Note: this page has not been peer reviewed yet, however, all references to www.pubmed.org have been peer reviewed.
- 1 What is DCA?
- 2 Is DCA Effective?
- 3 Is DCA Safe in Humans?
- 4 Is DCA Effective for Human Cancers?
- 5 Is DCA+Caffeine Safe and Effective for Humans?
- 6 Intermittent Dosing
- 7 Dosage
- 8 Toxicity and Side Effects
- 9 DCA Literature
- 10 FAQ
- 11 Links
- 12 Citations
What is DCA?
DCA is Sodium Dichloroacetate.
The balance of evidence points towards DCA being safe and effective against cancer, if used at the correct dose.
For a broad overview of DCA and its effectiveness against cancer see Sodium Dichloroacetate – Clinical Trials for cancer and glioblastoma (1).
This page will also show that, from a statisticians and Bayes theorem point of view, DCA is more effective than chemotherapy, given that chemotherapy will increase your chance of survival by only 2%.
DCA is a promising cancer therapy, and works well when combined with other protocols such as the Budwig protocol, the Ketogenic Diet, Low Dose Naltrexone. Other combination therapies, such as DCA+Low Dose Metformin, may work well for certain cancers such as glioblastoma.
This is a composite video from when DCA was first discovered (33):
Is DCA Effective?
Yes. There are thousands of people that are alive today, due to DCA (3) (7) (8) (13).
There are many more papers are available on http://www.pubmed.org/, search for “dichloroacetate cancer”.
Here is one of the more interesting papers from Oncogene 2013 Mar 28 (2):
Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer
G Sutendra et. al.
Most solid tumors are characterized by a metabolic shift from glucose oxidation to glycolysis, in part due to actively suppressed mitochondrial function, a state that favors resistance to apoptosis. Suppressed mitochondrial function may also contribute to the activation of hypoxia-inducible factor 1 (HIF1) and angiogenesis. We have previously shown that the inhibitor of pyruvate dehydrogenase kinase (PDK) dichloroacetate (DCA) activates glucose oxidation and induces apoptosis in cancer cells in vitro and in vivo. We hypothesized that DCA will also reverse the ‘pseudohypoxic’ mitochondrial signals that lead to HIF1a activation in cancer, even in the absence of hypoxia and inhibit cancer angiogenesis. We show that inhibition of PDKII inhibits HIF1a in cancer cells using several techniques, including HIF1a luciferase reporter assays. Using pharmacologic and molecular approaches that suppress the prolyl-hydroxylase (PHD)-mediated inhibition of HIF1a, we show that DCA inhibits HIF1a by both a PHD-dependent mechanism (that involves a DCA-induced increase in the production of mitochondria-derived a-ketoglutarate) and a PHD-independent mechanism, involving activation of p53 via mitochondrial-derived H2O2, as well as activation of GSK3ß. Effective inhibition of HIF1a is shown by a decrease in the expression of several HIF1a regulated gene products as well as inhibition of angiogenesis in vitro in matrigel assays. More importantly, in rat xenotransplant models of non-small cell lung cancer and breast cancer, we show effective inhibition of angiogenesis and tumor perfusion in vivo, assessed by contrast-enhanced ultrasonography, nuclear imaging techniques and histology. This work suggests that mitochondria-targeting metabolic modulators that increase pyruvate dehydrogenase activity, in addition to the recently described pro-apoptotic and anti-proliferative effects, suppress angiogenesis as well, normalizing the pseudo-hypoxic signals that lead to normoxic HIF1a activation in solid tumors.
Dichloroacetate (DCA), a small molecule that inhibits PDK (thus activating pyruvate dehydrogenase (PDH), the gatekeeper of GO) decreases tumor growth in many cancers including non-small cell lung, pancreatic, metastatic breast, colon, prostate, endometrial, ovarian cancer and neuroblastoma. Importantly, preliminary data from a small human trial showed that DCA may hold promise in patients with advanced recurrent glioblastoma multiforme (GBM).
Full paper: DCA – Glioblastoma – Oncogene – 2012.pdf
Notice the photos showing the difference in tumor size.
In addition, notice the survival rates in the graph above: after 7 months, all of the mice without DCA had died, whereas 90% of the mice on DCA were alive, with tumors that were 15% of the volume.
At the end of this article, there are more journal papers that demonstrate that DCA is effective.
Is DCA Safe in Humans?
DCA is an FDA approved drug, and as such it has been through all of the human usual trials required by the FDA.
There are many people that are alive today, due to DCA (3) (7) (8) (13).
The Medicor Centre has treated over 1,500 patients with DCA (28), with no deaths or non-reversible side effects due to DCA.
