Capsaicin: Difference between revisions

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| ImageClass2    = bg-transparent
| ImageClass2    = bg-transparent
| PIN            = (6''E'')-''N''-[(4-Hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide
| PIN            = (6''E'')-''N''-[(4-Hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide
| 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
| 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 />
| 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}}
| 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}}
| Section1      = {{Chembox Identifiers
| Section1      = {{Chembox Identifiers
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|C=18 | H=27 | N=1 | O=3
|C=18 | H=27 | N=1 | O=3
|LambdaMax = 280 nm
|LambdaMax = 280 nm
|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>
|Appearance = Crystalline white powder<ref>{{cite web|url=http://www.chemspider.com/Chemical-Structure.1265957.html|website=[[ChemSpider]] |publisher=[[Royal Society of Chemistry]] |title=Capsaicin|date=2018|access-date=9 June 2018}}</ref>
|Odor = Highly pungent
|Odor = Highly pungent
|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>
|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>
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}}
}}
{{Infobox pepper <!-- The given scoville rating is for the pure chemical compound, this should not be mistaken for food. -->
{{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/>
| heat = Above peak<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>
| 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|.|ə|.|s|I|n}}, rarely {{IPAc-en|k|ae|p|ˈ|s|eI|s|I|n}})<ref>{{cite web | url=https://dictionary.cambridge.org/dictionary/english/capsaicin | title=Capsaicin }}</ref><ref>{{cite web | url=https://www.merriam-webster.com/dictionary/capsaicin | title=Definition of CAPSAICIN }}</ref><ref>{{cite web | url=https://www.ahdictionary.com/word/search.html?q=capsaicin | title=The American Heritage Dictionary entry: Capsaicin }}</ref> 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/><ref>{{Cite journal |last=David |first=William I. F. |last2=Shankland |first2=Kenneth |last3=Shankland |first3=Kenneth |last4=Shankland |first4=Norman |date=1998 |title=Routine determination of molecular crystal structures from powder diffraction data |url=https://xlink.rsc.org/?DOI=a800855h |journal=Chemical Communications |issue=8 |pages=931–932 |doi=10.1039/a800855h}}</ref><ref>{{Cite journal |last=Lozinšek |first=Matic |date=2025-04-01 |title=Single-crystal structure of the spicy capsaicin |url=https://journals.iucr.org/paper?S2053229625001706 |journal=Acta Crystallographica Section C Structural Chemistry |volume=81 |issue=4 |pages=188–192 |doi=10.1107/S2053229625001706 |issn=2053-2296 |pmc=11970115 |pmid=40052876}}</ref>
'''Capsaicin''' ('''8-methyl-''N''-vanillyl-6-nonenamide''') ({{IPAc-en|k|ae|p|ˈ|s|eI|.|ə|.|s|I|n}}, commonly {{IPAc-en|k|ae|p|ˈ|s|eI|s|I|n}})<ref>{{cite web | url=https://dictionary.cambridge.org/dictionary/english/capsaicin | title=Capsaicin }}</ref><ref>{{cite web | url=https://www.merriam-webster.com/dictionary/capsaicin | title=Definition of CAPSAICIN }}</ref><ref>{{cite web | url=https://www.ahdictionary.com/word/search.html?q=capsaicin | title=The American Heritage Dictionary entry: Capsaicin }}</ref> is a toxin that is the main active component of [[chili pepper]]s and gives them their "spicy" or "hot" taste. It is a potent [[Irritation|irritant]] for [[Mammal|mammals]], including humans, for which it 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 eating by mammals and against the growth of [[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/><ref>{{Cite journal |last1=David |first1=William I. F. |last2=Shankland |first2=Kenneth |last3=Shankland |first3=Kenneth |last4=Shankland |first4=Norman |date=1998 |title=Routine determination of molecular crystal structures from powder diffraction data |url=https://xlink.rsc.org/?DOI=a800855h |journal=Chemical Communications |issue=8 |pages=931–932 |doi=10.1039/a800855h|url-access=subscription }}</ref><ref>{{Cite journal |last=Lozinšek |first=Matic |date=2025-04-01 |title=Single-crystal structure of the spicy capsaicin |url=https://journals.iucr.org/paper?S2053229625001706 |journal=Acta Crystallographica Section C Structural Chemistry |volume=81 |issue=4 |pages=188–192 |doi=10.1107/S2053229625001706 |issn=2053-2296 |pmc=11970115 |pmid=40052876 |bibcode=2025AcCrC..81..188L }}</ref>


== Natural function ==
== Natural function ==
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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]] that 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.
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]] that 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.


