Posted on by Daniel

How to potentially enhance Chemotheraphy effectivness

It is well know that tumors often develop resistance to (chemo) therapies via various mechanisms. Some of the mechanisms are well understood today and there are various drugs or supplements that may have the ability to suppress some of these resistance mechanisms. Bellow, I tried to cover most of the known resistance mechanism and indicate drugs or supplements to address them. In order to maximize the treatment outcome, I would use one element from each of the following categories. In general, I would probably use them about one week before the chemo, during the chemo and some days/weeks after chemo.

Based on the categories mentioned below, here is a nice cocktail:

  • Palmitoylethanolamide – 3 x 400 mg/day – (supplement)
  • Pyrvinium pamoate – 5 mg/kg/day – (over the counter in countries like Sweden, Norway, etc.)
  • Scorpion Venom – (supplement)
  • Omeprazole – 40 to 80mg/day – (over the counter in countries like the Netherlands, Belgium, etc.)
    • to use only if the chemo used is weak basis – if it is weak acid I would not use Omeprazole and stop all proton pump inhibitors during chemo as the weak acid chemo effectiveness may be lowered by proton pump inhibitors.
  • Verapamil – 3 x 80mg/day – (on prescription or online pharmacies)
  • Dipyridamole – 2 x 200mg/day – (over the counter in countries like Belgium, etc.)
  • Metformin – 2 x 500mg/day – (on prescription or online pharmacies)
  • Chloroquine – 200 to 400mg/day – (over the counter – for those traveling to countries with malaria risk)
  • Doxycycline – 200 to 400mg/day – (on prescription or online pharmacies) and or Mebendazole 200mg – 1g/day (this is one of my favorites – over the counter and available on eBay)
  • Omega-3 (EPA and DHA) – 10g-15g/day

Note: The list bellow will be continuously updated and refers to various elements that if used prior or during the chemo sessions may enhance the effectiveness of the chemo.

Update 08.03.2016: Dear All reading this website, based on recent personal experience I suggest that while using chemo the strong anti oxidants (such as Alpha Lipoic Acid, NAC, etc.) shoudl not be used in high dose forms such as Intra Venous. Not even several days after or before chemo as they will clearly protect cancer cells. I know that this  is what the oncologist are saying and many are questioning this statement but now I support 100% that statement. Low dose oral supplements such as Alpha Lipoic Acid may help and support e.g. the liver (so I may still use that?) but high dose will help cancer cells defend the pro oxidant anti cancer effect of chemo or other pro oxidant treatments such as 3BP.

Update 28.05.2018: Here is a very good scientific paper describing each known major point that could influence the effectiveness of chemo: “Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp“.

chemotherapyReducing Side Effects

Reducing Glutathione – Glutathione (GSH) is the most abundant non-enzymatic antioxidant molecule in the cell and is essential for cell survival and redox homeostasis – Glutathione is used by cancer cells to compensate for increase oxidative stress due to treatments such as chemo or radiation

Therefore, during Chemo we need to avoid strong anti oxidants such as IV Alpha Lipoic Acid or NAC supplements. To me that doesn’t mean that we need to avoid food with anti oxidant properties.

“Cancer cells have a high demand for ATP because it provides the ‘fuel’ for aberrant proliferation. However, the dark side of this uncontrolled energy production is the accumulation of ROS, which needs to be counteracted by scavenging mechanisms to ensure cell survival. At high levels, ROS promote cell death and severe cellular damage. Cancer cells need to combat this high levels of ROS. Therefore, cancer cells characteristically have a high antioxidant capacity that regulates ROS to levels that are compatible with cellular biological functions but still higher than in normal cells. We believe that targeting these enhanced antioxidant defence mechanisms may represent a strategy that can specifically kill cancer cells.” (Ref.)

“ROS are broadly defined as oxygen-containing chemical species with reactive properties. These include the superoxide (O2 •−) and hydroxyl (HO• ) free radicals as well as non-radical molecules such as hydrogen peroxide (H2 O2 )” (Ref.)

“Thus, although treatments such as chemotherapy and radiotherapy — which induce the production of ROS — are useful for eliminating the bulk of cancer cells, such approaches may fail to cure the patient owing to the superior ability of cancer stem cells to survive in conditions of high ROS by upregulating levels of antioxidants. As ROS are critical mediators of the lethal effects of ionizing radiation and some anticancer drugs, TICs may be preferentially spared and actively selected by treatments that depend on high ROS levels.” (Ref.)

Reducing acidity around the tumors – most of the tumors are using glucose as one of the main fuels for energy production. During this energy production, acidity (protons) are being produced and continuously pushed out into the tumor environment, via several types of transporters, creating an acidic environment. This environment promotes tumor progression, inhibits the action of the immune system and “deactivates” various chemotheraphies that are weak basis (but is helping the weak acid chemos). Various elements that lead to reduction of acidity around tumors:

Therefore, I would check if the chemo I use is weak basis and if yes I would consider this approach to increase its effectiveness. If on the other hand is weak acid, I would stay away from combing proton pump inhibitors with the chemo.

Reducing Multi Drug Resistence – many cancers can resist chemotheraphy due to specific pumps that are located in the cell membrane and are used to push the drugs out of the cells. These pumps are over expressed in cancer. Various elements that can reduce or inhibit these pumps are:

  • Verapamil (e.g. Ref.)
  • Ketoconazole
    • Note: Coadministration of simvastatin (or lovastatin) with antifungals (itraconazole or ketoconazole) can result in rhabdomyolysis and acute renal failure (Ref.) Simvastatin & lovastatin should therefore not be used concomitantly with itraconazole and other potent CYP3A4 inhibitors, or the dosage of lovastatin should be greatly reduced while using a CYP3A4 inhibitor (Ref.). This increased toxicity is not apparent with fluvastatin (Ref.)
  • Tetrandrine (this is a natural Ca channel inhibitor – cheap – used in China before and during Radiotherapy and Chemo to enhance the effect of the therapies – I very much like it)
  • Mebendazole was recently found to inhibit MDR (Ref.)
  • Low Doses of the Anti-psychotic Drug Aripiprazole more effective than Verapamil? (Ref.)

Alternatively, Tepoxalin (a NSAID drug) kills cells expressing high level of MDR (Ref.1, Ref.2)

Increasing blood flow – tumors usually have leaky blood supply and that limits the chemotheraphy that may reach the tumors. Various elements that can help dilated the vessels are:

Reduce glucose to cancer cells – reducing glucose available will lead to lower energy in the cancer cells available to fight chemotheraphy. Below are a few elements that can help reduce the glucose availability of energy production:

Increase RedOx – chemotheraphy puts constant stress on the cancer cells and there are other theraphies who can further add additional stress next to that:

  • DCA (Dichloroacetate)
  • Scorpion Venom
  • Hyperthermia
  • 3BP
  • Exercise & Oxygen

Inhibiting Autophagy – “Autophagy has dual roles in cancer, acting as both a tumor suppressor by preventing the accumulation of damaged proteins and organelles and as a mechanism of cell survival that can promote the growth of established tumors. Tumor cells activate autophagy in response to cellular stress and/or increased metabolic demands related to rapid cell proliferation. Autophagy-related stress tolerance can enable cell survival by maintaining energy production that can lead to tumor growth and therapeutic resistance. As shown in preclinical models, inhibition of autophagy restored chemosensitivity and enhanced tumor cell death.” (Ref)

Bacteria, Parazites, etc. – Tumors (specifically thos ein the lungs) may be “populated” by bacteria and other parasites that just because of their mostly peripheral location may “absorb” the administrated (chemo) substance which as a result may not reach the tumor in high enough dose. There are various medicines that are both know to posed anti cancer properties and can at the same time address this issue:

Others:

Fasting 2-3 days prior to chemo (or radiation) will also help: Fasting-like diet turns the immune system against cancer https://news.usc.edu/103972/fasting-like-diet-turns-the-immune-system-against-cancer/

See Also: this comment https://www.cancertreatmentsresearch.com/pyrvinium-pamoate/#comment-3065

References:

Modulation of oxidative stress as an anticancer strategy (Ref.) http://www.nature.com/nrd/journal/v12/n12/full/nrd4002.html?message-global=remove

The regulation of oxidative stress is an important factor in both tumour development and responses to anticancer therapies. Many signalling pathways that are linked to tumorigenesis can also regulate the metabolism of reactive oxygen species (ROS) through direct or indirect mechanisms. High ROS levels are generally detrimental to cells, and the redox status of cancer cells usually differs from that of normal cells. Because of metabolic and signalling aberrations, cancer cells exhibit elevated ROS levels. The observation that this is balanced by an increased antioxidant capacity suggests that high ROS levels may constitute a barrier to tumorigenesis. However, ROS can also promote tumour formation by inducing DNA mutations and pro-oncogenic signalling pathways. These contradictory effects have important implications for potential anticancer strategies that aim to modulate levels of ROS. In this Review, we address the controversial role of ROS in tumour development and in responses to anticancer therapies, and elaborate on the idea that targeting the antioxidant capacity of tumour cells can have a positive therapeutic impact.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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118 thoughts on “How to potentially enhance Chemotheraphy effectivness”

  1. A little update about my mother :

    like I said before , she was on Taxotere 160mg (every 3 weeks) + DCA , after 4 months the tumor markers went from 2000 to 350

    then she took Taxotere 160mg only with no DCA , after 2 months the markers became 745 (that was on Feb 16)

    on (Feb,17) she took another shot of (Taxotere 160mg) , there is still no DCA , only Taxotere alone

    but I decided to add other things , on (Feb,22) I add the following :-

    Lansoprazol 60mg , HydroxyChloroquine 400mg , Cimetidine 800mg , Metformin 1g , Paracetamol 2g , Sulfasalazine 2g , Mebendazol 200mg , Aspirine 100mg
    (I gave them on low doses at the beginning then increased it gradually)

    Today : tumor marker CA 15-3 is : 712 ! (slight decrease) the oncologist didn’t expect that !

    i think she (the oncologist) is wondering how Taxotere was not working and effective at all then suddenly it shows some little effect !

    now what do you think about this result 😀

    1. Dear Emad,

      I was reading your old message today and was wondering if Taxotere-resistance can be overcome one way or another. I am not sure how relevant this is to you and your mom now but I found this: “Resveratrol chemosensitizes HER-2-overexpressing breast cancer cells to docetaxel chemoresistance by inhibiting docetaxel-mediated activation of HER-2–Akt axis” http://www.nature.com/articles/cddiscovery201561

      It is quite remarkable also because resveratrol is a natural product. Also: “Docetaxel and resveratrol exerts synergistic cytotoxic effect in breast cancer cells, while normal immortalized breast epithelial cells are unaffected” – I wonder of Taxotere (Docetaxel) is used in other cancers than that of the breast?

