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{{Short description|Pungent chemical compound in chili peppers}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Use dmy dates|date=February 2023}}
{{chembox
{{chembox
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 443496864
| verifiedrevid = 443496864
| ImageFile1 = kapsaicyna.svg
| ImageFile1 = Capsaicin.svg
| ImageFile2 = Capsaicin-3D-vdW.png
| ImageSize1 = 250px
| PIN = (6''E'')-''N''-[(4-Hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide
| ImageFile2 = Capsaicin-3D-vdW.png
| OtherNames = (''E'')-''N''-(4-Hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide<br />8-Methyl-''N''-vanillyl-''trans''-6-nonenamide<br />''trans''-8-Methyl-''N''-vanillylnon-6-enamide<br />(''E'')-Capsaicin<br />Capsicine<br />Capsicin<br />CPS<br />Drug
| ImageSize2 = 250px
| pronounce = {{IPAc-en|k|ae|p|ˈ|s|eI|s|I|n}} or {{IPAc-en|k|ae|p|ˈ|s|eI|ə|s|I|n}}
| IUPACName = 8-Methyl-''N''-vanillyl-''(trans)''-6-nonenamide
| Section1 = {{Chembox Identifiers
| OtherNames = (''E'')-N-(4-Hydroxy-3-methoxybenzyl)<br>-8-methylnon-6-enamide,<br> trans-8-Methyl-''N''-vanillylnon<br>-6-enamide, (''E'')-Capsaicin, Capsicine, Capsicin,<br> CPS, C
|IUPHAR_ligand = 2486
| Section1 = {{Chembox Identifiers
|InChI = 1/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
| UNII_Ref = {{fdacite|correct|FDA}}
|InChIKey = YKPUWZUDDOIDPM-SOFGYWHQBQ
| UNII = S07O44R1ZM
|ChEMBL_Ref = {{ebicite|correct|EBI}}
| InChI = 1/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
|ChEMBL = 294199
| InChIKey = YKPUWZUDDOIDPM-SOFGYWHQBQ
| ChEMBL_Ref = {{ebicite|correct|EBI}}
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
| ChEMBL = 294199
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = YKPUWZUDDOIDPM-SOFGYWHQSA-N
| StdInChI = 1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo = 404-86-4
| StdInChIKey = YKPUWZUDDOIDPM-SOFGYWHQSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID =1265957
| CASNo = 404-86-4
|EINECS = 206-969-8
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|PubChem = 1548943
| ChemSpiderID =1265957
|ChEBI_Ref = {{ebicite|correct|EBI}}
| EINECS = 206-969-8
| PubChem = 1548943
|ChEBI = 3374
|Beilstein = 2816484
| ChEBI_Ref = {{ebicite|correct|EBI}}
|UNII = S07O44R1ZM
| ChEBI = 3374
|UNII_Ref = {{fdacite|correct|FDA}}
| SMILES = O=C(NCc1cc(OC)c(O)cc1)CCCC/C=C/C(C)C
|DrugBank = DB06774
| ATCCode_prefix = M02
|SMILES = O=C(NCc1cc(OC)c(O)cc1)CCCC/C=C/C(C)C
| ATCCode_suffix = AB01
| ATC_Supplemental = {{ATC|N01|BX04}}
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = C06866
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C06866
}}
| Section2 = {{Chembox Properties
| C=18|H=27|N=1|O=3
| LambdaMax = 280 nm
| Appearance = crystalline white powder<ref>[http://www.chemspider.com/Chemical-Structure.1265957.html ChemSpider - Capsaicin]</ref>
| Odor = highly volatile and pungent
| Density =
| MeltingPtC = 62
| MeltingPtCH = 65
| BoilingPtC = 210
| BoilingPtCH = 220
| Boiling_notes = 0.01 Torr
| Solubility = 0.0013 g/100 mL
| SolubleOther = soluble in alcohol, [[ether]], [[benzene]] <br> slightly soluble in [[carbon disulfide|CS<sub>2</sub>]], [[hydrochloric acid|HCl]], [[petroleum]]
}}
| Section3 = {{Chembox Structure
| CrystalStruct = monoclinic
}}
}}
| Section4 = {{Chembox Hazards
| Section2 = {{Chembox Properties
|C=18 | H=27 | N=1 | O=3
| ExternalMSDS = [https://docs.google.com/viewer?a=v&q=cache:0qEFkQwng5sJ:www.sciencelab.com/msds.php?msdsId%3D9923296+capsaiacin+msds&hl=en&gl=us&pid=bl&srcid=ADGEESiVORhJth5_Ji4WTD0mNETNU8rIwY2C3LTNaj9MfdynWiapqmSB8w7p-TfQqYC3--kKvFWW7u9EZ5QOmriEfLKRsWPquEQtjWo1joKGpqhvyfm-XUGbr17v162HlzZSU9SWdKZI&sig=AHIEtbSLvraa7YE_jZ4cDurp9iX-TCGPiA Capsaicin, Natural MSDS]
|LambdaMax = 280 nm
| MainHazards = Toxic ('''T''')
|Appearance = Crystalline white powder<ref>{{cite web|url=http://www.chemspider.com/Chemical-Structure.1265957.html|publisher=ChemSpider, Royal Society of Chemistry, Cambridge, UK|title=Capsaicin|date=2018|access-date=9 June 2018}}</ref>
| RPhrases = {{R24/25}}
|Odor = Highly pungent
| SPhrases = {{S26}}, {{S36/37/39}}, {{S45}}
|VaporPressure = {{val|1.32|e=-8|u=mm Hg}} at {{val|25|u=degC}}<ref name="pubchem">{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/1548943|publisher=PubChem, US National Library of Medicine|title=Capsaicin|date=27 May 2023|access-date=1 June 2023}}</ref>
| FlashPt =
|MeltingPtC = 62 to 65
| Autoignition =
|BoilingPtC = 210 to 220
| NFPA-H = 2
|BoilingPt_notes = 0.01{{nbsp}}Torr
| NFPA-F = 1
|Solubility = 0.0013{{nbsp}}g/100{{thinsp}}mL
| NFPA-R = 0
|SolubleOther = {{ubl
}}
|Soluble in alcohol, [[diethyl ether|ether]], [[benzene]]
|Slightly soluble in [[carbon disulfide|CS<sub>2</sub>]], [[hydrochloric acid|HCl]], [[petroleum]]
}}
}}
{{pepper
| boxwidth=250px
| image=Hottest-chili-rating.gif
| heat= Above Peak ([[Scoville scale|SR]]: 15,000,000-16,000,000)
}}
}}
| Section3 = {{Chembox Structure
'''Capsaicin''' ({{IPAc-en|k|æ|p|ˈ|s|eɪ|.|ɨ|s|ɪ|n}}; 8-[[methyl]]-''N''-[[vanillyl]]-6-nonen[[amide]]) is an active component of [[chili pepper]]s, which are [[plants]] belonging to the [[genus]] ''[[Capsicum]]''. It is an [[Irritation|irritant]] for [[mammal]]s, including [[human]]s, and produces a sensation of burning in any [[Biological tissue|tissue]] with which it comes into contact. Capsaicin and several related compounds are called '''capsaicinoids''' and are produced as [[secondary metabolite]]s by chili peppers, probably as deterrents against certain [[mammals]] and [[fungi]].<ref name="totn">[http://www.npr.org/templates/story/story.php?storyId=93636630 What Made Chili Peppers So Spicy?] Talk of the Nation, 15 August 2008.</ref> Pure capsaicin is a [[Volatility (chemistry)|volatile]], [[hydrophobic]], colorless, odorless, crystalline to waxy compound.
|CrystalStruct = Monoclinic
}}
| Section4 = {{Chembox Pharmacology
|ATCCode_prefix = M02
|ATCCode_suffix = AB01
|ATC_Supplemental = {{ATC|N01|BX04}}
|Licence_EU=yes
|Legal_US = Rx-only
|Legal_US_comment = <ref name="Qutenza FDA label">{{cite web | title=Qutenza- capsaicin kit | website=DailyMed | date=10 January 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ffbbcb0-ad93-4f15-bb38-5da76a71c735 | access-date=22 February 2023}}</ref><ref>{{cite web | title=Drug Approval Package: Qutenza (capsaicin) NDA #022395 | website=U.S. [[Food and Drug Administration]] (FDA) | date=3 October 2013 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022395_qutenza_toc.cfm | access-date=22 February 2023}}</ref>
}}
| Section5 = {{Chembox Hazards
|ExternalSDS = <ref name=pubchem/>
|GHSPictograms = {{GHS05}}{{GHS06}}{{GHS07}}{{GHS08}}
|GHSSignalWord = Danger
|HPhrases = {{H-phrases|301|302|315|318}}
|PPhrases = {{P-phrases|264|270|280|301+310|301+312|302+352|305+351+338|310|321|330|332+313|362|405|501}}
|NFPA-H = 2
|NFPA-F = 1
|NFPA-R = 0
}}
}}
{{Infobox pepper <!-- The given scoville rating is for the pure chemical compound, this should not be mistaken for food. -->
| heat = Above peak<br /> (pure capsaicin is toxic)<ref name=pubchem/>
| scoville = 16,000,000<ref name="pmid2039598">{{cite journal | vauthors = Govindarajan VS, Sathyanarayana MN | title = Capsicum--production, technology, chemistry, and quality. Part V. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences | journal = Critical Reviews in Food Science and Nutrition | volume = 29 | issue = 6 | pages = 435–474 | year = 1991 | pmid = 2039598 | doi = 10.1080/10408399109527536 }}</ref>
}}


'''Capsaicin''' ('''8-methyl-''N''-vanillyl-6-nonenamide''') ({{IPAc-en|k|ae|p|ˈ|s|eI|s|I|n}} or {{IPAc-en|k|ae|p|ˈ|s|eI|ə|s|I|n}}) is an active component of [[chili pepper]]s, which are plants belonging to the genus ''[[Capsicum]]''. It is a potent [[Irritation|irritant]] for [[Mammal|mammals]], including humans, and produces a sensation of burning in any [[Tissue (biology)|tissue]] with which it comes into contact. Capsaicin and several related [[amide]]s (capsaicinoids) are produced as [[secondary metabolite]]s by chili peppers, likely as deterrents against certain mammals and fungi.<ref name="totn">{{cite web | url = https://www.npr.org/templates/story/story.php?storyId=93636630 | title = What Made Chili Peppers So Spicy? | work = Talk of the Nation | date = 15 August 2008 }}</ref> Pure capsaicin is a [[hydrophobic]], colorless, highly [[pungent]] (i.e., spicy) [[crystalline]] solid.<ref name=pubchem/>
==History==
The compound<ref>History of early research on capsaicin:
* Harvey W. Felter and John U. Lloyd, ''King's American Dispensatory'' (Cincinnati, Ohio: Ohio Valley Co., 1898), vol. 1, page 435. Available on-line at: [http://www.henriettesherbal.com/eclectic/kings/capsicum.html Henriette's Herbal].
* Andrew G. Du Mez, "A century of the United States pharmocopoeia 1820-1920. I. The galenical oleoresins" (Ph.D. dissertation, University of Wisconsin, 1917), pages 111-132. Available on-line at: [http://www.archive.org/stream/centuryofuniteds00dumerich/centuryofuniteds00dumerich_djvu.txt Archive.org].</ref> was first extracted (albeit in impure form) in 1816 by Christian Friedrich Bucholz (1770–1818).<ref>See:
* C. F. Bucholz (1816) "Chemische Untersuchung der trockenen reifen spanischen Pfeffers" [Chemical investigation of dry, ripe Spanish peppers], ''Almanach oder Taschenbuch für Scheidekünstler und Apotheker'' (Weimar) [Almanac or Pocket-book for Analysts (Chemists) and Apothecaries], vol. 37, pages 1-30. [Note: Christian Friedrich Bucholz's surname has been variously spelled as "Bucholz", "Bucholtz", or "Buchholz".]
* The results of Bucholz's and Braconnot's analyses of ''Capsicum annuum'' appear in: Jonathan Pereira, ''The Elements of Materia Medica and Therapeutics'', 3rd U.S. ed. (Philadelphia, Pennsylvania: Blanchard and Lea, 1854), vol. 2, [http://books.google.com/books?id=IrXszQ77xhYC&pg=PA506&lpg=PA506#v=onepage&q&f=false page 506].
* Biographical information about Christian Friedrich Bucholz is available in: Hugh J. Rose, Henry J. Rose, and Thomas Wright, ed.s, ''A New General Biographical Dictionary'' (London, England: 1857), vol. 5, [http://books.google.com/books?id=nNRySUejNcYC&pg=PA186&lpg=PA186#v=onepage&q&f=false page 186].
* Biographical information about C. F. Bucholz is also available (in German) on-line at: [http://de.wikisource.org/wiki/ADB:Bucholtz,_Christian_Friedrich Allgemeine Deutsche Biographie].
* Some other early investigators who also extracted the active component of peppers:
:# Benjamin Maurach (1816) "Pharmaceutisch-chemische Untersuchung des spanischen Pfeffers" (Pharmaceutical-chemical investigation of Spanish peppers), ''Berlinisches Jahrbuch für die Pharmacie'', vol. 17, pages 63-73. Abstracts of Maurach's paper appear in: (i) ''Repertorium für die Pharmacie'', vol. 6, [http://books.google.com/books?id=euo8AAAAcAAJ&pg=PA117&lpg=PA117#v=onepage&q&f=false page 117-119] (1819); (ii) ''Allgemeine Literatur-Zeitung'', vol. 4, no. 18, [http://books.google.com/books?id=rRo4AAAAMAAJ&pg=RA2-PA20-IA2&lpg=RA2-PA20-IA2#v=onepage&q&f=false page 146] (Feb. 1821); (iii) "Spanischer oder indischer Pfeffer", ''System der Materia medica'' ... , vol. 6, [http://books.google.com/books?id=jgA9AAAAcAAJ&pg=PA381&lpg=PA381#v=onepage&q&f=false pages 381-386] (1821) (this reference also contains an abstract of Bucholz's analysis of peppers).
:# French chemist [[Henri Braconnot]] (1817) "Examen chemique du Piment, de son principe âcre, et de celui des plantes de la famille des renonculacées" (Chemical investigation of the chili pepper, of its pungent principle [constituent, component], and of that of plants of the family ''Ranunculus''), ''Annales de Chemie et de Physique'', vol. 6, [http://books.google.com/books?id=b2luVw2yngoC&pg=PA122#v=onepage&q&f=false pages 122- 131].
:# Danish geologist [[Johann Georg Forchhammer]] in: Hans C. Oersted (1820) "Sur la découverte de deux nouveaux alcalis végétaux" (On the discovery of two new plant alkalis), ''Journal de physique, de chemie, d'histoire naturelle et des arts'', vol. 90, [http://books.google.com/books?id=E-YPAAAAQAAJ&pg=PA173&lpg=PA174#v=onepage&q&f=false pages 173-174].
:# German apothecary Ernst Witting (1822) "Considerations sur les bases vegetales en general, sous le point de vue pharmaceutique et descriptif de deux substances, la capsicine et la nicotianine" (Thoughts on the plant bases in general from a pharmaceutical viewpoint, and description of two substances, capsicin and nicotine), ''Beiträge für die pharmaceutische und analytische Chemie'', vol. 3, pages 43ff.</ref> He called it "capsicin", after the genus ''[[Capsicum]]'' from which it was extracted. John Clough Thresh (1850–1932), who had isolated capsaicin in almost pure form,<ref>In a series of articles, J. C. Thresh obtained capsaicin in almost pure form:
* J. C. Thresh (1876) "Isolation of capsaicin," ''The Pharmaceutical Journal and Transactions'', 3rd series, vol. 6, pages 941-947;
* J. C. Thresh (8 July 1876) "Capsaicin, the active principle in Capsicum fruits," ''The Pharmaceutical Journal and Transactions'', 3rd series, vol. 7, no. 315, pages 21 ff. [Note: This article is summarized in: "Capsaicin, the active principle in Capsicum fruits," ''The Analyst'', vol. 1, no. 8, [http://pubs.rsc.org/en/Content/ArticleLanding/1876/AN/an876010148b pages 148-149], (1876).]. In ''The Pharmaceutical Journal and Transactions'', volume 7, see also pages 259ff and 473 ff and in vol. 8, see pages 187ff;
* ''Year Book of Pharmacy…'' (1876), pages 250 and 543;
* J. C. Thresh (1877) "Note on Capsaicin," [http://www.archive.org/stream/yearbookofpharma1877londuoft/yearbookofpharma1877londuoft_djvu.txt ''Year Book of Pharmacy…''], pages 24-25;
* J. C. Thresh (1877) "Report on the active principle of Cayenne pepper," ''Year Book of Pharmacy...'', pages 485-488.</ref><ref>Obituary notice of J. C. Thresh: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2521090/?page=1 "John Clough Thresh, M.D., D. Sc., and D.P.H.,"] ''The British Medical Journal'', vol. 1, no. 3726, pages 1057-1058 (4 June 1932).</ref> gave it the name "capsaicin" in 1876.<ref>J King, H Wickes Felter, J Uri Lloyd (1905) A King's American Dispensatory. Eclectic Medical Publications (ISBN 1888483024)</ref> But it was Karl Micko who first isolated capsaicin in pure form in 1898.<ref>Karl Micko (1898) [http://books.google.com/books?id=8SbOAAAAMAAJ&pg=PA818#v=onepage&q&f=false "Zur Kenntniss des Capsaïcins"] (On our knowledge of capsaicin), ''Zeitschrift für Untersuchung der Nahrungs- und Genussmittel'' (Journal for the Investigation of Necessities and Luxuries), vol. 1, pages 818-829. See also: Karl Micko (1899) [http://books.google.com/books?id=0zwDAAAAYAAJ&pg=PA411#v=onepage&q&f=false "Über den wirksamen Bestandtheil des Cayennespfeffers"] (On the active component of Cayenne pepper), ''Zeitschrift für Untersuchung der Nahrungs- und Genussmittel'', vol. 2, pages 411-412.</ref> Capsaicin's empirical formula (chemical composition) was first determined by E. K. Nelson in 1919; he also partially elucidated capsaicin's chemical structure.<ref>E. K. Nelson. [http://books.google.com/books?id=Ra4UAAAAYAAJ&pg=PA1115&lpg=PA1115#v=onepage&q&f=false "The constitution of capsaicin, the pungent principle of capsicum".] ''J. Am. Chem. Soc.'' '''1919''', ''41'', 1115–1121. {{|10.1021/ja02228a011}}</ref> Capsaicin was first synthesized in 1930 by E. Spath and S. F. Darling.<ref>Ernst Späth, Stephen F. Darling. Synthese des Capsaicins. ''Chem. Ber.'' '''1930''', ''63B'', 737–743.</ref> In 1961, similar substances were isolated from [[chili pepper]]s by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.<ref>S Kosuge, Y Inagaki, H Okumura (1961). Studies on the pungent principles of red pepper. Part VIII. On the chemical constitutions of the pungent principles. Nippon Nogei Kagaku Kaishi (J. Agric. Chem. Soc.), 35, 923–927; (en) Chem. Abstr. 1964, 60, 9827g.</ref><ref>(ja) S Kosuge, Y Inagaki (1962) Studies on the pungent principles of red pepper. Part XI. Determination and contents of the two pungent principles. Nippon Nogei Kagaku Kaishi (J. Agric. Chem. Soc.), 36, pp. 251</ref>


