Capsaicin#Capsaicinoids

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.{{cite web| publisher = New Mexico State University – College of Agriculture and Home Economics |title=Chile Information – Frequently Asked Questions |year=2005 |url=http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub |access-date=17 May 2007 |archive-url = https://web.archive.org/web/20070504035555/http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub |archive-date = 4 May 2007}}

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.{{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 }} There is also evidence that capsaicin may have evolved as an anti-fungal agent.{{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 }} 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.{{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}}

{{Main|Pungency}}

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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.{{cite news|url=https://www.nytimes.com/2010/09/21/science/21peppers.html|title=A Perk of Our Evolution: Pleasure in Pain of Chilies|newspaper=New York Times|date=20 September 2010| vauthors = Gorman J |access-date=16 March 2015}} In high concentrations, capsaicin will also cause a burning effect on other sensitive areas, such as skin or eyes.{{cite journal | vauthors = Rollyson WD, Stover CA, Brown KC, Perry HE, Stevenson CD, McNees CA, Ball JG, Valentovic MA, Dasgupta P | title = Bioavailability of capsaicin and its implications for drug delivery | journal = Journal of Controlled Release | volume = 196 | pages = 96–105 | date = December 2014 | pmid = 25307998 | pmc = 4267963 | doi = 10.1016/j.jconrel.2014.09.027 }} The degree of heat found within a food is often measured on the Scoville scale.

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

{{anchor|Medical}}

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

It is also used to reduce the symptoms of peripheral neuropathy, such as post-herpetic neuralgia caused by shingles. 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){{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}}{{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}}

• {{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}} and the European Union.{{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}} A subsequent application to the FDA for Qutenza to be used as an analgesic in HIV neuralgia was refused.{{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}} 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.{{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 }}

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

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

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

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

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."{{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 }}

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

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

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.{{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 }}{{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}}

Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers.{{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}} 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.{{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 }}

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

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.{{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 }}

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.{{cite journal | vauthors = Diepvens K, Westerterp KR, Westerterp-Plantenga MS | title = Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 292 | issue = 1 | pages = R77–R85 | date = January 2007 | pmid = 16840650 | doi = 10.1152/ajpregu.00832.2005 | s2cid = 7529851 | url = https://cris.maastrichtuniversity.nl/en/publications/d418019f-bac5-49bd-b3de-dfaf8f2c6736 }} 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.{{cite journal | vauthors = Whiting S, Derbyshire EJ, Tiwari B | title = Could capsaicinoids help to support weight management? A systematic review and meta-analysis of energy intake data | journal = Appetite | volume = 73 | pages = 183–188 | date = February 2014 | pmid = 24246368 | doi = 10.1016/j.appet.2013.11.005 | s2cid = 30252935 }}

One 2006 review concluded that capsaicin may relieve symptoms of a peptic ulcer rather than being a cause of it.{{cite journal | vauthors = Satyanarayana MN | title = Capsaicin and gastric ulcers | journal = Critical Reviews in Food Science and Nutrition | volume = 46 | issue = 4 | pages = 275–328 | date = 2006 | pmid = 16621751 | doi = 10.1080/1040-830491379236 | s2cid = 40023195 }}

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

The burning and painful sensations associated with capsaicin result from "defunctionalization" of nociceptor nerve fibers by causing a topical hypersensitivity reaction in the skin.{{cite web |title=Capsaicin |url=https://go.drugbank.com/drugs/DB06774 |publisher=DrugBank |access-date=1 June 2023 |date=4 January 2023}} As a member of the vanilloid family, capsaicin binds to a receptor on nociceptor fibers called the vanilloid receptor subtype 1 (TRPV1).{{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}}{{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 }} TRPV1, which can also be stimulated with heat, protons and physical abrasion, permits cations to pass through the cell membrane when activated. The resulting depolarization of the neuron stimulates it to send impulses to the brain. 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.

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.{{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}}{{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}}

The compound was first extracted in impure form in 1816 by Christian Friedrich Bucholz (1770–1818).

{{cite book| vauthors = Bucholz CF |date=1816|chapter=Chemische Untersuchung der trockenen reifen spanischen Pfeffers|trans-chapter=Chemical investigation of dry, ripe Spanish peppers|title=Almanach oder Taschenbuch für Scheidekünstler und Apotheker|location=Weimar|trans-title=Almanac or Pocketbook for Analysts and Apothecaries|volume=37|pages=1–30}} [Note: Christian Friedrich Bucholz's surname has been variously spelled as "Bucholz", "Bucholtz", or "Buchholz".]

