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'''Curcumin''' is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal [[curcuminoid]] of [[turmeric]] (''Curcuma longa''), a member of the [[ginger]] family, [[Zingiberaceae]]. It is sold as a [[herbal supplement]], [[cosmetics]] ingredient, food flavoring, and [[food coloring]].<ref name=":0">{{Cite web |url= http://www.naturalproductsinsider.com/articles/2015/12/the-state-of-the-curcumin-market.aspx |title= The State of the Curcumin Market |vauthors= Majeed S |date= December 28, 2015 |website= Natural Products Insider |language= en-US |df= dmy |access-date= February 29, 2016 |archive-date= October 17, 2017 |archive-url= https://web.archive.org/web/20171017095015/https://www.naturalproductsinsider.com/articles/2015/12/the-state-of-the-curcumin-market.aspx }}</ref>
'''Curcumin''' is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal [[curcuminoid]] of [[turmeric]] (''Curcuma longa''), a member of the [[ginger]] family, [[Zingiberaceae]]. It is sold as an [[herbal supplement]], [[cosmetics]] ingredient, food flavoring, and [[food coloring]].<ref name=":0">{{Cite web |url= http://www.naturalproductsinsider.com/articles/2015/12/the-state-of-the-curcumin-market.aspx |title= The State of the Curcumin Market |vauthors= Majeed S |date= December 28, 2015 |website= Natural Products Insider |language= en-US |df= dmy |access-date= February 29, 2016 |archive-date= October 17, 2017 |archive-url= https://web.archive.org/web/20171017095015/https://www.naturalproductsinsider.com/articles/2015/12/the-state-of-the-curcumin-market.aspx }}</ref>


Chemically, curcumin is a [[polyphenol]], more particularly a [[diarylheptanoid]], belonging to the group of curcuminoids, which are [[natural phenol|phenolic]] [[pigment]]s responsible for the yellow color of turmeric.<ref name="pubchem">{{PubChem|969516}}</ref>
Chemically, curcumin is a [[polyphenol]], more particularly a [[diarylheptanoid]], belonging to the group of curcuminoids, which are [[natural phenol|phenolic]] [[pigment]]s responsible for the yellow color of turmeric.<ref name="pubchem">{{PubChem|969516}}</ref>


Laboratory and clinical research have not confirmed any medical use for curcumin. It is difficult to study because it is both unstable and poorly [[bioavailable]]. It is unlikely to produce useful leads for [[drug development]] as a [[lead compound]].<ref name=nelson/>
Extensive studies have consistently failed to show any medical value for curcumin. It is difficult to study because it is both unstable and poorly [[bioavailable]]. It is unlikely to produce useful leads for [[drug development]] as a [[lead compound]].<ref name=nelson/>


==History==
==History==
Curcumin was named in 1815 when Henri Auguste <!-- from fr:wiki 'Vogel' (disambigulation) as the only chemist/pharmacist reasonably in early 1800s--> Vogel and [[Pierre Joseph Pelletier]] reported the first isolation of a "yellow coloring-matter" from the [[rhizome]]s of turmeric.<ref>{{cite journal |last1=Vogel |first1=A |last2=Pelletier |first2=J |title=Examen chimique de la racine de Curcuma |language=fr |trans-title=Chemical examination of turmeric root |journal=Journal de Pharmacie et des Sciences Accessoires |volume=1 |date=July 1815 |pages=289–300 |id={{gallica|id=bpt6k781358/f290.item}} |url=https://books.google.com/books?id=dqU8AAAAcAAJ&pg=PA289 }}</ref> Later, it was found to be a mixture of [[resin]] and turmeric oil. In 1910, Milobedzka and Lampe reported the chemical structure of curcumin to be as diferuloylmethane.<ref name=History>{{cite book |doi=10.1016/B978-0-12-815461-8.00002-5 |chapter=Curcumin: Historical Background, Chemistry, Pharmacological Action, and Potential Therapeutic Value |title=Curcumin for Neurological and Psychiatric Disorders |year=2019 |last1=Farooqui |first1=Tahira |last2=Farooqui |first2=Akhlaq A. |pages=23–44 |isbn=978-0-12-815461-8 |s2cid=146070671 }}</ref> Later in 1913, the same group accomplished the synthesis of the compound.
Curcumin was named in 1815 when Henri Auguste <!-- from fr:wiki 'Vogel' (disambigulation) as the only chemist/pharmacist reasonably in early 1800s--> Vogel and [[Pierre Joseph Pelletier]] reported the first isolation of a "yellow coloring-matter" from the [[rhizome]]s of turmeric.<ref>{{cite journal |last1=Vogel |first1=A |last2=Pelletier |first2=J |title=Examen chimique de la racine de Curcuma |language=fr |trans-title=Chemical examination of turmeric root |journal=Journal de Pharmacie et des Sciences Accessoires |volume=1 |date=July 1815 |pages=289–300 |id={{gallica|id=bpt6k781358/f290.item}} |url=https://books.google.com/books?id=dqU8AAAAcAAJ&pg=PA289 }}</ref> Later, it was found to be a mixture of [[resin]] and turmeric oil. In 1910, Milobedzka and Lampe reported the chemical structure of curcumin to be as diferuloylmethane.<ref name=History>{{cite book |doi=10.1016/B978-0-12-815461-8.00002-5 |chapter=Curcumin: Historical Background, Chemistry, Pharmacological Action, and Potential Therapeutic Value |title=Curcumin for Neurological and Psychiatric Disorders |year=2019 |last1=Farooqui |first1=Tahira |last2=Farooqui |first2=Akhlaq A. |pages=23–44 |isbn=978-0-12-815461-8 |s2cid=146070671 }}</ref> Later in 1913, the same group accomplished the synthesis of the compound.


Although used in [[traditional medicine]], the possible therapeutic properties of turmeric or curcumin remain undetermined.<ref name=nelson/><ref name=baker/><ref>{{cite web | url= https://nccih.nih.gov/health/turmeric/ataglance.htm | title=Turmeric | publisher=US National Center for Complementary and Integrative Health, National Institutes of Health | date=April 2020 | access-date=24 October 2023}}</ref>
Although used in [[traditional medicine]], the possible therapeutic properties of turmeric or curcumin remain undetermined.<ref name=nelson/><ref name=baker/><ref>{{cite web | url= https://www.nccih.nih.gov/health/turmeric | title=Turmeric | publisher=US National Center for Complementary and Integrative Health, National Institutes of Health | date=April 2020 | access-date=24 October 2023}}</ref>


