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Not to be confused with Flavonol.

Chemical structure of flavan-3-ol

Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids.[1] They are derivatives of flavans, are structurally diverse, and include compounds such as catechins, epicatechin gallate, epigallocatechin gallate, proanthocyanidins, theaflavins, and thearubigins.[1]

Present in tea leaves, berries, apples, cocoa beans, and grapes, they participate in diverse plant functions, including regulation of cell growth, attraction of pollinating insects, and defense against environmental stress.[1][2]

Chemical structure

Flavanols exist both as monomers (catechins) and as polymers (proanthocyanidins).[2] The single-molecule (monomer) catechin, or isomer epicatechin (see diagram), adds four hydroxyls to flavan-3-ol, making building blocks for polymers (proanthocyanidins) and higher order polymers (anthocyanidins).[1][2]

Flavan-3-ols possess two chiral carbons, meaning four diastereoisomers occur for each of them. They are distinguished from the yellow, ketone-containing flavonoids, such as quercetin.[1] Catechin monomers, dimers, and trimers (oligomers) are colorless, while higher order polymers, anthocyanidins, exhibit deepening reds and become tannins.[1][2]

Catechin and epicatechin are epimers, with (–)-epicatechin and (+)-catechin being the most common optical isomers of flavanols found in nature.[2] Catechin was first isolated from the plant extract, catechu, from which it derives its name.[3]

Epigallocatechin and gallocatechin contain an additional phenolic hydroxyl group when compared to epicatechin and catechin, respectively.[1]

Catechin gallates are gallic acid esters of the catechins; an example is epigallocatechin gallate, the most abundant catechin in tea.[1][2] Proanthocyanidins and thearubigins are also in the flavan-3-ol subclass.[2]

In contrast to many other flavonoids, flavan-3-ols do not generally exist as glycosides in plants.[2]

Structures of (epi)catechin, (epi)catechin gallate, (epi)gallocatechin and (epi)gallocatechin gallate.

Biosynthesis of (–)-epicatechin

The flavonoids are derived from phenylalanine and malonyl-coenzyme A in reactions catalyzed by polyketide synthase.[4] Chain extension of 4-hydroxycinnamoyl-CoA with three molecules of malonyl-CoA gives initially a polyketide (figure), which can be folded, allowing Claisen-like reactions to occur, generating aromatic rings.[5] Fluorescence-lifetime imaging microscopy can be used to detect flavanols in plant cells.[6]

Schematic overview of the flavan-3-ol (–)-epicatechin biosynthesis from tyrosine (Tyr) or phenylalanine (Phe) in plants. Enzymes are indicated in blue, abbreviated as follows:

Aglycones

Flavan-3-ols
Image Name Formula Oligomers
(+)-Catechin Catechin, C, (+)-Catechin C15H14O6 Procyanidins
Epicatechin Epicatechin, EC, (–)-Epicatechin (cis) C15H14O6 Procyanidins
Epigallocatechin Epigallocatechin, EGC C15H14O7 Prodelphinidins
Epicatechin gallate Epicatechin gallate, ECG C22H18O10
Epigallocatechin gallate Epigallocatechin gallate, EGCG,
(–)-Epigallocatechin gallate		 C22H18O11
Epiafzelechin Epiafzelechin C15H14O5
Fisetinidol Fisetinidol C15H14O5
Guibourtinidol Guibourtinidol C15H14O4 Proguibourtinidins
Mesquitol Mesquitol C15H14O6
Robinetinidol Robinetinidol C15H14O6 Prorobinetinidins

Dietary sources

See also: Polyphenols in tea, Polyphenols in wine, and Cocoa bean § Phytochemicals and research
Reported range of flavan-3-ol content in foods commonly consumed.[1][7]

Flavan-3-ols are abundant in teas derived from the tea plant Camellia sinensis, in particular green tea.[1] Apart from tea, main sources in the human diet are chocolate, pome fruits, and berries and their products, such as juices or red wine.[1][7] Their content in food is highly variable and affected by various factors, such as cultivar, processing and preparation.[2] Tea extracts are sold as dietary supplements labeled as tea catechins or tea polyphenols.[1] Green tea extracts typically have higher levels of catechins, while black tea extracts have high levels of theaflavins and thearubigins.[1]