The balance of evidence is that DCA is safe, if:
- The correct DCA dosage is observed;
- Caffeine intake is monitored;
- Nerve neuropathy is controlled using vitamin B1 (thaimine);
- Sufficient water is taken to avoid Tumor Lysis Syndrome (TLS); (9)
- The dosage schedule has regular breaks.
All of these topics will be covered shortly.
Is DCA Effective for Human Cancers?
Ideally, there would be a large scale, double blind clinical trial for DCA and/or DCA+Caffeine. However, as this does not exist yet, we have to fall back to Bayes theorem to evaluate this evidence:
- I went through thousands of forum posts (3), and distilled all of the posts into a list of case studies;
- I analysed the data from DCA-Caffeine Survey (7) and the DCA-Caffeine Survey Results (8), see DCA_Survey_24_Jan_2010_uploadable.xlsx;
- I went through the DCA Reports Page (14);
- I went through the case studies on medicocancer.com (13);
- I examined the original study on DCA by Michelakis (37);
- This was for DCA alone, and did not use any companion therapies such as caffeine, Vitamin B1 (thaimine), Alpha Lipoic Acid (ALA) or DCA+Low Dose Metformin, which led to less than exceptional results;
- I stored all of this data in my private database, and used Bayes theorem on the results [todo: upload calculations].
Talking into account confounding variables such as survivorship bias, partial sampling and a small sample set, the data shows that the balance of evidence points towards DCA being safe and effective for cancer, if:
- The correct DCA dosage is observed*
- caffeine intake is monitored*
- nerve neuropathy is controlled using vitamin B1 (thaimine)*
- sufficient water is taken to avoid Tumor Lysis Syndrome (TLS)(9)*
- the dosage schedule has regular breaks*
*All of these topics will be covered shortly.
Is DCA+Caffeine Safe and Effective for Humans?
At this point, we need to decide whether we want to use DCA, or DCA+Caffeine.
Quote from DCA Dosage (12):
DCA Dosage and the DCA-Tea-B1 Protocol
It appears that DCA works vastly better when used in combination with caffeinated tea and vitamin B1. Reports and an early survey indicate that caffeinated tea is critical. Vitamin B1 may be essential as well. We recommend using all three: DCA, black tea and vitamin B1.
Approximately 143 people responded to the DCA-Caffeine Survey(7). According to the DCA and Caffeine Survey Results (8), DCA is much more likely to work if you take caffeine as well as it radically accelerates the effects of DCA (7) (8). Recent research supports caffeine as a tool to help fight cancer (4) (5) (6).
This diagram is from the DCA and Caffeine Survey Results:
In other words, according to the data above, from the subset of 34 people who were definitely sure that DCA did or did not work:
- If you take DCA+Caffeine, there is a 96% chance that DCA worked.
- This is easily calculated: in total, 26 people drank caffeine, and it worked for 25 of them.
- If you take DCA but no Caffeine, there is a 50% chance that DCA worked.
- This is easily calculated: in total 8 people did not drink caffeine, and DCA worked for 4 of them.
Raw data: Excel Spreadsheet, see DCA_Survey_24_Jan_2010_uploadable.xlsx.
The Khan Hippocrates Lecture on DCA Therapy (28) gives statistics on their treatment of over 1,500 patients. They use DCA, but have not tried DCA +Caffeine. Their statistics are as expected: approximately 60% of people respond to DCA alone.
Ideally, there would be a large scale, double blind clinical trial for DCA and/or DCA+Caffeine. However, as this does not exist yet, we have to fall back to Bayes theorem to evaluate this evidence. Yes, there are confounding variables such as survivorship bias, partial sampling and a very small sample set, but Bayes theorem still shows that the balance of evidence points towards both DCA and DCA+Caffeine being safe and effective for cancer [todo: upload calculations].
In conclusion, caffeine radically accelerates the activity of DCA:
- Taking high doses of DCA and high doses of caffeine can harm you (11), This is probably due to Tumor Lycis Syndrome (TLS) (9), which can be avoided by drinking enough water (this topic is covered shortly).
- However, taking DCA but not taking caffeine will dramatically reduce your chances of a cure (8).
- Therefore, the best chance of a cure is achieved by taking DCA+Caffeine, starting with a low dose, ramping up slowly, monitoring side effects, and drinking sufficient water.
At this point, we need to decide how often to take DCA.
Most people do not take DCA continuously (12). They take breaks every second day, or perhaps in the weekends. This is for two reasons:
- Minimising side effects such as peripheral neuropathy (i.e. numb fingers and toes);
- DCA tends to build up in the body over time, which can lead to more side effects;
- Tumor Lysis Syndrome (TLS).