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>
The [[vanillotoxin]]-containing venom of a certain [[tarantula]] species (''[[Psalmopoeus cambridgei]])'' activates the same pathway of pain as is activated by capsaicin. It is an example of a shared pathway in both plant and animal anti-mammalian defense.<ref name="Siemens-2006">{{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 (journal)|Nature]] |volume=444 |issue=7116 |pages=208–212 |bibcode=2006Natur.444..208S |doi=10.1038/nature05285 |pmid=17093448 |s2cid=4387600}}</ref>


==Uses==
==Uses==
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{{anchor|Medical}}
{{anchor|Medical}}


===Research and pharmaceutical use===
===Research===
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/>
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}}</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}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}
*{{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> One 2017 review of clinical studies found, with limited quality, 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 | article-number = 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 | 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>


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}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}
Although capsaicin creams have been used to treat [[psoriasis]] for reduction of itching,<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> 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>  
*{{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 found, with limited quaity, 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>
Low-quality evidence indicates that oral capsaicin may decrease [[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>
 
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/>


===Pepper spray and pests===
===Pepper spray and pests===
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/>
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>
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 |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 | bibcode = 2003PMSci..59.1007J }}</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>


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| volume = 41 | issue = 8 | pages = 1383–1391 | year = 2006 | pmid = 17090499 | doi = 10.1080/0360123060096419 | bibcode = 2006JESHB..41.1383A | s2cid = 19121573 }}</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| volume = 41 | issue = 8 | pages = 1383–1391 | year = 2006 | pmid = 17090499 | doi = 10.1080/0360123060096419 | bibcode = 2006JESHB..41.1383A | s2cid = 19121573 }}</ref>
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===Equestrian sports===
===Equestrian sports===
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>
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=https://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==
==Irritant effects==
===Acute health effects===
===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>
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 }}</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>
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>
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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" />
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>
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 | access-date = 4 October 2021 | archive-date = 29 April 1999 | archive-url = https://web.archive.org/web/19990429142516/https://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml }}</ref>


===Weight loss and regain===
===Weight loss and regain===
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===Death===
===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>
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 | article-number = 5 | date = January 2012 | pmid = 22264348 | pmc = 3284873 | doi = 10.1186/1865-1380-5-5 | doi-access = free }}</ref>


==Mechanism of action==
==Mechanism of action==
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/>
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/>


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>
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|access-date=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>


==History==
==History==
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:# [[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] }}
:# [[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] }}
:# [[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] }}  
:# [[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:  
:# 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 | page = 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 = 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. }}
*{{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 | page = 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. | url-access = subscription }}
*''Year Book of Pharmacy…'' (1876),  pages 250 and 543;
*''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 = 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>  
*{{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 = 1-888483-02-4}})</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]].
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 | page = 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==
==Capsaicinoids==
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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>
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 | page = 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/>
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/>
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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>
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>
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 = 978-1-4419-7299-6 }}</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"/>
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"/>


== Evolution ==
== Evolution ==
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>
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 exhibits 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 ===
=== Antifungal properties ===
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>
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 | page = 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 | page = 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 | page = 795 | date = July 2020 | pmid = 32679672 | pmc = 7397035 | doi = 10.3390/genes11070795 | doi-access = free }}</ref>


=== Insecticidal properties ===
=== Insecticidal properties ===
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.
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 | article-number = 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 | page = 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.