==Uses==
==Uses==
[[File:Kurkumina.jpg|thumb|Curcumin powder]]
[[File:Kurkumina.jpg|thumb|Curcumin powder]]
The most common applications are as an ingredient in [[dietary supplement]], in [[cosmetics]], as flavoring for foods, such as turmeric-flavored beverages in [[South Asia|South]] and [[Southeast Asia]],<ref name=":0" /> and as coloring for foods, such as [[curry powder]]s, [[Mustard (condiment)|mustard]]s, [[butter]]s, and [[cheese]]s. As a [[food additive]] for orange-yellow coloring in prepared foods, its [[E number]] is E{{nbs}}100 in the European Union.<ref name="fanl">{{cite web |author= European Commission |author-link= European Commission |title= Food Additives |url= https://webgate.ec.europa.eu/foods_system/main/index.cfm?event=substance.view&identifier=5 |access-date= February 15, 2014 |archive-date= October 8, 2022 |archive-url= https://web.archive.org/web/20221008043354/https://webgate.ec.europa.eu/foods_system/main/index.cfm?event=substance.view&identifier=5 }}</ref><ref>{{cite web|url=https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:2012R0231:20121129:EN:PDF|title=Curcumin, E 100, page 9|publisher=Specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament|date=March 9, 2012|access-date=July 24, 2019 }}</ref> It is also approved by the U.S. [[Food and Drug Administration|FDA]] to be used as a [[food coloring]] in US.<ref>{{cite web |title=CFR – Code of Federal Regulations Title 21 |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=73.600 |website=www.accessdata.fda.gov}}</ref>
The most common applications are as an ingredient in [[dietary supplement]], in [[cosmetics]], as flavoring for foods, such as turmeric-flavored beverages in [[South Asia|South]] and [[Southeast Asia]],<ref name=":0" /> and as coloring for foods, such as [[curry powder]]s, [[Mustard (condiment)|mustard]]s, [[butter]]s, and [[cheese]]s. As a [[food additive]] for orange-yellow coloring in prepared foods, its [[E number]] is E{{nbs}}100 in the European Union.<ref name="fanl">{{cite web |author= European Commission |author-link= European Commission |title= Food Additives |url= https://webgate.ec.europa.eu/foods_system/main/index.cfm?event=substance.view&identifier=5 |access-date= February 15, 2014 |archive-date= October 8, 2022 |archive-url= https://web.archive.org/web/20221008043354/https://webgate.ec.europa.eu/foods_system/main/index.cfm?event=substance.view&identifier=5 }}</ref><ref>{{cite web|url=https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:2012R0231:20121129:EN:PDF|title=Curcumin, E 100, page 9|publisher=Specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament|date=March 9, 2012|access-date=July 24, 2019 }}</ref> It is also approved by the U.S. [[Food and Drug Administration|FDA]] to be used as a [[food coloring]] in US.<ref>{{cite web |title=CFR – Code of Federal Regulations Title 21 |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=73.600 |website=www.accessdata.fda.gov}}</ref>
Curcumin is used as a [[complexometric indicator]] for [[boron]].<ref name=pubchem/><ref>{{Cite web |url=https://www.nemi.gov/methods/method_summary/5279/ |title=EPA-NERL: 212.3: Boron by Colorimetry – Boron (Colorimetric, Curcumin) |date=1974 |access-date=2024-02-18 |website=National Environmental Methods Index |author=National Exposure Research Laboratory (EPA-NERL) |author-link=National Exposure Research Laboratory|archive-url=https://web.archive.org/web/20170203100710/https://www.nemi.gov/methods/method_summary/5279/ |archive-date=2017-02-03 |url-status=live }}</ref> It reacts with [[boric acid]] to form a red-colored compound, [[rosocyanine]].


== Chemistry ==
== Chemistry ==
[[File:Curcumin thin lipid film.jpg|alt=A bright red substance in a small glass flask, held by gloved fingers|thumb|Curcumin becomes bright red when it interacts [[electrostatics|electrostatically]] with a [[phospholipid]] film]]
[[File:Curcumin thin lipid film.jpg|alt=A bright red substance in a small glass flask, held by gloved fingers|thumb|Curcumin becomes bright red when it interacts [[electrostatics|electrostatically]] with a [[phospholipid]] film]]


Curcumin incorporates a seven carbon linker and three major functional groups: an α,β-unsaturated β-diketone moiety and an aromatic O-methoxy-phenolic group.<ref name=pubchem/><ref name=History /> The aromatic ring systems, which are [[phenols]], are connected by two α,β-unsaturated [[carbonyl]] groups.<ref name=pubchem/><ref>{{cite journal |doi=10.1002/cber.191004302168 |title=Zur Kenntnis des Curcumins |trans-title=Knowing about curcumin |language=de |year=1910 | vauthors = Miłobȩdzka J, van Kostanecki S, Lampe V |journal= Berichte der Deutschen Chemischen Gesellschaft |volume= 43 |issue= 2 |pages= 2163–2170 |url=https://zenodo.org/record/1426403 }}</ref> It is a [[diketone]] [[tautomer]], existing in [[enol]]ic form in [[organic solvent]]s and in [[ketone|keto]] form in water.<ref>{{cite journal | vauthors = Manolova Y, Deneva V, Antonov L, Drakalska E, Momekova D, Lambov N | title = The effect of the water on the curcumin tautomerism: a quantitative approach | journal = Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy | volume = 132 | pages = 815–820 | date = November 2014 | pmid = 24973669 | doi = 10.1016/j.saa.2014.05.096 | url = http://eprints.ugd.edu.mk/10453/1/The%20effect%20of%20the%20water%20on%20the%20curcumin%20tautomerism.pdf | bibcode = 2014AcSpA.132..815M }}</ref> The diketones form stable enols and are readily deprotonated to form [[enolate]]s; the α,β-unsaturated carbonyl group is a good [[Michael acceptor]] and undergoes [[nucleophilic addition]].{{citation needed|date=September 2021}} Because of its hydrophobic nature, curcumin is poorly soluble in water<ref name=pubchem/> but is easily soluble in organic solvents.<ref name=History />
Curcumin incorporates a seven carbon linker and three major functional groups: an α,β-unsaturated β-diketone moiety and an aromatic O-methoxy-phenolic group.<ref name=pubchem/><ref name=History /> The aromatic ring systems, which are [[phenols]], are connected by two α,β-unsaturated [[carbonyl]] groups.<ref name=pubchem/><ref>{{cite journal |doi=10.1002/cber.191004302168 |title=Zur Kenntnis des Curcumins |trans-title=Knowing about curcumin |language=de |year=1910 | vauthors = Miłobȩdzka J, van Kostanecki S, Lampe V |journal= Berichte der Deutschen Chemischen Gesellschaft |volume= 43 |issue= 2 |pages= 2163–2170 |url=https://zenodo.org/record/1426403 }}</ref> It is a [[diketone]] [[tautomer]], existing in [[enol]]ic form in [[organic solvent]]s and in [[ketone|keto]] form in water.<ref>{{cite journal | vauthors = Manolova Y, Deneva V, Antonov L, Drakalska E, Momekova D, Lambov N | title = The effect of the water on the curcumin tautomerism: a quantitative approach | journal = Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy | volume = 132 | pages = 815–820 | date = November 2014 | pmid = 24973669 | doi = 10.1016/j.saa.2014.05.096 | url = http://eprints.ugd.edu.mk/10453/1/The%20effect%20of%20the%20water%20on%20the%20curcumin%20tautomerism.pdf | bibcode = 2014AcSpA.132..815M }}</ref> The diketones form stable enols and are readily deprotonated to form [[enolate]]s, which bind metal ions to form [[metal acetylacetonate|acetylacetonate-like complexes]].<ref>{{cite journal |doi=10.1002/zaac.202000088 |title=Syntheses, Structures, and Bioactivities Evaluation of some Transition Metal Complexes with 4,4'-Diacetylcurcumin |date=2020 |last1=Pham |first1=Chien Thang |last2=Pham |first2=Thu Thuy |last3=Nguyen |first3=Hung Huy |last4=Trieu |first4=Thi Nguyet |journal=Zeitschrift für Anorganische und Allgemeine Chemie |volume=646 |issue=11–12 |pages=495–499 |bibcode=2020ZAACh.646..495P }}</ref> Its complexing properties are manifesting in its reaction with [[boric acid]] to give a red-colored [[rosocyanine]].<ref name=pubchem/><ref>{{Cite web |url=https://www.nemi.gov/methods/method_summary/5279/ |title=EPA-NERL: 212.3: Boron by Colorimetry – Boron (Colorimetric, Curcumin) |date=1974 |access-date=2024-02-18 |website=National Environmental Methods Index |author=National Exposure Research Laboratory (EPA-NERL) |author-link=National Exposure Research Laboratory|archive-url=https://web.archive.org/web/20170203100710/https://www.nemi.gov/methods/method_summary/5279/ |archive-date=2017-02-03 |url-status=live }}</ref>
 