      It seems that this synergy is not limited to breast cancer: https://www.ncbi.nlm.nih.gov/pubmed/22011009 “Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro.” It might be important because resveratrol is an antioxidant, still it works synergistically with these two chemos.

      1. Hi Helga , how you are fine today 🙂

        my mother is on Gemzar + Carboplatin for months ago , she is no more taking Taxotere

        but I really remember how the results were great when she were taking high amounts of black grapes (eating and juicing) , what I know is that black grapes are one of the best natural source of resveratrol , also she was taking a lot of things including DCA but those results were more better than Taxotere and DCA alone

  3. yes its a good result for only 10 days !
    about paracetamol , its not used every day but that’s the problem I’m afraid of the toxicity of these drugs
    can you suggest to me which of these drugs are less useful ? or which of them are more likely to cause toxicity ?
    i didn’t like to use all of them , but DCA will take some time to arrive so i don’t have another choice to help the chemo effectiveness
    ———
    for now looks like we are confused , the oncologist suggest one of these choices : continue on Taxotere , or change to vinorelbine !
    personally it doesn’t matter which chemo we gonna use
    it will be Chemo + DCA + Escozul ,
    I’m thinking about adding other strong treatments :
    3-BromoPyrovate ?
    or maybe Diflunisal IV ?
    but I’m not sure will it be a good idea to use Diflunisal ? i heard from Dr.Nolting (from Hallwang Private Oncology clinic) that it may cause bleeding from the colon ? i don’t know if its true or not
    Salinomycin is very expensive we can’t get it right now
    a lot of options , i don’t know from where to start

  4. Hi Emad, all are useful to me and if things seem to work well, why change that?
    Diflunisal IV: Yes, I did had a few discussions with dr. Nolting and yes it is well known that salicylates in high dose are coming with risks of bleeding. So dr. Nolting is right about that but I am sure that as a doctor he knew about those risks before offering the theraphy at Hallwang. I think we as patients need to make distinction between relation and competition between various doctors offering various treatments and the efectivness of those treatments. With that in mind, I think that both dr. Nolting and prof. Drevs have relevant treatments that they offer and both are very very expensive, while we know that some of those treatments can be more accessible given the low cost of the material. Coming back to your question, yes Diflunisal has risks (actually this is not only due to Diflunisal alone but also because the treatment protocol requires Aspirin IV in high dose as well) and this is why it has to be done with care. We did it (at home) and my wife felt that helped a lot. Indeed I know people who were even cured with Diflunisal – this i why is listed as a “top treatment” on my website. Btw, recently I found a pharmacy in the Netherlands that would sell Diflunisal IV that would be required for one day treatment with <100euro. I will list that source soon on my website.
    Salomicyn Sodium Salt is 10x cheaper than the base various and expected to be effective as well.

    1. They are working well but I don’t want to be hard on the liver

      Diflunisal < 100 euro is expensive for only one day treatment

      Salinomycin Sodium Salt is cheap and better , but do you know about anyone who tried it ?

      injecting it to the blood maybe risky ! i really don't know

      my decision will be based on : which one has more risk

      long term side effects from chemo ? or injecting the salt version of Salinomycin ?

      i just hope i can find someone who tried the salt version , so i can be more confident to try it

  5. Dear Emad, first please read my disclaimer. Just so that you know I only share what I know but the decision is yours on how to use the info. Having that in mind, I would not be worried about the sodium salt version – I know w clinic in Germany that is using that on their patients. Based on that, I dont think is more risk than using the base version of Salinomycin. The only questions is related to the effectiveness of the salt version compared to the base one which I know for sure that can be effective in the right context as discussed in the other post on this website.
    Regarding the impact on the liver of those that you are using, just check each of them in the literature. To me, the only one that stands out in terms of impact on the liver is high dose Paracetamol. If I remember correctly, the toxicity induced by Paracetamol was lowered by TM. Just check the article I wrote on TM.
    Diflunisal <100 eur/day is cheap compared to the price they asked at Hallwang and Tubingen which was 30k/3weeks which was in total 12 administration so that is >2000 euro/day … Indeed, in terms of material that included Aspirin IV which is about 50 euro/day and one othet element IV that is about 10 euro/day. That means that you end up with about 120 to 150 euro/day at home instead of >2000 euro/day at the clinic which to me is totally in accessible.

  6. Thank you so much Daniel , I agree with you 100%

    I will continue on all these drugs (with lowering the dose of paracetamol) , and soon I will receive both DCA and Escozul

    the oncologist will change from Taxotere to ( Vinorelbine + 5-Fluorouracil )

    I hope all these medications will give us a very good response , and in the near future I will add Salinomycin Sodium Salt or Diflunisal

    that’s for now , I will continue sharing any results , thanks a lot my friend 🙂

  7. Dear Emad and All reading this website, based on recent personal experience I suggest that while using chemo the strong anti oxidants (such as Alpha Lipoic Acid, NAC, etc.) shoudl not be used in IV forms. Not even several days after or before chemo as they will clearly protect cancer cells. I know that this is what the oncologist are saying and many are questioning this statement but now I support 100% that statement. Low dose supplements such as Alpha Lipoic Acid may help and support e.g. the liver (so I may still use that?) but high dose will help cancer cells defend the pro oxidant anti cancer effect of chemo or other pro oxidant treatments such as 3BP.

    1. Hi Daniel, would you mind sharing what event caused you to change your mind about combining antioxidants with chemotherapy? All the papers I have read until now seem to reach the conclusion that antioxidants don’t reduce the anti-tumor effects of chemotherapy and may even increase its effectiveness while decreasing its side effects.

      1. Hi DaYoung,

        I have two answers, one theoretical and one practical:

        1. It is well known that antioxidants are cancelling the pro oxidant action of chemo when used at the same time. One of the strongest antioxidant, NAC, is often used in the lab for that purpose. Indeed, there are many papers showing that natural substances that we call anti oxidants may enhance chemo effectivness. However, such enhancement is not due to an anti oxidant action but often due to a pro oxidant action (such as discussed e.g. in my post on Quercetin where depending on the dose it can act pro or against chemo). In addition, most of the natural extracts are targeting so many pathways (beyond anti-oxidant or pro oxidant action) that it may often be difficult to predict the outcome for each specific tumor type.

        2. From personal experience and without going into the details, I have seen how Alpha Lipoic Acid performed IV even one day after 3BP, succeeded to stop the (pro-oxidant) action of 3BP and save cancer cells – seen on CT – while that was not the case when 3BP alone was performed. Note that ALA is a strong anti oxidant and performed IV will exert its anti oxidant nature even more effectively.

        Based on the above, I would always avoid the combination of chemo with strong antioxidants. At least not during the same day and a few days after chemo.

        I hope this answers your question?

        Kind regards,
        Daniel

  8. What are your thoughts on how to best achieve COX inhibition and antiplatelet effect? Aspirin and/or Dipyridamole? Or a combination with Celebrex, Nattokinase etc. What doses are safe?

    1. Hi Carl, difficult to say which one is best specifically because each of the elements you mentioned have other anti cancer effects behind. But if this would be my goal than I would strongly consider Diflunisla therapy (which includes aspirin too): https://www.cancertreatmentsresearch.com/?p=348 As maintanance, in our case, we used for some time Aspirin and Celebrex and Nato …. Aspirin was 100mg/day, the others I have to check.

  9. http://www.medicalnewstoday.com/releases/312121.php

    “Immunotherapy to stimulate the body’s immune system has increasingly become the way we treat people with aggressive cancers. It’s effective for a subset of patients, but the truth is that only about 20 to 40 percent of patients will respond to the treatment, and it is still unclear why,”

    “It’s a huge question in the cancer immunotherapy field, and we think we’ve found a big part of the answer.”

    “Dr. Delgoffe is partnering with other scientists to test various mitochondria-boosting strategies, including using drugs that already have proven safe in humans, such as those for type 2 diabetes…”

    Is it Metformin he is refering to? Metformin certainly affects the mitochondria…

    1. Hi Carl and thanks for the very interesting link.
      Actually Metformin is suppressing mito activity: e.g. http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002309
      Here is a paper indicating ways to support mitochondria including Resveratrol, Retinoic acid, Rosiglitazone (a former Diabetic medication), etc.: https://www.researchgate.net/publication/236692311_Pharmacological_approaches_to_restore_mitochondrial_function
      I like a lot Metformin as it has strong aticancer effects but based on this research you could argue that during anti PD1/PDL1 treatments it should be removed and others like Resveratrol shoudl be included.