{{efn|1=History of early research on capsaicin:

• {{cite book| vauthors = Felter HW, Lloyd JU |title=King's American Dispensatory|location=Cincinnati, Ohio|publisher=Ohio Valley Co.|date=1898|volume=1|page=435|url=http://www.henriettesherbal.com/eclectic/kings/capsicum.html}}
• {{cite thesis| vauthors = Du Mez AG |title=A century of the United States pharmocopoeia 1820–1920. I. The galenical oleoresins|type=PhD|publisher=University of Wisconsin|date=1917|pages=111–132|url=https://archive.org/stream/centuryofuniteds00dumerich/centuryofuniteds00dumerich_djvu.txt}}
• The results of Bucholz's and Braconnot's analyses of Capsicum annuum appear in: {{cite book| vauthors = Pereira J |title=The Elements of Materia Medica and Therapeutics|edition=3rd US|location=Philadelphia, Pennsylvania|publisher=Blanchard and Lea|date=1854|volume=2|url=https://books.google.com/books?id=IrXszQ77xhYC&pg=PA506|page=506}}
• Biographical information about Christian Friedrich Bucholz is available in: {{cite book| veditors = Rose HJ, Wright T |title=A New General Biographical Dictionary|location=London, England | publisher = T. Fellowes |date=1857|volume=5|url=https://books.google.com/books?id=nNRySUejNcYC&pg=PA186|page=186 | vauthors = Rose HJ }}
• Biographical information about C. F. Bucholz is also available (in German) online at: [http://de.wikisource.org/wiki/ADB:Bucholtz,_Christian_Friedrich Allgemeine Deutsche Biographie].
• Some other early investigators who also extracted the active component of peppers:

:# {{cite journal | vauthors = Maurach B | date = 1816 | title = Pharmaceutisch-chemische Untersuchung des spanischen Pfeffers | trans-title = Pharmaceutical-chemical investigation of Spanish peppers | journal = Berlinisches Jahrbuch für die Pharmacie | language = de | volume = 17 | pages = 63–73 }} Abstracts of Maurach's paper appear in: (i) Repertorium für die Pharmacie, vol. 6, [https://books.google.com/books?id=euo8AAAAcAAJ&pg=PA117 page 117-119] (1819); (ii) Allgemeine Literatur-Zeitung, vol. 4, no. 18, [https://books.google.com/books?id=rRo4AAAAMAAJ&pg=RA2-PA20-IA2 page 146] (February 1821); (iii) "Spanischer oder indischer Pfeffer", System der Materia medica ..., vol. 6, [https://books.google.com/books?id=jgA9AAAAcAAJ&pg=PA381 pages 381–386] (1821) (this reference also contains an abstract of Bucholz's analysis of peppers).

:# 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] }}

:# 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,In a series of articles, J. C. Thresh obtained capsaicin in almost pure form:

• {{cite journal | vauthors = Thresh JC | date = 1876 | title = Isolation of capsaicin | journal = The Pharmaceutical Journal and Transactions |series=3rd Series | volume = 6 | pages = 941–947 }}
• {{cite journal | vauthors = Thresh JC | date = 8 July 1876 | title = Capsaicin, the active principle in Capsicum fruits | journal = The Pharmaceutical Journal and Transactions |series=3rd Series | volume = 7 | issue = 315 | pages = 21| doi = | bibcode = }} [Note: This article is summarized in: {{cite journal | title = Capsaicin, the active principle in Capsicum fruits | journal = The Analyst | volume = 1 | issue = 8 | url = http://pubs.rsc.org/en/Content/ArticleLanding/1876/AN/an876010148b | pages = 148–149 | date = 1876 | doi = 10.1039/an876010148b | bibcode = 1876Ana.....1..148. }}
• Year Book of Pharmacy… (1876), pages 250 and 543;
• {{cite journal | vauthors = Thresh JC | date = 1877 | title = Note on Capsaicin | url = https://archive.org/stream/yearbookofpharma1877londuoft/yearbookofpharma1877londuoft_djvu.txt | journal = Year Book of Pharmacy | pages = 24–25 }}
• {{cite journal | vauthors = Thresh JC | date = 1877 | title = Report on the active principle of Cayenne pepper | journal = Year Book of Pharmacy | pages = 485–488 }}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 }} gave it the name "capsaicin" in 1876.{{cite book | vauthors = King J, Felter HW, Lloys JU | date = 1905 | title = A King's American Dispensatory. | publisher = Eclectic Medical Publications | isbn = 1888483024}}) Karl Micko isolated capsaicin in its pure form in 1898.{{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}}{{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}} Capsaicin's chemical composition was first determined in 1919 by E. K. Nelson, who also partially elucidated capsaicin's chemical structure.{{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 }} Capsaicin was first synthesized in 1930 by Ernst Spath and Stephen F. Darling.{{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 }} In 1961, similar substances were isolated from chili peppers by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.{{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 }}{{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 }}

}}

In 1873 German pharmacologist Rudolf Buchheim{{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 }}{{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 }}{{cite journal | vauthors = Buchheim R | title = Fructus Capsici. | journal = Proceedings of the American Pharmaceutical Association | date = 1873 | volume = 22 | pages = 106 }} (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes{{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 }}{{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 }} stated that "capsicol" (partially purified capsaicin{{cite book | vauthors = Flückiger FA | title = Pharmakognosie des Pflanzenreiches | location = Berlin, Germany | publisher = Gaertner's Verlagsbuchhandlung | date = 1891 }}) caused the burning feeling when in contact with mucous membranes and increased secretion of gastric acid.

