Wednesday, 23 August 2017

DCA and glioma

Human glioblastoma patients require at least a 6.25 mg/kg oral, twice-a-day dose of DCA (Dichloroacetate) to inhibit PDK (Pyruvate dehydrogenase kinase) and kill cancer cells as indicated in the study below (5).

http://artemisinin.pbworks.com/f/Metabolic+Modulation+of+Glioblastoma+with+Dichloroacetate.pdf



A reliable source of DCA can be found here:

https://www.dcalab.com


It comes in tablet form as well as a powder.



The main problems I see here is that you would need to have enough of the product to get the appropriate therapeutic dose and it is not cheap!


Simple background as to why DCA might be useful:

As many reading this will already know, most tumours display unique metabolism described as the 'Warburg Effect' which has long been associated with the resistance to apoptosis which characterises cancer. Even in tumours where glucose is maybe not the primary fuel, it appears to still play a key role as a major energy source. 

the Warburg Effect (9)


Cancer is clever, there are parallels with Darwinian natural selection (1), meaning it can adapt to use different fuels in the absense of others. With this in mind, I believe it is key to note that the best result is unlikely to come from a monotherapy approach. Nevertheless, this glycolytic phenotype in most cancers appears to be a common denominator and gives reason as to why all these molecular abnormalities occur, and as a result lead to defective mitochondria. The good news is that research suggests this suppression of mitochondrial function we see in cancer may be reversible with DCA at therapeutic doses.

Mitochondrial physiology (8)


DCA exerts its anti-cancer effects by inhibiting an enzyme called PDK (Pyruvate Dehydrogenase Kinase), a mitochondrial enzyme that is activated in a variety of cancers. Inhibition of PDK with DCA shifts the metabolism of cancer cells from glycolysis to glucose oxidation (7). As a result we would hope to see restoration of normal mitochondrial function and suppression of mitochondrial dependent apoptosis.



As I say, typically nothing works as effectively in isolation as with a multi-modal approach. Personally I would recommend a low carb, fasting mimicking diet, time restricted feeding and/or longer periods of just water fasting alongside DCA. 

Why?... 

Well, I get lots of people asking about how some tumours appear to be able to use fatty acids for energy after reading certain studies showing up regulation of lipogenic enzymes in cancer cells (4). It is well established that deregulated lipogenesis plays an important role in tumour cell survival (3) and as a result, FASN (fatty acid synthase) is also a therapeutic target. However... 

I wouldn't worry about this in the context of a continuous ketotic state or through implementation of a low carb diet and I will tell you why. Despite the fact that this phenomenon exists, research shows that the expression of FASN is highly dependent on nutritional conditions in lipogenic tissues. 

'FASN-catalysed endogenous FA biosynthesis in liver and adipose tissue is stimulated by a high carbohydrate diet, whereas it is suppressed by the presence of small amounts of FAs in the diet and by fasting.' (2,6) 




References

1. Greaves, M. and Maley, C.C., 2012. Clonal evolution in cancer. Nature481(7381), p.306.

2. Katsurada, A. et al. Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in liver. Eur. J. Biochem190, 427–433 (1990).

3. Mashima, T., Seimiya, H. and Tsuruo, T., 2009. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. British journal of cancer100(9), p.1369.

4. Menendez, J.A. and Lupu, R., 2007. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nature reviews. Cancer7(10), p.763.

5. Michelakis, E.D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E., Maguire, C., Gammer, T.L., Mackey, J.R., Fulton, D. and Abdulkarim, B., 2010. Metabolic modulation of glioblastoma with dichloroacetate. Science translational medicine2(31), pp.31ra34-31ra34.

6. Sul, H. S. & Wang, D. Nutritional and hormonal regulation of enzymes in fat synthesis: studies of fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase gene transcription. Annu. Rev. Nutr. 18, 331–351 (1998).

7. Sutendra, G. and Michelakis, E.D., 2013. Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology. Frontiers in oncology3.

8. Wallace, D.C., 2012. Mitochondria and cancer. Nature reviews. Cancer12(10), p.685.

9. Vander Heiden, M.G., Cantley, L.C. and Thompson, C.B., 2009. Understanding the Warburg effect: the metabolic requirements of cell proliferation. science324(5930), pp.1029-1033.
  


25 comments:

  1. This post is really nice, Thanks for it and keep updating.

    Brain Cancer doctor In noida

    ReplyDelete
  2. My family is now a brand new one, so stop your worries and go get your medication and set the family free of the deadly disease that hold no respect to family harmony. Make your health a better one by using cannabis oil in your everyday life. contact Dr.Patrick on: drpatrickoscar@yandex.com for all type of cancer cure

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  3. Hi Andrew. Do you have any comments on using DCA on you? Thanks.

    ReplyDelete
  4. Hi Andrew, I was diagnosed grade 2/3 in 2007. would love to chat sometime. drop me an email at jpc14_99@yahoo.com

    ReplyDelete
  5. Thank you for this post, Andrew.
    I have used DCA for 3 months now (glioblastoma), purchased it from puredca.com. So far, so good :)

    Not many other dca manufacturers stress and point out the fact that:

    1) if you have brain cancer, you should absolutely not drink coffee at same time you are using dca. Otherwise you could risk serious side effects. (You have to be careful with anything that contains caffeine: teas, cocoa, energy drinks, etc.)

    2) You can counter the risk of periphreral neuropathy when supplementing with Thiamine (vitamin B1).

    ReplyDelete
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