Dichloroacetate danger and risk by Ray Sahelian, M.D.

Dichloroacetate (DCA) is a potential environmental hazard, owing to its wide presence in the biosphere and its association with animal and human toxicity.

Dichloracetate benefit
Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency.
Mitochondrion. 2006. Division of Endocrinology and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
We reviewed the use of oral dichloroacetate in the treatment of children with congenital lactic acidosis caused by mutations in the pyruvate dehydrogenase complex (PDC). The case histories of 46 subjects were analyzed with regard to diagnosis, clinical presentation and response to this medication. Dichloroacetate decreased blood and cerebrospinal fluid lactate concentrations, and was generally well tolerated. Dichloroacetate may be particularly effective in children with PDC deficiency by stimulating residual enzyme activity and, consequently, cellular energy metabolism. A controlled trial is needed to determine the definitive role of dichloroacetate in the management of this devastating disease.

Use for cancer treatment
At this time, March 2012, I cannot find randomized, double-blind clinical trials regarding its influence on various types of cancer in humans. Therefore I do not know if it is of benefit.

J Palliat Med. 2011 .Use of oral dichloroacetate for palliation of leg pain arising from metastatic poorly differentiated carcinoma: a case report. Medicor Cancer Centres, Toronto, Canada. Dichloroacetate sodium (DCA) is a nonproprietary drug currently used for treatment of inherited mitochondrial diseases. It was discovered in 2007 that DCA promotes human cancer cell death by a novel mechanism. Soon after this discovery, physicians began using DCA off-label for cancer treatment in a palliative setting. A case report is presented of a 71-year-old male with poorly differentiated carcinoma of unknown primary metastatic to the right leg and liver who achieved excellent palliation of leg pain by using oral DCA after failing conventional therapy.

J Biomed Biotechnol. 2011. Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer.Tong J, Xie G, He J, Li J, Pan F, Liang H.SourceDepartment of Oncology, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China.AbstractDichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been recently demonstrated as a promising nontoxic antineoplastic agent that promotes apoptosis of cancer cells. In the present study, we aimed to investigate the antitumor effect of DCA combined with 5-Fluorouracil (5-FU) on colorectal cancer (CRC) cells. Four human CRC cell lines were treated with DCA or 5-FU, or a combination of DCA and 5-FU. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The interaction between DCA and 5-FU was evaluated by the median effect principle. Immunocytochemistry with bromodeoxyuridine (BrdU) was carried out to determine the proliferation of CRC cells. Cell cycle and apoptosis were measured by flow cytometry, and the expression of apoptosis-related molecules was assessed by western blot. Our results demonstrated that DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU. Moreover, compared with 5-FU alone, the apoptosis of CRC cells treated with DCA and 5-FU was enhanced and demonstrated with the changes of Bcl-2, Bax, and caspase-3 proteins. Our results suggest that DCA has a synergistic antitumor effect with 5-FU on CRC cell lines in vitro.

Dichloroacetate studies in rodents
Maternal exposure to high doses of trichloroethylene (TCE) and its oxidative metabolites, trichloroacetic acid (TCA) and dichloroacetic acid, has been implicated in eye malformations in fetal rats.

Dichloroacetate and neuropathy
Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology. 2006 Oct 10;67(7):1313; Comment on: Neurology. 2006 Feb 14;66(3):324-30.