View source for Resveratrol

{{Short description|Polyphenol with a stilbene skeleton}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 477172311
| Name = Resveratrol
| ImageFile = resveratrol.svg
| ImageSize = 250px
| ImageClass = skin-invert
| ImageName = Chemical 9–69 structure of ''trans''-resveratrol
| ImageFile1 = Resveratrol3d.png
| ImageSize1 = 180px
| ImageName1 = Chemical structure of ''trans''-resveratrol
| ImageFile2 = Cis_and_trans_resveratrol_notext.svg
| ImageSize2 = 250px
| ImageClass2 = skin-invert
| ImageName2 = Chemical structures of ''cis-'' and ''trans''-resveratrols
| ImageCaption2 = Chemical structures of ''cis-'' ((''Z'')-resveratrol, left) and ''trans''-resveratrol ((''E'')-resveratrol, right)<ref name=Camont>{{cite journal | vauthors = Camont L, Cottart CH, Rhayem Y, Nivet-Antoine V, Djelidi R, Collin F, Beaudeux JL, Bonnefont-Rousselot D | title = Simple spectrophotometric assessment of the trans-/cis-resveratrol ratio in aqueous solutions | journal = Analytica Chimica Acta | volume = 634 | issue = 1 | pages = 121–128 | date = February 2009 | pmid = 19154820 | doi = 10.1016/j.aca.2008.12.003 | bibcode = 2009AcAC..634..121C }}</ref>
| PIN = 5-[(''E'')-2-(4-Hydroxyphenyl)ethen-1-yl]benzene-1,3-diol
| OtherNames = ''trans''-3,5,4′-Trihydroxystilbene;<br />3,4′,5-Stilbenetriol;<br />''trans''-Resveratrol;<br />(''E'')-5-(''p''-Hydroxystyryl)resorcinol;<br />(''E'')-5-(4-hydroxystyryl)benzene-1,3-diol
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 501-36-0
| PubChem = 445154
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 392875
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 165
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB02709
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q369O8926L
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 45713
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C03582
| RTECS = CZ8987000
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LUKBXSAWLPMMSZ-OWOJBTEDSA-N
| SMILES = Oc1ccc(cc1)\C=C\c2cc(O)cc(O)c2
| InChI =1/C14H12O3/c15-<br />12-5-3-10(4-6-12)<br />1-2-11-7-13(16)9-<br />14(17)8-11/h1-9,15-<br />17H/b2-1+
 }}
|Section2={{Chembox Properties
| C=14 | H=12 | O=3
| Appearance = white powder with<br /> slight yellow cast
| MeltingPtC = 261 to 263
| MeltingPt_ref = <ref name=FisherScientificMSDS>{{Cite web |url=http://www.fishersci.com/ecomm/servlet/msdsproxy?productName=AC430075000&productDescription=RESVERATROL+99%25+500MG&catNo=AC43007-5000&vendorId=VN00032119&s |title=Resveratrol MSDS on Fisher Scientific website |access-date=2012-03-06 |archive-date=2012-11-03 |archive-url=https://web.archive.org/web/20121103030802/http://www.fishersci.com/ecomm/servlet/msdsproxy?productName=AC430075000&productDescription=RESVERATROL+99%25+500MG&catNo=AC43007-5000&vendorId=VN00032119&s }}</ref>
| Solubility1 = 0.03 g/L
| Solvent1 = water
| Solubility2 = 16 g/L
| Solvent2 = Dimethyl sulfoxide{{!}}DMSO
| Solubility3 = 50 g/L
| Solvent3 = ethanol
| LambdaMax = 304nm (trans-resveratrol, in water)<br />286nm (cis-resveratrol, in water)<ref name=Camont/>
 }}
|Section7={{Chembox Hazards
| ExternalSDS = Fisher Scientific<ref name=FisherScientificMSDS/><br />Sigma Aldrich<ref name=SigmaAldrichMSDS>[http://www.sigmaaldrich.com/catalog/DisplayMSDSContent.do Resveratrol MSDS on www.sigmaaldrich.com]</ref>
| MainHazards =
| NFPA-H =
| NFPA-F =
| NFPA-R =
| NFPA-S =
| GHSPictograms = {{GHS07}}
| GHSSignalWord = warning
| HPhrases      = {{HPhrases|H319}}
| PPhrases      = {{PPhrases|P264 | P280 | P305 + P351 + P338 | P337 + P313}}
| GHS_ref       = <ref>GHS: [https://www.sigmaaldrich.com/product/SIGMA/R5010 Sigma-Aldrich R5010]</ref>
| FlashPt =
| AutoignitionPt =
| ExploLimits =
| LD50 = 23.2 μM (5.29 g)<ref name="pmid19207580">{{cite journal | vauthors = Bechmann LP, Zahn D, Gieseler RK, Fingas CD, Marquitan G, Jochum C, Gerken G, Friedman SL, Canbay A | title = Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells | journal = Hepatology Research | volume = 39 | issue = 6 | pages = 601–608 | date = June 2009 | pmid = 19207580 | pmc = 2893585 | doi = 10.1111/j.1872-034X.2008.00485.x }}</ref>
| PEL =
 }}
}}

'''Resveratrol''' (3,5,4′-trihydroxy-''trans''-stilbene) is a [[stilbenoid]], a type of [[natural phenol]] or [[polyphenol]] and a [[phytoalexin]] produced by several plants in response to injury or when the plant is under attack by [[pathogen]]s, such as [[bacterium|bacteria]] or [[fungus|fungi]].<ref name="lpi">{{cite web | title=Resveratrol | publisher = Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR |date=11 June 2015 | url = https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/resveratrol|access-date=28 October 2025}}</ref><ref>{{cite journal | vauthors = Frémont L | title = Biological effects of resveratrol | journal = Life Sciences | volume = 66 | issue = 8 | pages = 663–673 | date = January 2000 | pmid = 10680575 | doi = 10.1016/S0024-3205(99)00410-5 }}</ref> Sources of resveratrol in food include the skin of [[grape]]s, [[blueberries]], [[raspberries]], [[mulberries]], and [[peanut]]s.<ref name=lpi/><ref name="Jansiski2013">{{cite journal | vauthors = Jasiński M, Jasińska L, Ogrodowczyk M | title = Resveratrol in prostate diseases - a short review | journal = Central European Journal of Urology | volume = 66 | issue = 2 | pages = 144–149 | date = August 2013 | pmid = 24579014 | pmc = 3936154 | doi = 10.5173/ceju.2013.02.art8 }}</ref><ref name="pe" />

