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{{chembox
{{chembox
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| ImageFileR1 = Dichloroacetic-acid-3D-vdW.png
| ImageFileR1 = Dichloroacetic-acid-3D-vdW.png
| IUPACName = Dichloroacetic acid
| PIN = Dichloroacetic acid
| OtherNames = Dichloroethanoic acid
| OtherNames = Dichloroethanoic acid, bichloroacetic acid, DCA, BCA, dichloracetic acid, bichloracetic acid
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| CASNo = 79-43-6
| CASNo = 79-43-6
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| EINECS = 201-207-0
| Beilstein = 1098596
| Gmelin = 2477
| UNNumber = 1764
| PubChem = 6597
| PubChem = 6597
| SMILES = ClC(Cl)C(O)=O
| SMILES = ClC(Cl)C(O)=O
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| RTECS = AG6125000
| RTECS = AG6125000
| MeSHName = Dichloroacetate
| MeSHName = Dichloroacetate
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| C=2 | H=2 | Cl=2 | O=2
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| Section2 = {{Chembox Properties
| C=2|H=2|Cl=2|O=2
| Appearance = Colorless liquid
| Appearance = Colorless liquid
| Density = 1.5634 g/cm<sup>3</sup> (20 °C)
| Density = 1.5634 g/cm<sup>3</sup> (20&nbsp;°C)
| MeltingPtCL = 9
| MeltingPtC = 9 to 11
| MeltingPt_notes =
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| BoilingPtC = 194
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| Solubility = miscible
| Solubility = miscible
| SolubleOther = miscible with [[ethanol]], [[diethyl ether]]<ref name="hand">
| SolubleOther = miscible with [[ethanol]], [[diethyl ether]]<ref name = CRC/>
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| OtherFunctn = [[Chloroacetic acid]]<br />[[Trichloroacetic acid]]
| OtherFunction = [[Chloroacetic acid]]<br />[[Trichloroacetic acid]]
| Function = [[chloroacetic acids]]
| OtherFunction_label = [[chloroacetic acids]]
| OtherCpds = [[Acetic acid]]<br />[[Difluoroacetic acid]]<br />[[Dibromoacetic acid]]}}
| OtherCompounds = [[Acetic acid]]<br />[[Difluoroacetic acid]]<br />[[Dibromoacetic acid]]}}
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'''Dichloroacetic acid''', often abbreviated '''DCA''', is the [[chemical compound]] with [[chemical formula|formula]] {{chem|[[Carbon|C]][[Hydrogen|H]][[Chlorine|Cl]]|2|[[Carboxylic acid|COOH]]}}. It is an [[acid]], an [[Analog (chemistry)|analogue]] of [[acetic acid]] in which two of the three [[hydrogen]] [[atom]]s of the [[methyl]] group have been replaced by [[chlorine]] atoms. The [[salt]]s and [[ester]]s of dichloroacetic acid are called '''dichloroacetates'''. Salts of DCA have been studied as potential drugs because they inhibit the [[enzyme]] [[pyruvate dehydrogenase kinase]].
'''Dichloroacetic acid''' ('''DCA'''), sometimes called '''bichloroacetic acid''' ('''BCA'''), is the [[organic compound]] with [[chemical formula|formula]] {{chem2|CHCl2CO2H}}. It is an [[Analog (chemistry)|analogue]] of [[acetic acid]], in which 2 of the 3 hydrogen [[atoms]] of the [[methyl group]] have been replaced by [[chlorine]] atoms. Like the other [[chloroacetic acids]], it has various practical applications. The [[salts]] and [[esters]] of dichloroacetic acid are called '''dichloroacetates'''.


==Reactions==
Cancer cells change the way they metabolize oxygen in a way that promotes their survival. In laboratory studies of isolated cancer cells grown in tissue culture, DCA restores the original metabolism, and promotes their self-destruction. This has led to the use of DCA for treating cancer, by individuals experimenting with it themselves, by doctors administering it to patients as a non-approved drug, by scientists testing it in cancer tissue cultures in cell culture and in mice, and in human Phase II studies. DCA has improved certain biochemical parameters, but it has not demonstrated improved survival.
The chemistry of dichloroacetic acid is typical for [[halogen]]ated [[organic acids]]. It is an alkylating agent. It forms esters.


It is a member of the [[chloroacetic acids]] family. As such it is more acidic than acetic acid. It fully dissociates into dichloroacetate when dissolved in water, consistent with it [[Acid dissociation constant|p''K''<sub>a</sub>]] of 1.35,<ref name=CRC>{{RubberBible92nd}}</ref> pure dichloroacetic acid is classed as a [[acid strength|strong organic acid]]; it is very [[corrosive]] and extremely destructive to tissues of the [[mucous membrane]]s and [[upper respiratory tract]] via [[inhalation]].<ref name="MSDS">{{cite web|url=http://hazard.com/msds/mf/baker/baker/files/d2144.htm |title=Dichloroacetic Acid |publisher=Hazard.com |date=1998-04-21 |access-date=2015-04-17}}</ref>
A study in mice at the [[University of Alberta]] showed that "DCA induces [[apoptosis]], decreases proliferation, and inhibits tumor growth, without apparent toxicity."<ref>{{cite journal |doi=10.1016/j.ccr.2006.10.020 |title=A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth |year=2007 |last1=Bonnet |first1=SéBastien |last2=Archer |first2=Stephen L. |last3=Allalunis-Turner |first3=Joan |last4=Haromy |first4=Alois |last5=Beaulieu |first5=Christian |last6=Thompson |first6=Richard |last7=Lee |first7=Christopher T. |last8=Lopaschuk |first8=Gary D. |last9=Puttagunta |first9=Lakshmi |journal=Cancer Cell |volume=11 |pages=37–51 |pmid=17222789 |issue=1}}</ref> In 2010, a small human trial on 5 cancer patients and 49 samples of tissue was conducted.<ref name="Science"/> The results were encouraging and DCA "appeared to extend the lives of four of the five study participants".<ref>http://www.foxnews.com/health/2011/05/18/big-pharma-ignoring-potential-cancer-cure</ref>


