Flavan-3-ol

thumb|right|250px|Chemical structure of flavan-3-ol

Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compounds, such as catechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, proanthocyanidins, theaflavins, thearubigins. They play a part in plant defense and are present in the majority of plants.

Chemical structure

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).

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 quercitin and rutin, which are called flavonols. Early use of the term bioflavonoid was imprecisely applied to include the flavanols, which are distinguished by the absence of ketones. Catechin monomers, dimers, and trimers (oligomers) are colorless. Higher order polymers, anthocyanidins, exhibit deepening reds and become tannins. Fluorescence-lifetime imaging microscopy can be used to detect flavanols in plant cells.

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: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:

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Aglycones

{| class="wikitable sortable"

|+ Flavan-3-ols

! Image!!Name!!Formula!!Oligomers

|-

| 100px|(+)-Catechin || Catechin, C, (+)-Catechin || C₁₅H₁₄O₆ || Procyanidins

|-

| 100px|Epicatechin || Epicatechin, EC, (–)-Epicatechin (cis) || C₁₅H₁₄O₆ || Procyanidins

|-

| 100px|Epigallocatechin || Epigallocatechin, EGC || C₁₅H₁₄O₇ || Prodelphinidins

|-

| 100px|Epicatechin gallate || Epicatechin gallate, ECG || C₂₂H₁₈O₁₀ ||

|-

| 100px|Epigallocatechin gallate || Epigallocatechin gallate, EGCG,<br />(–)-Epigallocatechin gallate || C₂₂H₁₈O₁₁ ||

|-

| 100px|Epiafzelechin || Epiafzelechin || C₁₅H₁₄O₅ ||

|-

| 100px|Fisetinidol || Fisetinidol || C₁₅H₁₄O₅ ||

|-

| 100px|Guibourtinidol || Guibourtinidol || C₁₅H₁₄O₄ || Proguibourtinidins

|-

| 100px|Mesquitol || Mesquitol || C₁₅H₁₄O₆ ||

|-

| 100px|Robinetinidol || Robinetinidol || C₁₅H₁₄O₆ || Prorobinetinidins

|}

Dietary sources

right|thumb|Reported range of flavan-3-ol content in foods commonly consumed.

Flavan-3-ols are abundant in teas derived from the tea plant Camellia sinensis, in particular green tea. Apart from tea, main sources in the human diet are pome fruits and berries and their products such as juices or wine. While cocoa beans (the seeds of Theobroma cacao) contain high amounts of flavan-3-ols, these are largely destroyed during processing and the flavanol content in cocoa products such as chocolate is usually very low. The bioavailability can be affected by nutrient-nutrient interactions with foods containing polyphenol oxidase.

Bioavailability and metabolism

The bioavailability of flavan-3-ols depends on the food matrix, type of compound and their stereochemical configuration. While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed. Most data for human metabolism of flavan-3-ols are available for monomeric compounds, especially epiatechin. These compounds are taken up and metabolized upon uptake in the jejunum, mainly by O-methylation and glucuronidation, 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, such as 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones and hippuric acid. recommending intake from supplements should not exceed 800&nbsp;milligrams (mg) per day.

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.

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

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".

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". 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.

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."

File:Flavan-3-ol precursors of the microbial metabolite 5-(3′-4′-dihydroxyphenyl)-γ-valerolactone.jpg|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.

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References

External links