Written by Irene Fischer, Markus Horneber, Katja Boehm and the CAM-Cancer Consortium.
Updated August 31, 2010

Dichloroacetate

Is it safe?

There are several studies that reported a low toxicity profile of DCA when used over a short period of time.6,23-26 Nevertheless, animal studies did not provide a so-called “No Observed Adverse Effect Level”.

Adverse effects

There are several studies that reported a low toxicity profile of DCA when used over a short period of time.6,23-26 Nevertheless, animal studies did not provide a so-called “No Observed Adverse Effect Level”.2

Data from animals suggest renal, glandular and bone marrow toxicity and demonstrate unequivocally that DCA causes benign and malignant liver tumors in inbred rat and mouse strains.2,7,27 In humans the nervous system and the liver have been identified as being sensitive to the toxicity of DCA, especially in adults.3,28

Neuropathies have been observed, especially after long-term application for metabolic illnesses. Kaufmann et al. reported axonal sensory-motor peripheral neuropathy without demyelization in adolescents and adults with a genetic mitochondrial disease who received 25 mg/kg/day DCA for several weeks or months.29 Although severe courses are reported,30 most of the neurologic toxicities are regarded as being reversible, however, their regression can take up to several months.31 Dependent on dose and duration of treatment, DCA induces hepatocellular injury, also being reversible after stopping DCA-treatment.32 There is no evidence that DCA causes liver cancer in humans.

In a recent phase II trial, five participants received DCA 12.5mg/kg orally twice a day for one month followed by 25 mg/kg orally twice a day. The authors then followed a dose de-escalation protocol by which the dose was decreased by 50% when dose-limiting toxicity occurred. The only reported toxicities were reversible grade I-III peripheral neuropathies at the 12.5mg/kg and 25 mg/kg dose levels. At the 6.25 mg/kg level, none of the patients had clinically significant peripheral neuropathy.8

Precautions/warnings

There are no data on the use of DCA during pregnancy and lactation. The majority of in vitro analyses did not show any mutagenic effects of DCA. However, in rats DCA has an embryotoxic and teratogenic effect with dose-dependent damages to the cardiovascular and uro-genital tract.2 Several institutions, including the FDA have listed DCA as a possible “cancer-inducing“ agent in humans.

Interactions

As neurological toxicities often occur in patients being treated with chemotherapy, the risk of neuropathy could escalate.4 This could, for instance, be the case for agents such as bortezomib, oxaliplatin, cisplatin, or thalidomide.
In a recent study, the effects of DCA in combination with cisplatin, doxorubicin and temozolomide on mitochondrial membrane potential, cell viability and induction of apoptosis in malignant and non-malignant cell lines were investigated. The results suggest that DCA might reduce the cytotoxicity of cisplatin and doxorubicin but not that of temozolomide.33

Quality issues

DCA is often sold as industrial or technical grade, which might not be produced with the quality standards as pharmaceutical grade. Regarding the shelf life and storage the providers state that DCA can be stored for up to 1 year.21

Citation Irene Fischer, Markus Horneber, Katja Boehm, CAM-Cancer Consortium. Dichloroacetate [online document]. http://www.cam-cancer.org/CAM-Summaries/Dietary-approaches/Dichloroacetate. August 31, 2010.

References

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  3. Ammini, C. V. & Stacpoole, P. W. The Handbook of Environmental Chemistry. Gribble, G. W. (ed.), pp. 215-234 (Springer Verlag, Berlin,2003).
  4. Michelakis, E. D., Webster, L. & Mackey, J. R. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br J Cancer 99, 989-994 (2008).
  5. Stacpoole, P. W., Nagaraja, N. V. & Hutson, A. D. Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol 43, 683-691 (2003).
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  8. Michelakis, E. D. et al. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med 2, 31ra34 (2010).
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