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Combo Metformin And Syrosingopine!!!! Looks Awesome!

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John Pizzuto
(@jpizzuto)
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@yudaitheska

Yes, I was pretty sure.  She was crying, saying she won't take the combo if it means diarrhea.  I told her diarrhea is temporary, leaving unsaid, death from cancer is permanent.  She's over that now, ready to fight again.

According to the graphs I posted above, it looks like you could omit metformin if you had to, though it would take more syro.  Have to dig to find the max sryo dose.  I ran across the trade name for it some time ago but never wrote it down.  The earliest reference I've seen is from 1959.


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John Pizzuto
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@jcancom

I did some reading on metformin last night and ran across mitomet as well.

From what I can tell, the anti-gluconeogenesis effect of metformin happens in the gut, while the MCT1 inhibitor effect is related to serum concentration.  I saw reference to a test where they infused metformin...

So, let's invent a metformin pump, like an insulin delivery system.  Bypass the gut, no more diarrhea, higher serum dose. 


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Shanti
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@jpizzuto

Hi John, 

we have found sustained release metformin to solve the intestinal issues for us.

Best,

Shanti


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John Pizzuto
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@shanti

Yes, (thank you) I thought so, but I think I read there is a 20% reduction in serum concentration.  Not an issue for diabetes, but it could be for this application.


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Daniel
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@jpizzuto

Hi John,

1. As Shanti said, sustained release version of Metformin typically solves the diarrhea issue - it did for my wife too

2. However, 500mg Metformin may be still a too low dose 

3. A better option to achieve Mitochondria inhibition may be Atovaquone. Please read this Nature paper https://www.nature.com/articles/ncomms12308 At usual dose, Atovaquone can reach the level required to have anticancer activity. In addition, it has a long half life(2-3 days) - so it stays in the blood for long time. 

4. Atovaquone can be found as a FDA approved drug - sometimes it is also found in combination with Proguanil - they are used together against malaria. Proguanil has activity against breast cancer https://academic.oup.com/ofid/article/6/9/ofz314/5560073
Best is to use the Atovaquone suspension under the brand name Mepron.

5. To go forward, one option I would consider is to keep Syrosingopine, keep 250mg or 500mg Metformin that makes your dear wife comfortable, and add Atovaquone suspension which is administered in humans with food at the standard regimen of 750 mg twice daily https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085139/

Kind regards,
Daniel


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John Pizzuto
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@daniel

"Table 1" ranks Berberine way above Atovaquone (2 vs 15), at concentrations of 10uM each.

Is that achievable with a Berberine capsule or two a day?

Atovaquone affects complex 3 of the electron transport chain.  I didn't see a reference that it inhibits NAD+.

Metformin affects complex 1:

"NAD+ is reduced to NADH during glycolysis, and a constant supply of NAD+ is required to sustain a continuous high rate of glycolysis...(snip)The other major route for NAD+ regeneration is via mitochondrial complex I, the target of metformin. "

In the paper, 4mM concentration of metformin is mentioned in a few places.  I think this requires more than 500mg/day.  Trying to work that out.

The paper also mentions a range of serum concentration levels of syro they tested with.  Will try to decipher that as well.  StevenK, my penpal in Thailand, is getting results with 4mgs syro twice a day, plus 1g metformin (extended release) twice a day.


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John Pizzuto
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4mM is about 1000 times a normal serum value.

This page states in vitro concentrations require mM rather than uM levels:

https://www.omicsonline.org/open-access/metformin-a-case-study-in-the-meaning-of-serum-concentrations-2329-9053.1000e111.php?aid=25819

From the article:

"A primary question for any drug is the value of its serum concentration. What is not commonly considered is the relationship between this value and the drug concentration at the physiological target site. In the case of metformin, the issue is in some ways simple: metformin is water soluble and has negligible binding to serum proteins. It is not converted to other compounds, but excreted unchanged by the kidney [1]. Yet, the volume of distribution is very high: above 500 l. This is because its serum concentration is low (micromolar) and yet the dosing is very high (up to nearly gram amounts)."

