Editing Polyphenol

{{short description|Class of chemical compounds}}
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{{Use American English|date=May 2022}}
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[[File:Tannic acid.svg|290px|thumb|Representative chemical structure of one of many plant-derived polyphenols that comprise [[tannic acid]]. Such compounds are formed by esterification of [[phenylpropanoid]]-derived [[gallic acid]] to a monosaccharide (glucose) core.]]
'''Polyphenols''' ({{IPAc-en|ˌ|p|ɒ|l|i|ˈ|f|iː|n|oʊ|l|,_|-|n|ɒ|l}}) are a large family of naturally occurring [[phenols]].<ref name="Quideau">{{cite journal | vauthors = Quideau S, Deffieux D, Douat-Casassus C, Pouységu L | title = Plant polyphenols: chemical properties, biological activities, and synthesis | journal = Angewandte Chemie | volume = 50 | issue = 3 | pages = 586–621 | date = January 2011 | pmid = 21226137 | doi = 10.1002/anie.201000044 | doi-access = free }}</ref> They are abundant in plants and structurally diverse.<ref name="Quideau" /><ref name="lpi">{{cite web |title=Flavonoids |url=https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids |publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University |access-date=28 October 2020 |date=1 February 2016}}</ref><ref name=Nonaka>{{cite journal | vauthors = Nonaka G | year = 1989 | title = Isolation and structure elucidation of tannins | url = http://www.iupac.org/publications/pac/1989/pdf/6103x0357.pdf | journal = Pure Appl. Chem. | volume = 61 | issue = 3| pages = 357–360 | doi=10.1351/pac198961030357| s2cid = 84226096 }}</ref> Polyphenols include [[phenolic acid]]s, [[flavonoid]]s, [[tannic acid]], and [[ellagitannin]], some of which have been used historically as [[dye]]s and for [[tanning (leather)|tanning garments]].
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[[File:curcumin.svg|thumb|[[Curcumin]], a bright yellow component of [[turmeric]] (''Curcuma longa''), is a well-studied polyphenol.]]

==Etymology==
The name derives from the [[Ancient Greek]] word {{lang|grc|πολύς}} ({{Transliteration|grc|polus}}, meaning "many, much") and the word ‘phenol’ which refers to a chemical structure formed by attachment of an aromatic [[benzenoid]] ([[phenyl]]) ring to a [[hydroxyl]] (-OH) group (hence the ''-ol'' suffix). The term "polyphenol" has been in use at least since 1894.<ref>{{cite web|date=2019|title=Polyphenol|url=https://www.merriam-webster.com/dictionary/polyphenol|access-date=23 February 2019|publisher=Merriam-Webster, Inc}}</ref>

==Definition==
[[File:Ellagic acid.svg|thumb|right|[[Ellagic acid]], a polyphenol]]

Polyphenols are [[natural product]]s with "one or several [[hydroxyl groups]] on [[aromatic ring]]s",  including four principal classes: phenolic acids, flavonoids, [[stilbene]]s, and [[lignan]]s.<ref name=lpi/><ref name="manach">{{cite journal | vauthors = Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L | title = Polyphenols: food sources and bioavailability | journal = The American Journal of Clinical Nutrition | volume = 79 | issue = 5 | pages = 727–747 | date = May 2004 | pmid = 15113710 | doi = 10.1093/ajcn/79.5.727 | doi-access = free }}</ref> Flavonoids can be grouped as flavones, flavonols, flavanols, flavanones, isoflavones, [[proanthocyanidin]]s, and anthocyanins.<ref name=lpi/> Particularly abundant flavanoids in foods are [[catechin]] (tea, fruits), [[hesperetin]] (citrus fruits), [[cyanidin]] (red fruits and berries), [[daidzein]] ([[soybean]]), proanthocyanidins (apple, grape, cocoa), and [[quercetin]] (onion, tea, apples).<ref name="lpi" /> Polyphenols also include phenolic acids, such as [[caffeic acid]], and lignans, which are derived from phenylalanine present in [[flax]] seed and other cereals.<ref name=lpi/>

===WBSSH definition===

The White–Bate-Smith–Swain–Haslam (WBSSH) definition<ref name="Haslam_and_Cai">{{cite journal | vauthors = Haslam E, Cai Y | title = Plant polyphenols (vegetable tannins): gallic acid metabolism | journal = Natural Product Reports | volume = 11 | issue = 1 | pages = 41–66 | date = January 1994 | pmid = 15206456 | doi = 10.1039/NP9941100041 }}</ref> characterized structural characteristics common to plant phenolics used in [[Tanning (leather)|tanning]] (i.e., the tannins).<ref>Practical Polyphenolics, Edwin Haslam, 1998, {{ISBN|0-521-46513-3}}</ref>

In terms of properties, the WBSSH describes the polyphenols as follows:
* generally moderately [[water-soluble]] compounds
* with molecular weight of 500–4000 Da
* with >12 phenolic hydroxyl groups
* with 5–7 aromatic rings per 1000 Da
In terms of structures, the WBSSH recognizes two structural family that have these properties:
* proanthocyanidins and its derivatives
* [[gallic acid|galloyl]] and hexahydroxydiphenoyl esters and their derivatives

===Quideau definition===
[[File:Raspberry ellagitannin.png|thumb|upright=1.35|right|[[Raspberry ellagitannin]], a [[tannin]] composed of 14 gallic acid units around a core of three units of glucose, with two gallic acids as simple esters, and the remaining 12 appearing in 6 ellagic acid-type units. Ester, ether, and biaryl linkages are present, see below.]]

According to Stéphane Quideau, the term "polyphenol" refers to compounds derived from the [[shikimate]]/phenylpropanoid and/or the [[polyketide]] pathway, featuring more than one phenolic unit and deprived of nitrogen-based functions.{{Citation needed|date=July 2021}}

[[Ellagic acid]], a molecule at the core of naturally occurring phenolic compounds of varying sizes, is itself not a polyphenol by the WBSSH definition, but is by the Quideau definition. The [[raspberry ellagitannin]],<ref>{{Cite web |url=http://www.scri.ac.uk/scri/image/Research/qhn/cardiovascular/Raspberry-Ellagitannin.jpg|title=Cardiovascular disease and phytochemicals. Anonymous. C. Hamilton et al.}}</ref> on the other hand, with its 14 [[gallic acid]] moieties (most in ellagic acid-type components), and more than 40 phenolic hydroxyl groups, meets the criteria of both definitions of a polyphenol. Other examples of compounds that fall under both the WBSSH and Quideau definitions include the [[black tea]] [[theaflavin-3-gallate]] shown below, and the hydrolyzable tannin, [[tannic acid]].{{Citation needed|date=July 2021}}

==Chemistry==
[[File:Theaflavin 3-gallate.svg|thumb|left|upright|[[Theaflavin-3-gallate]], a plant-derived polyphenol, an ester of gallic acid and a [[theaflavin]] core. There are nine phenolic hydroxyl groups and two phenolic [[ether]] linkages.]]

