Doxycycline, Metformin, and Chemo
Great blog and spreadsheet, Johan! I wanted to get your thoughts on the use of Doxycycline and Metformin during chemotherapy. In the article, "Shutting Down the Power House of Cancer," it says, "In case this strategy [the Shut-Down-the-Energy-Engines strategy] is combined with chemotherapy, I would stop all fermentation inhibitors 3 days before chemo (including Metformin/Berberine as it also affects fermentation but not Doxycicline or Atorvaquone), and restart them in the day of chemo . . ." According to this, you would use Doxycycline continuously during chemotherapy and stop metformin 3 days before chemo and restart it on the day of chemo. However, the same article says, "The strategy we chose should be inline with the core treatment we decide to have. For example, if we go for Chemotherapy or Radiotherapy we may chose the pro-oxidant strategy as our Central strategy, and build our treatments around that . . ." I interpreted this statement to mean that the pro-oxidant strategy is preferable if chemotherapy is the central strategy.
In the article, "Modulating the Yin and Yang Energy of Cells to Fight Cancer: Pro-Oxidant Strategy," it says, "in general I would not rely on mitochondria inhibitors to do the job as a part of this strategy [the pro-oxidant strategy], unless we know exactly what we are doing." So, according to this, you should stop both metformin and doxycycline when using the pro-oxidant strategy since they are both mitochondria inhibitors. However, the same article says, "Furthermore, it has been shown that re-activating mitochondria with DCA while interfering with mitochondrial complexes I, with the help of Metformin, can further enhance ROS production . . ." So, according to this statement, metformin can be used with the pro-oxidant strategy even though it is a mitochondria inhibitor.
I am trying to synthesize the above information found in these two articles. Would you please help me, Johan?
@ram thanks! In a pro-oxidant strategy, you're pushing cancer cells beyond their capacity to deal with oxidative stress. In my view, chemotherapy already does a great job at this. If you disrupt or inhibit mitochondria, this could induce more ROS indeed. But it could also trigger cancer cells to enhance antioxidant defense mechanisms or other adaptive responses especially if the inhibition is too moderate. It's very complicated and the outcome will be context and cancer-cell type-specific. I think what Daniel points to is that by inhibiting mitochondria the possibility is greater you provoke an antioxidant defense mechanism, but I'm not sure. So factors such as dosage and timing, the dosage of the chemotherapy, and the type of chemo come into play and will be decisive for the outcome.
What I suggest is to look in the scientific literature for studies that have shown effectiveness in enhancing the chemo your mother will be using on her cancer type. Because these compounds can affect cancer in different ways e.g. reducing drug resistance etc.
Thank you, Johan. Unfortunately, my mom's cancer is a rare form of cancer called pancreatic acinar cell carcinoma. There is not much in the way of research. She has decided to go with this chemotherapy protocol: paclitaxel (60 mg/m²) or Abraxane, oxaliplatin (50 mg/m²), Leucovorin (20 mg/m², minimum dose of 40 mg), and 5-FU (425 mg/m²) administered weekly.
I am concerned about using doxy during chemo for two reasons: (1) The microbiome (2) Mitochondria inhibition.
For the first 3 days, starting with the day of chemo, I am thinking Mom should use Metformin 500mg 2x/day, atorvastatin 80mg 1x/d, DCA 500mg 2x/day, dipyridamole, 200mg 2x/day. Because she is getting chemo infusions weekly, she can't take these medications for more than 3 days. I've read that DCA can be taken prior to chemo, but that makes me a bit nervous because of how it affects fermentation, though it is a mitochondria activator. Are there any other repurposed drugs we should research and think about adding to the Metformin, DCA, Atorvastatin, and Dipyridamole?
@ram just recently I started looking into pancreatic cancer, from my specific perspective of anti-synergies I must add, but I'll expand my searches and take your information into account. I'll get back to you over the weekend.
meant to type "anticancer synergies"