== Natural function ==
In 1873 German pharmacologist [[Rudolf Buchheim]]<ref>Rudolf Buchheim (1873) "Über die 'scharfen' Stoffe" (On the "hot" substance), ''Archiv der Heilkunde'' (Archive of Medicine), vol. 14, pages 1ff. See also: R. Buchheim (1872) "Fructus Capsici," ''Vierteljahresschrift fur praktische Pharmazie'' (Quarterly Journal for Practical Pharmacy), vol. 4, pages 507ff.; reprinted (in English) in: ''Proceedings of the American Pharmaceutical Association'', vol. 22, pages 106ff (1873).</ref> (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes<ref>Endre Hőgyes, "Adatok a paprika (Capsicum annuum) élettani hatásához" [Data on the physiological effects of the pepper (Capsicum annuum)], ''Orvos-természettudumányi társulatot Értesítője'' [Bulletin of the Medical Science Association] (1877); reprinted in: ''Orvosi Hetilap'' [Medical Journal] (1878), 10 pages. Published in German as: "Beitrage zur physiologischen Wirkung der Bestandtheile des ''Capiscum annuum'' (Spanischer Pfeffer)" [Contributions on the physiological effects of components of ''Capsicum annuum'' (Spanish pepper)], ''Archiv für Experimentelle Pathologie und Pharmakologie'', vol. 9, pages 117-130 (1878). See: http://www.springerlink.com/content/n54508568351x051/ .</ref> stated that "capsicol" (partially purified capsaicin<ref>F.A. Flückiger, ''Pharmakognosie des Pflanzenreiches'' ( Berlin, Germany: Gaertner's Verlagsbuchhandlung, 1891).</ref>) caused the burning feeling when in contact with [[mucous membrane]]s and increased secretion of [[gastric acid]].
Capsaicin is present in large quantities in the [[Placentation#In plants|placental tissue]] (which holds the seeds), the internal membranes and, to a lesser extent, the other fleshy parts of the fruits of plants in the genus ''[[Capsicum]]''. The seeds themselves do not produce any capsaicin, although the highest concentration of capsaicin can be found in the white [[Fruit anatomy#Mesocarp|pith]] of the inner wall, where the seeds are attached.<ref name="NMSU Q&A 2005">{{cite web| publisher = New Mexico State University – College of Agriculture and Home Economics |title=Chile Information – Frequently Asked Questions |year=2005 |url=http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub |access-date=17 May 2007 |archive-url = https://web.archive.org/web/20070504035555/http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub <!-- Bot retrieved archive --> |archive-date = 4 May 2007}}</ref>


The seeds of ''Capsicum'' plants are dispersed predominantly by birds. In birds, the [[TRPV1]] channel does not respond to capsaicin or related chemicals but mammalian TRPV1 is very sensitive to it. This is advantageous to the plant, as chili pepper seeds consumed by birds pass through the digestive tract and can germinate later, whereas mammals have [[molar (tooth)|molar teeth]] which destroy such seeds and prevent them from germinating.<!-- Tewksbury & Nabhan 2001, Nature 412 --> Thus, [[natural selection]] may have led to increasing capsaicin production because it makes the plant less likely to be eaten by animals that do not help it disperse.<ref name="Tewksbury Nabhan 2001">{{cite journal | vauthors = Tewksbury JJ, Nabhan GP | title = Seed dispersal. Directed deterrence by capsaicin in chilies | journal = Nature | volume = 412 | issue = 6845 | pages = 403–404 | date = July 2001 | pmid = 11473305 | doi = 10.1038/35086653 | bibcode = 2001Natur.412..403T | s2cid = 4389051 }}</ref> There is also evidence that capsaicin may have evolved as an [[Fungicide|anti-fungal]] agent.<ref>{{cite journal | vauthors = Tewksbury JJ, Reagan KM, Machnicki NJ, Carlo TA, Haak DC, Peñaloza AL, Levey DJ | title = Evolutionary ecology of pungency in wild chilies | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 33 | pages = 11808–11811 | date = August 2008 | pmid = 18695236 | pmc = 2575311 | doi = 10.1073/pnas.0802691105 | title-link = doi | doi-access = free | bibcode = 2008PNAS..10511808T }}</ref> The fungal pathogen ''[[Fusarium]]'', which is known to infect wild chilies and thereby reduce seed viability, is deterred by capsaicin, which thus limits this form of predispersal seed mortality.
==Capsaicinoids==
Capsaicin is the main capsaicinoid in chili peppers, followed by [[dihydrocapsaicin]]. These two compounds are also about twice as potent to the taste and nerves as the minor capsaicinoids [[nordihydrocapsaicin]], [[homodihydrocapsaicin]], and [[homocapsaicin]]. Dilute solutions of pure capsaicinoids produced different types of pungency; however, these differences were not noted using more concentrated solutions.


The [[vanillotoxin]]-containing venom of a certain [[tarantula]] species (''[[Psalmopoeus cambridgei]])'' activates the same pathway of pain as is activated by capsaicin, an example of a shared pathway in both plant and animal anti-mammalian defense.<ref name="auto">{{cite journal |vauthors=Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D |date=November 2006 |title=Spider toxins activate the capsaicin receptor to produce inflammatory pain |journal=Nature |volume=444 |issue=7116 |pages=208–212 |bibcode=2006Natur.444..208S |doi=10.1038/nature05285 |pmid=17093448 |s2cid=4387600}}</ref>
Capsaicin is believed to be synthesized in the [[Locule|interlocular]] [[wiktionary:septum|septum]] of chili peppers by addition of a branched-chain [[fatty acid]] to [[vanillylamine]]; specifically, capsaicin is made from vanillylamine and 8-methyl-6-nonenoyl CoA.<ref>{{cite journal | author = Fujiwake H., Suzuki T., Oka S., Iwai K. | year = 1980 | title = Enzymatic formation of capsaicinoid from vanillylamine and iso-type fatty acids by cell-free extracts of Capsicum annuum var. annuum cv. Karayatsubusa | url = | journal = Agricultural and Biological Chemistry | volume = 44 | issue = | pages = 2907–2912 | doi=10.1271/bbb1961.44.2907}}</ref><ref>I. Guzman, P.W. Bosland, and M.A. O'Connell, "Chapter 8: Heat, Color, and Flavor Compounds in ''Capsicum'' Fruit" in David R. Gang, ed., ''Recent Advances in Phytochemistry 41: The Biological Activity of Phytochemicals'' (New York, New York: Springer, 2011), [http://books.google.com/books?id=--nQIHiE3QwC&pg=PA117&lpg=PA117#v=onepage&q&f=false pages 117-118].</ref> Biosynthesis depends on the gene ''AT3'', which resides at the ''pun1'' [[Locus (genetics)|locus]], and which encodes a putative [[acyltransferase]].<ref>{{Cite journal|author=Stewart C, Kang BC, Liu K, ''et al.'' |title=The Pun1 gene for pungency in pepper encodes a putative acyltransferase |journal=Plant J. |volume=42 |issue=5 |pages=675–88 |date=June 2005 |pmid=15918882 |doi=10.1111/j.1365-313X.2005.02410.x |url=}}</ref>


==Uses==
Besides the six natural capsaicinoids, one synthetic member of the capsaicinoid family exists. [[nonivamide|Vanillylamide of n-nonanoic acid]] (VNA, also PAVA) is used as a reference substance for determining the relative pungency of capsaicinoids.
===Food===
{{Main|Pungency}}
[[Image:Karnatakadishes.jpg|thumb|[[Curry]] dishes]]


Because of the burning sensation caused by capsaicin when it comes in contact with [[mucous membranes]], it is commonly used in food products to provide added spiciness or "heat" (piquancy), usually in the form of [[spices]] such as [[chili powder]] and [[paprika]].<ref name="nyt">{{cite news|url=https://www.nytimes.com/2010/09/21/science/21peppers.html|title=A Perk of Our Evolution: Pleasure in Pain of Chilies|newspaper=New York Times|date=20 September 2010| vauthors = Gorman J |access-date=16 March 2015}}</ref> In high concentrations, capsaicin will also cause a burning effect on other sensitive areas, such as skin or eyes.<ref name="bio">{{cite journal | vauthors = Rollyson WD, Stover CA, Brown KC, Perry HE, Stevenson CD, McNees CA, Ball JG, Valentovic MA, Dasgupta P | title = Bioavailability of capsaicin and its implications for drug delivery | journal = Journal of Controlled Release | volume = 196 | pages = 96–105 | date = December 2014 | pmid = 25307998 | pmc = 4267963 | doi = 10.1016/j.jconrel.2014.09.027 }}</ref> The degree of heat found within a food is often measured on the [[Scoville scale]].<ref name="nyt"/>
{| class="wikitable"
|-
! Capsaicinoid name || Abbrev. || Typical<br />relative<br />amount || [[Scoville scale|Scoville]]<br>heat units || Chemical structure
|-
| Capsaicin || C || 69% || 16,000,000
| [[Image:Kapsaicyna.svg|200px|Chemical structure of capsaicin]]
|-
| [[Dihydrocapsaicin]] || DHC || 22% || 15,000,000
| [[Image:Dihydrocapsaicin.svg|200px|Chemical structure of dihydrocapsaicin]]
|-
| [[Nordihydrocapsaicin]] || NDHC || 7% || 9,100,000
| [[Image:Nordihydrocapsaicin chemical structure.png|200px|Chemical structure of nordihydrocapsaicin]]
|-
| [[Homodihydrocapsaicin]] || HDHC || 1% || 8,600,000
| [[Image:Homodihydrocapsaicin.svg|200px|Chemical structure of homodihydrocapsaicin]]
|-
| [[Homocapsaicin]] || HC || 1% || 8,600,000
| [[Image:Homocapsaicin.svg|200px|Chemical structure of homocapsaicin]]
|-
| [[Nonivamide]] || PAVA || || 9,200,000
| [[Image:Nonivamide.svg|200px|Chemical structure of nonivamide]]
|}


There has long been a demand for capsaicin-spiced products like [[chili pepper]], and [[hot sauce]]s such as [[Tabasco sauce]] and Mexican [[salsa (sauce)|salsa]].<ref name="nyt" /> It is common for people to experience pleasurable and even [[euphoria|euphoric]] effects from ingesting capsaicin.<ref name="nyt"/> Folklore among self-described "[[wikt:chilihead|chilihead]]s" attribute this to pain-stimulated release of [[endorphins]], a different mechanism from the local receptor overload that makes capsaicin effective as a topical [[analgesic]].<ref name="bio"/>
==Natural function==
Capsaicin is present in large quantities in the placental tissue (which holds the seeds), the internal membranes and, to a lesser extent, the other fleshy parts of the [[fruit]]s of plants in the genus ''[[Capsicum]]''. The seeds themselves do not produce any capsaicin, although the highest concentration of capsaicin can be found in the white pith of the inner wall, where the seeds are attached.<ref>{{cite web|author=New Mexico State University - College of Agriculture and Home Economics |title=Chile Information - Frequently Asked Questions |year=2005 |url=http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub |accessdate=May 17, 2007 |archiveurl = http://web.archive.org/web/20070504035555/http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub <!-- Bot retrieved archive --> |archivedate = May 4, 2007}}</ref>


{{anchor|Medical}}
The seeds of ''Capsicum'' plants are dispersed predominantly by [[bird]]s: in birds, the [[TRPV1]] channel does not respond to capsaicin or related chemicals (avian vs mammalian TRPV1 show functional diversity and selective sensitivity). This is advantageous to the plant, as chili pepper seeds consumed by birds pass through the digestive tract and can germinate later, whereas mammals have [[molar (tooth)|molar teeth]] which destroy such seeds and prevent them from germinating.<!-- Tewksbury & Nabhan 2001, Nature 412 --> Thus, natural selection may have led to increasing capsaicin production because it makes the plant less likely to be eaten by animals that do not help it reproduce.<ref>{{cite doi|10.1038/35086653}}</ref> There is also evidence that capsaicin may have evolved as an [[anti-fungal]] agent:<ref>{{citation
|date=2008-08-19
|doi=10.1073/pnas.0802691105
|journal=Proceedings of the National Academy of Sciences
|volume=105 | issue=33 | pages=11808–11811
|url=http://www.pnas.org/content/105/33/11808.abstract
|title=Evolutionary ecology of pungency in wild chilies
|author=Joshua J. Tewksbury, Karen M. Reagan, Noelle J. Machnicki, Tomás A. Carlo,
David C. Haak, Alejandra Lorena Calderón Peñaloza, and Douglas J. Levey
|accessdate=2010-06-30
}}</ref> the fungal pathogen ''[[Fusarium]]'', which is known to infect wild chilies and thereby reduce seed viability, is deterred by capsaicin, which thus limits this form of predispersal seed mortality.