Polyphenols are [[Reactivity (chemistry)|reactive]] species toward [[oxidation]], hence their description as [[antioxidant]]s [[in vitro]].<ref>{{cite journal|vauthors=Martín Santos MA, Bonilla Venceslada JL, Martín Martín A, García García I |year=2005|title=Estimating the selectivity of ozone in the removal of polyphenols from vinasse|journal=Journal of Chemical Technology and Biotechnology|volume=80|issue=4 |pages=433–438|doi=10.1002/jctb.1222|bibcode=2005JCTB...80..433M |id={{INIST|16622840}}}}</ref>

=== Structure ===
Polyphenols, such as lignin, are larger molecules ([[macromolecule]]s). Their upper molecular weight limit is about 800 [[Dalton (unit)|dalton]]s, which allows for the possibility to rapidly diffuse across cell membranes so that they can reach intracellular sites of action or remain as pigments once the cell [[senesce]]s. Hence, many larger polyphenols are biosynthesized ''in situ'' from smaller polyphenols to non-hydrolyzable tannins and remain undiscovered in the plant matrix. Most polyphenols contain repeating phenolic moieties of pyrocatechol, resorcinol, pyrogallol, and phloroglucinol connected by [[esters]] (hydrolyzable tannins) or more stable C-C bonds (nonhydrolyzable [[condensed tannins]]). Proanthocyanidins are mostly polymeric units of catechin and [[epicatechin]].
[[File:Puerarin.svg|thumb|The C-glucoside substructure of polyphenols is exemplified by the phenol-saccharide conjugate puerarin, a midmolecular-weight plant natural product. The attachment of the phenol to the saccharide is by a carbon-carbon bond. The [[isoflavone]] and its 10-atom [[benzopyran]] "fused ring" system, also a structural feature here, is common in polyphenols.]]

Polyphenols often have functional groups beyond [[hydroxyl group]]s. [[Ether]] [[ester]] linkages are common, as are [[carboxylic acid]]s.
[[File:Tellimagrandin II.svg|thumb|An example of a synthetically achieved small ellagitannin, [[tellimagrandin II]], derived biosynthetically and sometimes synthetically by oxidative joining of two of the galloyl moieties of [[1,2,3,4,6-pentagalloyl-glucose]]]]

===Analytical chemistry===
The analysis techniques are those of [[phytochemistry]]: [[Extraction (chemistry)|extraction]], isolation, [[structural elucidation]],<ref>{{cite journal | vauthors = Owen RW, Haubner R, Hull WE, Erben G, Spiegelhalder B, Bartsch H, Haber B | title = Isolation and structure elucidation of the major individual polyphenols in carob fibre | journal = Food and Chemical Toxicology | volume = 41 | issue = 12 | pages = 1727–1738 | date = December 2003 | pmid = 14563398 | doi = 10.1016/S0278-6915(03)00200-X }}</ref> then [[Quantification (science)|quantification]].{{Citation needed|date=July 2021}}

===Reactivity===
Polyphenols readily react with metal ions to form [[coordination complexes]], some of which form [[Metal-phenolic network|Metal-phenolic Networks]].<ref>{{Cite journal |last=Geng |first=Huimin |title=Metal Ion-Directed Functional Metal−Phenolic Materials |url=https://pubs.acs.org/doi/abs/10.1021/acs.chemrev.1c01042 |journal=Chemical Reviews |volume=122 |pages=11432-11473 |doi=10.1021/acs.chemrev.1c01042|url-access=subscription }}</ref>

====Extraction====
[[Extraction (chemistry)|Extraction]] of polyphenols<ref>{{cite book| vauthors = Escribano-Bailon MT, Santos-Buelga C |chapter=Polyphenol Extraction From Foods | veditors = Santos-Buelga C, Williamson G |title=Methods in Polyphenol Analysis|publisher=Royal Society of Chemistry|year=2003|isbn=978-0-85404-580-8|pages=1–16|chapter-url=http://kurdchemists.org/files/Polyphenols.pdf}}</ref> can be performed using a solvent like water, [[hot water extraction|hot water]], methanol, methanol/formic acid, methanol/water/acetic or formic acid. [[Liquid–liquid extraction]] can be also performed or [[countercurrent chromatography]]. [[Solid phase extraction]] can also be made on C18 sorbent cartridges. Other techniques are ultrasonic extraction, heat reflux extraction, microwave-assisted extraction,<ref>{{cite journal| vauthors = Pan X |year=2003|title=Microwave-assisted extraction of tea polyphenols and tea caffeine from green tea leaves|journal=Chemical Engineering and Processing|volume=42|issue=2|pages=129–133|doi=10.1016/S0255-2701(02)00037-5|bibcode=2003CEPPI..42..129P }}</ref> [[critical carbon dioxide]],<ref name=":0">{{cite journal | vauthors = Aizpurua-Olaizola O, Ormazabal M, Vallejo A, Olivares M, Navarro P, Etxebarria N, Usobiaga A | title = Optimization of supercritical fluid consecutive extractions of fatty acids and polyphenols from ''Vitis vinifera'' grape wastes | journal = Journal of Food Science | volume = 80 | issue = 1 | pages = E101–E107 | date = January 2015 | pmid = 25471637 | doi = 10.1111/1750-3841.12715 }}</ref><ref>{{cite journal | vauthors = Palma M, Taylor LT | title = Extraction of polyphenolic compounds from grape seeds with near critical carbon dioxide | journal = Journal of Chromatography A | volume = 849 | issue = 1 | pages = 117–124 | date = July 1999 | pmid = 10444839 | doi = 10.1016/S0021-9673(99)00569-5 }}</ref> high-pressure [[Extract#Extraction techniques|liquid extraction]]<ref>{{cite journal | vauthors = Alonso-Salces RM, Korta E, Barranco A, Berrueta LA, Gallo B, Vicente F | title = Pressurized liquid extraction for the determination of polyphenols in apple | journal = Journal of Chromatography A | volume = 933 | issue = 1–2 | pages = 37–43 | date = November 2001 | pmid = 11758745 | doi = 10.1016/S0021-9673(01)01212-2 }}</ref> or use of ethanol in an immersion extractor.<ref>{{cite journal| vauthors = Sineiro J, Domínguez H, Núñez MJ, Lema JM |year=1996|title=Ethanol extraction of polyphenols in an immersion extractor. Effect of pulsing flow|journal=Journal of the American Oil Chemists' Society|volume=73|issue=9|pages=1121–1125|doi=10.1007/BF02523372|s2cid=96009875}}</ref> The extraction conditions (temperature, extraction time, ratio of solvent to raw material, particle size of the sample, solvent type, and solvent concentrations) for different raw materials and extraction methods have to be optimized.<ref name=papoutsis2018a>{{cite journal|title=Screening the effect of four ultrasound-assisted extraction parameters on hesperidin and phenolic acid content of aqueous citrus pomace extracts|journal=Food Bioscience|date=2018|pages=20–26|volume=21|last1=Papoutsis|doi=10.1016/j.fbio.2017.11.001|first1=Konstantinos |last2=Pristijono |first2=Penta |last3=Golding |first3=John |last4=Stathopoulos |first4=Costas |last5=Bowyer |first5=Michael |last6=Scarlett |first6=Christopher |last7=Vuong |first7=Quan|url=https://rke.abertay.ac.uk/ws/files/14225156/Stathopoulos_ScreeningTheEffectOfFourUltrasound_AssistedExtractionParameters_Author_2017.pdf }}</ref><ref name=papoutsis2018b>{{cite journal|title=Pretreatment of citrus by-products affects polyphenol recovery: a review|journal=Food Reviews International|date=2018|pages=770–795|volume=34|last1=Papoutsis|doi=10.1080/87559129.2018.1438471|first1=Konstantinos |last2=Vuong |first2=Quan |last3=Golding |first3=John |last4=Hasperué |first4=Joaquín |last5=Pristijono |first5=Penta |last6=Bowyer |first6=Michael |last7=Scarlett |first7=Christopher |last8=Stathopoulos |first8=Costas|issue=8 |hdl=11336/87660 |s2cid=89981908 |url=https://rke.abertay.ac.uk/ws/files/14378631/Stathopoulos_PretreatmentOfCitrusBy_ProductsAffectsPolyphenolRecovery_Author_2018.pdf }}</ref>