Although commonly used as a [[dietary supplement]] and studied in laboratory models of human diseases, there is no [[evidence-based medicine|high-quality evidence]] that resveratrol improves [[longevity|lifespan]] or has a substantial positive effect on any human disease.<ref name=lpi/><ref name=pmid21698226/><ref name="saheb">{{cite journal | vauthors = Sahebkar A, Serban C, Ursoniu S, Wong ND, Muntner P, Graham IM, Mikhailidis DP, Rizzo M, Rysz J, Sperling LS, Lip GY, Banach M | title = Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors--Results from a systematic review and meta-analysis of randomized controlled trials | journal = International Journal of Cardiology | volume = 189 | pages = 47–55 | year = 2015 | pmid = 25885871 | doi = 10.1016/j.ijcard.2015.04.008 |url=https://www.sciencedirect.com/science/article/abs/pii/S0167527315007184| url-access = subscription }}</ref>  In particular, its effect on [[cancer prevention]] is so slight that drinking [[red wine]] for the sake of consuming resveratrol causes 100,000 alcohol-induced cancers for each single case of cancer that might be prevented by the resveratrol in the wine.<ref>{{Cite journal |last=Rehm |first=Jürgen |last2=Shield |first2=Kevin D. |last3=Weiderpass |first3=Elisabete |date=November 2020 |title=Alcohol consumption. A leading risk factor for cancer |url=https://linkinghub.elsevier.com/retrieve/pii/S0009279719308506 |journal=Chemico-Biological Interactions |language=en |volume=331 |article-number=109280 |doi=10.1016/j.cbi.2020.109280|url-access=subscription }}</ref>
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==Research==
Resveratrol has been studied for its potential therapeutic use,<ref>{{cite journal | vauthors = Singh AP, Singh R, Verma SS, Rai V, Kaschula CH, Maiti P, Gupta SC | title = Health benefits of resveratrol: Evidence from clinical studies | journal = Medicinal Research Reviews | volume = 39 | issue = 5 | pages = 1851–1891 | date = September 2019 | pmid = 30741437 | doi = 10.1002/med.21565 | s2cid = 73443806 }}</ref> with little evidence of anti-disease effects or health benefits in humans.<ref name=lpi/><ref name="hba1c">{{cite journal | vauthors = Zeraattalab-Motlagh S, Jayedi A, Shab-Bidar S | title = The effects of resveratrol supplementation in patients with type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease: an umbrella review of meta-analyses of randomized controlled trials | journal = The American Journal of Clinical Nutrition | volume = 114 | issue = 5 | pages = 1675–1685 | date = November 2021 | pmid = 34320173 | doi = 10.1093/ajcn/nqab250 | doi-access = free| url=https://www.sciencedirect.com/science/article/pii/S0002916522004993| url-access = subscription }}</ref>

===Cardiovascular disease===
Resveratrol supplementation does not affect [[biomarker]]s for [[cardiovascular diseases]].<ref name=lpi/><ref name=saheb/> There is no evidence of benefit from resveratrol in people who already have [[heart disease]].<ref>{{cite journal | vauthors = Tomé-Carneiro J, Gonzálvez M, Larrosa M, Yáñez-Gascón MJ, García-Almagro FJ, Ruiz-Ros JA, Tomás-Barberán FA, García-Conesa MT, Espín JC | title = Resveratrol in primary and secondary prevention of cardiovascular disease: a dietary and clinical perspective | journal = Annals of the New York Academy of Sciences | volume = 1290 | issue = 1 | pages = 37–51 | date = July 2013 | pmid = 23855464 | doi = 10.1111/nyas.12150 | s2cid = 206223647 | bibcode = 2013NYASA1290...37T }}</ref> A 2018 [[meta-analysis]] found no effect on [[systolic blood pressure|systolic]] or [[diastolic blood pressure]]; a sub-analysis revealed a 2&nbsp;mmHg decrease in systolic pressure only from resveratrol doses of 300&nbsp;mg per day, and only in [[diabetes|diabetic people]].<ref name="pmid29359958">{{cite journal | vauthors = Fogacci F, Tocci G, Presta V, Fratter A, Borghi C, Cicero AF | title = Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials | journal = Critical Reviews in Food Science and Nutrition | volume = 59 | issue = 10 | pages = 1605–1618 | date = January 2018 | pmid = 29359958 | doi = 10.1080/10408398.2017.1422480 | s2cid = 30351462 }}</ref> A 2014 Chinese meta-analysis found no effect on systolic or diastolic blood pressure; a sub-analysis found an 11.90&nbsp;mmHg reduction in [[systolic blood pressure]] from resveratrol doses of 150&nbsp;mg per day.<ref name=ResBP>{{cite journal | vauthors = Liu Y, Ma W, Zhang P, He S, Huang D | title = Effect of resveratrol on blood pressure: a meta-analysis of randomized controlled trials | journal = Clinical Nutrition | volume = 34 | issue = 1 | pages = 27–34 | date = February 2015 | pmid = 24731650 | doi = 10.1016/j.clnu.2014.03.009 }}</ref>