===Research and pharmaceutical use===
In 2006, it was discovered that the [[venom]] of a certain [[tarantula]] species activates the same pathway of pain as is activated by capsaicin; this was the first demonstrated case of such a shared pathway in both plant and animal anti-mammal defense.<ref>{{Cite journal|author=Siemens J, Zhou S, Piskorowski R, ''et al.'' |title=Spider toxins activate the capsaicin receptor to produce inflammatory pain |journal=Nature |volume=444 |issue=7116 |pages=208–12 |date=November 2006 |pmid=17093448 |doi=10.1038/nature05285 |url=}}</ref>
Capsaicin is used as an [[analgesic]] in [[Topical medication|topical ointments]] and [[dermal patch]]es to relieve pain, typically in concentrations between 0.025% and 0.1%.<ref name="fattori">{{cite journal | vauthors = Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA | title = Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses | journal = Molecules | volume = 21 | issue = 7 | pages = 844 | date = June 2016 | pmid = 27367653 | pmc = 6273101 | doi = 10.3390/molecules21070844 | title-link = doi | doi-access = free }}</ref> It may be applied in cream form for the temporary relief of minor aches and pains of [[muscle]]s and joints associated with [[arthritis]], backache, strains and [[sprain]]s, often in compounds with other [[rubefacients]].<ref name=fattori/>


It is also used to reduce the symptoms of peripheral [[neuropathy]], such as [[herpes|post-herpetic]] [[neuralgia]] caused by [[shingles]].<ref name=fattori/> A capsaicin [[transdermal]] patch (''Qutenza'') for the management of this particular therapeutic indication (pain due to post-herpetic neuralgia) was approved in 2009, as a [[therapeutic]] by both the U.S. [[Food and Drug Administration]] (FDA)<ref>{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191003.htm|title=FDA Approves New Drug Treatment for Long-Term Pain Relief after Shingles Attacks|publisher=U.S. Food and Drug Administration|date=17 November 2009|access-date=5 January 2016|archive-date=23 November 2015|archive-url=https://web.archive.org/web/20151123231205/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191003.htm|url-status=dead}}</ref><ref>{{cite web | title=Drug Approval Package: Qutenza (capsaicin) NDA #022395 | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 June 2010 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022395_qutenza_toc.cfm | access-date=19 August 2020}}
==Uses==
*{{cite web |date=13 November 2009 |title=Application Number: 22-395: Summary Review |website=FDA Center for Drug Evaluation and Research |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022395s000Sumr.pdf}}</ref> and the European Union.<ref>{{cite web | title=Qutenza EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/qutenza | access-date=19 August 2020}}</ref> A subsequent application to the FDA for Qutenza to be used as an analgesic in [[HIV]] neuralgia was refused.<ref>{{cite web|url=http://www.medscape.com/viewarticle/759986|title=FDA Turns Down Capsaicin Patch for Painful Neuropathy in HIV|publisher=Medscape Medical News, WebMD| vauthors = Hitt E |date=9 March 2012|access-date=5 January 2016}}</ref> One 2017 review of clinical studies having limited quality found that high-dose topical capsaicin (8%) compared with control (0.4% capsaicin) provided moderate to substantial pain relief from post-herpetic neuralgia, [[HIV]]-neuropathy, and [[diabetic neuropathy]].<ref>{{cite journal | vauthors = Derry S, Rice AS, Cole P, Tan T, Moore RA | title = Topical capsaicin (high concentration) for chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD007393 | date = January 2017 | pmid = 28085183 | pmc = 6464756 | doi = 10.1002/14651858.CD007393.pub4 | url = https://spiral.imperial.ac.uk:8443/bitstream/10044/1/49554/2/Derry_et_al-2017-.sup-2.pdf | access-date = 27 September 2018 | url-status = dead | archive-date = 15 February 2021 | archive-url = https://web.archive.org/web/20210215024258/https://spiral.imperial.ac.uk:8443/bitstream/10044/1/49554/2/Derry_et_al-2017-.sup-2.pdf | hdl = 10044/1/49554 }}</ref>


Although capsaicin creams have been used to treat [[psoriasis]] for reduction of itching,<ref name=fattori/><ref>{{cite journal | vauthors = Glinski W, Glinska-Ferenz M, Pierozynska-Dubowska M | title = Neurogenic inflammation induced by capsaicin in patients with psoriasis | journal = Acta Dermato-Venereologica | volume = 71 | issue = 1 | pages = 51–54 | year = 1991 | doi = 10.2340/00015555715154 | pmid = 1711752 | s2cid = 29307090 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ellis CN, Berberian B, Sulica VI, Dodd WA, Jarratt MT, Katz HI, Prawer S, Krueger G, Rex IH, Wolf JE | title = A double-blind evaluation of topical capsaicin in pruritic psoriasis | journal = Journal of the American Academy of Dermatology | volume = 29 | issue = 3 | pages = 438–442 | date = September 1993 | pmid = 7688774 | doi = 10.1016/0190-9622(93)70208-B }}</ref> a review of six [[clinical trial]]s involving topical capsaicin for treatment of [[pruritus]] concluded there was insufficient evidence of effect.<ref>{{cite journal | vauthors = Gooding SM, Canter PH, Coelho HF, Boddy K, Ernst E | title = Systematic review of topical capsaicin in the treatment of pruritus | journal = International Journal of Dermatology | volume = 49 | issue = 8 | pages = 858–865 | date = August 2010 | pmid = 21128913 | doi = 10.1111/j.1365-4632.2010.04537.x | s2cid = 24484878 }}</ref> Oral capsaicin decreases [[Low-density lipoprotein|LDL cholesterol]] levels moderately.<ref name="pmid33840333">{{cite journal | vauthors = Kelava L, Nemeth D, Hegyi P, Keringer P, Kovacs DK, Balasko M, Solymar M, Pakai E, Rumbus Z, Garami A | title = Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level: a meta-analysis of controlled human trials | journal = Critical Reviews in Food Science and Nutrition | volume = 62 | issue = 25 | pages = 7025–7035 | date = April 2021 | pmid = 33840333 | doi = 10.1080/10408398.2021.1910138 | title-link = doi | doi-access = free }}</ref>
===Food===


There is insufficient clinical evidence to determine the role of ingested capsaicin on several human disorders, including obesity, [[diabetes]], [[cancer]] and [[cardiovascular diseases]].<ref name=fattori/>
Because of the burning sensation caused by capsaicin when it comes in contact with mucous membranes, it is commonly used in food products to give them added spice or "heat" ([[piquancy]]). In high concentrations, capsaicin will also cause a burning effect on other sensitive areas of skin. The degree of heat found within a food is often measured on the [[Scoville scale]]. In some cases, people enjoy the heat; there has long been a demand for capsaicin-spiced food and beverages.<ref>[http://www.nytimes.com/2010/09/21/science/21peppers.html A Perk of Our Evolution: Pleasure in Pain of Chilies], ''[[New York Times]]'', September 20, 2010</ref> There are many cuisines and food products featuring capsaicin such as hot sauce, salsa, and beverages.


===Pepper spray and pests===
For information on treatment, see the section [[#Treatment after exposure|Treatment after exposure]].
Capsaicinoids are also an active ingredient in riot control and personal defense [[pepper spray]] agents.<ref name=pubchem/> When the spray comes in contact with skin, especially eyes or [[mucous membrane]]s, it produces pain and breathing difficulty in the affected individual.<ref name=pubchem/>


Capsaicin is also used to deter pests, specifically mammalian pests. Targets of capsaicin repellants include voles, deer, rabbits, squirrels, [[Bear spray|bears]], insects, and attacking dogs.<ref name="EPA facts capsaicin">{{cite web |title=R.E.D. Facts for Capsaicin |url=http://www.epa.gov/oppsrrd1/REDs/factsheets/4018fact.pdf |publisher=United States Environmental Protection Agency |access-date=13 November 2012 |url-status=dead |archive-url=https://web.archive.org/web/20121024014940/http://www.epa.gov/oppsrrd1/REDs/factsheets/4018fact.pdf |archive-date=24 October 2012 }}</ref> Ground or crushed dried chili pods may be used in birdseed to deter rodents,<ref>{{cite journal | vauthors = Jensen PG, Curtis PD, Dunn JA, Austic RE, Richmond ME | title = Field evaluation of capsaicin as a rodent aversion agent for poultry feed | journal = Pest Management Science | volume = 59 | issue = 9 | pages = 1007–1015 | date = September 2003 | pmid = 12974352 | doi = 10.1002/ps.705 }}</ref> taking advantage of the insensitivity of birds to capsaicin. The Elephant Pepper Development Trust claims that using chili peppers as a barrier crop can be a sustainable means for rural African farmers to deter elephants from eating their crops.<ref>{{cite web |title=Human Elephant Conflict and Chilli Pepper |url=http://www.elephantpepper.org/human-elephant-conflict-chilli.php |publisher=Elephant Pepper |access-date=31 May 2019}}</ref>
It is common for people to experience pleasurable and even euphoriant effects from ingesting capsaicin. [[Folklore]] among self-described "[[wikt:chilihead|chilihead]]s" attributes this to pain-stimulated release of [[endorphins]], a different mechanism from the local receptor overload that makes capsaicin effective as a topical analgesic. In support of this theory, there is some evidence that the effect can be blocked by [[naloxone]] and other compounds that compete for receptor sites with endorphins and opiates.<ref>[http://www.liebertonline.com/doi/abs/10.1089/10755530260128032?cookieSet=1&journalCode=acm Mary Ann Liebert, Inc. - The Journal of Alternative and Complementary Medicine - 8(3):341<!-- Bot generated title -->]</ref>


An article published in the ''Journal of Environmental Science and Health Part B'' in 2006 states that "Although hot chili pepper extract is commonly used as a component of household and garden insect-repellent formulas, it is not clear that the capsaicinoid elements of the extract are responsible for its repellency."<ref name="pmid17090499">{{cite journal | vauthors = Antonious GF, Meyer JE, Snyder JC | title = Toxicity and repellency of hot pepper extracts to spider mite, Tetranychus urticae Koch | journal = Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes | volume = 41 | issue = 8 | pages = 1383–1391 | year = 2006 | pmid = 17090499 | doi = 10.1080/0360123060096419 | bibcode = 2006JESHB..41.1383A | s2cid = 19121573 }}</ref>
===Medical===
Capsaicin is used as an [[analgesic]] in topical [[ointment]]s, nasal sprays (Sinol-M), and [[dermal patch]]es to relieve [[pain]], typically in concentrations between 0.025% and 0.25%. It may be applied in cream form for the temporary relief of minor aches and pains of [[muscle]]s and joints associated with [[arthritis]], backache, strains and [[sprain]]s, often in compounds with other [[rubefacients]].<ref>[http://www.medicine.ox.ac.uk/bandolier/booth/painpag/Chronrev/Analges/CP063.html Topical capsaicin for pain relief<!-- Bot generated title -->]</ref> It is also used to reduce the symptoms of peripheral [[neuropathy]] such as post-herpetic [[neuralgia]] caused by [[shingles]].<ref>{{Cite journal|title= Which Treatment for Postherpetic Neuralgia? |publisher= PLoS Med |date=July 2005 |volume = 2 | issue = 7 |doi= 10.1371/journal.pmed.0020238|url= |journal= PLoS Medicine |pages= e238 }}</ref> In direct application the treatment area is typically numbed first with a topical [[anesthetic]]; capsaicin is then applied by a [[therapist]] wearing [[rubber glove]]s and a face mask. The capsaicin remains on the skin until the patient starts to feel the "heat", at which point it is promptly removed. Capsaicin is also available in large [[Capsicum plaster|bandage]]s (plasters) that can be applied to the back.


The first pesticide product using solely capsaicin as the active ingredient was registered with the U.S. Department of Agriculture in 1962.<ref name="EPA facts capsaicin"/>
Capsaicin creams are used to treat [[psoriasis]] as an effective way to reduce itching and inflammation.<ref>{{Cite journal|author = Glinski W, Glinska-Ferenz M, Pierozynska-Dubowska M. |title= Neurogenic inflammation induced by capsaicin in patients with psoriasis. |publisher= Acta Derm Venereol. |year=1991 |volume = 71 | issue = 1 | pages = 51–4|pmid = 1711752|url= |journal = Acta dermato-venereologica }}</ref><ref>{{Cite journal|doi = 10.1016/0190-9622(93)70208-B |author = Arnold WP, van de Kerkhof PC. |title= Topical capsaicin in pruritic psoriasis. |publisher= J Am Acad Dermatol. |date=September 1993 |volume = 29 | issue = 3 | pages = 438–42|pmid = 8021363|url= |journal = Journal of the American Academy of Dermatology }}</ref>


===Equestrian sports===
The mechanism by which capsaicin's analgesic and/or anti-inflammatory effects occurs is purportedly by mimicing a burning sensation; overwhelming the [[nerve]]s by the calcium influx, and thereby rendering the nerves unable to report pain for an extended period of time. With chronic exposure to capsaicin, [[neuron]]s are depleted of [[neurotransmitters]], leading to reduction in sensation of pain and blockade of [[neurogenic inflammation]]. If capsaicin is removed, the neurons recover.<ref>{{cite pmid|18307678}}</ref><ref>{{cite pmid|18635498}}</ref>{{Citation needed|date=April 2011}}
Capsaicin is a banned substance in [[Equestrianism|equestrian sports]] because of its hypersensitizing and pain-relieving properties.<ref name="BBC 20080821" /> At the show jumping events of the [[2008 Summer Olympics]], four horses tested positive for capsaicin, which resulted in disqualification.<ref name="BBC 20080821">{{Cite news| url=http://news.bbc.co.uk/sport2/hi/olympics/equestrian/7574220.stm | publisher=[[BBC News Online]] | title=Olympic horses fail drugs tests | date=21 August 2008 | access-date=1 April 2010}}</ref>


==Irritant effects==
Capsaicin selectively binds to a protein known as [[TRPV1]] that resides on the membranes of pain and heat-sensing neurons.<ref name="pmid9349813">{{Cite journal| author = Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D | title = The capsaicin receptor: a heat-activated ion channel in the pain pathway | journal = Nature | volume = 389 | issue = 6653 | pages = 816–24 |date=October 1997 | pmid = 9349813 | doi = 10.1038/39807 | url = }}</ref><ref name="The Lipid Chronicles">{{cite web|title=How Hot is Hot? A Burning Question About a Hot Condiment|url=http://www.samuelfurse.com/2012/01/how-hot-is-hot-a-burning-question-about-a-hot-condiment/|work=The Lipid Chronicles|accessdate=2012-01-21}}</ref> TRPV1 is a heat-activated calcium channel that opens between 37 and 45&nbsp;°C (98.6 and 113&nbsp;°F, respectively). When capsaicin binds to TRPV1, it causes the channel to open below 37&nbsp;°C ([[normal human body temperature]]), which is why capsaicin is linked to the sensation of heat. Prolonged activation of these neurons by capsaicin depletes presynaptic [[substance P]], one of the body's neurotransmitters for pain and heat. Neurons that do not contain TRPV1 are unaffected.<!--This reference has nothing to do with this effect. See talk. [http://www.sciam.com/article.cfm?articleID=674E972E-E7F2-99DF-39A3406D0D2B2A7C&chanID=sa007 Chili Pepper Cocktail Blunts Pain: Scientific American]-->
===Acute health effects===
Capsaicin is a strong irritant requiring proper protective goggles, respirators, and proper hazardous material-handling procedures. Capsaicin takes effect upon skin contact (irritant, sensitizer), eye contact (irritant), ingestion, and inhalation (lung irritant, lung sensitizer). The {{LD50}} in mice is 47.2&nbsp;mg/kg.<ref name="tox">{{cite web |url=http://www.sciencelab.com/xMSDS-Capsaicin_Natural-9923296 |title=Capsaicin Material Safety Data Sheet |access-date=13 July 2007 |publisher=sciencelab.com |year=2007 |format=PDF |archive-url=https://web.archive.org/web/20070929083820/http://www.sciencelab.com/xMSDS-Capsaicin_Natural-9923296 |archive-date=29 September 2007 |url-status=dead }}</ref><ref name="pmid17365137">{{cite journal | vauthors = Johnson W | title = Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin | journal = International Journal of Toxicology | volume = 26 | issue = Suppl 1 | pages = 3–106 | year = 2007 | pmid = 17365137 | doi = 10.1080/10915810601163939 | s2cid = 208154058 | doi-access = free}}</ref>


Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers.<ref>{{cite journal | vauthors = Krenzelok EP, Jacobsen TD | title = Plant exposures ... a national profile of the most common plant genera | journal = Veterinary and Human Toxicology | volume = 39 | issue = 4 | pages = 248–249 | date = August 1997 | pmid = 9251180}}</ref> They cause burning or stinging pain to the skin and, if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produces intense tearing, pain, [[conjunctivitis]], and [[blepharospasm]].<ref name="tox2">{{Cite book|title=Goldfrank's Toxicologic Emergencies | veditors = Goldfrank LR |page=1167 |publisher=McGraw-Hill |location=New York, New York|isbn=978-0-07-144310-4|date=23 March 2007 }}</ref>
Animal and human studies have demonstrated that the oral intake of capsaicin may increase the production of heat by the body for a short time.{{cn}}


===Treatment after exposure===
One study with human subjects indicates that capsaicin may be used to help regulate [[blood sugar level]]s by affecting [[carbohydrate]] breakdown after a meal.<ref>{{Cite journal|doi = 10.1079/BJN2003938 |author = Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. |title= Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects.|publisher= Br J Nutr. |date=September 2003 |volume = 90 | issue = 3 | pages = 651–59|pmid = 13129472|url= |journal = The British journal of nutrition }}</ref>
The primary treatment is removal of the offending substance. Plain water is ineffective at removing capsaicin.<ref name="tox" /> Capsaicin is soluble in alcohol, which can be used to clean contaminated items.<ref name="tox" />


When capsaicin is ingested, cold milk may be an effective way to relieve the burning sensation due to [[casein]]s in milk, and the water of milk acts as a [[surfactant]], allowing the capsaicin to form an [[emulsion]] with it.<ref>{{Cite web | vauthors = Senese F | date = 23 February 2018 |url= https://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml| work = General Chemistry Online | title = Fire and Spice| publisher = Department of Chemistry, Frostburg State University }}</ref>
Rodent studies have shown that capsicum may have some effectiveness against cancer. However, the [[American Cancer Society]] warns "available scientific research does not support claims for the effectiveness of capsicum or whole pepper supplements in preventing or curing cancer at this time".<ref name=acs>{{cite web |url=http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/herbsvitaminsandminerals/capsicum |title=Capsicum |date=2008-11-30 |publisher=[[Amrerican Cancer Society]] |accessdate=2014-04-10}}</ref> Other uses not supported by evidence are: "addiction, malaria, yellow fever, heart disease, stroke, weight loss, poor appetite, and sexual potency".<ref name=acs/>


