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Pesticide exposure link to ME/CFS
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== Detoxification of pesticides == Organophosphate pesticides are detoxified from the body by an enzyme called paraoxonase, whose gene is [[Paraoxonase 1| PON1]]. Mutations in the PON1 gene greatly reduce the ability of paraoxonase to detoxify organophosphates.<ref>{{Cite journal | last = Mackness | first = Bharti | last2 = Durrington | first2 = Paul | last3 = Povey | first3 = Andrew | last4 = Thomson | first4 = Stuart | last5 = Dippnall | first5 = Martin | last6 = Mackness | first6 = Mike | last7 = Smith | first7 = Ted | last8 = Cherry | first8 = Nicola | date = Feb 2003 | title = Paraoxonase and susceptibility to organophosphorus poisoning in farmers dipping sheep | url =https://www.ncbi.nlm.nih.gov/pubmed/12563177|journal=Pharmacogenetics|volume=13|issue=2 | pages = 81–88|doi=10.1097/01.fpc.0000054058.98065.38|issn=0960-314X|pmid=12563177|pmc=|quote=|access-date=|via=}}</ref><ref>{{Cite journal | last = Costa | first = Lucio G. | last2 = Richter | first2 = Rebecca J. | last3 = Li | first3 = Wan-Fen | last4 = Cole | first4 = Toby | last5 = Guizzetti | first5 = Marina | last6 = Furlong | first6 = Clement E. | date = Jan 2003 | title = Paraoxonase (PON 1) as a biomarker of susceptibility for organophosphate toxicity|url=https://www.ncbi.nlm.nih.gov/pubmed/12519632|journal=Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals|volume=8|issue=1|pages=1–12|doi=10.1080/13547500210148315|issn=1354-750X|pmid=12519632|pmc=|quote=|access-date=|via=}}</ref> The person-to-person variation in the ability of paraoxonase to detoxify organophosphate is in the range of 10- to 40-fold, and is determined in part by four SNP mutations in the PON1 gene.<ref>{{Cite journal | last = Rozek | first = Laura S. | last2 = Hatsukami | first2 = Thomas S. | last3 = Richter | first3 = Rebecca J. | last4 = Ranchalis | first4 = Jane | last5 = Nakayama | first5 = Karen | last6 = McKinstry | first6 = Laura A. | last7 = Gortner | first7 = David A. | last8 = Boyko | first8 = Edward | last9 = Schellenberg | first9 = Gerard D. | date = 2005-09-01 | title = The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status|url=http://www.jlr.org/content/46/9/1888|journal=Journal of Lipid Research|language=en|volume=46|issue=9|pages=1888–1895|doi=10.1194/jlr.M400489-JLR200|issn=0022-2275|pmid=15995178}}</ref> Individuals who have PON1 mutations which make paraoxonase less active are much more susceptible to the damage caused by organophosphates. The hormone leptin markedly decreases plasma PON1 activity.<ref>{{Cite journal | last = Bełtowski | first = Jerzy | last2 = Wójcicka | first2 = Grazyna | last3 = Jamroz | first3 = Anna | date = Sep 2003 | title = Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia|url=https://www.ncbi.nlm.nih.gov/pubmed/12957679|journal=Atherosclerosis|volume=170|issue=1|pages=21–29|doi=10.1016/s0021-9150(03)00236-3|issn=0021-9150|pmid=12957679|pmc=|quote=|access-date=|via=}}</ref> High leptin is found in obesity. Organophosphate and carbamates pesticides do not bioaccumulate to a great degree, and so are removed from the body quickly (the metabolic half-live of organophosphates in the body is in the range of hours to days).<ref>{{Cite web|url=http://www.inchem.org/documents/pims/chemical/pimg001.htm#SectionTitle:6.3%20%20Biological%20half-life%20by%20route%20of%20exposure | title = Organophosphorus pesticides | last = | first = | authorlink = | date = |website=INCHEM|archive-url=|archive-date=|url-status=|access-date=}}</ref> They also have low environmental persistence. Organochlorines pesticides on the other hand are environmentally persistent and bioaccumulate in the body fat tissues, so can remain in the body for years or decades (this is the reason organochlorines were banned and largely replaced by organophosphates and carbamates). One study found organochlorines are expelled during sweating in a sauna.<ref>{{Cite journal | last = Genuis | first = Stephen J. | last2 = Lane | first2 = Kevin | last3 = Birkholz | first3 = Detlef | date = 2016 | title=Human Elimination of Organochlorine Pesticides: Blood, Urine, and Sweat Study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069380/|journal=BioMed Research International|volume=|doi=10.1155/2016/1624643|issn=2314-6133|pmc=5069380|pmid=27800487}}</ref> Some ME/CFS patients with high blood levels of organochlorines achieved remission from their symptoms after a detoxification regimen comprising choline and ascorbic acid.<ref>{{Cite journal | last = Richardson | first = John | date = 2000-01-01 | title = Four Cases of Pesticide Poisoning, Presenting as “ME,” Treated with a Choline and Ascorbic Acid Mixture|url=https://doi.org/10.1300/J092v06n02_03|journal=Journal of Chronic Fatigue Syndrome|volume=6|issue=2|pages=11–21|doi=10.1300/J092v06n02_03|issn=1057-3321}}</ref>
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