Sunday, 21 May 2017

Targeting Tumor Metabolism - DCA, Selenium, and CoQ10

Hi all,

My Dad (diagnosed GBM Nov. 2016) is soon to be on his 6th TMZ cycle and has had two Avastin Infusions. I've mentioned before on here we are going to use the minimal amount of Avastin, spread out as far as possible, as to not allow the tumor to adapt. We have had great results from Avastin so far.

My hunt to find ways to make Avastin more effective quickly led me to the idea of adding DCA to our cocktail. Originally when I mentioned DCA to our NO he didn't think it was worthy for reasons I didn't full understand.

Now that we are using Avastin I will bring this up again, but my research on DCA and it's "support" of the mitochondrial function also led me to Selenium and CoQ10.

We already have a hefty daily cocktail so I'm just checking in if others have opinions:

Few quick questions:

  • Are there any other current studies that show dosage amounts for DCA with Avastin and it's benefits when taken together? I really want to show a good reason for pushing DCA when I see the NO next. I have only found the one referred to on the astrocytomaoptions website here (using mice): 
https://www.ncbi.nlm.nih.gov/pubmed/23361368

  • CoQ10 - I'm curious why this supplement is not on the shared "Pharma/Non Pharma List Rankings for GBM" spreadsheet. This appears to be just as beneficial as Selenium in supporting mitochondrial function. Any thoughts on why this isn't mentioned as often as Selenium? Preferred dosage and brand?
  • Selenium - I was excited to see is ranked fairly high on the spreadsheet. I also have read it not only helps with mitochondrial function but can potentially make TMZ treatments more effective - looks like standard dosage is 200mcg/day. Any opinions on good brand?

Thank you all for reading and supporting.

Ari

3 comments:

  1. Hello Ari, these are interesting questions.

    1) Unfortunately there has never been a formal trial or study testing Avasting + DCA in humans. People on this blog have tried that combination, but as far as dosing I think people are mainly using standard recommended DCA doses. However, the proper dose for an individual can only be determined by trial and error as differences in DCA metabolism vary so greatly from person to person - 5 mg/kg twice daily may be enough for someone with slow DCA metabolism, but not therapeutic for someone with fast DCA metabolism. For this reason even small clinical trials cannot determine a dose that will work for each individual, unless genetic testing is performed on each patient's blood to predict how quickly they will metabolize DCA.

    2) The mechanisms of DCA versus coenzyme Q10 are vastly different. The primary function of DCA is to reverse the negative regulation of the pyruvate dehydrogenase complex, causing more pyruvate to be shuttled into the mitochondrial citric acid cycle rather than being converted into lactate outside the mitochondria.

    While DCA could be expected to disrupt the tumor's metabolic adapation to increased hypoxia post-Avastin (as in the mouse study with Avastin + DCA), coenzyme q10 and selenium cannot be expected to work the same way.

    There is actually a significant amount of literature on targeting and destabilizing mitochondrial function rather than enhancing it, as a form of cancer therapy.
    http://www.sciencedirect.com/science/article/pii/S1567724912002000

    The pharma/non-pharma spreadsheet is not the last word on anything, it's simply a reflection of what I've researched, and is mostly based on evidence rather than theory. I've not seen any in vivo or human evidence for coenzyme q10 for glioma/GBM and have not made it a focus of research. DCA has far more experimental evidence and even some human evidence. Selenium was included on the spreadsheet mainly because of the human evidence for immune enhancement in head and neck cancer patients.

    There is not complete agreement about the reasons for the Warburg effect (anaerobic fermentation of pyruvate to lactate even in the presence of oxygen) in cancer cells. Some theorists say it's due to defective mitochondria, while other research says there are other reasons that this would happen. I'm not personally convinced that mitochondrial support in the form of coenzyme q10 would be disruptive to cancer cells, but there are likely other reasons to take it. Chemoprotection for patients taking anthracycline chemotherapy is one of it's documented beneficial uses.

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  2. Truly appreciate the breakdown. Moving forward a step at a time. Thank you

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  3. Ari,

    We use selenium cruciferate, as it is supposed to be a more natural form. I'd have to dig up the literature (from Jeanne Wallace) as to why that is the preferred form. Here is a link to it on Amazon, but I don't purchase it through there and it's not an affiliate link - just for your informational purposes:

    https://www.amazon.com/Ecological-Formulas-Selenium-Cruciferate-Health/dp/B003TVGFVU

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