Mainly found in the fruit skins and seeds, high levels of polyphenols may reflect only the ''measured extractable'' polyphenol (EPP) content of a fruit which may also contain non-extractable polyphenols. Black tea contains high amounts of polyphenol and makes up for 20% of its weight.<ref>{{cite journal | vauthors = Arranz S, Saura-Calixto F, Shaha S, Kroon PA | title = High contents of nonextractable polyphenols in fruits suggest that polyphenol contents of plant foods have been underestimated | journal = Journal of Agricultural and Food Chemistry | volume = 57 | issue = 16 | pages = 7298–7303 | date = August 2009 | pmid = 19637929 | doi = 10.1021/jf9016652 | hdl = 10261/82508 }}</ref>

Concentration can be made by [[ultrafiltration]].<ref>{{cite journal| vauthors = Nawaz H, Shi J, Mittal GS, Kakuda Y |year=2006|title=Extraction of polyphenols from grape seeds and concentration by ultrafiltration|journal=Separation and Purification Technology|volume=48|issue=2|pages=176–181|doi=10.1016/j.seppur.2005.07.006}}</ref> Purification can be achieved by [[preparative chromatography]].

====Analysis techniques====
[[File:RP HPLC.PNG|thumb|right|Reversed-phase HPLC plot of separation of phenolic compounds. Smaller [[natural phenol]]s formed individual peaks while [[tannin]]s form a ''hump''.]]

[[Phosphomolybdic acid]] is used as a reagent for staining phenolics in [[thin layer chromatography]]. Polyphenols can be studied by [[spectroscopy]], especially in the ultraviolet domain, by [[fractionation]] or [[paper chromatography]]. They can also be analysed by chemical characterisation.

[[Instrumental chemistry]] analyses include [[Separation process|separation]] by [[high performance liquid chromatography]] (HPLC), and especially by [[reversed-phase liquid chromatography]] (RPLC), can be coupled to [[mass spectrometry]].<ref name=":0" />

=====Microscopy analysis=====
The [[DMACA reagent]] is an histological dye specific to polyphenols used in microscopy analyses. The [[autofluorescence]] of polyphenols can also be used, especially for localisation of lignin and [[suberin]].  Where fluorescence of the molecules themselves is insufficient for visualization by light microscopy, DPBA (diphenylboric acid 2-aminoethyl ester, also referred to as Naturstoff reagent A) has traditionally been used, at least in [[Botany|plant science]], to enhance the fluorescence signal.<ref>{{cite journal | vauthors = Ferrara BT, Thompson EP | title = A method for visualizing fluorescence of flavonoid therapeutics in vivo in the model eukaryote Dictyostelium discoideum | journal = BioTechniques | volume = 66 | issue = 2 | pages = 65–71 | date = February 2019 | pmid = 30744410 | doi = 10.2144/btn-2018-0084 | type = Paper | doi-access = free }}{{open access}}</ref>

==== Quantification ====
Polyphenolic content in vitro can be quantified by [[volumetric titration]]. An oxidizing agent, [[permanganate]], is used to oxidize known concentrations of a standard tannin solution, producing a [[standard curve]]. The tannin content of the unknown is then expressed as equivalents of the appropriate hydrolyzable or condensed tannin.<ref>{{cite journal | vauthors = Tempel AS | title = Tannin-measuring techniques : A review | journal = Journal of Chemical Ecology | volume = 8 | issue = 10 | pages = 1289–1298 | date = October 1982 | pmid = 24414735 | doi = 10.1007/BF00987762 | bibcode = 1982JCEco...8.1289T | s2cid = 39848160 }}</ref>

Some methods for quantification of total polyphenol content in vitro are based on [[colorimetry|colorimetric]] measurements. Some tests are relatively specific to polyphenols (for instance the Porter's assay). Total phenols (or antioxidant effect) can be measured using the [[Folin–Ciocalteu reaction]].<ref name=":0" /> Results are typically expressed as gallic acid equivalents. Polyphenols are seldom evaluated by [[antibody]] technologies.<ref>{{Cite journal| vauthors = Gani M, Mcguinness BJ, Da Vies AP |year=1998|title=Monoclonal antibodies against tea polyphenols: A novel immunoassay to detect polyphenols in biological fluids|journal=Food and Agricultural Immunology|volume=10|pages=13–22|doi=10.1080/09540109809354964}}</ref>

Other tests measure the antioxidant capacity of a fraction. Some make use of the [[ABTS]] radical [[cation]] which is reactive towards most antioxidants including phenolics, [[thiol]]s and [[vitamin C]].<ref>{{cite journal | vauthors = Walker RB, Everette JD | title = Comparative reaction rates of various antioxidants with ABTS radical cation | journal = Journal of Agricultural and Food Chemistry | volume = 57 | issue = 4 | pages = 1156–1161 | date = February 2009 | pmid = 19199590 | doi = 10.1021/jf8026765 }}</ref> During this reaction, the blue ABTS radical cation is converted back to its colorless neutral form. The reaction may be monitored spectrophotometrically. This assay is often referred to as the [[Trolox equivalent antioxidant capacity]] (TEAC) assay. The reactivity of the various antioxidants tested are compared to that of [[Trolox]], which is a [[vitamin E]] analog.

Other antioxidant capacity assays which use Trolox as a standard include the [[diphenylpicrylhydrazyl]] (DPPH), [[oxygen radical absorbance capacity]] (ORAC),<ref>{{cite journal | vauthors = Roy MK, Koide M, Rao TP, Okubo T, Ogasawara Y, Juneja LR | title = ORAC and DPPH assay comparison to assess antioxidant capacity of tea infusions: relationship between total polyphenol and individual catechin content | journal = International Journal of Food Sciences and Nutrition | volume = 61 | issue = 2 | pages = 109–124 | date = March 2010 | pmid = 20109129 | doi = 10.3109/09637480903292601 | s2cid = 1929167 }}</ref> [[ferric reducing ability of plasma]] (FRAP)<ref>{{cite journal | vauthors = Pulido R, Bravo L, Saura-Calixto F | title = Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay | journal = Journal of Agricultural and Food Chemistry | volume = 48 | issue = 8 | pages = 3396–3402 | date = August 2000 | pmid = 10956123 | doi = 10.1021/jf9913458 | hdl-access = free | hdl = 10261/112476 }}</ref> assays or inhibition of copper-catalyzed ''in vitro'' human [[low-density lipoprotein]] oxidation.<ref>{{Cite journal| vauthors = Meyer AS, Yi OS, Pearson DA, Waterhouse AL, Frankel EN |year=1997|title=Inhibition of Human Low-Density Lipoprotein Oxidation in Relation to Composition of Phenolic Antioxidants in Grapes (Vitis vinifera)|journal=Journal of Agricultural and Food Chemistry|volume=45|issue=5|pages=1638–1643|doi=10.1021/jf960721a}}</ref>