== Chemistry and occurrence==
==Natural occurrence==
DCA has been shown to occur in nature in at least one seaweed, ''[[Asparagopsis taxiformis]]'' <ref>[http://paradigmslip.ca/references/uhm_phd_7810263_r.pdf] {{webarchive|url=https://web.archive.org/web/20150416152003/http://paradigmslip.ca/references/uhm_phd_7810263_r.pdf|date=April 16, 2015}}</ref> and also in the mushroom ''[[Russula nigricans]]''.<ref name="chemosphere">{{cite journal |doi=10.1016/j.chemosphere.2021.130819 |pmid= 33991903 |title=Is the water disinfection by-product dichloroacetic acid biosynthesized in the edible mushroom ''Russula nigricans''? |journal=Chemosphere |volume=281 |pages=130819 |year=2021 |last1=Lajin |first1=B. |last2=Braeuer |first2=S. |last3=Borovička |first3=J. |last4=Goessler |first4=W. |bibcode= 2021Chmsp.28130819L |doi-access=free }}</ref> It is a trace product of the [[Water chlorination|chlorination]] of drinking water and is produced by the [[metabolism]] of various [[chlorine]]-containing drugs or chemicals.<ref name=toxicology>{{cite journal |doi=10.1093/jnci/djx071|pmid=9703483 |pmc=1533324 |jstor=3434142 |title=Clinical Pharmacology and Toxicology of Dichloroacetate |journal=Environmental Health Perspectives |volume=106 |pages=989–94 |year=1998 |last1=Stacpoole |first1=Peter W. |last2=Henderson |first2=George N. |last3=Yan |first3=Zimeng |last4=James |first4=Margaret O. |issue=Suppl 4 }}</ref> DCA is typically prepared by the [[redox|reduction]] of [[trichloroacetic acid]] (TCA).<ref>{{Cite journal |last1=Doughty |first1=Howard Waters. |last2=Derge |first2=Gerhard Julius. |date=1931 |title=Preparation of Dichloroacetic Acid |url=https://pubs.acs.org/doi/abs/10.1021/ja01355a066 |journal=Journal of the American Chemical Society |language=en |volume=53 |issue=4 |pages=1594–1596 |doi=10.1021/ja01355a066 |issn=0002-7863}}</ref> DCA is prepared from [[chloral hydrate]] also by the reaction with [[calcium carbonate]] and [[sodium cyanide]] in water followed by acidifying with [[hydrochloric acid]].<ref>{{Cite journal |date=1939 |title=Dichloroacetic Acid |url=http://orgsyn.org/demo.aspx?prep=CV2P0181 |journal=Organic Syntheses |volume=19 |pages=38 |doi=10.15227/orgsyn.019.0038 }}</ref>


As a laboratory [[reagent]], both DCA and TCA<ref>{{Cite book |last=Koontz |first=Laura |title=Laboratory Methods in Enzymology: Protein Part C |date=2014 |chapter=TCA precipitation |chapter-url=https://pubmed.ncbi.nlm.nih.gov/24674058/ |volume=541 |pages=3–10 |doi=10.1016/B978-0-12-420119-4.00001-X |issn=1557-7988 |pmid=24674058|isbn=978-0-12-420119-4 }}</ref> are used as [[precipitant]]s to prompt [[macromolecule]]s such as [[protein]]s to [[precipitation (chemistry)|precipitate out of solution]].<ref>{{Cite journal |last1=Rajalingam |first1=Dakshinamurthy |last2=Loftis |first2=Charles |last3=Xu |first3=Jiashou J |last4=Kumar |first4=Thallapuranam Krishnaswamy S |date=2009 |title=Trichloroacetic acid-induced protein precipitation involves the reversible association of a stable partially structured intermediate |journal=Protein Science |volume=18 |issue=5 |pages=980–993 |doi=10.1002/pro.108 |issn=0961-8368 |pmc=2771300 |pmid=19388015}}</ref>
The chemistry of dichloroacetic acid is typical for [[halogen]]ated [[organic acid]]s. It is a member of the [[chloroacetic acids]] family. The dichloroacetate ion is produced when the acid is mixed with water. As an acid with a [[Acid dissociation constant|pK<sub>a</sub>]] of 1.48,<ref>Lide, D. R. (Ed.) (1990). CRC Handbook of Chemistry and Physics (70th Edn.). Boca Raton (FL):CRC Press.</ref> pure dichloroacetic acid is very corrosive and extremely destructive to tissues of the mucous membranes and upper respiratory tract.<ref name="MSDS">[http://hazard.com/msds/mf/baker/baker/files/d2144.htm MSDS (jtbaker)]</ref>


==Therapeutic uses==
DCA does not occur in nature. It is a trace product of the [[chlorination]] of drinking water and is produced by the [[metabolism]] of various [[chlorine]]-containing drugs or chemicals.<ref name=toxicology/> It is typically prepared by the [[redox|reduction]] of [[trichloroacetic acid]].
Salts of DCA have been studied as potential [[drug]]s because they inhibit the [[enzyme]] [[pyruvate dehydrogenase kinase]].<ref>{{cite journal |doi=10.1093/jnci/djx071 |title=Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer |date=2017 |last1=Stacpoole |first1=Peter W. |journal=JNCI: Journal of the National Cancer Institute |volume=109 |issue=11 |pmid=29059435 |doi-access=free }}</ref> Although preliminary studies found that DCA can slow the growth of certain tumors in [[animal studies]] and ''[[in vitro]]'' studies, as of 2012 insufficient evidence supported the use of DCA for cancer treatment.<ref name="Dichloracetate DCA">{{cite web |title=Dichloracetate (DCA) |url=http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/dichloroacetate--dca- |publisher=American Cancer Society |access-date=1 December 2012 |archive-date=3 May 2015 |archive-url=https://web.archive.org/web/20150503003338/http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/dichloroacetate--dca- |url-status=dead }}</ref>