Because of its hydrophobic nature, curcumin is poorly soluble in water<ref name=pubchem/> but is easily soluble in organic solvents.<ref name=History />


===Biosynthesis===
===Biosynthesis===
The biosynthetic route of curcumin is uncertain. In 1973, Peter J. Roughley and Donald A. Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involves a chain extension reaction by [[cinnamic acid]] and 5 [[malonyl-CoA]] molecules that eventually arylize into a curcuminoid. The second mechanism involves two cinnamate units coupled together by malonyl-CoA. Both use cinnamic acid as their starting point, which is derived from the amino acid [[phenylalanine]].<ref name="Kita, T. 2008" />
The biosynthetic route of curcumin is uncertain. In 1973, Peter J. Roughley and Donald A. Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involves a chain extension reaction by [[cinnamic acid]] and 5 [[malonyl-CoA]] molecules that eventually arylize into a curcuminoid. The second mechanism involves two cinnamate units coupled together by malonyl-CoA. Both use cinnamic acid as their starting point, which is derived from the amino acid [[phenylalanine]].<ref name="Kita, T. 2008" />


Plant biosynthesis starting with cinnamic acid is rare compared to the more common [[p-Coumaric acid|''p''-coumaric acid]].<ref name="Kita, T. 2008">{{cite journal | vauthors = Kita T, Imai S, Sawada H, Kumagai H, Seto H | title = The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealed by 13C-labeled precursors | journal = Bioscience, Biotechnology, and Biochemistry | volume = 72 | issue = 7 | pages = 1789–1798 | date = July 2008 | pmid = 18603793 | doi = 10.1271/bbb.80075 | doi-access = free }}</ref> Only a few identified compounds, such as [[anigorufone]] and [[pinosylvin]], build from cinnamic acid.<ref>{{cite journal | vauthors = Schmitt B, Hölscher D, Schneider B | title = Variability of phenylpropanoid precursors in the biosynthesis of phenylphenalenones in Anigozanthos preissii | journal = Phytochemistry | volume = 53 | issue = 3 | pages = 331–337 | date = February 2000 | pmid = 10703053 | doi = 10.1016/S0031-9422(99)00544-0 | bibcode = 2000PChem..53..331S }}</ref><ref>{{cite journal | vauthors =  Gehlert R, Schoeppner A, Kindl H |title= Stilbene Synthase from Seedlings of ''Pinus sylvestris'': Purification and Induction in Response to Fungal Infection |journal= Molecular Plant-Microbe Interactions |year= 1990 |volume= 3 |issue= 6 |pages= 444–449 |doi= 10.1094/MPMI-3-444 |url= http://www.apsnet.org/publications/mpmi/backissues/Documents/1990Articles/Microbe03_444.pdf }}</ref>
Plant biosynthesis starting with cinnamic acid is rare compared to the more common [[p-Coumaric acid|''p''-coumaric acid]].<ref name="Kita, T. 2008">{{cite journal | vauthors = Kita T, Imai S, Sawada H, Kumagai H, Seto H | title = The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealed by 13C-labeled precursors | journal = Bioscience, Biotechnology, and Biochemistry | volume = 72 | issue = 7 | pages = 1789–1798 | date = July 2008 | pmid = 18603793 | doi = 10.1271/bbb.80075 | doi-access = free }}</ref> Only a few identified compounds, such as [[anigorufone]] and [[pinosylvin]], build from cinnamic acid.<ref>{{cite journal | vauthors = Schmitt B, Hölscher D, Schneider B | title = Variability of phenylpropanoid precursors in the biosynthesis of phenylphenalenones in Anigozanthos preissii | journal = Phytochemistry | volume = 53 | issue = 3 | pages = 331–337 | date = February 2000 | pmid = 10703053 | doi = 10.1016/S0031-9422(99)00544-0 | bibcode = 2000PChem..53..331S }}</ref><ref>{{cite journal | vauthors =  Gehlert R, Schoeppner A, Kindl H |title= Stilbene Synthase from Seedlings of ''Pinus sylvestris'': Purification and Induction in Response to Fungal Infection |journal= Molecular Plant-Microbe Interactions |year= 1990 |volume= 3 |issue= 6 |pages= 444–449 |doi= 10.1094/MPMI-3-444 |bibcode= 1990MPMI....3..444G |url= http://www.apsnet.org/publications/mpmi/backissues/Documents/1990Articles/Microbe03_444.pdf }}</ref>


[[File:Curcumin biosynthesis.svg|500px|center|thumb|class=skin-invert-image|alt= Curcumin biosynthesis diagram|Biosynthetic pathway of curcumin in ''[[Curcuma longa]]''.<ref name="Kita, T. 2008"/>]]
[[File:Curcumin biosynthesis.svg|500px|center|thumb|class=skin-invert-image|alt= Curcumin biosynthesis diagram|Biosynthetic pathway of curcumin in ''[[Curcuma longa]]''.<ref name="Kita, T. 2008"/>]]
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[[File:Curcumin fluorescence.jpg|thumb|Curcumin displays green fluorescence under UV light]]
[[File:Curcumin fluorescence.jpg|thumb|Curcumin displays green fluorescence under UV light]]


