Should I be worried? I know we are dealing with GBM but a drug study that has found that DCA can promote progression in mice with Neuroblastoma tumours raises issues for me. I'm the first to admit, extrapolation can lead me down the garden path.... thoughts anybody.
http://www.ncbi.nlm.nih.gov/pubmed/25973318
Also how do we know if we are fast or slow metabolisers? Half life of DCA can vary from 1 week to greater then 3 months.
http://www.ncbi.nlm.nih.gov/pubmed/1878534
Do I just go on symptoms of neuropathy? I ask this because extended use or high dosage can cause cancer itself.
Just trying to keep our heads above water
Linda
I've seen this study too, and agree it is concerning, although every study I've seen with DCA and glioma shows the opposite outcome - tumor inhibition.
ReplyDeleteThe outcomes in any rodent study depend on the cell line used, whether the animals are athymic/nude (immunodeficient) or not, and whether the tumor cells are injected orthotopically (in glioma studies that would be in the brain), or not.
My position is that the human evidence we have for DCA and GBM trumps any rodent evidence. I will add this human evidence (Michelakis, 2010) to the Brain Tumor Library.
http://stm.sciencemag.org/content/2/31/31ra34
Regarding the second link, the 1 week to 3 month interval is the time required to elapse between DCA doses "in order to prevent second doses having relatively long half-life values". The actual average half-life varies from 1.58 hrs (initial dose) to 9.9 hrs (subsequent doses) according to the same abstract.
The only way I'm aware of to predict whether one is a fast or slow metabolizer beforehand is genetic testing of the GSTZ1 gene. Peter Stacpoole, an authority on DCA at the University of Florida has written about this. Additionally, blood plasma levels of DCA could be measured following DCA ingestion, and that would also give you some idea about fast vs. slow metabolism.
According to Stacpoole: "Indeed, no epidemiological investigations have
studied the carcinogenicity of DCA in humans."
Liver carcinogenicity has been shown in inbred rats and mice, although this sort of toxicological study in rodents usually use doses far higher than humans would be exposed to. However, monitoring of liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) is generally a good idea, while on a drug cocktail, for early detection of liver toxicity.
Review by Peter Stacpoole:
http://ehp.niehs.nih.gov/1002554/
If I were going to start taking DCA, I would probably start with a dose of ~5-7 mg/kg twice daily and stay there for maybe 2 months. If that dose is tolerated well I would gradually increase the dose after that. If I began to experience any sign of neuropathy I would probably stop taking it for awhile until symptoms disappeared.
From Stacpoole again:
"Clinical features [of peripheral neuropathy] include tingling of the fingers and toes and weakness of the facial and distal muscles of the extremities, accompanied by reduction in nerve conduction velocity in the sural and tibial nerves"