Flavanols (with an "a") are not to be confused with flavonols (with an "o"), a class of flavonoids containing a ketone group.
The single-molecule (monomer) catechin, or isomer epicatechin (see diagram), adds four hydroxyls to flavan-3-ol, making building blocks for concatenated polymers (proanthocyanidins) and higher order polymers (anthocyanidins).
Flavanols possess two chiral carbons, meaning four diastereoisomers occur for each of them.
Catechins are distinguished from the yellow, ketone-containing flavonoids such as quercitin and rutin, which are called flavonols. Early use of the term bioflavonoid was imprecisely applied to include the flavanols, which are distinguished by absence of ketone(s). Catechin monomers, dimers, and trimers (oligomers) are colorless. Higher order polymers, anthocyanidins, exhibit deepening reds and become tannins.
Catechin and epicatechin are epimers, with (-)-epicatechin and (+)-catechin being the most common optical isomers found in nature. Catechin was first isolated from the plant extract catechu, from which it derives its name. Heating catechin past its point of decomposition releases pyrocatechol (also called catechol), which explains the common origin of the names of these compounds.
The flavonoids are products from a cinnamoyl-CoA starter unit, with chain extension using three molecules of malonyl-CoA. Reactions are catalyzed by a type III PKS enzyme. These enzyme do not use ACPSs, but instead employ coenzyme A esters and have a single active site to perform the necessary series of reactions, e.g. chain extension, condensation, and cyclization. Chain extension of 4-hydroxycinnamoyl-CoA with three molecules of malonyl-CoA gives initially a polyketide (Figure 1), which can be folded. These allow Claisen-like reactions to occur, generating aromatic rings.
Schematic representation of the flavan-3-ol (-)-epicatechin metabolism in humans as a function of time post-oral intake. SREM: structurally related (-)-epicatechin metabolites. 5C-RFM: 5-carbon ring fission metabolites. 3/1C-RFM: 3- and 1-carbon-side chain ring fission metabolites. The structures of the most abundant (-)-epicatechin metabolites present in the systemic circulation and in urine are depicted.
Flavan-3-ol precursors of the microbial metabolite 5-(3?/4?-dihydroxyphenyl)-?-valerolactone (gVL). Only compounds with intact (epi)catechin moiety result in the formation of ?VL by the intestinal microbiome. ECG, (-)-epicatechin-3-O-gallate; EGCG, Epigallocatechin gallate; EGC, Epigallocatechin
Most data for human metabolism of flavan-3-ols are available for monomeric compounds, especially Catechin. These compounds are taken up and metabolised upon uptake in the jejunum, mainly by O-methylation and glucuronidation, and then further metabolised by the liver. The colonic microbiome has also an important role in the metabolism of flavan-3-ols and they are catabolised to smaller compounds such as 5-(3?/4?-dihydroxyphenyl)-?-valerolactones and hippuric acid. Only flavan-3-ols with an intact (epi)catechin moiety can be metabolised 5-(3?/4?-dihydroxyphenyl)-?-valerolactones.
Potential health effects of catechins
The supposed health benefits of catechins have been studied extensively in humans and animal models, but there are no proven effects that apply to human health. Until 2013, neither the Food and Drug Administration nor the European Food Safety Authority had approved any health claim for catechins or approved any as pharmaceutical drugs. Moreover, several companies have been cautioned by the FDA over misleading health claims.
In 2014, the European Food Safety Authority approved the following health claim for cocoa products containing 200 mg of flavanols and meeting the qualification in dietary supplement products: "cocoa flavanols help maintain the elasticity of blood vessels, which contributes to normal blood flow".
Possible reduced benefits
An editorial warned against increasing one's intake of dark chocolate to improve health because the beneficial compounds, suggested to be flavanols, are sometimes removed due to their bitter taste without an indication on the label. Additionally, such a product is high in fat, sugar and Calories, contributing to a poor diet if consumed in large amounts.
Recent study tested catechins employed to coat nanoparticles of iron oxides in the blood. These particles allow visualization of vessels - and especially cancer tumors in mice - in an MRI exam. The nanoparticles would clump together without the catechin coating.
^ abOPC in Practice, 1995 3rd Edition, by Bert Schwitters in collaboration with Prof. Jack Masquelier.
^Actis-Goretta, Lucas; Lévèques, Antoine; Rein, Maarit; Teml, Alexander; Schäfer, Christian; Hofmann, Ute; Li, Hequn; Schwab, Matthias; Eichelbaum, Michel (October 2013). "Intestinal absorption, metabolism, and excretion of (-)-epicatechin in healthy humans assessed by using an intestinal perfusion technique". The American Journal of Clinical Nutrition. 98 (4): 924-933. doi:10.3945/ajcn.113.065789. ISSN1938-3207. PMID23864538.
^Kuhnle, G.; Spencer, J. P.; Schroeter, H.; Shenoy, B.; Debnam, E. S.; Srai, S. K.; Rice-Evans, C.; Hahn, U. (2000-10-22). "Epicatechin and catechin are O-methylated and glucuronidated in the small intestine". Biochemical and Biophysical Research Communications. 277 (2): 507-512. doi:10.1006/bbrc.2000.3701. ISSN0006-291X. PMID11032751.
^EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3 European Food Safety Authority (EFSA), Parma, Italy (2010). "Scientific Opinion on the substantiation of health claims related to various food(s)/food constituent(s) and protection of cells from premature aging, antioxidant activity, antioxidant content and antioxidant properties, and protection of DNA, proteins and lipids from oxidative damage pursuant to Article 13(1) of Regulation (EC) No 1924/20061". EFSA Journal. 8 (2): 1489. doi:10.2903/j.efsa.2010.1489.CS1 maint: multiple names: authors list (link)
^"Scientific Opinion on the modification of the authorisation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/20061 following a request in accordance with Article 19 of Regulation (EC) No 1924/2006". EFSA Journal. 12 (5). 2014. doi:10.2903/j.efsa.2014.3654.