While cocoa beans (the seeds of Theobroma cacao) contain flavan-3-ols, these are susceptible to heat degradation during processing, causing the flavanol content in cocoa products, such as chocolate, to be relatively low.[1][8][9] The bioavailability can be affected by nutrient-nutrient interactions with foods containing polyphenol oxidase.[2]

Bioavailability and metabolism

The bioavailability of flavan-3-ols depends on the food matrix, type of compound and their stereochemical configuration.[1][2] While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed.[2] Most data for human metabolism of flavan-3-ols are available for monomeric compounds, especially epicatechin. These compounds are taken up and metabolized upon uptake in the small intestine,[1][2] mainly by O-methylation and glucuronidation,[10] and then further metabolized by the liver. The colonic microbiome also has a role in the metabolism of flavan-3-ols, which are catabolized to smaller compounds.[1][2]

Possible adverse effects

As catechins, in particular epigallocatechin gallate, in green tea extract can be hepatotoxic, Health Canada and EFSA have advised for caution,[11] recommending intake from supplements should not exceed 800 milligrams (mg) per day.[12]

Research

See also: Cocoa bean § Phytochemicals and research

Research has shown that flavan-3-ols may affect vascular function, blood pressure, and blood lipids, with only minor effects demonstrated, as of 2019.[13][14]

As of 2022, food-based evidence indicates that intake of 400–600 mg per day of flavan-3-ols – up to twice the normal dietary intake of flavanols by European adults – could have a small positive effect on cardiovascular biomarkers.[15]

Regulation

In 2015, the European Commission approved a health claim for cocoa flavanols, stating that an intake of 200 mg per day “may contribute to maintenance of vascular elasticity and normal blood flow”.[16][17]

In 2023, the US Food and Drug Administration assessed a health claim for consuming 200 mg per day of cocoa powder flavanols, stating in a letter of enforcement discretion that “there is very limited credible scientific evidence for a qualified health claim for cocoa flavanols in high flavanol cocoa powder and a reduced risk of cardiovascular disease”.[18] Reasons for this assessment included a small number of credible studies, questionable methodology, inadequate number of subjects, short study duration, and poor replication and inconsistency of results.[19]

The letter of enforcement discretion further stated that the evidence “does not support the establishment of a daily intake of 200 mg of cocoa flavanols or any other daily dietary intake recommendation levels for the general U.S. population.”[19]

  • 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.[20]
    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.[20]
  • Flavan-3-ol precursors of the microbial metabolite 5-(3′/4′-dihydroxyphenyl)-γ-valerolactone (γVL). Only compounds with intact (epi)catechin moiety result in the formation of γVL by the intestinal microbiome. ECG, (−)-epicatechin-3-O-gallate; EGCG, Epigallocatechin gallate; EGC, Epigallocatechin.[21]
    Flavan-3-ol precursors of the microbial metabolite 5-(3′/4′-dihydroxyphenyl)-γ-valerolactone (γVL). Only compounds with intact (epi)catechin moiety result in the formation of γVL by the intestinal microbiome. ECG, (−)-epicatechin-3-O-gallate; EGCG, Epigallocatechin gallate; EGC, Epigallocatechin.[21]