Quote from DCA Dosage:
Tumor Lysis Syndrome (TLS) concerns might also indicate a less aggressive use of DCA. DCA is working so well against lymphatic cancers that an “on and off strategy” of taking DCA might be a good idea; taking DCA one day and not the next. We have had reports of severe TLS symptoms by patients with lymphomas.
If you look through the example Excel spreadsheet in the next section, it will give examples of how often most people took DCA.
How to Avoid Tumor Lysis Syndrome (TLS) by Drinking Sufficient Water
Note: This section can be skipped if you want a broad overview of DCA.
Before we talk about dosage in the next section, we need to understand how fundamentally important it is to drink the correct amount of water:
- Not enough water is fatal due to dehydration (31);
- Too much water is fatal due to water intoxication (32).
Tumor Lysis Syndrome (TLS) (9) is caused by the breakdown products of dying cells, with insufficient water to flush these breakdown products out.
Tumor Lysis Syndrome (TLS) is rare:
- If we look at standard chemotherapy (which is far more toxic than DCA), Tumor Lysis Syndrome (TLS) is a factor in the cause of death of 2% of patients (29).
- If we look at DCA, according to the Khan Hippocrates Lecture on DCA Therapy (28), over 1,500 patients have taken DCA with no deaths or non-reversible side effects due to DCA.
- There have been a total of two reported deaths due to DCA. Of these, at least one death was due to Tumor Lysis Syndrome (TLS) (11), which could have been avoided if the patient had started with a smaller dose of DCA, had been drinking enough water, and perhaps if they had been monitored by a nurse or a doctor.
To put this into perspective, approximately 210,000 patients die per year due to medical mistakes at hospital, (35) many of these mistakes are from simple arithmetic errors, such as multiplying instead of dividing, or mistaking 500 micrograms for 500 milligrams. In any case, approximately 1 in 4 people will eventually die of cancer (38).
Tumor Lysis Syndrome (TLS) can occur spontaneously (9) without any treatment for cancer. However, both DCA and DCA+caffeine are effective at killing cancer cells, so it is wise to take precautions to avoid TLS. Quote from DCA Dosage and the DCA-Tea-B1 Protocol (12):
Tumor Lysis Syndrome (TLS):
When a tumor starts to die, the cancer cells break apart and must be removed from the body. This can create a problem when large tumors die quickly, something that DCA can do. This can be fatal. People on standard chemotherapy have died from TLS. Take this seriously.
Consult your doctor or veterinarian and be knowledgeable about this.
Quote from Tumor Lysis Syndrome (TLS) Prevention (9):
Tumor Lysis Syndrome (TLS) Prevention
People about to receive chemotherapy for a cancer with a high cell turnover rate … as well as adequate IV hydration to maintain high urine output (> 2.5 L/day).
Alkalization of the urine with acetazolamide or sodium bicarbonate is controversial.
Given the importance of drinking enough water, is recommended that you play it safe by observing these three strategies:
- Go easy on the DCA dose. Start with a low DCA dose, ramp up, monitor yourself continuously, add caffeine only after trying DCA alone.
- Adequate water. In practice, you don’t need an IV to consume 2.5 litres of water per day, you can simply drink the water (18). And you probably don’t need 2.5 litres of water per day. As long as you have sufficient water to flush the tumor breakdown byproducts out, TLS will not be a factor. This depends on the size of the tumor, how responsive it is to DCA, and whether its a brain or non-brain tumor. Recommend at least 1.5 litres of water, and no more than 2.5. Whatever you do, certainly do not take more than 3 litres of water per day, as some have died due to water intoxication (32).
- Avoid metabolic acidosis using sodium bicarbonate if urine pH is too low. If urine pH is low, this indicates acidosis (29). In practice, you can use sodium bicarbonate to increase the alkalinity of the urine pH so it is between 7.0 and 8.0 (16). You can use pH strips to monitor the alkalinity of your urine (17). It would be unwise to push the pH of urine above 8.0 (15). Avoiding acidosis will also alleviate the severe pain that some terminal cancer patients have, due to acidic tissues.
Of course, if there was some inexpensive method to detect Tumor Lysis Syndrome (TLS), it would be possible to monitor it daily, for peace of mind. Until then, drink a responsible amount of water.
In summary, don’t let this discourage you from using DCA: according to the Khan Hippocrates Lecture on DCA Therapy (28), over 1,500 patients have taken DCA with no deaths or non-reversible side effects due to DCA.
With DCA, dosage is everything:
- If the dosage is to low, then it will have little effect.
- If the dosage is just right, then it will help you.
- If the dosage is too high, it will harm you.
- Unless you severely overdose, and do not drink a responsible amount of water, the harm will be limited to reversible neuropathy, i.e. numb fingers or toes that will heal when you stop the dose.
