DCA The Solution To Metformin Induced Lactate?

[LucyL]

This was quite interesting, and as a user of the Care Oncology Clinic protocol (Metformin, Atorvastatin, Doxycycline & Menbendezole) information I've been looking for.

I have been using Pyrucet occasionally, but may increase it with this information.

Dichloroacetate Enhances Apoptotic Cell Death via Oxidative Damage and Attenuates Lactate Production in Metformin-Treated Breast Cancer Cells

Metformin, a promising breast cancer therapeutic, targets complex I of the electron transport chain leading to an accumulation of reactive oxygen species (ROS) that eventually lead to cell death. Inhibition of complex I leads to lactate production, a metabolic byproduct already highly produced by reprogrammed cancer cells and associated with a poor prognosis. While metformin remains a promising cancer therapeutic, we sought a complementary agent to increase apoptotic promoting effects of metformin while attenuating lactate production possibly leading to greatly improve efficacy. Dichloroacetate (DCA) is a well-established drug used in the treatment of lactic acidosis which functions through inhibition of pyruvate dehydrogenase kinase (PDK) promoting mitochondrial metabolism.
...
We demonstrate that DCA and metformin combine to synergistically induce caspase-dependent apoptosis involving oxidative damage with simultaneous attenuation of metformin promoted lactate production.

 

[mouse]

This was quite interesting, and as a user of the Care Oncology Clinic protocol (Metformin, Atorvastatin, Doxycycline & Menbendezole) information I've been looking for.

I have been using Pyrucet occasionally, but may increase it with this information.

Dichloroacetate Enhances Apoptotic Cell Death via Oxidative Damage and Attenuates Lactate Production in Metformin-Treated Breast Cancer Cells

Metformin, a promising breast cancer therapeutic, targets complex I of the electron transport chain leading to an accumulation of reactive oxygen species (ROS) that eventually lead to cell death. Inhibition of complex I leads to lactate production, a metabolic byproduct already highly produced by reprogrammed cancer cells and associated with a poor prognosis. While metformin remains a promising cancer therapeutic, we sought a complementary agent to increase apoptotic promoting effects of metformin while attenuating lactate production possibly leading to greatly improve efficacy. Dichloroacetate (DCA) is a well-established drug used in the treatment of lactic acidosis which functions through inhibition of pyruvate dehydrogenase kinase (PDK) promoting mitochondrial metabolism.
...
We demonstrate that DCA and metformin combine to synergistically induce caspase-dependent apoptosis involving oxidative damage with simultaneous attenuation of metformin promoted lactate production.

Thank you for posting this.

Considering the hepatoxicity of DCA (e.g. Fatal Liver and Bone Marrow Toxicity by Combination Treatment of Dichloroacetate and Artesunate in a Glioblastoma Multiforme Patient: Case Report and Review of the Literature), I wonder if ALA in high doses (if there is no mercury toxicity present) would also increase PDH as sufficiently as DCA (e.g. alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with ... - PubMed - NCBI).

Incidentally graviola also reportedly inhibits complex I, (in addition to the often mentioned metformin alternative berberine,) though I have no idea if it does it enough in real people.

 

[LucyL]

The poor (very sick) patient in that report was on a lot of stuff, some very toxic and all affecting the central nervous system. The paper was a purely speculative hatchet job on alternative treatments. Of course all practitioners should be very careful, no matter what they are administering, but I think this kind of stuff is written to give big pharma cover so people won't call for their prosecution.

 

[mouse]

The hepatoxicity of DCA is based on their literature review collated in Table 2. I'm not convinced that DCA is not hepatoxic, unlike ALA. If it was a hatchet job, they would have made spurious accusations of artesunate, but they did not.