Editing Tryptophan (section)

==Society and culture==

=== Showa Denko contamination scandal ===
There was a large [[outbreak]] of [[eosinophilia-myalgia syndrome]] (EMS) in the U.S. in 1989, with more than 1,500 cases reported to the [[Centers for Disease Control and Prevention|CDC]] and at least 37 deaths.<ref>{{cite book|last1=Allen|first1=J.A.|last2=Varga|first2=J|editor1-last=Wexler|editor1-first=Philip|title=Encyclopedia of Toxicology|date=2014|publisher=Elsevier Science|location=Burlington|isbn=978-0-12-386455-0|edition=3rd|chapter=Eosinophilia–Myalgia Syndrome}}</ref> After preliminary investigation revealed that the outbreak was linked to intake of tryptophan, the U.S. [[Food and Drug Administration]] (FDA) recalled tryptophan supplements in 1989 and banned most public sales in 1990,<ref name= FDA_Tryptophan_Info>{{cite web | url = http://www.cfsan.fda.gov/~dms/ds-tryp1.html | archive-url = https://web.archive.org/web/20050225100757/http://www.cfsan.fda.gov/~dms/ds-tryp1.html | archive-date = 2005-02-25 | title = Information Paper on L-tryptophan and 5-hydroxy-L-tryptophan | date = 2001-02-01 | publisher = FU. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements | access-date = 2012-02-08 }}</ref><ref>{{cite web |url=http://www.webmd.com/vitamins-and-supplements/l-tryptophan-uses-and-risks#1 |title=L-tryptophan: Uses and Risks |website=[[WebMD]] |date=2017-05-12 |access-date=2017-06-05}}</ref><ref>{{cite news|last1=Altman|first1=Lawrence K.|title=Studies Tie Disorder to Maker of Food Supplement|url=https://www.nytimes.com/1990/04/27/us/studies-tie-disorder-to-maker-of-food-supplement.html|work=The New York Times|date=27 April 1990}}</ref> with other countries following suit.<ref>{{cite journal|last1=Castot|first1=A|last2=Bidault|first2=I|last3=Bournerias|first3=I|last4=Carlier|first4=P|last5=Efthymiou|first5=ML|title=["Eosinophilia-myalgia" syndrome due to L-tryptophan containing products. Cooperative evaluation of French Regional Centers of Pharmacovigilance. Analysis of 24 cases].|journal=Thérapie|date=1991|volume=46|issue=5|pages=355–65|pmid=1754978}}</ref><ref>{{cite web|title=COT Statement on Tryptophan and the Eosinophilia-Myalgia Syndrome|url=https://cot.food.gov.uk/sites/default/files/cot/tryptophanamend200401.pdf|publisher=UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment|date=June 2004}}</ref>

Subsequent studies suggested that EMS was linked to specific batches of <small>L</small>-tryptophan supplied by a single large Japanese manufacturer, [[Showa Denko]].<ref name= FDA_Tryptophan_Info /><ref name="pmid2355442">{{cite journal | vauthors = Slutsker L, Hoesly FC, Miller L, Williams LP, Watson JC, Fleming DW | title = Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer | journal = JAMA | volume = 264 | issue = 2 | pages = 213–7 | date = July 1990 | pmid = 2355442 | doi = 10.1001/jama.264.2.213 }}</ref><ref name="pmid8496862">{{cite journal | vauthors = Back EE, Henning KJ, Kallenbach LR, Brix KA, Gunn RA, Melius JM | title = Risk factors for developing eosinophilia myalgia syndrome among L-tryptophan users in New York | journal = The Journal of Rheumatology | volume = 20 | issue = 4 | pages = 666–72 | date = April 1993 | pmid = 8496862 }}</ref><ref name="pmid8895184">{{cite journal | vauthors = Kilbourne EM, Philen RM, Kamb ML, Falk H | title = Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome | journal = The Journal of Rheumatology. Supplement | volume = 46 | pages = 81–8; discussion 89–91 | date = October 1996 | pmid = 8895184 }}</ref> It eventually became clear that recent batches of Showa Denko's <small>L</small>-tryptophan were contaminated by trace impurities, which were subsequently thought to be responsible for the 1989 EMS outbreak.<ref name= FDA_Tryptophan_Info /><ref name="pmid2270484">{{cite journal | vauthors = Mayeno AN, Lin F, Foote CS, Loegering DA, Ames MM, Hedberg CW, Gleich GJ | title = Characterization of "peak E," a novel amino acid associated with eosinophilia-myalgia syndrome | journal = Science | volume = 250 | issue = 4988 | pages = 1707–8 | date = December 1990 | pmid = 2270484 | doi = 10.1126/science.2270484 | bibcode = 1990Sci...250.1707M }}</ref><ref name="pmid1544609">{{cite journal | vauthors = Ito J, Hosaki Y, Torigoe Y, Sakimoto K | title = Identification of substances formed by decomposition of peak E substance in tryptophan | journal = Food and Chemical Toxicology | volume = 30 | issue = 1 | pages = 71–81 | date = January 1992 | pmid = 1544609 | doi = 10.1016/0278-6915(92)90139-C }}</ref> However, other evidence suggests that tryptophan itself may be a potentially major contributory factor in EMS.<ref name = "pmid16307217">{{cite journal | vauthors = Smith MJ, Garrett RH | title = A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation | journal = Inflammation Research | volume = 54 | issue = 11 | pages = 435–50 | date = November 2005 | pmid = 16307217 | doi = 10.1007/s00011-005-1380-7 | s2cid = 7785345 }}</ref> There are also claims that a precursor reached sufficient concentrations to form a toxic [[Dimer (chemistry)|dimer]].<ref name="pred">{{cite web |author = Michael Predator Carlton |title = Molecular Biology and Genetic Engineering explained by someone who's done it |url = http://conway.cat.org.au/%7Epredator/mol.html  |archive-url=https://web.archive.org/web/20070624165916/http://conway.cat.org.au/%7Epredator/mol.html |archive-date=24 June 2007 |url-status=dead}}</ref>