New methods including the use of [[biosensor]]s can help monitor the content of polyphenols in food.<ref>{{cite journal| vauthors = Mello LD, Sotomayor MD, Kubota LT |year=2003|title=HRP-based amperometric biosensor for the polyphenols determination in vegetables extract|journal=Sensors and Actuators B: Chemical|volume=96|issue=3|pages=636–645|doi=10.1016/j.snb.2003.07.008|bibcode=2003SeAcB..96..636M }}</ref>

Quantitation results produced by the mean of [[diode array detector]]–coupled HPLC are generally given as relative rather than [[absolute value]]s as there is a lack of commercially available [[Standard (metrology)|standards]] for all polyphenolic molecules.{{Citation needed|date=July 2021}}

==Applications==
Some polyphenols are traditionally used as [[dye]]s in [[leather tanning]]. For instance, in the [[Indian subcontinent]], [[pomegranate]] [[peel (fruit)|peel]], high in tannins and other polyphenols, or its juice, is employed in the dyeing of non-synthetic fabrics.<ref name="jindal2004">{{Cite book| vauthors = Jindal KK, Sharma RC |url=https://books.google.com/books?id=LlogqveEFVgC|title=Recent trends in horticulture in the Himalayas |publisher=Indus Publishing|year=2004|isbn=978-81-7387-162-7|quote=... bark of tree and rind of fruit is commonly used in ayurveda ... also used for dyeing ...}}</ref>

Of some interest in the era of silver-based photography, pyrogallol and pyrocatechin are among the oldest [[photographic developer]]s.<ref>{{Cite book| vauthors = Anchell SG, Troop B |title=The Film Developing Cookbook|year=1998|isbn=978-0240802770|page=25 }}</ref><ref name="Gernsheim & Gernsheim">{{cite book | vauthors = Gernsheim H, Gernsheim A |title=The History of PHOTOGRAPHY |date=1969 |publisher=Oxford University Press |pages=38,79,81,89,90-91,176-177, etc. |edition=2nd |url=https://archive.org/details/aa052-TheHistoryOfPhotography/page/n3/mode/1up?q=gallic}}</ref>

===Aspirational use as green chemicals===
Natural polyphenols have long been proposed as [[green chemistry|renewable]] precursors to produce plastics or resins by [[polymerization]] with [[formaldehyde]],<ref>{{Cite journal| vauthors = Hillis WE, Urbach G |year=1959|title=Reaction of polyphenols with formaldehyde|journal=Journal of Applied Chemistry|volume=9|issue=12|pages=665–673|doi=10.1002/jctb.5010091207}}</ref> as well as [[adhesive]]s for particleboards.<ref>{{cite journal| vauthors = Pizzi A, Valenezuela J, Westermeyer C |year=1994|title=Low formaldehyde emission, fast pressing, pine and pecan tannin adhesives for exterior particleboard|journal=Holz Als Roh- und Werkstoff|volume=52|issue=5|pages=311–315|doi=10.1007/BF02621421|s2cid=36500389}}</ref> The aims are generally to make use of plant residues from grape, olive (called [[pomace]]s), or [[pecan]] shells left after processing.<ref name=":0" />{{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=May 2025}}

==Occurrence ==
The most abundant polyphenols are the [[condensed tannin]]s, found in virtually all families of plants. Larger polyphenols are often concentrated in leaf tissue, the epidermis, bark layers, flowers and fruits but also play important roles in the decomposition of forest litter, and [[nutrient cycle]]s in forest ecology. Absolute concentrations of total phenols in plant tissues differ widely depending on the literature source, type of polyphenols and assay; they are in the range of 1–25% total [[natural phenol]]s and polyphenols, calculated with reference to the dry green leaf mass.<ref>{{cite journal | vauthors = Hättenschwiler S, Vitousek PM | title = The role of polyphenols in terrestrial ecosystem nutrient cycling | journal = Trends in Ecology & Evolution | volume = 15 | issue = 6 | pages = 238–243 | date = June 2000 | pmid = 10802549 | doi = 10.1016/S0169-5347(00)01861-9 | doi-access = free }}</ref>

Polyphenols are also found in animals. In [[arthropod]]s, such as insects,<ref>{{cite journal | vauthors = Wigglesworth VB | title = The source of lipids and polyphenols for the insect cuticle: The role of fat body, oenocytes and oenocytoids | journal = Tissue & Cell | volume = 20 | issue = 6 | pages = 919–932 | year = 1988 | pmid = 18620248 | doi = 10.1016/0040-8166(88)90033-X }}</ref> and [[crustacean]]s<ref>{{cite journal | vauthors = Dennell R | title = The occurrence and significance of phenolic hardening in the newly formed cuticle of Crustacea Decapoda | journal = Proceedings of the Royal Society of Medicine | volume = 134 | issue = 877 | pages = 485–503 | date = September 1947 | pmid = 20265564 | doi = 10.1098/rspb.1947.0027 | doi-access = free | bibcode = 1947RSPSB.134..485D }}</ref> polyphenols play a role in [[epicuticle]] hardening ([[sclerotization]]). The hardening of the cuticle is due to the presence of a [[polyphenol oxidase]].<ref>{{cite journal | vauthors = Locke M, Krishnan N | title = The distribution of phenoloxidases and polyphenols during cuticle formation | journal = Tissue & Cell | volume = 3 | issue = 1 | pages = 103–126 | year = 1971 | pmid = 18631545 | doi = 10.1016/S0040-8166(71)80034-4 }}</ref> In crustaceans, there is a second oxidase activity leading to cuticle [[pigmentation]].<ref>{{cite journal | vauthors = Krishnan G | title = Phenolic Tanning and Pigmentation of the Cuticle in Carcinus maenas | url = http://jcs.biologists.org/cgi/content/abstract/s3-92/19/333 | journal = Quarterly Journal of Microscopical Science | volume = 92 | issue = 19| pages = 333–342 | date = September 1951 }}</ref> There is apparently no polyphenol tanning occurring in [[arachnid]]s cuticle.<ref>{{cite journal | vauthors = Krishnan G  | title = The Epicuticle of an Arachnid, Palamneus swammerdami | url = http://jcs.biologists.org/cgi/content/abstract/s3-95/31/371 | journal = Quarterly Journal of Microscopical Science | volume = 95 | issue = 31| pages = 371–381 | date = September 1954 }}</ref>

==Biochemistry==
Polyphenols are thought to play diverse roles in the ecology of plants. These functions include:<ref>V. Lattanzio et al. (2006). [http://www.trnres.com/ebook/uploads/imperato/T_1231133597Imperato-2.pdf "Role of phenolics in the resistance mechanisms of plants against fungal pathogens and insects"] (and references therein). ''Phytochemistry'': Advances in Research, 23–67. {{ISBN|81-308-0034-9}}.</ref>
* Release and suppression of growth hormones such as [[auxin]].
* UV screens to protect against ionizing radiation and to provide coloration ([[plant pigment]]s).<ref name="manach" />
* Deterrence of herbivores (sensory properties).
* Prevention of microbial infections ([[phytoalexins]]).<ref name="manach" /><ref>{{cite journal | vauthors = Huber B, Eberl L, Feucht W, Polster J | title = Influence of polyphenols on bacterial biofilm formation and quorum-sensing | journal = Zeitschrift für Naturforschung C | volume = 58 | issue = 11–12 | pages = 879–884 | year = 2003 | pmid = 14713169 | doi = 10.1515/znc-2003-11-1224 | s2cid = 25764128 | doi-access = free }}</ref>
* Signaling molecules in ripening and other growth processes.
* In some woods can explain their natural [[wood preservation|preservation]] against rot.<ref>{{cite journal |title=Inhibition of wood-rotting fungi by stilbenes and other polyphenols in Eucalyptus sideroxylon | vauthors = Hart JH, Hillis WE |journal=Phytopathology |volume=64 |pages=939–948 |year=1974 |doi=10.1094/Phyto-64-939 |issue=7}}</ref>