And:

"studies on cells in vitro require concentrations of millimolar rather than micromolar [3,4]. Our own proposal for the action of metformin (inhibition of AMP deaminase [4]) has been criticized partly on the basis of using millimolar concentrations rather than its serum concentration [5]. "

Not much help, so just take as much as you can stand, up to the max dose of 35mg/kg.  In my wife's case, that would be 2g, vs the 500mg she is now taking.

My reading taught that it settles in the gut, causing distress.  But that's not where it's needed to work with syro.  It needs to get to the cancer cells, by way of the blood.  How about a pump that injects it, like an insulin pump? 


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Daniel
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@jpizzuto

Dear John,

There are scientists arguing that Metformin can get in high amounts at the tumor side (at least via tissue accumulation) and others suggesting that is not enough. However, there are a lot of studies demonstrating anti cancer effects in humans next to the huge amount of scientific research suggesting the same. Based on all the research it has been concluded that 1g to 2g/day it's enough to contribute.

In general, my point is that we should pick some of the best (such as Metformin) but not rely completely on that to do the job. This is why I often suggest to use at least two drugs to target the same mechanism. So, I would stop studying Metformin, take as much as possible (max 1-2g/day) while making sure your wife feels well with it and select another one to target the same (in this case mitochondria). If your wife is not feeling well with Metformin you can select other mitochondria inhibitors - I published a list of those earlier. There are several such inhibitors that are as promising as Metformin, and should go well with Syrosingopine.

So I like your conclusion: "just take as much as you can stand up to .." and move on to improve the strategy in order to increase the chance for effectivness.

As a support, I would also add the natural extracts such as Berberine expected to have similar action as Metformin - but this may also upset the stomach.

Kind regards,

Daniel


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John Pizzuto
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@daniel

Atovaquone inhibits complex 3 in the ETC, which is good, but is not related to the action of syro/metformin.  I will look into getting some.  I assume it's available from the source you earlier linked?

The syro/metformin combination blocks the flow of lactate out of the cell, through the MCT1 and MCT4 transporters in the cytosol.  Syrosingopine blocks MCT1 by some amount "n" and MCT4 by 60 x "n".  Metformin further blocks  the transporter MCT1, and inhibits NAD+ in complex 1 of the ETC in the mitochondria.

Depending on the release profile of your metformin, highest concentration is reached in about two hours if quick release, or eight hours if extended release.  I want to find out how long it takes for syro to reach the highest concentration.  It makes sense to time the medications so the highest concentrations are reached at the same time.


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Daniel
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@jpizzuto

Dear John,

Although Atovaquone blocks mitochondria complex III, the outcome is expected to be the same as Metformin, i.e. inhibition of respiration. Doxycicline also inhibits respiration, via yet another mechanism https://www.cancertreatmentsresearch.com/a-list-of-mitochondria-inhibitors/

Therefore, regardless if we use Syrosingopine + Metformin, or Syrosingopine_Atovaquone or Syrosingopine+Doxycicline, I would expect similar results, assuming all reach the tumor in a high enough dose required for action. 

Syro + Met (or Ato, etc.) will also acidify the cells - this is why was previously suggested the benefit of adding e.g. Amiloride and/or Acetozolamide  - this will acidify the tumors even more.

If you find information on Syrosingopine's pharmacokinetics (such as elimination half-life) please let em know.

Kind regards,
Daniel

 


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John Pizzuto
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@daniel

Syro doesn't work on the mitochondria.  It blocks MCT1 and MCT4, the lactate transporters of the cytosol.  Metformin helps syro block MCT1, and prevents recycling of NAD+ from complex1.

I agree, we should use as many things as we can, but to be clear, ATO and doxy don't help syro block MCT1.  Syro blocks both transporters, but weakly on MCT1, AND it potentiates the effect of metformin on MCT1.

I checked the side effects of ATO.  aarrrghhh.  More diarrhea and nausea.

 


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Jcancom
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ATO is a great find. Always great to have another potent OXPHOS on the shelf. It also started me thinking immediately about mito-Q, as Co-Q10 relates to OXPHOS subumit IV. Interestingly, the below pdf (pdf page 51) mentions that Mito-Q has selective cytotoxicity against breast cancer.