===Lactic acidosis===
== Therapeutic use ==
A [[randomized controlled trial]] in children with [[congenital lactic acidosis]] found that while DCA was well tolerated, it was ineffective in improving clinical outcomes.<ref name="stacpoole2006">{{cite journal |doi=10.1542/peds.2005-1226 |pmid=16651305 |title=Controlled Clinical Trial of Dichloroacetate for Treatment of Congenital Lactic Acidosis in Children |journal=Pediatrics |volume=117 |issue=5 |pages=1519–31 |year=2006 |last1=Stacpoole |first1=P. W. |last2=Kerr |first2=D. S. |last3=Barnes |first3=C |last4=Bunch |first4=S. T. |last5=Carney |first5=P. R. |last6=Fennell |first6=E. M. |last7=Felitsyn |first7=N. M. |last8=Gilmore |first8=R. L. |last9=Greer |first9=M |last10=Henderson |first10=G. N. |last11=Hutson |first11=A. D. |last12=Neiberger |first12=R. E. |last13=O'Brien |first13=R. G. |last14=Perkins |first14=L. A. |last15=Quisling |first15=R. G. |last16=Shroads |first16=A. L. |last17=Shuster |first17=J. J. |last18=Silverstein |first18=J. H. |last19=Theriaque |first19=D. W. |last20=Valenstein |first20=E |s2cid=38328451 }}</ref> A separate trial of DCA in children with [[MELAS]] (a syndrome of inadequate [[Mitochondrion|mitochondria]]l function, leading to lactic acidosis) was halted early, as all 15 of the children receiving DCA experienced significant [[peripheral neuropathy|nerve toxicity]] without any evidence of benefit from the medication.<ref name="neurology.org">{{cite journal |doi=10.1212/01.wnl.0000196641.05913.27 |pmid=16476929 |title=Dichloroacetate causes toxic neuropathy in MELAS: A randomized, controlled clinical trial |journal=Neurology |volume=66 |issue=3 |pages=324–30 |year=2006 |last1=Kaufmann |first1=P. |last2=Engelstad |first2=K. |last3=Wei |first3=Y. |last4=Jhung |first4=S. |last5=Sano |first5=M. C. |last6=Shungu |first6=D. C. |last7=Millar |first7=W. S. |last8=Hong |first8=X. |last9=Gooch |first9=C. L. |last10=Mao |first10=X. |last11=Pascual |first11=J. M. |last12=Hirano |first12=M. |last13=Stacpoole |first13=P. W. |last14=Dimauro |first14=S. |last15=De Vivo |first15=D. C. |s2cid=19623200 }}</ref> A randomized controlled trial of DCA in adults with lactic acidosis found that while DCA lowered blood lactate levels, it had no clinical benefit and did not improve [[hemodynamic]]s or survival.<ref name="stacpoole1992">{{cite journal |doi=10.1056/NEJM199211263272204 |pmid=1435883 |title=A Controlled Clinical Trial of Dichloroacetate for Treatment of Lactic Acidosis in Adults |journal=New England Journal of Medicine |volume=327 |issue=22 |pages=1564–9 |year=1992 |last1=Stacpoole |first1=Peter W. |last2=Wright |first2=Elizabeth C. |last3=Baumgartner |first3=Thomas G. |last4=Bersin |first4=Robert M. |last5=Buchalter |first5=Scott |last6=Curry |first6=Stephen H. |last7=Duncan |first7=Charles A. |last8=Harman |first8=Eloise M. |last9=Henderson |first9=George N. |last10=Jenkinson |first10=Steven |last11=Lachin |first11=John M. |last12=Lorenz |first12=Anthea |last13=Schneider |first13=Stephen H. |last14=Siegel |first14=John H. |last15=Summer |first15=Warren R. |last16=Thompson |first16=Douglas |last17=Wolfe |first17=Christopher L. |last18=Zorovich |first18=Barbara |doi-access=free }}</ref>

Owing to the highly corrosive action of the acid, only the salts of dichloroacetic acid are used therapeutically, including its [[sodium]] and [[potassium]] salts, sodium dichloroacetate and potassium dichloroacetate.

=== Lactic acidosis ===

The dichloroacetate [[ion]] stimulates the activity of the [[enzyme]] [[pyruvate dehydrogenase]] by inhibiting the enzyme [[pyruvate dehydrogenase kinase]].<ref>{{cite journal |author=Stacpoole P |title=The pharmacology of dichloroacetate |journal=Metabolism |volume=38 |issue=11 |pages=1124–1144 |year=1989 |pmid=2554095 |doi=10.1016/0026-0495(89)90051-6}}</ref> Thus, it decreases [[lactic acid|lactate]] production by shifting the metabolism of [[pyruvate]] from [[glycolysis]] towards [[oxidation]] in the [[mitochondria]]. This property has led to trials of DCA for the treatment of [[lactic acidosis]] in humans.<ref name="stacpoole 1988">{{cite journal |author=Stacpoole P, Lorenz A, Thomas R, Harman E |title=Dichloroacetate in the treatment of lactic acidosis |journal=Ann Intern Med |volume=108 |issue=1 |pages=58–63 |year=1988 |pmid=3337517}}</ref><ref name="stacpoole2006">{{cite journal |author=Stacpoole P, Kerr D, Barnes C, Bunch S, Carney P, Fennell E, Felitsyn N, Gilmore R, Greer M, Henderson G, Hutson A, Neiberger R, O'Brien R, Perkins L, Quisling R, Shroads A, Shuster J, Silverstein J, Theriaque D, Valenstein E |title=Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children |journal=Pediatrics |volume=117 |issue=5 |pages=1519–1531 |year=2006 |pmid=16651305 |doi=10.1542/peds.2005-1226}}</ref><ref name="kaufmann2006">{{cite journal |author=Kaufmann P, Engelstad K, Wei Y, Jhung S, Sano M, Shungu D, Millar W, Hong X, Gooch C, Mao X, Pascual J, Hirano M, Stacpoole P, DiMauro S, De Vivo D |title=Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial |journal=Neurology |volume=66 |issue=3 |pages=324–330 |year=2006 |pmid=16476929 |doi=10.1212/01.wnl.0000196641.05913.27}}</ref><ref name="stacpoole1992">{{cite journal |doi=10.1056/NEJM199211263272204 |author=Stacpoole P, Wright E, Baumgartner T, Bersin R, Buchalter S, Curry S, Duncan C, Harman E, Henderson G, Jenkinson S |title=A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group |journal=N Engl J Med |volume=327 |issue=22 |pages=1564–1569 |year=1992 |pmid=1435883}}</ref>

A [[randomized controlled trial]] in children with congenital [[lactic acidosis]] found that while DCA was well tolerated, it was ineffective in improving clinical outcomes.<ref name="stacpoole2006"/> A separate trial of DCA in children with [[MELAS]] (a syndrome of inadequate [[Mitochondrion|mitochondria]]l function, leading to lactic acidosis) was halted early, as all 15 of the children receiving DCA experienced significant [[peripheral neuropathy|nerve toxicity]] without any evidence of benefit from the medication.<ref name="kaufmann2006"/> A randomized controlled trial of DCA in adults with lactic acidosis found that while DCA lowered blood lactate levels, it had no clinical benefit and did not improve [[hemodynamic]]s or survival.<ref name="stacpoole1992"/>


Thus, while early case reports and pre-clinical data suggested that DCA might be effective for lactic acidosis, subsequent controlled trials have found no clinical benefit of DCA in this setting. In addition, clinical trial subjects were incapable of continuing on DCA as a study medication owing to progressive toxicities.
Thus, while early case reports and pre-clinical data suggested that DCA might be effective for lactic acidosis, subsequent controlled trials have found no clinical benefit of DCA in this setting. In addition, clinical trial subjects were incapable of continuing on DCA as a study medication owing to progressive toxicities.


