Dichloroacetic acid

Both DCA and TCA are used for cosmetic treatments (such as chemical peels and tattoo removal) and as topical medication for the chemoablation of warts, including genital warts. It can kill normal cells as well.

A randomized controlled trial in children with congenital lactic acidosis found that while DCA was well tolerated, it was ineffective in improving clinical outcomes.[7] A separate trial of DCA in children with MELAS (a syndrome of inadequate mitochondrial function, leading to lactic acidosis) was halted early, as all 15 of the children receiving DCA experienced significant nerve toxicity without any evidence of benefit from the medication.[8] 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 hemodynamics or survival.[9]

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.

In 2007 reports emerged in the press and via the Internet that Evangelos Michelakis and coworkers at the University of Alberta had found that dichloroacetic acid, or rather its sodium salt sodium dichloroacetate, reduced tumors in rats and killed cancer cells in vitro. A story in New Scientist sparked "unprecedented interest among readers", as it spoke of "a cheap and simple drug" that was "known to be relatively safe" and could kill most cancers.[10] An accompanying editorial pointed out that no drug company would be interested in getting the compound approved as a cancer treatment because it is unpatentable.[11] The magazine later published an article emphasizing the dangers involved, such as damage to nerves.[12] The US Food and Drug Administration began enforcing a law that prohibits the sale of substances with the suggestion that they are cancer treatments unless they have been approved by the FDA.[13]

The American Cancer Society in 2012 stated that "available evidence does not support the use of DCA for cancer treatment at this time."[3] Physicians warned of potential problems if people attempt to try DCA outside a controlled clinical trial.[14] 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 cancer sufferers.[15]

The only monitored in vivo dosage of five human patients suffering from 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.[16][17] Observations in vitro and of tumours extracted from those five patients suggest that DCA might act against cancer cells by depolarising abnormal mitochondria found in glioblastoma cancer cells – allowing the mitochondria to induce apoptosis (cell death) of the malignant cells.[16] In vitro work with DCA on neuroblastomas (which have fewer recognised mitochondrial abnormalities) showed activity against malignant, undifferentiated cells.[18] A 2016 case report discusses and reviews the potential application of DCA in central nervous system malignancies.[19] A 2018 study found that DCA could trigger a metabolic switch from glycolysis (the Warburg effect) to mitochondrial OXPHOS and increase reactive oxygen stress affecting tumor cells. These effects were not observed in non-tumor cells.[20]

Neuropathy has been a problem in some clinical trials with DCA causing them to be effectively halted,[8] but a 2008 BJC review found that it has not occurred in other DCA trials.[21] The mechanism of DCA induced neuropathy is not well understood.[22] 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.[23] On the other hand, the 2008 review in BJC [21] states "This neurotoxicity resembled the pattern of length-dependent, axonal, sensorimotor polyneuropathy without demyelination." with regard to the 2006 study by Kaufman et al.[8]

DCA has been investigated as a treatment for post-ischemic recovery.[24] There is also evidence that DCA improves metabolism by NADH production stimulation, but may lead to a depletion of NADH in normoxia.[25]