Flax and ''[[Myriophyllum spicatum]]'' (a submerged aquatic plant) secrete polyphenols that are involved in [[allelopathy|allelopathic]] interactions.<ref>{{cite journal | vauthors = Popa VI, Dumitru M, Volf I, Anghel N |title=Lignin and polyphenols as allelochemicals |journal=Industrial Crops and Products |volume=27 |pages=144–149 |year=2008 |doi=10.1016/j.indcrop.2007.07.019 |issue=2}}</ref><ref>{{cite journal | vauthors = Nakai S |title= Myriophyllum spicatum-released allelopathic polyphenols inhibiting growth of blue-green algae Microcystis aeruginosa |journal=Water Research |volume=34 |pages=3026–3032 |year=2000 |doi=10.1016/S0043-1354(00)00039-7 |issue=11|bibcode= 2000WatRe..34.3026N }}</ref>

===Biosynthesis and metabolism===
Polyphenols incorporate smaller parts and building blocks from simpler [[natural phenol]]s, which originate from the phenylpropanoid pathway for the phenolic acids or the [[shikimic acid]] pathway for [[gallotannin]]s and analogs. Flavonoids and caffeic acid derivatives are biosynthesized from [[phenylalanine]] and [[malonyl-CoA]]. Complex gallotannins develop through the ''in vitro'' oxidation of [[1,2,3,4,6-Pentagalloyl glucose|1,2,3,4,6-pentagalloylglucose]] or dimerization processes resulting in hydrolyzable tannins. For anthocyanidins, precursors of the condensed tannin biosynthesis, [[dihydroflavonol reductase]] and [[leucoanthocyanidin reductase]] (LAR) are crucial enzymes with subsequent addition of catechin and epicatechin moieties for larger, non-hydrolyzable tannins.<ref>{{cite journal | vauthors = Tanner GJ, Francki KT, Abrahams S, Watson JM, Larkin PJ, Ashton AR | title = Proanthocyanidin biosynthesis in plants. Purification of legume leucoanthocyanidin reductase and molecular cloning of its cDNA | journal = The Journal of Biological Chemistry | volume = 278 | issue = 34 | pages = 31647–31656 | date = August 2003 | pmid = 12788945 | doi = 10.1074/jbc.M302783200 | doi-access = free }}</ref>

The glycosylated form develops from [[glucosyltransferase]] activity and increases the [[solubility]] of polyphenols.<ref>{{cite journal | vauthors = Krasnow MN, Murphy TM | title = Polyphenol glucosylating activity in cell suspensions of grape (Vitis vinifera) | journal = Journal of Agricultural and Food Chemistry | volume = 52 | issue = 11 | pages = 3467–3472 | date = June 2004 | pmid = 15161217 | doi = 10.1021/jf035234r }}</ref>

[[Polyphenol oxidase]] (PPO) is an enzyme that catalyses the oxidation of [[o-diphenol]]s to produce [[o-quinone]]s. It is the rapid polymerisation of o-quinones to produce black, brown or red polyphenolic pigments that causes [[fruit browning]]. In insects, PPO is involved in cuticle hardening.<ref>{{Cite journal | vauthors = Malek SR | doi = 10.1016/0010-406X(61)90071-8 | title = Polyphenols and their quinone derivatives in the cuticle of the desert locust, Schistocerca gregaria (Forskål) | journal = Comparative Biochemistry and Physiology | volume = 2 | pages = 35–77 | year = 1961 }}</ref>

===Occurrence in food===
{{See also|List of phytochemicals in food}}
{{Main|Natural phenols and polyphenols in wine|Natural phenols and polyphenols in tea}}

Polyphenols comprise up to 0.2–0.3% fresh weight for many fruits. Consuming common servings of wine, chocolate, [[legume]]s or tea may also contribute to about one gram of intake per day.<ref name="lpi" /><ref>{{cite journal | vauthors = Pandey KB, Rizvi SI | title = Plant polyphenols as dietary antioxidants in human health and disease | journal = Oxidative Medicine and Cellular Longevity | volume = 2 | issue = 5 | pages = 270–278 | year = 2009 | pmid = 20716914 | pmc = 2835915 | doi = 10.4161/oxim.2.5.9498 }}</ref> According to a 2005 review on polyphenols:

<blockquote>The most important food sources are commodities widely consumed in large quantities such as fruit and vegetables, green tea, black tea, red wine, coffee, chocolate, olives, and extra virgin olive oil. Herbs and spices, nuts and algae are also potentially significant for supplying certain polyphenols. Some polyphenols are specific to particular food (flavanones in citrus fruit, isoflavones in soya, phloridzin in apples); whereas others, such as quercetin, are found in all plant products such as fruit, vegetables, cereals, leguminous plants, tea, and wine.<ref name="BioavailRev2005">{{cite journal | vauthors = D'Archivio M, Filesi C, Varì R, Scazzocchio B, Masella R | title = Bioavailability of the polyphenols: status and controversies | journal = International Journal of Molecular Sciences | volume = 11 | issue = 4 | pages = 1321–1342 | date = March 2010 | pmid = 20480022 | pmc = 2871118 | doi = 10.3390/ijms11041321 | doi-access = free }}</ref></blockquote>

Some polyphenols are considered [[antinutrient]]s – compounds that interfere with the absorption of [[essential nutrient]]s – especially iron and other metal ions, which may bind to [[digestive enzyme]]s and other proteins, particularly in [[ruminant]]s.<ref>{{cite journal | vauthors = Mennen LI, Walker R, Bennetau-Pelissero C, Scalbert A | title = Risks and safety of polyphenol consumption | journal = The American Journal of Clinical Nutrition | volume = 81 | issue = 1 Suppl | pages = 326S–329S | date = January 2005 | pmid = 15640498 | doi = 10.1093/ajcn/81.1.326S | doi-access = free }}</ref>

In a comparison of cooking methods, phenolic and [[carotenoid]] levels in vegetables were retained better by [[steaming]] compared to [[frying]].<ref>{{cite journal | vauthors = Miglio C, Chiavaro E, Visconti A, Fogliano V, Pellegrini N | title = Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetables | journal = Journal of Agricultural and Food Chemistry | volume = 56 | issue = 1 | pages = 139–147 | date = January 2008 | pmid = 18069785 | doi = 10.1021/jf072304b | doi-access = free }}</ref> Polyphenols in wine, beer and various nonalcoholic juice beverages can be removed using [[finings]], substances that are usually added at or near the completion of the processing of brewing.{{citation needed|date=October 2020}}

==== Astringency ====
With respect to food and beverages, the cause of [[astringency]] is not fully understood, but it is measured chemically as the ability of a substance to precipitate proteins.<ref>Staff, Sensory Society. [http://www.sensorysociety.org/ssp/wiki/Astringency/ Basic Tastes: Astringency] {{webarchive|url=https://web.archive.org/web/20130927232634/http://www.sensorysociety.org/ssp/wiki/Astringency|date=27 September 2013}}</ref>