Curcumin, which shows positive results in most [[drug discovery]] assays, is regarded as a false lead that [[Medicinal chemistry|medicinal chemists]] include among "[[pan-assay interference compounds]]". This attracts undue experimental attention while failing to advance as viable therapeutic or drug leads,<ref name="nelson">{{cite journal | vauthors = Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA | title = The Essential Medicinal Chemistry of Curcumin | journal = Journal of Medicinal Chemistry | volume = 60 | issue = 5 | pages = 1620–1637 | date = March 2017 | pmid = 28074653 | pmc = 5346970 | doi = 10.1021/acs.jmedchem.6b00975 }}<br /> See also: {{cite journal | vauthors = Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA | title = Curcumin May (Not) Defy Science | journal = ACS Medicinal Chemistry Letters | volume = 8 | issue = 5 | pages = 467–470 | date = May 2017 | pmid = 28523093 | pmc = 5430405 | doi = 10.1021/acsmedchemlett.7b00139 }}</ref><ref name="baker">{{cite journal | vauthors = Baker M | title = Deceptive curcumin offers cautionary tale for chemists | journal = Nature | volume = 541 | issue = 7636 | pages = 144–145 | date = January 2017 | pmid = 28079090 | doi = 10.1038/541144a | bibcode = 2017Natur.541..144B | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bisson J, McAlpine JB, Friesen JB, Chen SN, Graham J, Pauli GF | title = Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery? | journal = Journal of Medicinal Chemistry | volume = 59 | issue = 5 | pages = 1671–1690 | date = March 2016 | pmid = 26505758 | pmc = 4791574 | doi = 10.1021/acs.jmedchem.5b01009 }}</ref> although some derivatives of curcumin such as [[EF-24]] have seen a significant amount of research.<ref>{{cite journal |last1=He |first1=Yonghan |last2=Li |first2=Wen |last3=Hu |first3=Guangrong |last4=Sun |first4=Hui |last5=Kong |first5=Qingpeng |title=Bioactivities of EF24, a Novel Curcumin Analog: A Review |journal=Frontiers in Oncology |date=11 December 2018 |volume=8 |page=614 |doi=10.3389/fonc.2018.00614 |pmid=30619754 |pmc=6297553 |doi-access=free }}</ref>
Curcumin, which shows positive results in most [[drug discovery]] assays, is regarded as a false lead that [[Medicinal chemistry|medicinal chemists]] include among "[[pan-assay interference compounds]]". This attracts undue experimental attention while failing to advance as viable therapeutic or drug leads,<ref name="nelson">{{cite journal | vauthors = Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA | title = The Essential Medicinal Chemistry of Curcumin | journal = Journal of Medicinal Chemistry | volume = 60 | issue = 5 | pages = 1620–1637 | date = March 2017 | pmid = 28074653 | pmc = 5346970 | doi = 10.1021/acs.jmedchem.6b00975 }}<br /> See also: {{cite journal | vauthors = Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA | title = Curcumin May (Not) Defy Science | journal = ACS Medicinal Chemistry Letters | volume = 8 | issue = 5 | pages = 467–470 | date = May 2017 | pmid = 28523093 | pmc = 5430405 | doi = 10.1021/acsmedchemlett.7b00139 }}</ref><ref name="baker">{{cite journal | vauthors = Baker M | title = Deceptive curcumin offers cautionary tale for chemists | journal = Nature | volume = 541 | issue = 7636 | pages = 144–145 | date = January 2017 | pmid = 28079090 | doi = 10.1038/541144a | bibcode = 2017Natur.541..144B | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bisson J, McAlpine JB, Friesen JB, Chen SN, Graham J, Pauli GF | title = Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery? | journal = Journal of Medicinal Chemistry | volume = 59 | issue = 5 | pages = 1671–1690 | date = March 2016 | pmid = 26505758 | pmc = 4791574 | doi = 10.1021/acs.jmedchem.5b01009 }}</ref> although some derivatives of curcumin such as [[EF-24]] have been well-studied.<ref>{{cite journal |last1=He |first1=Yonghan |last2=Li |first2=Wen |last3=Hu |first3=Guangrong |last4=Sun |first4=Hui |last5=Kong |first5=Qingpeng |title=Bioactivities of EF24, a Novel Curcumin Analog: A Review |journal=Frontiers in Oncology |date=11 December 2018 |volume=8 |article-number=614 |doi=10.3389/fonc.2018.00614 |pmid=30619754 |pmc=6297553 |doi-access=free }}</ref>


Factors that limit the bioactivity of curcumin or its analogs include chemical instability, water insolubility, absence of potent and selective target activity, low bioavailability, limited tissue distribution, and extensive metabolism.<ref name=nelson/>  Very little curcumin escapes the [[GI tract]] and most is excreted in feces unchanged.<ref>{{cite journal | vauthors = Metzler M, Pfeiffer E, Schulz SI, Dempe JS | title = Curcumin uptake and metabolism | journal = BioFactors | volume = 39 | issue = 1 | pages = 14–20 | date = 2013 | pmid = 22996406 | doi = 10.1002/biof.1042 | s2cid = 8763463 }}</ref>  If curcumin enters plasma in reasonable amounts, there is a high risk of toxicity since it is promiscuous, and interacts with several proteins known to increase the risk of adverse effects, including [[hERG]], [[cytochrome P450]]s, and [[glutathione S-transferase]].<ref name=nelson/>
Factors that limit the bioactivity of curcumin or its analogs include chemical instability, water insolubility, absence of potent and selective target activity, low bioavailability, limited tissue distribution, and extensive metabolism.<ref name=nelson/>  Very little curcumin escapes the [[GI tract]] and most is excreted in feces unchanged.<ref>{{cite journal | vauthors = Metzler M, Pfeiffer E, Schulz SI, Dempe JS | title = Curcumin uptake and metabolism | journal = BioFactors | volume = 39 | issue = 1 | pages = 14–20 | date = 2013 | pmid = 22996406 | doi = 10.1002/biof.1042 | s2cid = 8763463 }}</ref>  If curcumin enters plasma in reasonable amounts, there is a high risk of toxicity since it is promiscuous, and interacts with several proteins known to increase the risk of adverse effects, including [[hERG]], [[cytochrome P450]]s, and [[glutathione S-transferase]].<ref name=nelson/>


==Safety==
==Safety==
Although curcumin has been assessed in numerous laboratory and [[clinical research|clinical studies]], it has no medical uses.<ref name="lpi">{{cite web | url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/curcumin | title=Curcumin | publisher=Linus Pauling Institute, Oregon State University, Corvallis | work=Micronutrient Information Center; Phytochemicals | date=2016 | access-date=June 18, 2016}}</ref> Its instability, [[Reactivity (chemistry)|reactivity]], and poor bioavailability, make curcumin an unlikely drug candidate.<ref name=nelson/> Curcumin exhibits numerous interference properties which may lead to misinterpretation of results.<ref name=nelson/><ref name=baker/><ref>{{cite news |last1=Lowe |first1=Derek |title=Curcumin Will Waste Your Time |url=https://www.science.org/content/blog-post/curcumin-waste-your-time |work=Science Blogs |date=12 January 2017 }}</ref>
Between 1995 and 2017, the US government funded US$150&nbsp;million in biomedical research into curcumin through the [[National Center for Complementary and Integrative Health]]. No support was found for curcumin as a medical treatment.<ref name="nelson"/>
As a component of turmeric, curcumin may interact with [[prescription drug]]s and dietary supplements.<ref name="drugs">{{cite web |title=Turmeric |url=https://www.drugs.com/mtm/turmeric.html |publisher=Drugs.com |access-date=November 28, 2018 |date=December 6, 2017}}</ref> In high amounts, it may be unsafe for women during pregnancy.<ref name=drugs/> It may cause side effects, such as [[nausea]], [[diarrhea]], [[hives]], or dizziness.<ref name=drugs/> Between 2004 and 2022 there were ten cases of liver injury caused by curcumin herbal and dietary supplements.<ref name="Halegoua-DeMarzio Navarro Ahmad Avula 2023 pp. 200–206">{{cite journal | last1=Halegoua-DeMarzio | first1=Dina | last2=Navarro | first2=Victor | last3=Ahmad | first3=Jawad | last4=Avula | first4=Bharathi | last5=Barnhart | first5=Huiman | last6=Barritt | first6=A. Sidney | last7=Bonkovsky | first7=Herbert L. | last8=Fontana | first8=Robert J. | last9=Ghabril | first9=Marwan S. | last10=Hoofnagle | first10=Jay H. | last11=Khan | first11=Ikhlas A. | last12=Kleiner | first12=David E. | last13=Phillips | first13=Elizabeth | last14=Stolz | first14=Andrew | last15=Vuppalanchi | first15=Raj | title=Liver Injury Associated with Turmeric—A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN] | journal=The American Journal of Medicine | publisher=Elsevier BV | volume=136 | issue=2 | year=2023 | issn=0002-9343 | doi=10.1016/j.amjmed.2022.09.026 | pages=200–206| pmid=36252717 | pmc=9892270}}</ref> Curcumin is a [[contact allergen]].<ref name="pmid26705440">{{cite journal |vauthors=Chaudhari SP, Tam AY, Barr JA |title=Curcumin: A Contact Allergen |journal=J Clin Aesthet Dermatol |volume=8 |issue=11 |pages=43–48 |date=November 2015 |pmid=26705440 |pmc=4689497 |doi= |url=}}</ref>
As a component of turmeric, curcumin may interact with [[prescription drug]]s and dietary supplements.<ref name="drugs">{{cite web |title=Turmeric |url=https://www.drugs.com/mtm/turmeric.html |publisher=Drugs.com |access-date=November 28, 2018 |date=December 6, 2017}}</ref> In high amounts, it may be unsafe for women during pregnancy.<ref name=drugs/> It may cause side effects, such as [[nausea]], [[diarrhea]], [[hives]], or dizziness.<ref name=drugs/> Between 2004 and 2022 there were ten cases of liver injury caused by curcumin herbal and dietary supplements.<ref name="Halegoua-DeMarzio Navarro Ahmad Avula 2023 pp. 200–206">{{cite journal | last1=Halegoua-DeMarzio | first1=Dina | last2=Navarro | first2=Victor | last3=Ahmad | first3=Jawad | last4=Avula | first4=Bharathi | last5=Barnhart | first5=Huiman | last6=Barritt | first6=A. Sidney | last7=Bonkovsky | first7=Herbert L. | last8=Fontana | first8=Robert J. | last9=Ghabril | first9=Marwan S. | last10=Hoofnagle | first10=Jay H. | last11=Khan | first11=Ikhlas A. | last12=Kleiner | first12=David E. | last13=Phillips | first13=Elizabeth | last14=Stolz | first14=Andrew | last15=Vuppalanchi | first15=Raj | title=Liver Injury Associated with Turmeric—A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN] | journal=The American Journal of Medicine | publisher=Elsevier BV | volume=136 | issue=2 | year=2023 | issn=0002-9343 | doi=10.1016/j.amjmed.2022.09.026 | pages=200–206| pmid=36252717 | pmc=9892270}}</ref> Curcumin is a [[contact allergen]].<ref name="pmid26705440">{{cite journal |vauthors=Chaudhari SP, Tam AY, Barr JA |title=Curcumin: A Contact Allergen |journal=J Clin Aesthet Dermatol |volume=8 |issue=11 |pages=43–48 |date=November 2015 |pmid=26705440 |pmc=4689497 |doi= |url=}}</ref>