Deciding on your DCA Dosage
Fortunately, we have a reasonable amount of data on hundreds of people that have successfully used DCA. Here are some examples of DCA dosages:
- See the DCA-Caffeine Survey (7);
- Excel spreadsheet with 143 examples of DCA dosages: DCA_Survey_24_Jan_2010_uploadable.xlsx.
- See the DCA-Caffeine Survey Results (8);
- See the DCA-Dosage (12);
- See the DCA, Tea and B1 Protocol (10);
- See Brain Cancer Patients Must Use Extreme Caution When Taking DCA (11);
- See DCA Case Studies from Medicor Cancer Centre (13);
- Note that Medicor Cancer Centres do not use caffeine, so their results are not as good as the results reported elsewhere;
- For more examples of dosages, see DCA Reports (14);
- For more examples of dosages, see the DCA Forums (3). The old forum has a lot of very useful information.
The best way to select a dosage is to look at prior examples, and work out the average dose that worked in that situation.
The dosage for DCA varies depending on whether you wish to take caffeine, or not:
- With caffeine: No more than 12 milligrams (mg)/kg/day. Start low, at 2 milligrams(mg)/kg/day, and work your way upwards, monitoring side effects.
- Without caffeine: Up to 25 milligrams (mg)/kg/day. Start low, at 5 milligrams(mg)/kg/day, and work your way upwards, monitoring side effects.
The dosage for DCA varies on whether brain cancer is involved:
- If brain cancer is involved: exercise caution, start on a very low dose and move upwards. DCA works so quickly on brain tumors that if dehydrated, the body can have a difficult time dealing with Tumor Lysis Syndrome (TLS) (9) which we have already learned about. Caffeine is recommended to increase the chance of a cure, but ramp it up very slowly, carefully monitoring the side effects.
- If brain cancer is not involved: then you can safely use a greater range of dosages.
Dosage Example (Glioblastoma)
Note: this dosage example is recommended for patients who have just had surgery for glioblastoma and are aiming for a maintenance dose. Patients without brain cancer would need a much higher dose to maximize their chances of a full remission.
- To avoid even the remotest possibility of Tumor Lysis Syndrome (TLS) (9), start with getting yourself fully hydrated. Drink at least 1.5 litres (and no more than 2.5 litres) of water/day, for a few days before you start on DCA, and continue for as long as you are on DCA. See a previous section for this.
- Start with a low dosage of DCA, 2 milligrams(mg)/kg/day. For a 100kg person, this would be 200 milligrams (mg) of DCA. Work your way up to 4 milligrams(mg)/kg/day over the course of one month, carefully monitoring side effects (12).
- Must dose intermittently, In this case, suggest one day on, one day off.
- Avoid caffeine for the first 2 weeks, then introduce it slowly into your diet. Start with one cup of black tea per day, then work your way up to five cups. One cup of tea contains 40mg of caffeine, we are aiming for 200mg of caffeine per day.
- Vitamin B1 (Thiamine) 300 milligrams (mg), 3 times per day, for a total of 900 miligrams (mg) (12). Could substitute Benfotiamine instead.
- To avoid metabolic acidosis, monitor urine with pH test strips, and take Baking Soda (Sodium Bicarbonate), see Sodium Bicarbonate by Mark Sircus (36). For patients with large tumors in the torso, this can help deal with some of the severe pain that some cancer patients have, due to acidic tissues.
- At this dose, it is entirely safe and completely non-toxic (16).
- Alpha Lipoic Acid (ALA) which works well with DCA (19), 100 milligrams (mg), 3x per day, for a total of 300 milligrams (mg) per day. Start the dosage low, and ramp up.
- Alpha Lipoic Acid is known be a mercury chelator (20), so if you have mercury fillings, or mercury toxicity, would advise skipping ALA.
- ALA increases glutathione is is useful to address for symptoms of diabetic peripheral neuropathy which are similar to the symptoms of a DCA peripheral neuropathy (see below).
- At this dose, ALA is entirely safe and completely non-toxic (21).
- Magnesium Chloride, 500 milligrams (mg) per day.
- See this site’s page on Magnesium Chloride.
- Note that there is a difference between the amount of Magnesium Chloride, and the amount of Elemental Magnesium. In a typical 520mg magnesium chloride pill, there is 62mg of magnesium.
- At this dosage, magnesium chloride is entirely safe and completely non -toxic (22).
Most people that use DCA use it in conjunction with other therapies. If you look through the data from the diet spreadsheet referenced by the DCA-Caffeine Survey (7), or look through the DCA Forums (3), you will find many examples of companion therapies.
- See Low Dosage Naltrexone (LDN). This is so safe that it should be used in combination with any cancer therapy.
- In the Khan Hippocrates Lecture on DCA Therapy (28), they mention that that they are trying DCA in conjunction with the Ketogenic Diet.
