Posted on by Daniel

Drugs and Supplements that Block Fermentation and Help Fight Cancer

Energy production inside cells

In order to maintain normal function including biosynthesis and transport of molecules across cell membranes, cells require energy (called ATP). There are two “engines” inside the cells that they can use to produce energy:

  • One engine is called (aerobic) respiration. This is the engine that is typically used by the cells to produce energy during their normal function. The process involves cells organs called mitochondria, and it requires oxygen in order for this process to function.
    • Nutrients that are commonly used as a fuel by animal and plant cells in respiration include sugar, amino acids and fatty acids
  • The other engine is called (anaerobic) fermentation. This is the engine that is typically used by the cells in abnormal conditions, when cells require a higher amount of energy as fast as possible. Fermentation, takes place in the cytosol of the cells and it relies mainly on a process called glycolisis and it does not require oxygen (this is why it is called anaerobic).
    • As a fuel fermentation requires sugar (glucose).

This is the common way of energy production in cells as we are aware of. Although not relevant here, it is interesting to mention that it has been recently (2019) discovered organisms breathing sulfur instead of oxygen (Ref.). Other organisms use nitrate. 

Fermentation: fast energy with no oxygen

Fermentation, takes place for example when we lift heavy weights. In this conditions the cells require faster access to energy. However, even if we bread very fast, the oxygen required to produce the much needed energy via normal cellular respiration is not enough. As a result cells switch to fermentation that doesn’t require oxygen. The drawback with fermentation is that this is a process less efficient in converting glucose into energy compared to respiration. This is why fermentation, requires a lot more glucose compared to respiration. Another drawback is that the fermenting engine also produced a lot of “smoke”, or in scientific terms, it produces a large number of protons. These protons are acidifying the intracellular space, which would soon kill the cell. As a result, the cells export these protons, via different “doors” (transporters), outside the cell.

One main mechanism used by the cells to export protons is by binding protons with lactate. This generates the lactic acid, that is exported outside the cells via the transporters called MCT, a main one being the transporter called MCT4. This in turn leads to the acidification of the extracellular space. This is the same lactic acid that causes muscle pain after e.g. a day of lifting heavy weights. Fermentation is also the process that is used by the immune cells (including T cells, dendridic cells, macrophages), when they become overactive (see discussion here). Therefore, in general, fermentation is the capability of our cells to produce energy fast, without the need of oxygen, but with the drawback that it is a less efficient process and it increases the acidity of the extracellular space. Red blood cells produce their energy via glycolisis as they do not contain mithocondria (Ref.). 

In fermentation, the only energy extraction pathway is glycolysis, with one additional reaction at the end of the pathway. This is why fermentation and glycolisis are two different words often used to refer to the same pathway.

As tumours require to divide fast, and as oxygen becomes less and less available (this situation is called hypoxia) due to their size and chaotic growth, they rely more and more on fermentation as a way to produce energy and continue their development. The hunger for glucose required to feed fermentation is the reason why most tumours are visible on glucose-based imagining (PET-CT scan). This is the reason why tumours are known to acidify their extracellular space (which can deactivate/protonate some chemotherapeutic drugs before getting inside the cells, as well as reduce the activity of the immune cells in the vicinity of tumours). This dependence of cancer cells on glucose metabolism, even in the presence of oxygen, is known as the Warburg Effect.

So there are two major reasons why tumours require glucose more than most of the normal cells:

  • Glucose can be used to generate energy and other relevant cellular building blocks even when oxygen is not available
  • Glucose can be used to generate energy and other relevant cellular building blocks faster – this is why glucose will be used in high amounts even in the presence of oxygen

All of the above is general knowledge. As most statements have been often referenced throughout this website, I will not spend time now to add more references.

Fermentation related approaches to inhibit tumour growth

Metabolic alteration (such as the increased fermentation in tumours compared to normal cells) are not only mechanism characteristic to tumors at a latter stage of development, but it is possible that they are at the origin of cancer. Indeed, it has been recently shown that breast cancer is likely not a genetic disease but a metabolic one (Ref.). Furthermore, it has also been suggested that breast cancer (and probably other cancers) can be triggered by chronic stress that in turn activates fermentation in cells (Ref.).

The fact that tumours are relying so much on fermentation makes them also vulnerable and susceptible to the following approaches:

  • blocking tumor access to glucose
  • blocking tumor capability to export protons (the byproduct of fermentation)
  • blocking fermentation

(It should be noted that the words “blocking” or “inhibiting” are related to the intended action. But in reality, what we usually achieve when we intend to inhibit a process is it’s reduction mainly. However, reducing the activity of mechanism that are essential in tumours will have negative impact on the tumours, while no or limited impact on normal cells.)

Blocking tumour access to glucose can be done either by targeting the transporters responsible for glucose transport across the cell membrane, or by reducing the blood glucose. Reducing the blood glucose, it is a different subject that I do not intend to discuss here. However, two major ways to reduce blood glucose is via the diet (using low carbohydrade diets or restricted Ketogenic Diet) and in advanced cancer patients inhibiting the capability of the body to create it’s own glucose as discussed here (Ref.). Targeting glucose membrane transporters has been discussed here (Ref.) and here (Ref.), and it will be further addressed below.

Blocking tumor capability to export protons is an entire strategy that alone can represent an approach to inhibit the growth and possibly kill tumors. This strategy has been addressed previously on this website, here (Ref.).

Blocking fermentation will be further discussed here. When speaking about inhibiting or reducing fermentation, I will also address the inhibition of glucose transporters and lactic acid transporter, or in other words the beginning and the end of the fermentation process. As glycolisis process is a major part of the fermentation process, I may often refer to  glycolisis inhibitors which will mean the same as fermentation inhibitors.

Fermentation Inhibitors

Below, I will discuss Fermentation step by step and the possible inhibitors of those steps, according to the available scientific literature. In order to present relevant background information related to mechanisms while making it easier for the reader, I will use italic and gray text for the background information so that the reader can easily browse through the fermentation inhibitors. While all the inhibitors presented below I find relevant, those inhibitors that have in my view the highest potential effectiveness against the specific target (also having in mind their bio-availability), are highlighted with bold.

When trying to inhibit fermentation, I would use not one but three of the inhibitors discussed below in combo, during the same time. This is because some drugs/supplements may not be absorbed well in some patients or may be metabolised differently or depending on the tumour location may or may not reach the tumour. To cope with potential side effects of some of the drugs listed here, I would probably cycle them every several weeks, i.e. switch to a different combo every several weeks.

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Fermentation and Respiration inhibition: Shutting Down the Power House of Cancer

Inhibiting Fermentation only will help fight tumors by reducing their growth rate, as we reduce their capability to produce energy fast. In some cases we may even be able to kill tumors. Inhibition of fermentation will also support chemotherapy (via e.g. reduction of multi drug resistance pumps that are energy dependent as well as increasing pH around the tumors) and depending on the inhibited steps also radiotherapy (e.g. reducing GLUT transporters will lower the glucose available to produce anti-oxidants required to fight the pro-oxidant nature of radio- and chemo-therapy). However, to increase the chance of success against cancer, it’s best to try inhibit both energy producing engines at the same time, i.e. inhibit fermentation using inhibitors discussed above and inhibit respiration using mithocondria inhibitors discussed here (Ref.).