===Weight loss and regain===
Capsaicin is the key ingredient in the experimental drug [[Discovery and development of TRPV1 antagonists#Current status|Adlea]], which is in (as of 2007) 'Phase 2 Trials' as a long-acting analgesic to treat post-surgical and osteoarthritic pain for weeks to months after a single injection to the site of pain.<ref>{{cite web|url=http://www.mail.com/Article.aspx?articlepath=APNews%5CTop%20Headlines%5C20071030%5CHealthBeat_Peppers___Pain_20071030.xml&cat=topheadlines&subcat=&pageid=1 |title=Doctors Test Hot Sauce For Pain Relief |accessdate=2007-10-30}}{{dead link|date=June 2011}}</ref> Moreover, the drug purportedly reduces pain caused by [[osteoarthritis]]<ref>{{Cite journal|author = Liana Fraenkel; Sidney T. Bogardus Jr; John Concato; Dick R. Wittink |title= Treatment Options in Knee Osteoarthritis: The Patient's Perspective |publisher= Arch Intern Med, |date=June 2004 |volume = 164 | pages = 1299–1304 |doi= |url= http://archinte.ama-assn.org/cgi/reprint/164/12/1299?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Capsaicin+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT |issue=12}}</ref>,joint and/or muscle pain from [[fibromyalgia]] and from other causes.
As of 2007, there was no evidence showing that weight loss is directly correlated with ingesting capsaicin. Well-designed [[clinical research]] had not been performed because the [[pungency]] of capsaicin in prescribed doses under research prevented subjects from complying in the study.<ref>{{cite journal | vauthors = Diepvens K, Westerterp KR, Westerterp-Plantenga MS | title = Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 292 | issue = 1 | pages = R77–R85 | date = January 2007 | pmid = 16840650 | doi = 10.1152/ajpregu.00832.2005 | s2cid = 7529851 | url = https://cris.maastrichtuniversity.nl/en/publications/d418019f-bac5-49bd-b3de-dfaf8f2c6736 }}</ref> A 2014 [[meta-analysis]] of further trials found weak evidence that consuming capsaicin before a meal might slightly reduce the amount of food consumed, and might drive food preference toward [[carbohydrate]]s.<ref>{{cite journal | vauthors = Whiting S, Derbyshire EJ, Tiwari B | title = Could capsaicinoids help to support weight management? A systematic review and meta-analysis of energy intake data | journal = Appetite | volume = 73 | pages = 183–188 | date = February 2014 | pmid = 24246368 | doi = 10.1016/j.appet.2013.11.005 | s2cid = 30252935 }}</ref>


===Non-lethal force===
===Peptic ulcer ===
One 2006 review concluded that capsaicin may relieve symptoms of a [[peptic ulcer]] rather than being a cause of it.<ref name="pmid16621751">{{cite journal | vauthors = Satyanarayana MN | title = Capsaicin and gastric ulcers | journal = Critical Reviews in Food Science and Nutrition | volume = 46 | issue = 4 | pages = 275–328 | date = 2006 | pmid = 16621751 | doi = 10.1080/1040-830491379236 | s2cid = 40023195 }}</ref>
Capsaicin is also the active ingredient in riot control and personal defense [[pepper spray]] chemical agents. When the spray comes in contact with [[Human skin|skin]], especially [[Human eye|eye]]s or [[mucous membrane]]s, it is very painful, and breathing small particles of it as it disperses can cause breathing difficulty, which serves to discourage assailants. Refer to the [[Scoville scale]] for a comparison of pepper spray to other sources of capsaicin.


===Pest deterrent===
===Death===
Ingestion of high quantities of capsaicin can be deadly,<ref>{{Cite web |url=https://health.clevelandclinic.org/health-risks-of-spicy-food |title=The Health Risks of Eating Extremely Spicy Foods |website=[[Cleveland Clinic]] |date=March 12, 2023}}</ref> particularly in people with heart problems.<ref>{{Cite web |url=https://apnews.com/article/paqui-spicy-chip-challenge-death-autopsy-f81c220c549ec497bcc626dec4fc2be4 |title=Teen died from eating a spicy chip as part of social media challenge, autopsy report concludes |date=2024-05-16 |website=[[AP News]]}}</ref> Even healthy young people can suffer adverse health effects like [[myocardial infarction]] after ingestion of capsaicin capsules.<ref>{{cite journal | vauthors = Sogut O, Kaya H, Gokdemir MT, Sezen Y | title = Acute myocardial infarction and coronary vasospasm associated with the ingestion of cayenne pepper pills in a 25-year-old male | journal = International Journal of Emergency Medicine | volume = 5 | pages = 5 | date = January 2012 | pmid = 22264348 | pmc = 3284873 | doi = 10.1186/1865-1380-5-5 | doi-access = free }}</ref>
Capsaicin is also used to deter pests, specifically mammalian pests. Targets of capsaicin repellants include voles, deer, rabbits, squirrels, insects, and attacking dogs.<ref name="EPA facts capsaicin">{{cite web|title=R.E.D. Facts for Capsaicin|url=http://www.epa.gov/oppsrrd1/REDs/factsheets/4018fact.pdf|publisher=United States Environmental Protection Agency|accessdate=2012-11-13}}</ref> Ground or crushed dried chili pods may be used in birdseed to deter squirrels,<ref>{{cite pmid|12974352}}</ref> taking advantage of the insensitivity of birds to capsaicin. The [[Elephant Pepper Development Trust]] claims the use of chili peppers to improve crop security for rural African communities{{cn}}. Noteably, an article published in the Journal of Enviromental Science and Health in 2006 states that "Although hot chili pepper extract is commonly used as a component of household and garden insect-repellent formulas, it is not clear that the capsaicinoid elements of the extract are responsible for its repellency."<ref name="pmid17090499">{{Cite journal|author=Antonious GF, Meyer JE, Snyder JC |title=Toxicity and repellency of hot pepper extracts to spider mite, Tetranychus urticae Koch |journal=J Environ Sci Health B |volume=41 |issue=8 |pages=1383–91 |year=2006 |pmid=17090499 |doi=10.1080/0360123060096419 |url=}}</ref>


==Mechanism of action==
The first pesticide product using solely capsaicin as the active ingredient was registered with the U.S. Department of Agriculture in 1962.<ref name="EPA facts capsaicin">41</ref>
The burning and painful sensations associated with capsaicin result from "defunctionalization" of [[nociceptor]] nerve fibers by causing a topical [[Hypersensitivity|hypersensitivity reaction]] in the skin.<ref name=pubchem/><ref name="drugbank">{{cite web |title=Capsaicin |url=https://go.drugbank.com/drugs/DB06774 |publisher=DrugBank |access-date=1 June 2023 |date=4 January 2023}}</ref> As a member of the [[vanilloid]] family, capsaicin binds to a [[transmembrane receptor|receptor]] on nociceptor fibers called the [[vanilloid receptor subtype 1]] (TRPV1).<ref name=drugbank/><ref>{{Cite journal|vauthors=Story GM, Crus-Orengo L | title = Feel the burn| journal = American Scientist| volume = 95| issue = 4| pages = 326–333| date = July–August 2007| doi = 10.1511/2007.66.326}}</ref><ref>{{cite journal | vauthors = Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D | title = The capsaicin receptor: a heat-activated ion channel in the pain pathway | journal = Nature | volume = 389 | issue = 6653 | pages = 816–824 | date = October 1997 | pmid = 9349813 | doi = 10.1038/39807 | s2cid = 7970319 | bibcode = 1997Natur.389..816C | doi-access = free }}</ref> TRPV1, which can also be stimulated with heat, protons and physical abrasion, permits [[cation]]s to pass through the [[cell membrane]] when activated.<ref name=drugbank/> The resulting [[depolarization]] of the neuron stimulates it to send [[action potential|impulses]] to the brain.<ref name=drugbank/> By binding to TRPV1 receptors, capsaicin produces similar sensations to those of excessive heat or abrasive damage, such as warming, tingling, itching, or stinging, explaining why capsaicin is described as an irritant on the skin and eyes or by ingestion.<ref name=drugbank/>
There are multiple manufacturers of a capsaicin-based gel product claiming to be a [[Feral pigeon|feral-pigeon]] (''Columba livia'') deterrent from specific roosting and loafing areas. Some of these products have an EPA label and NSF approval{{cn}}.


Clarifying the mechanisms of capsaicin effects on skin nociceptors was part of awarding the 2021 [[List of Nobel laureates in Physiology or Medicine|Nobel Prize in Physiology or Medicine]], as it led to the discovery of skin sensors for temperature and touch, and identification of the single [[gene]] causing sensitivity to capsaicin.<ref>{{Cite web|url=https://www.nobelprize.org/prizes/medicine/2021/summary/|title=The Nobel Prize in Physiology or Medicine 2021|publisher=Nobel Prize Outreach|accessdate=1 June 2023}}</ref><ref>{{Cite news|url=https://www.nytimes.com/2021/10/04/health/nobel-prize-medicine-physiology-temperature-touch.html|title=Nobel Prize Awarded to Scientists for Research About Temperature and Touch| vauthors = Santora M, Engelbrecht C |newspaper=The New York Times|date=4 October 2021}}</ref>
===Equestrian sports===
Capsaicin is a banned substance in [[Equestrianism|equestrian sports]] because of its hypersensitizing and pain-relieving properties. At the show jumping events of the [[2008 Summer Olympics]], four horses tested positive for the substance, which resulted in disqualification.<ref>{{Cite news| url=http://news.bbc.co.uk/sport1/hi/olympics/equestrian/7574220.stm | work=BBC News | title=Olympic horses fail drugs tests | date=2008-08-21 | accessdate=2010-04-01}}</ref>


==History==
==Mechanism of action==
The compound was first extracted in impure form in 1816 by [[Christian Friedrich Bucholz]] (1770–1818).<ref>
The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory [[neuron]]s. Capsaicin, as a member of the [[vanilloid]] family, binds to a [[transmembrane receptor|receptor]] called the [[vanilloid receptor subtype 1]] (TRPV1).<ref>
{{cite book| vauthors = Bucholz CF |date=1816|chapter=Chemische Untersuchung der trockenen reifen spanischen Pfeffers|trans-chapter=Chemical investigation of dry, ripe Spanish peppers|title=Almanach oder Taschenbuch für Scheidekünstler und Apotheker|location=Weimar|trans-title=Almanac or Pocketbook for Analysts and Apothecaries|volume=37|pages=1–30}} [Note: Christian Friedrich Bucholz's surname has been variously spelled as "Bucholz", "Bucholtz", or "Buchholz".]
{{Cite journal
</ref>{{efn|1=History of early research on capsaicin:
|author=Story GM, Crus-Orengo L
* {{cite book| vauthors = Felter HW, Lloyd JU |title=King's American Dispensatory|location=Cincinnati, Ohio|publisher=Ohio Valley Co.|date=1898|volume=1|page=435|url=http://www.henriettesherbal.com/eclectic/kings/capsicum.html}}
|title=Feel the burn
* {{cite thesis| vauthors = Du Mez AG |title=A century of the United States pharmocopoeia 1820–1920. I. The galenical oleoresins|type=PhD|publisher=University of Wisconsin|date=1917|pages=111–132|url=https://archive.org/stream/centuryofuniteds00dumerich/centuryofuniteds00dumerich_djvu.txt}}
|journal=American Scientist
* The results of Bucholz's and Braconnot's analyses of ''Capsicum annuum'' appear in: {{cite book| vauthors = Pereira J |title=The Elements of Materia Medica and Therapeutics|edition=3rd US|location=Philadelphia, Pennsylvania|publisher=Blanchard and Lea|date=1854|volume=2|url=https://books.google.com/books?id=IrXszQ77xhYC&pg=PA506|page=506}}
|volume=95
* Biographical information about Christian Friedrich Bucholz is available in: {{cite book| veditors = Rose HJ, Wright T |title=A New General Biographical Dictionary|location=London, England | publisher = T. Fellowes |date=1857|volume=5|url=https://books.google.com/books?id=nNRySUejNcYC&pg=PA186|page=186 | vauthors = Rose HJ }}
|issue=4
* Biographical information about C. F. Bucholz is also available (in German) online at: [http://de.wikisource.org/wiki/ADB:Bucholtz,_Christian_Friedrich Allgemeine Deutsche Biographie].
|pages=326–333
* Some other early investigators who also extracted the active component of peppers:
|date=July–August 2007
:# {{cite journal | vauthors = Maurach B | date = 1816 | title = Pharmaceutisch-chemische Untersuchung des spanischen Pfeffers | trans-title = Pharmaceutical-chemical investigation of Spanish peppers | journal = Berlinisches Jahrbuch für die Pharmacie | language = de | volume = 17 | pages = 63–73 }} Abstracts of Maurach's paper appear in: (i) ''Repertorium für die Pharmacie'', vol. 6, [https://books.google.com/books?id=euo8AAAAcAAJ&pg=PA117 page 117-119] (1819); (ii) ''Allgemeine Literatur-Zeitung'', vol. 4, no. 18, [https://books.google.com/books?id=rRo4AAAAMAAJ&pg=RA2-PA20-IA2 page 146] (February 1821); (iii) "Spanischer oder indischer Pfeffer", ''System der Materia medica'' ..., vol. 6, [https://books.google.com/books?id=jgA9AAAAcAAJ&pg=PA381 pages 381–386] (1821) (this reference also contains an abstract of Bucholz's analysis of peppers).
|doi=10.1511/2007.66.326}}
:# [[Henri Braconnot]], French chemist {{cite journal | vauthors = Braconnot H | date = 1817 | title = Examen chemique du Piment, de son principe âcre, et de celui des plantes de la famille des renonculacées | trans-title = Chemical investigation of the chili pepper, of its pungent principle [constituent, component], and of that of plants of the family ''Ranunculus'' | journal = Annales de Chimie et de Physique | language = fr | volume = 6 | pages = [https://books.google.com/books?id=b2luVw2yngoC&pg=PA122 122- 131] }}
</ref> First cloned in 1997, TRPV1 is an [[ion channel]]-type receptor. TRPV1, which can also be stimulated with heat, protons and physical abrasion, permits [[cation]]s to pass through the [[cell membrane]] and into the cell when activated. The resulting [[depolarization]] of the neuron stimulates it to [[action potential|signal]] the brain. By binding to the TRPV1 receptor, the capsaicin molecule produces similar sensations to those of excessive heat or abrasive damage, explaining why the spiciness of capsaicin is described as a burning sensation.
:# [[Johann Georg Forchhammer]], Danish geologist {{cite journal | vauthors = Oersted HC | date = 1820 | title = Sur la découverte de deux nouveaux alcalis végétaux | trans-title = On the discovery of two new plant alkalis | journal = Journal de physique, de chemie, d'histoire naturelle et des arts | trans-journal = Journal of Physics, Chemistry, Natural History and the Arts | language = fr | volume = 90 | pages = [https://books.google.com/books?id=E-YPAAAAQAAJ&pg=PA173 173–174] }}
:# Ernst Witting, German apothecary {{cite journal | vauthors = Witting E | date = 1822 | title = Considerations sur les bases vegetales en general, sous le point de vue pharmaceutique et descriptif de deux substances, la capsicine et la nicotianine | trans-title = Thoughts on the plant bases in general from a pharmaceutical viewpoint, and description of two substances, capsicin and nicotine | language = fr | journal = Beiträge für die Pharmaceutische und Analytische Chemie | trans-journal = Contributions to Pharmaceutical and Analytical Chemistry | volume = 3 | pages = 43}} He called it "capsicin", after the genus ''[[Capsicum]]'' from which it was extracted. John Clough Thresh (1850–1932), who had isolated capsaicin in almost pure form,<ref>In a series of articles, J. C. Thresh obtained capsaicin in almost pure form:
*{{cite journal | vauthors = Thresh JC | date = 1876 | title = Isolation of capsaicin | journal = The Pharmaceutical Journal and Transactions |series=3rd Series | volume = 6 | pages = 941–947 }}
*{{cite journal | vauthors = Thresh JC | date = 8 July 1876 | title = Capsaicin, the active principle in ''Capsicum'' fruits | journal = The Pharmaceutical Journal and Transactions |series=3rd Series | volume = 7 | issue = 315 | pages = 21| doi = <!-- --> | bibcode = <!-- --> }} [Note: This article is summarized in: {{cite journal | title = Capsaicin, the active principle in ''Capsicum'' fruits | journal = The Analyst | volume = 1 | issue = 8 | url = http://pubs.rsc.org/en/Content/ArticleLanding/1876/AN/an876010148b | pages = 148–149 | date = 1876 | doi = 10.1039/an876010148b | bibcode = 1876Ana.....1..148. }}
*''Year Book of Pharmacy…'' (1876), pages 250 and 543;
*{{cite journal | vauthors = Thresh JC | date = 1877 | title = Note on Capsaicin | url = https://archive.org/stream/yearbookofpharma1877londuoft/yearbookofpharma1877londuoft_djvu.txt | journal = Year Book of Pharmacy | pages = 24–25 }}
*{{cite journal | vauthors = Thresh JC | date = 1877 | title = Report on the active principle of Cayenne pepper | journal = Year Book of Pharmacy | pages = 485–488 }}</ref><ref>Obituary notice of J. C. Thresh: {{cite journal | vauthors = | title = John Clough Thresh, M.D., D.Sc., D.P.H | journal = British Medical Journal | volume = 1 | issue = 3726 | pages = 1057–1058 | date = June 1932 | pmid = 20776886 | pmc = 2521090 | doi = 10.1136/bmj.1.3726.1057-c }}</ref> gave it the name "capsaicin" in 1876.<ref>{{cite book | vauthors = King J, Felter HW, Lloys JU | date = 1905 | title = A King's American Dispensatory. | publisher = Eclectic Medical Publications | isbn = 1888483024}})</ref> Karl Micko isolated capsaicin in its pure form in 1898.<ref>{{cite journal | vauthors = Micko K | year = 1898 | url = https://books.google.com/books?id=8SbOAAAAMAAJ&pg=PA818|title= Zur Kenntniss des Capsaïcins |trans-title= On our knowledge of capsaicin|journal= Zeitschrift für Untersuchung der Nahrungs- und Genussmittel |volume= 1| issue = 12 |pages=818–829|language=de | doi=10.1007/bf02529190}}</ref><ref>{{cite journal| vauthors = Micko K |year=1899|url=https://books.google.com/books?id=0zwDAAAAYAAJ&pg=PA411|title= Über den wirksamen Bestandtheil des Cayennespfeffers|trans-title=On the active component of Cayenne pepper | journal = Zeitschrift für Untersuchung der Nahrungs- und Genussmittel | volume = 2 | issue = 5| pages = 411–412 |language=de | doi=10.1007/bf02529197}}</ref> Capsaicin's chemical composition was first determined in 1919 by E. K. Nelson, who also partially elucidated capsaicin's chemical structure.<ref>{{cite journal | vauthors = Nelson EK | year = 1919 | title = The constitution of capsaicin, the pungent principle of capsicum | url = https://books.google.com/books?id=Ra4UAAAAYAAJ&pg=PA1115 | journal = Journal of the American Chemical Society | volume = 41 | issue = 7| pages = 1115–1121 | doi = 10.1021/ja02228a011 | bibcode = 1919JAChS..41.1115N }}</ref> Capsaicin was first synthesized in 1930 by Ernst Spath and Stephen F. Darling.<ref>{{cite journal | vauthors = Späth E, Darling SF | year = 1930 | title = Synthese des Capsaicins | journal = Chem. Ber. | volume = 63B | issue = 3| pages = 737–743 | doi = 10.1002/cber.19300630331 }}</ref> In 1961, similar substances were isolated from [[chili pepper]]s by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.<ref>{{cite journal | vauthors = Kosuge S, Inagaki Y, Okumura H | date = 1961 | title = Studies on the pungent principles of red pepper. Part VIII. On the chemical constitutions of the pungent principles. | journal = Nippon Nogeikagaku Kaishi | trans-journal = Journal of the Agricultural Chemical Society of Japan | language = ja | volume = 35 | pages = 923–927 | doi = 10.1271/nogeikagaku1924.35.10_923 | url = https://www.jstage.jst.go.jp/article/nskkk1962/14/9/14_9_407/_pdf | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kosuge S, Inagaki Y | date = 1962 | title = Studies on the pungent principles of red pepper. Part XI. Determination and contents of the two pungent principles. | journal = Nippon Nogeikagaku Kaishi | trans-journal = Journal of the Agricultural Chemical Society of Japan | language = ja | volume = 36 | page = 251 | doi = 10.1271/nogeikagaku1924.36.251 | doi-access = free }}</ref>
}}
In 1873 German pharmacologist [[Rudolf Buchheim]]<ref>{{cite journal | vauthors = Buchheim R | date = 1873 | title = Über die 'scharfen' Stoffe | trans-title = On the "hot" substance | journal = Archiv der Heilkunde | trans-journal = Archive of Medicine | volume = 14 }}</ref><ref>{{cite journal | vauthors = Buchheim R | date = 1872 | title = Fructus Capsici | journal = Vierteljahresschrift für praktische Pharmazie | trans-journal = Quarterly Journal for Practical Pharmacy | volume = 4 | page = 507ff | language = de }}</ref><ref>{{cite journal | vauthors = Buchheim R | title = Fructus Capsici. | journal = Proceedings of the American Pharmaceutical Association | date = 1873 | volume = 22 | pages = 106 }}</ref> (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes<ref>{{cite journal | vauthors = Hőgyes E | title = Adatok a Capsicum annuum (paprika) alkatrészeinek élettani hatásához. | trans-title = Data on the physiological effects of the pepper (''Capsicum annuum'') | language = hu | journal = Orvos-természettudumányi társulatot Értesítője | trans-journal = ulletin of the Medical Science Association | date = 1877 }}</ref><ref>{{cite journal | vauthors = Högyes A | title = Mittheilungen aus dem Institute für allgemeine Pathologie und Pharmakologie an der Universität zu Klausenburg. | journal = Archiv für experimentelle Pathologie und Pharmakologie | date = June 1878 | volume = 9 | issue = 1–2 | pages = 117–130 | doi = 10.1007/BF02125956 | s2cid = 32414315 | url = https://zenodo.org/record/2330422 }}</ref> stated that "capsicol" (partially purified capsaicin<ref>{{cite book | vauthors = Flückiger FA | title = Pharmakognosie des Pflanzenreiches | location = Berlin, Germany | publisher = Gaertner's Verlagsbuchhandlung | date = 1891 }}</ref>) caused the burning feeling when in contact with [[mucous membrane]]s and increased secretion of [[gastric acid]].