"MitoQ was shown to inhibit proliferation of breast cancer cells but not nontumorigenic cells, with concomitant induction of autophagy, cellular oxidants, and activation of the oxidant-sensitive Nrf2 antioxidant transcription factor."

Also pdf page 65: " ... The inhibition of OCR persisted even up to 60 h after washout of Mito-CP or MitoQ in MCF-7 but not in MCF-10A cells (Figure 21)."

 Earlier pages speak of combining with 2-DG and rhodamine.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611849/pdf/nihms894690.pdf

Considering that Mito-Q is an off-the-shelf product that is not overly expensive, it might be well worth considering it. mito drugs are a21st Century product with extreme levels of precise accumulation in mitochondria. "inhibit proliferation of breast cancer cells but not nontumorigenic cells" Further, a 60 hour window of inhibiting OCR opens up a range of possibilities. Basically with OXPHOS off-line, the potential to then use an anti-glycolytic is almost too good to miss.   

This is very exciting that we have restarted deliberations on dual metabolic inhibition. We know how powerful this can be, though working through all the combinations eventually has worn us down in the past.

 


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John Pizzuto
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@daniel

This page has some info from 1959, but you have to pay or be a member to read the full article:

https://www.nejm.org/doi/full/10.1056/NEJM195910152611603


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Daniel
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@jpizzuto

Dear John,

My last comment was probably to short and not clear.

1. I agree Syro is a MCT1 and more importantly here MCT4 inhibitor according to this paper https://www.cell.com/cell-reports/pdf/S2211-1247(18)31806-0.pdf More MCT inhibitors have been discussed recently in this post https://www.cancertreatmentsresearch.com/drugs-and-supplements-that-block-fermentation-and-help-fight-cancer/

2. The great point about combo of Metformin and Syro is that:
- Metformin inhibits respiration via mito complex I inhibition. Usually, mitochondria inhibition leads to an increase in fermentation, and as a result excess lactate production.
- Syro inhibits MCTs and so lactate cannot be exported (or at much lower amounts).
The result of this is the increase of acididity inside the cancer cell (that is Cytosolic acidification). As a result of the increase acidity inside the cell, one of the major enzyme that will be inhibited is PFK1. This is an important enzyme in the fermentation process.

Therefore, the result of combining the two drugs is ATP depletion and potential tumor death. 

My point before was that I like this idea, but in order to increase the chance of effectiveness in humans of this approach I would:

- add one more mithocondria inhibitor such as ATO, more are discussed here https://www.cancertreatmentsresearch.com/a-list-of-mitochondria-inhibitors/

- add one more glyco inhibitors, more are discussed here https://www.cancertreatmentsresearch.com/drugs-and-supplements-that-block-fermentation-and-help-fight-cancer/

- add more cell acidifyiers, more are discussed here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/

This is why I wrote the following idea to you sometime ago https://www.cancertreatmentsresearch.com/community/metabolic-inhibitors/combo-metformin-and-syrosingopine-looks-awesome/paged/3/#post-1368

I enclosed the 1959 paper you mentioned above, in case you like to read it.

Kind regards,
Daniel


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John Pizzuto
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@daniel

Thank you very much for that paper.  3mg per day is the highest dose they used.  I have been using close to 3mg twice a day.

I didn't measure my wife's blood pressure this morning, but it's usually 123/68 or so.  One hour after administering 2.8mg syro, it was 114/68.  After two hours it was 99/63.  I'll update with readings every hour.


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John Pizzuto
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Daniel:

Hour three, 114/64, so 2.8mg every 12 hours appears to be a safe dose for her.  I will have to adjust if she keeps losing weight.

I just ordered a two months supply of loratadine and doxycycline from Buy Pharma.  I will study your references for more, but wanted to get something in the pipeline right away.  I have mebendazole on the way from another source.  I notice niclosamide is a similar drug, but not available from BP.