  10. There is a synergy between metformin and dichloroacetate in several cancer cell lines, which could be translated into therapy.

    Sensitization of metformin-cytotoxicity by dichloroacetate via reprogramming glucose metabolism in cancer cells.
    http://www.ncbi.nlm.nih.gov/pubmed/24480191
    Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells.
    http://www.ncbi.nlm.nih.gov/pubmed/25212175
    Dichloroacetate and metformin synergistically suppress the growth of ovarian cancer cells.
    http://www.ncbi.nlm.nih.gov/pubmed/27449090

    1. Thanks Ovidiu. Actually I was thinking about this subject several times during the past years as you could argue that they may help each other or they may work against each other. This is because Metformin slows down mito and DCA would work by letting again pyruvate to be processed by mito. Given these mechanisms you can argue both ways but after all the investigations I also concluded the two have good chance to work nicely together.
      Indeed, I know that very innovator doctors (like prof. Dana Flavin) are recommending the combination of the two, to cancer patients.

  11. There is more, according to this article, it is very important to inhibit HIF-1a in order to get DCA + Metformin efficacy.
    Targeting HIF-1α is a prerequisite for cell sensitivity to dichloroacetate (DCA) and metformin.
    http://www.ncbi.nlm.nih.gov/pubmed/26616058

    There are many compounds that inhibit HIF-1a, with more or less clinical effectiveness, I list a couple.
    Potent inhibition of tumoral hypoxia-inducible factor 1alpha by albendazole.
    http://www.ncbi.nlm.nih.gov/pubmed/20398289
    Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1α.
    http://www.ncbi.nlm.nih.gov/pubmed/21421285

    By searching for mebendazole and hypoxia, I found something interesting.
    Antihelminthic benzimidazoles are novel HIF activators that prevent oxidative neuronal death via binding to tubulin.
    http://www.ncbi.nlm.nih.gov/pubmed/24766300
    So it appears that albendazole and mebendazole are HIF activators in normal cells, at least in neurons.
    This needs further investigation, to find out the effects of mebendazole – with respect to HIF-1a – on various cancer lines, normal cells, and tumoral stromal cells.
    In the article there is a list of drugs that induce HIF, and probably should be avoided during chemo, unless they are proven to act the opposite way in cancer cells.

  12. Hi Daniel,

    You mentioned bacteria and parasites as inhibiting the activity or chemo. Would you then advise against things like probiotics or fermented drinks (kefir, yogurt, etc).

    You also mentioned increasing blood flow to the tumour(s); would you advise against anti-angiogenic therapies for the duration of chemo?

    1. Hi Meech,

      These are very good questions, indeed. Regarding the first question, I would indeed use anti parasites before chemo specifically when we target lung tumors while I do think the probiotics and fermented drinks help improve and balance the gut bacteria which has a strong impact on the immune system. The two strategies are not necessarily against each other although some of the medications anti parasits anti bacterial will affect the gut bacteria in which case we need to repopulate with probiotics and fermented food as often as possible.

      Second one is debatable. I would anyway use the anti angiogenesis. In time that may inhibit the growth of new vessels and the tumor may adapt regarding the feeding mechanisms, if the tumor is not killed. Also in this case the tumor will become more resistant to chemo as it cannot reach the tumor. But this is a longer term process. Against this process I would use anti fibroblast drugs that would otherwise be one way for the tumor to feed, an alternative to the blood vessels. When I mentioned increasing the blood flow to the tumor, this is something I would do only before, during and immediately after chemo. But otherwise I would avoid this.

      On short answering your questions:
      1. Probiotic would be a continuous treatment to me while the opposite, anti biotic would be just short term, focused with a specific purpose
      2. Anti angiogenesis is a continuous long term treatment, while increasing the blood flow to the tumor would be a short term, focused approach for a specific purpose such as helping chemo

      That is how I see it Meech. But I know doctors who do not like anti angiogenesis due to potentially developing resistance.

      I hope this answers your questions – now I have to run to bed as it is 1am and I need to wake up at 7am for work 🙂

      Kind regards,
      Daniel

  13. Dear friends.
    So if metformin fails, try with diclofenac or resveratrol?
    Sorry i don’t have the science knoledge yet to understand the conversation, looking for a more clear view.

    Good Luck,
    Alex

    1. Hi Helga,
      Thank you. The comments you were trying to post were in the “trash” – some keyword may have triggered that reaction of the automatic filter. I just went there and approved your comment which is now visible. Whenever that happens again just let me know and I will approve it. At least now, since I disable a plug in, the posts are not lost.
      Kind regards,
      Daniel

  15. Here is a very interesting article about combining a polyphenol (like resveratrol) and a chemo. Quite often they work synergistically, NFKB downregulated (suppressed). NFKB is a central gene in cancer, usually overexpressed.

    https://www.researchgate.net/profile/Aarti_Mohan2/publication/227855952_Combinations_of_Plant_Polyphenols_Anti-Cancer_Molecules_A_Novel_Treatment_Strategy_for_Cancer_Chemotherapy/links/56d51a8d08ae2cd682b94641.pdf
    “Interestingly, curcumin has also been reported to cause apoptosis by
    generation of reactive oxygen species (ROS) causing the release of
    Endo–G (endonuclease G) and apoptosis inducing factor (AIF) into
    the nucleus and cytosol which in turn causes DNA fragmentation
    and chromatin condensation [68]. This phenomenon where the
    same molecule has been reported to exhibit anti–oxidant activity in
    certain cases and pro–oxidant behaviour in certain others has been a
    subject of much debate in the research world. This phenomenon is
    now referred to as the “antioxidant paradox” and is reported to be
    primarily influenced by concentration of the molecule but may also
    involve other pathways that are yet to be explored. ”

    There is a big table showing several combinations and their effect on cancer (cells). I find this important because Daniel writes somewhere that it is important not to use certain antioxidants while having chemo. While that may be true of the molecules he mentions, it looks like using polyphenols is beneficial and synergistic.

    1. So maybe there is some help from getting the 5 drops of resveratrol extract under the tonge like we are doing?
      I got some drops under the tongue myself just to see how it feels, it felt good, like in 5 minutes i started to feel my joints less stiff, the rest of the body felt like i took diclofenac.
      I managed to get some grain sprouts today for mother as suggested.
      Yesterday mother had migranes, gave her a bit of chocolate and that went well for her. (low blood sugar levels)
      Today i notice the bump or her arm became softer again. And mother is feeling better. This could be the effect of what went on yesterday but it may also be an advantage, a clear indication of success or failure, or maybe not.
      DCA arrived today, feeling optimistic and wish to thank again for the much much help received.

      THANK YOU! HUGGS!
      Alex

  16. Dear Daniel,
    There are some glyco inhibitors which we didnt talk before.
    They are working on another mechanism different than insuline or metformin.
    They can be easily reachable.They are working like Phlorizin in your post.(SGLT inhibitor)

    Mechanism of action
    Canagliflozin is an inhibitor of subtype 2 sodium-glucose transport proteins (SGLT2), which is responsible for at least 90% of renal glucose reabsorption (SGLT1 being responsible for the remaining 10%). Blocking this transporter causes up to 119 grams of blood glucose per day to be eliminated through the urine,[15] corresponding to 476 kilocalories. Additional water is eliminated by osmotic diuresis, resulting in a lowering of blood pressure.

    This mechanism is associated with a low risk of hypoglycaemia (too low blood glucose) compared to other types of anti-diabetic drugs such as sulfonylurea derivatives and insulin.[16]

    I am very sure that it will enhance chemo effectiveness,but dosage?protocol?
    I wonder your thoughts about SGLT inhibitors.
    Kind Regards
    Ergin

    2. Hi Ergin,

      I did’n not know this drug. I just checked and here is a recently published patent supporting your believe:

      Use of canagliflozin and derivatives thereof in the treatment of cancer http://google.com/patents/WO2016134486A1?cl=en
      “This study is the first to investigate the effects of sodium- dependent glucose transporter inhibitors on AMPK activity in cancer models. It was found that Canagliflozin, at concentrations within the therapeutic levels used for treating type 2 diabetes, inhibits the growth and survival of a variety of different cancer cell lines. These effects were not observed with the other approved SGLT2 inhibitor Dapagliflozin. It was demonstrated that clinically relevant concentrations of Canagliflozin activate AMPK; while not wishing to be limited by theory, potentially through a mechanism involving the inhibition of the mitochondrial complex I. Furthermore, it was shown that suppression of growth and survival in PC3 cells is associated with the inhibition of glucose uptake, de novo lipogenesis and AKT/mTORCI signaling. Further, the usefulness of combining low dose Canagliflozin with Docetaxel, Cisplatin and radiation therapies to further reduce the growth of lung and prostate cancer was shown.”

      So, it sound interesting, indeed.

