Enter the world of Dichloroacetic acid (DCA), or as some might know it, bichloroacetic acid. This compound, with its scientific name CHCl2COOH, is like a sibling to acetic acid, but with a small twist – two of the three hydrogen atoms in its methyl group are replaced by chlorine atoms. It’s a member of the chloroacetic acid family, a group with a myriad of potential uses. When we talk about the salts and esters of dichloroacetic acid, we call them dichloroacetates. Fascinatingly, these DCA salts are being explored as possible medicines due to their knack for inhibiting a substance called pyruvate dehydrogenase kinase.
Animal and laboratory studies hint that DCA may put the brakes on the progression of certain cancers. However, the jury’s still out on its use for cancer treatment, as we need more evidence to back this up.
An Intriguing Mix of Chemistry and Randomness
Dichloroacetic acid shares a bond with other halogenated organic acids – its unique chemical recipe. This intriguing concoction releases dichloroacetate ions when watered down. In its pure form, dichloroacetic acid, sporting a pKa of 1.35, is a strong organic acid that, if inhaled, could cause significant harm to the upper respiratory tract’s sensitive mucous membranes and airways.
DCA hides in plain sight in nature, too. It’s found in the seaweed species, Asparagopsis taxiformis. It also makes a sneaky appearance in chlorinated drinking water and even pops up during the metabolism of certain chlorine-containing drugs and substances. Typically, DCA is created by scaling down trichloroacetic acid (TCA). Interestingly, you can also get DCA by introducing chloral hydrate to a cocktail of calcium carbonate, sodium cyanide, and water, then adding hydrochloric acid into the mix. A reaction between acetylene and hypochlorous acid could also yield DCA.
In the realm of labs, both DCA and TCA are used quite often, acting as ‘precipitants’ – substances that help transform large molecules like proteins from a liquid to a solid state.
Efficacy in Treatment Applications
Making the Invisible, Visible
In the world of medicine and cosmetic procedures, DCA and TCA wear many hats. They play roles in both topical genital wart chemoablation and cosmetic procedures like chemical peels and tattoo removal. Surprisingly, they can also be used to intentionally eliminate healthy cells.
Navigating the Labyrinth of Lactic Acidosis
While DCA demonstrated tolerance in a randomized trial, it fell short in improving clinical results for newborns battling congenital lactic acidosis. A follow-up trial of DCA for MELAS (a condition resulting from low mitochondrial activity and leading to lactic acidosis) didn’t fare much better. All 15 children in the study experienced significant nerve damage without any positive drug effects, prompting an early end to the trial. Even though DCA managed to reduce blood lactate levels in adults suffering from lactic acidosis, it didn’t make a therapeutic difference. Patient hemodynamics or survival didn’t improve.
So, despite prior case reports and preclinical studies hinting at DCA’s potential benefit for lactic acidosis, controlled trials did not show a therapeutic advantage. Increasing toxicity levels also thwarted continued use of DCA as a study drug in clinical trials.
Cancer: A Battle Yet to be Won
In 2007, word spread in media and internet circles that researchers from the University of Alberta, led by Evangelos Michelakis, had found that sodium dichloroacetate (DCA’s sodium salt form) shrank tumors in rats and wiped out cancer cells in the lab. Readers flocked to a New Scientist story touting a “cheap and simple therapy,” deemed relatively safe, that could potentially cure most cancers.
However, an accompanying editorial cautioned that the inability to patent this chemical could discourage pharmaceutical companies from pursuing its approval as a cancer medication. A follow-up paper in the journal underscored potential side effects, like nerve damage. A crucial point to remember: in the United States, selling substances as cancer treatments without FDA approval is now prohibited. It’s crucial to separate fact from hopeful fiction.
The DCA Dilemma in Cancer Treatment
In 2012, the American Cancer Society cast a cloud of doubt over the use of DCA in cancer treatment, saying the available evidence just didn’t stack up to support its use. Many medical professionals have since echoed this cautionary stance, urging care before using DCA and advising against its use outside of tightly regulated clinical trials. Going down this road, you might hit a stumbling block in acquiring the compound. To illustrate, one individual masquerading as a savior to cancer patients was handed a 33-month sentence for selling them a white powder claimed to be DCA, which was nothing more than starch.
However, human trials with DCA have been limited. Only five people with glioblastoma participated in a controlled, in-person DCA trial. The purpose wasn’t to determine the drug’s potency against their disease, but to see if a certain dosage could be given without causing adverse reactions, such as nerve damage. All five participants were also undergoing other treatments.
Lab-based (in vitro) and specimen (ex vivo) studies hint at DCA’s potential in fighting glioblastoma cancer cells. It seems to force their abnormal mitochondria to destabilize, triggering a self-destruct mechanism within the cells, known as apoptosis.
Further lab studies on neuroblastomas, cancers with mysterious mitochondrial abnormalities, have suggested that DCA can combat malignant, undeveloped cells. A 2016 case report investigated DCA’s potential in treating central nervous system cancers. In 2018, a study surfaced showing that DCA sparked a metabolic shift in tumor cells from glycolysis to mitochondrial OXPHOS (also known as the Warburg effect), while boosting reactive oxygen stress. Intriguingly, this shift was not observed in normal cells.
Navigating the Maze of Neuropathy
DCA’s journey in clinical studies has been somewhat rocky, with some trials being called off due to neuropathy, a condition affecting the nerves. Yet, a 2008 study published in the British Journal of Clinical Pharmacology reported that neuropathy didn’t surface in other DCA trials. The mechanism through which DCA induces neuropathy remains shrouded in mystery.
Insights into DCA’s neuropathic side effects have been gleaned from in vitro studies on cultured neurons. Findings suggest that DCA may cause dose- and time-dependent demyelination (stripping of the nerve’s protective sheath), a process that can partially reverse over time once the drug is stopped.
However, an alternate viewpoint emerged in 2008 when researchers reanalyzed the data, concluding that the neurotoxicity pattern mirrored that of length-dependent, axonal, sensory polyneuropathy, but without any demyelination.
A Glimmer of Hope for Long-Term Heart Failure
As per DCA Guide – DCA has drawn attention as a potential tool for recovery after ischemia, a condition characterized by reduced blood supply to the heart.
An intriguing bonus of DCA is its potential to accelerate metabolism by increasing NADH production. However, a word of caution: this could potentially deplete NADH if there’s ample oxygen present.