I will discuss this strategy (Shutting Down the Power House of Cancer) in details in the next post where I will also address the priorities in my view. Lately, cancer patients have started to search for ways to inhibit all possible survival pathways at the same time. That sounds logical, but in doing that there is a tendency to mix various strategies and try to address more mechanism than its necessarily. Doing a little of everything may have limited activity. Instead, since we have a limit in the number of drugs and supplements we can use, focusing on specific strategies and addressing the related pathways with more inhibitors at the same time is best in my view.

Note: Since immune cell activity has an important metabolic profile (Ref.), combining strong metabolic inhibitors with immunotherapy should be carefully considered prior to its implementation. Targeting metabolism can be used as a means of regulating (not suppressing) immune responses (Ref.).

Update March 2020: Here is a nice recent review that helps understanding why glycolisis inhibitors have an anti-inflammatory activity, which is very important in cancer as well as supportive for chemo, radio and immuno therapy (Ref.).

References

Targeting lactate metabolism for cancer therapeutics

Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion 

Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma 

Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Cancer metabolism: a therapeutic perspective

Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH

In vitro effects of some flavonoids and phenolic acids on human pyruvate kinase isoenzyme M2

Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways

The Monocarboxylate Transporter Family—Structure and Functional Characterization

2-Deoxyglucose and Newcastle Disease Virus Synergize to Kill Breast Cancer Cells by Inhibition of Glycolysis Pathway Through Glyceraldehyde3-Phosphate Downregulation

Effects of a Series of Acidic Drugs on L-Lactic Acid Transport by the Monocarboxylate Transporters MCT1 and MCT4

Sulforaphane induces apoptosis in human hepatic cancer cells through inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase4, mediated by hypoxia inducible factor-1-dependent pathway

A Glycolysis Outsider Steps into the Cancer Spotlight

Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor 

6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4: A pair of valves for fine-tuning of glucose metabolism in human cancer

Small-molecule inhibitors of human LDH5

Novel drugs that target the metabolic reprogramming in renal cell cancer

Cancer metabolism: current perspectives and future directions

HIF-1α pathway: role, regulation and intervention for cancer therapy

mTOR as a central hub of nutrient signalling and cell growth

Metabolic Regulation of Immune Responses

c-Myc and Cancer Metabolism

Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy?

Role of Oncogenes and Tumor Suppressors in Metabolic Reprogramming and Cancer Therapeutics: A Review

Fermentation and anaerobic respiration

Anti-cancer agents counteracting tumor glycolysis

mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging

Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities

Antimetabolic Effects of Polyphenols in Breast Cancer Cells: Focus on Glucose Uptake and Metabolism

Lactate and cancer: spinal metastases and potential therapeutic targets

Targeting immunometabolism as an anti-inflammatory strategy

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.

Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?page_id=1794

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81 thoughts on “Drugs and Supplements that Block Fermentation and Help Fight Cancer”

      1. Hi Daniel, I have been doing some research looking for a PMI inhibitor. I have some leads and wondered if they can be posted for discussion and expansion.

        Blocking PMI with D Mannose use
        Phosphomannose isomerase isolated from brewers’ yeast was found to be inhibited in a time-dependent process by 8-hydroxyquinoline, ethylenediaminetetraacetate, o-phenanthroline, oc-dipyridyl, cysteine, and dithiothreitol. The effectiveness of these agents in bringing about inhibition paralleled their ability to bind zinc, and the inhibition could be prevented by blocking the coordination sites of the metalbinding agents. An instantaneous reversal of inhibition occurred upon the addition of metals to the EDTA-inhibited enzyme, and the extent of reversal or prevention of inhibition was proportional to the ability of the added metals to form a complex with EDTA. Ref.

        The action of silver ion on cell walls is illustrated by reference to the yeast Candida albicans. Silver has been shown to inhibit the enzyme phosphomannose isomerase (PMI) by binding cysteine residues.34
        https://www.sciencedirect.com/topics/nursing-and-health-professions/mannose-phosphate-isomerase
        GDP-MP inhibitors (Lackovic et al., 2010). From this study, the most potent inhibitor identified was a piperazinyl quinoline derivative. The mannose activation enzyme systems leading to GDP-mannose biosynthesis are essential for host-parasite interactions. Thus, GDP-MP, but also PMI and PMM, are interesting targets to be inhibited for impairing glycoconjugate biosynthesis.
        https://www.nature.com/articles/s41586-018-0729-3
        Mannose impairs tumor growth and enhances chemotherapy
        sci-hub.tw/10.1038/s41586-018-0729-3
        MPI knockdown followed by labeling with [2-3H]mannose indicated that 50–70% Mpi inhibition increases [3H]mannose incorporation into proteins by 4–7-fold (Fig. 2b). These data show that reducing MPI activity by even 40–50% could increase Man-6-P flux into the glycosylation pathway. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234766/
        We report the discovery and validation of a series of benzoisothiazolones as potent inhibitors of phosphomannose isomerase (PMI) C:\Users\Darle\Documents\sci-hub.tw\10.1021\jm101401a
        Some benzoisothiazolones possible inhibitors: Benzisothiazolinone, Estradiol 3-saccharinylmethyl ether, Repinotan, Saccharin https://en.wikipedia.org/wiki/Category:Benzoisothiazolinones
        Evaluation of malonate-based inhibitors of phosphosugar-metabolizing enzymes: Class II fructose-1,6-bis-phosphate aldolases, type I phosphomannose isomerase, and phosphoglucose isomerase https://www.sciencedirect.com/science/article/pii/S0968089611010686
        Inhibition of Phosphomannose Isomerase by Fructose 1-Phosphate. Fructose 1-phosphate is a powerful inhibitor of phosphomannose isomerase (PMI) https://www.nature.com/articles/pr19962957
        Herein we disclose the discovery and validation of benzoisothiazolone derivatives that are selective inhibitors of human PMI.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437750/

          1. Hi Daniel,

            I was actually hoping to find an alternate to those 2, what would you chose as your 3rd choice.
            I was looking at melonate, it appears to have anti cancer benefits on its own but I was not sure if the negatives still outweigh the positives.
            I was interested in Saccarin, it is in the right family and it is implied that it works but I can’t find anything that confirms it. I would be interested to know if anyone has any information on this.

      2. @daniel Starting fenbendazole pancur for my dad. What dosage to give him 200g? After food or before? Stage 4 squamous cell carcinoma head and neck. List of other supplements :-

        Health reset
        Immunity men’s health
        Giloy
        Morniga
        Vitamin E complex
        Vitamin D monthly 60k
        Ganoderma
        Beta Glucan
        Curcumin

        At the moment we have not started any conventional treatment. What do you suggest?

        thoughts on rife frequency machine? And nano silver particles?

    1. Very good point.
      – This is why its best to use drugs and supplements that have been already used on humans and where the safe dose it is known. When using this dose, the normal cells will not be seriously affect but cancer cells that are strongly dependent on the target mechanism will be affected according to the literature.
      – However, we may want to increase our chance of success. One way to increase the impact on cancer cells would be to increase the dose of a specific drug beyond the safe dose. However this is undesirable approach. Instead, it’s best to inhibit multiple targets at the same time that are important to cancer, along the same line (such as using multiple glycolisis inhibitors) – in this case it is more likely that we can affect cancer cells even at lower doses of the drugs and supplements we use.
      – Furthermore, when using multiple drugs and supplements, we should add one by one every several days and observe if any side effects are occurring – I would never add all at once.