The FDA loosened its restrictions on sales and marketing of tryptophan in February 2001,<ref name=FDA_Tryptophan_Info /> but continued to limit the importation of tryptophan not intended for an exempted use until 2005.<ref>{{cite journal|last1=Allen|first1=JA|last2=Peterson|first2=A|last3=Sufit|first3=R|last4=Hinchcliff|first4=ME|last5=Mahoney|first5=JM|last6=Wood|first6=TA|last7=Miller|first7=FW|last8=Whitfield|first8=ML|last9=Varga|first9=J|title=Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan.|journal=Arthritis and Rheumatism|date=November 2011|volume=63|issue=11|pages=3633–9|pmid=21702023|pmc=3848710|doi=10.1002/art.30514}}</ref>

The fact that the Showa Denko facility used [[genetically engineered]] bacteria to produce the contaminated batches of <small>L</small>-tryptophan later found to have caused the outbreak of eosinophilia-myalgia syndrome has been cited as evidence of a need for "close monitoring of the chemical purity of biotechnology-derived products".<ref name="pmid7765187">{{cite journal | vauthors = Mayeno AN, Gleich GJ | title = Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale | journal = Trends in Biotechnology | volume = 12 | issue = 9 | pages = 346–52 | date = September 1994 | pmid = 7765187 | doi = 10.1016/0167-7799(94)90035-3 }}</ref> Those calling for purity monitoring have, in turn, been criticized as anti-[[Genetically modified organism|GMO]] activists who overlook possible non-GMO causes of contamination and threaten the development of biotech.<ref name=Science2000>{{cite journal | vauthors = Raphals P | title = Does medical mystery threaten biotech? | journal = Science | volume = 250 | issue = 4981 | pages = 619 | date = November 1990 | pmid = 2237411 | doi = 10.1126/science.2237411 | bibcode = 1990Sci...250..619R }}</ref>

===Turkey meat and drowsiness hypothesis===
{{See also|Postprandial somnolence#Turkey and tryptophan}}