===Cancer===
{{as of|2020}}, there is no evidence of an effect of resveratrol on cancer in humans.<ref name=lpi/><ref name="pmid24500760">{{cite journal | vauthors = Carter LG, D'Orazio JA, Pearson KJ | title = Resveratrol and cancer: focus on in vivo evidence | journal = Endocrine-Related Cancer | volume = 21 | issue = 3 | pages = R209–R225 | date = June 2014 | pmid = 24500760 | pmc = 4013237 | doi = 10.1530/ERC-13-0171 }}</ref>

===Metabolic syndrome===
There is no conclusive evidence for an effect of resveratrol on human [[metabolic syndrome]].<ref name=lpi/><ref name=hba1c/><ref name=Poul2013>{{cite journal | vauthors = Poulsen MM, Jørgensen JO, Jessen N, Richelsen B, Pedersen SB | title = Resveratrol in metabolic health: an overview of the current evidence and perspectives | journal = Annals of the New York Academy of Sciences | volume = 1290 | issue = 1 | pages = 74–82 | date = July 2013 | pmid = 23855468 | doi = 10.1111/nyas.12141 | s2cid = 206223623 | bibcode = 2013NYASA1290...74P }}</ref><ref name=2014DiabetMeta>{{cite journal | vauthors = Hausenblas HA, Schoulda JA, Smoliga JM | title = Resveratrol treatment as an adjunct to pharmacological management in type 2 diabetes mellitus--systematic review and meta-analysis | journal = Molecular Nutrition & Food Research | volume = 59 | issue = 1 | pages = 147–159 | date = January 2015 | pmid = 25138371 | doi = 10.1002/mnfr.201400173 }}</ref> One 2015 review found little evidence for use of resveratrol to treat [[diabetes]].<ref name="ligt">{{cite journal | vauthors = de Ligt M, Timmers S, Schrauwen P | title = Resveratrol and obesity: Can resveratrol relieve metabolic disturbances? | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1852 | issue = 6 | pages = 1137–1144 | date = June 2015 | pmid = 25446988 | doi = 10.1016/j.bbadis.2014.11.012 | doi-access = free | url = https://cris.maastrichtuniversity.nl/files/73055919/schrauwen_2015_resveratrol_and_obesity_can_resveratrol.pdf }}</ref> Meta-analyses in 2021 and 2015 found little evidence for an effect of resveratrol on diabetes biomarkers.<ref name=hba1c/><ref name=2014DiabetMeta/>

One review found limited evidence that resveratrol lowered [[fasting plasma glucose]] in people with diabetes.<ref>{{cite journal | vauthors = Zhu X, Wu C, Qiu S, Yuan X, Li L | title = Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis | journal = Nutrition & Metabolism | volume = 14 | issue = 1 | article-number = 60 | date = 22 September 2017 | pmid = 29018489 | pmc = 5610395 | doi = 10.1186/s12986-017-0217-z | doi-access = free }}</ref> Two reviews  indicated that resveratrol supplementation may reduce [[body weight]] and [[body mass index]], but not [[fat mass]] or total [[blood cholesterol]].<ref>{{cite journal | vauthors = Mousavi SM, Milajerdi A, Sheikhi A, Kord-Varkaneh H, Feinle-Bisset C, Larijani B, Esmaillzadeh A | title = Resveratrol supplementation significantly influences obesity measures: a systematic review and dose-response meta-analysis of randomized controlled trials | journal = Obesity Reviews | volume = 20 | issue = 3 | pages = 487–498 | date = March 2019 | pmid = 30515938 | doi = 10.1111/obr.12775 | s2cid = 54563469 }}</ref><ref>{{cite journal | vauthors = Asgary S, Karimi R, Momtaz S, Naseri R, Farzaei MH | title = Effect of resveratrol on metabolic syndrome components: A systematic review and meta-analysis | journal = Reviews in Endocrine & Metabolic Disorders | volume = 20 | issue = 2 | pages = 173–186 | date = June 2019 | pmid = 31065943 | doi = 10.1007/s11154-019-09494-z | s2cid = 146806930 }}</ref> A 2018 review found some evidence that resveratrol supplementation could reduce biomarkers of [[inflammation]], [[TNF-α]] and [[C-reactive protein]],<ref>{{cite journal | vauthors = Koushki M, Dashatan NA, Meshkani R | title = Effect of Resveratrol Supplementation on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials | journal = Clinical Therapeutics | volume = 40 | issue = 7 | pages = 1180–1192.e5 | date = July 2018 | pmid = 30017172 | doi = 10.1016/j.clinthera.2018.05.015 | s2cid = 51677307 }}</ref> while a 2015 review reported no evidence for effects of resveratrol on biomarkers of inflammation or  cardiovascular diseases.<ref name=saheb/>

===Lifespan===
{{As of|2015}},{{Update inline|date=June 2025|?=yes}} there is insufficient evidence to indicate that consuming resveratrol has an effect on human lifespan.<ref name=lpi/><ref name="pmid21698226">{{cite journal | vauthors = Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, Das DK, Delmas D, Gottfried C, Lin HY, Ma QY, Mukhopadhyay P, Nalini N, Pezzuto JM, Richard T, Shukla Y, Surh YJ, Szekeres T, Szkudelski T, Walle T, Wu JM | title = What is new for an old molecule? Systematic review and recommendations on the use of resveratrol | journal = PLOS ONE | volume = 6 | issue = 6 | article-number = e19881 | year = 2011 | pmid = 21698226 | pmc = 3116821 | doi = 10.1371/journal.pone.0019881 | doi-access = free | bibcode = 2011PLoSO...619881V }}</ref>

===Cognition===
Resveratrol has been assessed for a possible effect on [[cognition]], but with mixed evidence for an effect. One review concluded that resveratrol had no effect on neurological function, but reported that supplementation improved recognition and [[mood (psychology)|mood]], although there were inconsistencies in study designs and results.<ref>{{cite journal | vauthors = Marx W, Kelly JT, Marshall S, Cutajar J, Annois B, Pipingas A, Tierney A, Itsiopoulos C | 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 | date = June 2018 | pmid = 29596658 | doi = 10.1093/nutrit/nuy010 | hdl-access = free | s2cid = 4472410 | hdl = 10072/389251 }}</ref>