      1. Not sure where to post this. Two current trials for mebendazole, one gives 1,500mg/day, the other gives from 50mg/kg/day to 200mg/kg/day, for 90kg man this would be 4,500mg/day minimum ?!

        Febendazole at 220mg/day on days 1-3 of each week ?

        Taken with Vitamin E, Curcumin and CBD ?

        2. Great point Akis!

          Here I discussed Mebendazole https://www.cancertreatmentsresearch.com/the-over-the-counter-drug-mebendazole-acts-like-chemotherapy-but-with-virtually-no-side-effects/ (when you want to know where to post something, you can always use the search option to check if a subject has been already discussed. If the subject was not discussed and is not related to any of my posts, you can always start a new topic on the forum, here https://www.cancertreatmentsresearch.com/community/)

          Yes, although Mebendazole has very low toxicity in my view, that is a huge dose of Mebendazole in the clinical trials you mentioned, using 50mg/kg/day. I discussed some of these aspects in my post on Mebendazole.
          1500mg has already been used even in children for months. 200mg/day range has been already shown to induce response and this is why many are going with that. However, Mebendazole and Fenebendazole are not so well absorbed in the body and when using 200mg/day, we may stay just at the limit of effectivness. And if absorption is poor we may not get anything out of that. If I would use Mebendazole against cancer, I would probably go with a dose of 1g/day. I would start with 200mg/day and move step by step up to reach the target dose in e.g. two weeks. I would probably use the same approach for Fenbendazole. Others such as Vit e, Curc and CBD are optional in my view. Curcumin I very much like but in high doses as discussed here https://www.cancertreatmentsresearch.com/curcumin-an-universal-cancer-treatment/ CBD I like but best with THC. Vit E is debatable due to some studies indicating pro-cancer effects, and others anti-cancer effects.

          Kind regards,
          Daniel

          1. I think from what I have read here, Fenbendazole is easier to take requiring only 222mg/day for days 1-3, with days 4-7 off.

            Mebendazole at 50mg/kg/day works out as 4,500mg/day for me, and even as per your suggestion of 1,000 mg/day I would need to take 10 tablets a day, as they come in 100mg over here (Vermox).

            I am thinking of trying this: fenbendazole 222mg/day, days 1-3 out of 7 and mebendazole 300mg/day, days 1-3 out of 7.

            1. I expect Fenbendazole has similar effective dose as Mebendazole. Using 222mg/day was a choice of those who first suggested the use of fenbendazole in humans, aligning with the typical dose of Mbendazole, i.e. 200mg/day. For MBZ, the dose in clinical trials was pushed to much higher doses trying to maximise it’s anti cancer potential. So I would not say that Fenbendazole is easier to take compared to Mebendazole, since the doses are related to choices to use more or less. However, your choice of combining Fenbendazole and Mebendazole sounds fair to me. Please note that tables of 500mg Mebendazole can be found online. Kind regards, Daniel

        3. I am a new member. I read a lot of the posts here. Thank Daniel for the huge effort!

          I would share with you that my son was enrolled in the Mebendazole study. He takes Mebendazole at the highest dose for kids (4.5 grams/day). No significant side effects have been observed so far (two weeks). His appetite is a little low, that’s it.

          The problem of Mebendazole is that it is poorly absorbed in humans. Unlike mice, which absorb Mebendazole well, the plasma concentration of Mebendazole in human is about 30 to 100 times lower than what was observed in mice. That is why they try such a huge dose.

          Hope this helps.
          Jeff

          1. Dear Jeff,

            Thank you for your comment and for sharing this very valuable piece of information. Mebendazole is indeed poorly absorbed and that may also vary from person to person. (Fenbendazole has similar challenges.) Have you seen my post on Mebendazole? https://www.cancertreatmentsresearch.com/the-over-the-counter-drug-mebendazole-acts-like-chemotherapy-but-with-virtually-no-side-effects/ Here I also discussed the fatty food and Cimetidine as options to increase MBZ levels in the blood.

            Kind regards,
            Daniel

            1. Dear Daniel,

              I certainly read your post on Mebendazole. Thank you for your suggestions on increasing the absorption of Mebendazole with fat and Cimetidine. I actually give my son the medicine with meal and with milk plus coconut a teaspoon of coconut oil. I have used Cimetidine for a couple of days (with low dose mebendazole on COC protocol). Then I realized that Cimetidine may lower platelet counts. So I stopped this. I also tried and stopped CBD oil for the same reason. This may not apply to everyone, but my son’s tumor may bleed once the platelet count drops to around 100. This happened twice.

              Thanks,
              Jeff

    1. Hi Johan, thank u for your interesting question. If I think of isoprenoids such as Limonene I feel they fit first as a modulators on the mevalonate pathway, as discussed here https://www.ncbi.nlm.nih.gov/pubmed/30662405 and previously discussed here https://www.cancertreatmentsresearch.com/reduce-cholesterol-in-cancer-cells-to-fight-cancer/ This in turn can have impact on RAS which interacts with the PI3K/Akt/mTOR pathway. This is nicely explained here http://flipper.diff.org/app/items/info/5343 On this line, from fermentation point of view, I would call them 3rd level due to RAS modulation -> PI3K/Akt/mTOR modulation -> glycolisis enzymes modulation. So it could make sense to start another category above called 3rd level modulators? What do you think?

    1. Thank you Johan! Your comments, website and knowledge demonstrate we are more captains of exploration around 🙂 Same for J and Shanti. And they are more fallowing this website but they like to stay low profile. We don’t know everything but we learn together, share and make steps forward!

  7. D, thank you for providing this list of glyco inhibitors!
    I have thought for some time that we really needed a page like this.
    We should all go out online and add our own contribution to what D has given us.

    This is one of the central mechanisms that we have been interested in for all of these years along with OXPHOS subunits.
    Having all of this information in one place for people will be such a great resource.

    I came across another one of these today (there must be many many more out there).
    This one is peptide that silences VDAC-1 specifically in GBM (some on thread have spoken previously of an interest in these peptides,I think last time the discussion might have been related to an HK-2 peptide) and then all sorts of glyco enzymes that we know so well GADPH … are down regulated. There are a few of these treatments emerging that very specifically target a particular aspect of the metabolic machine; another one that springs to mind is the result arising from this year’s Nobel related to HIF1-alpha. These next generation approaches might eventually displace more generic treatments such as 3-BP.

    https://www.mdpi.com/2073-4409/8/11/1330

  9. I am very much looking forward to your next post regarding Shutting Down the Power House of Cancer. I am guilty of trying to inhibit all possible survival pathways at the same time to help my Mom (very aggressive stage IV breast cancer). I do fear that in “doing a little of everything may lead to nothing”. The science is somewhat overwhelming to the layperson, but I am here to learn (quickly).

    1. Dear Janet,

      Please, with my posts I do not want to trigger fear but would like to help improve and sharpen our approaches. Trying to inhibit all possible pathways is natural, what I am saying is that we better focus our guns on the most relevant pathways. That is my view, and I also may be wrong. Nobody knows everything. We just try to learn more and act more consistent. The fact that you are here and discussing and helping your mom with metabolic approaches means you are already doing a lot. If you like me to give you my view on the strategy you are currently using, please send me an e-mail or write it here and I will respond asap, probably in the second part of this week.