==Capsaicinoids==
Early research showed capsaicin to evoke a strikingly long-onset current in comparison to other chemical agonists, suggesting the involvement of a significant rate-limiting factor.<ref>Geppetti, Pierangelo & Holzer, Peter (1996). Neurogenic Inflammation. CRC Press, 1996.</ref> Subsequent to this, the TRPV1 [[ion channel]] has been shown to be a member of the superfamily of [[transient receptor potential|TRP]] [[ion channels]], and as such is now referred to as {{Gene|TRPV1}}. There are a number of different [[transient receptor potential|TRP]] [[ion channels]] that have been shown to be sensitive to different ranges of temperature and probably are responsible for our range of temperature sensation. Thus, capsaicin does not actually cause a [[chemical burn]], or indeed any direct tissue damage at all, when chili peppers are the source of exposure. The inflammation resulting from exposure to capsaicin is believed to be the result of the body's reaction to nerve excitement. For example, the mode of action of capsaicin in inducing bronchoconstriction is thought to involve stimulation of [[C fibers]] <ref>Fuller, R. W., Dixon, C. M. S. & Barnes, P. J. (1985). Bronchoconstrictor response to inhaled capsaicin in humans" ''J. Appl. Physiol'' 58, 1080–1084.
<!-- The article "Scoville scale" links here. -->
PubMed, CAS, Web of Science® Times Cited: 174</ref> culminating in the release of neuropeptides. In essence, the body inflames tissues as if it has undergone a burn or abrasion and the resulting inflammation can cause tissue damage in cases of extreme exposure, as is the case for many substances that cause the body to trigger an inflammatory response.
The most commonly occurring capsaicinoids are capsaicin (69%), dihydrocapsaicin (22%), nordihydrocapsaicin (7%), homocapsaicin (1%), and homodihydrocapsaicin (1%).<ref>{{cite journal | vauthors = Bennett DJ, Kirby GW | year = 1968 |title = Constitution and biosynthesis of capsaicin| journal = J. Chem. Soc. C | pages = 442 | doi = 10.1039/j39680000442 }}</ref>


Capsaicin and dihydrocapsaicin (both 16.0 million [[Scoville scale|SHU]]) are the most [[Pungency|pungent]] capsaicinoids. Nordihydrocapsaicin (9.1 million SHU), homocapsaicin and homodihydrocapsaicin (both 8.6 million SHU) are about half as hot.<ref name=pmid2039598/>
==Toxicity==


There are six natural capsaicinoids (table below). Although [[nonivamide|vanillylamide of n-nonanoic acid]] (Nonivamide, VNA, also PAVA) is produced synthetically for most applications, it does occur naturally in ''Capsicum'' species.<ref>{{cite journal | vauthors = Constant HL, Cordell GA, West DP |title = Nonivamide, a Constituent of ''Capsicum'' oleoresin |journal = Natural Products | date = April 1996 | volume = 59 | issue = 4 | pages = 425–426 | doi = 10.1021/np9600816}}</ref>
===Acute health effects===
Capsaicin is a highly irritant material requiring proper protective goggles, respirators, and proper hazardous material-handling procedures. Capsaicin takes effect upon skin contact (irritant, sensitizer), eye contact (irritant), ingestion, and inhalation (lung irritant, lung sensitizer). The {{LD50}} in mice is 47.2&nbsp;mg/kg.<ref name="tox">{{cite web|url=http://www.sciencelab.com/xMSDS-Capsaicin_Natural-9923296 |title=Capsaicin Material Safety Data Sheet |accessdate=2007-07-13 |publisher=sciencelab.com |year=2007 |format=PDF}}</ref><ref name="pmid17365137">{{Cite journal|author= Johnson, Wilbur|title=Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin |journal=Int. J. Toxicol. |volume=26 Suppl 1 |issue= |pages=3–106 |year=2007 |pmid=17365137 |doi=10.1080/10915810601163939 |url=}}</ref>


{| class="wikitable sortable"
Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers.{{Citation needed|date=May 2013}} They cause burning or stinging pain to the skin and, if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produces intense tearing, pain, [[conjunctivitis]], and [[blepharospasm]].<ref name="tox2">{{Cite book|title=Goldfrank's Toxicologic Emergencies |last=Goldfrank |first=L R. (ed.) |page=1167 |publisher=McGraw-Hill |location=New York, New York|isbn=0-07-144310-X}}</ref>
|-
! Capsaicinoid name
! {{abbr|Abbrev.|Abbreviation}}
! Typical <br />relative <br />amount
! [[Scoville scale|Scoville]] <br/>heat units
! class="unsortable" | Chemical structure
|-
| Capsaicin || CPS
|| 69% || 16,000,000
| [[File:Kapsaicyna.svg|x64px|Chemical structure of capsaicin]]
|-
| [[Dihydrocapsaicin]] || DHC || 22% || 16,000,000
| [[File:Dihydrocapsaicin.svg|x64px|Chemical structure of dihydrocapsaicin]]
|-
| [[Nordihydrocapsaicin]] || NDHC || 7% || 9,100,000
| [[File:Nordihydrocapsaicin chemical structure.png|x64px|Chemical structure of nordihydrocapsaicin]]
|-
| [[Homocapsaicin]] || HC || 1% || 8,600,000
| [[File:Homocapsaicin.svg|x64px|Chemical structure of homocapsaicin]]
|-
| [[Homodihydrocapsaicin]] || HDHC || 1% || 8,600,000
| [[File:Homodihydrocapsaicin.svg|x64px|Chemical structure of homodihydrocapsaicin]]
|-
| [[Nonivamide]] || PAVA || || 9,200,000
| [[File:Nonivamide.svg|x64px|Chemical structure of nonivamide]]
|}


==Biosynthesis==
When used for weight loss in capsules, there has been a report of heart attack; this was thought to be due to excess sympathetic output.<ref>Sayin MR, et al. A case of acute myocardial infarction due to the use of cayenne pepper pills. Wiener Klinische Wochenschrift-The Central European Journal of Medicine (2012) 124:285-287</ref>
[[File:BhutJolokia09 Asit.jpg|thumb|Chili peppers]]
[[Image:Vanillamine biosynthesis.gif|thumb|Vanillamine is a product of the phenylpropanoid pathway.]]
[[Image:8-methyl-6-nonenoyl biosynthesis.gif|thumb|Valine enters the branched fatty acid pathway to produce 8-methyl-6-nonenoyl-CoA.]]
[[Image:Condensation to capsaicin.gif|thumb|Capsaicin synthase condenses vanillamine and 8-methyl-6-nonenoyl-CoA to produce capsaicin.]]


===Treatment after exposure===
=== History ===
The general biosynthetic pathway of capsaicin and other capsaicinoids was elucidated in the 1960s by Bennett and Kirby, and Leete and Louden. Radiolabeling studies identified phenylalanine and valine as the precursors to capsaicin.<ref>Bennett DJ, Kirby GW (1968) Constitution and biosynthesis of capsaicin. J Chem Soc C 4:442–446</ref><ref name="Leete, E. 1968"/> Enzymes of the [[phenylpropanoid]] pathway, phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), caffeic acid ''O''-methyltransferase (COMT) and their function in capsaicinoid biosynthesis were identified later by Fujiwake et al.,<ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Intracellular distributions of enzymes and intermediates involved in biosynthesis of capsaicin and its analogues in Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = November 1982 | volume = 46 | issue = 11 | pages = 2685–2689 | doi = 10.1080/00021369.1982.10865495 }}</ref><ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Capsaicinoid formation in the protoplast from the placenta of Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = October 1982 | volume = 46 | issue = 10 | pages = 2591–2592 | doi = 10.1080/00021369.1982.10865477 }}</ref> and Sukrasno and Yeoman.<ref>{{cite journal | vauthors = Sukrasno N, Yeoman MM | year = 1993 | title = Phenylpropanoid metabolism during growth and development of ''Capsicum frutescens'' fruits | journal = Phytochemistry | volume = 32 | issue = 4| pages = 839–844 | doi=10.1016/0031-9422(93)85217-f| bibcode = 1993PChem..32..839S }}</ref> Suzuki et al. are responsible for identifying leucine as another precursor to the branched-chain [[Fatty acid synthesis|fatty acid pathway]].<ref>{{cite journal | vauthors = Suzuki T, Kawada T, Iwai K | year = 1981 | title = Formation and metabolism of pungent principle of ''Capsicum'' fruits. 9. Biosynthesis of acyl moieties of capsaicin and its analogs from valine and leucine in ''Capsicum'' fruits | journal = Plant & Cell Physiology | volume = 22 | pages = 23–32 | doi = 10.1093/oxfordjournals.pcp.a076142 }}</ref> It was discovered in 1999 that pungency of chili peppers is related to higher transcription levels of key enzymes of the phenylpropanoid pathway, phenylalanine ammonia lyase, cinnamate 4-hydroxylase, caffeic acid ''O''-methyltransferase. Similar studies showed high transcription levels in the placenta of chili peppers with high pungency of genes responsible for branched-chain fatty acid pathway.<ref>{{cite journal | vauthors = Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O'Connell MA | year = 1999 | title = Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent ''Capsicum'' spp | journal = Plant Sci | volume = 148 | issue = 1 | pages = 47–57 | doi = 10.1016/s0168-9452(99)00118-1 | bibcode = 1999PlnSc.148...47C | s2cid = 86735106 }}</ref>
The primary treatment is removal from exposure. Contaminated clothing should be removed and placed in airtight bags to prevent secondary exposure.