A common assertion in the US and the UK<ref>{{Cite news |last=Harding |first=Nick |date=2023-12-21 |title=How to stop Christmas food from ruining your sleep |language=en-GB |work=The Telegraph |url=https://www.telegraph.co.uk/health-fitness/wellbeing/sleep/why-christmas-foods-negatively-affect-sleep-quality/ |access-date=2023-12-25 |issn=0307-1235}}</ref> is that heavy consumption of [[turkey meat]]—as seen during [[Thanksgiving (United States)|Thanksgiving]] and [[Christmas]]—results in [[Somnolence|drowsiness]], due to high levels of tryptophan contained in turkey.<ref name = "McCue">{{cite web | vauthors = McCue K | title = Chemistry.org: Thanksgiving, Turkey, and Tryptophan | url = http://www.chemistry.org/portal/a/c/s/1/feature_ent.html?DOC=enthusiasts%5Cent_tryptophan.html | access-date = 2007-08-17 | archive-url = https://web.archive.org/web/20070404111342/http://www.chemistry.org/portal/a/c/s/1/feature_ent.html?DOC=enthusiasts%5cent_tryptophan.html | archive-date = 2007-04-04 }}</ref> However, the amount of tryptophan in turkey is comparable with that of other meats.<ref name = "scientificamerican" /><ref name = "USDA" /> [[Postprandial somnolence|Drowsiness after eating]] may be caused by other foods eaten with the turkey, particularly [[carbohydrate]]s.<ref name="HighBeam Research Interview">{{cite journal | title = Food & mood. (neuroscience professor Richard Wurtman) (Interview) | journal = Nutrition Action Healthletter | url = https://www.questia.com/read/1G1-12520128 |date=September 1992 }}{{dead link|date=July 2021}}</ref> Ingestion of a meal rich in carbohydrates triggers the release of [[insulin]].<ref name="pmid3279747">{{cite journal | vauthors = Lyons PM, Truswell AS | title = Serotonin precursor influenced by type of carbohydrate meal in healthy adults | journal = The American Journal of Clinical Nutrition | volume = 47 | issue = 3 | pages = 433–9 | date = March 1988 | pmid = 3279747 | doi =  10.1093/ajcn/47.3.433| doi-access = free }}</ref><ref name="pmid12499331">{{cite journal | vauthors = Wurtman RJ, Wurtman JJ, Regan MM, McDermott JM, Tsay RH, Breu JJ | title = Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios | journal = The American Journal of Clinical Nutrition | volume = 77 | issue = 1 | pages = 128–32 | date = January 2003 | pmid = 12499331 | doi =  10.1093/ajcn/77.1.128| doi-access = free }}</ref><ref name="pmid17284739">{{cite journal | vauthors = Afaghi A, O'Connor H, Chow CM | title = High-glycemic-index carbohydrate meals shorten sleep onset | journal = The American Journal of Clinical Nutrition | volume = 85 | issue = 2 | pages = 426–30 | date = February 2007 | pmid = 17284739 | doi =  10.1093/ajcn/85.2.426| doi-access = free }}</ref><ref name="Banks-2012">{{Cite journal|vauthors=Banks WA, Owen JB, Erickson MA|date=2012|title=Insulin in the Brain: There and Back Again|journal=Pharmacology & Therapeutics|volume=136|issue=1|pages=82–93|doi=10.1016/j.pharmthera.2012.07.006|issn=0163-7258|pmc=4134675|pmid=22820012}}</ref> Insulin in turn stimulates the uptake of large neutral [[branched-chain amino acids]] (BCAA), but not tryptophan, into muscle, increasing the ratio of tryptophan to BCAA in the blood stream. The resulting increased tryptophan ratio reduces competition at the [[large neutral amino acid transporter]] (which transports both BCAA and aromatic amino acids), resulting in more uptake of tryptophan across the [[blood–brain barrier]] into the [[cerebrospinal fluid]] (CSF).<ref name="Banks-2012" /><ref name="pmid1148286">{{cite journal | vauthors = Pardridge WM, [[William H. Oldendorf|Oldendorf WH]] | title = Kinetic analysis of blood-brain barrier transport of amino acids | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 401 | issue = 1 | pages = 128–36 | date = August 1975 | pmid = 1148286 | doi = 10.1016/0005-2736(75)90347-8 }}</ref><ref name="pmid6538743">{{cite journal | vauthors = Maher TJ, Glaeser BS, Wurtman RJ | title = Diurnal variations in plasma concentrations of basic and neutral amino acids and in red cell concentrations of aspartate and glutamate: effects of dietary protein intake | journal = The American Journal of Clinical Nutrition | volume = 39 | issue = 5 | pages = 722–9 | date = May 1984 | pmid = 6538743 | doi =  10.1093/ajcn/39.5.722}}</ref> Once in the CSF, tryptophan is converted into [[serotonin]] in the [[raphe nuclei]] by the normal enzymatic pathway.<ref name="pmid12499331" /><ref name="pmid5120086">{{cite journal|vauthors=Fernstrom JD, Wurtman RJ|date=1971|title=Brain serotonin content: increase following ingestion of carbohydrate diet|journal=Science|volume=174|issue=4013|pages=1023–5|doi=10.1126/science.174.4013.1023|pmid=5120086|bibcode=1971Sci...174.1023F|s2cid=14345137}}</ref> The resultant serotonin is further metabolised into the hormone [[melatonin]]—which is an important mediator of the [[circadian rhythm]]<ref>{{Cite journal |last=Atul Khullar |first=M. D. |date=2012-07-10 |title=The Role of Melatonin in the Circadian Rhythm Sleep-Wake Cycle |url=https://www.psychiatrictimes.com/view/role-melatonin-circadian-rhythm-sleep-wake-cycle |journal =Psychiatric Times | issue = 7 |language=en |volume=29}}</ref>—by the [[pineal gland]].<ref name="pmid4391290" /> Hence, these data suggest that "feast-induced drowsiness"—or [[postprandial somnolence]]—may be the result of a heavy meal rich in carbohydrates, which indirectly increases the production of melatonin in the brain, and thereby promotes sleep.<ref name="pmid3279747" /><ref name="pmid12499331" /><ref name="pmid17284739" /><ref name="pmid5120086" />