      Kind regards,
      Daniel

  10. Thank you Daniel!
    All your content is so full of help for everyone!
    Thank you for all the effort you put on every post. We are all growing together in knowledge and that is amazing to see.

  11. Thank you, Daniel!

    I am a new member but already read a lot of your posts. This topic is important, because the abnormality of metabolism of cancer is universal. Targeting this area should work no matter what mutations cancer cells carry. I am looking forward to reading the next post. After that, it would be really nice to discuss any strategies to avoid harming immune cells which act a lot like cancer cells metabolically.

    I have read a lot of your posts and am deeply moved by the love you gave to your wife. I applaud that you expend your love to the fight against cancers that affects many people’s lives.

    Thank you!
    Jeff

    1. Thank you so much for your kind message Jeff! It’s the same quality that brings most of us together here, i.e. care for others!
      I hope the website will help. There is a lot of info on this website, even if I made summary of various areas of science. Just fly across the info, don’t read all. Don’t try to understand all. Stop only where you think/feel it is specifically relevant to you. That is what I do in order to navigate through large amount of info, and it helps.

      Kind regards,
      Daniel

  12. Thank you Daniel.
    Your website is full of great information and all the science you reference really helps.

    I’m in the UK and have metastatic triple negative breast cancer. I really would like to try the metformin/syrosingopine combination. Could anyone help me with sourcing syrosingopine? I’ve seen it on alibaba but would prefer a European source if possible?

    I’d love to connect with anyone currently trying this combination too.

    Thank you Daniel for your commitment to helping people and sharing such great research.

    Jo

    2. Dear Jo,

      I was recently informed by a clinic that a TNBC patient progressing on chemo has responded well to metabolic treatment including 2DG metronomic (intravenous) combined with Metformin, Doxycycline, Satin and Mebendazole, and a few others. If interested let me know as I will soon get more details on the complete treatment and dose.

      Kind regards,
      Daniel

      1. Dear Daniel
        Thank you so much for posting this. It sounds very interesting and I would like very much to know more. I am based in the UK but have travelled to Germany to have TACE which reduced my tumour load by 50% but I definitely need more to stress it further. I would be very interested in the details
        Thanks again.
        Jo

        1. Hi Jo,

          Great! I am very happy to hear that! Could you please let me know:
          – What chemo combo did they used? Mytomycin C, Gemcitabine, Cisplatin or a combo of these?
          – What was the location of the tumor? Liver?
          – How many interventions were required to achieve 50% reduction?
          – Was this at prof Vogl at Frankfurt University Hospital?
          This may help others.

          On the exact 2DG metronomic and metabolic protocol used I will get details after Christmas. If I did not added the details, please remind me after 1st of January and I will share them here.

          Kind regards,
          Daniel

          1. Hi Daniel

            Sorry for the very late reply but I didn’t see your response.

            Yes Prof Vogel in Frankfurt.
            Prof Vogel used a mixture of Mitomycin, Irinoctecan and Cisplatin over 4 TACE procedures.
            50% reduction on first TACE.
            Subsequent TACE showed limited response.
            Location of the tumours were in lung, multiple, scattered lesions.

            I hope this information may help others.

            I also followed the TACE with 3 microwave ablations but did not have a good response and by the third treatment the tumours were growing.

            I have since tried IV chemos (carboplatin/Gemcitabine) with limited response. I am in the UK and we are only able to access chemo for metastatic triple negative breast cancer. I also use a range of off labels and supplements.

            I would very much like to hear of the 2DG metronomic and metabolic protocol you shared before Christmas. Or any other treatments you might consider helpful to me. I am currently looking at which drugs I could use to decrease my LDH which is unfortunately rising month on month.

            Kind regards
            Jo

  13. Daniel – Thank you so much for your kindness. I will post my list here in hopes that perhaps the comments and thoughts of you and others will also perhaps help someone else. My Mom was diagnosed with aggressive Stage IV breast cancer, grade 3, 40% ER positive, mets to lungs and mediastinum nodes. She underwent 12 grueling weekly Taxol treatments with reduced dosages as time progressed as she landed in the hospital twice for neutropenic fever.

    After Taxol, her oncologist gave her a break to recover from chemo. In just a few weeks time, prior to a surgical consult for mastectomy, the tumor doubled in size and appeared to be on the verge of ulcerating! Post-mastectomy tumor analysis now shows additional axillary lymph node involvement and change to hormone status of triple negative.

    She is currently undergoing radiation and will likely start Xeloda (I will be arguing for a lower-than-standard dose) and perhaps Kisqali as her oncologist says the lung mets may still be hormone positive. She is also currently taking Letrozole. I know that some of the supplements are metabolized via the CP450 enzyme route, the same as Letrozole, but at this point, I am taking that risk until I have more time to research fully.

    THE LIST: I do alternate some supplements in order to reduce the sheer number of pills each day. I tried to ensure that each metabolic pathways is still covered in doing so. I am open to any thoughts on additions, deletions, dosages, redundancies, etc. Thank you so much to Daniel and all the brilliant people here! I’ve already learned so much.