===Biosynthetic pathway===
Plants exclusively of the genus ''[[Capsicum]]'' produce capsaicinoids, which are [[alkaloid]]s.<ref>{{cite journal|vauthors=Nelson EK, Dawson LE|title=Constitution of capsaicin, the pungent principle of ''Capsicum''. III|journal=J Am Chem Soc|date=1923|volume=45|issue=9|pages=2179–2181|doi=10.1021/ja01662a023|bibcode=1923JAChS..45.2179N }}</ref> Capsaicin is believed to be synthesized in the [[Locule|interlocular]] [[septum#Botany|septum]] of chili peppers and depends on the gene ''AT3'', which resides at the ''pun1'' [[Locus (genetics)|locus]], and which encodes a putative [[acyltransferase]].<ref>{{cite journal | vauthors = Stewart C, Kang BC, Liu K, Mazourek M, Moore SL, Yoo EY, Kim BD, Paran I, Jahn MM | title = The Pun1 gene for pungency in pepper encodes a putative acyltransferase | journal = The Plant Journal | volume = 42 | issue = 5 | pages = 675–688 | date = June 2005 | pmid = 15918882 | doi = 10.1111/j.1365-313X.2005.02410.x | title-link = doi | doi-access = free }}</ref>

Biosynthesis of the capsaicinoids occurs in the glands of the pepper fruit where capsaicin synthase condenses [[vanillylamine]] from the [[phenylpropanoid]] pathway with an acyl-CoA moiety produced by the branched-chain [[Fatty acid synthesis|fatty acid pathway]].<ref name="Leete, E. 1968">{{cite journal | vauthors = Leete E, Louden MC | title = Biosynthesis of capsaicin and dihydrocapsaicin in Capsicum frutescens | journal = Journal of the American Chemical Society | volume = 90 | issue = 24 | pages = 6837–6841 | date = November 1968 | pmid = 5687710 | doi = 10.1021/ja01026a049 | bibcode = 1968JAChS..90.6837L }}</ref><ref name="Bennett, D.J. 1968">{{cite journal | vauthors = Bennett DJ, Kirby GW | year = 1968 | title = Constitution and biosynthesis of capsaicin | journal = J. Chem. Soc. C | volume = 1968 | pages = 442–446 | doi = 10.1039/j39680000442 }}</ref><ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Oka S, Iwai K | year = 1980 | title = Enzymatic formation of capsaicinoid from vanillylamine and iso-type fatty acids by cell-free extracts of ''Capsicum annuum'' var. ''annuum'' cv. Karayatsubusa | journal = Agricultural and Biological Chemistry | volume = 44 | issue = 12| pages = 2907–2912 | doi=10.1271/bbb1961.44.2907| doi-access = free | title-link=doi }}</ref><ref>{{cite book | vauthors = Guzman I, Bosland PW, O'Connell MA | chapter = Chapter 8: Heat, Color, and Flavor Compounds in ''Capsicum'' Fruit | veditors = Gang DR | title = Recent Advances in Phytochemistry 41: The Biological Activity of Phytochemicals | location = New York, New York | publisher = Springer | date = 2011 | chapter-url = https://books.google.com/books?id=--nQIHiE3QwC&pg=PA117 | pages = 117–118 | isbn = 9781441972996 }}</ref>


Capsaicin is the most abundant capsaicinoid found in the genus ''[[Capsicum]]'', but at least ten other capsaicinoid variants exist.<ref>{{cite journal | vauthors = Kozukue N, Han JS, Kozukue E, Lee SJ, Kim JA, Lee KR, Levin CE, Friedman M | title = Analysis of eight capsaicinoids in peppers and pepper-containing foods by high-performance liquid chromatography and liquid chromatography-mass spectrometry | journal = Journal of Agricultural and Food Chemistry | volume = 53 | issue = 23 | pages = 9172–9181 | date = November 2005 | pmid = 16277419 | doi = 10.1021/jf050469j }}</ref> Phenylalanine supplies the precursor to the [[phenylpropanoid pathway]] while leucine or valine provide the precursor for the branched-chain fatty acid pathway.<ref name="Leete, E. 1968"/><ref name="Bennett, D.J. 1968"/> To produce capsaicin, 8-methyl-6-nonenoyl-CoA is produced by the branched-chain fatty acid pathway and condensed with vanillylamine. Other capsaicinoids are produced by the condensation of vanillylamine with various acyl-CoA products from the branched-chain fatty acid pathway, which is capable of producing a variety of acyl-CoA moieties of different chain length and degrees of unsaturation.<ref>{{cite journal | vauthors = Thiele R, Mueller-Seitz E, Petz M | title = Chili pepper fruits: presumed precursors of fatty acids characteristic for capsaicinoids | journal = Journal of Agricultural and Food Chemistry | volume = 56 | issue = 11 | pages = 4219–4224 | date = June 2008 | pmid = 18489121 | doi = 10.1021/jf073420h | bibcode = 2008JAFC...56.4219T }}</ref> All condensation reactions between the products of the phenylpropanoid and branched-chain fatty acid pathway are mediated by capsaicin synthase to produce the final capsaicinoid product.<ref name="Leete, E. 1968"/><ref name="Bennett, D.J. 1968"/>
For external exposure, bathing the mucous membrane surfaces that have contacted capsaicin with oily compounds such as [[vegetable oil]], [[Mineral oil|paraffin oil]], [[petroleum jelly]] ([[Vaseline]]), [[cream (pharmaceutical)|creams]], or [[polyethylene glycol]] is the most effective way to attenuate the associated discomfort;{{Citation needed|date=January 2010}} since oil and capsaicin are both hydrophobic hydrocarbons the capsaicin that has not already been absorbed into tissues will be picked up into solution and easily removed. Capsaicin can also be washed off the skin using [[soap]], [[shampoo]], or other [[detergent]]s. Plain water is ineffective at removing capsaicin,<ref name="tox" /> as are [[bleach]], [[sodium metabisulfite]] and topical [[antacid]] suspensions.{{Citation needed|date=January 2010}} Capsaicin is soluble in [[alcohol]], which can be used to clean contaminated items.<ref name="tox" />


== Evolution ==
When capsaicin is ingested, cold [[milk]] is an effective way to relieve the burning sensation (due to [[casein]]s having a [[detergent]] effect on capsaicin<ref>[http://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml General Chemistry Online: Fire and Spice<!-- Bot generated title -->]</ref>); and room-temperature sugar solution (10%) at {{convert|20|°C|°F}} is almost as effective.<ref>Temporal effectiveness of mouth-rinsing on capsaicin mouth-burn. Christina Wu Nasrawia and Rose Marie Pangborn. http://dx.doi.org/10.1016/0031-9384(90)90067-E</ref> The cooling sensation may, however, only be temporary, and drinking any beverage will enhance the burning sensation{{Citation needed|date=May 2012}} by spreading the capsaicin throughout the mouth and maximizing receptors' exposure to it, making bread or white rice a better alternative. The burning sensation will slowly fade away over several hours if no actions are taken.
The ''Capsicum'' genus split from ''Solanaceae'' 19.6 million years ago, 5.4 million years after the appearance of ''Solanaceae'', and is native only to the Americas.<ref>{{Cite journal | vauthors = Yang HJ, Chung KR, Kwon DY |date=2017-09-01 |title=DNA sequence analysis tells the truth of the origin, propagation, and evolution of chili (red pepper) |journal=Journal of Ethnic Foods |language=en |volume=4 |issue=3 |pages=154–162 |doi=10.1016/j.jef.2017.08.010 |s2cid=164335348 |issn=2352-6181|doi-access=free }}</ref> Chilies only started to quickly evolve in the past 2 million years into markedly different species. This evolution can be partially attributed to a key compound found in peppers, 8-methyl-N-vanillyl-6-nonenamide, otherwise known as capsaicin. Capsaicin evolved similarly across species of chilies that produce capsaicin. Its evolution over the course of centuries is due to [[genetic drift]] and [[natural selection]], across the genus ''[[Capsicum]]''. Despite the fact that chilies within the ''Capsicum'' genus are found in diverse environments, the capsaicin found within them all exhibit similar properties that serve as defensive and adaptive features. Capsaicin evolved to preserve the [[Fitness (biology)|fitness]] of peppers against fungi infections, insects, and [[Seed predation|granivorous]] mammals.<ref>{{cite journal | vauthors = Tewksbury JJ, Reagan KM, Machnicki NJ, Carlo TA, Haak DC, Peñaloza AL, Levey DJ | title = Evolutionary ecology of pungency in wild chilies | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 33 | pages = 11808–11811 | date = August 2008 | pmid = 18695236 | pmc = 2575311 | doi = 10.1073/pnas.0802691105 | bibcode = 2008PNAS..10511808T | doi-access = free }}</ref>


=== Antifungal properties ===
Burning and pain symptoms can also be relieved by cooling, such as from ice, cold water, cold bottles, cold surfaces, or a flow of air from wind or a fan.{{Citation needed|date=January 2010}} In severe cases, eye burn might be treated symptomatically with topical ophthalmic [[anesthetic]]s, and mucous membrane burn with [[lidocaine]] gel. The gel from the aloe plant has also been shown to be very effective.{{Citation needed|date=January 2013}} Capsaicin-induced [[asthma]] might be treated with nebulized [[bronchodilator]]s{{Citation needed|date=January 2010}} or oral [[antihistamine]]s or [[corticosteroid]]s.<ref name="tox2"/>
Capsaicin acts as an antifungal agent in four primary ways. First, capsaicin inhibits the metabolic rate of the cells that make up the fungal biofilm.<ref>{{cite journal | vauthors = Behbehani JM, Irshad M, Shreaz S, Karched M | title = Anticandidal Activity of Capsaicin and Its Effect on Ergosterol Biosynthesis and Membrane Integrity of ''Candida albicans'' | journal = International Journal of Molecular Sciences | volume = 24 | issue = 2 | pages = 1046 | date = January 2023 | pmid = 36674560 | doi = 10.3390/ijms24021046 | pmc = 9860720 | doi-access = free }}</ref> This inhibits the area and growth rate of the fungus, since the biofilm creates an area where a fungus can grow and adhere to the chili in which capsaicin is present.<ref>{{cite journal | vauthors = Costa-Orlandi CB, Sardi JC, Pitangui NS, de Oliveira HC, Scorzoni L, Galeane MC, Medina-Alarcón KP, Melo WC, Marcelino MY, Braz JD, Fusco-Almeida AM, Mendes-Giannini MJ | title = Fungal Biofilms and Polymicrobial Diseases | journal = Journal of Fungi | volume = 3 | issue = 2 | pages = 22 | date = May 2017 | pmid = 29371540 | doi = 10.3390/jof3020022 | pmc = 5715925 | doi-access = free }}</ref> Capsaicin also inhibits fungal [[hypha]]e formation, which impacts the amount of nutrients that the rest of the fungal body can receive.<ref>{{Cite web |title=How fungi are constructed |url=http://website.nbm-mnb.ca/mycologywebpages/NaturalHistoryOfFungi/Thallus.html#:~:text=Hyphae%20perform%20a%20variety%20of,the%20thallus%20(fungus%20body). |access-date=2023-05-05 |website=website.nbm-mnb.ca}}</ref> Thirdly, capsaicin disrupts the structure<ref name="Yang-2017">{{cite journal | vauthors = Yang F, Zheng J | title = Understand spiciness: mechanism of TRPV1 channel activation by capsaicin | journal = Protein & Cell | volume = 8 | issue = 3 | pages = 169–177 | date = March 2017 | pmid = 28044278 | pmc = 5326624 | doi = 10.1007/s13238-016-0353-7 }}</ref> of fungal cells and the fungal cell membranes. This has consequential negative impacts on the integrity of fungal cells and their ability to survive and proliferate. Additionally, the [[ergosterol]] synthesis of growing fungi decreases in relation to the amount of capsaicin present in the growth area. This impacts the fungal cell membrane, and how it is able to reproduce and adapt to stressors in its environment.<ref>{{cite journal | vauthors = Jordá T, Puig S | title = Regulation of Ergosterol Biosynthesis in ''Saccharomyces cerevisiae'' | journal = Genes | volume = 11 | issue = 7 | pages = 795 | date = July 2020 | pmid = 32679672 | pmc = 7397035 | doi = 10.3390/genes11070795 | doi-access = free }}</ref>


=== Insecticidal properties ===
===Effects of dietary consumption===
Capsaicin deters insects in multiple ways. The first is by deterring insects from laying their eggs on the pepper due to the effects capsaicin has on these insects.<ref>{{cite journal | vauthors = Li Y, Bai P, Wei L, Kang R, Chen L, Zhang M, Tan EK, Liu W | title = Capsaicin Functions as Drosophila Ovipositional Repellent and Causes Intestinal Dysplasia | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 9963 | date = June 2020 | pmid = 32561812 | pmc = 7305228 | doi = 10.1038/s41598-020-66900-2 | bibcode = 2020NatSR..10.9963L }}</ref> Capsaicin can cause intestinal [[dysplasia]] upon ingestion, disrupting insect metabolism and causing damage to cell membranes within the insect.<ref>{{Cite web |title=Capsaicin Technical Fact Sheet |url=http://npic.orst.edu/factsheets/archive/Capsaicintech.html#references |access-date=2023-05-05 |website=npic.orst.edu}}</ref><ref>{{cite journal | vauthors = Claros Cuadrado JL, Pinillos EO, Tito R, Mirones CS, Gamarra Mendoza NN | title = Insecticidal Properties of Capsaicinoids and Glucosinolates Extracted from ''Capsicum chinense'' and ''Tropaeolum tuberosum'' | journal = Insects | volume = 10 | issue = 5 | pages = 132 | date = May 2019 | pmid = 31064092 | pmc = 6572632 | doi = 10.3390/insects10050132 | doi-access = free }}</ref> This in turn disrupts the standard feeding response of insects.
Ingestion of spicy food or ground jalapeño peppers does not cause mucosal erosions or other abnormalities.<ref name="bleed1">{{Cite journal|author=Graham DY, Smith JL, Opekun AR. |title=Spicy food and the stomach. Evaluation by videoendoscopy |journal=JAMA |year=1988 |volume=260 |issue=23 |pages=3473–5 |url=https://www.ncbi.nlm.nih.gov/pubmed/3210286 |doi=10.1001/jama.260.23.3473 |pmid=3210286 |last2=Smith |last3=Opekun }}</ref> Some mucosal microbleeding has been found after eating red and black peppers, but there was no significant difference between [[aspirin]] (used as a [[Scientific control|control]]) and peppers.<ref name="effects-pepper">{{Cite journal|author=Myers BM, Smith JL, Graham DY |title=Effect of red pepper and black pepper on the stomach |journal=Am. J. Gastroenterol. |volume=82 |issue=3 |pages=211–4 |date=March 1987 |pmid=3103424 |doi= |url=}}</ref> The question of whether chili ingestion increases or decreases risk of stomach cancer is mixed: a study of Mexican patients found self-reported capsaicin intake levels associated with increased stomach cancer rates (and this is independent of infection with ''[[Helicobacter pylori]]''<ref name="cancer2">{{Cite journal|author=López-Carrillo L, López-Cervantes M, Robles-Díaz G, ''et al.'' |title=Capsaicin consumption, [[Helicobacter pylori]] positivity and gastric cancer in Mexico |journal=Int. J. Cancer |volume=106 |issue=2 |pages=277–82 |year=2003 |pmid=12800206 |doi=10.1002/ijc.11195}}</ref>) while a study of Italians suggests eating hot peppers regularly was protective against stomach cancer.<ref name="pmid2335393">{{Cite journal|doi=10.1002/ijc.2910450520 |author=Buiatti|title=A case-control study of gastric cancer and diet in Italy: II. Association with nutrients |journal=[Int J Cancer] |volume=45 |issue=5 |pages=896–901 |date=May 1990 |pmid=2335393 |last2=Palli |first2=D |last3=Decarli |first3=A |last4=Amadori |first4=D |last5=Avellini |first5=C |last6=Bianchi |first6=S |last7=Bonaguri |first7=C |last8=Cipriani |first8=F |last9=Cocco |first9=P|last10=Giacosa|first10=Attilio|last11=Marubini|first11=Ettore|last12=Minacci|first12=Chiara|last13=Puntoni|first13=Riccardo|last14=Russo|first14=Antonio|last15=Vindigni|first15=Carla|last16=Fraumeni|first16=Joseph F.|last17=Blot|first17=William J.|display-authors=8}}</ref> Carcinogenic, co-carcinogenic, and anticarcinogenic effects of capsaicin have been reported in animal studies.<ref name=autogenerated1>{{Cite journal|author= |title=Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin |journal=Int. J. Toxicol. |volume=26 Suppl 1 |issue= |pages=3–106 |year=2007 |pmid=17365137 |doi=10.1080/10915810601163939 |url= |last1= Johnson |first1= Wilbur}}</ref><ref>{{cite pmid|21487045}}</ref>


=== Seed dispersion and deterrents against granivorous mammals ===
===Effects on weight loss and regain===
[[Seed predation|Granivorous]] mammals pose a risk to the propagation of chilies because their molars grind the seeds of chilies, rendering them unable to grow into new chili plants.<ref>{{cite journal | vauthors = Levey DJ, Tewksbury JJ, Cipollini ML, Carlo TA | title = A field test of the directed deterrence hypothesis in two species of wild chili | journal = Oecologia | volume = 150 | issue = 1 | pages = 61–68 | date = November 2006 | pmid = 16896774 | doi = 10.1007/s00442-006-0496-y | bibcode = 2006Oecol.150...61L | s2cid = 10892233 }}</ref><ref name="Tewksbury Nabhan 2001"/> As a result, modern chilies evolved defense mechanisms to mitigate the risk of granivorous mammals. While capsaicin is present at some level in every part of the pepper, the chemical has its highest concentration in the tissue near the seeds within chilies.<ref name="NMSU Q&A 2005" /> Birds are able to eat chilies, then disperse the seeds in their excrement, enabling propagation.<ref name="Tewksbury Nabhan 2001"/>


