DCA - Dichloroacetate Repurposed for CANCER - What is THE WARBURG EFFECT?
DCA - the bouncer on the door to the lactate pathway....
The Warburg Effect is the name we give to the way that cancers primarily make their energy. The name comes from Dr Otto Warburg who realised in the 1920s that cancers had a different metabolism to regular, healthy cells.
Imagine your mitochondria are like a big, efficient log burner. When there is enough of the right fuel, with all the right ingredients from the fire triangle, oxygen, fuel and heat, the output can be really neat and efficient. This is called OXPHOS or Oxidative Phosphorylation.
Since cancers have broken mitochondrial function they are unable to produce energy efficiently through OXPHOS. Instead they produce ROS (radical oxygen species or free radicals) which are highly toxic elements that damage DNA and threaten to kill our cells. Because of this threat the cell switches its metabolism, to the Warburg Effect instead, to avoid cell death (apoptosis).
You could say that cancer is, in a way, a survival adaptation of the cell. It should die because it is broken. All cells should go through a normal cell cycle of life and death. Normally the immune system would come along and kill cells that are broken or damaged, but in cancer, ‘normal’ turns on its head and the immune system is suppressed, so cancers continue to live and grow.
In fact, we all have some cancer in our bodies and our immune systems are doing just that, all the time. A healthy immune system seeks out and destroys foreign invaders, rogue organisms, cells with DNA damage from ROS and cancerous cells. A healthy body deals with a little cancer every day.
There are many compounding reasons why cancer starts. SNPs (mutations) on genes like TYMS or SOD, TP53 or VEGFA that mean these genes don’t do the repair or clear up of faulty cells so well, or they are faster at growing tumors or all of the above.
Disordered metabolism is always involved one way or another.
On top of that a high stress event, a high carbohydrate diet, taking anabolic (growth) drugs including TRT, and Biologics like Humira and often immune system suppression which could be deficiency or toxicity.
In today’s world we are bombarded by stressors, nutritional, physical, emotional and spiritual. Our connection to each other and our Earth has lost vitality.
The Warburg Effect
This is the name of a pathway that is activated when the regular energy pathways in our log burner (the mitochondria) are broken. The Warburg Effect is also known as the Pyruvate-Lactate pathway and there are a few important steps to understand about it before we move into how DCA works as a repurposed drug against cancer.
We bring glucose (sugar) which comes from carbohydrates like rice, bread, pasta, potatoes, fruit, juices, starchy vegetables and yes of course lots of sugary foods too, into the cell using a little carrier called GLUT1. That carries the sugar into the cell. There it gets converted through a series of steps to become something called Pyruvate.
Pyruvate is turned into the main fuel called Acetyl-CoA for our main energy production factory inside the Mitochondria called 'The Krebs Cycle’ or The Citric Acid Cycle or (TCA).
Acetyl-CoA is like the logs you feed into the log burner, you want to keep the logs feeding into the burner or the fire will go out and there will be a back up.
The log feeder is called PDH - Pyruvate Dehydrogenase. This keeps the logs coming and the fire burning.
There is a switch that can shut off the log feeder PDH though and in cancer this switch is often ‘upregulated’ or increased in activity. That switch is called PDK - Pyruvate Dehydrogenase Kinase.
It makes sense in cancer that the log feeders for the mitochondria are switched off, because the mitochondria burners are broken and if they were to continue burning logs they would malfunction and explode with lots of poisonous smoke, leaving a massive clean up job for the body.
So the PDK switch turns off the log feeder for the mitochondria and instead the logs are fed into The Warburg Effect which is much less efficient but keeps the cell alive. The Warburg Effect makes very little energy through a process of fermenting sugar inefficiently, without oxygen present, so it uses up massive amounts of sugar/glucose. We also call this process Glycolysis. Glycolysis is a typical, cancer glucose metabolic pathway.
Dichloroacetate - DCA - The Metabolic Modulator
Originally considered a dangerous, toxic waste, DCA is steeped in controversy with even suspicions of it having carcinogenic properties of its own. (see contraindications below)
DCA is a lab created, organic acid that was originally found in humans to impact metabolic conditions like lactic acidosis. It was discovered to have application in cancer in around 2007 when a group of non oncology researchers discovered that DCA had an important impact on cancer cell metabolism.