- The Budwig Protocol is suspiciously close to the Ketogenic Diet, as it has a high amount of fats in the form of cottage cheese. Both these protocols work well in conjunction with DCA, and it is possible that there is some underlying similarity between these diets.
- Other combination therapies, such as DCA+Low Dose Metformin, may work well for certain cancers such as glioblastoma.
Keep a Dosage and Side Effect Diary
I cannot emphasize enough the importance of keeping a dosage diary, together with notes on how you feel that day. Put a notebook in the cupboard where you store your DCA, and note down the dose and how you feel, every time you take DCA.
This makes it easier to monitor your progress, and periodically adjust the dosage up or down according to your diary entries. You cannot rely on your memory for this, as it is too subjective.
Don’t be afraid to experiment with dosages, the only ones you really have to be careful with are DCA and Caffeine.
And don’t take my word for it: it’s your health, so feel free to experiment with anything different, and feel free add or subtract anything from your dosage regime according to the best evidence you can find.
Toxicity and Side Effects
DCA is a drug approved by the FDA under the brand name Ceresine. It has been through all of the usual human clinical trials that any drug requires. If taken in the correct dose, it is safe.
- This paper shows that 7 companies received FDA approval to use DCA to treat a variety of illnesses: DCA – GenericChemicalPdfServlet.pdf. Note that the term “orphaned drug” simply means “out of patent drug”, which means that there is no money to be made from manufacturing it.
- The Khan Hippocrates Lecture on DCA Therapy (28) talks about the side effects of DCA when treating 1,500 patients. No patients died due to DCA, and all side effects were reversed when DCA usage was halted.
- There have been a total of two reported deaths due to DCA, and of those, at least one death was due to Tumor Lysis Syndrome (11). This could have been avoided if the patient had started with a smaller dose of DCA, and had been drinking sufficient water (see previous topic).
- To put this into perspective, approximately 210,000 patients die per year due to medical mistakes at hospital (35). Many of these mistakes are from simple arithmetic errors, such as multiplying instead of dividing, or mistaking 500 micrograms for 500 milligrams.
- See DCA Safety and Side Effects (23).
Concerns: Reversible peripheral neuropathy at high doses; risk of cell lysis; caffeine may potentiate effects.
DCA inhibits itself after several days of metabolism, so you must use a on/off schedule. Michelakis reports that the benefits of DCA are dose-dependent, beginning at about 10 mg/kg/day. Neuropathy is usually the dose-limiting toxicity and occurs at different dosages in different patients. Thiamine (the water-soluble Vitamin B1) may help decrease peripheral neuropathy(5) as a dosage of at least 300 mg, divided equally into 3 mealtime dosages. Benfotiamine, a derivative of Vitamin B1, may be a suitable replacement. In fact, I believe DCA was once proposed to be called Vitamin B15(6). Dr. Khan also suggests taking the R+ form of alpha lipoic acid (ALA), 450 mg divided into 3 equal doses.
When they say “DCA Inhibits itself after several days of metabolism”, they mean that DCA will gradually build up in your body, so you should take regular breaks.
Note that the recommended dose of 10 mg/kg/day assumes no caffeine intake, and if caffeine is used, the dose must be lowered accordingly.
Many more papers are available on www.pubmed.org, search for “dichloroacetate cancer”.
See The DCA Site for papers on DCA.
Medicor Cancer Centres
Medicor Cancer Centres was the first cancer clinic in North America to begin prescribing DCA “off label” to cancer patients (in April 2007) under the full supervision of a medical team. We consulted with the relevant regulatory bodies in Canada and have been following their guidelines and policies. We would like to thank everyone who has expressed an interest in our DCA therapy, and gave feedback and encouragement. We would also like to acknowledge and extend a special thanks to two of our patients who brought DCA to our attention. As of this update of FAQ, we have treated over 1500 patients with DCA. This is the largest number of patients treated at any one clinic in the world. Even though we are not conducting a clinical trial, the experience gained by treating this large number of patients is extraordinary, and helps us to use DCA safely and effectively.
We also were the first to demonstrate the potential synergism of DCA with the diabetes drug metformin. We co-published a paper in which one can see an example of a glioblastoma tumour with 99% cell kill from a combination of DCA + metformin, but <10% cell kill from either drug alone.
Nerve injury (“peripheral neuropathy”). Neuropathy typically develops in the hands and feet (but not always), takes several weeks to months to develop, and is reversible if it is caught early. In the existing literature, neuropathy from DCA has always been shown to be reversible. We use vitamin B1 (benfotiamine or thiamine), acetyl L-carnitine and R alpha lipoic acid to prevent and reduce the severity of peripheral neuropathy. These medicines can be given orally or intravenously depending on the degree of neuropathy. Published data clearly demonstrates all of these medicines can help chemo and/or diabetic neuropathy, and our own extensive experience confirms that these supplements are effective for DCA neuropathy as well.