Astringency increases and bitterness decrease with the mean degree of [[polymerization]]. For water-soluble polyphenols, molecular weights between 500 and 3000 were reported to be required for protein precipitation. However, smaller molecules might still have astringent qualities likely due to the formation of unprecipitated complexes with proteins or cross-linking of proteins with simple phenols that have 1,2-dihydroxy or 1,2,3-trihydroxy groups.<ref>{{cite journal | vauthors = Lesschaeve I, Noble AC | title = Polyphenols: factors influencing their sensory properties and their effects on food and beverage preferences | journal = The American Journal of Clinical Nutrition | volume = 81 | issue = 1 Suppl | pages = 330S–335S | date = January 2005 | pmid = 15640499 | doi = 10.1093/ajcn/81.1.330S | doi-access = free }}</ref> Flavonoid configurations can also cause significant differences in sensory properties, e.g., epicatechin, is more bitter and astringent than its [[chiral]] [[isomer]] catechin. In contrast, hydroxycinnamic acids do not have astringent qualities, but are bitter.<ref>{{cite journal | vauthors = Hufnagel JC, Hofmann T | title = Orosensory-directed identification of astringent mouthfeel and bitter-tasting compounds in red wine | journal = Journal of Agricultural and Food Chemistry | volume = 56 | issue = 4 | pages = 1376–1386 | date = February 2008 | pmid = 18193832 | doi = 10.1021/jf073031n }}</ref>

==Research==

Polyphenols are a large, diverse group of compounds, making it difficult to determine their biological effects.<ref>{{cite journal | vauthors = Cory H, Passarelli S, Szeto J, Tamez M, Mattei J | title = The Role of Polyphenols in Human Health and Food Systems: A Mini-Review | journal = Frontiers in Nutrition | volume = 5 | pages = 87 | date = 21 September 2018 | pmid = 30298133 | pmc = 6160559 | doi = 10.3389/fnut.2018.00087 | doi-access = free }}</ref> They are not considered [[nutrient]]s, as they are not used for growth, survival or reproduction, nor do they provide [[Dietary energy supply|dietary energy]]. Therefore, they do not have recommended [[Reference Daily Intake|daily intake levels]], as exist for [[vitamin]]s, [[Mineral (nutrient)|minerals]], and [[Dietary fiber|fiber]].<ref name="efsa-nut">{{cite journal |title=Dietary Reference Values for nutrients: Summary report |journal=EFSA Supporting Publications |publisher=European Food Safety Authority |date=4 September 2019 |volume=14 |issue=12 |doi=10.2903/sp.efsa.2017.e15121 |doi-access=free }}</ref><ref name="nhs">{{cite web |title=Vitamins and minerals |url=https://www.nhs.uk/conditions/vitamins-and-minerals/ |publisher=UK National Health Service |access-date=25 August 2022 |date=3 August 2020}}</ref><ref name="usda">{{cite web |title=Vitamins and minerals |url=https://www.nal.usda.gov/legacy/fnic/vitamins-and-minerals |publisher=National Agricultural Library, US Department of Agriculture |access-date=25 August 2022 |date=2022}}</ref> In the United States, the [[Food and Drug Administration]] issued guidance to manufacturers that polyphenols cannot be mentioned on [[food label]]s as antioxidant nutrients unless [[physiology|physiological]] evidence exists to verify such a qualification and a Dietary Reference Intake value has been established {{ndash}} characteristics which have not been determined for polyphenols.<ref>{{cite web |date=July 2008 |title=Guidance for Industry: Food Labeling; Nutrient Content Claims; Definition for "High Potency" and Definition for "Antioxidant" for Use in Nutrient Content Claims for Dietary Supplements and Conventional Foods; Small Entity Compliance Guide |url=https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/LabelingNutrition/ucm063064.htm |archive-url=https://web.archive.org/web/20130402065721/http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/LabelingNutrition/ucm063064.htm |url-status=dead |archive-date=2 April 2013 |access-date=2 October 2017 |publisher=Center for Food Safety and Applied Nutrition, US Food and Drug Administration}}</ref><ref name="nutra">{{cite web |date=1 March 2009 |title=New Roles for Polyphenols. A 3-Part Report on Current Regulations and the State of Science |url=http://www.nutraceuticalsworld.com/issues/2009-03/view_features/new-roles-for-polyphenols/ |publisher=Nutraceuticals World |author=Gross, Paul}}</ref>

In the [[European Union]], two [[health claim]]s were authorized between 2012 and 2015: 1) flavanols in [[cocoa solid]]s at doses exceeding 200&nbsp;mg per day may contribute to maintenance of vascular elasticity and normal blood flow;<ref name="EC-cocoa">{{cite web |title=Article 13 (5): Cocoa flavanols; Search filters: Claim status – authorised; search – flavanols |url=https://ec.europa.eu/food/safety/labelling_nutrition/claims/register/public/?event=search |publisher=European Commission, EU Register |access-date=27 August 2022 |date=31 March 2015 |quote=Cocoa flavanols help maintain the elasticity of blood vessels, which contributes to normal blood flow}}</ref><ref name=":02">{{cite journal |date=May 2014 |title=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 1924/2006 following a request in accordance with Article 19 of Regulation (EC) No 1924/2006 |journal=EFSA Journal |volume=12 |issue=5 |doi=10.2903/j.efsa.2014.3654 |doi-access=free}}</ref> 2) olive oil polyphenols (5&nbsp;mg of [[hydroxytyrosol]] and its derivatives (e.g. [[oleuropein]] complex and [[tyrosol]]) may "contribute to the protection of blood lipids from oxidative damage", if consumed daily.<ref name="EC-olive">{{cite web |title=Article 13 (1): Olive polyphenols; Search filters: Claim status – authorised; search – polyphenols |url=https://ec.europa.eu/food/safety/labelling_nutrition/claims/register/public/?event=search |publisher=European Commission, EU Register |access-date=27 August 2022 |date=16 May 2012 |quote=Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress}}</ref><ref name=":1">{{cite journal |date=April 2011 |title=Scientific opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles from oxidative damage (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL cholesterol concentrations (ID 1639), mainte |journal=EFSA Journal |volume=9 |issue=4 |pages=2033 |doi=10.2903/j.efsa.2011.2033 |doi-access=free}}</ref>

As of 2022, [[clinical trial]]s that assessed the effect of polyphenols on health [[biomarker]]s are limited, with results difficult to interpret due to the wide variation of intake values for both individual polyphenols and total polyphenols.<ref>{{cite journal|vauthors=Condezo-Hoyos L, Gazi C, Pérez-Jiménez J|year=2021|title=Design of polyphenol-rich diets in clinical trials: A systematic review|journal=Food Research International|url=https://www.sciencedirect.com/science/article/pii/S0963996921005548|volume=149|issue=|pages=110655|doi=10.1016/j.foodres.2021.110655|pmid=34600657|hdl=10261/258758|hdl-access=free}}</ref>