We know that cancer cell metabolism (Glycolysis) is different to normal cell metabolism (OXPHOS):
It was found that DCA blocked PDK.
PDK is the OFF switch for the log feeding ‘PDH’ (stay with me..)
This means that instead of the logs being diverted to the Warburg Effect to inefficiently make fuel for cancer (but keep the cell alive), the logs are forced into the broken Mitochondria to make energy with OXPHOS
The broken Mitochondria are forced to try produce energy with Oxygen but they are faulty, so they start to produce lots of ROS (toxic elements that damage the cell)
This causes the cancer cell to die.
Like many promising compounds and off label drugs, the money doesn’t flow towards researching them because no-one stands to profit (apart from the patient). So there isn’t much research to support mainstream use of DCA.
DCA is detoxified from the body using glutathione, the master detoxifier. This can be problematic for some people who are prone to poor detoxification, such as those missing the gene GSTM1 or other GST genes (you can check your own detoxification genes with our Genetic DNA Detoxification Test). What that can lead to is more side effects, which can include peripheral neuropathy, a painful numbness and tingling in fingers and toes.
There is a happy flip side to this though. Depletion of glutathione in cells, reduces the potential of cancer to be able to repair itself after an assault like radiation and that makes DCA a potent radiosensitizer!
Cancers where DCA shows promise
DCA was shown to increase the activity of TP53 - our tumor suppressor gene. It also reduces HIF1a production which is a signal that happens in the cancer cell and in the area around the tumor called the tumor microenvironment. HIF1a tells the body to make vessels to feed the tumor to help it grow. DCA increased apoptosis and decreased VEGF too which meant again, less growth and less angiogenesis, all in GBM.
Head & Neck Squamous Cell Carcinoma
Whilst overall outcomes were not improved in this recent Phase 2 clinical trial, early response rates to using DCA with Cisplatin chemotherapy were good and the expected metabolic alterations (increased Pyruvate though PDK inhibition) were found.
Imagine if DCA were combined with HBOT and the Keto Diet where both the cancers were starved of glucose, forced to use the oxygen/glucose pathway and then flooded with oxygen AND chemotherapy creating masses of toxic ROS, killing the cancer cells. We really need more synergistic research to bring these complementary therapies to the forefront of oncology medicine.
Breast Cancer
It has been found that DCA isn’t universally effective across all cancer tumor types. With some cancers actually progressing instead of regressing. It pays to get very detailed in your own research when looking at what may work for your particular type of cancer.
Interesting research from 2025 shows that DCA downregulates ABCB transporters. What that means is that the pumps on the outside of cells which normally pump out toxins are slowed down. This is great for chemotherapy because cancers use these pumps to get the chemo out, so they can live. If DCA slows down these ABCB pumps, the chemo stays in longer and has a better effectiveness against cancer. (This was shown to work in wild type P53 Breast Cancers)
Colorectal Cancer
Here is a case study of a lady with Stage 4 CRC who stabilized after using DCA
It was found that DCA overcame chemoresistance to 5-FU which is the byproduct made in the body when FOLFIRI or FOLFOX chemotherapies are taken. The tumor suppressor gene TP53 was activated and the metabolic pathway PDK was inhibited as per the main metabolic function of DCA. All these contributed to making DCA a potent chemosensitizer in CRC.
Contraindications (but be careful with the data)
One paper found that DCA (as a metabolite in the body) increased VEGF (although other data shows it decreases it), it was also found that metastases were increased and that tumor growth was upregulated. This was when run with a High Fat Diet (HFD) - which in the research world is essentially Crisco. That yummy, vegetable based, highly processed, trans fat-laden, Omega 6 heavy fat that NO-ONE should be eating!
Was it the DCA or was it the Crisco?
There are many side effects that can occur with DCA including Fatigue, confusion, memory loss, sedation, tremors, gait abnormalities, central neuropathy, hallucination, agitation, depression, fever, diarrhea, heartburn, nausea, liver enzyme elevation, thrombocytopenia (low platelets), and low calcium. There can also be an increased likelihood of hallucinations with Benzodiazepam and Cannabinoids as well as other neurological drugs.
As always you must speak with your Integrative Oncology Practitioner, Doctor or Physician before you embark on any medication or supplement program.
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All good information. Can you recommend a integrative physician in New Jersey? Thank you.
I think I'll stick to cannabis oil for the time being rather than this one thanks Amanda.