      Kind regards,
      Daniel

      1. Thanks Daniel,
        Unfortunately i go to pharmacies today and i couldnt find Canagliflozin.
        There is only Dapagliflozin.Why it is so hard to find drugs?!!!
        I wonder and wonder lots of things about Phlorizin,Canagliflozin,Dapagliflozin and derivatives.
        May be Phlorizin is less effective only like Dapagliflozin,because of that they administrate it for 12-24 hours
        for total phlorizination?Or are mechanisms totally different.Any idea?I read patent which you send,but honestly didnt understand everything.
        Daniel,I want to try Dapagliflozin with hyperthermia,if i couldnt find Canagliflozin.May be it works like Phlorizin with heat.There will be some responce,sure of it,but what is the rate?And what will be the power of machine?50 watt same as Phlorizin(normally 180 watt)?If it doesnt work,our hyperthermia session will be lost,sounds a little bit gamble.
        Tomorrow ADRENALIN DAY! Blood counts day.May be talking for this treatment is too early.May be this treatment should be a golden shot.
        I will write everything including hormone treatment on ovarian post.
        Kind Regards
        Ergin

  17. With my mother’s situation deteriorating from day to day.
    She felt it would be best if someone more competent will lead they way, aka the oncologist.
    She will go with chemo maybe starting monday.
    We are feeling very bad.

    1. for me with our limited financial capabilities , I can only focus on making treatment more effective , sadly I can’t focus on what protects the body from chemo

      the only good thing is if the patient can drink juices and eat healthy food while on chemo

      the goal is to shrink cancer until no more chemo needed

      but as soon as you stop chemo you need to find another working drug

      for me I want to start my mother on MG when she no more needs chemo , as its not expensive and it can be given orally

      but really Alex you should not talk about chemo right now , CT Scan or MRI should done first , you have to find it and do it so you can know whats really going on and whether your mother needs chemo or not

      hope you don’t need it at all

      1. i may be able to help with ordering something for your mother. let me know…. i’m in the fight as well, more away from the computer and out to the oncology hospital here.
        Waiting for blood tests, markers, scan, it will take a few days.
        Looks like the tumor is pressing against the spine cord more and more.
        I don’t know where we’ll go from here, surgery, chemo, none?
        I may need 3bp, sal as well.
        It’s a nightmare and we all know it.
        Mosquitoes in the hospital are pottentialy spreading and mixing the disease to other sick ones or healty.
        Oncologist gave her the IV version of the vitamins we were doing at home LOL, except for glucose and cortizole.
        Too much suffering…. it’s not fair. Too many tears
        Thank you very much
        Alex

        1. hi Alex
          i would ask doctors about egfr inhibitors. again, these inhibitors are like chemo light. Gene inhibitors are not like Cisplatin or Vincristine..like the big guns. Your dear mother could take it, side effects are not brutal.
          wishing you all the best.
          W

        2. Hope there is nothing scary when the scan results show up

          thanks also for your willing to help , please focus on your mother treatment , I will be fine

          sorry to hear about these problems in the hospital , it sounds like our poor hospitals unfortunately

          regarding 3bp and sal , like I said before , you can have them once you have an email related to any university , its not hard I think , the other thing is to have a medical port placed on the patients chest , which is also available in any country and can be done in a small surgical procedure

          or if you have to buy some time you can focus on things like MG or T4 depletion or any other treatment that may work and easy to administrate orally

          stay strong , I believe you will feel better soon , I will pray for that

          Your friend Emad

            1. can you give more details about the scan results ?

              what did change for the last months ?

            2. Dear Alex,

              This might interest you too:
              “9. Spinal cancer, ozone sauna
              “Diagnosed with a rare spinal cancer in 1998. Her oncologist advised her to go to a local University cancer clinic for some radical new chemo treatments.
              Within six months, she was bedridden, her cancer-riddled spine unable to support the weight of her head, losing weight rapidly, deathly ill from the toxic drugs they gave her. She left there on a stretcher, advised to put her affairs in order.
              A friend of hers called me up and asked what could be done. Since I knew someone who lived near her, who had an ozona sauna, I connected them, and the ozone sauna ended up at DY’s place for six months. During that time, she gave herself daily ozone saunas (at first with considerable help from friends), did liver cleanses, ate fresh organic food and several varities of oriental mushrooms.
              Within six months, she could walk unassisted, hold her head upright, and had begun an exercise program. Now, three years later, she is free of cancer, and will be opening an ozone sauna clinic of her own in the spring. “

              http://thepowerofozone.com/116-reports-of-cancer-successfully-treated-with-ozone-therapy/

              See if you can locate an ozone sauna or ozone machine nearby! How is your mom doing?

              Kind regards,
              Helga

            4. Thank you very much dear Helga,
              If it wasn’t for you this place would have been a lot poorer in information.
              My mother is in a very bad shape, we need a neurosurgeon for her spine leftover tumor that has invaded the nervous system there and is pressing against it. ( so says the oncologist ).
              The oncologist delayed everything for insurance money sake i think…… now she is saying there’s nothing that she can suggest, not even a neurosurgeon. I need an ambulance to take my mother to another hospital and that depends on her to give us one but only after i talk to a neurosurgeon that will accept my mother there.
              A big system that is meant to fail one day…. meanwhile…. more problems.
              Once i see my mother on her own feet, i’ll take her to a sauna for sure. And should we see no more tumor on her nervous system, we’ll probably continue with DCA and others because we feel they did work.
              But for now we must deal with the paralisys, she’s unable to get out of bed at all. I had to order more DCA anyway… but not now.
              I’ll probably be away from here for a while…. someone up there loves me and my mother extremely much…..
              Cancer is not enough, there had to be complications too….
              So far we’ve been lucky enough in so many ways, i can only hope this time luck will favor us despite the extreme love received from up there.
              Let me know how things are going with you and your mother, ill read when i get the chance.
              Best wishes.
              Warm hugs
              Alex

            5. Dear Alex,

              I am so sorry to hear about the difficult times you are going through. 🙁 I very much know the feeling … I hope you will find the luck you are looking for.

              All the best,
              Daniel

        3. Dear Alex,

          so sorry to hear all about the tears and suffering. I suggested somewhere else but raise it here too: how about applying Diclofenac & heparin (both available in ointment, e.g. Voltaren+Lioton) locally? The tumor being near the spine must be fairly close to the skin so I imagine it could help somewhat. I used Lioton locally and it seemed to help me. Heparin should be able to work transdermally! Also, you could try to add DMSO to them.

          Best wishes,
          Helga

          1. multumesc, momentan nu stiu cum sa fac sa reduc tumora fara inflamatie pentru a elibera presiunea de pe maduva.
            Se pare ca avem nevoie de un neurochirurg capabil sa opereze pe coloana/maduva.
            Fostul neurochirurg a dat birul cu fugitii, raspunde la numere straine dar la al nostru nu. Cred ca ii este frica de ceva.
            DCA pare sa fi functionat in cazul nostru dar daca a facut asta este posibil sa fi cauzat si inflamatie, oxidare neuro-celulara am vazut si un raspuns imunitar.
            Doctora oncoloaga NU este interesata de nimic de genul.
            Tot doctora oncoloaga spune ca nu se poate intervenii decat chirurgical.
            Daca nu gasesc un doctor sau o echipa de doctori, este improbabil sa facem rost de o suma de genul 500 milioane pentru o astfel de interventie la privat.
            Legat de markeri unul din ei a scazut putin, insa markerii sunt si deceptivi din pacate.
            In concluzie am ajuns la parerea ca sunt mai bune tratamentele agresive temporare, 1-3 zile si apoi pauza pentru recuperare.
            Tratamentele pe termen lung au efecte mai adverse, insa aceasta agresivitate trebuie supravegheata de doctori calificati care din pacate de foarte multe ori nici nu vor sa auda de alternative or chiar anexe la ceea ce se considera a fi standardul de aur.
            Si in situatii unde e vorba de complicatii majore, e foarte recomandat sa se evite inflamatia sau stresul oxidativ, lucru greu de facut dupa cum se pare.
            Dupa ultimul CT insa, realizez importanta si impactul major al lucrurilor pe care le-am facut, dieta, strategie si speranta.
            Daca nu faceam ce am facut, lucrurile ar fi fost mult mai grave de mult cu certitudine.
            Eu sunt efectiv la pamant cu tot. Nervi, energie, speranta, si probabil in curand si cu banii.
            Insa am ambitie si perseverez, realizez insa ca probabil nu o sa fie suficient. E o lupta pe prea multe fronturi.
            Sper din suflet ca ai mai multa bafta.
            Cu mult drag,
            Alex

  19. Buna Alex,

    Sper sa gasesti un doctor neurochirug care sa opereze pe coloana, la Fundeni sunt doctori foarte buni, ma interesez si daca aud de cineva iti scriu. De asemena, mai este si varianta Cluj in cazul in care nu accepta nimeni in Bucuresti, o doamna pe care nu au avut curajul sa o mai opereze la Bucuresti pentru cancerul ovarian avansat, s-a operat la Cluj dupa ce a facut in prealabil chimioterapie, era foarte grav, o tumoare de 7 cm, markerul CA-125 de 2300, dar a avut noroc ca a facut chimioterapie inainte de operatie pentru diminuarea tumorilor, si nici pana acum la un an dupa, nu a recidivat. Mama mea a avut cancerul mai putin avansat, dar pentru ca nu a facut chimioterapie inainte de operatie care sa ii “distruga” tumorile, operatia a fost mult mai grea, acum are recidiva. De aceea medicii ar trebui sa schimbe protocolul care spune ca operatia se face inainte de chimioterapie, cel putin la cancerul ovarian, ultime studii arata ca e mai benefic cu chimioterapia inainte.

    Daca mai ai DCA in plus si vrei sa imi vinzi sau stii pe cineva care are sa imi spui, as dori sa incep sa ii dau si eu mamei si am auzit ca dureaza cateva saptamani pana ajunge din strainatate.