===Alzheimer's disease===

A 2022 meta-analysis provided preliminary evidence that resveratrol, alone or in combination with glucose and [[malate]], may slow cognitive decline in [[Alzheimer's disease]].<ref name="tosatti">{{cite journal | vauthors = Tosatti JA, Fontes AF, Caramelli P, Gomes KB | title = Effects of Resveratrol Supplementation on the Cognitive Function of Patients with Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials | journal = Drugs & Aging | volume = 39 | issue = 4 | pages = 285–295 | date = April 2022 | pmid = 35187615 | doi = 10.1007/s40266-022-00923-4 }}</ref>

===Diabetes===

Research on people with [[diabetes]] is limited and does not support the use of resveratrol for this purpose.<ref name=lpi/><ref name="hba1c"/><ref>{{cite journal | vauthors = Jeyaraman MM, Al-Yousif NS, Singh Mann A, Dolinsky VW, Rabbani R, Zarychanski R, Abou-Setta AM | title = Resveratrol for adults with type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | article-number = CD011919 | date = January 2020 | pmid = 31978258 | pmc = 6984411 | doi = 10.1002/14651858.CD011919.pub2 }}</ref>

===Other===
There is no [[evidence-based medicine|significant evidence]] that resveratrol affects [[Endothelium#Function|vascular endothelial function]], [[neuroinflammation]], [[skin infection]]s or [[aging]] skin.<ref name=lpi/> A 2019 review of human studies found mixed effects of resveratrol on certain bone [[biomarker]]s, such as increases in blood and bone [[alkaline phosphatase]], while reporting no effect on other biomarkers, such as [[calcium]] and [[collagen]].<ref>{{cite journal | vauthors = Asis M, Hemmati N, Moradi S, Nagulapalli Venkata KC, Mohammadi E, Farzaei MH, Bishayee A | title = Effects of resveratrol supplementation on bone biomarkers: a systematic review and meta-analysis | journal = Annals of the New York Academy of Sciences | volume = 1457 | issue = 1 | pages = 92–103 | date = December 2019 | pmid = 31490554 | doi = 10.1111/nyas.14226 | s2cid = 201846615 | bibcode = 2019NYASA1457...92A }}</ref>

== Pharmacology ==

=== Pharmacodynamics ===
Resveratrol has been identified as a [[pan-assay interference compounds|pan-assay interference compound]], which produces positive results in many different laboratory assays.<ref>{{cite journal | vauthors = Baell J, Walters MA | title = Chemistry: Chemical con artists foil drug discovery | journal = Nature | volume = 513 | issue = 7519 | pages = 481–483 | date = September 2014 | pmid = 25254460 | doi = 10.1038/513481a | doi-access = free | bibcode = 2014Natur.513..481B }}</ref> Its ability for varied interactions may be due to direct effects on [[cell membrane]]s.<ref>{{cite journal | vauthors = Ingólfsson HI, Thakur P, Herold KF, Hobart EA, Ramsey NB, Periole X, de Jong DH, Zwama M, Yilmaz D, Hall K, Maretzky T, Hemmings HC, Blobel C, Marrink SJ, Koçer A, Sack JT, Andersen OS | title = Phytochemicals perturb membranes and promiscuously alter protein function | journal = ACS Chemical Biology | volume = 9 | issue = 8 | pages = 1788–1798 | date = August 2014 | pmid = 24901212 | pmc = 4136704 | doi = 10.1021/cb500086e }}</ref>

As of 2015, many specific [[biological target]]s for resveratrol had been identified, including [[NAD(P)H dehydrogenase, quinone 2|NQO2]] (alone and in interaction with [[AKT1]]), [[GSTP1]], [[estrogen receptor beta]], [[CBR1]], and [[Alpha-v beta-3|integrin αVβ]]. It was unclear at that time if any or all of these were responsible for the observed effects in cells and model organisms.<ref>{{cite journal | vauthors = Vang O | title = Resveratrol: challenges in analyzing its biological effects | journal = Annals of the New York Academy of Sciences | volume = 1348 | issue = 1 | pages = 161–170 | date = August 2015 | pmid = 26315294 | doi = 10.1111/nyas.12879 | s2cid = 27108183 | bibcode = 2015NYASA1348..161V }}</ref>

=== Pharmacokinetics ===

The viability of an oral delivery method is unlikely due to the low aqueous solubility of the molecule. The [[bioavailability]] of resveratrol is about 0.5% due to extensive [[liver|hepatic]] [[glucuronidation]] and [[sulfation]].<ref name="Walle">{{cite journal | vauthors = Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle UK | title = High absorption but very low bioavailability of oral resveratrol in humans | journal = Drug Metabolism and Disposition | volume = 32 | issue = 12 | pages = 1377–1382 | date = December 2004 | pmid = 15333514 | doi = 10.1124/dmd.104.000885 | s2cid = 10020092 }}</ref> Glucuronidation occurs in the intestine as well as in the liver, whereas sulfonation not only occurs in the liver but in the intestine and by microbial gut activity.<ref name="pmid30614249">{{cite journal | vauthors = Luca SV, Macovei I, Bujor A, Miron A, Skalicka-Woźniak K, Aprotosoaie AC, Trifan A | title = Bioactivity of dietary polyphenols: The role of metabolites | journal = Critical Reviews in Food Science and Nutrition | volume = 60 | issue = 4 | pages = 626–659 | year = 2020 | pmid = 30614249 | doi = 10.1080/10408398.2018.1546669 | s2cid = 58651581 }}</ref>  Due to rapid metabolism, the [[Biological half-life|half-life]] of resveratrol is short (about 8–14 minutes), but the half-life of the sulphate and glucoronide metabolites is above 9&nbsp;hours.<ref name="pmid16732220" />