===Cancer===
== Potential cancer applications ==
In 2007 reports emerged in the press and via the Internet that Evangelos Michelakis and coworkers at the [[University of Alberta]] had reported that sodium dichloroacetate reduced tumors in rats and killed cancer cells ''[[in vitro]]''.<ref>{{cite journal |last1=Andy Coghlan |title=Cheap, 'safe' drug kills most cancers |journal=New Scientist |date=Jan 17, 2007 |url=https://www.newscientist.com/article/dn10971-cheap-safe-drug-kills-most-cancers/ |archive-url=https://web.archive.org/web/20190612101355/https://www.newscientist.com/article/dn10971-cheap-safe-drug-kills-most-cancers/ |url-status=dead |archive-date=June 12, 2019 }} The [https://web.archive.org/web/20070202235239/http://www.newscientist.com/channel/health/mg19325874.700-cheap-safe-drug-kills-most-cancers.html original article] did not have quotation marks around the word "safe".</ref> Because the drug cannot be patented, financing the broad and expensive testing required to obtain FDA approval is problematic.<ref>{{cite journal |title=No patent? No cancer drug development |journal=New Scientist |date=Jan 17, 2007 |url=https://www.newscientist.com/article/mg19325873-000-editorial-no-patent-no-cancer-drug-development/}}</ref> The [[US Food and Drug Administration]] enforces the law that prohibits the sale of substances with the suggestion that they are cancer treatments unless they have been approved by the FDA.<ref>{{cite journal |title='Cancer drug' site shut down |journal=New Scientist |date=Jul 25, 2007 |url=https://www.newscientist.com/article/mg19526143-600-cancer-drug-site-shut-down/}}</ref>


The [[American Cancer Society]] in 2012 stated that "available evidence does not support the use of DCA for cancer treatment at this time."<ref name="Dichloracetate DCA"/> Physicians warned of potential problems if people attempt to try DCA outside a controlled [[clinical trial]].<ref>{{cite news | url = https://www.pressreader.com/canada/edmonton-journal/20070318/281779919671127 | title = Patients tout database for drug treatment | author = Andrea Sands | publisher = Edmonton Journal | date = March 18, 2007 |page=A13 |quote= "If it starts going badly, who is following you before it gets out of control? By the time you realize your liver is failing, you're in big trouble", said Laura Shanner, Associate Professor of Health Ethics at the University of Alberta. }}</ref> One problem with attempting this is obtaining the chemical. One fraudster was sentenced to 33 months in prison for selling a white powder containing starch, but no DCA, to people with cancer.<ref>{{cite web | url = https://www.justice.gov/opa/pr/canadian-man-sentenced-33-months-prison-selling-counterfeit-cancer-drugs-using-internet | title = Canadian Man Sentenced to 33 Months in Prison for Selling Counterfeit Cancer Drugs Using the Internet | date = 25 August 2010 | publisher = US Department of Justice | access-date = January 5, 2018}}</ref>
Cancer cells generally use [[glycolysis]] rather than respiration ([[oxidative phosphorylation]]) for energy (the [[Warburg effect]]), as a result of [[Hypoxia (medical)|hypoxia]] that exists in [[tumor]]s and malfunctioning mitochondria.<ref>{{cite journal |author=Xu R, Pelicano H, Zhou Y, Carew J, Feng L, Bhalla K, Keating M, Huang P |title=Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia |journal=Cancer Res |volume=65 |issue=2 |pages=613–21 |year=2005 |pmid=15695406}}</ref> Usually dangerously damaged cells kill themselves via [[apoptosis]], a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells.


The only monitored ''[[in vivo]]'' dosage of five human patients with [[glioblastoma]] with DCA was not designed to test its efficacy against their cancer. This study was rather to see whether it could be given at a specific dosage safely without causing side effects (e.g. [[neuropathy]]). All five patients were receiving other treatments during the study.<ref name="stm.sciencemag.org">{{cite journal |doi=10.1126/scitranslmed.3000677 |pmid=20463368 |title=Metabolic Modulation of Glioblastoma with Dichloroacetate |journal=Science Translational Medicine |volume=2 |issue=31 |pages=31ra34 |year=2010 |last1=Michelakis |first1=E. D. |last2=Sutendra |first2=G. |last3=Dromparis |first3=P. |last4=Webster |first4=L. |last5=Haromy |first5=A. |last6=Niven |first6=E. |last7=Maguire |first7=C. |last8=Gammer |first8=T. L. |last9=MacKey |first9=J. R. |last10=Fulton |first10=D. |last11=Abdulkarim |first11=B. |last12=McMurtry |first12=M. S. |last13=Petruk |first13=K. C. |s2cid=616711 }}</ref><ref>{{cite web|url=http://scienceblog.cancerresearchuk.org/2010/05/12/potential-cancer-drug-dca-tested-in-early-trials |title=Potential Cancer Drug DCA Tested in Early Trials|archive-url=https://web.archive.org/web/20110218164139/http://scienceblog.cancerresearchuk.org/2010/05/12/potential-cancer-drug-dca-tested-in-early-trials |archive-date=February 18, 2011}}</ref> Observations ''in vitro'' and of tumours extracted from those five patients suggest that DCA might act against cancer cells by [[Depolarization|depolarising]] abnormal [[mitochondria]] found in glioblastoma cancer cells – allowing the mitochondria to induce apoptosis (cell death) of the [[malignant cells]].<ref name="stm.sciencemag.org"/> ''In vitro'' work with DCA on [[neuroblastoma]]s (which have fewer recognised mitochondrial abnormalities) showed activity against malignant, undifferentiated cells.<ref>{{cite journal |doi=10.1002/ijc.26173 |pmid=21557214 |title=Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells |journal=International Journal of Cancer |volume=130 |issue=7 |pages=1484–93 |year=2012 |last1=Vella |first1=Serena |last2=Conti |first2=Matteo |last3=Tasso |first3=Roberta |last4=Cancedda |first4=Ranieri |last5=Pagano |first5=Aldo |doi-access= |s2cid=19111145 }}</ref> A 2016 case report discussed and reviewed the application of DCA in central nervous system malignancies.<ref>{{cite journal |doi=10.14740/jmc2456w |title=Prolonged Survival After Dichloroacetate Treatment of Non-Small-Cell Lung Carcinoma-Related Leptomeningeal Carcinomatosis|journal=Journal of Medical Cases |volume=7 |issue=4 |pages=136–142 |year=2016 |last1=Lemmo |first1=W |last2=Tan |first2=G|url=http://www.journalmc.org/index.php/JMC/article/download/2456/1817 |doi-access=free }}</ref> A 2018 study found that DCA could trigger a metabolic switch from [[glycolysis]] (the [[Warburg effect (oncology)|Warburg effect]]) to mitochondrial [[Oxidative phosphorylation|OXPHOS]] and increase [[Reactive oxygen species|reactive oxygen stress]] affecting tumor cells. These effects were not observed in non-tumor cells.<ref>{{Cite journal|last1=Zhou|first1=Li|last2=Liu|first2=Lianlian|last3=Chai|first3=Wei|last4=Zhao|first4=Ting|last5=Jin|first5=Xin|last6=Guo|first6=Xinxin|last7=Han|first7=Liying|last8=Yuan|first8=Chunli|date=February 2019|title=Dichloroacetic acid upregulates apoptosis of ovarian cancer cells by regulating mitochondrial function|journal=OncoTargets and Therapy|volume= 12|pages=1729–1739|doi=10.2147/ott.s194329|pmid=30881027|pmc=6419601|doi-access=free}}</ref>
A phase one study published in January 2007 by researchers at the University of Alberta, who had tested DCA on cancer cells grown in mice, found that DCA restored mitochondrial function, thus restoring apoptosis, allowing cancer cells to self-destruct and shrink the tumor.<ref>Ibid. Bonnet.</ref>