    Sa pastrezi ambitia si perseverenta si o atitudinte pozitiva, pentru ca e extrem de important psihicul in lupta cu cancerul. EU voi lucra si cu o persoana care sa ii dea mamei energie, deoarece se simte mult mai bine cand are energie.
    Sanatate mamei tale,
    Cu drag,
    Anca

    1. Dear Anca,
      What I only understand from your message is CA125:2300.
      That means there is a huge ascite in the abdomen.You have to use a VEGF inhibitor.It is highly effective on ascites but not on periton.
      Please work on Thalidomide and Dr Hada’s protocol.I am almost sure that will work.
      Kind Regards
      Ergin

      1. Hi Ergin,
        Thak you very much for writing to me. I wrote all these substances that my help for my mom’s oncologyst and she will search information about them, abuut DCA and some others.
        I wrote above that in 2015 there was a lady diagnosed with ovarian cancer, twice operated for bowel obstruction in a week, and she had a big tumor of 7 cm and CA 125 of 2300 and the doctors didn’t want to remove her tumor, they didn’t have the courage, so she had chemotherapy sessions and after the tumors had been destroyed she found a doctor in another city in Romania, Cluj, who did the surgery, which was not so complicated because all the tumors were killed except a small one and that woman is in good shape now after one year in remission, my mother was in the same hospital with ovarian cancer in Seoptember 2015 with CA-125 of 700 and a tumor of 2 cm and the doctor did the surgery straight away and also cut a part from my mother’s colon, then after 6 months they put the colon back so my mom got rid of the colonostomy bag in 2016, and in December 2016 my mother had a recurrence of the ovarian cancer, which is very hard to treat. So that lady who had a more avanced ovarian cancer is healthy now because she had chemotherapy first, and then surgery, and my mother is suffering again. So I said the doctors should change the protocol and do the chemotherapy first and then surgery and then 3 more sessions of chemotherapy, because the newer research articles say that it is a better prognosis if they do the chemotherapy first then surgery in ovarian cancer.
        My mother has a CA-125 of 1890, which is high. But her blood analysis is very good, she has good blood sugar and all the rest, my mom is feeling good and that gives me hope. My mother is working with a therapist who is religious and is energising her by speaking with my mom on the phone for a few hours after chemotherapy and totally changed my mother’s state in good, she is optimistic again, she has energy, she cand walk, cook, a few weeks ago my mother had no energy. So I think God can help my mother heal. If your mother believes in God and her faith can help her heal.
        We don’t do anything if the doctor doesn’t approve, and I will see tomorrow what the doctor wants to use for my mother. She had today a session of chemotherapy with Caelix and yesterday Vitamin C IV. I also gave her Metformin.
        If we use Thalidomide, can you tell me how much it costs in Turkey? Maybe I will buy from your country.

        I hope your mom is doing well and wish all the best to her,
        Anca

        1. Hi Anca,
          Thanks for the msg.In theory and upto statistics,first surgery and then chemo gives more benefit for Ovarian cancer.
          Less tumor more benefit from chemo.
          I wonder if they have looked for Gemzar effectiveness on that test for your mother.
          Did you send blood or biopsy or she went to Greece for test?
          Could you please give me the contact details of lab.
          Unfortunately thalidomide is not sold here.I found it in Bulgaria with a price of nearly 500 euros for 28×50 mg.
          You can buy it from Mexico with Daniel’s help but can you take it from customs?
          Is there any tumor on periton of your mother?Does she have bad bowel syndromes?And what about ascites?
          Kind Regards
          Ergin

          1. Hi Ergin,

            For clarity, regarding Thalidomide, I can only help by sharing the contact details of the pharmacy in Mexico from where I bought it 2 years ago. If anyone needs that I will share on e-mail. Just let me know.

            Kind regards,
            Daniel

          2. Hi Ergin,

            I can give you the e-mail address of the clinic in Greece where they do the cancer test, RGCC Medical e-mail is: [email protected]. You can write to them, the test that my mom did is Onconomics and we payed around 2500 euros. We took blood 7 days after the last chemotherapy and sent the blood to Greece for the test, the results came after 10 days. The test is detailed, there are 12 pages with what chemotherapies my mother might be sensitive to, and in the last page we have some conclusions, I can paste them here:
            “From the investigation above we concluded to the following:
            1. From the whole neoplasmic population we have an expression of MDR1 in a percentage of 60% over control sample
            (positive in the check of resistance).
            2. The activity of GST is stable in the low limits (no resistance to platinum compounds).
            3. The activity of GammaGC is in normal range (no resistance to platinum compounds).
            4. The activity of CES1 and CES2 is in low limits (no resistance to camptothecin compounds).
            5. The concentration of p180 is in normal range.
            6. Increased activity of the Laminin and the MMP (increased invasive ability).
            7. There is partial sensitivity in taxanes (Paclitaxel, Docetaxel, Cabazitaxel).
            8. There is no sensitivity in alkaloids of vinca.
            9. There is no sensitivity in Eribulin.
            10. Partial sensitivity noticed in MTX, in Gemcitabine, but no sensitivity noticed in 5FU, in Capecitabine, in Fudr, in UFT, in
            Raltitrexed, in Pemetrexed, in Cytarabine, in Fludarabine
            11. There is no sensitivity in Epothilones.
            12. Increased sensitivity in alkylating factors (Νedaplatin).
            13. There is great overexpression of EGF (45% over control), TGF-b (35% over control), but there is normal expression of
            IkB(a, b, c), NFkB.
            14. It appears to have great sensitivity in the inhibitors of topoisomerase II (Liposomal Doxorubicin).
            15. There is no sensitivity in the inhibitors of Topoisomerase I.
            16. There is great over-expression of COX2 (10% over control), C-erb-B1 (55% over control), but there is normal expression
            of 5-LOX, SS-r, C-erb-B2, Estrogen-Receptor, Progesterone-Receptor.
            17. We notice great neoangiogenetic ability (overexpression of VEGF-R 55% over control sample).
            18. Finally, there is no sensitivity in Dacarbazine.
            19. We notice that taurolidine cannot induce the apoptosis to the malignant cells (in IV route dosage).
            20. We notice that taurolidine can induce the apoptosis to the malignant cells (in intraperitoneal route dosage).
            21. We notice no down-regulation of HSP72 (Heat Shock Protein), but we notice down-regulation of HSP27 (Heat Shock
            Protein) at 15% below control, HSP90 (Heat Shock Protein) at 10% below control.
            22. There is over-expression of ANG 1 at 30% over control, ANG 2 at 25% over control, IGF-r 2 at 15% over control, but we
            notice no down-regulation of ALK, EML-4-ALK, C-MET, NPM-ALK, CD 117 (c-kit), IGF-r 1, HDAC, HAT, NR3C4-
            A, NR3C4-B.
            Conclusion:
             The specific tumor appears to have resisting populations because of the MDR1 overexpression that can be reversed by the
            use of inhibitors of ABCG2 pumps.
             The neoplasmatic cells have the greatest sensitivity in the alkylating agent (Νedaplatin), in the inhibitors of
            Topoisomerase II (Liposomal Doxorubicin)
             Also can be used Bevacizumab as inhibitor of neo-angiogenesis, Ramucirumab as an inhibitor of VEGFR2, ZivAflibercept
            as an inhibitor of VEGF as inhibitor.”

            Based on the test, my mother is doing Caelix now IV. My mother has some tumors in the peritoneum, the biggest one was 4 cm large in April, but now it could be bigger.
            I hope it helps you.
            Kind regards,
            Anca

    2. Multumesc foarte mult Anca.
      Cand am fost la fundeni, si nu era asa complicat ca acum, ne-au trimis la spitalul militar, iar acolo a trebuit sa vorbim cu seful de sectie care a fost singurul neurochirug sa accepte “provocarea”. Desi nu s-a lucrat pe maduva, conform cunostintelor mele si scanarilor ulterioare dar si efectul vazut azi. Paralizie.
      Legat de chimioterapie inainte de operatie, mama este slabita rau, iar oncoloaga a spus ca nu face ca nu ar fi util in cazul ei la maduva, de radioterapie nici nu se mai pune problema.
      Noi am continua DCA dar este inoportun acum din mai multe motive. Aparent a functionat pana cand a aparut aceasta complicatie.
      Legat de vandut DCA, ti-as trimite gratuit, nu ca nu am nevoie de bani dar un DCA as putea si eu sa trimit asa cum si mie mi s-a oferit ajutor, asa vreau si eu sa ajut. Insa mai am doar o parte dintr-un flacon.
      Te avertizez insa ca daca functioneaza efectul este oxidativ si in functie de locatia bolii pot aparea complicatii, inflamatii, edem, marire de organ etc. Si alte efecte secundare descrise pe aici. Tind sa cred ca efectul oxidativ nu este limitat strict asupra tumorii si oxidarea celulelor invecinate are din pacate consecinte mai mult sau mai putin serioase in functie de locatie. In cazul nostru pe maduva unde….. ce sa zic ma iubeste cineva sus acolo mult de tot, are o dragoste enorma pentru mine si mama mea. 🙁
      Iti pot trimite ceea ce mai am in flacon, insa nu stiu cand ca maine trebuie sa plec la bucuresti sa caut doctori si apoi daca gasesc raman pe acolo cu mama.
      Iar acum e ora 23, trebuie sa luam legatura, cu toata bunavointa cred ca e posibil sa ajunga mai repede din strainatate decat pot eu sa trimit fiind in situatia asta foarte dificila.
      Intre timp cred ca ar fi buna o dieta vegana raw, nu neaparat stricta, cu carne alba, fiarta, la gril, fara uleiuri, fara paine, lapte, zahar, sucuri etc.
      Pentru energie, sucuri naturale facute acasa, fara miere, iar pentru energie, un energizant odata la 3-4 zile nu e tocmai rau.
      Clismele cu cafea au fost benefice in cazul nostru, facute ocazional.
      Metformin, aspirina, diclofenac, lansoprazol astea sa nu lipseasca din casa cred.
      Ar fi bine sa luam legatura cumva, skype, telefon insa din pacate sunt prins aiurea de tot acum.
      Snake_Systems sunt eu pe skype. online mereu, dar nu la pc pentru ca ….. probleme multe.
      Cu mult drag,
      Alex