=== Metabolism ===
Resveratrol is extensively metabolized in the body,<ref name=lpi/> with the liver and intestines as the major sites of its metabolism.<ref name="pmid23474649">{{cite journal | vauthors = Sharan S, Nagar S | title = Pulmonary metabolism of resveratrol: in vitro and in vivo evidence | journal = Drug Metabolism and Disposition | volume = 41 | issue = 5 | pages = 1163–1169 | date = May 2013 | pmid = 23474649 | pmc = 3629805 | doi = 10.1124/dmd.113.051326 }}</ref><ref name="pmid16732220">{{cite journal | vauthors = Baur JA, Sinclair DA | title = Therapeutic potential of resveratrol: the in vivo evidence | journal = Nature Reviews. Drug Discovery | volume = 5 | issue = 6 | pages = 493–506 | date = June 2006 | pmid = 16732220 | doi = 10.1038/nrd2060 | s2cid = 36628503 }}</ref> Liver metabolites are products of [[Drug metabolism#Phase II – conjugation|phase II]] (conjugation) enzymes,<ref name="pmid30893846">{{cite journal | vauthors = Chimento A, De Amicis F, Sirianni R, Sinicropi MS, Puoci F, Casaburi I, Saturnino C, Pezzi V | title = Progress to Improve Oral Bioavailability and Beneficial Effects of Resveratrol | journal = International Journal of Molecular Sciences | volume = 20 | issue = 6 | page = 1381 | date = March 2019 | pmid = 30893846 | pmc = 6471659 | doi = 10.3390/ijms20061381 | doi-access = free }}</ref> which are themselves induced by resveratrol in vitro.<ref name="pmid26221416">{{cite journal | vauthors = Gambini J, Inglés M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, Mas-Bargues C, Abdelaziz KM, Gomez-Cabrera MC, Vina J, Borras C | title = Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans | journal = Oxidative Medicine and Cellular Longevity | volume = 2015 | article-number = 837042 | year = 2015 | pmid = 26221416 | pmc = 4499410 | doi = 10.1155/2015/837042 | doi-access = free }}</ref>

== Chemistry ==
Resveratrol (3,5,4'-trihydroxystilbene) is a stilbenoid, a derivative of [[(E)-Stilbene|stilbene]].<ref name=lpi/> It exists as two [[cis-trans isomerism|geometric isomers]]: ''cis-'' (''Z'') and ''trans-'' (''E''), with the ''trans''-isomer shown in the top image. Resveratrol exists conjugated to glucose.<ref name="M1995">{{cite journal | vauthors = Mattivi F, Reniero F, Korhammer S | title = Isolation, characterization, and evolution in red wine vinification of resveratrol monomers | journal = Journal of Agricultural and Food Chemistry | volume = 43 | issue = 7 | pages = 1820–1823 | year = 1995 | doi = 10.1021/jf00055a013 | bibcode = 1995JAFC...43.1820M }}</ref>

The ''trans-'' form can undergo [[photoisomerization]] to the ''cis-'' form when exposed to [[ultraviolet]] irradiation.<ref>{{cite journal| vauthors = Lamuela-Raventos RM, Romero-Perez AI, Waterhouse AL, de la Torre-Boronat MC | title = Direct HPLC Analysis of cis- and trans-Resveratrol and Piceid Isomers in Spanish Red Vitis vinifera Wines | journal = Journal of Agricultural and Food Chemistry | volume = 43 | issue = 2| pages = 281–283 | doi = 10.1021/jf00050a003| year = 1995 | bibcode = 1995JAFC...43..281L }}</ref><ref>''Resveratrol Photoisomerization: An Integrative Guided-Inquiry Experiment'' Elyse Bernard, Philip Britz-McKibbin, Nicholas Gernigon Vol. 84 No. 7 July '''2007''' [[Journal of Chemical Education]] 1159.</ref>

[[File:Rasveratrol isomerization-en.svg|400px|thumb|class=skin-invert-image|Resveratrol photoisomerization]]

[[ultraviolet|UV]] irradiation to cis-resveratrol induces further photochemical reaction, producing a fluorescent molecule named "Resveratrone".<ref>{{cite journal | vauthors = Yang I, Kim E, Kang J, Han H, Sul S, Park SB, Kim SK | title = Photochemical generation of a new, highly fluorescent compound from non-fluorescent resveratrol | journal = Chemical Communications | volume = 48 | issue = 32 | pages = 3839–3841 | date = April 2012 | pmid = 22436889 | doi = 10.1039/C2CC30940H }}</ref>

''Trans''-resveratrol in the powder form was found to be stable under "accelerated stability" conditions of 75% humidity and 40&nbsp;°C in the presence of air.<ref name="pmid16579722">{{cite journal | vauthors = Prokop J, Abrman P, Seligson AL, Sovak M | title = Resveratrol and its glycon piceid are stable polyphenols | journal = Journal of Medicinal Food | volume = 9 | issue = 1 | pages = 11–14 | year = 2006 | pmid = 16579722 | doi = 10.1089/jmf.2006.9.11 }}</ref> The ''trans'' isomer is also stabilized by the presence of transport proteins.<ref name="pmid24773207">{{cite journal | vauthors = Pantusa M, Bartucci R, Rizzuti B | title = Stability of trans-resveratrol associated with transport proteins | journal = Journal of Agricultural and Food Chemistry | volume = 62 | issue = 19 | pages = 4384–4391 | date = May 2014 | pmid = 24773207 | doi = 10.1021/jf405584a | bibcode = 2014JAFC...62.4384P }}</ref> Resveratrol content also was stable in the skins of grapes and [[pomace]] taken after fermentation and stored for a long period.<ref name="pmid10051967">{{cite journal | vauthors = Bertelli AA, Gozzini A, Stradi R, Stella S, Bertelli A | title = Stability of resveratrol over time and in the various stages of grape transformation | journal = Drugs Under Experimental and Clinical Research | volume = 24 | issue = 4 | pages = 207–211 | year = 1998 | pmid = 10051967 }}</ref> <sup>l</sup>H- and <sup>13</sup>C-NMR data for the four most common forms of resveratrols are reported in literature.<ref name="M1995"/>