The intended use of curcumin as a food additive is [[generally recognized as safe]] by the U.S. Food and Drug Administration.<ref>{{cite web |title=GRAS Notice (GRN) No. 822 |url=https://www.fda.gov/media/132575/download |archive-url=https://web.archive.org/web/20201203015205/https://www.fda.gov/media/132575/download |url-status=dead |archive-date=December 3, 2020 |website=U.S. Food & Drug Administration |publisher=GRAS Notice Inventory}}</ref>
The intended use of curcumin as a food additive is [[generally recognized as safe]] by the U.S. Food and Drug Administration.<ref>{{cite web |title=GRAS Notice (GRN) No. 822 |url=https://www.fda.gov/media/132575/download |archive-url=https://web.archive.org/web/20201203015205/https://www.fda.gov/media/132575/download |url-status=dead |archive-date=December 3, 2020 |website=U.S. Food & Drug Administration |publisher=GRAS Notice Inventory}}</ref>


==Medical research==
=== Research fraud ===
Although curcumin has been assessed in numerous laboratory and [[clinical research|clinical studies]], it has no medical uses established by well-designed clinical research.<ref name="lpi">{{cite web | url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/curcumin | title=Curcumin | publisher=Linus Pauling Institute, Oregon State University, Corvallis | work=Micronutrient Information Center; Phytochemicals | date=2016 | access-date=June 18, 2016}}</ref> According to a 2017 review of more than 120 studies, curcumin has not been successful in any [[clinical trial]], leading the authors to conclude that "curcumin is an unstable, reactive, non-bioavailable compound and, therefore, a highly improbable lead".<ref name=nelson/> Curcumin exhibits numerous interference properties which may lead to misinterpretation of results.<ref name=nelson/><ref name=baker/><ref>{{cite news |last1=Lowe |first1=Derek |title=Curcumin Will Waste Your Time |url=https://www.science.org/content/blog-post/curcumin-waste-your-time |work=Science Blogs |date=12 January 2017 }}</ref>
 
The US government has supported US$150&nbsp;million in research into curcumin through the [[National Center for Complementary and Integrative Health]], and no support has been found for curcumin as a medical treatment.<ref name="nelson"/><ref name="Forbes-11917">{{cite news | vauthors = Lemonick S |title=Everybody Needs To Stop With This Turmeric Molecule |url= https://www.forbes.com/sites/samlemonick/2017/01/19/everybody-needs-to-quit-it-with-this-turmeric-molecule/#39ccce9079ff |access-date=May 27, 2018|work=[[Forbes (magazine)|Forbes]]|date=January 19, 2017}}</ref>
 
===Research fraud===
[[Bharat Aggarwal]], a former cancer researcher at the [[University of Texas MD Anderson Cancer Center]], had 29 papers retracted due to research fraud {{as of | July 2021 | lc=yes}}.<ref>{{cite web |title=The Retraction Watch Leaderboard |url=https://retractionwatch.com/the-retraction-watch-leaderboard/ |website=Retraction Watch |access-date=28 July 2021 |date=16 June 2015}}</ref><ref>{{cite web|url=http://www.chron.com/news/houston-texas/article/M-D-Anderson-professor-under-fraud-probe-3360037.php|title=M.D. Anderson professor under fraud probe| vauthors = Ackerman T |publisher=Houston Chronicle|date=February 29, 2012|access-date=March 8, 2016}}</ref><ref>{{cite news |title=Caught Our Notice: Researcher who once threatened to sue Retraction Watch now up to 19 retractions |url=https://retractionwatch.com/2018/04/10/caught-our-notice-researcher-who-once-threatened-to-sue-retraction-watch-now-up-to-19-retractions/#more-63985 |work=Retraction Watch |date=April 10, 2018}}</ref>  Aggarwal's research had focused on potential [[anti-cancer]] properties of herbs and spices, particularly curcumin, and according to a March 2016 article in the ''[[Houston Chronicle]]'', "attracted national media interest and laid the groundwork for ongoing clinical trials".<ref>{{cite news | vauthors = Ackerman T |title=M.D. Anderson scientist, accused of manipulating data, retires |url=https://www.houstonchronicle.com/news/houston-texas/houston/article/M-D-Anderson-scientist-accused-of-falsifying-6865704.php |work=Houston Chronicle |date=March 2, 2016}}</ref><ref name="SciAm">{{cite journal|title=Spice Healer| vauthors = Stix G |journal=Scientific American|date=February 2007|volume=296|issue=2|pages=66–69|doi=10.1038/scientificamerican0207-66|pmid=17367023|bibcode=2007SciAm.296b..66S}}</ref><ref>{{cite news|url=http://www.chron.com/news/houston-texas/article/In-cancer-fight-a-spice-brings-hope-to-the-table-1913487.php|title=In cancer fight, a spice brings hope to the table | vauthors = Ackerman T |work=Houston Chronicle|date=July 11, 2005|access-date=March 24, 2015}}</ref>   
[[Bharat Aggarwal]], a former cancer researcher at the [[University of Texas MD Anderson Cancer Center]], had 29 papers retracted due to research fraud {{as of | July 2021 | lc=yes}}.<ref>{{cite web |title=The Retraction Watch Leaderboard |url=https://retractionwatch.com/the-retraction-watch-leaderboard/ |website=Retraction Watch |access-date=28 July 2021 |date=16 June 2015}}</ref><ref>{{cite web|url=http://www.chron.com/news/houston-texas/article/M-D-Anderson-professor-under-fraud-probe-3360037.php|title=M.D. Anderson professor under fraud probe| vauthors = Ackerman T |publisher=Houston Chronicle|date=February 29, 2012|access-date=March 8, 2016}}</ref><ref>{{cite news |title=Caught Our Notice: Researcher who once threatened to sue Retraction Watch now up to 19 retractions |url=https://retractionwatch.com/2018/04/10/caught-our-notice-researcher-who-once-threatened-to-sue-retraction-watch-now-up-to-19-retractions/#more-63985 |work=Retraction Watch |date=April 10, 2018}}</ref>  Aggarwal's research had focused on potential [[anti-cancer]] properties of herbs and spices, particularly curcumin, and according to a March 2016 article in the ''[[Houston Chronicle]]'', "attracted national media interest and laid the groundwork for ongoing clinical trials".<ref>{{cite news | vauthors = Ackerman T |title=M.D. Anderson scientist, accused of manipulating data, retires |url=https://www.houstonchronicle.com/news/houston-texas/houston/article/M-D-Anderson-scientist-accused-of-falsifying-6865704.php |work=Houston Chronicle |date=March 2, 2016}}</ref><ref name="SciAm">{{cite journal|title=Spice Healer| vauthors = Stix G |journal=Scientific American|date=February 2007|volume=296|issue=2|pages=66–69|doi=10.1038/scientificamerican0207-66|pmid=17367023|bibcode=2007SciAm.296b..66S}}</ref><ref>{{cite news|url=http://www.chron.com/news/houston-texas/article/In-cancer-fight-a-spice-brings-hope-to-the-table-1913487.php|title=In cancer fight, a spice brings hope to the table | vauthors = Ackerman T |work=Houston Chronicle|date=July 11, 2005|access-date=March 24, 2015}}</ref>   