      1. Thank you, Alex. I hope your mother is ok and you found a doctor for her.
        My mother is doing chemotherapy with Caelix and also Vit C IV.
        We don’t use anything if the doctor doesn’t approve, so she has to read and will tell us tomorrow if DCA is good for my mother. After reading all the side-effect that you wrote, I honestly don’t know if we should use DCA. My mother doesn’t have the courage to test new things on her body. My mother is eating what she can, I don’t think she she can eat raw vegan, but she cut sugar completely and all unhealthy and unnatural stuff.
        I also gave my mother Metformin. My mother believes God will heal her, she is working with a person who helps her psychologically, and that changed my mother state in good and gave her energy.
        I live in Bucharest, I don’t know if I need DCA now, we see tomorrow what the doctor say. Thank you for offering me what you have.
        How is your mother doing?

  20. Dear Ergin,

    Anca talks about someone else, who had chemo before surgery and that made her surgery more successful than her mom’s who, on the other hand didn’t have chemo before surgery.

    By the way, you were right about me, I had an exam today with ultrasound and the doc said my ovary is quite small so she does not think I have ovarian cancer. She recommended mammogram just as routine but I had it only once and swore never to have it again. Thermography is a much safer and more pleasant option but the mammographic machine producers apparently

      1. Hi Ergin,

        no, I won’t leave, don’t worry. I am very interested in following your and other people’s updates and try to help, if I can. Sorry to hear that your mom is weak. Do you think you could try the ozone treatment? Intravenous ozone is very good, too. I had several sessions last year and it helped a lot with my fatigue. Here you can’t have it if you have cancer. But maybe you can in Turkey. Intravenous vit C is the same, it works as a pro-oxidant if given intravenously.

        Best,
        Helga

        1. Ive had percutaneous ozone from a fairly sketchy doctor. I had it for neuropathic pain. The injections were painful for a few minutes and then subsided.

          I can’t say if it helped but in the moment I felt as though it did.

          1. I am very interested in intraperitoneal drug delivery.Lots of drugs works for cancer on pertion by ip but not iv nor oral.
            We have very good knowledge in this website about effective drugs but some of them doesnt reach to tumors.
            For example Pyrivinium Pamoate.It has zero effect on everywhere except colon or stomach.
            If i can find a brave doctor who is experienced about ip delivery,i will directly get into contact with him/her.
            And what i wonder is, if patients have palpable tumors why they dont use these drugs as directly injected to tumors.
            Does it cause stg bad?Like bleeding or stg else?

            1. Sorry i meant subcutaneous, so only a little under the skin, not far enough to reach a tumour.

              I have wondered the same thing though. I’m wondering how well the drug would be contained within that tumour if it was directly injected.

  21. Ah, goody, I posted that. So apparently they lobbied more successfully for their machines to be used with insurance coverage, despite being more harmful than thermograms. We all should lobby for that safer option! I read somewhere that women who get more mammograms get more breast cancer! Mammogram can hurt the breast tissue for sure as they press on the breasts so hard that they are turned into pancakes temporarily. It is well known that breast tissue injury can later cause breast cancer (even though my doc denied it).

    How is your mom doing?

    Best wishes,
    Helga

    1. Very interesting Carl,thanks for sharing.I was just searching for direct injections of drugs to tumors.
      May be it can be used intraperitoneally also.

  23. Dear Daniel,
    I have a question for varapamil which you wrote in top of this page.
    Which one do we have to choose?
    A drug for lowering the denstity of tumor vessels or a drug to enhance the tumor vessels for drug delivery into tumors?
    Or on chemo days enhance vessels for drug delivery,other days using an anti-angiogenic drug?
    I am sure the answer is somewhere in this website but i couldnt find.

    ”Increasing chemotherapy delivery to tumors, while enhancing drug uptake and reducing side effects, is a primary goal of cancer research. In mouse and human cancer models in vivo, we show that coadministration of low-dose Cilengitide and Verapamil increases tumor angiogenesis, leakiness, blood flow, and Gemcitabine delivery. This approach reduces tumor growth, metastasis, and minimizes side effects while extending survival. At a molecular level, this strategy alters Gemcitabine transporter and metabolizing enzyme expression levels, enhancing the potency of Gemcitabine within tumor cells in vivo and in vitro. Thus, the dual action of low-dose Cilengitide, in vessels and tumor cells, improves chemotherapy efficacy. Overall, our data demonstrate that vascular promotion therapy is a means to improve cancer treatment.”
    http://www.sciencedirect.com/science/article/pii/S153561081400419X
    Kind Regards
    Ergin

    1. Hi Ergin,

      I will have to check the study to are referring to. For now, what I can say is:
      – Verpamil purpose in my list is to inhibit multi drug resistance pumps, not related to angio genesis
      – Regarding your other point, it is debatable. I know scientists saying do not use angio genesis inhibitors because other therapies will not work anymore and know scientists and docs who would actually use them. Both approaches have their advantages and potential disadvantages. On short term, I think using angio genesis inhibitors may add more value and since fighting cancer is fighting with time, agio genesis inhibitors may be a good approach. The risk is that on long term, some cancers learn how to survive without vessels and get their nutrients from the micro environment. I also addressed this subject in the article on Acetate as a fuel for cancer, and how to work against that (which could be a nice addition to anti angio genesis treatments).
      – I do not think that you can influence vessels formation on a few days time scale as you suggested – what you can influence on a short term is the with of the existing micro vessels using e.g. Quercetin, Niacin, Nitroglycerine, prior to chemo. There are some clinical trials using Nitroglycerine prior to chemo.

      I hope these answer your questions.

      Kind regards,
      Daniel

      1. Thank you very much Daniel for answers.
        I have some findings,for just a knowledge i am writing here.
        Viagra(Sildenafil) enhances vessels for some hours.May be we can work on it.
        Drugs will go to tumors easily than vessels come to actual size in same day.

        Combination of Viagra and anti-cancer drug shrinks tumors in vivo, researchers discover
        https://www.sciencedaily.com/releases/2010/09/100927155318.htm

        For brain cancer, other methods are used to cure the condition but the drugs used are not completely effective as very limited effects pass through the blood-brain barrier. Viagra, the PDE5 inhibitor,has shown that it can actually cross through this protective lining.
        http://www.nanomedpharm.com/viagra-and-brain-cancer.php

        Kind Regards
        Ergin

  24. Hello!
    Had to take my mom to the oncologist/hospital because she couldn’t walk anymore or get out of bed. – CT/MRI show the tumor invading the spine and causing paralysis aggressively – Doc say it’s permanent.
    My dear mom is doing Carboplatin
    Before that she was on Vitamins like B1, B6, B12, electrolites, and diuretics but also bisphosphonates.
    Help!?
    Thank you very much!
    My best wishes to you all,
    Alex

    2. Sorry to hear that Alex

      how is your mother now after carboplatin ?

      give us updates on her condition

      also , how doctor can make sure this paralysis is permanent ?

      maybe its sounds crazy but we all at the beginning thought that advanced cancer is a death sentence , which we now believe that its not , and there is something we can do about it

      also who knows if its not possible to regain health and overcome paralysis which may not be permanent ?

      I suggest to focus now on cancer , try to do whatever you can to shrink the tumors , especially the tumor that is invading the spine

      after that you can focus on the damage done to the nerves and see if there is something you can do about it

      you should not let those side problems make you feel weak and stressful

      always wish the best to you

      1. hi Alex,
        they say that with severe nerve damage if they can’t help you in 24 hours (surgery, superintense chemo, radiation) the paralysis is always permanent. Even if the tumor gets smaller Spinal cord is unable to restructure itself – its not like the brain. There are ongoing studies though and some compounds seem to help but…there is no real solution yet. Still, i agree Alex and Mo should not give up yet.

        2. Thank you very much Wondering.
          I highly appreciate your support and comments always.
          Without you this family here would have been a lot smaller.
          And i mean to say you’re a big and meaningful part of it.
          I wish to thank you personally for absolutely everything.
          Stay strong man, we need you. Everyone does.
          Do your best not to loose yourself, i know i should try harder too.
          If things weren’t so hard with my mother being paralized an maybe having some actual help around i would have had more time to give here. I hope one day things will get better,
          Till then,
          Please take care!
          Alex

          1. Hi Alex,

            thanks a lot for your kind words.

