Hydroxytyrosol: Difference between revisions

{{cs1 config|name-list-style=vanc}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 400107001

| Name = Hydroxytyrosol

| ImageFile = Hydroxytyrosol.svg

| ImageFile2 = Hydroxytyrosol.png

| ImageSize =

| ImageName = Hydroxytyrosol

| PIN = 4-(2-Hydroxyethyl)benzene-1,2-diol

| OtherNames = 3-Hydroxytyrosol<br />3,4-dihydroxyphenylethanol (DOPET)<br />Dihydroxyphenylethanol<br />2-(3,4-Di-hydroxyphenyl)-ethanol (DHPE)<br />3,4-dihydroxyphenolethanol (3,4-DHPEA)<ref name="oil">{{cite journal |title=Antioxidant activity of tocopherols and phenolic compounds of virgin olive oil | vauthors = Baldioli M, Servili M, Perretti G, Montedoro GF |journal=Journal of the American Oil Chemists' Society |date=1996 |issue=11 |volume=73 |pages=1589–1593 |doi=10.1007/BF02523530|s2cid=84749200 }}</ref>

|Section1={{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|??}}

| CASNo = 10597-60-1

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 74680

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 485747

| DrugBank = DB12771

| EINECS = 600-704-3

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 68889

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = QEU0NE4O90

| RTECS =

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| SMILES = Oc1ccc(cc1O)CCO

|Section2={{Chembox Properties

| C=8|H=10|O=3

| Appearance = colorless solid

| Density =

| Solubility = 5 g/100 ml

| MeltingPt =

| BoilingPtC =

|Section3={{Chembox Structure

| Dipole =

|Section7={{Chembox Hazards

| ExternalSDS = [http://www.sigmaaldrich.com/MSDS/MSDS/DisplayMSDSPage.do?country=GB&language=en&productNumber=H4291&brand=SIGMA&PageToGoToURL=http%3A%2F%2Fwww.sigmaaldrich.com%2Fcatalog%2Fsearch%3Finterface%3DAll%26term%3D2-%25283%252C4-dihydroxyphenyl%2529ethanol%26N%3D0%26mode%3Dmatch%2520partialmax%26focus%3Dproduct%26lang%3Den%26region%3DGB]

| MainHazards = Causes skin irritation.

Causes serious eye irritation.

May cause respiratory irritation.

| FlashPtC =

| GHS_ref=<ref>{{cite web |title=Hydroxytyrosol |url= https://pubchem.ncbi.nlm.nih.gov/compound/82755#section=Safety-and-Hazards | work = PubChem | publisher = U.S. National Library of Medicine |language=en}}</ref>

| GHSPictograms = {{GHS07}}

| GHSSignalWord = Warning

| HPhrases = {{H-phrases|315|319|335}}

| PPhrases = {{P-phrases|261|264|271|280|302+352|304+340|305+351+338|312|321|332+313|337+313|362|403+233|405|501}}

|Section8={{Chembox Related

| OtherFunction_label = [[alcohols]]

| OtherFunction = [[benzyl alcohol]], [[tyrosol]]

'''Hydroxytyrosol''' is an [[organic compound]] with the formula {{chem2|(HO)2C6H3CH2CH2OH}}. It is a [[phenylethanoid]], i.e. a relative of [[phenethyl alcohol]]. Its derivatives are found in a variety of natural sources, notably olive oils and wines. Hydroxytyrosol is a colorless solid,<ref>{{cite journal | vauthors = Charoenprasert S, Mitchell A | title = Factors influencing phenolic compounds in table olives (''Olea europaea'') | journal = [[Journal of Agricultural and Food Chemistry]] | volume = 60 | issue = 29 | pages = 7081–7095 | date = July 2012 | pmid = 22720792 | doi = 10.1021/jf3017699 }}</ref><ref>{{cite journal | vauthors = Karković Marković A, Torić J, Barbarić M, Jakobušić Brala C | title = Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health | journal = [[Molecules (journal)|Molecules]] | volume = 24 | issue = 10 | page = 2001 | date = May 2019 | pmid = 31137753 | pmc = 6571782 | doi = 10.3390/molecules24102001 | doi-access = free }}</ref> although samples often turn [[beige]] during storage. It is a derivative, formally speaking, of [[catechol]].