=== Adaptation to varying moisture levels ===
There is no evidence showing that weight loss is directly correlated with ingesting capsaicin, but there is a positive correlation between ingesting capsaicin and a decrease in weight regain. The effects of capsaicin are said to cause "a shift in substrate oxidation from carbohydrate to fat oxidation".<ref name="Lejeune, Manuela P. G 2003">Lejeune, Manuela P. G. M., Eva M. R. Kovacs, and Margriet S. Westerterp- Plantenga. "Effect of Capsaicin on Substrate Oxidation and Weight Maintenance after Modest Body-weight Loss in Human Subjects." British Journal of Nutrition 90.03 (2003): 651.</ref> This leads to a decrease in appetite as well as a decrease in food intake.<ref name="Lejeune, Manuela P. G 2003"/> Even though ingestion of capsaicin causes thermogenesis, the increase in body temperature does not affect weight loss. However, both oral and gastrointestinal exposure to capsaicin increases satiety and reduces energy as well as fat intake.<ref>Westerterp-Plantenga, M. S., A. Smeets, and M P G. Lejeune. "Sensory and Gastrointestinal Satiety Effects of Capsaicin on Food Intake." International Journal of Obesity 29.6 (2004): 682-88.</ref> Oral exposure proves to yield stronger reduction suggesting that capsaicin has sensory effects. Short-term studies suggest that capsaicin aids in the decrease of weight regain. However, long-term studies are limited because of the pungency of capsaicin.<ref>Diepvens, K., K. R. Westerterp, and M. S. Westerterp-Plantenga. "Obesity and Thermogenesis Related to the Consumption of Caffeine, Ephedrine, Capsaicin, and Green Tea." AJP: Regulatory, Integrative and Comparative Physiology 292.1 (2006): R77-85.</ref> Another recent study has suggested that the ingestion of capsaicinoids can increase energy expenditure and fat oxidation through the activation of [[brown adipose tissue]] (BAT) in humans from the effects of the capsaicin.<ref>Yoneshiro, Takeshi, Sayuri Aita, Yuko Kawai, Toshihiko Iwanaga, and Mayayuki Saito. "Nonpungent Capsaicin Analogs (capsinoids) Increase Energy Expenditure through the Activation of Brown Adipose Tissue in Humans." American Society for Nutrition (2012).</ref>
Capsaicin is a potent defense mechanism for chilies, but it does come at a cost. Varying levels of capsaicin in chilies currently appear to be caused by an evolutionary split between surviving in dry environments, and having defense mechanisms against fungal growth, insects, and granivorous mammals.<ref>{{cite journal | vauthors = Haak DC, McGinnis LA, Levey DJ, Tewksbury JJ | title = Why are not all chilies hot? A trade-off limits pungency | journal = Proceedings. Biological Sciences | volume = 279 | issue = 1735 | pages = 2012–2017 | date = May 2012 | pmid = 22189403 | pmc = 3311884 | doi = 10.1098/rspb.2011.2091 }}</ref> Capsaicin synthesis in chilies places a strain on their water resources.<ref>{{Cite journal | vauthors = Ruiz-Lau N, Medina-Lara F, Minero-García Y, Zamudio-Moreno E, Guzmán-Antonio A, Echevarría-Machado I, Martínez-Estévez M |date=2011-03-01 |title=Water Deficit Affects the Accumulation of Capsaicinoids in Fruits of Capsicum chinense Jacq. |url=https://journals.ashs.org/hortsci/view/journals/hortsci/46/3/article-p487.xml |journal=HortScience |language=en-US |volume=46 |issue=3 |pages=487–492 |doi=10.21273/HORTSCI.46.3.487 |s2cid=86280396 |issn=0018-5345|doi-access=free }}</ref> This directly affects their fitness, as it has been observed that standard concentration of capsaicin of peppers in high moisture environments in the seeds and [[pericarp]]s of the peppers reduced the seeds production by 50%.<ref>{{cite journal | vauthors = Mahmood T, Rana RM, Ahmar S, Saeed S, Gulzar A, Khan MA, Wattoo FM, Wang X, Branca F, Mora-Poblete F, Mafra GS, Du X | title = Effect of Drought Stress on Capsaicin and Antioxidant Contents in Pepper Genotypes at Reproductive Stage | journal = Plants | volume = 10 | issue = 7 | pages = 1286 | date = June 2021 | pmid = 34202853 | pmc = 8309139 | doi = 10.3390/plants10071286 | doi-access = free | bibcode = 2021Plnts..10.1286M }}</ref>


==See also==
== See also ==<!-- Please respect alphabetical order -->
* [[Allicin]], the active piquant flavor chemical in uncooked [[garlic]], and to a lesser extent [[onions]] (see those articles for discussion of other chemicals in them relating to pungency, and eye irritation)
* [[Allicin]], the active [[piquant]] flavor chemical in uncooked [[garlic]], and to a lesser extent [[onion]]s (see those articles for discussion of other chemicals in them relating to pungency, and eye irritation)
* [[Allyl isothiocyanate]], the active piquant chemical in [[mustard plant|mustard]], [[radish]]es, [[horseradish]], and [[wasabi]]
* [[Capsazepine]], capsaicin antagonist
* [[Capsazepine]], capsaicin antagonist
* [[Iodoresiniferatoxin]], an ultrapotent capsaicin antagonist derived from [[Resiniferatoxin]]
* [[Capsinoids]], similar in structure to capsaicin, but lack the extreme pungency, and density
* [[Discovery and development of TRPV1 antagonists]]
* [[Gingerol]] and [[shogaol]], the active piquant flavor chemicals in [[ginger]]
* [[Naga Viper|Naga Viper pepper]], [[Bhut Jolokia chili pepper|Bhut Jolokia Pepper]], [[Carolina Reaper]], [[Trinidad Moruga Scorpion]]; some of the world's most capsaicin-rich fruits
* [[Naga Viper|Naga Viper pepper]], [[Bhut Jolokia chili pepper|Bhut Jolokia Pepper]], [[Carolina Reaper]], [[Trinidad Moruga Scorpion]]; some of the world's most capsaicin-rich fruits
* [[Piperine]], the active piquant chemical in [[black pepper]]
* [[Piperine]] the active flavor chemical in [[black pepper]]
* [[List of capsaicinoids]]
* [[Scoville scale]], a measurement of the spicy heat (or pungency) of a chili pepper
* [[Sinus Buster]], a patent medicine containing capsaicin
* [[syn-Propanethial-S-oxide|''syn''-Propanethial-''S''-oxide]], the major active piquant chemical in onions
* [[TRPV1]], the only known receptor (a [[transient receptor potential]] channel) for capsaicin


==References==
== References ==
{{Reflist}}


===Footnotes===
===Notes===
{{Reflist|30em}}
{{notelist}}


== Further reading ==
===General references===
{{refbegin}}
* {{Cite journal|author=Dray A |title=Mechanism of action of capsaicin-like molecules on sensory neurons |journal=Life Sci. |volume=51 |issue=23 |pages=1759–65 |year=1992 |pmid=1331641 |doi= 10.1016/0024-3205(92)90045-Q|url=}}
* {{cite book | vauthors = Abdel-Salam OM | title = Capsaicin as a Therapeutic Molecule | publisher = Springer | date = 2014 | isbn = 978-3-0348-0827-9 }}
* Garnanez RJ, McKee LH (2001) "Temporal effectiveness of sugar solutions on mouth burn by capsaicin" [http://ift.confex.com/ift/2001/techprogram/paper_8185.htm IFT Annual Meeting 2001]
{{refend}}
* {{Cite journal|author=Henkin R |title=Cooling the burn from hot peppers |journal=JAMA |volume=266 |issue=19 |page=2766 |date=November 1991 |pmid=1942431 |doi= 10.1001/jama.266.19.2766b|url=}}
* {{Cite journal|author=Nasrawi CW, Pangborn RM |title=Temporal effectiveness of mouth-rinsing on capsaicin mouth-burn |journal=Physiol. Behav. |volume=47 |issue=4 |pages=617–23 |date=April 1990 |pmid=2385629 |doi=10.1016/0031-9384(90)90067-E |url=}}
* {{Cite journal|author=Tewksbury JJ, Nabhan GP |title=Seed dispersal. Directed deterrence by capsaicin in chilies |journal=Nature |volume=412 |issue=6845 |pages=403–4 |date=July 2001 |pmid=11473305 |doi=10.1038/35086653 |url=}}
* {{Cite journal|author=Kirifides ML, Kurnellas MP, Clark L, Bryant BP |title=Calcium responses of chicken trigeminal ganglion neurons to methyl anthranilate and capsaicin |journal=J. Exp. Biol. |volume=207 |issue=Pt 5 |pages=715–22 |date=February 2004 |pmid=14747403 |doi= 10.1242/jeb.00809|url=http://jeb.biologists.org/content/207/5/715.long}}
* Tarantula Venom, Chili Peppers Have Same "Bite," Study Finds http://news.nationalgeographic.com/news/2006/11/061108-tarantula-venom.html
* Minna M. Hamalainen, Alberto Subieta, Christopher Arpey, Timothy J. Brennan, "Differential Effect of Capsaicin Treatment on Pain-Related Behaviors After Plantar Incision," ''The Journal of Pain'', 10,6 (2009), 637-645.


== External links==
== External links==
{{commons category}}
{{commons category}}
{{Wiktionary}}
{{Wiktionary}}
* [http://npic.orst.edu/factsheets/Capsaicintech.pdf Capsaicin Technical Fact Sheet - National Pesticide Information Center]
* [http://npic.orst.edu/factsheets/capgen.html Capsaicin General Fact Sheet National Pesticide Information Center]
* [https://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml Fire and Spice: The molecular basis for flavor]
* [http://www.epa.gov/oppsrrd1/REDs/factsheets/4018fact.pdf EPA Capsaicin Reregistration Eligibility Decision Fact Sheet]

* [http://www.chm.bris.ac.uk/motm/chilli/capsaicin.htm Molecule of the Month]
{{Analgesics}}
* [http://ec.europa.eu/food/fs/sc/scf/out120_en.pdf European Commission], opinion of the Scientific Committee on Food on capsaicin.
{{Transient receptor potential channel modulators}}
* [http://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml Fire and Spice: The molecular basis for flavor]
{{Phytochemicals}}
* A [[WikiHow]] article on [http://www.wikihow.com/Cool--Burns-from-Chilli-Peppers How to Cool Chilli Pepper Burns].
{{Phenolic compounds}}
{{Topical products for joint and muscular pain}}
{{Histone deacetylase inhibitors}}
{{Chili peppers}}
{{Portal bar|Medicine}}
{{Authority control}}


[[Category:Capsaicinoids| ]]
[[Category:Capsaicinoids| ]]
[[Category:CYP3A4 inducers]]
[[Category:Transient receptor potential channel modulators]]

Latest revision as of 18:26, 22 December 2024

Capsaicin
Names
Pronunciation /kæpˈssɪn/ or /kæpˈsəsɪn/
Preferred IUPAC name
(6E)-N-[(4-Hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide
Other names
(E)-N-(4-Hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide
8-Methyl-N-vanillyl-trans-6-nonenamide
trans-8-Methyl-N-vanillylnon-6-enamide
(E)-Capsaicin
Capsicine
Capsicin
CPS
Drug
Identifiers
3D model (JSmol)
2816484
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.006.337 Edit this at Wikidata
EC Number
  • 206-969-8
KEGG
UNII
  • InChI=1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+ checkY
    Key: YKPUWZUDDOIDPM-SOFGYWHQSA-N checkY
  • InChI=1/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
    Key: YKPUWZUDDOIDPM-SOFGYWHQBQ
  • O=C(NCc1cc(OC)c(O)cc1)CCCC/C=C/C(C)C
Properties
C18H27NO3
Molar mass 305.418 g·mol−1
Appearance Crystalline white powder[1]
Odor Highly pungent
Melting point 62 to 65 °C (144 to 149 °F; 335 to 338 K)
Boiling point 210 to 220 °C (410 to 428 °F; 483 to 493 K) 0.01 Torr
0.0013 g/100mL
Solubility
Vapor pressure 1.32×10−8 mm Hg at 25 °C[2]
UV-vismax) 280 nm
Structure
Monoclinic
Pharmacology
M02AB01 (WHO) N01BX04 (WHO)
License data
Legal status
Hazards
GHS labelling:
GHS05: CorrosiveGHS06: ToxicGHS07: Exclamation markGHS08: Health hazard
Danger
H301, H302, H315, H318
P264, P270, P280, P301+P310, P301+P312, P302+P352, P305+P351+P338, P310, P321, P330, P332+P313, P362, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Safety data sheet (SDS) [2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)
Capsaicin
HeatAbove peak
(pure capsaicin is toxic)[2]
Scoville scale16,000,000[5] SHU

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) (/kæpˈssɪn/ or /kæpˈsəsɪn/) is an active component of chili peppers, which are plants belonging to the genus Capsicum. It is a potent irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact. Capsaicin and several related amides (capsaicinoids) are produced as secondary metabolites by chili peppers, likely as deterrents against certain mammals and fungi.[6] Pure capsaicin is a hydrophobic, colorless, highly pungent (i.e., spicy) crystalline solid.[2]

Natural function

[edit]

Capsaicin is present in large quantities in the placental tissue (which holds the seeds), the internal membranes and, to a lesser extent, the other fleshy parts of the fruits of plants in the genus Capsicum. The seeds themselves do not produce any capsaicin, although the highest concentration of capsaicin can be found in the white pith of the inner wall, where the seeds are attached.[7]

The seeds of Capsicum plants are dispersed predominantly by birds. In birds, the TRPV1 channel does not respond to capsaicin or related chemicals but mammalian TRPV1 is very sensitive to it. This is advantageous to the plant, as chili pepper seeds consumed by birds pass through the digestive tract and can germinate later, whereas mammals have molar teeth which destroy such seeds and prevent them from germinating. Thus, natural selection may have led to increasing capsaicin production because it makes the plant less likely to be eaten by animals that do not help it disperse.[8] There is also evidence that capsaicin may have evolved as an anti-fungal agent.[9] The fungal pathogen Fusarium, which is known to infect wild chilies and thereby reduce seed viability, is deterred by capsaicin, which thus limits this form of predispersal seed mortality.

The vanillotoxin-containing venom of a certain tarantula species (Psalmopoeus cambridgei) activates the same pathway of pain as is activated by capsaicin, an example of a shared pathway in both plant and animal anti-mammalian defense.[10]

Uses

[edit]

Food

[edit]
Curry dishes

Because of the burning sensation caused by capsaicin when it comes in contact with mucous membranes, it is commonly used in food products to provide added spiciness or "heat" (piquancy), usually in the form of spices such as chili powder and paprika.[11] In high concentrations, capsaicin will also cause a burning effect on other sensitive areas, such as skin or eyes.[12] The degree of heat found within a food is often measured on the Scoville scale.[11]

There has long been a demand for capsaicin-spiced products like chili pepper, and hot sauces such as Tabasco sauce and Mexican salsa.[11] It is common for people to experience pleasurable and even euphoric effects from ingesting capsaicin.[11] Folklore among self-described "chiliheads" attribute this to pain-stimulated release of endorphins, a different mechanism from the local receptor overload that makes capsaicin effective as a topical analgesic.[12]

Research and pharmaceutical use

[edit]

Capsaicin is used as an analgesic in topical ointments and dermal patches to relieve pain, typically in concentrations between 0.025% and 0.1%.[13] It may be applied in cream form for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, backache, strains and sprains, often in compounds with other rubefacients.[13]

It is also used to reduce the symptoms of peripheral neuropathy, such as post-herpetic neuralgia caused by shingles.[13] A capsaicin transdermal patch (Qutenza) for the management of this particular therapeutic indication (pain due to post-herpetic neuralgia) was approved in 2009, as a therapeutic by both the U.S. Food and Drug Administration (FDA)[14][15] and the European Union.[16] A subsequent application to the FDA for Qutenza to be used as an analgesic in HIV neuralgia was refused.[17] One 2017 review of clinical studies having limited quality found that high-dose topical capsaicin (8%) compared with control (0.4% capsaicin) provided moderate to substantial pain relief from post-herpetic neuralgia, HIV-neuropathy, and diabetic neuropathy.[18]

Although capsaicin creams have been used to treat psoriasis for reduction of itching,[13][19][20] a review of six clinical trials involving topical capsaicin for treatment of pruritus concluded there was insufficient evidence of effect.[21] Oral capsaicin decreases LDL cholesterol levels moderately.[22]

There is insufficient clinical evidence to determine the role of ingested capsaicin on several human disorders, including obesity, diabetes, cancer and cardiovascular diseases.[13]

Pepper spray and pests

[edit]

Capsaicinoids are also an active ingredient in riot control and personal defense pepper spray agents.[2] When the spray comes in contact with skin, especially eyes or mucous membranes, it produces pain and breathing difficulty in the affected individual.[2]

Capsaicin is also used to deter pests, specifically mammalian pests. Targets of capsaicin repellants include voles, deer, rabbits, squirrels, bears, insects, and attacking dogs.[23] Ground or crushed dried chili pods may be used in birdseed to deter rodents,[24] taking advantage of the insensitivity of birds to capsaicin. The Elephant Pepper Development Trust claims that using chili peppers as a barrier crop can be a sustainable means for rural African farmers to deter elephants from eating their crops.[25]

An article published in the Journal of Environmental Science and Health Part B in 2006 states that "Although hot chili pepper extract is commonly used as a component of household and garden insect-repellent formulas, it is not clear that the capsaicinoid elements of the extract are responsible for its repellency."[26]

The first pesticide product using solely capsaicin as the active ingredient was registered with the U.S. Department of Agriculture in 1962.[23]

Equestrian sports

[edit]

Capsaicin is a banned substance in equestrian sports because of its hypersensitizing and pain-relieving properties.[27] At the show jumping events of the 2008 Summer Olympics, four horses tested positive for capsaicin, which resulted in disqualification.[27]

Irritant effects

[edit]

Acute health effects

[edit]

Capsaicin is a strong irritant requiring proper protective goggles, respirators, and proper hazardous material-handling procedures. Capsaicin takes effect upon skin contact (irritant, sensitizer), eye contact (irritant), ingestion, and inhalation (lung irritant, lung sensitizer). The LD50 in mice is 47.2 mg/kg.[28][29]

Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers.[30] They cause burning or stinging pain to the skin and, if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produces intense tearing, pain, conjunctivitis, and blepharospasm.[31]

Treatment after exposure

[edit]

The primary treatment is removal of the offending substance. Plain water is ineffective at removing capsaicin.[28] Capsaicin is soluble in alcohol, which can be used to clean contaminated items.[28]

When capsaicin is ingested, cold milk may be an effective way to relieve the burning sensation due to caseins in milk, and the water of milk acts as a surfactant, allowing the capsaicin to form an emulsion with it.[32]

Weight loss and regain

[edit]

As of 2007, there was no evidence showing that weight loss is directly correlated with ingesting capsaicin. Well-designed clinical research had not been performed because the pungency of capsaicin in prescribed doses under research prevented subjects from complying in the study.[33] A 2014 meta-analysis of further trials found weak evidence that consuming capsaicin before a meal might slightly reduce the amount of food consumed, and might drive food preference toward carbohydrates.[34]

Peptic ulcer

[edit]

One 2006 review concluded that capsaicin may relieve symptoms of a peptic ulcer rather than being a cause of it.[35]

Death

[edit]

Ingestion of high quantities of capsaicin can be deadly,[36] particularly in people with heart problems.[37] Even healthy young people can suffer adverse health effects like myocardial infarction after ingestion of capsaicin capsules.[38]

Mechanism of action

[edit]

The burning and painful sensations associated with capsaicin result from "defunctionalization" of nociceptor nerve fibers by causing a topical hypersensitivity reaction in the skin.[2][39] As a member of the vanilloid family, capsaicin binds to a receptor on nociceptor fibers called the vanilloid receptor subtype 1 (TRPV1).[39][40][41] TRPV1, which can also be stimulated with heat, protons and physical abrasion, permits cations to pass through the cell membrane when activated.[39] The resulting depolarization of the neuron stimulates it to send impulses to the brain.[39] By binding to TRPV1 receptors, capsaicin produces similar sensations to those of excessive heat or abrasive damage, such as warming, tingling, itching, or stinging, explaining why capsaicin is described as an irritant on the skin and eyes or by ingestion.[39]

Clarifying the mechanisms of capsaicin effects on skin nociceptors was part of awarding the 2021 Nobel Prize in Physiology or Medicine, as it led to the discovery of skin sensors for temperature and touch, and identification of the single gene causing sensitivity to capsaicin.[42][43]

History

[edit]

The compound was first extracted in impure form in 1816 by Christian Friedrich Bucholz (1770–1818).[44][a] In 1873 German pharmacologist Rudolf Buchheim[54][55][56] (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes[57][58] stated that "capsicol" (partially purified capsaicin[59]) caused the burning feeling when in contact with mucous membranes and increased secretion of gastric acid.