These results received extensive media attention, beginning with an article in ''[[New Scientist]]'' titled "Cheap, ‘safe’ drug kills most cancers".<ref name="newscientist">{{cite web | url=http://www.newscientist.com/article.ns?id=dn10971 | title=Cheap, ‘safe’ drug kills most cancers | date=2007-01-17 | accessdate=2007-01-17 | publisher=New Scientist}}</ref> Subsequently, the [[American Cancer Society]] and other medical organizations have received a large volume of public interest and questions regarding DCA.<ref name="abcnews">[http://abcnews.go.com/Health/CancerPreventionAndTreatment/story?id=2848454&page=1 "DCA: Cancer Breakthrough or Urban Legend?"] From [[ABC News]], 5 February 2007. Accessed 15 February 2007.</ref> Clinical trials in humans with cancer have not been conducted in the USA and are not yet final in Canada, emphasizing the need for caution in interpreting the preliminary results.<ref name="abcnews"/><ref name="nowonderdrug">[http://www.newscientist.com/article/mg19325890.200-no-wonder-drug.html "No Wonder Drug"], letter to ''[[New Scientist]]'' from Ralph Moss Lemont. Published February 3, 2007. Accessed 16 February 2007.</ref>

===Results of phase II clinical trials ===

In ''in vitro'' studies, Evangelos Michelakis of University of Alberta found that in tissue samples from 49 patients, DCA caused depolarization of mitochondria in [[Glioblastoma multiforme|GBM tissue]] but not in normal brain tissue.<ref name="Science">{{cite journal | title = Metabolic Modulation of Glioblastoma with Dichloroacetate | journal = Sci Transl Med | year = 2010 | volume = 2 | issue = 31 | pages = 31ra34–31ra34 | doi = 10.1126/scitranslmed.3000677 | url = http://dca-information.pbworks.com/f/Metabolic%20Modulation%20of%20Glioblastoma%20with%20Dichloroacetate.pdf | last1 = Michelakis | first1 = E. D. | last2 = Sutendra | first2 = G. | last3 = Dromparis | first3 = P. | last4 = Webster | first4 = L. | last5 = Haromy | first5 = A. | last6 = Niven | first6 = E. | last7 = Maguire | first7 = C. | last8 = Gammer | first8 = T. L. | last9 = MacKey | first9 = J. R. | pmid=20463368}}</ref>

Five palliative patients with primary GBM were entered into a phase II trial. Three had not responded to several chemotherapies; two were newly diagnosed. After surgical removal of tumor mass, they were treated with DCA and chemotherapy.<ref name="Science"/>

Of the five patients tested, one died after three months. The surviving four were followed for 15 months. Their [[Performance status|Karnofsky scores ]] were unchanged in two cases, and decreased by 10 points in two patients.<ref name="Science"/>

DCA was associated with tumor regression and had a good safety profile. DCA side effects were minimal.<ref name="Science"/>

Michelakis is proceeding with phase three human studies with private funding from philanthropic groups and individuals. DCA's legal status as a discovery is public domain because it was made or discovered as far back as 1864<ref>T. E. (Thomas Edward) Thorpe. ''A Dictionary of Applied Chemistry''. Vol. 3. Page 9 of 189 at www.ebooksread.com/authors-eng/t-e-thomas-edward-thorpe/a-dictionary-of-applied-chemistry-volume-3-hci/page-9-a-dictionary-of-applied-chemistry-volume-3-hci.shtml</ref> and has been used in the treatment of canine and human lactic acidosis, some who presented at the beginning of treatment with cancer.

===Off-label use===

Akbar and Humaira Khan have since March 2007 treated cancer patients using DCA off-label at their private clinic, Medicor Cancer Centres, in [[Toronto]].<ref name="medicor2">[http://www.medicorcancer.com/NatPost-may28_2007.pdf Metabolic disease drug gains popularity among terminally ill cancer patients], Medicor Canter Centres, May 28, 2007</ref> They have treated several types of cancer and said on their web site that some patients "are showing varied positive responses to DCA including tumor shrinkage, reduction in tumor markers, symptom control, and improvement in lab tests".<ref name="medicor">[http://www.medicorcancer.com/DCAtherapy.html Medicor Cancer Centres – DCA Therapy<!-- Bot generated title -->]</ref> Although they have not reported results at medical conferences, they have published one peer-reviewed paper in The Journal of Palliative Medicine <ref>[http://www.liebertonline.com/doi/pdfplus/10.1089/jpm.2010.0472]</ref> and uploaded details of patient responses and overall statistics on their web site.<ref>[http://www.medicorcancer.com/DCAtherapy.html DCA (Dichloroacetate) Therapy]</ref> They report that two patients who had DCA added to traditional chemotherapy had complete remission of [[metastatic]] cancer. Medicor states that the clinical results they have been getting are in agreement with clinical trials.<ref>[http://www.medicorcancer.com/dca-data.html Medicor Cancer Centres' Observational DCA Treatment Data]</ref>

===Concerns about pre-trial use===

Following its initial publication, ''The New Scientist'' later editorialized, "The drug may yet live up to its promise as an anti-cancer agent – clinical trials are expected to start soon. It may even spawn an entirely new class of anti-cancer drugs. For now, however, it remains experimental, never yet properly tested in a person with cancer. People who self-administer the drug are taking a very long shot and, unlikely as it may sound, could even make their health worse."<ref>[http://www.newscientist.com/channel/health/mg19325972.900-editorial-gambling-with-your-life.html "Editorial: Gambling with your life"], New Scientist, 31 March 2007</ref>

In 2010 it was found that for human colorectal tumours grown in mice, under hypoxic conditions, DCA decreased rather than increased apoptosis, resulting in enhanced growth of the tumours.<ref name="Sharzad2010">{{cite journal |author=Shahrzad, Siranoush; Lacombe, Kristen; Adamcic, Una; Minhas, Kanwal; Coomber, Brenda L. |title=Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia |journal=Cancer Letters |volume=297 |issue=1 |pages=75–83 |year=2010 |month=November |pmid=20537792 |doi=10.1016/j.canlet.2010.04.027}}</ref> These findings suggest that at least in some cancer types DCA treatment could be detrimental to patient health, highlighting the need for further testing before it can be considered a safe and effective cancer treatment.<ref name="Sharzad2010"/>