It or its derivatives occurs in olives and in wines<ref name = "Fernández-Mar_2014">{{Cite journal|date=2012-02-15 |title= Bioactive compounds in wine: Resveratrol, hydroxytyrosol and melatonin: A review |journal=[[Food Chemistry (journal)|Food Chemistry]] |volume=130 |issue=4 |pages=797–813 |doi=10.1016/j.foodchem.2011.08.023 |issn=0308-8146 | vauthors = Fernández-Mar MI, Mateos R, Garcia-Parrilla MC, Puertas B, Cantos-Villar E }}</ref><ref>{{cite journal | vauthors = Hu T, He XW, Jiang JG, Xu XL | title = Hydroxytyrosol and its potential therapeutic effects | journal = [[Journal of Agricultural and Food Chemistry]] | volume = 62 | issue = 7 | pages = 1449–1455 | date = February 2014 | pmid = 24479643 | doi = 10.1021/jf405820v }}</ref>

==Occurrence==

===Olives===

[[image:Oleuropein structure.svg|thumb|left|[[Oleuropein]], bitter compound, an [[ester]] of hydroxytyrosol found in green [[olive]] skin]]

The olives, leaves, and olive pulp contain large amounts of hydroxytyrosol derivative [[Oleuropein]], more so than [[olive oil]].<ref name="oil" /> Unprocessed, green (unripe) olives, contain between 4.3 and 116&nbsp;mg of hydroxytyrosol per 100g of olives, while unprocessed, black (ripe) olives contain up to 413.3&nbsp;mg per 100g.<ref>{{Cite web|title=Showing all foods in which the polyphenol Hydroxytyrosol is found - Phenol-Explorer|url=http://phenol-explorer.eu/contents/polyphenol/674|access-date=2021-07-02|website=phenol-explorer.eu}}</ref> The ripening of an olive substantially increases the amount of hydroxytyrosol.<ref name="rocha">{{cite journal | vauthors = Rocha J, Borges N, Pinho O | title = Table olives and health: a review | journal = [[Journal of Nutritional Science]] | volume = 9 | pages = e57 | year = 2020 | pmid = 33354328 | pmc = 7737178 | doi = 10.1017/jns.2020.50 }}</ref> Processed olives, such as the common canned variety containing [[iron(II) gluconate]], contained little hydroxytyrosol, as iron salts are catalysts for its oxidation.<ref>{{cite journal |doi=10.1016/S0308-8146(00)00338-1 |title=Phenolic compounds change during California-style ripe olive processing | vauthors = Marsilio V, Campestre C, Lanza B |journal=Food Chemistry |volume =74 | issue =1 |date= July 2001 |pages= 55–60}}</ref>

=== Food safety ===

Hydroxytyrosol is considered safe as a [[novel food]] for human consumption, with a [[no-observed-adverse-effect level]] of 50&nbsp;mg/kg body weight per day, as evaluated by the [[European Food Safety Authority]] (EFSA).<ref>{{cite journal | vauthors = Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, Heinonen M, Hirsch-Ernst KI, Mangelsdorf I, McArdle HJ, Naska A, Neuhäuser-Berthold M, Nowicka G, Pentieva K, Sanz Y, Siani A, Sjödin A, Stern M, Tomé D, Vinceti M, Willatts P, Engel KH, Marchelli R, Pöting A, Poulsen M, Schlatter J, Turla E, van Loveren H | display-authors = 6 | title = Safety of hydroxytyrosol as a novel food pursuant to Regulation (EC) No 258/97 | journal = EFSA Journal | volume = 15 | issue = 3 | pages = e04728 | date = March 2017 | pmid = 32625437 | pmc = 7010075 | doi = 10.2903/j.efsa.2017.4728 }}</ref>

In the United States, hydroxytyrosol is considered to be a safe ingredient ([[Generally recognized as safe|GRAS]]) in processed foods at levels of 5&nbsp;mg per serving.<ref>{{Cite web|access-date=2 July 2021|title=GRAS notice for hydroxytyrosol|date=13 May 2016|url=https://www.cfsanappsexternal.fda.gov/scripts/fdcc/?set=GRASNotices&id=600&sort=GRN_No&order=DESC&startrow=1&type=basic&search=hydroxytyrosol|publisher=US Food and Drug Administration}}</ref>

===Function and production===

[[File:Synthesis of Hydroxytyrosol.jpg|thumb| ]]

In nature, hydroxytyrosol is generated by the [[hydrolysis]] of [[oleuropein]] that occurs during olive ripening. Oleuropein accumulates in olive leaves and fruit as a defense mechanism against [[pathogen]]s and [[herbivore]]s. During olive ripening or when the olive tissue is damaged by pathogens, herbivores, or mechanical damage, the enzyme [[β-glucosidase]] catalyzes hydroxytyrosol synthesis via hydrolysis from oleuropein.<ref>{{cite journal | vauthors = Charoenprasert S, Mitchell A | title = Factors influencing phenolic compounds in table olives (Olea europaea) | journal = Journal of Agricultural and Food Chemistry | volume = 60 | issue = 29 | pages = 7081–7095 | date = July 2012 | pmid = 22720792 | doi = 10.1021/jf3017699 }}</ref>

