Written by Timm Hoeres, Markus Horneber and the CAM-Cancer Consortium.
Updated July 13, 2016

Dichloroacetate

Is it safe?

Adverse effects

There are several studies that reported a low toxicity profile of DCA when used over a short period of time 5,27-30. However, animal studies did not provide a so-called “No Observed Adverse Effect Level” and found toxic effects of DCA on thekidney, peripheral nerves and the bone marrow 1,4,6,31,32.

Peripheral neuropathies are the most frequently reported adverse effects in clinical trials with numbness, paresthesia and gait disturbance. Kaufmann et al. reported axonal sensory-motor peripheral neuropathy without demyelisation in adolescents and adults with a genetic mitochondrial disease who received 25 mg/kg/day DCA for several weeks or months 33. In their phase I trial, Michelakis et al. reported no events of peripheral neuropathies at the 6.25 mg/kg dose level 5. Although severe courses of neuropathies are reported 34, most of the neurologic toxicities are regarded as being re­ver­sible; however, their regression can take up to several months 35.

Other adverse effects that were reported in the phase I clinical trials in cancer patients were fatigue, gastrointestinal symptoms, and reversible hepatocellular injury 9,36,37,23. One study with DCAwas closed prematurely due to safety concerns after the early death of two patients but it was unclear whether the early death was associated with the application of DCA 20.

Contraindications

The following conditions might be regarded as contraindication for the use of DCA: history of allergic reactions attributed to halogenated organic acids, presence of intermediate or higher grade peripheral neuropathy due to co-morbidities (such as multiple sclerosis) and hepatic diseases.

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 1. Several institutions, including the FDA have listed DCA as a possible “cancer-inducing” agent in humans.

Stacpoole reported mild sedative and/or anxiolytic effects after oral and parenteral administration of the DCA in occasional subjects 37.

Interactions

As neurological toxicities often occur in patients being treated with chemotherapy, the risk of neu­ro­pathy could escalate 3. This could, for instance, be the case for agents such as borte­zomib, oxaliplatin, cisplatin, or thalidomide.

Results of cell culture studies suggest that DCA might reduce the cytotoxicity of cisplatin and doxorubicin but not that of temozolomide 36.

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.

Citation Timm Hoeres, Markus Horneber, CAM-Cancer Consortium. Dichloroacetate [online document]. http://ws.cam-cancer.org/The-Summaries/Dietary-approaches/Dichloroacetate. July 13, 2016.

References

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