{{Anchor|Antioxidant activity}}<!--linked from [[Phenolic content in tea]] -->Polyphenols were once considered as [[Antioxidant effect of polyphenols and natural phenols|antioxidants]], but this concept is obsolete.<ref>{{cite journal | vauthors = Williams RJ, Spencer JP, Rice-Evans C | title = Flavonoids: antioxidants or signalling molecules? | journal = Free Radical Biology & Medicine | volume = 36 | issue = 7 | pages = 838–849 | date = April 2004 | pmid = 15019969 | doi = 10.1016/j.freeradbiomed.2004.01.001 }}</ref> Most polyphenols are metabolized by [[catechol-O-methyltransferase]], and therefore do not have the chemical structure allowing antioxidant activity in vivo; they may exert biological activity as [[Cell signaling|signaling molecules]].<ref name=lpi/><ref name=nutra/><ref>{{cite journal | vauthors = Williams RJ, Spencer JP, Rice-Evans C | title = Flavonoids: antioxidants or signalling molecules? | journal = Free Radical Biology & Medicine | volume = 36 | issue = 7 | pages = 838–849 | date = April 2004 | pmid = 15019969 | doi = 10.1016/j.freeradbiomed.2004.01.001 }}</ref> Some polyphenols are considered to be [[bioactive compound]]s<ref>{{Cite journal |last=Erdman |first=John W. |date=2022 |title=Health and nutrition beyond essential nutrients: The evolution of the bioactives concept for human health |url=https://linkinghub.elsevier.com/retrieve/pii/S0098299722000619 |journal=Molecular Aspects of Medicine|volume=89 |pmid=35965134|language=en |pages=101116 |doi=10.1016/j.mam.2022.101116|s2cid=251524113 |url-access=subscription }}</ref> for which development of dietary recommendations was under consideration in 2017.<ref>{{cite journal | vauthors = Yetley EA, MacFarlane AJ, Greene-Finestone LS, Garza C, Ard JD, Atkinson SA, Bier DM, Carriquiry AL, Harlan WR, Hattis D, King JC, Krewski D, O'Connor DL, Prentice RL, Rodricks JV, Wells GA| title = Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: report from a joint US-/Canadian-sponsored working group | journal = The American Journal of Clinical Nutrition | volume = 105 | issue = 1 | pages = 249S–285S | date = January 2017 | pmid = 27927637 | doi = 10.3945/ajcn.116.139097 | pmc = 5183726 }}</ref>

=== Cardiovascular diseases ===
[[Flavonoid#History|In the 1930s]], polyphenols (then called ''vitamin P'') were considered as a factor in [[Vascular permeability|capillary permeability]], followed by various studies through the 21st century of a possible effect on cardiovascular diseases. For most polyphenols, there is no evidence for an effect on cardiovascular regulation, although there are some reviews showing a minor effect of consuming polyphenols, such as [[chlorogenic acid]] or [[flavan-3-ol]]s, on blood pressure.<ref>{{Cite journal |last1=Onakpoya |first1=I J |last2=Spencer |first2=E A |last3=Thompson |first3=M J |last4=Heneghan |first4=C J |date=2014 |title=The effect of chlorogenic acid on blood pressure: a systematic review and meta-analysis of randomized clinical trials |url=https://www.nature.com/articles/jhh201446 |journal=Journal of Human Hypertension |language=en |volume=29 |issue=2 |pages=77–81 |doi=10.1038/jhh.2014.46 |pmid=24943289 |s2cid=2881228 |issn=0950-9240|url-access=subscription }}</ref><ref>{{cite journal |vauthors=Ried K, Fakler P, Stocks NP |date=April 2017 |title=Effect of cocoa on blood pressure |journal=The Cochrane Database of Systematic Reviews |volume=4 |issue=5 |pages=CD008893 |doi=10.1002/14651858.CD008893.pub3 |pmc=6478304 |pmid=28439881 |collaboration=Cochrane Hypertension Group}}</ref><ref>{{cite journal|vauthors=Raman G, Avendano EE, Chen S, Wang J, Matson J, Gayer B, Novotny JA, Cassidy A |date=November 2019 |title=Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies |journal=The American Journal of Clinical Nutrition |volume=110 |issue=5 |pages=1067–1078 |doi=10.1093/ajcn/nqz178 |pmc=6821550 |pmid=31504087}}</ref>

=== Cancer ===
Higher intakes of soy isoflavones may be associated with reduced risks of breast cancer in postmenopausal women and prostate cancer in men.<ref name=lpi/>

A 2019 systematic review found that intake of soy and soy isoflavones is associated with a lower risk of [[Mortality rate|mortality]] from gastric, colorectal, breast and lung cancers.<ref name="nach">{{Cite journal |last1=Nachvak |first1=Seyed Mostafa |last2=Moradi |first2=Shima |last3=Anjom-Shoae |first3=Javad |last4=Rahmani |first4=Jamal |last5=Nasiri |first5=Morteza |last6=Maleki |first6=Vahid |last7=Sadeghi |first7=Omid|date=September 2019 |title=Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies |journal=Journal of the Academy of Nutrition and Dietetics |volume=119 |issue=9 |pages=1483–1500.e17 |doi=10.1016/j.jand.2019.04.011 |issn=2212-2672 |pmid=31278047|s2cid=195812592 }}</ref> The study found that an increase in isoflavone consumption by 10&nbsp;mg per day was associated with a 7% decrease in risk from all cancers, and an increase in consumption of soy protein by 5 grams per day produced a 12% reduction in breast cancer risk.<ref name=nach/>

=== Cognitive function ===
Polyphenols are under preliminary research for possible [[Cognition|cognitive effects]] in healthy adults.<ref>{{cite journal|vauthors=Travica N, D'Cunha NM, Naumovski N, Kent K, Mellor DD, Firth J, Georgousopoulou EN, Dean OM, Loughman A, Jacka F, Marx W |date=March 2020 |title=The effect of blueberry interventions on cognitive performance and mood: A systematic review of randomized controlled trials |journal=Brain, Behavior, and Immunity |volume=85 |pages=96–105 |doi=10.1016/j.bbi.2019.04.001 |pmid=30999017 |s2cid=113408091|url=https://publications.aston.ac.uk/id/eprint/39190/1/Blueberry_interventions.pdf }}</ref><ref>{{cite journal |vauthors=Marx W, Kelly JT, Marshall S, Cutajar J, Annois B, Pipingas A, Tierney A, Itsiopoulos C |date=June 2018 |title=Effect of resveratrol supplementation on cognitive performance and mood in adults: a systematic literature review and meta-analysis of randomized controlled trials |journal=Nutrition Reviews |volume=76 |issue=6 |pages=432–443 |doi=10.1093/nutrit/nuy010 |pmid=29596658 |doi-access=free|hdl=10072/389251 |hdl-access=free }}</ref>

=== Phytoestrogens ===
[[Isoflavone]]s, which are structurally related to [[17β-estradiol]], are classified as [[phytoestrogen]]s.<ref>{{Cite web |author=((Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment)) |date=2003 |title=Phytoestrogens and Health |url=https://cot.food.gov.uk/sites/default/files/cot/phytoreport0503.pdf}}</ref> A risk assessment by the European Food Safety Authority found no cause for concern when isoflavones are consumed in a normal diet.<ref>{{Cite web |title=Risk assessment for peri- and post-menopausal women taking food supplements containing isolated isoflavones|publisher=European Food Safety Authority |url=https://www.efsa.europa.eu/en/efsajournal/pub/4246|date=21 October 2015 |access-date=26 August 2022}}</ref>