=== Seed dispersion and deterrents against granivorous mammals ===
=== Seed dispersion and deterrents against granivorous mammals ===
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=== Adaptation to varying moisture levels ===
=== Adaptation to varying moisture levels ===
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>
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 seed 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 | page = 1286 | date = June 2021 | pmid = 34202853 | pmc = 8309139 | doi = 10.3390/plants10071286 | doi-access = free | bibcode = 2021Plnts..10.1286M }}</ref>


== See also ==<!-- Please respect alphabetical order -->
== See also ==<!-- Please respect alphabetical order -->
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{{Wiktionary}}
{{Wiktionary}}
* [http://npic.orst.edu/factsheets/capgen.html Capsaicin General 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]
* [https://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml Fire and Spice: The molecular basis for flavor] {{Webarchive|url=https://web.archive.org/web/19990429142516/https://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml |date=29 April 1999 }}


{{Analgesics}}
{{Analgesics}}

Latest revision as of 07:43, 24 December 2025

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Capsaicin (8-methyl-N-vanillyl-6-nonenamide) (Template:IPAc-en, commonly Template:IPAc-en)[1][2][3] is a toxin that is the main active component of chili peppers and gives them their "spicy" or "hot" taste. It is a potent irritant for mammals, including humans, for which it 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 eating by mammals and against the growth of fungi.[4] Pure capsaicin is a hydrophobic, colorless, highly pungent (i.e., spicy) crystalline solid.[5][6][7]

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 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.[8]

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 that 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.[9] There is also evidence that capsaicin may have evolved as an anti-fungal agent.[10] 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. It is an example of a shared pathway in both plant and animal anti-mammalian defense.[11]

Uses

Food

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File:Karnatakadishes.jpg
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.[12] In high concentrations, capsaicin will also cause a burning effect on other sensitive areas, such as skin or eyes.[13] The degree of heat found within a food is often measured on the Scoville scale.[12]

There has long been a demand for capsaicin-spiced products like chili pepper, and hot sauces such as Tabasco sauce and Mexican salsa.[12] It is common for people to experience pleasurable and even euphoric effects from ingesting capsaicin.[12] 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.[13]

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Research

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] One 2017 review of clinical studies found, with limited quality, 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.[17]

Although capsaicin creams have been used to treat psoriasis for reduction of itching,[18] a review of six clinical trials involving topical capsaicin for treatment of pruritus concluded there was insufficient evidence of effect.[19]

Low-quality evidence indicates that oral capsaicin may decrease LDL cholesterol levels moderately.[20]

Pepper spray and pests

Capsaicinoids are also an active ingredient in riot control and personal defense pepper spray agents.[5] When the spray comes in contact with skin, especially eyes or mucous membranes, it produces pain and breathing difficulty in the affected individual.[5]

Capsaicin is also used to deter pests, specifically mammalian pests. Targets of capsaicin repellants include voles, deer, rabbits, squirrels, bears, insects, and attacking dogs.[21] Ground or crushed dried chili pods may be used in birdseed to deter rodents,[22] 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.[23]

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."[24]

The first pesticide product using solely capsaicin as the active ingredient was registered with the U.S. Department of Agriculture in 1962.[21]

Equestrian sports

Capsaicin is a banned substance in equestrian sports because of its hypersensitizing and pain-relieving properties.[25] At the show jumping events of the 2008 Summer Olympics, four horses tested positive for capsaicin, which resulted in disqualification.[25]

Irritant effects

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 mg/kg.[26][27]

Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers.[28] 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.[29]

Treatment after exposure

The primary treatment is removal of the offending substance. Plain water is ineffective at removing capsaicin.[26] Capsaicin is soluble in alcohol, which can be used to clean contaminated items.[26]

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.[30]

Weight loss and regain

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.[31] 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.[32]

Peptic ulcer

One 2006 review concluded that capsaicin may relieve symptoms of a peptic ulcer rather than being a cause of it.[33]

Death

Ingestion of high quantities of capsaicin can be deadly,[34] particularly in people with heart problems.[35] Even healthy young people can suffer adverse health effects like myocardial infarction after ingestion of capsaicin capsules.[36]