Full paper: DCA-FAQs.pdf.
Note that Medicor Cancer Centres do not use DCA + caffeine, so their results are not as good as reported elsewhere.
Science Translational Medicine
This is the original paper that sparked interest in DCA.
From from Science Translational Medicine (25):
Metabolic Modulation of Glioblastoma with Dichloroacetate
E. D. Michelakis, G. Sutendra, P. Dromparis, L. Webster, A. Haromy, E. Niven, C. Maguire, T.-L. Gammer, J. R. Mackey, D. Fulton, B. Abdulkarim, M. S. McMurtry, K. C. Petruk
(Published 12 May 2010; Volume 2 Issue 31 31ra34)
Solid tumors, including the aggressive primary brain cancer glioblastoma multiforme, develop resistance to cell death, in part as a result of a switch from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis. This metabolic remodeling is accompanied by mitochondrial hyperpolarization. We tested whether the small-molecule and orphan drug dichloroacetate (DCA) can reverse this cancer-specific metabolic and mitochondrial remodeling in glioblastoma. Freshly isolated glioblastomas from49 patients showed mitochondrial hyperpolarization, which was rapidly reversed by DCA. In a separate experiment with five patients who had glioblastoma, we prospectively secured baseline and serial tumor tissue, developed patient-specific cell lines of glioblastoma and putative glioblastoma stem cells (CD133+, nestin+ cells), and treated each patient with oral DCA for up to 15 months. DCA depolarized mitochondria, increased mitochondrial reactive oxygen species, and induced apoptosis in GBM cells, as well as in putative GBM stemcells, both in vitro and in vivo. DCA therapy also inhibited the hypoxia-inducible factor–1a, promoted p53 activation, and suppressed angiogenesis both in vivo and in vitro. The dose-limiting toxicity was a dose-dependent, reversible peripheral neuropathy, and there was no hematologic, hepatic, renal, or cardiac toxicity. Indications of clinical efficacy were present at a dose that did not cause peripheral neuropathy and at serum concentrations of DCA sufficient to inhibit the target enzyme of DCA, pyruvate dehydrogenase kinase II, which was highly expressed in all glioblastomas. Metabolic modulation may be a viable therapeutic approach in the treatment of glioblastoma.
Full Article: DCA – Glioblastoma – Michelakis – 2010.pdf
It should be noted that these patients used DCA by itself, and did not benefit from any other interventions which are known to help, such as caffeine, Vitamin B1 (thamina), Alpha Lipoic Acid (ALA), etc.
International Journal of Cancer
Paper from the International Journal of Cancer (26):
Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC
Luke H. Stockwin, et. al.
The ‘‘Warburg effect,’’ also termed aerobic glycolysis, describes the increased reliance of cancer cells on glycolysis for ATP production, even in the presence of oxygen. Consequently, there is continued interest in inhibitors of glycolysis as cancer therapeutics. One example is dichloroacetate (DCA), a pyruvate mimetic that stimulates oxidative phosphorylation through inhibition of pyruvate dehydrogenase kinase. In this study, the mechanistic basis for DCA anti-cancer activity was re-evaluated in vitro using biochemical, cellular and proteomic approaches. Results demonstrated that DCA is relatively inactive (IC50 17 mM, 48 hr), induces apoptosis only at high concentrations (25 mM, 48 hr) and is not cancer cell selective. Subsequent 2DPAGE proteomic analysis confirmed DCA-induced growth suppression without apoptosis induction. Furthermore, DCA depolarizes mitochondria and promotes reactive oxygen species (ROS) generation in all cell types. However, DCA was found to have selective activity against rho(0) cells [mitochondrial DNA (mtDNA) deficient] and to synergize with 2-deoxyglucose in complex IV deficient HCT116 p53(2/2) cells. DCA also synergized in vitro with cisplatin and topotecan, two antineoplastic agents known to damage mitochondrial DNA. These data suggest that in cells ‘‘hardwired” to selectively utilize glycolysis for ATP generation (e.g., through mtDNA mutations), the ability of DCA to force oxidative phosphorylation confers selective toxicity. In conclusion, although we provide a mechanism distinct from that reported previously, the ability of DCA to target cell lines with defects in the electron transport chain and to synergize with existing chemotherapeutics supports further
Full paper: IJOC DCA Warburg.pdf
In summary, DCA operates by targeting cancer cells that are using inefficient ATP production, something which normal, healthy cells do not do.