=== Phlebotonic ===
{{Main|Diosmin#Phlebotonics}}
Phlebotonics of heterogeneous composition, consisting partly of [[Peel (fruit)|citrus peel]] [[extract]]s ([[flavonoid]]s, such as [[hesperidin]]) and synthetic compounds, are used to treat [[chronic venous insufficiency]] and [[hemorrhoid]]s.<ref name="drugs">{{cite web |date=1 January 2019 |title=Diosmin |url=https://www.drugs.com/npp/diosmin.html |access-date=7 November 2019 |publisher=Drugs.com}}</ref> Some are [[Prescription drug|non-prescription]] [[dietary supplement]]s, such as [[diosmin]],<ref name="drugs" /> while one other – Vasculera (Diosmiplex) – is a prescription [[medical food]] intended for treating venous disorders.<ref name="dailymed-diosmiplex">{{cite web |date=26 April 2012 |title=Vasculera – diosmiplex tablet |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=563d3d34-a547-471e-aecd-f4a4a57cbf1d |access-date=8 November 2019 |website=dailymed.nlm.nih.gov |publisher=National Institutes of Health}}</ref> Their mechanism of action is undefined,<ref name="drugs" /> and [[Evidence-based medicine|clinical evidence]] of benefit for using phlebotonics to treat venous diseases is limited.<ref name="drugs" />

=== Gut microbiome ===
Polyphenols are extensively metabolized by the [[gut microbiota]] and are investigated as a potential metabolic factor in function of the gut microbiota.<ref>{{cite journal |vauthors=Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A |date=May 2013 |title=Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases |journal=Antioxidants & Redox Signaling |volume=18 |issue=14 |pages=1818–1892 |doi=10.1089/ars.2012.4581 |pmc=3619154 |pmid=22794138}}</ref><ref>{{Cite journal |vauthors=Catalkaya G, Venema K, Lucini L, Rocchetti G, Delmas D, Daglia M, De Filippis A, Xiao H, Quiles JL, Xiao J |date=2020 |title=Interaction of dietary polyphenols and gut microbiota: Microbial metabolism of polyphenols, influence on the gut microbiota, and implications on host health |journal=Food Frontiers |volume=1 |issue=2 |pages=109–133 |doi=10.1002/fft2.25|s2cid=225656010 |doi-access=free |hdl=10807/157865 |hdl-access=free }}</ref>

=== Toxicity and adverse effects ===
[[Adverse effect]]s of polyphenol intake range from mild (e.g., [[gastrointestinal tract]] symptoms)<ref name=lpi/> to severe (e.g., [[hemolytic anemia]] or [[hepatotoxicity]]).<ref name="davies">{{Cite book |url=https://www.worldcat.org/oclc/820665797 |title=Flavonoid pharmacokinetics: methods of analysis, pre-clinical and clinical pharmacokinetics, safety, and toxicology |date=2013 |isbn=978-1-118-35440-7 |veditors=Davies NM, Yanez JA|publisher=Wiley |location=Hoboken, New Jersey |chapter=Flavonoids and drug interactions |oclc=820665797|last1=Davies |first1=Neal M. |last2=Yáñez |first2=Jaime A. }}</ref> In 1988, hemolytic anemia following polyphenol consumption was documented, resulting in the withdrawal of a catechin-containing drug.<ref>{{cite journal |vauthors=Jaeger A, Wälti M, Neftel K |date=1988 |title=Side effects of flavonoids in medical practice |journal=Progress in Clinical and Biological Research |volume=280 |pages=379–394 |pmid=2971975}}</ref> Polyphenols, particularly in beverages that contain them in high concentrations (tea, coffee, etc), inhibit the [[Small_intestine#Absorption|absorption]] of [[heme|non-haem iron]] when consumed together in a single meal.<ref name=lpi/><ref name="SACN">{{cite book |title=SACN Iron and Health Report |date=2010 |publisher=The Stationery Office |isbn=9780117069923 |pages=65, 68, 70, 73, 74 |url=https://assets.publishing.service.gov.uk/media/5a7df3dd40f0b62305b7fd53/SACN_Iron_and_Health_Report.pdf |access-date=3 September 2024}}</ref><ref name="WHO">{{cite web |title=Iron Deficiency Anaemia Assessment, Prevention, and Control A guide for programme managers |url=https://cdn.who.int/media/docs/default-source/2021-dha-docs/ida_assessment_prevention_control.pdf?sfvrsn=fb8c459c_1&download=true |publisher=World Health Organization |access-date=3 September 2024 |date=2001}}</ref><ref name="CDC">{{cite journal |title=Recommendations to Prevent and Control Iron Deficiency in the United States |journal=[[Morbidity and Mortality Weekly Report|MMWR]] |date=3 April 1998 |volume=47 |issue=RR-3 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00051880.htm |access-date=3 September 2024 |publisher=Centers for Disease Control and Prevention}}</ref> Research is limited on the effect of this inhibition on [[Iron tests|iron status]].<ref name="SACN quote">{{cite book |title=SACN Iron and Health Report |date=2010 |publisher=The Stationery Office |isbn=9780117069923 |pages=74 |url=https://assets.publishing.service.gov.uk/media/5a7df3dd40f0b62305b7fd53/SACN_Iron_and_Health_Report.pdf |quote=Numerous cross-sectional studies have examined the association between total dietary iron intake and dietary modulators of iron absorption on biochemical markers of iron status ... These studies suffer from a number of limitations... Findings from cross-sectional studies assessing the effects of total iron intake, ascorbic acid, calcium and polyphenols, have been inconsistent...}}</ref>

Metabolism of polyphenols can result in flavonoid-drug interactions, such as in [[grapefruit–drug interactions]], which involves inhibition of the liver [[enzyme]], [[CYP3A4]], likely by grapefruit [[furanocoumarin]]s, a class of polyphenol.<ref name=lpi/><ref name="davies" /> The European Food Safety Authority established upper limits for some polyphenol-containing supplements and additives, such as [[green tea extract]] or [[curcumin]].<ref>{{cite journal|vauthors=Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, Frutos MJ, Galtier P, Gott D, Gundert-Remy U, Lambré C, Leblanc JC, Lillegaard IT, Moldeus P, Mortensen A, Oskarsson A, Stankovic I, Waalkens-Berendsen I, Woutersen RA, Andrade RJ, Fortes C, Mosesso P, Restani P, Arcella D, Pizzo F, Smeraldi C, Wright M |date=April 2018 |title=Scientific opinion on the safety of green tea catechins |journal=EFSA Journal |volume=16 |issue=4 |pages=e05239 |doi=10.2903/j.efsa.2018.5239 |pmc=7009618 |pmid=32625874}}</ref><ref>{{Cite journal |author=EFSA Panel on Food Additives and Nutrient Sources Added to Food |date=1 September 2010 |title=Scientific opinion on the re-evaluation of curcumin (E 100) as a food additive |url=https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2010.1679 |journal=EFSA Journal |volume=8 |issue=9 |doi=10.2903/j.efsa.2010.1679|url-access=subscription }}</ref> For most polyphenols found in the diet, an adverse effect beyond nutrient-drug interactions is unlikely.<ref name=lpi/>

== See also ==
* [[List of phytochemicals in food]]
* [[Dictionary of natural phenols and polyphenols molecular formulas]]
* [[Phytochemistry]]
* [[Polyphenolic protein]]s
* [[Secondary metabolite]]s

== References ==
{{Reflist}}

== External links ==
{{Wiktionary}}
* [http://www.phenol-explorer.eu/ Phenol-Explorer, electronic database of polyphenol content in foods]

{{Phytochemical}}
{{Secondary metabolites}}
{{Natural phenol}}
{{Authority control}}

[[Category:Polyphenols| ]]
[[Category:Phytochemicals]]