Mechanism of action

The burning and painful sensations associated with capsaicin result from "defunctionalization" of nociceptor nerve fibers by causing a topical hypersensitivity reaction in the skin.[5][37] As a member of the vanilloid family, capsaicin binds to a receptor on nociceptor fibers called the vanilloid receptor subtype 1 (TRPV1).[37][38][39] TRPV1, which can also be stimulated with heat, protons, and physical abrasion, permits cations to pass through the cell membrane when activated.[37] The resulting depolarization of the neuron stimulates it to send impulses to the brain.[37] 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.[37]

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.[40][41]

History

The compound was first extracted in impure form in 1816 by Christian Friedrich Bucholz (1770–1818).[42]Template:Efn In 1873 German pharmacologist Rudolf Buchheim[43][44][45] (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes[46][47] stated that "capsicol" (partially purified capsaicin[48]) caused the burning feeling when in contact with mucous membranes and increased secretion of gastric acid.

Capsaicinoids

The most commonly occurring capsaicinoids are capsaicin (69%), dihydrocapsaicin (22%), nordihydrocapsaicin (7%), homocapsaicin (1%), and homodihydrocapsaicin (1%).[49]

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.[50]

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.[51]

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

File:BhutJolokia09 Asit.jpg
Chili peppers
File:Vanillamine biosynthesis.gif
Vanillamine is a product of the phenylpropanoid pathway.
File:8-methyl-6-nonenoyl biosynthesis.gif
Valine enters the branched fatty acid pathway to produce 8-methyl-6-nonenoyl-CoA.
File:Condensation to capsaicin.gif
Capsaicin synthase condenses vanillamine and 8-methyl-6-nonenoyl-CoA to produce capsaicin.

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.[52][53] 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.,[54][55] and Sukrasno and Yeoman.[56] Suzuki et al. are responsible for identifying leucine as another precursor to the branched-chain fatty acid pathway.[57] 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.[58]

Biosynthetic pathway

Plants exclusively of the genus Capsicum produce capsaicinoids, which are alkaloids.[59] 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.[60]

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.[53][61][62][63]

Capsaicin is the most abundant capsaicinoid found in the genus Capsicum, but at least ten other capsaicinoid variants exist.[64] Phenylalanine supplies the precursor to the phenylpropanoid pathway while leucine or valine provide the precursor for the branched-chain fatty acid pathway.[53][61] 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.[65] 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.[53][61]

Evolution

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.[66] 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 exhibits similar properties that serve as defensive and adaptive features. Capsaicin evolved to preserve the fitness of peppers against fungi infections, insects, and granivorous mammals.[67]

Antifungal properties

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.[68] 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.[69] Capsaicin also inhibits fungal hyphae formation, which impacts the amount of nutrients that the rest of the fungal body can receive.[70] Thirdly, capsaicin disrupts the structure[71] 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.[72]

Insecticidal properties

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.[73] Capsaicin can cause intestinal dysplasia upon ingestion, disrupting insect metabolism and causing damage to cell membranes within the insect.[74][75] This in turn disrupts the standard feeding response of insects.

Seed dispersion and deterrents against granivorous mammals

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.[76][9] 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.[8] Birds are able to eat chilies, then disperse the seeds in their excrement, enabling propagation.[9]

Adaptation to varying moisture levels

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.[77] Capsaicin synthesis in chilies places a strain on their water resources.[78] 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 seed production by 50%.[79]