    1 Fenbendazole, 666 mg (3/4 tsp.)
    2 Simvastatin, 20 mg
    3 Melatonin, 20 mg
    3 Melatonin, 60 mg, Not yet Started
    4 D3, Vitamin, 75 mcg/3,000 IU (2) (Total D: 200 mcg/8,000 IU)
    4 Vitamin ADK, Vitamin A 900 mcg, D3 125 mcg/5000 IU, K1 K2, MK4 1500mcg, MK7 300mcg (1); (Total D: 200 mcg/8,000 IU), Vitamin A – not with radiation/chemo
    5 Boron, 3 mg/day
    6 EGCG (Green Tea), 400 mg
    7 Curcumin, 712.50 mg
    8 Resveratrol, 1,000 mg
    9 Loratadine (Claritin), 20 mg
    10 Glucosamine sulfphate, 1,500 mg, Not with radiation
    11 Omega 3 Fish Oil 1,575 mg
    12 Bergamot, 750 mg, Not with radiation
    13 Silymarin (milk thistle), 300 mg
    14 Cimetidine, 800 mg
    15 Quercetin, 1,000 mg
    16 Hydroxycitrate/Garcinia Cambogia, 1,500 mg HCA
    17 Berberine, 1,500 mg, Alternate with Genistein
    17 Genistein, 125 mg, Alternate with Berberine
    18 Chitosan, 1,500 mg, Alternate with Gymnema sylvestre
    18 Gymnema sylvestre, 900 mg, Alternate with Chitosan
    19 Holy Basil (Ursolic Acid), 500 mg, Alternate with Nigella Sative Black Seed Oil
    19 Nigella Sativa Black Seed Oil (Thymoquinone ), 15 mg, Alternate with Holy Basil
    20 Luteolin, 50 mg, Alternate with Sulforaphane. Not with radiation
    20 Sulforaphane, 9.5 mg, Alternate with Luteolin. Not with radiation or chemo
    21 7-Keto DHEA, 200 mg, Alternate with Fermented Wheat Germ
    21 Fermented Wheat Germ, 200 mg, Alternate with 7-Keto DHEA
    22 Hydroxytyrosol (Olive Leaf Extract), 0.08 mg, Alternate with Magnolia extract
    22 Magnolia extract (honokiol), 200 mg , Alternate with Hydroxytyrosol Olive Leaf
    23 Modified Citrus Pectin, 4.8 g, Alternate with Red Mineral Algae
    23 Red Mineral Algae (seaweed), 3.5 g, Alternate with Modified Citrus Pectin
    24 5 Mushroom Complex: shitake, maitake and turkey tail, 1,000 mg, Alternate with Reishi Mushroom
    24 Reishi Mushroom (fruiting body), 1.2 g, Alternate with 5 Mushroom Complex. Not yet started
    25 IP-6 Inositol (Inocellip-6), 1,500 mg
    26 Phloridzin (f/AppleWise Polyphenol extract), 30 mg, Alternate with Chrysin
    26 Chrysin (Passion Flower), 500 mg, Alternate with Phloridzin
    27 MSM, 4 g, Alternate with Omeprazole
    27 Omeprazole (Prilosec), 20 mg, Alternate with MSM
    28 Aspirin, 81 mg, Alternate with Sea Buckthorn Oil Omega 7
    28 Sea Buckthorn Oil Omega 7, 1,000 mg, Alternate with Aspirin
    29 Ashwaganda, 470 mg
    30 Serrapeptase, 74 mg, Not yet started
    31 Gelum Drops, 20 drops 3x daily, Not yet started
    32 Folate, 1,000 mcg, Not yet started. (Research folic vs folate acid. Benefits vs. risks.)
    33 Niacin B3 Nicotinamide, 1,000 mcg, Not yet started. Likely will not use as efficacy is not clear. 1) Niacin decreases LDL and increases HDL which is bad for scavenger receptor class B type 1 (SR-B1). Appears that breast cancer uses SR-B1 “Our data show that HDL is capable of stimulating migration and can activate signal transduction pathways in the two human breast cancer cell lines, MDA-MB-231 and MCF7.” 2) However, “As a result, we confirmed an inhibitory effect of nicotinamide on cell growth in highly aggressive TNBC cells.”
    34 D-Limonene, 1,000 mg, Not yet started. Redundant?
    35 Graviola, 2 g, Not yet started
    36 Nattokinase, 2,000 fu, Not yet started
    37 Magnesium Gluconate, 27 mg, Not yet started; concern re: diarrhea

    For Digestion/Diarrhea/Possible Colitis, IBS
    1) SunButyrate-TG Liquid
    2) Seed Pre and Probiotic
    3) TIncture of Opium, as needed

    Under Consideration
    Low Dose Naltrexone
    Menbendazole, Prescription needed; possibly available via eBay (expensive)
    Dipydriamole , May cause diarrhea / May cause low blood pressure; May cause headaches; Prescription needed
    Metformin, May cause diarrhea / Prescription needed
    Artemsinin, Not with radiation
    Chloroquine or Hydroxychloroquine, Prescription needed
    Honokiol, Consider increased dose (3-4 g)
    Propranolol, Low blood pressure during chemo; monitor for BP recovery before starting

    1. Dear Janet,

      Thank you for your kind words. This is indeed a long list. At this point I can only react on the every components sating my opinion, but I can not discuss what I would remove and what I would keep. That can only be done when starting with a strategy in mind. If latter you can share a strategy and connect them with that strategy, we can discuss the strategy as well as how they fit to that.

      First, I would suggest that whenever you have doubts regarding the interaction between the drugs, you can use the drug checker here https://reference.medscape.com/drug-interactionchecker?src=google

      Here is my reaction on the list:

      1 Fenbendazole, 666 mg (3/4 tsp.)
      2 Simvastatin, 20 mg
      – better Atorvastatin due to half life and other characteristics. Pitavastatin may also be better due to the reason discussed here https://www.cancertreatmentsresearch.com/cholesterol-lowering-statin-drugs-to-fight-cancer/
      3 Melatonin, 20 mg
      3 Melatonin, 60 mg, Not yet Started
      4 D3, Vitamin, 75 mcg/3,000 IU (2) (Total D: 200 mcg/8,000 IU)
      4 Vitamin ADK, Vitamin A 900 mcg, D3 125 mcg/5000 IU, K1 K2, MK4 1500mcg, MK7 300mcg (1); (Total D: 200 mcg/8,000 IU), Vitamin A – not with radiation/chemo
      5 Boron, 3 mg/day
      6 EGCG (Green Tea), 400 mg
      – too low dose – I would go with about least 2000mg
      7 Curcumin, 712.50 mg
      – too low dose – I would go with about 5000mg
      8 Resveratrol, 1,000 mg
      9 Loratadine (Claritin), 20 mg
      10 Glucosamine sulfphate, 1,500 mg, Not with radiation
      11 Omega 3 Fish Oil 1,575 mg
      – too low dose – I would go with about 5000mg
      12 Bergamot, 750 mg, Not with radiation
      13 Silymarin (milk thistle), 300 mg
      – too low dose – I would go with about 2000mg
      14 Cimetidine, 800 mg
      15 Quercetin, 1,000 mg
      – too low dose – I would go with about 2000mg
      16 Hydroxycitrate/Garcinia Cambogia, 1,500 mg HCA
      17 Berberine, 1,500 mg, Alternate with Genistein
      17 Genistein, 125 mg, Alternate with Berberine
      – too low dose – I would go with about 1000mg
      18 Chitosan, 1,500 mg, Alternate with Gymnema sylvestre
      18 Gymnema sylvestre, 900 mg, Alternate with Chitosan
      19 Holy Basil (Ursolic Acid), 500 mg, Alternate with Nigella Sative Black Seed Oil
      19 Nigella Sativa Black Seed Oil (Thymoquinone ), 15 mg, Alternate with Holy Basil
      20 Luteolin, 50 mg, Alternate with Sulforaphane. Not with radiation
      20 Sulforaphane, 9.5 mg, Alternate with Luteolin. Not with radiation or chemo
      21 7-Keto DHEA, 200 mg, Alternate with Fermented Wheat Germ
      21 Fermented Wheat Germ, 200 mg, Alternate with 7-Keto DHEA
      22 Hydroxytyrosol (Olive Leaf Extract), 0.08 mg, Alternate with Magnolia extract
      22 Magnolia extract (honokiol), 200 mg , Alternate with Hydroxytyrosol Olive Leaf
      – too low dose – I would go with about 3000mg
      23 Modified Citrus Pectin, 4.8 g, Alternate with Red Mineral Algae
      23 Red Mineral Algae (seaweed), 3.5 g, Alternate with Modified Citrus Pectin
      24 5 Mushroom Complex: shitake, maitake and turkey tail, 1,000 mg, Alternate with Reishi Mushroom
      24 Reishi Mushroom (fruiting body), 1.2 g, Alternate with 5 Mushroom Complex. Not yet started
      25 IP-6 Inositol (Inocellip-6), 1,500 mg
      26 Phloridzin (f/AppleWise Polyphenol extract), 30 mg, Alternate with Chrysin
      – not sure if it makes sense so low dose
      26 Chrysin (Passion Flower), 500 mg, Alternate with Phloridzin
      27 MSM, 4 g, Alternate with Omeprazole
      27 Omeprazole (Prilosec), 20 mg, Alternate with MSM
      – low dose – but I am not sure what is the purpose
      28 Aspirin, 81 mg, Alternate with Sea Buckthorn Oil Omega 7
      28 Sea Buckthorn Oil Omega 7, 1,000 mg, Alternate with Aspirin
      29 Ashwaganda, 470 mg
      30 Serrapeptase, 74 mg, Not yet started
      31 Gelum Drops, 20 drops 3x daily, Not yet started
      32 Folate, 1,000 mcg, Not yet started. (Research folic vs folate acid. Benefits vs. risks.)
      33 Niacin B3 Nicotinamide, 1,000 mcg, Not yet started. Likely will not use as efficacy is not clear. 1) Niacin decreases LDL and increases HDL which is bad for scavenger receptor class B type 1 (SR-B1). Appears that breast cancer uses SR-B1 “Our data show that HDL is capable of stimulating migration and can activate signal transduction pathways in the two human breast cancer cell lines, MDA-MB-231 and MCF7.” 2) However, “As a result, we confirmed an inhibitory effect of nicotinamide on cell growth in highly aggressive TNBC cells.”
      34 D-Limonene, 1,000 mg, Not yet started. Redundant?
      35 Graviola, 2 g, Not yet started
      36 Nattokinase, 2,000 fu, Not yet started
      37 Magnesium Gluconate, 27 mg, Not yet started; concern re: diarrhea
      – diarrhea only if Mg too high

