavonoids. The terms flavonoid and bioflavonoid have also been more loosely used to describe non-ketone polyhydroxy polyphenol compounds, which are more specifically termed flavanoids.
History
In the 1930s, Albert Szent-Györgyi and other scientists discovered that vitamin C alone was not as effective at preventing scurvy as the crude yellow extract from oranges, lemons or paprika. They attributed the increased activity of this extract to the other substances in this mixture, which they referred to as "citrin" or "vitamin P". The substances in question were later shown not to fulfil the criteria of a vitamin, so that the term "vitamin P" is now obsolete.Biosynthesis
Flavonoids are secondary metabolites synthesized mainly by plants. The general structure of flavonoids is a fifteen-carbon skeleton, containing two benzene rings connected by a three-carbon linking chain. Therefore, they are depicted as C6-C3-C6 compounds. Depending on the chemical structure, degree of oxidation, and unsaturation of the linking chain, flavonoids can be classified into different groups, such as anthocyanidins, flavonols, flavanones, flavan-3-ols, flavanonols, flavones, and isoflavones. Chalcones, also called chalconoids, although lacking the heterocyclic ring, are also classified as flavonoids. Furthermore, flavonoids can be found in plants in glycoside-bound and free aglycone forms. The glycoside-bound form is the most common flavone and flavonol form consumed in the diet.Functions in plants
Numbering some 5,000 individual compounds, flavonoids are widely distributed in plants, fulfilling numerous functions, including attraction of pollinating insects, deterrence of environmental stresses, and regulation of cell growth. They are the most important plant pigments for flower coloration, producing yellow, red or blue pigmentation in petals evolved to attract pollinators.In higher plants, they are involved in antioxidant roles in plant cells, filtration of ultraviolet light, symbiotic nitrogen fixation, and defense against pathogens and pests. They also act as plant chemical messengers, physiological regulators, and cell cycle inhibitors. Flavonoids secreted by the root of their host plant help Rhizobia in the infection stage of their symbiotic relationship with legumes such as peas, beans, clover, and soy. Rhizobia living in soil are able to sense the flavonoids and this triggers the secretion of Nod factors, which in turn are recognized by the host plant and can lead to root hair deformation and several cellular responses such as ion fluxes and the formation of a root nodule. In addition, some flavonoids have inhibitory activity against organisms that cause plant diseases, e.g. Fusarium oxysporum.
Subgroups
Flavonoids have been classified according to their chemical structure, and are usually subdivided into the following subgroups:Anthocyanidins
s are the aglycones of anthocyanins; they use the flavylium ion skeleton.Anthoxanthins
s are divided into two groups:Flavanones
Flavanonols
Flavans
Include flavan-3-ols, flavan-4-ols, and flavan-3,4-diols.| Skeleton | Name |
| Flavan-3-ol | |
| Flavan-4-ol | |
| Flavan-3,4-diol |
- Flavan-3-ols
- * Flavan-3-ols use the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton
- :Examples: catechin, gallocatechin, catechin 3-gallate, gallocatechin 3-gallate, epicatechins, epigallocatechin, epicatechin 3-gallate, epigallocatechin 3-gallate
- * Theaflavin
- :Examples: theaflavin-3-gallate, theaflavin-3'-gallate, theaflavin-3,3'-digallate
- * Thearubigin
- * Proanthocyanidins are dimers, trimers, oligomers, or polymers of the flavanols
Isoflavonoids
- Isoflavonoids
- *Isoflavones use the 3-phenylchromen-4-one skeleton
- :Examples: genistein, daidzein, glycitein
- *Isoflavanes
- *Isoflavandiols
- *Isoflavenes
- *Coumestans
- *Pterocarpans
Dietary sources
Foods with a high flavonoid content include blackberries, black currants, parsley, onions, blueberries and strawberries, red cabbage, black tea, dark chocolate, and citrus fruits. One study found high flavonoid content in buckwheat.
Citrus flavonoids include hesperidin, quercitrin, rutin.
Peanut skin contains significant polyphenol content, including flavonoids.
Dietary intake
for flavonoids were provided by the USDA database on flavonoids. In the United States NHANES survey, mean flavonoid intake was 190 mg per day in adults, with flavan-3-ols as the main contributor. In the European Union, based on data from the European Food Safety Authority, mean flavonoid intake was 140 mg/d, although there were considerable differences among individual countries. The main type of flavonoids consumed in the EU and USA were flavan-3-ols, mainly from tea or cocoa in chocolate, while intake of other flavonoids was considerably lower.Non-nutrient status in humans
Flavonoids are not considered as nutrients because there is no evidence for a cause-and-effect on specific cells or organs in vivo. The European Food Safety Authority determined that dietary flavonoids do not have the characteristics of nutrients, as they do not reduce disease risk, affect physiological or behavioral functions, improve satiety, contribute calories, or influence the growth and development of children. The bioavailability of flavonoids is low because they are extensively metabolized in the stomach, small intestine and liver, and are rapidly excreted.In the United States, flavonoids and other polyphenols are not included on the FDA list of nutrients.
Metabolism and excretion
Flavonoids are poorly absorbed in the human body, then are quickly metabolized into smaller fragments with unknown properties, and rapidly excreted. Flavonoids have negligible antioxidant activity in the body, and the increase in antioxidant capacity of blood seen after consumption of flavonoid-rich foods is not caused directly by flavonoids, but by production of uric acid resulting from flavonoid depolymerization and excretion. Microbial metabolism is a major contributor to the overall metabolism of dietary flavonoids.Safety
Likely due to the low bioavailability and rapid metabolism and excretion of flavonoids, there are no safety concerns and no adverse effects associated with high dietary intakes of flavonoids from plant foods.Regulatory status
Due to the absence of proof for flavonoid health effects in clinical research, neither the United States FDA nor the European Food Safety Authority has approved any flavonoids as prescription drugs.The FDA has warned numerous dietary supplement and food manufacturers, including Unilever, producer of Lipton tea in the U.S., about illegal advertising and misleading health claims regarding flavonoids, such as that they lower cholesterol or relieve pain.
From 2020 to 2023, the FDA issued 11 warning letters to American manufacturers of flavonoid dietary supplements for false advertising of health claims and illegal misbranding of products.