In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed “the Warburg effect.” Aerobic glycolysis is an inefficient way to generate adenosine 5′-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
Full Article: Warburg Effect.pdf
Question: What makes industrial grade sodium dichloroacetate a concern?
Answer, (by Jim T): Industrial grade sodium dichloroacetate contains toluene, a very poisonous chemical. Purity is not the issue with the industrial grade sodium dcichloroacetate. The issue is the solvent they use to refine it. The industrial grade is high purity because manufacturers of pesticides and other chemicals also need high grade product. However, they have no concern for what solvent is used. The solvent used to create industrial grade sodium dichloroacetate is toluene. As much as 100 ppm can exist in the industrial grade. Toluene, which is of no concern to a pesticide manufacturer, is a serious health hazard for people. And toluene at 100 ppm can cause serious brain damage.
Conclusion: If DCA in the form of the FDA approved drug Ceresine is available, use that. If not, always use pharmaceutical grade DCA. Look for the words “pharmaceutical grade” in the description.
Here is a quote from an online supplier of DCA. To keep this site objective, I am deliberately not recommending any DCA manufacturer.
- Microbial testing is done on each batch to ensure there are no microorganisms
- COA, certificate of analysis. This testing is done to ensure the purity and identity of the DCA. Each batch has its own COA. COA tests various chemical properties such as PH level and PPM readings. This proves a chemical’s identity.
… several customers have had our DCA tested at labs of their choosing and the labs have been amazed at the incredible purity of our DCA. The cost for this testing ranges between $200-$400. There are two types of tests that can be done, make sure that the lab you choose understands the differences and uses the correct test.
Question: Is DCA toxic?
Answer posted by Jay C.:
Researchers at the University of Alberta have reported that DCA is relatively non-toxic, since it has already been used as a medicine on adults and children to treat metabolic disease, and for hypertension. It has been known to have some mild side effects in a minority of patients and they include a change in gait, some nerve problems, but both of these symptoms appear to be reversible upon cessation of DCA. This is certainly in positive contract to most of the poisons being administered today as “chemo”, including IL-2 (requires on week in ICU, Interferon, and DTIC.
Keep in mind any (every) drug/chemical has a threshold, which if crossed will make the drug toxic. From the company (Sigma) website: LD50 Oral – rat – 2,820 mg/kg – meaning about 3 grams of DCA per Kilogram of body mass can kill 50 rats out of a sample of 100. Humans will have a different tolerance. Compared to some drugs out there that are either expensive as diamonds or have side effects like heck, this is definitely worth a shot.
The [upper limit] of the recommended dose of DCA is 20/mg per kilogram of body weight.
This is less than 1% of the dangerous dose. DCA is incredibly safe to use at the recommended 20mg/kg of body weight level.
Question: There is no evidence to show that DCA is safe and effective against cancer?
This is the wrong question. If you hear somebody use these exact words, then they are thinking in from a frequentist point of view, not a Bayes Theorem point of view. They are aware that there are no large scale double blind medical studies for DCA and cancer, but they are ignoring Bayes theorem and the available case studies.
The correct questions are:
- “Is the balance of evidence in favour of using DCA for cancer?”
- “Is DCA more likely to help than harm?”
The answer to these two questions is yes, and yes.
At some point in the future, there will be a large scale, double blind medical study for DCA and cancer, and the probability that DCA is definitely effective will approach 100%. However, until then, we have to use Bayes theorem to work with the best evidence we have: we cannot show that the probability of help vs. harm is close to 100%, but it is definitely well above 75%.
Question: Less toxic forms of DCA?
In the future, there may be forms of DCA that have lesser side effects, see Beyond DCA.
Full paper: LessToxicDCA.pdf
Question: DCA Alternatives?
- (1) www.canceractive.com – Sodium Dichloroacetate or DCA – Clinical Trials for cancer and glioblastoma.
- (2) Oncogene. 2013 Mar 28;32(13):1638-50. doi: 10.1038/onc.2012.198. Epub 2012 May 21. Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer by Sutendra G et. al.
- (3) www.thedcasite.com, The DCA Forum, see http://www.thedcasite.com/DCA_forum.html.
- (4) Caffeine-Mediated Inhibition of Calcium Release Channel IP3R3 Blocks Glioblastoma invasion and Extends Survival. Justin Lee et. al, Cancer Res; 70(3) February 1, 1174 (2010)
- (5) Coffee, Tea, Caffeine Intake, and Risk of Adult Glioma in Three Prospective Cohort Studies 2009. Crystal N. Holick, Scott G. Smith, Edward Giovannucci and Dominique S. Michaud “Our findings suggest that consumption of caffeinated beverages, including coffee and tea, may reduce the risk of adult glioma, but further research is warranted to confirm these findings in other populations”
- (6) Caffeine inhibits cell proliferation and regulates PKA/GSK3β pathways in U87MG human glioma cells. Dec 30, 2010.