      For Digestion/Diarrhea/Possible Colitis, IBS
      1) SunButyrate-TG Liquid
      2) Seed Pre and Probiotic
      3) TIncture of Opium, as needed

      Under Consideration
      Low Dose Naltrexone
      Menbendazole, Prescription needed; possibly available via eBay (expensive)
      Dipydriamole , May cause diarrhea / May cause low blood pressure; May cause headaches; Prescription needed
      Metformin, May cause diarrhea / Prescription needed
      Artemsinin, Not with radiation
      Chloroquine or Hydroxychloroquine, Prescription needed
      Honokiol, Consider increased dose (3-4 g)
      Propranolol, Low blood pressure during chemo; monitor for BP recovery before starting

      In general I think you use a lot of good supplements and a few debatable, while not so many re purposed drugs. I like supplements and I think they are good support, but when fighting advanced cancers, I think we need to push a little bit more on re-purposed drugs and integrate them with the conventional options.

      If you connect them with a strategy that you want to follow, we can discuss what to remove and what to add.

      Kind regards,
      Daniel

    2. Hi Janet, sorry to hear of your mom’s battle with cancer. You’ve done an impressive job of selecting supplements to help your mother. The toughest part, however, is to find the supplements that can actually help and how much of any supplement you need to take. There’s no doubt that curcumin has anti-cancer effects, it’s therapeutic potential is beyond any doubt, but the minimum requirement for it to have any effect on the cancer cells is it needs to reach those cells. Only then there’s a chance it’ll do some damage to the cancer. Many studies show that at less than 8 grams of curcumin, there’s no trace of free curcumin in the blood. 712mg of curcumin may provide some health benefits, but there’s almost no chance of it doing any harm to your mom’s cancer.

      Sulforaphane is another great supplement. But 9.5mg is too low. I think you’ll need at least 60grams of broccoli sprouts a day or a supplement that can provide a similar dose.

      IP6, again too low. And most other supplements, the same issue.

      Personally I think it’s best to add one supplement at a time and to work up to the desired dosage. For example. Dr. Bharat B. Aggarwal (MD Anderson) recommends dose-escalating of curcumin over an 8 week period. So you could start at 1 gram/day and if no adverse effects are observed increase the dose, up to 8 grams, or even a few grams above.

      Genistein, at a low dose probably does more harm than good. The use of Resveratrol is also very debatable.

      Best Regards,
      Johan

    4. Dear Janet,

      So sorry to for your mom. I understand that you want to help as much as you could. But sometimes it is not the more the better. I would cut out those that do not play an essential role in inhibiting cancers unless you have a reason to use them. My 2 cents on safety:

      1) When being treated with radiation, it would be helping cancer cells to survive if the patient takes antioxidants. For vitamins, a doctor told me that vitamin A, C, and E should not be taken during radiation therapy.

      2) Cimetidine may cause thrombocytopenia. Monitor the platelet count, stop it if you see a decreasing trend.

      3) Chloroquine and to a lessor extent, hydroxychloroquine, could cause irreversible vision loss due to their toxicity to optical nerves over time. Long term use should come with close monitoring of optical nerves. They may also cause thrombocytopenia.

      Best wishes,
      Jeff

  14. A priority for the forum should be finding powerful formulations of fermentation inhibitors that could be combined with the many OXPHOS formulations.

    A highly effective cancer treatment strategy involves targeting glycolysis and OXPHOS at the same time. There are a number of extremely effective OXPHOS inhibitors including mito-Met, mito-HK, NanoMg and others. These formulations are up to a thousand fold more potent than the unformulated versions. Combining these formulations with properly formulated glycolysis inhibitors could be massively effective.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930686/
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137433/
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435252/pdf/ijn-10-3499.pdf

    1. Hi J,

      You are totally right! We need to find ways to increase the level of glyco inhibitors that can reach the tumor. With those used intravenously it’s easier. It’s more challenging when it comes to those taken orally.

      The other challenge is to come up with ideas for improvement that are also actionable ideas for most people.

      I think a first step could be just to have a view on how the blood levels in humans of specific compounds compare to the levels used for anti-cancer action, and the half life of those drugs. This can help design more effective approaches in terms of dose and administration frequency for each drug. Next step will be to find ways for each drug that is on top of the list in terms of effectiveness, to deliver a higher dose to the tumors, via formulations such as those you mentioned.

      Kind regards,
      Daniel

  15. D, always good to expand the list.

    koningic acid inhibitor of GAPDH
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629112/
    Perhaps combining with an OXPHOS inhibitor would amplify this effect as suggested by the above article

    mannose inhibits hexokinases
    https://spiral.imperial.ac.uk:8443/handle/10044/1/65247
    “a single oral gavage of mannose, which resulted in a serum concentration of approximately 3mM ”
    “As mannose impedes hexokinases”
    “colorectal tumours generally have very low PMI levels, indicating they may be broadly sensitive to mannose”
    “mannose is taken up by the same transporter(s) as glucose3, but accumulates as mannose-6-phosphate in cells and this impairs the further metabolism of glucose in glycolysis, the TCA cycle, the pentose phosphate pathway and glycan synthesis.”

    D, thank you for considering writing an article on dual metabolic inhibition. We have seen several times that such an approach can be extremely powerful. Our assembled, large and growing list of both glycolysis and OXPHOS inhibitors could then be put into action.

    I have also been thinking of how we might create a more effective overall anti-cancer strategy by thinking more abstractly.
    For example, the number of escape routes to cancer from metabolic approaches begins to greatly diminish. After all these years we have read time and time again about MCT-1, MCT-4, glycolysis, OXPHOS, HK-2, GLUTs, stem cells, etc. . There are in fact a highly limited number of these central metabolic players. Creating a treatment plan that first knocked down MCT-1 cells with perhaps 3-BP, followed by an ATP depletion round that could target remaining cells, then knock down stem cells … . This is probably the approach used at cancer clinics. They could rotate through the main pathways with their favorite approaches and then remix to give cancer a new challenge.