===Planned and ongoing clinical trials===

DCA is non-[[patent]]able as a compound, though a patent has been filed for its use in cancer treatment.<ref>{{cite web |url=http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070120/DCA_feature_070121/20070122?hub=Health |title=CTV.ca: Researchers launch website on new cancer research |accessdate=2007-10-08 |format= |work=}}</ref> Research by [[Evangelos Michelakis]] has received no support from the [[pharmaceutical industry]]. Concerns have been raised that without strong intellectual property protection, the financial incentive for drug development is reduced, and therefore clinical trials of DCA may not be funded.<ref name="newscientist"/><ref name="abcnews"/><ref name="nowonderdrug"/><ref name="express">[http://www.expressnews.ualberta.ca/article.cfm?id=8153 "Small molecule offers big hope against cancer"], by Ryan Smith. From ExpressNews, a University of Alberta publication. Published January 16, 2007. Accessed 15 February 2007.</ref> However, other sources of funding exist; previous studies of DCA have been funded by government organizations such as the [[National Institutes of Health]], the [[Food and Drug Administration]], the [[Canadian Institutes of Health Research]] and by private charities (''e.g.'' the [[Muscular Dystrophy Association]]). Recognizing anticipated funding challenges, Michelakis's lab took the unorthodox step of directly soliciting online donations to fund the research.<ref>[http://www.depmed.ualberta.ca/dca/ Official University of Alberta DCA Site<!-- Bot generated title -->]</ref> After 6 months, his lab had raised over $800,000, enough to fund a small Clinical Phase 2 study. Michelakis and Archer have applied for a patent on the use of DCA in the treatment of cancer.<ref>[http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070120/DCA_feature_070121/20070122?hub=Health Researchers launch website on new cancer research], CTV.ca, 22 January 2007</ref><ref>[http://www.wipo.int/pctdb/en/wo.jsp?wo=2006108276 A Method of Treating Cancer Using Dichloroacetate], Application to the European Patent Office, 19 October 2006</ref>

On 24 September 2007, the Department of Medicine of Alberta University reported that after the trial funding was secured, both the Alberta local ethics committee and [[Health Canada]] approved the first DCA clinical trial for cancer.<ref>[http://www.depmed.ualberta.ca/dca/letter_092407.pdf DCA Update: Health Canada Approves First DCA Clinical Trial in Cancer], 24 September 2007</ref> This initial trial was relatively small with enrollment of up to 50 patients. The trial was completed in August 2009.<ref>[http://clinicaltrials.gov/ct2/show/NCT00540176 The Safety and Efficacy of DCA for the Treatment of Brain Cancer], ClinicalTrials.gov identifier: NCT00540176</ref> In May 2010 the team published a press release<ref name=Tufts>[http://www.dca.med.ualberta.ca/Home/Updates/2010-05-12_Update.cfm Outlook 2008], Tufts Center for the Study of Drug Development</ref> stating no conclusions could be drawn as a result of the trial. A paper describing the results was published<ref>{{cite journal |pmid=20463368 |year=2010 |last1=Michelakis |first1=ED |last2=Sutendra |first2=G |last3=Dromparis |first3=P |last4=Webster |first4=L |last5=Haromy |first5=A |last6=Niven |first6=E |last7=Maguire |first7=C |last8=Gammer |first8=TL |last9=MacKey |first9=JR |title=Metabolic modulation of glioblastoma with dichloroacetate |volume=2 |issue=31 |pages=31ra34–31ra34 |doi=10.1126/scitranslmed.3000677 |journal=Science translational medicine}}</ref> but not linked from the press release. Only five patients had been treated with the drug during the trial.

In May 2011, online reports<ref>[http://technorati.com/lifestyle/article/the-cure-for-cancer-has-been/ The Cure for Cancer Has Been Found and is Purposely Being Ignored] - Technorati blog (accessed 16/05/2011)</ref> suggested that the Alberta group had released new data which the media "had not reported". However, this appeared to be caused by confusion between dates (the previous update was May 2010<ref>[http://www.dca.med.ualberta.ca/Home/Updates/2010-05-12_Update.cfm DCA Research Team publishes results of Clinical Trials] - University of Alberta website</ref>) and cancer charities moved quickly to counter these rumours,<ref>[http://scienceblog.cancerresearchuk.org/2010/05/12/potential-cancer-drug-dca-tested-in-early-trials/ Potential cancer drug DCA tested in early trials] - Cancer Research UK science blog</ref><ref>[http://twitter.com/#!/CR_UK/status/70073173365891072 @CR_UK tweet] - tweeted 16/05/11</ref> which were subsequently covered in New Scientist magazine.<ref>[http://www.newscientist.com/blogs/shortsharpscience/2011/05/cure-for-cancer-resurfaces-and.html Cancer drug resurfaces and threatens false optimism] - New Scientist, 16 May 2011</ref>

== Side effects ==

Reports in the lay press after the 2007 [[University of Alberta]] announcement claim that dichloroacetate "has actually been used safely in humans for decades",<ref name="DCA Cancer 2">{{cite news | url=http://www.theglobeandmail.com/servlet/story/RTGAM.20070117.wxhcancer17/BNStory/specialScienceandHealth/home | title=Long-used drug shows new promise for cancer | date=2007-01-17 | accessdate=2007-01-17 | publisher=[[The Globe and Mail]]}}</ref> DCA is generally well-tolerated, even in children.<ref name="pmid18647626">{{cite journal | author = Pearson H | title = Role of dichloroacetate in the treatment of genetic mitochondrial diseases | journal = Adv Drug Deliv Rev. | volume = 60 | issue = 13,14 | pages = 1478–1487 | year = 2008 | pmid = 18647626 | doi = 10.1016/j.addr.2008.02.014 | last2 = Kurtz | first2 = TL | last3 = Han | first3 = Z | last4 = Langaee | first4 = T }}</ref> Short-term, infused, [[bolus dose|bolus doses]] of DCA at 50&nbsp;mg/kg/day have been well-tolerated.<ref name="pmid12723459">{{cite journal | author = Agbenyega T, Planche T, Bedu-Addo G, Ansong D, Owusu-Ofori A, Bhattaram VA, Nagaraja NV, Shroads AL, Henderson GN, Hutson AD, Derendorf H, Krishna S, Stacpoole PW | title = Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children | journal = J Clin Pharmacol. | volume = 43 | issue = 4 | pages = 386–396 | year = 2003 | pmid = 12723459 | doi = 10.1177/0091270003251392 }}</ref> However, at sustained, higher doses(generally 25&nbsp;mg/kg/day taken orally, or greater), there is increased risk of several reversible toxicities, especially [[peripheral neuropathy]], [[neurotoxicity]], and [[gait disturbance]].<ref name="DCA Cancer 2"/><ref name="pmid2554095">{{cite journal | author = Stacpoole PW | title = The pharmacology of dichloroacetate | journal = Metabolism | volume = 38 | issue = 11 | pages = 1124–1144 | year = 1989 | pmid = 2554095 | doi = 10.1016/0026-0495(89)90051-6 }}</ref> Studies have also shown that it can be carcinogenic at high doses.<ref name="pmid 2055364"/> The Medicor Cancer Centre reports on its website that doses of 20–25&nbsp;mg/kg/day on a two-week on, one week off cycle are effective in identifying side effects due to DCA, to support decisions on discontinuing treatment for safety reasons.<ref>{{cite web |url=http://www.medicorcancer.com/dca-data.html |title=Medicor Cancer Centre’s Observational DCA Treatment Data |author=Medicor Cancer Centre |date= July, 2009 |accessdate=10 November 2010}}</ref>


