Note: this page has not been peer reviewed yet, however, all references to www.pubmed.org have been peer reviewed.
Low Dose Metformin Boosts DCA?
We have shown that DCA (Sodium Dichloroacetate) is effective against cancer.
Metformin is a common diabetes drug with over 40 million prescriptions issued in 2008 alone(2). In a 4-year study of 51,675 patients in Sweden, it was shown to be safe and effective against diabetes (3).
From the Medicor Cancer FAQ on DCA (6):
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.
This diagram from their paper says (5) says it all:
It is interesting to note that the combination of DCA+Low Dose Metformin does not work for all cancers, as evidenced by this diagram (5):
However, this is not the entire story. It is not the percent kill rate which is important, its the total number of cancer cells that can be killed without side effects that is important. Cynaide has a 100% kill rate but it is not useful as an anti-cancer drug as it will kill the patient too. DCA is relatively non-toxic compared to many of the standard chemotherapy drugs, so the amount of DCA that can be safely taken is a lot higher. This means that:
Milligram for milligram, DCA+Metformin could be as effective as any of the big name chemotherapy drugs, but with a tiny fraction of the side effects of chemotherapy.
According to this paper, Metformin is effective against glioblastoma (1), a form of cancer:
Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect.
According to this paper, Metformin may boost DCA (2):
By itself, metformin was ineffective in treating tumors. In a one-two punch, metformin reduced tumors faster and prolonged remission in mice longer than chemotherapy alone, apparently by targeting cancer stem cells …
… The results fit within the cancer stem cell hypothesis, an intensely studied idea that a small subset of cancer cells has a special power to initiate tumors, fuel tumor growth, and promote recurrence of cancer. Cancer stem cells appear to resist conventional chemotherapies, which kill the bulk of the tumor. …
… In mice, pretreatment with the diabetes drug prevented the otherwise dramatic ability of human breast cancer stem cells to form tumors. In other mice where tumors were allowed to take hold for 10 days, the dual therapy also reduced tumor mass more quickly and prevented relapse for longer than doxorubicin alone. In the two months between the end of treatment and the end of the experiment, tumors regrew in mice treated with chemotherapy alone, but not in mice that had received both drugs.
The team was further encouraged by the low dose of metformin needed for the effect in the laboratory, compared to the amount needed for analogous molecular experiments in basic diabetes research. The relative dosage in people for treating or preventing cancer is unknown and untested.
Apart from this interesting effect on cancer stem cells, the ability of metformin to enhance peripheral glucose uptake and increase fatty acid oxidation could be synergistic with the DCA ability to increase the intracellular metabolism of glucose, causing cancer cell apoptosis. Metaphorically, adding more fuel to the already accelerated engine of cancer cells would lead them to break down. Experiments are needed to verify this hypothesis.
- Metformin enhances the effect of DCA;
- It didn’t take much Metformin to enhance the effect of DCA.
Is DCA + Low Dose Metformin Safe?
Unfortunately, there is little data on human trials with DCA + Low Dose Metformin. We can sum up the likely safety of this combination as follows:
- We know that Metformin had over 40 million prescriptions issued in 2008 alone(2).
- We know that DCA has been safely used by 1,500 people (8).
- We know that Metformin by itself is effective against glioblastoma.
- Metformin targets the “cancer stem cells”, a small subset of cancer cells has a special power to initiate tumors, fuel tumor growth, and promote recurrence of cancer.
- We know that DCA by itself is safe and effective against glioblastoma.
- We know that DCA+Metformin is even more effective against glioblastoma, with a 99% kill rate vs. a 3 – 10 % kill rate.
- We know that we don’t need much Metformin to enhance the effectiveness of DCA. Thus, we coin the term Low Dose Metformin.
- Therefore, we know that DCA+Low Dose Metformin is effective against glioblastoma.