    We continue to increase our understanding of cancer and it is exciting to see those new to the forum push forward with innovative treatment strategies.

    Best Wishes, J

    1. Thanks a lot J!

      I added Mannose to the list above. I think this is very interesting – I think is good to use it in combo with a PMI inhibitor (I still have to find one that is accessible). In collorectal cancer I would probably just go with it even without PMI. The big advantage is that is available as a supplement online.
      Koningic acid is also very interesting but I will not add it for now to the list as it is not accessible.

      Yes J, we learned a lot during these years and on this road we came across both knowledge also also good tools. And I am sure there are out there many more relevant tools left to be uncovered and added to our arsenal. As a next step, I think it’s important to start simplifying things. Even if for some of us the list above is nice and easy, for those new to the field its still too complex. I will do my best to simplify things as we go forward.

      Kind regards,
      Daniel

  16. Today I was thinking about the longstanding fact that erythrocytes rely on glycolisis for energy… And how around the internet some people ask about the effect of glyco inhibitors on them.. Will inhibiting glycolysis produce hemolysis? And I saw this article:
    Reference
    Apparently mature erythrocytes can also metabolize citrate. It would be an interesting addition when thinking of combining strong glyco inhibitors.
    Or what do you guys think?

    1. Hi Yudatheska,
      It is mention above in the blog post citrate in the form of citric acid inhibits glycolysis by inhibiting hexokinase, and can be used to shut down glycolysis in RBCs to preserve them, but citrate in a non-acid form, as you point out may be used as fuel for RBCs. Apparently, RBCs contain some cytosolic forms of kreb cycle enzymes that allow this to happen, but how often it happens in vivo is not clear: https://www.frontiersin.org/articles/10.3389/fmed.2017.00175/full.
      Is your thought that adding citrate to strong glyco-inhibitors would protect RBCs? It is an interesting concept if I am interpreting your question correctly. My understanding is that since RBCs have a much slower metabolism than cancer cells and since glycolysis inhibition is not a complete inhibition, they are not impacted enough for hemolysis. If anyone has seen hemolysis result from glycolysis inhibition, I would be interested to know.

  17. Daniel: Thanks for the great compilation. This is a very comprehensive list of inhibitors that can fight cancer.

    Since Loratadine is an MCT1 and MCT4 inhibitor, would it not make a combination with Metformin,
    like Syrosingopine and Metformin?
    Syrosingopine is hard to procure, and expensive. Loratadine is easily available as a tablet.

    I tried looking up the effectiveness of Loratadine as an MCT1 and 4 inhibitor, but could not find many articles. None comparing performance against syrosingopine.

    Regards,
    Prashant

    1. Hi Prashant,

      I discussed shortly Loratadine here https://www.cancertreatmentsresearch.com/community/metabolic-inhibitors/combo-metformin-and-syrosingopine-looks-awesome/paged/3/#post-1418
      Atorvastatine could be another option that has been suggested to induce lactic acid accumulation. See my comments at the link above where I addressed Loratadine.
      Please check this thread https://www.cancertreatmentsresearch.com/community/metabolic-inhibitors/combo-metformin-and-syrosingopine-looks-awesome/

      Kind regards,
      Daniel

      Kind regards,
      Daniel

  18. Hi Daniel et. al.,

    This has been the most useful site I have found overall for taking cancer therapy into one’s own hands. Thank you! (My friend has the cancer.)

    I have questions about maitake and am not sure where else to post this, so here goes. I followed a link somewhere on this site to a MaitakeGold 404 plus shiitake powder research that showed synergy between these two. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202470/

    Then I was frustrated when comparing products that contain MaitakeGold 404. Like so many supplements, they contain varying amounts and have different recommendations for dosages, and of course they can’t recommend any dosage to treat any disease. Then I came across an article – by yet another manufacturer, Oriveda – which tells why we can’t trust anyone’s commercial maitake to be strong enough to have a therapeutic effect. The research was done using pure MaitakeGold 404, and nobody sells that. The article sounded reasonable. It concluded by saying that Oriveda’s maitake was stronger than anyone else’s commercial product, but I am still wondering if even theirs is strong enough for a therapeutic effect. To Oriveda’s credit, they publish laboratory analyses of their products on the website: https://oriveda.com/

    Has anyone seriously looked into maitake product quality, strength and dosage? I have heard that Transfer Point’s beta glucans is the “best” brand because it has been used in research. The research claim seemed true if I remember right from 6 months ago… https://transferpoint.com/ (In Canada, buy from https://betaglucancanada.ca/ ) It has not fixed my friend’s immune system, but maybe he was taking too low a dose and maybe he would benefit by adding shiitake to it?

    If maitake extract weren’t so expensive, this would be of less concern; just take a whole bunch…

    (Unfortunately, my friend with squamous-cell oral and now sinus cancer would rather argue with people than experiment on himself very much, until someone gives him THE solution – cures cancer, minimal side effects, not too much work on his part – and now he’s going downhill fast, so if I couldn’t convince him even to go with Care Oncology 6 months ago – they were too slow getting back to him, so he dumped the idea entirely – he’s not going to jump into this website and attack cancer from as many angles as possible. He doesn’t even have the mental or physical stamina to do so anymore. But he wanted me to reorder beta glucans and I thought if I could make it as effective as possible, it just might help, especially if he goes down to Seattle to get low-dose chemo with Dr. Chen. He just might do that.)

    Thanks again, Daniel and all you other kind folks. Your work has helped me find good leads to research and a better overall understanding.

    1. Hi Margaret,

      Thank you so much for your very kind comment. I am glad you find this website helpful. I haven’t look deep enough in Maitake to have an opinion on best brands and most suitable doses, but in general I like these mushrooms due to their impact on immune system, and Coriolus is the one I find most relevant. Other contributors here may have more info on Maitake. If your friend goes for low dose chemo at dr. Chen, it will make sense to consider also the addition of repurpused drugs as well as 2DG metronomic after the low dose chemo. https://www.cancertreatmentsresearch.com/a-new-approach-to-improve-effectiveness-of-cancer-therapies-is-getting-ready-to-begin-human-trials/
      If your friend doesn’t want to do much or he doesn’t have much energy, he can at least consider this option as it is very easy to implement https://www.cancertreatmentsresearch.com/a-silver-bullet-to-kill-cancer/

      Kind regards,
      Daniel

    2. Hi Margeret,
      I believe the mushroom extract with the most research and clinical evidence is one called AHCC, it’s well-known in Japan.
      (Quality of Life Labs, Kinoko Platinum AHCC). It’s for sale on iherb.com. The best way to take (2 to 3 grams) would be 1 hour before breakfast.
      You might want to read -The Ultimate Synergy Against Cancer: Fucoidan and AHCC: Learn about two nutrients that can precisely target and kill cancer cells by modulating the immune system. by Susana Trujillo. It’s an easy read, I think I got it for free on Amazon Kindle Unlimited.
      Best,
      Johan

  19. I used high doses of coriolus versicolor PSP for quite some time. The Oriveda company always seemed to me the one that showed the best quality.

    kind regards

  20. yes, coriolus versicolor(turkey tail) is a wonderful supplement. What dose did you use Manuel?

    Margeret, a less expensive alternative for Maitake from Oriveda, is Fungi Perfecti, they also make high-quality products, and have been studied in a clinical trial(turkey tail).