===Neuropathy===
===Neuropathy===
[[Neuropathy]] has been a problem in some clinical trials with DCA causing them to be effectively halted,<ref name="neurology.org"/> but a 2008 BJC review found that it has not occurred in other DCA trials.<ref name="nature.com">{{cite journal |doi=10.1038/sj.bjc.6604554 |pmid=18766181 |pmc=2567082 |title=Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer |journal=British Journal of Cancer |volume=99 |issue=7 |pages=989–94 |year=2008 |last1=Michelakis |first1=E D |last2=Webster |first2=L |last3=MacKey |first3=J R }}</ref> The mechanism of DCA induced neuropathy is not well understood.<ref>{{Cite web|url=https://cancerquest.org/patients/integrative-oncology/dichloroacetate-dca|archiveurl=https://web.archive.org/web/20150406023506/http://www.cancerquest.org/complementary-alternative-medicine-dca.html|url-status=dead|title=Complementary Approaches: Dichloroacetate (DCA)|archivedate=April 6, 2015|website=CancerQuest}}</ref> On the one hand ''in vitro'' work with nerves has suggested a mechanism for the neuropathic effect of DCA; with DCA showing a dose and exposure dependent demyelination of nerves (stripping of the nerve 'sheath'), which demyelination was partially reversible over time, following washout of DCA.<ref>{{cite journal |doi=10.1111/j.1471-4159.2006.04248.x |pmid=17241159 |title=Dichloroacetate causes reversible demyelination in vitro: Potential mechanism for its neuropathic effect |journal=Journal of Neurochemistry |volume=100 |issue=2 |pages=429–36 |year=2007 |last1=Felitsyn |first1=Natalia |last2=Stacpoole |first2=Peter W. |last3=Notterpek |first3=Lucia |doi-access=free }}</ref> On the other hand, the 2008 review in BJC <ref name="nature.com"/> states "This neurotoxicity resembled the pattern of length-dependent, axonal, sensorimotor polyneuropathy without demyelination." with regard to the 2006 study by Kaufman ''et al''.<ref name="neurology.org"/>


===Heart failure===
A clinical trial where DCA was given to patients of [[MELAS]] (a form of genetically inherited [[lactic acidosis]]) at 25&nbsp;mg/kg/day was ended prematurely due to excessive peripheral nerve toxicity.<ref>{{cite journal |author=Kaufmann P |title=Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial |journal=Neurology |volume=66 |issue=3 |pages=324–330 |year=2006 |pmid=16476929 |doi=10.1212/01.wnl.0000196641.05913.27 |author-separator=, |author2=Engelstad K |author3=Wei Y |display-authors=3 |last4=Jhung |first4=S |last5=Sano |first5=MC |last6=Shungu |first6=DC |last7=Millar |first7=WS |last8=Hong |first8=X |last9=Gooch |first9=CL}}</ref> Dichloroacetate can also have [[anxiolytic]] or [[sedation|sedative]] effects.<ref name=toxicology>{{cite journal |author=Stacpoole P, Henderson G, Yan Z, James M |title=Clinical pharmacology and toxicology of dichloroacetate |journal=Environ Health Perspect |volume=106 Suppl 4 |issue= |pages=989–994 |year=1998 |pmid=9703483 |doi=10.2307/3434142 |pmc=1533324 |publisher=Environmental Health Perspectives, Vol. 106 |jstor=3434142}} [http://www.ehponline.org/members/1998/Suppl-4/989-994stacpoole/stacpoole-full.html Free full text]</ref>
DCA has been investigated as a treatment for post-ischemic recovery.<ref name="Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts.">{{cite journal |pmid=2221115 |title=Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. | volume=259 |issue=4 Pt 2 | date=Oct 1990 |journal=Am J Physiol |pages=H1079-85 |author=McVeigh JJ, Lopaschuk GD|doi=10.1152/ajpheart.1990.259.4.H1079 }}</ref> There is also evidence that DCA improves metabolism by NADH production stimulation, but may lead to a depletion of NADH in normoxia.<ref name="Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate.">{{cite journal |pmid=26142699 |title=Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate. |last1=Jaimes |first1=R 3rd |doi=10.1007/s00424-015-1717-1 |date=Jul 2015 |journal=Pflügers Arch |pmc=4701640 |volume=468 |issue=1 |pages=131–42}}</ref>


==See also==
Animal studies suggest that the [[neuropathy]] and [[neurotoxicity]] during chronic dichloroacetate treatment may be partly due to depletion of [[thiamine]], and thiamine supplementation in rats reduced these effects.<ref>{{cite journal |author=Stacpoole P, Harwood H, Cameron D, Curry S, Samuelson D, Cornwell P, Sauberlich H |title=Chronic toxicity of dichloroacetate: possible relation to thiamine deficiency in rats |journal=Fundam Appl Toxicol |volume=14 |issue=2 |pages=327&ndash;37 |year=1990 |pmid=2318357 |doi=10.1016/0272-0590(90)90212-3}}</ref> However, more recent studies in humans suggest that peripheral neuropathy is a common side effect during chronic DCA treatment, even with coadministration of oral thiamine.<ref>{{cite journal |author=Kurlemann G, Paetzke I, Moller H, Masur H, Schuierer G, Weglage J, Koch HG |title=Therapy of complex I deficiency: peripheral neuropathy during dichloroacetate therapy |journal=Eur J Pediatr |volume=154 |issue=11 |pages=928&ndash;32 |year= 1995 |pmid=8582409 |doi=10.1007/BF01957508}}</ref><ref>{{cite journal |author=Spruijt L, Naviaux RK, McGowan KA, Nyhan WL, Sheean G, Haas RH, Barshop BA |title=Nerve conduction changes in patients with mitochondrial diseases treated with dichloroacetate |journal=Muscle Nerve |volume=24 |issue=7 |pages=916&ndash;24 |year=2001 |pmid=11410919 |doi=10.1002/mus.1089}}</ref> An additional study reported that 50&nbsp;mg/kg/day DCA treatment resulted in unsteady gait and lethargy in two patients, with symptoms occurring after one month for one patient and two months for the second. Gait disturbance and consciousness were recovered with cessation of DCA, however [[sensory nerve]] [[action potential]]s did not recover in one month.<ref>{{cite journal |author=Oishi K, Yoshioka M, Ozawa R, Yamamoto T, Oya Y, Ogawa M, Kawai M |title=Dichloroacetate treatment for adult patients with mitochondrial disease |journal=Rinsho Shinkeigaku |volume=43 |issue=4 |pages=154&ndash;61 |year=2003 |pmid=12892050}}</ref>
* [[Dalapon]] (dichloropropionic acid)