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Daniel
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@jpizzuto

John, I was checking last night for a study on Syrosingopine in humans that would show the half life and max concentration in blood but could not find any yet. When I find time, I will contact the author of the paper syngo+metformin - he may know. 

Regarding Loratadine, I will make things complicated and than simple again:

I checked Loratadine: The half life for Loratadine is about 8h which is good but the max level in the blood is only 26ng/mL https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/j.1552-4604.1987.tb03090.x that converts in about 68nM. This is much lower, compared to the 61uM found to inhibit MCT4 https://www.ncbi.nlm.nih.gov/pubmed/29521223

Atorvastatin has a similar profile in terms of reachable plasma level vs concentration required to inhibit MCTs.

However, according to recent studies it seems that statins, induce muscle pain as a result of lactic acid accumulation due to the MCTs inhibition. This pain increases during heavy exercise which further support the fact that this effect is due to lactic acid accumulation. Here is a PhD thesis discussing this subject https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/21823/Leung_Yat_Hei_2017_these.pdf?sequence=2&isAllowed=y

Therefore, as in case of e.g. Metformin (which has been found effective against cancer in patients although estimations suggests the blood level would be too low to do that), comparing blood concentrations of drugs vs concentration required to act on certain targets is not enough. Accumulation of drugs in various organs seems to be essential and that is more difficult to estimate.

As a result, making things simple again, although at a first look normal dose of Loratadine may seem too low to achieve MCT inhibition, there is still a chance that will happen. The chance is higher when combined with other MCT inhibitors such as Syrosingopine.

Again, I expect this protocol will work even better when combined with well known inhibitors of "acidity exporters" Amiloride and Acetozolamide (but Amiloride would require checking potassium blood level every two weeks to make sure it stays in the safe range).

Regarding your other point, Niclosmaide acts against cancer via a different mechanism compared to Mebendazole. Niclosamide can be found here http://smartproduct4u.com

Kind regards,
Daniel

 

 

 


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Daniel
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@jcancom

Nice to hear you like it J. My next post will be on dual inhibition. That is very powerful. If we do that well we do not need anymore glutamine inhibitors and autophagy inhibitors, etc.


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John Pizzuto
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@daniel

Shirley had some diarrhea about five hours into her last dose, so she asked me to cut back a bit on the syro, as the metformin was only 250mg.  I'll reduce it to 2.2 or so this evening.

Thanks for the link to the drugstore.  🙂

I'll do more studying on your further comments.


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Jcancom
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Topic starter  

JohnnyP, thank you for staying on track with the syro met combo. Often some on thread tend to go far off topic at times (especially me).

The figure that I have added from one of the syro met articles is what originally excited me about the combo. The figure shows that NADH/NAD+ recycling is cut off at OXPHOS by met and at MCT1/4 and downstream at LDHA by syro. One of these articles noted that the combo, in fact, results in complete loss of NAD+ recyclying. This is a very striking claim; cancer would not remain viable for long without such ability. This combo offers a great opportunity to observe a set of interrelated features of cancer (viz., NADH/NAD+ cycle, ATP/ADP, pHi/pHe, glycolysis/OXPHOS, ROS,  MCT1/4, lactate/electron flow) respond to treatment. Quantifying these changes has increased my understanding of these processes and helped to reveal to me cancer's vulnerabilities.

 D has noted that a great number of enhancers and/or modifications could be made to the basic treatment. When starting out though, one might give it a week pro forma and then note any changes on biomarkers. As your confidence increases you might then include some modifications.

This is one of the more powerful anti-cancer treatments that we have found. D's ole banana in the tailpipe picture (while admittedly in the category of Schadenfreude) graphically suggests the power of this idea. Plugging up the MCTs and pickling the inside of the cancer cells has clear intuitive appeal. One of the articles shows how lactate levels increase for hours after treatment. Clearly it offers great potential, though it would be wise not to attempt to turbo charge it so much that the risk of TLS might emerge. Cancer clinics appear to be satisfied when they can generate a sustained somewhat moderate response instead of the more dangerous instant metabolic collapse of a tumor mass.