  21. Should inhibiting MCT1 & MCT 4 using various drugs result in accumulation of lactic acid in blood? Assuming we cannot inhibito all MCT1 and MCT4, the extracellular lactic acid may end up in blood? What would be implications of this? More muscle paint and more acidic TME?

    1. MCT4 is in general responsible for the export and MCT1 for the import of lactic acid. Inhibiting MCT4 leads to lactic acid accumulation in the cell, inducing intracellular acidification. If that is not inhibited and due to various reasons tumours, or in general cells, produce a lot of lactic acid, that may indeed end up in the blood inducing lactic acidosis https://en.wikipedia.org/wiki/Lactic_acidosis
      Typically, due to the fermentation of tumours there is a lot of lactic acid release which may cause pain in the tumour area and inhibit the activity of the immune cells. Some will be absorbed by other cancer cells via MCT1 and converted into pyruvate and energy, while the one that ends up in the blood may be converted back by the liver, in glucose, leading to increase glucose level in the blood (gluconeogenesis). Is this answering your question?

  22. Yes, it does make sense. But for some reason, we have been seeing increase in lactic acid from 6.5->10.5->12.2 while using atorvastatin.. I am not sure why that would be.

    For the period from 10.5->12.2 we also used diclofenac (4 times a day).

    LDH also increased 323->325->499. We also so liver enzymes go up so I could speculate that LDH are form the dead liver cells, but I thinks this is an optimistic view.

  23. @johan

    Good afternoon,

    I want to add a good sulforaphane amount with the possible radiotherapy that is planned in the armpit.

    I eat brocoli sprouts but I need to find a good one supplement that I can buy from Spain :

    What about these?
    Prostaphane: Active Sulforaphane Supplement*France only.
    Thorne Research Crucera-SGS Supplement

    Thank you

  24. Thank you for the great information.

    I am taking about 15 different natural supplements for low grade prostate cancer. Many of the supplements you mentioned in the article.

    I apologize if you have already answered this question elsewhere, but my question is — how do we determine the right dose for humans? Much of the research is ‘in vitro’ or based on animal tests. When I take the concentration levels used in many of the experiments and convert to an equivalent human dose, I get huge amounts that no one could take. Adding all of the doses for my 15 supplements, I’d be taking hundreds of pills a day, which is not practical.

    Any advice?

    Thank you.
    Dave

    1. HI Dave,

      Thank you for your question. This is a fair question. In order to convert doses used in the lab to doses that can be used in humans, this document may help Reference. With this, you can convert doses used in animals to dose relevant in humans. However, you may still end up with the need for high doses. This is why the best in my view is to use high doses (below the maximum that is know as safe) and hope this will work. One aspect that is known to help is that even if we don’t reach the blood level suggested in the lab to be effective, with many drugs and supplements there is accumulation in specific organs that finally may increase the dose to which the cell is exposed. This has been previously shown to be the case. Nevertheless, this means that often we can not be sure we achieve the required level of a specific substance. This is why we best use cocktails including more drugs and supplements that can also work in synergy and help each other to increase the chance of a positive outcome.

      Kind regards,
      Daniel

  25. @Daniel

    Dear Daniel,

    How much of diclofenac is required to consider that can help with fermentation process? I´m aware with the side effects but it´s for short period in this case …

    Has any of the following NSADID also has this feature (fermentation inhibitor)? Flarin (ibuprofen), celecoxib or Etodoloc?

    Kind regards,

    Inaki

    1. HI Inaki,

      Nice to hear from you. It is an entire science to clarify what is the dose required for a drug to achieve similar levels as in the lab and therefore effectiveness. To estimate that, you need to have a view on the bio-availability that may vary from persons to persons (but an average can be determined on this). What is more difficult to estimate is the drug accumulation in specific organs and tumors, which can depend on many variables, including the cells types, tumor vascularisation, drug profile acidic/basic, tumor pH, etc.

      Since at these point we do not have all these details at hand, what we can do is to select the most promising drugs and supplements with potential to target the desired mechanism, and add several not just one to increase the chance of modulating the specific target. This is why I tried to create lists to address specific mechanisms and not mention only one drug or supplement.

      Therefore, I would use the doses that are known to be safe and possible add another drug/supplement to target the same.

      For the second question, please check the post above. If there are not listed above but still like to have an answer just check in Pubmed. Ibuprofen should act on MCT4 but please check that.

      Kind regards,
      Daniel

      1. @Daniel

        Dear Daniel,

        How much of diclofenac is required to consider that can help with fermentation process? I´m aware with the side effects but it´s for short period in this case …

        Has any of the following NSADID also has this feature (fermentation inhibitor)? Flarin (ibuprofen), celecoxib or Etodoloc?

        Thank you Daniel

        Kind regards,

        Inaki

    1. Melatonin is a very interesting subject. I really need to dive deep into this. To my knowledge doses up to 800 mg/day were used in some clinics around the world. Of course, they would move step by step to such high doses. Mot more typical are around 300 mg/day.

      Kind regards,
      Daniel

  29. Hello Daniel, thank you very much for the many informations.
    I have a important Question: Do I have to pick an Inhibitor for each Fermentation Step ?
    My 18 years old brother has his Sarcoma (MPNST) removed and he finished Chemotherapy before Surgery and now getting Chemo/Radiation after Surgery. I want keep him NED.

    His current Protocol:
    Niclosamid
    Hydroxychloroquine
    Atorvastatin
    Dipyridamole
    DCA
    Metformin
    Modified Citrus Pectin
    Mebendazole
    Tudca (Liver Support)
    Melatonin (on and off)
    Meldonium
    Sulfasalazine
    Diclofenac
    Berberine

    You said that mechanism of DCA is not direct blocking of Fermentation, that’s why I am concerned, I hope you can help me..

    1. Dear Danial,

      Thank you for your question. Fermentation is more challenging to reduce vs. mitochondria activity based on the compounds we currently have available. As a result, I woudl indeed consider the use, at the same time, of about 3 compounds that stand out in inhibiting fermentation.

      DCA is indeed not directly inhibiting fermentation, but instead facilitating the activity of mitochondria and as a result potential decrease of fermentation.

      Looking at your list I see the following with good potential against fermentation: Diclofenac, Atorvastatin, Mebendazole which is already good.

      When focussing on NED, in my view, the following areas should be addressed next to fermentation inhibition:
      – inflammation (e.g. Aspirin, Black Cumin, Boswellia)
      – metastasis (e.g. Cimetidine, Thimoquinone, NAC if possible when no radio or chemo used)
      – immune system (e.g. pro/pre biotics, mushrooms, Vit D, etc.)

      Kind regards,
      Daniel

      1. Hello Daniel, thank you for answering my question. I would like to know if I can use Tetrathiomolybdate in addition to the drugs listed ? Isn’t it the case that the blood supply to the tumor (my brother is ned, therefore blood supply to possible micrometastases) is prevented by TTM and the active ingredients listed then no longer have any effect because they don’t get to the tumor?

        Kind regards, Danial.

  30. Hello Daniel. You state in the article that you “do not see PDK inhibitors as fermentation inhibitors, but as mitochondria activators. Is that why DCA can be taken before chemo infusions? Elsewhere, you state that fermentation inhibitors should not be taken for 3 days before chemo. But is DCA an exception because its pro-oxidant effects outweigh any fermentation-inhibiting effects?

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