==References==
It has been reported that animals and patients treated with DCA have elevated levels of [[delta-aminolevulinic acid]] (delta-ALA) in the urine. A study published in 2008 suggests that this product may be the cause of the neurotoxic side effect of DCA by blocking peripheral [[myelin]] formation.<ref>{{cite journal | author = Felitsyn N, McLeod C, Shroads AL, Stacpoole PW, Notterpek L | title = The heme precursor delta-aminolevulinate blocks peripheral myelin formation | journal =J Neurochem. | volume = 106 | issue =5 | pages =2068–79 | year = 2008 | pmid =18665889 | pmc = 2574579 | doi = 10.1111/j.1471-4159.2008.05552.x }}</ref><ref>{{cite journal | last1 = Felitsyn | first1 = N | last2 = McLeod | first2 = C | last3 = Shroads | first3 = AL | last4 = Stacpoole | first4 = PW | last5 = Notterpek | first5 = L | title = The heme precursor delta-aminolevulinate blocks peripheral myelin formation | journal = Journal of neurochemistry | volume = 106 | issue = 5 | pages = 2068–79 | year = 2008 | pmid = 18665889 | pmc = 2574579 | doi = 10.1111/j.1471-4159.2008.05552.x}}</ref>
{{Reflist|colwidth=30em}}

===Carcinogenicity===

Long term use (a year or more) of high doses (> 77&nbsp;mg/kg/day) of DCA has been shown to increase risk of liver cancer in mice.<ref name="pmid 2055364">{{cite journal | author = DeAngelo AB, Daniel FB, Stober JA, Olson GR | title = The carcinogenicity of dichloroacetic acid in the male B6C3F1 mouse | journal = Fundam Appl Toxicol. | volume = 16 | issue = 2 | pages = 337–347 | year = 1991 | pmid = 2055364 | doi = 10.1016/0272-0590(91)90118-N }}</ref>
Studies of the [[trichloroethylene]] (TCE) metabolites dichloroacetic acid (DCA), [[trichloroacetic acid]] (TCA), and [[chloral hydrate]] suggest that both DCA and TCA are involved in TCE-induced liver [[tumorigenesis]] and that many DCA effects are consistent with conditions that increase the risk of [[Hepatocellular carcinoma|liver cancer]] in humans.<ref name="">Environ Health Perspect. 2006 Sep;114(9):1457-63 PMID 16966105 ([http://www.ehponline.org/members/2006/8692/8692.html free full text])</ref>

== Self-medication ==

<!-- Anonymous self-reports are not a reliable source and should not be included in Wikipedia articles, please read [[Wikipedia:No_original_research]], [[Wikipedia:Verifiability]], and [[Wikipedia:Reliable sources]]. Please do not add them. -->
The promise of DCA as a cheap, effective and safe treatment for cancer generated a great deal of public interest. Many people turned to self-medication.<ref>{{cite journal | doi = 10.1038/446474a | title = Cancer patients opt for unapproved drug | year = 2007 | last1 = Pearson | first1 = Helen | journal = Nature | volume = 446 | issue = 7135 | pages = 474–475 | pmid = 17392750}}</ref><ref>[http://www.newscientist.com/article/mg19526171.600 Interview: Would you try an untested cancer drug?], [[New Scientist]], August 15, 2007</ref>

Doctors warned of potential problems if people attempt to try DCA outside a controlled [[clinical trial]]. "If it starts going badly, who is following you before it gets out of control? By the time you realize your liver is failing, you're in big trouble", said Laura Shanner, Associate Professor of Health Ethics at the University of Alberta.<ref>{{cite news | url = http://www.canada.com/topics/news/national/story.html?id=80b15f9d-cb4a-46a0-a4bc-f1a4ddea60d3&k=56245 | title = Experts caution against patients compiling own data on unapproved cancer drug | author = Andrea Sands | publisher = Edmonton Journal | date = March 18, 2007}}</ref>

== References ==
{{Ibid|date=January 2011}}
{{Reflist|2}}

== External links ==


==External links==
* {{ICSC|0868|08}}
* {{ICSC|0868|08}}
* [https://dcaguide.org/dca-information/dca-dosage-and-usage-long-guide/ Sodium dichloroacetate (DCA) dosage and usage]
* {{cite news |author = CTV.ca News Staff |title = Small molecule offers hope for cancer treatment | url = http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070116/cancer_dca_070116/20070116 | work = CTV.ca Website |publisher = [[CTV television network]] | date = 16 January 2007 |accessdate = 2007-01-31 }}
* {{cite news |author = Evangelos Michelakis and Stephen Archer |title = Researchers launch website on new cancer research | url = http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070120/DCA_feature_070121/20070122?hub=Health | work = CTV.ca Website |publisher = [[CTV television network]] | date = 22 January 2007 |accessdate = 2007-01-31 }}
* [http://www.dca.med.ualberta.ca/Home/index.cfm DCA Research Information Website] ([[University of Alberta]])
* [http://www.newscientisttech.com/article/mg19325920.400-wait-for-clinical-trials.html Wait for Clinical Trials], New Scientist, 24 February 2007
* [http://scienceblog.cancerresearchuk.org/2010/05/12/potential-cancer-drug-dca-tested-in-early-trials/ Potential cancer drug DCA tested in early trials], by Cancer Research UK
* [http://www.martincwiner.com/between-the-lines-episode-1-dca/ Interviewing Drs. Akbar and Humaira Khan about DCA]
* [http://www.economist.com/science/displaystory.cfm?story_id=8548706 Cancer Biology – Cramping Tumors] Economist, January 18, 2007
* [http://www.dca.med.ualberta.ca/Home/Updates/2007-03-15_Update.cfm/The Official University of Alberta DCA (dichloroacetate) Website], The University of Alberta Discovery. March 15, 2007


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[[Category:IARC Group 2B carcinogens]]
[[Category:IARC Group 2B carcinogens]]
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[[Category:Alternative cancer treatments]]
[[Category:Experimental cancer drugs]]
[[Category:Experimental cancer drugs]]

[[de:Dichloressigsäure]]
[[es:Ácido dicloroacético]]
[[fr:Acide dichloroacétique]]
[[id:Asam dikloroasetat]]
[[it:Acido dicloroacetico]]
[[nl:Dichloorazijnzuur]]
[[no:Dikloretansyre]]
[[ja:ジクロロ酢酸]]
[[pl:Kwas dichlorooctowy]]
[[pt:Ácido dicloroacético]]
[[ru:Дихлоруксусная кислота]]
[[fi:Dikloorietikkahappo]]
[[sv:Diklorättiksyra]]
[[no:Dikloretansyre]]
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