===Metabolism===

Shortly after olive oil consumption, 98% of hydroxytyrosol in plasma and urine appears in conjugated forms (65% glucuronoconjugates), suggesting extensive first-past metabolism and a [[half-life]] of 2.43 hours.<ref name="metabolism">{{cite journal | vauthors = Miro-Casas E, Covas MI, Farre M, Fito M, Ortuño J, Weinbrenner T, Roset P, de la Torre R | display-authors = 6 | title = Hydroxytyrosol disposition in humans | journal = Clinical Chemistry | volume = 49 | issue = 6 Pt 1 | pages = 945–952 | date = June 2003 | pmid = 12765992 | doi = 10.1373/49.6.945 | doi-access = free }}</ref>

== Mediterranean diet ==

[[Mediterranean diet]]s, characterized by regular intake of olive oil, have been shown to positively affect human health, including reduced rates of [[cardiovascular diseases]].<ref name = "Fernández-Mar_2014" /><ref>{{cite journal | vauthors = Hu T, He XW, Jiang JG, Xu XL | title = Hydroxytyrosol and its potential therapeutic effects | journal = Journal of Agricultural and Food Chemistry | volume = 62 | issue = 7 | pages = 1449–1455 | date = February 2014 | pmid = 24479643 | doi = 10.1021/jf405820v }}</ref><ref>{{cite journal | vauthors = Martínez-González MA, Gea A, Ruiz-Canela M | title = The Mediterranean Diet and Cardiovascular Health | journal = Circulation Research | volume = 124 | issue = 5 | pages = 779–798 | date = March 2019 | pmid = 30817261 | doi = 10.1161/CIRCRESAHA.118.313348 | doi-access = free }}</ref> Research on consumption of olive oil and its components includes hydroxytyrosol and oleuropein, which may inhibit oxidation of LDL cholesterol {{ndash}} a [[risk factor]] for atherosclerosis, heart attack or stroke.<ref>{{cite journal | vauthors = Marcelino G, Hiane PA, Freitas KC, Santana LF, Pott A, Donadon JR, Guimarães RC | title = Effects of Olive Oil and Its Minor Components on Cardiovascular Diseases, Inflammation, and Gut Microbiota | journal = Nutrients | volume = 11 | issue = 8 | page = 1826 | date = August 2019 | pmid = 31394805 | pmc = 6722810 | doi = 10.3390/nu11081826 | doi-access = free }}</ref> The daily intake of hydroxytyrosol within the Mediterranean diet is estimated to be between 0.15 and 30&nbsp;mg.<ref>{{cite journal | vauthors = de Pablos RM, Espinosa-Oliva AM, Hornedo-Ortega R, Cano M, Arguelles S | title = Hydroxytyrosol protects from aging process via AMPK and autophagy; a review of its effects on cancer, metabolic syndrome, osteoporosis, immune-mediated and neurodegenerative diseases | journal = Pharmacological Research | volume = 143 | pages = 58–72 | date = May 2019 | pmid = 30853597 | doi = 10.1016/j.phrs.2019.03.005 | s2cid = 73726654 }}</ref>

== Regulation ==

===Europe===

The EFSA has issued a scientific opinion on health claims in relation to dietary consumption of hydroxytyrosol and related polyphenol compounds from olive fruit and oil, and protection of blood lipids from potential oxidative damage.<ref name="efsa">{{Cite web|title=Scientific Opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles | quote = From oxidative damage (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL cholesterol concentrations (ID 1639), maintenance of normal blood pressure (ID 3781), “anti-inflammatory properties” (ID 1882), “contributes to the upper respiratory tract health” (ID 3468), “can help to maintain a normal function of gastrointestinal tract” (3779), and “contributes to body defences against external agents” (ID 3467) pursuant to Article 13(1) of Regulation (EC) No 1924/2006|url=https://www.efsa.europa.eu/en/efsajournal/pub/2033|access-date=2021-04-13|website=European Food Safety Authority| date = 8 April 2011|language=en}}</ref>

EFSA concluded that a [[causal relationship|cause-and-effect relationship]] existed between the consumption of hydroxytyrosol and related compounds from olives and olive oil and protection of blood lipids from oxidative damage,<ref name=efsa/> providing a [[health claim]] for consumption of olive oil polyphenols containing at least 5&nbsp;mg of hydroxytyrosol and its derivatives ([[oleuropein]] complex and tyrosol) per 20 g of olive oil.<ref>{{Cite web|title=EU Register of nutrition and health claims made on foods (v.3.6)|url=https://ec.europa.eu/food/safety/labelling_nutrition/claims/register/public/?event=search|access-date=2021-04-13|website=ec.europa.eu}}</ref>

* [[Echinacoside]], a hydroxytyrosol-containing glycoside

* [[Verbascoside]], another hydroxytyrosol-containing glycoside

* [[Resveratrol]]

{{Phytoestrogens}}

{{Estrogen receptor modulators}}

[[Category:GPER agonists]]

[[Category:Phenylethanoids]]

[[Category:Phenol antioxidants]]

[[Category:Phytoestrogens]]