Aggarwal cofounded a company in 2004 called Curry Pharmaceuticals based in [[Research Triangle Park]], [[North Carolina]], which planned to develop drugs based on synthetic analogs of curcumin.<ref name="SciAm"/><ref name="Singh1">{{cite journal | vauthors = Singh S | title = From exotic spice to modern drug? | journal = Cell | volume = 130 | issue = 5 | pages = 765–768 | date = September 2007 | pmid = 17803897 | doi = 10.1016/j.cell.2007.08.024 | s2cid = 16044143 | doi-access = free }}</ref> SignPath Pharma, a company seeking to develop [[Liposome|liposomal]] formulations of curcumin, licensed three patents by Aggarwal related to that approach from MD Anderson in 2013.<ref>{{cite news | vauthors = Baum S |title=Biotech startup raises $1M for lung cancer treatment using component of tumeric |url=https://medcitynews.com/2013/03/biotech-startup-raises-1m-for-lung-cancer-treatment-using-component-of-tumeric/ |work=Med City News |date=March 26, 2013}}</ref>
Aggarwal cofounded a company in 2004 called Curry Pharmaceuticals based in [[Research Triangle Park]], [[North Carolina]], which planned to develop drugs based on synthetic analogs of curcumin.<ref name="SciAm"/><ref name="Singh1">{{cite journal | vauthors = Singh S | title = From exotic spice to modern drug? | journal = Cell | volume = 130 | issue = 5 | pages = 765–768 | date = September 2007 | pmid = 17803897 | doi = 10.1016/j.cell.2007.08.024 | s2cid = 16044143 | doi-access = free }}</ref> SignPath Pharma, a company seeking to develop [[Liposome|liposomal]] formulations of curcumin, licensed three patents by Aggarwal related to that approach from MD Anderson in 2013.<ref>{{cite news | vauthors = Baum S |title=Biotech startup raises $1M for lung cancer treatment using component of tumeric |url=https://medcitynews.com/2013/03/biotech-startup-raises-1m-for-lung-cancer-treatment-using-component-of-tumeric/ |work=Med City News |date=March 26, 2013}}</ref>


==FDA warnings about dietary supplements==
===Warnings about dietary supplements===
Between 2018 and 2023, the FDA issued 29 [[FDA warning letter|warning letters]] to American manufacturers of [[dietary supplement]]s for making false claims of anti-disease effects from using  products containing curcumin.<ref name="fdawarn">{{cite web |title=Warning Letters: Curcumin (search term) |url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters |archive-url=https://web.archive.org/web/20190428002400/https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters |url-status=dead |archive-date=April 28, 2019 |publisher=US Food and Drug Administration |access-date=23 April 2023 |date=23 April 2023}}</ref> In each letter, the FDA stated that the supplement product was not an [[prescription drug|approved new drug]] because the "product is not generally recognized as safe and effective" for the advertised uses, that "new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA", and that the "FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective".<ref name=fdawarn/>
Between 2018 and 2023, the U.S. FDA issued 29 [[FDA warning letter|warning letters]] to American manufacturers of [[dietary supplement]]s for making false claims of anti-disease effects from using  products containing curcumin.<ref name="fdawarn">{{cite web |title=Warning Letters: Curcumin (search term) |url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters |archive-url=https://web.archive.org/web/20190428002400/https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters |url-status=dead |archive-date=April 28, 2019 |publisher=US Food and Drug Administration |access-date=23 April 2023 |date=23 April 2023}}</ref> In each letter, the FDA stated that the supplement product was not an [[prescription drug|approved new drug]] because the "product is not generally recognized as safe and effective" for the advertised uses, that "new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA", and that the "FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective".<ref name=fdawarn/>


==Alternative medicine==
===Alternative medicine===
Though there is no evidence for the safety or efficacy of using curcumin as a therapy,<ref name=nelson/><ref name=baker/> some [[alternative medicine]] practitioners give it [[intravenous]]ly, supposedly as a treatment for numerous diseases.<ref name="FDA_080417">{{cite web |url=https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm570192.htm |archive-url=https://web.archive.org/web/20171102192121/https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm570192.htm |url-status=dead |archive-date=November 2, 2017 |publisher=[[Food and Drug Administration]] |title=FDA investigates two serious adverse events associated with ImprimisRx's compounded curcumin emulsion product for injection |date=August 4, 2017}}</ref><ref name="Hermes-1">{{cite news| vauthors = Hermes BM |author-link1=Britt Marie Hermes|title=Naturopathic Doctors Look Bad After California Woman Dies From Turmeric Injection|url=https://www.forbes.com/sites/brittmariehermes/2017/03/27/naturopathic-doctors-look-bad-after-california-woman-dies-from-turmeric-injection/|access-date=May 12, 2017|work=[[Forbes]]|date=March 27, 2017}}</ref><ref name="Forbes_120417">{{cite news| vauthors = Hermes BM |title=Confirmed: Licensed Naturopathic Doctor Gave Lethal 'Turmeric' Injection|url=https://www.forbes.com/sites/brittmariehermes/2017/04/10/confirmed-licensed-naturopathic-doctor-gave-lethal-turmeric-injection/#3f73874d6326|access-date=December 9, 2017|work=[[Forbes (magazine)|Forbes]]|date=April 10, 2017}}</ref> In 2017, two serious cases of [[adverse drug reaction|adverse events]] were reported from curcumin or turmeric products—one severe [[allergic reaction]] and one death<ref name="FDA_080417"/>—that were caused by administration of a curcumin-[[polyethylene glycol]] (PEG40) [[emulsion]] product by a [[naturopath]].<ref name=Forbes_120417/> One treatment caused [[anaphylaxis]] leading to death.<ref name="FDA_080417"/><ref name=Forbes_120417/>
Though there is no evidence for the safety or efficacy of using curcumin as a therapy,<ref name=nelson/><ref name=baker/> some [[alternative medicine]] practitioners give it [[intravenous]]ly, supposedly as a treatment for numerous diseases.<ref name="FDA_080417">{{cite web |url=https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm570192.htm |archive-url=https://web.archive.org/web/20171102192121/https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm570192.htm |url-status=dead |archive-date=November 2, 2017 |publisher=[[Food and Drug Administration]] |title=FDA investigates two serious adverse events associated with ImprimisRx's compounded curcumin emulsion product for injection |date=August 4, 2017}}</ref><ref name="Hermes-1">{{cite news| vauthors = Hermes BM |author-link1=Britt Marie Hermes|title=Naturopathic Doctors Look Bad After California Woman Dies From Turmeric Injection|url=https://www.forbes.com/sites/brittmariehermes/2017/03/27/naturopathic-doctors-look-bad-after-california-woman-dies-from-turmeric-injection/|access-date=May 12, 2017|work=[[Forbes]]|date=March 27, 2017}}</ref><ref name="Forbes_120417">{{cite news| vauthors = Hermes BM |title=Confirmed: Licensed Naturopathic Doctor Gave Lethal 'Turmeric' Injection|url=https://www.forbes.com/sites/brittmariehermes/2017/04/10/confirmed-licensed-naturopathic-doctor-gave-lethal-turmeric-injection/#3f73874d6326|access-date=December 9, 2017|work=[[Forbes (magazine)|Forbes]]|date=April 10, 2017}}</ref> In 2017, two serious cases of [[adverse drug reaction|adverse events]] were reported from curcumin or turmeric products—one severe [[allergic reaction]] and one death<ref name="FDA_080417"/>—that were caused by administration of a curcumin-[[polyethylene glycol]] (PEG40) [[emulsion]] product by a [[naturopath]].<ref name=Forbes_120417/> One treatment caused [[anaphylaxis]] leading to death.<ref name="FDA_080417"/><ref name=Forbes_120417/>


