Talk:Dichloroacetic acid

Origins

Can anyone one say where this chemical comes from? is it found in nature anywhere? or is it made in a lab or something? Murderbike 08:18, 24 January 2007 (UTC)

As the introduction says, it is prepared by the reduction of trichloroacetic acid. The Wednesday Island 14:22, 25 January 2007 (UTC)

That doesn't address the interesting question of whether it occurs naturally or not. --Michael C. Price ^talk 16:32, 28 January 2007 (UTC)

Agreed. Murderbike 19:07, 28 January 2007 (UTC)

How old is it?

Trying to find info about how long this has been used for other things. Footnote 7 looks promising, but you have to purchase the article to read it, and it was only posted two weeks ago. Any other info about prior usage? Thanks. 70.23.167.239 14:29, 30 January 2007 (UTC)

Multi-decade prior use is described in the literature. See abstracts below. -- Alan2012 14:53, 1 February 2007 (UTC)

DCA in cancer teraphy

You should be interested in this article: http://www.newscientist.com/article/dn10971-cheap-safe-drug-kills-most-cancers.html. —The preceding unsigned comment was added by 83.175.176.208 (talk) 10:36, 31 January 2007 (UTC).

I find it interesting that U of Alberta has proven that the mitochondria is not "damaged" in cancer cells as had been long thought. DCA merely switches the mitochondria from glycolysis mode (now know as fetus mode and/or also cancer mode) to normal surgar utilization mode. This lays a ton of additional proof on Dr. Lairds work at USC whose work recently published in Nature Genetics, showed that cancer is caused by an embryonic stem cell that is "silenced", then later in life, it is reawakened. Laird claims that the silencing and the reawakening occur due to "epigenetic" effects, meaning effects that are not genetic. In other words, smoking, drinking, air pollution, water pollution, and food additive poisons, as well as processed foods probably. In Jan 2006, E. V. Gostjeva et al, (MIT) published a study that imaged and compared colon cancer stem cells, v.s. fetal embryonic stem cells that were making a brand new colon. They were identical in appearance, and both were making the identical cell types. Gostjeva discussed that cancer may well be caused by an embryonic stem cell that fails to mature, or, an adult stem cell, that reverts to its embryonic state. They then start to make a new organ in a fully formed body, we call this cancer. In a paper in 2006 USF researchers showed that telomerase activates glycolysis in melanonma cancer cells. Here we have a way to switch it off, despite the overexpression of telomerase, with little toxicity compared to chemo, radiation, and surgery. Also notice a fetus and an untreated caner have approximately the same growth rate. Astoundingly, DCA also reactivates the P-53 suicide gene, which kills the errant cancer cell.

The truth is out, to understand cancer will require the unrestricted study of all human cell types, including embryonic stem cells that are going to be thrown away, and adult stem cells. DCA still hasn't made the t.v. news. This is a broken system.

Dichloroacetate Abstracts (a smattering, not a systematic culling)

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1533324

Environ Health Perspect. 1998 August; 106(Suppl 4): 989-994.

Research Article

Clinical pharmacology and toxicology of dichloroacetate.

P W Stacpoole, G N Henderson, Z Yan, and M O James

Department of Medicine, College of Medicine, University of Florida, Gainesville, USA. stacpool@gcrc.ufl.edu

Abstract

Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and clinicians. The chemical is a product of water chlorination and of the metabolism of various drugs and industrial chemicals. Its accumulation in groundwater and at certain Superfund sites is considered a potential health hazard. However, concern about DCA toxicity is predicated mainly on data obtained in inbred rodent strains administered DCA at doses thousands of times higher than those to which humans are usually exposed. In these animals, chronic administration of DCA induces hepatotoxicity and neoplasia. Ironically, the DCA doses used in animal toxicology experiments are very similar to those used clinically for the chronic or acute treatment of several acquired or hereditary metabolic or cardiovascular diseases. As a medicinal, DCA is generally well tolerated and stimulates the activity of the mitochondrial pyruvate dehydrogenase enzyme complex, resulting in increased oxidation of glucose and lactate and an amelioration of lactic acidosis. By this mechanism, the drug may also enhance cellular energy metabolism. DCA is dehalogenated in vivo to monochloroacetate and glyoxylate, from which it can be further catabolized to glycolate, glycine, oxalate, and carbon dioxide. It remains to be determined whether important differences in its metabolism and toxicology exist in humans between environmentally and clinically relevant doses.