Capsaicinoids

[edit]

The most commonly occurring capsaicinoids are capsaicin (69%), dihydrocapsaicin (22%), nordihydrocapsaicin (7%), homocapsaicin (1%), and homodihydrocapsaicin (1%).[60]

Capsaicin and dihydrocapsaicin (both 16.0 million SHU) are the most pungent capsaicinoids. Nordihydrocapsaicin (9.1 million SHU), homocapsaicin and homodihydrocapsaicin (both 8.6 million SHU) are about half as hot.[5]

There are six natural capsaicinoids (table below). Although vanillylamide of n-nonanoic acid (Nonivamide, VNA, also PAVA) is produced synthetically for most applications, it does occur naturally in Capsicum species.[61]

Capsaicinoid name Abbrev. Typical
relative
amount
Scoville
heat units
Chemical structure
Capsaicin CPS 69% 16,000,000 Chemical structure of capsaicin
Dihydrocapsaicin DHC 22% 16,000,000 Chemical structure of dihydrocapsaicin
Nordihydrocapsaicin NDHC 7% 9,100,000 Chemical structure of nordihydrocapsaicin
Homocapsaicin HC 1% 8,600,000 Chemical structure of homocapsaicin
Homodihydrocapsaicin HDHC 1% 8,600,000 Chemical structure of homodihydrocapsaicin
Nonivamide PAVA 9,200,000 Chemical structure of nonivamide

Biosynthesis

[edit]
Chili peppers
Vanillamine is a product of the phenylpropanoid pathway.
Valine enters the branched fatty acid pathway to produce 8-methyl-6-nonenoyl-CoA.
Capsaicin synthase condenses vanillamine and 8-methyl-6-nonenoyl-CoA to produce capsaicin.

History

[edit]

The general biosynthetic pathway of capsaicin and other capsaicinoids was elucidated in the 1960s by Bennett and Kirby, and Leete and Louden. Radiolabeling studies identified phenylalanine and valine as the precursors to capsaicin.[62][63] Enzymes of the phenylpropanoid pathway, phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), caffeic acid O-methyltransferase (COMT) and their function in capsaicinoid biosynthesis were identified later by Fujiwake et al.,[64][65] and Sukrasno and Yeoman.[66] Suzuki et al. are responsible for identifying leucine as another precursor to the branched-chain fatty acid pathway.[67] It was discovered in 1999 that pungency of chili peppers is related to higher transcription levels of key enzymes of the phenylpropanoid pathway, phenylalanine ammonia lyase, cinnamate 4-hydroxylase, caffeic acid O-methyltransferase. Similar studies showed high transcription levels in the placenta of chili peppers with high pungency of genes responsible for branched-chain fatty acid pathway.[68]

Biosynthetic pathway

[edit]

Plants exclusively of the genus Capsicum produce capsaicinoids, which are alkaloids.[69] Capsaicin is believed to be synthesized in the interlocular septum of chili peppers and depends on the gene AT3, which resides at the pun1 locus, and which encodes a putative acyltransferase.[70]

Biosynthesis of the capsaicinoids occurs in the glands of the pepper fruit where capsaicin synthase condenses vanillylamine from the phenylpropanoid pathway with an acyl-CoA moiety produced by the branched-chain fatty acid pathway.[63][71][72][73]

Capsaicin is the most abundant capsaicinoid found in the genus Capsicum, but at least ten other capsaicinoid variants exist.[74] Phenylalanine supplies the precursor to the phenylpropanoid pathway while leucine or valine provide the precursor for the branched-chain fatty acid pathway.[63][71] To produce capsaicin, 8-methyl-6-nonenoyl-CoA is produced by the branched-chain fatty acid pathway and condensed with vanillylamine. Other capsaicinoids are produced by the condensation of vanillylamine with various acyl-CoA products from the branched-chain fatty acid pathway, which is capable of producing a variety of acyl-CoA moieties of different chain length and degrees of unsaturation.[75] All condensation reactions between the products of the phenylpropanoid and branched-chain fatty acid pathway are mediated by capsaicin synthase to produce the final capsaicinoid product.[63][71]

Evolution

[edit]

The Capsicum genus split from Solanaceae 19.6 million years ago, 5.4 million years after the appearance of Solanaceae, and is native only to the Americas.[76] Chilies only started to quickly evolve in the past 2 million years into markedly different species. This evolution can be partially attributed to a key compound found in peppers, 8-methyl-N-vanillyl-6-nonenamide, otherwise known as capsaicin. Capsaicin evolved similarly across species of chilies that produce capsaicin. Its evolution over the course of centuries is due to genetic drift and natural selection, across the genus Capsicum. Despite the fact that chilies within the Capsicum genus are found in diverse environments, the capsaicin found within them all exhibit similar properties that serve as defensive and adaptive features. Capsaicin evolved to preserve the fitness of peppers against fungi infections, insects, and granivorous mammals.[77]

Antifungal properties

[edit]

Capsaicin acts as an antifungal agent in four primary ways. First, capsaicin inhibits the metabolic rate of the cells that make up the fungal biofilm.[78] This inhibits the area and growth rate of the fungus, since the biofilm creates an area where a fungus can grow and adhere to the chili in which capsaicin is present.[79] Capsaicin also inhibits fungal hyphae formation, which impacts the amount of nutrients that the rest of the fungal body can receive.[80] Thirdly, capsaicin disrupts the structure[81] of fungal cells and the fungal cell membranes. This has consequential negative impacts on the integrity of fungal cells and their ability to survive and proliferate. Additionally, the ergosterol synthesis of growing fungi decreases in relation to the amount of capsaicin present in the growth area. This impacts the fungal cell membrane, and how it is able to reproduce and adapt to stressors in its environment.[82]

Insecticidal properties

[edit]

Capsaicin deters insects in multiple ways. The first is by deterring insects from laying their eggs on the pepper due to the effects capsaicin has on these insects.[83] Capsaicin can cause intestinal dysplasia upon ingestion, disrupting insect metabolism and causing damage to cell membranes within the insect.[84][85] This in turn disrupts the standard feeding response of insects.

Seed dispersion and deterrents against granivorous mammals

[edit]

Granivorous mammals pose a risk to the propagation of chilies because their molars grind the seeds of chilies, rendering them unable to grow into new chili plants.[86][8] As a result, modern chilies evolved defense mechanisms to mitigate the risk of granivorous mammals. While capsaicin is present at some level in every part of the pepper, the chemical has its highest concentration in the tissue near the seeds within chilies.[7] Birds are able to eat chilies, then disperse the seeds in their excrement, enabling propagation.[8]

Adaptation to varying moisture levels

[edit]

Capsaicin is a potent defense mechanism for chilies, but it does come at a cost. Varying levels of capsaicin in chilies currently appear to be caused by an evolutionary split between surviving in dry environments, and having defense mechanisms against fungal growth, insects, and granivorous mammals.[87] Capsaicin synthesis in chilies places a strain on their water resources.[88] This directly affects their fitness, as it has been observed that standard concentration of capsaicin of peppers in high moisture environments in the seeds and pericarps of the peppers reduced the seeds production by 50%.[89]

See also

[edit]

References

[edit]
  1. ^ "Capsaicin". ChemSpider, Royal Society of Chemistry, Cambridge, UK. 2018. Retrieved 9 June 2018.
  2. ^ a b c d e f g "Capsaicin". PubChem, US National Library of Medicine. 27 May 2023. Retrieved 1 June 2023.
  3. ^ "Qutenza- capsaicin kit". DailyMed. 10 January 2023. Retrieved 22 February 2023.
  4. ^ "Drug Approval Package: Qutenza (capsaicin) NDA #022395". U.S. Food and Drug Administration (FDA). 3 October 2013. Retrieved 22 February 2023.
  5. ^ a b Govindarajan VS, Sathyanarayana MN (1991). "Capsicum--production, technology, chemistry, and quality. Part V. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences". Critical Reviews in Food Science and Nutrition. 29 (6): 435–474. doi:10.1080/10408399109527536. PMID 2039598.
  6. ^ "What Made Chili Peppers So Spicy?". Talk of the Nation. 15 August 2008.
  7. ^ a b "Chile Information – Frequently Asked Questions". New Mexico State University – College of Agriculture and Home Economics. 2005. Archived from the original on 4 May 2007. Retrieved 17 May 2007.
  8. ^ a b c Tewksbury JJ, Nabhan GP (July 2001). "Seed dispersal. Directed deterrence by capsaicin in chilies". Nature. 412 (6845): 403–404. Bibcode:2001Natur.412..403T. doi:10.1038/35086653. PMID 11473305. S2CID 4389051.
  9. ^ Tewksbury JJ, Reagan KM, Machnicki NJ, Carlo TA, Haak DC, Peñaloza AL, et al. (August 2008). "Evolutionary ecology of pungency in wild chilies". Proceedings of the National Academy of Sciences of the United States of America. 105 (33): 11808–11811. Bibcode:2008PNAS..10511808T. doi:10.1073/pnas.0802691105. PMC 2575311. PMID 18695236.
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  14. ^ "FDA Approves New Drug Treatment for Long-Term Pain Relief after Shingles Attacks" (Press release). U.S. Food and Drug Administration. 17 November 2009. Archived from the original on 23 November 2015. Retrieved 5 January 2016.
  15. ^ "Drug Approval Package: Qutenza (capsaicin) NDA #022395". U.S. Food and Drug Administration (FDA). 29 June 2010. Retrieved 19 August 2020.
  16. ^ "Qutenza EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 19 August 2020.
  17. ^ Hitt E (9 March 2012). "FDA Turns Down Capsaicin Patch for Painful Neuropathy in HIV". Medscape Medical News, WebMD. Retrieved 5 January 2016.
  18. ^ Derry S, Rice AS, Cole P, Tan T, Moore RA (January 2017). "Topical capsaicin (high concentration) for chronic neuropathic pain in adults" (PDF). The Cochrane Database of Systematic Reviews. 1 (1): CD007393. doi:10.1002/14651858.CD007393.pub4. hdl:10044/1/49554. PMC 6464756. PMID 28085183. Archived from the original (PDF) on 15 February 2021. Retrieved 27 September 2018.
  19. ^ Glinski W, Glinska-Ferenz M, Pierozynska-Dubowska M (1991). "Neurogenic inflammation induced by capsaicin in patients with psoriasis". Acta Dermato-Venereologica. 71 (1): 51–54. doi:10.2340/00015555715154. PMID 1711752. S2CID 29307090.
  20. ^ Ellis CN, Berberian B, Sulica VI, Dodd WA, Jarratt MT, Katz HI, et al. (September 1993). "A double-blind evaluation of topical capsaicin in pruritic psoriasis". Journal of the American Academy of Dermatology. 29 (3): 438–442. doi:10.1016/0190-9622(93)70208-B. PMID 7688774.
  21. ^ Gooding SM, Canter PH, Coelho HF, Boddy K, Ernst E (August 2010). "Systematic review of topical capsaicin in the treatment of pruritus". International Journal of Dermatology. 49 (8): 858–865. doi:10.1111/j.1365-4632.2010.04537.x. PMID 21128913. S2CID 24484878.
  22. ^ Kelava L, Nemeth D, Hegyi P, Keringer P, Kovacs DK, Balasko M, et al. (April 2021). "Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level: a meta-analysis of controlled human trials". Critical Reviews in Food Science and Nutrition. 62 (25): 7025–7035. doi:10.1080/10408398.2021.1910138. PMID 33840333.
  23. ^ a b "R.E.D. Facts for Capsaicin" (PDF). United States Environmental Protection Agency. Archived from the original (PDF) on 24 October 2012. Retrieved 13 November 2012.
  24. ^ Jensen PG, Curtis PD, Dunn JA, Austic RE, Richmond ME (September 2003). "Field evaluation of capsaicin as a rodent aversion agent for poultry feed". Pest Management Science. 59 (9): 1007–1015. doi:10.1002/ps.705. PMID 12974352.
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    • Thresh JC (8 July 1876). "Capsaicin, the active principle in Capsicum fruits". The Pharmaceutical Journal and Transactions. 3rd Series. 7 (315): 21. [Note: This article is summarized in: "Capsaicin, the active principle in Capsicum fruits". The Analyst. 1 (8): 148–149. 1876. Bibcode:1876Ana.....1..148.. doi:10.1039/an876010148b.
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    • Thresh JC (1877). "Report on the active principle of Cayenne pepper". Year Book of Pharmacy: 485–488.
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Notes

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  1. ^ History of early research on capsaicin:
    1. Maurach B (1816). "Pharmaceutisch-chemische Untersuchung des spanischen Pfeffers" [Pharmaceutical-chemical investigation of Spanish peppers]. Berlinisches Jahrbuch für die Pharmacie (in German). 17: 63–73. Abstracts of Maurach's paper appear in: (i) Repertorium für die Pharmacie, vol. 6, page 117-119 (1819); (ii) Allgemeine Literatur-Zeitung, vol. 4, no. 18, page 146 (February 1821); (iii) "Spanischer oder indischer Pfeffer", System der Materia medica ..., vol. 6, pages 381–386 (1821) (this reference also contains an abstract of Bucholz's analysis of peppers).
    2. Henri Braconnot, French chemist Braconnot H (1817). "Examen chemique du Piment, de son principe âcre, et de celui des plantes de la famille des renonculacées" [Chemical investigation of the chili pepper, of its pungent principle [constituent, component], and of that of plants of the family Ranunculus]. Annales de Chimie et de Physique (in French). 6: 122- 131.
    3. Johann Georg Forchhammer, Danish geologist Oersted HC (1820). "Sur la découverte de deux nouveaux alcalis végétaux" [On the discovery of two new plant alkalis]. Journal de physique, de chemie, d'histoire naturelle et des arts [Journal of Physics, Chemistry, Natural History and the Arts] (in French). 90: 173–174.
    4. Ernst Witting, German apothecary Witting E (1822). "Considerations sur les bases vegetales en general, sous le point de vue pharmaceutique et descriptif de deux substances, la capsicine et la nicotianine" [Thoughts on the plant bases in general from a pharmaceutical viewpoint, and description of two substances, capsicin and nicotine]. Beiträge für die Pharmaceutische und Analytische Chemie [Contributions to Pharmaceutical and Analytical Chemistry] (in French). 3: 43. He called it "capsicin", after the genus Capsicum from which it was extracted. John Clough Thresh (1850–1932), who had isolated capsaicin in almost pure form,[45][46] gave it the name "capsaicin" in 1876.[47] Karl Micko isolated capsaicin in its pure form in 1898.[48][49] Capsaicin's chemical composition was first determined in 1919 by E. K. Nelson, who also partially elucidated capsaicin's chemical structure.[50] Capsaicin was first synthesized in 1930 by Ernst Spath and Stephen F. Darling.[51] In 1961, similar substances were isolated from chili peppers by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.[52][53]

Further reading

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