References

  1. ^ a b c d e f g h i j k l m n o p q “Flavonoids”. Micronutrient Information Center, Linus Pauling Institute, Oregon State University. 2026. Retrieved 3 June 2026.
  2. ^ a b c d e f g h i j k l m n Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (May 2004). “Polyphenols: food sources and bioavailability”. The American Journal of Clinical Nutrition. 79 (5): 727–747. doi:10.1093/ajcn/79.5.727. PMID 15113710.
  3. ^ “Catechin”. PubChem, US National Library of Medicine. 30 May 2026. Retrieved 3 June 2026.
  4. ^ Winkel-Shirley B (June 2001). “Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology”. Plant Physiology. 126 (2): 485–493. doi:10.1104/pp.126.2.485. PMC 1540115. PMID 11402179.
  5. ^ Dewick PM (2009). Medicinal Natural Products: A Biosynthetic Approach (3 ed.). New York: John Wiley & Sons. p. 168. doi:10.1002/9780470742761. ISBN 9780470742761.
  6. ^ Mueller-Harvey I, Feucht W, Polster J, Trnková L, Burgos P, Parker AW, Botchway SW (March 2012). “Two-photon excitation with pico-second fluorescence lifetime imaging to detect nuclear association of flavanols”. Analytica Chimica Acta. 719: 68–75. doi:10.1016/j.aca.2011.12.068. PMID 22340533. S2CID 24094780.
  7. ^ a b “Database on polyphenol content in foods, v3.6”. Phenol Explorer. 2016.
  8. ^ Hammerstone JF, Lazarus SA, Schmitz HH (August 2000). “Procyanidin content and variation in some commonly consumed foods”. The Journal of Nutrition. 130 (8 Suppl.): 2086S–2092S. doi:10.1093/jn/130.8.2086S. PMID 10917927.
  9. ^ Payne MJ, Hurst WJ, Miller KB, Rank C, Stuart DA (October 2010). “Impact of fermentation, drying, roasting, and Dutch processing on epicatechin and catechin content of cacao beans and cocoa ingredients”. Journal of Agricultural and Food Chemistry. 58 (19): 10518–10527. doi:10.1021/jf102391q. PMID 20843086.
  10. ^ Kuhnle G, Spencer JP, Schroeter H, Shenoy B, Debnam ES, Srai SK, et al. (October 2000). “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. PMID 11032751.
  11. ^ Health Canada (12 December 2017). “Summary Safety Review – Green tea extract-containing natural health products – Assessing the potential risk of liver injury (hepatotoxicity)”. Health Canada, Government of Canada. Retrieved 2022-05-06.
  12. ^ Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, et al. (April 2018). “Scientific opinion on the safety of green tea catechins”. EFSA Journal. 16 (4): e05239. doi:10.2903/j.efsa.2018.5239. PMC 7009618. PMID 32625874.
  13. ^ Ried K, Fakler P, Stocks NP, et al. (Cochrane Hypertension Group) (April 2017). “Effect of cocoa on blood pressure”. The Cochrane Database of Systematic Reviews. 4 (5) CD008893. doi:10.1002/14651858.CD008893.pub3. PMC 6478304. PMID 28439881.
  14. ^ Raman G, Avendano EE, Chen S, et al. (November 2019). “Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies”. The American Journal of Clinical Nutrition. 110 (5): 1067–1078. doi:10.1093/ajcn/nqz178. PMC 6821550. PMID 31504087.
  15. ^ Crowe-White, Kristi M; Evans, Levi W; Kuhnle, Gunter G C; et al. (3 October 2022). “Flavan-3-ols and cardiometabolic health: First ever dietary bioactive guideline”. Advances in Nutrition. 13 (6): 2070–2083. doi:10.1093/advances/nmac105. PMC 9776652. PMID 36190328.
  16. ^ “Article 13(5): Cocoa flavanols; Search filters: Claim status – authorised; search – flavanols”. European Commission, EU Register. 31 March 2015. Retrieved 8 September 2022.
  17. ^ “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.
  18. ^ “FDA Announces Qualified Health Claim for Cocoa Flavanols in High Flavanol Cocoa Powder and Reduced Risk of Cardiovascular Disease: Constituent Update”. US Food and Drug Administration. 3 February 2023. Retrieved 29 May 2026.
  19. ^ a b Kavanaugh, CS (1 February 2023). “FDA Letter of Enforcement Discretion on a Petition for a Qualified Health Claim for Cocoa Flavanols and Reduced Risk of Cardiovascular Disease (Docket No. FDA-2019-Q-0806)”. Office of Nutrition Food Labeling, Center for Food Safety and Applied Nutrition, US Food and Drug Administration. Retrieved 29 May 2026.
  20. ^ Ottaviani JI, Borges G, Momma TY, et al. (July 2016). “The metabolome of [2-14C](−)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives”. Scientific Reports. 6 (1) 29034. Bibcode:2016NatSR…629034O. doi:10.1038/srep29034. PMC 4929566. PMID 27363516.
  21. ^ Ottaviani JI, Fong R, Kimball J, Ensunsa JL, Britten A, Lucarelli D, et al. (June 2018). “Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies”. Scientific Reports. 8 (1): 9859. Bibcode:2018NatSR…8.9859O. doi:10.1038/s41598-018-28333-w. PMC 6026136. PMID 29959422.