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or see the PubMed citation or the full text of some References or click on a page below to browse page by page.

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URL: go medline + pmid

N Engl J Med. 1978 Mar 9;298(10):526-30.

Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia.

Stacpoole PW, Moore GW, Kornhauser DM.

Dichloroacetate is known to reduce plasma glucose and triglycerides in diabetic and starved animals and to lower plasma lactate under various experimental conditions. To investigate its metabolic effects in man, we administered oral doses (3 to 4 g) of dichloroacetate as the sodium salt to patients with diabetes mellitus or hyperlipoproteinemia or both for six to seven days. Dichloroacetate significantly reduced fasting hyperglycemia an average of 24 per cent (P less than 0.01) from base line and produced marked, concomitant falls in plasma lactate (73 per cent; P less than 0.05 to less than 0.01) and alanine (82 per cent; P less than 0.01 to less than 0.001). In addition, it significantly decreased plasma cholesterol (22 per cent; P less than 0.01 to less than 0.001) and triglyceride (61 per cent; P less than 0.01) levels while increasing (71 per cent; P less than 0.01) plasma ketone-body concentrations. Plasma insulin, free fatty acid and glycerol levels were not affected. Serum uric acid rose, whereas excretion and renal clearance fell. Some patients experienced mild sedation, but no other laboratory or clinical evidence of adverse effects was noted during or immediately after the treatment phase.

PMID: 625308

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URL: go medline + pmid

Am Heart J. 1997 Nov;134(5 Pt 1):841-55.

Dichloroacetate as metabolic therapy for myocardial ischemia and failure.

Bersin RM, Stacpoole PW.

Sanger Clinic and the Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.

This article critically reviews the pharmacologic effects of the investigational drug dichloroacetate (DCA), which activates the mitochondrial pyruvate dehydrogenase enzyme complex in cardiac tissue and thus preferentially facilitates aerobic oxidation of carbohydrate over fatty acids. The pharmacologic effects of DCA are compared with other interventions, such as glucose plus insulin, inhibitors of long chain fatty acid oxidation and adenosine, that are also thought to exert their therapeutic effects by altering myocardial energy metabolism. Short-term clinical and laboratory experiments demonstrate that intravenous DCA rapidly stimulates pyruvate dehydrogenase enzyme complex activity and, therefore, aerobic glucose oxidation in myocardial cells. Typically these effects are associated with suppression of myocardial long chain fatty acid metabolism and increased left ventricular stroke work and cardiac output without changes in coronary blood flow or myocardial oxygen consumption. Although long-term studies are lacking, short-term parenteral administration of DCA appears to be safe and capable of significantly improving myocardial function in conditions of limited oxygen availability by increasing the efficient conversion of myocardial substrate fuels into energy.

PMID: 9398096

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URL: go medline + pmid

Metabolism. 1989 Nov;38(11):1124-44.

The pharmacology of dichloroacetate.

Stacpoole PW.

Department of Medicine, University of Florida, College of Medicine, Gainesville 32610.

Dichloroacetate (DCA) exerts multiple effects on pathways of intermediary metabolism. It stimulates peripheral glucose utilization and inhibits gluconeogeneis, thereby reducing hyperglycemia in animals and humans with diabetes mellitus. It inhibits lipogenesis and cholesterolgenesis, thereby decreasing circulating lipid and lipoprotein levels in short-term studies in patients with acquired or hereditary disorders of lipoprotein metabolism. By stimulating the activity of pyruvate dehydrogenase, DCA facilitates oxidation of lactate and decreases morbidity in acquired and congenital forms of lactic acidosis. The drug improves cardiac output and left ventricular mechanical efficiency under conditions of myocardial ischemia or failure, probably by facilitating myocardial metabolism of carbohydrate and lactate as opposed to fat. DCA may also enhance regional lactate removal and restoration of brain function in experimental states of cerebral ischemia. DCA appears to inhibit its own metabolism, which may influence the duration of its pharmacologic actions and lead to toxicity. DCA can cause a reversible peripheral neuropathy that may be related to thiamine deficiency and may be ameliorated or prevented with thiamine supplementation. Other toxic effects of DCA may be species-specific and reflect marked interspecies variation in pharmacokinetics. Despite its potential toxicity and limited clinical experience, DCA and its derivatives may prove to be useful in probing regulatory aspects of intermediary metabolism and in the acute or chronic treatment of several metabolic disorders.