- We know that for very effective anti-cancer therapies, we should be very careful with Tumor Lysis Syndrome (TLS). We know that this is even more important with patients with a large glioblastoma tumor. Please read the page on DCA (Sodium Dichloroacetate) which describes how to prevent Tumor Lysis Syndrome (TLS), as at least one patient has unnecessarily died from this entirely preventable condition.
We don’t know what the safe dose is.
We do know that as DCA + Low Dose Metformin is so effective against Glioblastoma, we would have to take extreme caution:
- Start with an extremely low dose (3%?) of the standard dose of DCA that is safe for glioblastoma.
- Start with a small fraction of the dose (10%?) of the standard dose of Metformin used for Diabetes patients.
- Do not use caffeine.
Please read the page on DCA (Sodium Dichloroacetate) which describes how to prevent Tumor Lysis Syndrome (TLS), as at least one patient has unnecessarily died from this entirely preventable condition.
We can always ramp up the dose if no negative side effects are encountered.
At the present time, it appears that the only people in the world that have information on the appropriate dosage of DCA+Metformin is www.medicorcancer.com, the authors of the paper. I hesitate to mention this, as I want to keep the site completely objective and free from any commercial conflict of interest, but I feel I have to in order to keep the options open. For the record, I am not affiliated in any way with Medico Cancer, see my No Conflicts of Interest statement.
The bottom line is this: if you’re completely out of options, then there is always hope.
If you do try this, please keep a blog so we can follow your progress, and let us know how you go.
Appendix A: We have a positive drug interaction?
Metformin poisoning is characterised by lactic acidosis (7).
There were concerns that Metformin increased the risk of death due to lactic acidosis (3). These concerns were found to be not statistically significant, as out of 51,675 patients in Sweden that have taken Metformin, 8 have died due to lactic acidosis (3), and there were other complicating factors such as other drug interactions.
The original purpose of DCA was to treat congenital lactic acidosis in children (4). It has also been used to treat lactic acidosis in patients with severe malaria.
This is interesting: a potential side effect of Metformin is lactic acidosis, and DCA is used to treat lactic acidosis. That sounds like a positive drug interaction rather than a negative drug interaction.
- (1) Cell Cycle. 2013 Jan 1; 12(1): 145–156. doi: 10.4161/cc.23050. PMCID: PMC3570504. Metformin selectively affects human glioblastoma tumor-initiating cell viability. A role for metformin-induced inhibition of Akt. By Roberto Würth. See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570504/.
- (2) Metformin Boosts DCA, see http://www.cancerevolution.info/cancer-therapies/dca-therapy/93-can-metformin-boost-dca.html.
- (3) BMJ Open 2012;2:e001076 doi:10.1136/bmjopen-2012-001076. Diabetes and endocrinology. Effectiveness and safety of metformin in 51,675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register. Nils Ekström. See http://bmjopen.bmj.com/content/2/4/e001076.
- (4) Pediatrics. 2006 May;117(5):1519-31. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children, by Stacpoole PW et. al. See http://www.ncbi.nlm.nih.gov/16651305.
- (5) Bradford and Khan, J Cancer Sci Ther 2013, 5.3. Individualizing Chemotherapy using the Anti-Diabetic Drug, Metformin, as an “Adjuvant”: An Exploratory Study. Sherry A. Bradford and Akbar Khan. See http://dx.doi.org/10.4172/1948-5956.1000197.
- Full paper: DCA+Metformin for Glioblastoma.pdf.
- (6) See www.medicorcancer.com and http://medicorcancer.com/document-downloads/. See paper entitled “DCA (dichloroacetate) Frequently Asked Questions.”.
- Full paper: DCA-FAQs.pdf.
- (7) Indian J Anaesth. 2011 Mar-Apr; 55(2): 190–192.. doi: 10.4103/0019-5049.79890. PMCID: PMC3106398. Metformin poisoning: A complex presentation. Manish Jagia. See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106398/.
- (8) www.youtube.com – Khan Hippocrates Lecture on DCA Therapy, see https://www.youtube.com/watch?v=9o12uT_d-Co.