See also

References

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  6. ↑ Script error: No such module "Citation/CS1".
  7. ↑ Script error: No such module "Citation/CS1".
  8. ↑ a b Script error: No such module "citation/CS1".
  9. ↑ a b c Script error: No such module "Citation/CS1".
  10. ↑ Script error: No such module "Citation/CS1".
  11. ↑ Script error: No such module "Citation/CS1".
  12. ↑ a b c d Script error: No such module "citation/CS1".
  13. ↑ a b Script error: No such module "Citation/CS1".
  14. ↑ Script error: No such module "citation/CS1".
  15. ↑ Script error: No such module "citation/CS1".Script error: No such module "Unsubst".Template:Cbignore
    • Script error: No such module "citation/CS1".
  16. ↑ Script error: No such module "citation/CS1".
  17. ↑ Script error: No such module "Citation/CS1".
  18. ↑ Script error: No such module "Citation/CS1".
  19. ↑ Script error: No such module "Citation/CS1".
  20. ↑ Script error: No such module "Citation/CS1".
  21. ↑ a b Script error: No such module "citation/CS1".
  22. ↑ Script error: No such module "Citation/CS1".
  23. ↑ Script error: No such module "citation/CS1".
  24. ↑ Script error: No such module "Citation/CS1".
  25. ↑ a b Script error: No such module "citation/CS1".
  26. ↑ a b c Script error: No such module "citation/CS1".
  27. ↑ Script error: No such module "Citation/CS1".
  28. ↑ Script error: No such module "Citation/CS1".
  29. ↑ Script error: No such module "citation/CS1".
  30. ↑ Script error: No such module "citation/CS1".
  31. ↑ Script error: No such module "Citation/CS1".
  32. ↑ Script error: No such module "Citation/CS1".
  33. ↑ Script error: No such module "Citation/CS1".
  34. ↑ Script error: No such module "citation/CS1".
  35. ↑ Script error: No such module "citation/CS1".
  36. ↑ Script error: No such module "Citation/CS1".
  37. ↑ a b c d e Script error: No such module "citation/CS1".
  38. ↑ Script error: No such module "Citation/CS1".
  39. ↑ Script error: No such module "Citation/CS1".
  40. ↑ Script error: No such module "citation/CS1".
  41. ↑ Script error: No such module "citation/CS1".
  42. ↑ Script error: No such module "citation/CS1". [Note: Christian Friedrich Bucholz's surname has been variously spelled as "Bucholz", "Bucholtz", or "Buchholz".]
  43. ↑ Script error: No such module "Citation/CS1".
  44. ↑ Script error: No such module "Citation/CS1".
  45. ↑ Script error: No such module "Citation/CS1".
  46. ↑ Script error: No such module "Citation/CS1".
  47. ↑ Script error: No such module "Citation/CS1".
  48. ↑ Script error: No such module "citation/CS1".
  49. ↑ Script error: No such module "Citation/CS1".
  50. ↑ Cite error: Script error: No such module "Namespace detect".Script error: No such module "Namespace detect".
  51. ↑ Script error: No such module "Citation/CS1".
  52. ↑ Bennett DJ, Kirby GW (1968) Constitution and biosynthesis of capsaicin. J Chem Soc C 4:442–446
  53. ↑ a b c d Script error: No such module "Citation/CS1".
  54. ↑ Script error: No such module "Citation/CS1".
  55. ↑ Script error: No such module "Citation/CS1".
  56. ↑ Script error: No such module "Citation/CS1".
  57. ↑ Script error: No such module "Citation/CS1".
  58. ↑ Script error: No such module "Citation/CS1".
  59. ↑ Script error: No such module "Citation/CS1".
  60. ↑ Script error: No such module "Citation/CS1".
  61. ↑ a b c Script error: No such module "Citation/CS1".
  62. ↑ Script error: No such module "Citation/CS1".
  63. ↑ Script error: No such module "citation/CS1".
  64. ↑ Script error: No such module "Citation/CS1".
  65. ↑ Script error: No such module "Citation/CS1".
  66. ↑ Script error: No such module "Citation/CS1".
  67. ↑ Script error: No such module "Citation/CS1".
  68. ↑ Script error: No such module "Citation/CS1".
  69. ↑ Script error: No such module "Citation/CS1".
  70. ↑ Script error: No such module "citation/CS1".
  71. ↑ Script error: No such module "Citation/CS1".
  72. ↑ Script error: No such module "Citation/CS1".
  73. ↑ Script error: No such module "Citation/CS1".
  74. ↑ Script error: No such module "citation/CS1".
  75. ↑ Script error: No such module "Citation/CS1".
  76. ↑ Script error: No such module "Citation/CS1".
  77. ↑ Script error: No such module "Citation/CS1".
  78. ↑ Script error: No such module "Citation/CS1".
  79. ↑ Script error: No such module "Citation/CS1".

Script error: No such module "Check for unknown parameters".

Notes

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Further reading

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  • Script error: No such module "citation/CS1".

External links

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