=== Biosynthesis ===
Resveratrol is produced in plants via the enzyme [[resveratrol synthase]] ([[stilbene synthase]]).<ref name=":0">{{cite journal | vauthors = Valletta A, Iozia LM, Leonelli F | title = Impact of Environmental Factors on Stilbene Biosynthesis | journal = Plants | volume = 10 | issue = 1 | page = 90 | date = January 2021 | pmid = 33406721 | pmc = 7823792 | doi = 10.3390/plants10010090 | doi-access = free | bibcode = 2021Plnts..10...90V }}</ref><ref name=":1">{{cite journal | vauthors = Dubrovina AS, Kiselev KV | title = Regulation of stilbene biosynthesis in plants | journal = Planta | volume = 246 | issue = 4 | pages = 597–623 | date = October 2017 | pmid = 28685295 | doi = 10.1007/s00425-017-2730-8 | s2cid = 4015467 | bibcode = 2017Plant.246..597D }}</ref> Its immediate precursor is a tetraketide derived from [[malonyl CoA]] and [[Coumaroyl-CoA|4-coumaroyl CoA]].<ref name=":0" /><ref name=":1" /> The latter is derived from [[phenylalanine]].<ref name="pmid2450022">{{cite journal | vauthors = Wang C, Zhi S, Liu C, Xu F, Zhao A, Wang X, Ren Y, Li Z, Yu M | title = Characterization of Stilbene Synthase Genes in Mulberry (Morus atropurpurea) and Metabolic Engineering for the Production of Resveratrol in Escherichia coli | journal = Journal of Agricultural and Food Chemistry | volume = 65 | issue = 8 | pages = 1659–1668 | date = March 2017 | pmid = 28168876 | doi = 10.1021/acs.jafc.6b05212 | bibcode = 2017JAFC...65.1659W }}</ref>

=== Biotransformation ===
The grapevine fungal [[plant pathogen|pathogen]] ''[[Botrytis cinerea]]'' is able to oxidise resveratrol into metabolites showing attenuated antifungal activities. Those include the resveratrol dimers restrytisol A, B, and C, [[resveratrol trans-dehydrodimer]], leachinol F, and [[pallidol]].<ref name="pmid10650073">{{cite journal | vauthors = Cichewicz RH, Kouzi SA, Hamann MT | title = Dimerization of resveratrol by the grapevine pathogen Botrytis cinerea | journal = Journal of Natural Products | volume = 63 | issue = 1 | pages = 29–33 | date = January 2000 | pmid = 10650073 | doi = 10.1021/np990266n | bibcode = 2000JNAtP..63...29C }}</ref> The soil bacterium ''[[Bacillus cereus]]'' can be used to transform resveratrol into [[piceid]] (resveratrol 3-O-beta-D-[[glucoside]]).<ref name="pmid9784180">{{cite journal | vauthors = Cichewicz RH, Kouzi SA | title = Biotransformation of resveratrol to piceid by Bacillus cereus | journal = Journal of Natural Products | volume = 61 | issue = 10 | pages = 1313–1314 | date = October 1998 | pmid = 9784180 | doi = 10.1021/np980139b | bibcode = 1998JNAtP..61.1313C }}</ref>

== Adverse effects ==
Only a few human studies have been done to determine the [[adverse effect]]s of resveratrol, all of them preliminary with small participant numbers. Adverse effects resulted mainly from long-term use (weeks or longer) and daily doses of 1000&nbsp;mg or higher, causing [[nausea]], [[abdominal pain|stomach pain]], [[flatulence]], and [[diarrhea]].<ref name=lpi/> A review of 136 patients in seven studies who were given more than 500&nbsp;mg for a month showed 25&nbsp;cases of diarrhea, 8&nbsp;cases of abdominal pain, 7&nbsp;cases of nausea, and 5&nbsp;cases of flatulence.<ref name="pmid23740855">{{cite journal | vauthors = Cottart CH, Nivet-Antoine V, Beaudeux JL | title = Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans | journal = Molecular Nutrition & Food Research | volume = 58 | issue = 1 | pages = 7–21 | date = January 2014 | pmid = 23740855 | doi = 10.1002/mnfr.201200589 }}</ref> A 2018 review of resveratrol effects on blood pressure found that some people had increased frequency of [[bowel movement]]s and loose [[Human feces|stools]].<ref name="pmid29359958" />

== Occurrences ==

=== Plants ===
Resveratrol is a [[phytoalexin]], a class of compounds produced by many plants when they are infected by pathogens or physically harmed by cutting, crushing, or ultraviolet radiation.<ref name=Sales2014rev/> Plants that synthesize resveratrol include [[Reynoutria japonica|Japanese knotweed]], [[pine]] trees (including [[Scots pine]] and [[Eastern white pine]]), Concord grape vines, raspberries, mulberries, peanut plants, cocoa bushes, and ''[[Vaccinium]]'' shrubs that produce berries, including blueberries, cranberries, and bilberries.<ref name=lpi/><ref name="Jansiski2013"/><ref name=Sales2014rev/>

=== Foods ===
The levels of resveratrol found in food varies considerably, even in the same food from season to season and batch to batch.<ref name=lpi/>

==== Wine and grape juice ====
{| class="wikitable"
|-
! rowspan="2" | Beverage
! colspan="2" |Resveratrol (μg/100&nbsp;mL)<ref name=pe/>
|-
! mean !! range
|-
| [[Red wine]]
|  270 || style="text-align:center;" | 0 — 2780
|-
| [[Rosé|Rosé wine]]
| 120 || style="text-align:center;" | 5 — 290
|-
| [[White wine]]
| 40 || style="text-align:center;" | 0 — 170
|-
| [[Sparkling wine]]
| 9 || style="text-align:center;" | 8 — 10

|-
| [[Sémillon|Green grape juice]]
| 5.08 || style="text-align:center;" | 0 — 10
|-
|}