PMID: 2554095

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http://toxsci.oxfordjournals.org/cgi/content/abstract/14/2/327

Toxicological Sciences - Volume 14, Number 2 Pp. 327-337

c 1990 Oxford University Press other

Chronic Toxicity of Dichloroacetate: Possible Relation to Thiamine Deficiency in Rats

PETER W. STACPOOLE*, H. JAMES HARWOOD, JR, DON F. CAMERON, STEPHEN H. CURRY(th), DON A. SAMUELSNO, PHILLIP E. CORNWELL and HOWARDE E. SAUBERLICH

• Departments of Medicine (Division of Endocrinology and

Metabolism), University of Florida, Colleges of Medicine, Pharmacy and Veterinary Sciences Gainesville, Florida 32610 Departments of Pharmacology, University of Florida, Colleges of Medicine, Pharmacy and Veterinary Sciences Gainesville, Florida 32610 Departments of Anatomy, University of Florida, Colleges of Medicine, Pharmacy and Veterinary Sciences Gainesville, Florida 32610 (th)Departments of Clinical Pharmacokinetics, University of Florida, Colleges of Medicine, Pharmacy and Veterinary Sciences Gainesville, Florida 3261 0Departments of Veterinary Opthalmology, University of Florida, Colleges of Medicine, Pharmacy and Veterinary Sciences Gainesville, Florida 32610 Department of Nutrition Sciences, University of Alabama Birmingham, Alabama 35294

Received April 21, 1989; Chronic Toxicity of Dichloroacetate: Possible Relation to Thiamine Deficiency in Rats. STACPOOLE, P. W., HARWOOD, H. J., JR., CAMERON, D. F., CURRY, S. H., SAMUELSON, D. A., CORNWELL, P. E., AND SAUBERLICH, H. E. (1990). Fundam. Appl. Toxicol. 14, 327-337. The chronic use of dichloroacetate (DCA) for diabetes mellitus or hyperlipoproteinemias has been compromised by neurologic and other forms of toxicity. DCA is metabolized to glyoxylate, which is converted to oxalate and, in the presence of adequate thiamine levels, to other metabolites. DCA stimulates the thiamine-dependent enzymes pyruvate dehydrogenase and a-ketoacid dehydrogenase. We postulated that the neurotoxicity from chronic DCA administration could result from depletion of body thiamine stores and abnormal metabolism of oxalate, a known neurotoxin. For 7 weeks, rats were fed ad lib. Purina chow and water or chow plus sodium DCA (50 mg/kg or 1.1 g/kg) in water. A portion of the DCA-treated animals also received intraperitoneal injections of 600 æ thiamine three times weekly or 600 æ thiamine daily by mouth. Thiamine status was assessed by determining red cell transketolase activity and, in a blinded manner, by recording the development of clinical signs known to be associated with thiamine deficiency. At the 50 mg/kg dose, chronic administration of DCA showed no clinical toxicity or effect on transketolase activity. At the 1.1 g/kg dose, however, DCA markedly increased the frequency and severity of toxicity and decreased transketolase activity 25%, compared to controls. Coadministration of thiamine substantially reduced evidence of thiamine deficiency and normalized transketolase activity. Inhibition of transketolase by DCA In vivo was not due to a direct action on the enzyme, however, since DCA, glyoxylate, or oxalate had no appreciable effects on transketolase activity in vitro. After 7 weeks, plasma DCA concentrations were similar in rats receiving DCA alone or DCA plus thiamine, while urinary oxalate was 86% above control in DCA-treated rats but only 28% above control in DCA plus thiamine-treated animals. No light microscopic changes were seen in peripheral nerve, lens, testis, or kidney morphology in either DCA-treated group, nor was there disruption of normal sperm production in the DCA-treated group. We conclude that stimulation by DCA of thiamine-requiring enzymes may lead to depletion of total body thiamine stores and to both a fall in transketolase activity and an increase in oxalate accumulation In vivo. DCA neurotoxicity may thus be due, at least in part, to thiamine deficiency and may be preventable with thiamine treatment.

-- Alan2012 14:52, 1 February 2007 (UTC)

Chemistry

"The chemistry of dichloroacetic acid is closely related to halogenated organic acids." I'm confused... I thought dichloroacetic acid WAS a halogenated organic acid? Geoff 06:40, 2 February 2007 (UTC)

Copyvio

Several long segments of the article were copied and pasted directly from the pages linked to or referenced at the end.