- (7) www.thedcasite.com The DCA-Caffeine Survey.
- (8) www.thedcasite.com DCA and Caffeine Survey Results, A First Report.
- (9) Tumor Lysis Syndrome from Wikipedia.
- (10) www.thedcasite.com – The DCA, Tea & B1 Protocol.
- (11) www.thedcasite.com – Alert – Brain Cancer Patients Must Use Extreme Caution When Taking DCA, see http://www.thedcasite.com/DCA_protocol/Brain_cancer_risks.html.
- (12) www.thedcasite.com – DCA Dosage and the DCA-Tea-B1 Protocol.
- (13) www.medicorcancer.com – Case Studies, see http://medicorcancer.com/treatments/case-studies/.
- (14) www.thedcasite.com – DCA Reports.
- (15) www.chemcraft.net – Part 2. The Role of pH and Healthy Living.
- (16) Am J Emerg Med. 2013 Dec;31(12):1703-6. doi: 10.1016/j.ajem.2013.08.031. Epub 2013 Sep 20. Efficacy of urine alkalinization by oral administration of sodium bicarbonate: a prospective open-label trial by Cohen B. et. al.
- (17) Urine test strip. Wikipedia.
- (18) www.mayoclinic.org – Water: How much should you drink every day? by Mayo Clinic Staff
- (19) www.thedcasite.com – Dichloroacetate synergizes Alpha Lipoic Acid. There is a U.S. Patent showing that alpha lipoic acid works well with dichloroacetate. See http://www.thedcasite.com/alpha_lipoic_acid_and_dca.html.
- (20) forums.phoenixrising.me – Andrew Cutler and Alpha Lipoic Acid.
- (21) Pauling Institute on Alpha Lipoic Acid.
- (22) Pauling Institute on Magnesium Toxicity.
- (23) www.thedcasite.com – DCA Safety and Side Effects.
- (24) www.treatingglioblastoma.com – Glioblastoma Treatments: Dichloroacetate (DCA)
- (25) Science Translational Medicine 12 May 2010, Vol. 2, Issue 31, pp. 31ra34, DOI: 10.1126/scitranslmed.3000677, Metabolic Modulation of Glioblastoma with Dichloroacetate by E. D. Michelakis at http://stm.sciencemag.org/content/2/31/31ra34.abstract.
- (26) IJC – International Journal of Cancer – Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC by Luke H. Stockwin at http://www.ncbi.nlm.nih.gov/20533281.
- (27) Science. 2009 May 22;324(5930):1029-33. doi: 10.1126/science.1160809. Understanding the Warburg effect: the metabolic requirements of cell proliferation by Vander Heiden MG at http://www.ncbi.nlm.nih.gov/19460998.
- (28) www.youtube.com – Khan Hippocrates Lecture on DCA Therapy, see https://www.youtube.com/watch?v=9o12uT_d-Co.
- (29) Tumor lysis syndrome: Prevention and treatment by Richard A Larson, MD et. al. at http://www.uptodate.com/contents/tumor-lysis-syndrome-prevention-and-treatment.
- (30) Intravenous Therapy, see Wikipedia at https://en.wikipedia.org/wiki/Intravenous_therapy.
- (31) Terminal Dehydration, see Wikipedia at https://en.wikipedia.org/wiki/Terminal_dehydration.
- (32) Water Intoxication, see Wikpedia at https://en.wikipedia.org/wiki/Water_intoxication.
- (33) www.youtube.com – Cancer Cure DCA Sodium Dichloroacetate (DCA) – The Cancer Cure!! from https://www.youtube.com/watch?v=8nTg53izwpE.
- (34) How Many Die from Medical Mistakes in U.S. Hospitals?
- (35) An updated estimate says it could be at least 210,000 patients a year, more than twice the number in a frequently quoted Institute of Medicine report. See http://www.scientificamerican.com/article/how-many-die-from-medical-mistakes-in-us-hospitals/.
- (36) Sodium Bicarbonate – Second Edition E-Book: Rich Man’s Poor Man’s Cancer Treatment, Written by Mark Sircus, AC., OMD. See http://drsircus.com/books/e-book/sodium-bicarbonate-second-edition.
- (37) Science Translation Medicine. Metabolic Modulation of Glioblastoma with Dichloroacetate by E. D. Michelakis, et al., see http://stm.sciencemag.org/content/2/31/31ra34.abstract.
- (38) Cancer Research UK, see Home > Health professional > Cancer Statistics > Cancer mortality statistics > Cancer mortality statistics. See http://www.cancerresearchuk.org/health-professional/cancer-statistics/mortality/.