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

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.

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.{{cite journal | vauthors = Constant HL, Cordell GA, West DP |title = Nonivamide, a Constituent of Capsicum oleoresin |journal = Natural Products | date = April 1996 | volume = 59 | issue = 4 | pages = 425–426 | doi = 10.1021/np9600816|bibcode = 1996JNAtP..59..425C }}

File:BhutJolokia09 Asit.jpg

Image:Vanillamine biosynthesis.gif

Image:8-methyl-6-nonenoyl biosynthesis.gif

Image:Condensation to capsaicin.gif

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.Bennett DJ, Kirby GW (1968) Constitution and biosynthesis of capsaicin. J Chem Soc C 4:442–446 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.,{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Intracellular distributions of enzymes and intermediates involved in biosynthesis of capsaicin and its analogues in Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = November 1982 | volume = 46 | issue = 11 | pages = 2685–2689 | doi = 10.1080/00021369.1982.10865495 }}{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Capsaicinoid formation in the protoplast from the placenta of Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = October 1982 | volume = 46 | issue = 10 | pages = 2591–2592 | doi = 10.1080/00021369.1982.10865477 }} and Sukrasno and Yeoman.{{cite journal | vauthors = Sukrasno N, Yeoman MM | year = 1993 | title = Phenylpropanoid metabolism during growth and development of Capsicum frutescens fruits | journal = Phytochemistry | volume = 32 | issue = 4| pages = 839–844 | doi=10.1016/0031-9422(93)85217-f| bibcode = 1993PChem..32..839S }} Suzuki et al. are responsible for identifying leucine as another precursor to the branched-chain fatty acid pathway.{{cite journal | vauthors = Suzuki T, Kawada T, Iwai K | year = 1981 | title = Formation and metabolism of pungent principle of Capsicum fruits. 9. Biosynthesis of acyl moieties of capsaicin and its analogs from valine and leucine in Capsicum fruits | journal = Plant & Cell Physiology | volume = 22 | pages = 23–32 | doi = 10.1093/oxfordjournals.pcp.a076142 }} 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.{{cite journal | vauthors = Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O'Connell MA | year = 1999 | title = Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum spp | journal = Plant Sci | volume = 148 | issue = 1 | pages = 47–57 | doi = 10.1016/s0168-9452(99)00118-1 | bibcode = 1999PlnSc.148...47C | s2cid = 86735106 }}

Plants exclusively of the genus Capsicum produce capsaicinoids, which are alkaloids.{{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 }} 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.{{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 }}

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.{{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 }}{{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 }}{{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 }}{{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 }}

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

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

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.{{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 }} 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.{{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 }} Capsaicin also inhibits fungal hyphae formation, which impacts the amount of nutrients that the rest of the fungal body can receive.{{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}} Thirdly, capsaicin disrupts the structure{{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 }} 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.{{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 }}

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

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.{{cite journal | vauthors = Levey DJ, Tewksbury JJ, Cipollini ML, Carlo TA | title = A field test of the directed deterrence hypothesis in two species of wild chili | journal = Oecologia | volume = 150 | issue = 1 | pages = 61–68 | date = November 2006 | pmid = 16896774 | doi = 10.1007/s00442-006-0496-y | bibcode = 2006Oecol.150...61L | s2cid = 10892233 }} 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. Birds are able to eat chilies, then disperse the seeds in their excrement, enabling propagation.

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.{{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 }} Capsaicin synthesis in chilies places a strain on their water resources.{{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 }} This directly affects their fitness, as it has been observed that standard concentration of capsaicin of peppers in high moisture environments in the seeds and pericarps of the peppers reduced the seeds production by 50%.{{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 }}

== See also ==

• Allicin, the active piquant flavor chemical in uncooked garlic, and to a lesser extent onions (see those articles for discussion of other chemicals in them relating to pungency, and eye irritation)
• Capsazepine, capsaicin antagonist
• Iodoresiniferatoxin, an ultrapotent capsaicin antagonist derived from Resiniferatoxin
• Naga Viper pepper, Bhut Jolokia Pepper, Carolina Reaper, Trinidad Moruga Scorpion; some of the world's most capsaicin-rich fruits
• Piperine, the active flavor chemical in black pepper
• List of capsaicinoids

{{Reflist}}

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• {{cite book | vauthors = Abdel-Salam OM | title = Capsaicin as a Therapeutic Molecule | publisher = Springer | date = 2014 | isbn = 978-3-0348-0827-9 }}

{{refend}}

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{{Wiktionary}}

• [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]

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