== Stability ==
== Stability ==
[[Decontamination]] of food by ionizing radiation, or [[food irradiation]], is considered a safe and efficient process for elimination of [[pathogenic bacteria]].<ref name=":2">{{Cite journal|last1=Cosentino|first1=Helio M.|last2=Takinami|first2=Patricia Y.I.|last3=del Mastro|first3=Nelida L.|date=2016|title=Comparison of the ionizing radiation effects on cochineal, annatto and turmeric natural dyes|url=https://linkinghub.elsevier.com/retrieve/pii/S0969806X1530058X|journal=Radiation Physics and Chemistry|language=en|volume=124|pages=208–211|doi=10.1016/j.radphyschem.2015.09.016|bibcode=2016RaPC..124..208C |url-access=subscription}}</ref><ref>{{Cite journal|last1=Farkas|first1=József|last2=Mohácsi-Farkas|first2=Csilla|date=2011|title=History and future of food irradiation|url=https://linkinghub.elsevier.com/retrieve/pii/S0924224410001044|journal=Trends in Food Science & Technology|language=en|volume=22|issue=2–3|pages=121–126|doi=10.1016/j.tifs.2010.04.002|url-access=subscription}}</ref> Ionizing radiation treatment can be applied to either raw materials or ready to eat foods, with some countries, like the United States, imposing limitations on its use.<ref name=":2" /><ref>{{cite web|title=Code of Federal Regulations: Title 21, Section 179.26|url=https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-179/subpart-B/section-179.26|publisher=U.S. Food and Drug Administration|access-date=7 Feb 2022}}</ref> In 2016, laboratory research established and compared the [[radiosensitivity]] of three organic food colorants including curcumin, [[carmine]], and [[annatto]] to create data to be used for application whenever food products containing these food colors were to undergo the radiation process.<ref name=":2" /> The researchers used [[spectrophotometry]] and [[capillary electrophoresis]] to establish radiosensitivity of the three organic food colorants. Carmine samples were quite stable against radiation treatment, annatto showed limited stability, and curcumin was found to be unstable, particularly when diluted.<ref name=":2" />
In 2016, laboratory research established and compared the [[radiosensitivity]] of three organic food colorants including curcumin, [[carmine]], and [[annatto]] to create data to be used for application whenever food products containing these food colors were to undergo the radiation process.<ref name=":2">{{Cite journal|last1=Cosentino|first1=Helio M.|last2=Takinami|first2=Patricia Y.I.|last3=del Mastro|first3=Nelida L.|date=2016|title=Comparison of the ionizing radiation effects on cochineal, annatto and turmeric natural dyes|url=https://linkinghub.elsevier.com/retrieve/pii/S0969806X1530058X|journal=Radiation Physics and Chemistry|language=en|volume=124|pages=208–211|doi=10.1016/j.radphyschem.2015.09.016|bibcode=2016RaPC..124..208C |url-access=subscription}}</ref> The researchers used [[spectrophotometry]] and [[capillary electrophoresis]] to establish radiosensitivity of the three organic food colorants. Carmine samples were quite stable against radiation treatment, annatto showed limited stability, and curcumin was found to be unstable, particularly when diluted.<ref name=":2" />


== References ==
== References ==
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[[Category:Curcuminoids]]
[[Category:Curcuminoids]]
[[Category:CYP2B6 inhibitors]]
[[Category:CYP2D6 inhibitors]]
[[Category:CYP2D6 inhibitors]]
[[Category:E-number additives]]
[[Category:E-number additives]]
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[[Category:Food colorings]]
[[Category:Food colorings]]
[[Category:Histone deacetylase inhibitors]]
[[Category:Histone deacetylase inhibitors]]
[[Category:Natural dyes]]
[[Category:Plant dyes]]

Latest revision as of 03:42, 24 December 2025

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Curcumin
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Curcumin is a bright yellow chemical produced by plants of the Curcuma longa species. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family, Zingiberaceae. It is sold as an herbal supplement, cosmetics ingredient, food flavoring, and food coloring.[1]

Chemically, curcumin is a polyphenol, more particularly a diarylheptanoid, belonging to the group of curcuminoids, which are phenolic pigments responsible for the yellow color of turmeric.[2]

Extensive studies have consistently failed to show any medical value for curcumin. It is difficult to study because it is both unstable and poorly bioavailable. It is unlikely to produce useful leads for drug development as a lead compound.[3]

History

Curcumin was named in 1815 when Henri Auguste Vogel and Pierre Joseph Pelletier reported the first isolation of a "yellow coloring-matter" from the rhizomes of turmeric.[4] Later, it was found to be a mixture of resin and turmeric oil. In 1910, Milobedzka and Lampe reported the chemical structure of curcumin to be as diferuloylmethane.[5] Later in 1913, the same group accomplished the synthesis of the compound.