Resveratrol concentrations in red wines average  {{val|1.9|1.7|u=mg}} trans-resveratrol/L ({{val|8.2|7.5|u=μM}}), ranging from nondetectable levels to 14.3&nbsp;mg/L (62.7&nbsp;μM) ''trans''-resveratrol. Levels of ''cis''-resveratrol follow the same trend as ''trans''-resveratrol.<ref name=Stervbo2007>{{cite journal | vauthors = Stervbo U, Vang O, Bonnesen C | year = 2007 | title = A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine | journal = Food Chemistry | volume = 101 | issue = 2 | pages = 449–457 | doi = 10.1016/j.foodchem.2006.01.047}}</ref>

In general, wines made from grapes of the [[Pinot noir]] and [[St. Laurent (grape)|St. Laurent]] varieties showed the highest level of ''trans''-resveratrol, though no wine or region can yet be said to produce wines with significantly higher concentrations than any other wine or region.<ref name=Stervbo2007/> [[Champagne]] and [[vinegar]] also contain appreciable levels of resveratrol.<ref name=pe/>

[[Red wine]] contains between 0.2 and 5.8&nbsp;mg/L, depending on the grape variety. White wine has much less because red wine is [[fermentation (wine)|fermented]] with the skins, allowing the wine to extract the resveratrol, whereas [[white wine]] is fermented after the skin has been removed.<ref name=lpi/>  The composition of wine is different from that of grapes since the extraction of resveratrol from grapes depends on the duration of the skin contact, and the resveratrol 3-glucosides are in part hydrolysed, yielding both ''trans''- and ''cis''-resveratrol.<ref name=lpi/><ref>{{Cite journal | vauthors = Naiker M, Anderson S, Johnson JB, Mani JS, Wakeling L, Bowry V |date=2020-07-21 |title=Loss of trans -resveratrol during storage and ageing of red wines |journal=Australian Journal of Grape and Wine Research |volume=26 |issue=4 |language=en |pages=385–387 |doi=10.1111/ajgw.12449 |s2cid=225590316|issn=1322-7130|doi-access=free }}</ref>

Though its extraction (i.e. from wood chips or other sources) during artificial ageing, resveratrol is added in red wines to improve the color and sensory properties.<ref>{{cite journal | vauthors = Gortzi O, Metaxa X, Mantanis G, Lalas S | title = Effect of artificial ageing using different wood chips on the antioxidant activity, resveratrol and catechin concentration, sensory properties and colour of two Greek red wines | journal = Food Chemistry | volume = 141 | issue = 3 | pages = 2887–2895 | date = December 2013 | pmid = 23871038 | doi = 10.1016/j.foodchem.2013.05.051 | publisher = Elsevier BV | author3-link = George Mantanis }}</ref>

==== Selected foods ====
{| class="wikitable"
|-
! Food
! Serving
! Total resveratrol (mg)<ref name=lpi/>
|-
| Peanuts (raw)
| 1 cup (146&nbsp;grams)
| 0.01 – 0.26
|-
| Peanut butter
| 1 cup (258&nbsp;grams)
| 0.04 – 0.13
|-
| Red grapes
| 1 cup (160&nbsp;grams)
| 0.24 – 1.25
|-
| Cocoa powder
| 1 cup (200&nbsp;grams)
| 0.28 – 0.46
|}

Ounce for ounce, peanuts have about 25% as much resveratrol as red wine.<ref name=lpi/>  [[Peanut]]s, especially [[Sprouting|sprouted]] peanuts, have a content similar to grapes in a range of 2.3 to 4.5&nbsp;μg/g before sprouting, and after sprouting, in a range of 11.7 to 25.7&nbsp;μg/g, depending on peanut [[cultivar]].<ref name="pe">{{cite web|url=http://phenol-explorer.eu/contents/polyphenol/592|title=Stilbenes-resveratrol in foods and beverages, version 3.6|publisher=Phenol-Explorer|date=2016|access-date=13 May 2016}}</ref><ref name=Sales2014rev/>

[[Mulberry|Mulberries]] (especially the skin) are a source of as much as 50 micrograms of resveratrol per gram dry weight.<ref name="pmid12840221">{{cite journal | vauthors = Stewart JR, Artime MC, O'Brian CA | title = Resveratrol: a candidate nutritional substance for prostate cancer prevention | journal = The Journal of Nutrition | volume = 133 | issue = 7 Suppl | pages = 2440S–2443S | date = July 2003 | pmid = 12840221 | doi = 10.1093/jn/133.7.2440S | doi-access = free }}</ref>

Most US supplements of resveratrol are derived from the root of [[Reynoutria japonica]] (also called Japanese knotweed, Hu Zhang, etc.)<ref name=lpi/>