            I am sure your dear mother is aware of what a caring son he has. by the way i read that with a spine met the average survival time is 6 month, for her it has been a lot more and she is still with you. believe that the things you did helped her to be still here. Of course no one can prove it but it is very likely.

            i wish you strength and luck …

            1. Thank you very much wondering.
              The spine thing is not a “distant” metastasis, its more of an invasion from the lung.
              The original tumor is said according to the post-surgery biopsy that it started from the lung/outside of it and then invaded the spine bones/nerves and now the cord.
              Indeed it sounds like we did great compared to statistics. Still we hope for more 🙂

      2. Thank you very much for everything.
        I hear of people recovering from very similar situations so we still hope and try our best to fight.
        She can’t move any muscle bellow her chest, involuntary movements in her legs. Burning sensations, cold feet, difficult to caugh, pain in her chest/bone/spine/back on left side, tumor on right?! MRI shows swell in spine medular channel and tumor invading from outside in the swell.
        I hope your mother and you are doing better?!
        Best wishes,
        Alex

  25. Fighting cancer with methadone – making chemotherapy more powerful:
    http://www.dw.com/en/fighting-cancer-with-methadone-making-chemotherapy-more-powerful/a-19482264
    https://www.gesundheitsindustrie-bw.de/en/article/news/methadone-the-last-step-to-becoming-an-anti-cancer-drug/
    http://www.campus-technologies.de/wp-content/uploads/TO_UEE20120404Methadon-Short-1_.pdf
    https://www.ncbi.nlm.nih.gov/pubmed/24626197
    https://www.ncbi.nlm.nih.gov/pubmed/28314286

        1. Hi Marco,

          Based on prescription: “40mg to 60mg each time, 3 times a day.” for cancer http://www.bdkyf.com/goods-2695.html
          This should be a good reference point but please do more research and make sure you have a few other sources, stating the dose.
          Also check the side effects and interactions to make sure it is suitable with other drugs or illnesses that are relevant to your wife.
          Whenever starting a new drug or supplements, always increase the daily dose step by step towards the target dose. Never jump to he target dose too fast.

          Kind regards,
          Daniel

  26. Hi ,
    I would like to find out from you what is the opinion regarding vitamin C IV and ozonotherapy IV, in relation to the title of the article, whether it helps or not during chemotherapy? I personally did not find any study but only opinions (came from some naturopaths)

  27. siven01, these might help.

    The second url speaks to the shared frustration that so much of science has not embraced a more systematic methodology.
    As noted below even after 60 years of vitamin C cancer treatment, an optimized treatment protocol has yet to emerge.
    However, cancer treatment, at least in children, became much more effective when such optimized protocols were created.

    https://www.isom.ca/article/increasing-the-effectiveness-of-intravenous-vitamin-c-as-an-anticancer-agent/
    https://www.isom.ca/article/editorial-how-can-we-advance-the-clinical-application-of-intravenous-vitamin-c-among-patients-with-cancer/

  28. Hello everyone, I just joined this wonderful site and I am trying to get a little information that could help me help my mother. It is a lot though and seems confusing!
    My mother has stage 4 high grade serous ovarian cancer with no Boca mutation. She was diagnosed 2 years ago but could not do any debunking surgery or surgery at all, she has a big EPOC and after carbo/taxol chemo she was absolutely exhausted. First treatment was very successful but we had no idea of any adjuvant therapies that could help her chemo, and the residious that remained there have never disappeared and all the following treatment, not only did not work, but gave her all side effects, and she can hardly walk. All we know about her tumor is she has a EGFR mutation, and TP53 mutation. I do not know if she is ER positive or negative. Ovarian cancer is highly aggressive. She has even tried immunotherapy. Keytruda, that seemed to work, but die to pneumonitis side effects, her one destroyed the treatment by using high dose cortisone, and 4 antibiotics that have put her 2 months in bed.
    She has metastasis on her liver, lungs, bones, peritoneal… Many years ago she suffered from trombocytopenia, that I need to be aware….
    Next Monday sept 3 she is starting low dose paclitaxel, and I really urge for some help.
    I want to give her off label drugs and supplements that could enhance the taxol. I am confused. But she really needs to make that option again….
    Thank you for any help

    1. Hi, sorry to hear about your mother. You probably know about curcumin but just wanted to mention it, as it works synergistically in combination with taxol. Stage 4 cancer patients might benefit from bovine tracheal cartilage and/or apatone/Anti-C Liposomal and maybe turkey tail. Good luck! J.

    2. Dear Helena,
      Given that the condition of your mom sounds advanced, I would consider something stronger. Off label drugs and supplements could help but stronger systemic treatments are required. Why are you considering low dose taxol? Is this what the medical doctor recommended? Please let me know in what country you are located so that I think of treatment options near you.
      Kind regards,
      Daniel

      1. doctor recommends low dose chemo at this stage.
        she has been under chemo for 2 years, she has never been ned. all that worked was carbo/taxol combo, right at the beginning of diagnosis. I had no idea about synergies, supplements and off label drugs. first chemo almost made everything disappear except residious on her liver and peritoneum.
        but from there on, since the introduction of Avastin, all started to re-grow, and she started to have huge side effects, and nothing worked. Carbo/caelyx, gemcytabine/avastin, gemcytabine/cetuximab, and then keytruda…
        immunotherapy started to work, but she had pneumonitis side effects, and her one gave her huge cortisone, surpassing the keytruda effect, and then, instead of waiting for her to recover, he re-shoot keytruda and she re-had pneumonitis, and other inflammation, so her one, to cover himself, gave all the max cortisone, and 4 antibiotics. after 25 days at the hospital, I took her home with me, and tried to supplement her, and little by little she has been recovering. We live in Spain, this is may be the worst country for cancer patients. Oncologists do not believe stage 4 patients have any chance at all, the just shoot protocols, and they truly make war to any supplement forms.
        When I had her home, I gave her, cimetidine, probiotics/prebiotics, curcumin, omega3, ahcc, fucoidan, genistein, resveratrol, milkthistle, and indole 3 carbinol. All I know is her CA marker dropped from 1300 to 800. Sometimes she can’t follow this as strictly as I would wish, because she has many many gas. I do not know if I gave her the right doses, and I do not know if her ovarian cancer is ER positive or negative…
        But then she went back home, and did not follow this protocol, and CA jumped, is now in 3000…
        We have today taxol chemo…
        I have just finished reading How to Starve Cancer, by Jane Mc Lelland, which is really a good good advising book, I plan making a consultation with the care oncology clinic.
        As you all can know, I am desperate…
        Thank you again

        1. Your mother is very lucky to have you! Oncologists see to many deaths, but fact is even stage 4 cancer patients can make a recovery. I’ve seen it first hand, my father-in-law recovered from glioblastoma, which is a stage 4 brain tumor, the worst. He’s alive almost 16 years after dx. Here’s a testimonial from Paul stamets about his 80-year old mother who recovered from stage 4 breast cancer: https://www.youtube.com/watch?v=mWT09ZDqFlE. Some supplements have low bioavailability, such as curcumin. Instead of taking the regular standarized extract, use a supplement with better delivery of the curcumin compound, this way your mother has to take less capsules. Consider synergies, for example curcumin with: boswellia, egcg, garcinol, berberine, Tinospora cordifolia, ursolic acid. Check on artemisinin/artesunate, d-limonene, sodium selenite, zinc & iodine.

        2. Dear Helena,

          Thank you for the details. In order to be fast and effective it’s best to have a call. Is that an option for you? If yes, we could use for example Skype or Facebook.

          Kind regards,
          Daniel

  29. Should the dosage for quercetin be adjusted carefully because of:
    Low Concentration of Quercetin Antagonizes the Cytotoxic Effects of Anti-Neoplastic Drugs in Ovarian Cancer
    https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0100314&type=printable

    Today i met with cancer dietician and argued with her about grapefruit juice. She said it is ok to have it in diet. But after looking to the papers below this statement looks questionable:
    Effect of grapefruit juice intake on etoposide bioavailability
    https://www.ncbi.nlm.nih.gov/pubmed/12389073
    Pretreatment with grapefruit juice resulted in an unexpected decrease of 26.2% in the AUC after oral treatment. Median absolute bioavailability with and without pretreatment with grapefruit juice was 52.4% and 73.2%, respectively. Interindividual variability was large in all treatment arms.
    Grapefruit juice seems to reduce rather than increase oral bioavailability of etoposide. Moreover, we did not observe a reduction in interpatient variability of bioavailability.

    Pharmacokinetic parameters of ifosfamide in mouse pre-administered with grapefruit juice or naringin
    https://www.researchgate.net/publication/337190199_Pharmacokinetic_parameters_of_ifosfamide_in_mouse_pre-administered_with_grapefruit_juice_or_naringin
    (seems grapefruit alters pharmakinetics of ifosfamide too)

    1. Hi asafsh,

      I think its best to just stop all plant extracts a few days before and after chemo, even if we expect them to be pro-oxidant. Otherwise, in general, I think the real anti-oxidants that we need to avoid and never use them with chemo and radio are the strong antioxidants such as Alphal Lipoic Acid, GSH, NAC and a few others.