Although used in traditional medicine, the possible therapeutic properties of turmeric or curcumin remain undetermined.[3][6][7]

Uses

File:Kurkumina.jpg
Curcumin powder

The most common applications are as an ingredient in dietary supplement, in cosmetics, as flavoring for foods, such as turmeric-flavored beverages in South and Southeast Asia,[1] and as coloring for foods, such as curry powders, mustards, butters, and cheeses. As a food additive for orange-yellow coloring in prepared foods, its E number is ETemplate:Nbs100 in the European Union.[8][9] It is also approved by the U.S. FDA to be used as a food coloring in US.[10]

Chemistry

A bright red substance in a small glass flask, held by gloved fingers
Curcumin becomes bright red when it interacts electrostatically with a phospholipid film

Curcumin incorporates a seven carbon linker and three major functional groups: an α,β-unsaturated β-diketone moiety and an aromatic O-methoxy-phenolic group.[2][5] The aromatic ring systems, which are phenols, are connected by two α,β-unsaturated carbonyl groups.[2][11] It is a diketone tautomer, existing in enolic form in organic solvents and in keto form in water.[12] The diketones form stable enols and are readily deprotonated to form enolates, which bind metal ions to form acetylacetonate-like complexes.[13] Its complexing properties are manifesting in its reaction with boric acid to give a red-colored rosocyanine.[2][14]

Because of its hydrophobic nature, curcumin is poorly soluble in water[2] but is easily soluble in organic solvents.[5]

Biosynthesis

The biosynthetic route of curcumin is uncertain. In 1973, Peter J. Roughley and Donald A. Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involves a chain extension reaction by cinnamic acid and 5 malonyl-CoA molecules that eventually arylize into a curcuminoid. The second mechanism involves two cinnamate units coupled together by malonyl-CoA. Both use cinnamic acid as their starting point, which is derived from the amino acid phenylalanine.[15]

Plant biosynthesis starting with cinnamic acid is rare compared to the more common p-coumaric acid.[15] Only a few identified compounds, such as anigorufone and pinosylvin, build from cinnamic acid.[16][17]

Curcumin biosynthesis diagram
Biosynthetic pathway of curcumin in Curcuma longa.[15]

Pharmacology

File:Curcumin fluorescence.jpg
Curcumin displays green fluorescence under UV light

Curcumin, which shows positive results in most drug discovery assays, is regarded as a false lead that medicinal chemists include among "pan-assay interference compounds". This attracts undue experimental attention while failing to advance as viable therapeutic or drug leads,[3][6][18] although some derivatives of curcumin such as EF-24 have been well-studied.[19]

Factors that limit the bioactivity of curcumin or its analogs include chemical instability, water insolubility, absence of potent and selective target activity, low bioavailability, limited tissue distribution, and extensive metabolism.[3] Very little curcumin escapes the GI tract and most is excreted in feces unchanged.[20] If curcumin enters plasma in reasonable amounts, there is a high risk of toxicity since it is promiscuous, and interacts with several proteins known to increase the risk of adverse effects, including hERG, cytochrome P450s, and glutathione S-transferase.[3]

Safety

Although curcumin has been assessed in numerous laboratory and clinical studies, it has no medical uses.[21] Its instability, reactivity, and poor bioavailability, make curcumin an unlikely drug candidate.[3] Curcumin exhibits numerous interference properties which may lead to misinterpretation of results.[3][6][22]

Between 1995 and 2017, the US government funded US$150 million in biomedical research into curcumin through the National Center for Complementary and Integrative Health. No support was found for curcumin as a medical treatment.[3] As a component of turmeric, curcumin may interact with prescription drugs and dietary supplements.[23] In high amounts, it may be unsafe for women during pregnancy.[23] It may cause side effects, such as nausea, diarrhea, hives, or dizziness.[23] Between 2004 and 2022 there were ten cases of liver injury caused by curcumin herbal and dietary supplements.[24] Curcumin is a contact allergen.[25]

The intended use of curcumin as a food additive is generally recognized as safe by the U.S. Food and Drug Administration.[26]

Research fraud

Bharat Aggarwal, a former cancer researcher at the University of Texas MD Anderson Cancer Center, had 29 papers retracted due to research fraud since July 2021Template:Dated maintenance category (articles)Script error: No such module "Check for unknown parameters"..[27][28][29] Aggarwal's research had focused on potential anti-cancer properties of herbs and spices, particularly curcumin, and according to a March 2016 article in the Houston Chronicle, "attracted national media interest and laid the groundwork for ongoing clinical trials".[30][31][32]

Aggarwal cofounded a company in 2004 called Curry Pharmaceuticals based in Research Triangle Park, North Carolina, which planned to develop drugs based on synthetic analogs of curcumin.[31][33] SignPath Pharma, a company seeking to develop liposomal formulations of curcumin, licensed three patents by Aggarwal related to that approach from MD Anderson in 2013.[34]

Warnings about dietary supplements

Between 2018 and 2023, the U.S. FDA issued 29 warning letters to American manufacturers of dietary supplements for making false claims of anti-disease effects from using products containing curcumin.[35] In each letter, the FDA stated that the supplement product was not an approved new drug because the "product is not generally recognized as safe and effective" for the advertised uses, that "new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA", and that the "FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective".[35]

Alternative medicine

Though there is no evidence for the safety or efficacy of using curcumin as a therapy,[3][6] some alternative medicine practitioners give it intravenously, supposedly as a treatment for numerous diseases.[36][37][38] In 2017, two serious cases of adverse events were reported from curcumin or turmeric products—one severe allergic reaction and one death[36]—that were caused by administration of a curcumin-polyethylene glycol (PEG40) emulsion product by a naturopath.[38] One treatment caused anaphylaxis leading to death.[36][38]

Stability

In 2016, laboratory research established and compared the radiosensitivity of three organic food colorants including curcumin, carmine, and annatto to create data to be used for application whenever food products containing these food colors were to undergo the radiation process.[39] The researchers used spectrophotometry and capillary electrophoresis to establish radiosensitivity of the three organic food colorants. Carmine samples were quite stable against radiation treatment, annatto showed limited stability, and curcumin was found to be unstable, particularly when diluted.[39]

References

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  1. ↑ a b Script error: No such module "citation/CS1".
  2. ↑ a b c d e CID 969516 from PubChemTemplate:EditAtWikidataTemplate:WikidataCheck
  3. ↑ a b c d e f g h i Script error: No such module "Citation/CS1".
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  4. ↑ Script error: No such module "Citation/CS1".
  5. ↑ a b c Script error: No such module "citation/CS1".
  6. ↑ a b c d Script error: No such module "Citation/CS1".
  7. ↑ Script error: No such module "citation/CS1".
  8. ↑ Script error: No such module "citation/CS1".
  9. ↑ Script error: No such module "citation/CS1".
  10. ↑ Script error: No such module "citation/CS1".
  11. ↑ Script error: No such module "Citation/CS1".
  12. ↑ Script error: No such module "Citation/CS1".
  13. ↑ Script error: No such module "Citation/CS1".
  14. ↑ Script error: No such module "citation/CS1".
  15. ↑ a b c Script error: No such module "Citation/CS1".
  16. ↑ Script error: No such module "Citation/CS1".
  17. ↑ Script error: No such module "Citation/CS1".
  18. ↑ Script error: No such module "Citation/CS1".
  19. ↑ Script error: No such module "Citation/CS1".
  20. ↑ Script error: No such module "Citation/CS1".
  21. ↑ Script error: No such module "citation/CS1".
  22. ↑ Script error: No such module "citation/CS1".
  23. ↑ a b c Script error: No such module "citation/CS1".
  24. ↑ Script error: No such module "Citation/CS1".
  25. ↑ Script error: No such module "Citation/CS1".
  26. ↑ Script error: No such module "citation/CS1".
  27. ↑ Script error: No such module "citation/CS1".
  28. ↑ Script error: No such module "citation/CS1".
  29. ↑ Script error: No such module "citation/CS1".
  30. ↑ Script error: No such module "citation/CS1".
  31. ↑ a b Script error: No such module "Citation/CS1".
  32. ↑ Script error: No such module "citation/CS1".
  33. ↑ Script error: No such module "Citation/CS1".
  34. ↑ Script error: No such module "citation/CS1".
  35. ↑ a b Script error: No such module "citation/CS1".
  36. ↑ a b c Script error: No such module "citation/CS1".
  37. ↑ Script error: No such module "citation/CS1".
  38. ↑ a b c Script error: No such module "citation/CS1".
  39. ↑ a b Script error: No such module "Citation/CS1".

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External links

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