== History ==
The first mention of resveratrol was in a [[Japanese language|Japanese]] article in 1939 by Michio Takaoka, who isolated it from ''[[Veratrum album]]'', variety ''grandiflorum'',  and later, in 1963, from the roots of [[Reynoutria japonica|Japanese knotweed]].<ref name=Sales2014rev>{{cite journal | vauthors = Sales JM, Resurreccion AV | title = Resveratrol in peanuts | journal = Critical Reviews in Food Science and Nutrition | volume = 54 | issue = 6 | pages = 734–770 | date = 2014 | pmid = 24345046 | doi = 10.1080/10408398.2011.606928 | s2cid = 13183809 }}</ref><ref name="takaoka">{{cite journal|title=Resveratrol, a new phenolic compound, from ''Veratrum grandiflorum''|author=Takaoka M|journal=Journal of the Chemical Society of Japan|year=1939|volume=60|issue=11|pages=1090–1100|url=http://www.mendeley.com/research/resveratrol-new-phenolic-compound-veratrum-grandiflorum/|doi=10.1246/nikkashi1921.60.1090|doi-access=free}}</ref><ref name="takaoka1">{{cite journal|doi=10.1246/nikkashi1921.61.1067|title=The Phenolic Substances of White Hellebore (Veratrum Grandiflorum Loes. Fill). V|journal=Nippon Kagaku Kaishi|volume=61|issue=10|pages=1067–1069|year=1940| vauthors = Takaoka M |doi-access=free}}</ref><ref>{{Cite journal| vauthors = Nonomura S, Kanagawa H, Makimoto A |date=1963|title=Chemical constituents of Polygonaceous plants. I. studies on the components of Ko-jo-kon. (Polygonum cuspidatum SIEB et ZUCC)|journal=Yakugaku Zasshi|volume=83|issue=10|pages=988–990|doi=10.1248/yakushi1947.83.10_988|doi-access=free}}</ref> In 2004, [[Harvard University]] professor [[David Sinclair (biologist)|David Sinclair]] co-founded [[Sirtris Pharmaceuticals]], the initial product of which was a resveratrol formulation.<ref>{{cite news | author = Rimas A | title = His research targets the aging process | date =2006-12-11 | url = http://www.boston.com/news/globe/health_science/articles/2006/12/11/his_research_targets_the_aging_process/ | publisher = [[The Boston Globe]]}}</ref><ref>{{cite news | author = Stipp D | title = Can red wine help you live forever? | date = 2007-01-19 | publisher = [[Fortune magazine]] | url = https://money.cnn.com/2007/01/18/magazines/fortune/Live_forever.fortune/index.htm?postversion=2007011912}}</ref><ref>{{cite news | author = Weintraub A |date = 2009-07-29 | title = Resveratrol: The Hard Sell on Anti-Aging | url = http://www.businessweek.com/magazine/content/09_32/b4142000175800.htm | archive-url = https://web.archive.org/web/20090731015836/http://www.businessweek.com/magazine/content/09_32/b4142000175800.htm | archive-date = July 31, 2009 | publisher = Bloomberg Businessweek }}</ref> Sirtris was purchased and made a subsidiary of [[GlaxoSmithKline]] in 2008 for $720 million and shut down in 2013, without successful drug development.<ref>{{Cite news | vauthors = Carroll J, McBride R |date=March 12, 2013 |title=Updated: GSK moves to shutter Sirtris' Cambridge office, integrate R&D |language=en |work=FierceBiotech |url=http://www.fiercebiotech.com/r-d/updated-gsk-moves-to-shutter-sirtris-cambridge-office-integrate-r-d |access-date=August 17, 2017 |archive-date=April 28, 2019 |archive-url=https://web.archive.org/web/20190428120955/https://www.fiercebiotech.com/r-d/updated-gsk-moves-to-shutter-sirtris-cambridge-office-integrate-r-d |url-status=live }}</ref><ref>{{Cite web |title=GSK absorbs controversial 'longevity' company: News blog |url=http://blogs.nature.com/news/2013/03/gsk-absorbs-controversial-longevity-company.html |publisher=Nature Blog |access-date=2017-08-17 |archive-date=2013-12-17 |archive-url=https://web.archive.org/web/20131217235120/http://blogs.nature.com/news/2013/03/gsk-absorbs-controversial-longevity-company.html |url-status=live }}.</ref>

== Related compounds ==
* [[Dihydro-resveratrol]]
* [[Epsilon-viniferin]], [[Pallidol]] and [[Quadrangularin A]] three different resveratrol dimers
* [[Elafibranor]], a structurally related compound that acts as a dual PPARα/δ agonist
* Tetrahydroxystilbene glucoside, a glycoside compound found in [[He Shou Wu]] which is very similar to resveratrol.
* [[Trans-diptoindonesin B]], a resveratrol trimer
* [[Hopeaphenol]], a resveratrol tetramer
* [[Oxyresveratrol]], the aglycone of [[mulberroside A]], a compound found in ''[[Morus alba]]'', the white mulberry<ref name="pmid20411402">{{cite journal | vauthors = Kim JK, Kim M, Cho SG, Kim MK, Kim SW, Lim YH | title = Biotransformation of mulberroside A from Morus alba results in enhancement of tyrosinase inhibition | journal = Journal of Industrial Microbiology & Biotechnology | volume = 37 | issue = 6 | pages = 631–637 | date = June 2010 | pmid = 20411402 | doi = 10.1007/s10295-010-0722-9 | s2cid = 21236818 | doi-access = free }}</ref>
* [[Piceatannol]], an active metabolite of resveratrol found in red wine
* [[Piceid]], a resveratrol glucoside
* [[Pterostilbene]], a doubly methylated resveratrol
* 4'-Methoxy-(E)-resveratrol 3-O-rutinoside, a compound found in the stem bark of ''[[Boswellia dalzielii]]''<ref>Alemika Taiwo E, Onawunmi Grace O and Olugbade Tiwalade O, [https://web.archive.org/web/20130730080304/http://dspace.unijos.edu.ng/handle/10485/1174 Antibacterial phenolics from Boswellia dalzielii.] ''Nigerian Journal of Natural Products and Medicines'', 2006</ref>
* [[Rhaponticin]] a glucoside of the stilbenoid [[rhapontigenin]], found in [[rhubarb]] [[rhizome]]s

== See also ==
* [[Phenolic compounds in wine]]
* [[Polyphenol antioxidant]]
* [[List of phytochemicals in food]]
* [[Phytochemistry]]
* [[Secondary metabolites]]

== References ==
{{reflist}}

== External links ==
* {{Commons category-inline}}

{{Antioxidants}}
{{Phytoestrogens}}
{{Estrogen receptor modulators}}
{{Prostanoid signaling modulators}}
{{Stilbenes}}

[[Category:Resveratrol| ]]
[[Category:Aromatase inhibitors]]
[[Category:GPER agonists]]
[[Category:Phytoalexins]]
[[Category:Phytoestrogens]]
[[Category:Stilbenoids]]
[[Category:CYP2C9 inhibitors]]