{D might yo be able to extract the figure from my attached file and post the figure to this thread? I think having it visible to all on the thread in stead of locked away in an attached file would be helpful. I would have provided a url for this purpose, though I was unable to locate such a url. Thank you.} 

Best Wishes, J 


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Jcancom
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Topic starter  


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Jcancom
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No worries, D. I found the url.

This is great! The figure above dramatically shows what the syro met combo is doing. It is very powerful.

#1. Shut off OXPHOS at omplex 1 with met and thus stop mitochondrial NADH--> NAD+ recycling.                  

#2. Shut down MCT1/4 lactate efflux and then downstream shutdown LDH activity and thereby stop NADH--> NAD+ recycling.

Considering that glycolysis can spin upwards of 20 faster in cancer cells, this could have substantial differential effects on tumor versus normal cells.

It would help if we had a better idea of the pharma of syro and metformin. I am wondering whether methylglyoxal might be a better OXPHOS complex 1 inhibitor. MG is selective and there is an entire protocol all worked out for it. It also draws down GSH which might also suggest that metronomic MG lead in might be a reasonable add on.


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GgE
 GgE
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@jpizzuto

1. I know infinitely less about cancer than Daniel, John and most of the regular collaborators in this site. But I have seen one cancer patient unnecessarily lose an organ from the addition of a treatment ingredient that was added just to make the regimen stronger and know how badly this loss has limited this person’s options regarding future treatments. It is in this spirit that I suggest, with all due respects that the traditional “if it ain’t broken don’t fix it” might be a safe way to start.

StevenK had mesothelioma, a totally incurable type of cancer as far as I understand. If the regimen he is following is working and safe, I would try it for a while without any changes.

Adding other drugs to this regimen is entering uncharted territory. It is theoretically advantageous but there are no info sources about the potential negative consequences from these additions. Nobody knows how some of these drugs interact inside the body; whether their combinations may seriously damage the liver or kidneys, cause a patient to need an organ transplant or permanent dialysis; and/or if they may preclude future treatments or being admitted to clinical trials.

If StevenK’s regimen proves not to work after trying it for a few months (not weeks), or one is completely unable to follow it, then I might give some thought to whether taking the extra risk is the best (and may be the only) course of action at that time.

Also, I would try to dose the patient with the same mg per kg StevenK uses. He may be a much taller or heavier person than the patient you are trying to help and this may be causing too many side effects. In any case, I would start on the low side and go up gradually monitoring for side effects before they become too severe.

2. If changing StevenK’s protocol is desired, the closest way to improve upon his regimen without deviating substantially from the original study is using Phenformin, another drug that worked very well in the study. The study proved that Phenformin, an anti-diabetic drug that was used by millions for decades (before metformin I think) with minimum side effects, works much better to kill cancer cells than metformin and in much smaller amounts (in the order of 25 mg a day versus 1000 to 2000 mg of metformin if I remember it correctly).

However, Phenformin is hard to find (it is sold as a powder for about $30 a gram for research purposes) and if you use it, you need to make sure the patient’s kidneys are working well; that he is constantly well hydrated; and monitor several other factors to avoid a minor risk of lactic acidosis. Phenformin is being resurrected and studied now and I think it will make a major comeback as an anti-cancer agent soon. Similar story to syrosingopine. (Daniel, you may consider adding Phenformin to your Mitochondria Inhibitors list, even though it is not obtainable as a pharmaceutical product.)

3. In regards to choosing Metformin (Glucophage) instant release vs extended or sustained release, the package insert reads that its “Peak plasma levels are approximately 20% lower compared to the same dose of GLUCOPHAGE, however, the extent of absorption (as measured by AUC) is similar to GLUCOPHAGE.” I think that what counts most in this case is the area under the curve rather than the peak value. I believe that having a continuous, medium-high level of metformin and syrosingopine in the tissues (rather than in serum or plasma) is most efficient because in my opinion, the syro+metformin war on cancer cells is a war of attrition and it is fought in the tumor tissues, not in the blood or the serum (unless you are fighting a hematologic cancer rather than a solid one.)