      Indeed, grapefruit juice and various drugs such as Cimetidine are well known to interact with a liver enzyme that affects the metabolising process of various drugs leading to either a too high plasma level or too low plasma level of specific drugs. Sometime ago, I addressed this point shortly here https://www.cancertreatmentsresearch.com/tips-on-treatments-a-list-to-be-constantly-updated/

      Kind regards,
      Daniel

  30. Dear Daniel

    I have 2 general questions that may be relevant to this article:
    1. We have tried Doxycycline for more than 3 weeks continuously (thanks to your great web site), and it helped a lot to reduce inflammantion in tumor area. iirc, doxycycline has dual effect on bacteria and cancer cells, and in regards to former antibacterial effect, will the prolonged usage of this antibiotics induce resistance in intratumoral bacteria and reduce its effectiveness to address that kind of inflammation when used for long duration of time as part of anti-cancer treatment. If it is true, then could it be feasible to recycle it with other antibiotics having similar effects (posted via link to article “Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease”) to prohibit possible bacteria resistance to doxocycline?
    2. I cam across EGCG cytotoxicity related articles below:
    “Anti‑proliferative activity of epigallocatechin‑3‑gallate and silibinin on soft tissue sarcoma cells” https://www.spandidos-publications.com/mmr/15/1/103 ,
    “Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucose-regulated protein 78” https://www.ncbi.nlm.nih.gov/pubmed/16982771
    “Epigallocate chin-3-Gallate Induc es Cell Apoptosis ofHuman Chondrosarcoma Cells Through ApoptosisSignal-Regulating Kinase 1 Pathway” https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcb.23072 “EGCG induced upregulation of Bax and Bak, downregulation of Bcl‐2 and Bcl‐XL, and dysfunction of mitochondria in chondrosarcoma.”
    I don’t know whether suppression of anti-apoptotic proteins from BCL family is direct result of EGCG or a consequence, but for my and other cases it might be relevant together with dose to achieve significant impact on treatment.
    Based on above articles do you think that EGCG could be included as main treatment synergistic drug to enhance chemotherapy by using it directly during chemo cycle? (of course prior to that all chemo drugs must be searched for possible interactions)

    1. Dear Asafsh,

      Thank you for your questions.

      1. Indeed, antibiotics have multiple actions against tumors, acting both against cancer cells and against intra-tumour bacteria. I think cycling Doxycicline, would be beneficial for maintaining the effectiveness against the intra-tumour bacteria. The one that we discussed by e-mail, Ciprofaxacin, could be a good idea as it is also relevant against the type of cancer you are investigating. Are you still considering Ciprofaxacin?

      2. EGCG it’s on my top list of supplements that can help in cancer. I would consider to use it, but I would still keep it off for some days after chemo, and introduce it from that point on. It can be taken orally and also intravenous.

      Kind regards,
      Daniel

      1. Dear Daniel

        Thank a lot for your answers. Really appreciate your willingness to help.

        1. Yes we consider the Ciprofaxacin. But before have to figure out few issues:
        – the feasibility of co-administration of doxycycline (one week prior to chemo) and ciprofaxacin (continuous?)
        – with hepatotoxicity of antibiotics and other toxic chemo staff the liver has to be preserved imho. Yes, broccoli sprouts having hepatoprotection features was prescribed. Yet we may add Urtica dioica and nigella sativa (native to our place of residence). But all that lead us to the next issue below
        – the openly available online databases for drug and substance interaction aren’t complete and aren’t properly aligned to each other. This is true for webmd drug interactions page commonly referred here. (e.g. etoposide/hydroxychloroquine interaction)
        i have tried to study the feasibility of automation of drug (using primitive scripts on drug cocktail we are preparing for patient) interaction queries via open drug interaction API available from https://rxnav.nlm.nih.gov/InteractionAPIs.html# and came across few articles on drug interaction DB assessment where significant diff’s between them were highlighted. (e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079490/) May be i am wrong but i estimate that this service will be more wanted after ReDO and other approaches will gain popularity across physicians.
        in my understanding there is a need for online independent DB for drug interaction where ReDO and other drugs will be present, driven by drug practicing physicians/volunteers (anonymously to outsiders) including moderation (similar to wiki). I don’t know whether such project can be financed through gofundme or government organizations, but at least in the beginning all those known interactions can be written on one page (very lengthy) where interested in subject will do simple brute force search and add values to their treatments. Yep, adding protocol and treatment strategy tagging to the drug names will be helpful too.
        – another issue, open (preferably cheap) available labs to test drug interactions with cell assays (cheap too) before going in-vivo on patient try. At least those who can afford may order such tests and the result could be updated into the open drug DB available for all.

        Thank you and kind regards

        Asaf

  31. Case report of full remission (> 7 years) of SCLC patient treated with standard chemotherapy and supplements (curcumin, parthenolide, betuline, sulforaphane, withanolides, lactoferrin, pomegranate fruit extract, flaxseed, dioscorea, metformin and atorvastatin):

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256253/
    “Beneficial effect of additional treatment with widely available anticancer agents in advanced small lung cell carcinoma: A case report”

    1. Thank you asafsh! This is a nice one that also supports both the advantage of using additional options to increase effectivness of conventional treatments and the need to use those additions at a higher dose (although I would have used even higher dose compared to what they used). I will add this article in the forum too, in the lung cancer section.

      Kind regards,
      Daniel

  32. I was discussing with oncology physician about Metformin and chemo co-administration and he was arguing with not so noted efficacy of Metformin in clinical trials.
    There is an old article “Metformin as an Adjuvant Drug against Pediatric Sarcomas: Hypoxia Limits Therapeutic Effects of the Drug” stating that “Despite in vitro metformin gave remarkable antiproliferative and chemosensitizing effects both in sensitive and chemoresistant cells, its efficacy was not confirmed against Ewing sarcoma xenografts neither as single agent nor in combination with vincristine. This discrepancy between in vitro and in vivo effects may be due to hypoxia, a common feature of solid tumors.”

    And newest article on subject “Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways”
    https://www.sciencedirect.com/science/article/abs/pii/S0304383519305373?via%3Dihub
    claims that “A drug repositioning and combination screening identified seven synergistic drug combinations in inhibiting the viability of Ewing sarcoma cell lines under hypoxia.
    The imatinib and metformin combination regimen has potent synergistic anti-tumor effect in Ewing sarcoma in vitro and in vivo models. This combination suppresses dominant mechanisms in Ewing sarcoma including the key EWS-FLI1 downstream targets that are convergent into the PI3K/AKT/mTOR signaling pathway. The drug combination-related 48 gene signature showed significant correlation with clinical outcomes in Ewing sarcoma, sarcoma, GBM, stage III-IV ovarian cancer and early stage breast cancer cohorts.”

    Very much appreciate for expert opinion on these 2 articles.

    Kind Regards
    Asaf

  33. Could the PPI administration schedule described in article below be used as a general guideline? Any variations from that?

    Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients’ bed
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815282/
    All patients eligible for the study received the study drug ESOM (esomeprazole). This was orally administered in the two days prior to each cytotoxic agent. Patients had to receive ESOM the two days before chemotherapy because preclinical studies have clearly shown that this is the only effective approach is the pretreatment [3]

    Thanks

  34. Hi Daniel

    verapamil may affect toxicity and metabolism (because of cyp3a4) of chemo drugs so dose must be carefully adjusted. e.g.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033743/
    five courses required a dose reduction owing to cardiovascular toxicity.

    Another side of the coin – one hospital in China uses interesting approach for local delivery of Verapamil and chemo drugs:
    https://pubmed.ncbi.nlm.nih.gov/21562945/
    In order to determine the clinical efficacy and adverse reactions of chemotherapy and verapamil infusion through a target artery to treat colorectal cancer patients with metastasis after failure with previous conventional treatments.
    Efficacy was evaluated after at least two treatment courses.
    The objective response including complete or partial response was 58.3% in the 36 patients;
    No patient experienced side effects associated with heart function. Post-treatment, the P-R period, Q-T period, QRS, and heart rate were not significantly different than before treatment. Liver function was significantly improved. Side effects of chemotherapy were minor in comparison to those observed with intravenous chemotherapy.
    Infusion of verapamil and chemotherapy directly into pelvic tumor tissue can increase treatment efficacy and has been shown to be a relatively safe technique.

  35. Hi Daniel and friends,

    I came across the following article describing a potential interaction between metformin and hydroxychloroquine:
    https://www.forbes.com/sites/victoriaforster/2020/04/05/researchers-warn-that-covid-19-treatment-touted-by-trump-may-be-toxic-when-combined-with-diabetes-drug/?sh=71ff7a1155f8

    We know that hydroxychloroquine is an agent that inhibits autophagy. The article mentions metformin as an inducer of autophagy, as follows:
    “Metformin, on the other hand can actually induce autophagy, so it is possible that two drugs interfering with this recycling pathway at the same time could be toxic. The researchers looked to see whether this process was disrupted in the mice dying after treatment with the combination, finding increased numbers of “autophagosomes” (essentially recycling bins, containing cell proteins to be re-purposed), in the heart, liver and kidneys of the mice.”

    Interested in your thoughts about having both metformin and hydroxychloroquine in the same combination to improve chemosensitivity, is there a potential that this is actually counterproductive? If we had to choose, which drug would take priority for patients undergoing immuno/chemo?

    1. Hi Jun,

      Thank you for your question. Indeed, Metformin is one of those who are known to starve cancer cells and as a result trigger autophagy, which is a way for cells to try and survive. Therefore, adding an autophagy inhibitor such as Hydroxychloroquine should indeed help improve chemosensitivity.

      It’s difficult to say which one should have priority if it is to choose one since both act via different mechanisms. I would use both if possible (Metformin as discussed starting with day 0 of chemo and stop 3 days before, while HCQ continuously). From activity point of view, I would say that it is easier to replace Metformin with another drug/supplements targeting similar mechanisms wile it is more difficult to find effective autophagy inhibitors.

      Kind regards,
      Daniel

      1. Thank you for the feedback Daniel, that makes it very clear indeed. It sounds like the addition of HCQ to the combination including Metformin can potentially have more positive impacts rather than negative effects detailed in the article, so we will start including this into our daily regime.

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