If you have high peaks and valleys the cancer cells will use the valleys to recover (i.e. de-acidify and re-energize themselves) and be ready to resist the next peak. Do you imagine an army surrounding a medieval city during the day, then going away at night? The city dwellers would undoubtedly go out at night to restock water, food, weapons, and everything they needed. This strategy would render the siege useless. The army would tire much sooner than the city dwellers and leave.

With 24/7 continuous medium-high concentration levels of both drugs in the system rather than peaks, the cancer cells have no break from the siege and should eventually succumb, as seems to be the case with StevenK.

If having high peaks of metformin were more important than the AUC then you would have to time the metformin pill intake in such a way that its peak occurred in sync with the peak of syrosingopine. I don’t think this would be practical, given the lack of pharmacodynamics and pharmacokinetics info available on syrosingopine.

4. In regards to skipping the metformin and taking syrosingopine alone but in higher doses, the study says that syro’s anticancer effect is very limited, just as is the effectiveness of metformin alone at doses humans can tolerate. I would not go that route because you may be desensitizing the cancer cells to syro by natural selection and when you finally conclude that this monotherapy doesn’t work, you might have closed the door to using it with metformin also.

In summary, although I am all in favor of learning all the possible drugs I could add or replace in the syro+metformin protocol, just in case it fails, I would not try to reinvent the wheel (or add new drugs) until I knew for sure that the "wheel" invented at Basel doesn’t work.

And I think it will work for most of us. Sorry for this uber-long comment.


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John Pizzuto
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@gge

Thank you so much for your thoughts.

An email from Steve last week:

"Your dose sounds about right to me  try to get the metformin when you get more on slow release. Body takes it better, like sipping on something slowely all day not taking it one wallop. If not maybe 3 times daily with the met. try totaly daily met up to 1000 mg

I am on 2000 mg daily  JARDIANCE DUO   But that,s now for cancer and blood sugar looks like I got some diabetes from the chemo killed off some pancras cells producing insulin.   My weight now 70 Kg."
 
In an earlier email, he said he is taking 4mg twice a day.  He was using a $16 scale with 1mg resolution, then it broke after two weeks, so he is guessing.  If accurate, that would work out to a 3.2mg dose for my wife's weight.  I started at 2.9mg twice a day, but her blood pressure dipped to 99/63 after two hours, so I cut it back to 2.2mg, twice a day.  And all she can tolerate is 250mg metformin twice a day.  That's why I feel I need to do more.

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Daniel
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@gge

Dear gge,

I read your comment, and I find the points you addressed very relevant - I know they were addressed to John but since it is related to this thread I would like to add a few comments:

(although I have also 4 points below, the numbers below are not directly related to your numbers)

1. I totally agree that we need to be very very careful and move step by step with both the dose and the drugs we are using - hopefully that would happen with the support of a medical doctor.

2. While we all hope that the Basel idea will work, by working on identifying ways to further improve that idea we do not reinvent the wheel but we create options to make that concept stronger in case it's not strong enough (in general or for specific patients/cancers). Similar approaches but using different drugs have been discussed in academic space for many years now. But Basel did not stop there - they moved forward and came up with this idea. Innovation has to move forward, specifically in oncology space. We here have a stronger motivation to innovate compared to the academic space, and in line with our motivation we need to move even faster in terms of creating options.

3. Every patient is different: some may cope with some drugs others not; some may be in a very difficult situation regarding various organs, others not; some may deal with very aggressive cancers others with more manageable cancers (such as those of breast or prostate). Only the patients, care giver and their doctor can decide what makes sense to do for the specific situation - some may need to take higher risks and move faster others may have the time to wait and see. Therefore, in principle, your thought on wait and see what happens with those implementing Basel concept is fair, but regardless of the outcome, it will still be difficult to conclude if something worked or now as long as there is no clinical trial. Life extension will typically not be recognised when looking at a few patients only. Also, in my experience, the reality is that when cancer is in advanced phase (which is the case not for all but for most of the people visiting this website) stronger combinations have to be employed to see important and conclusive results.

4. Speaking about possible organ failure - here were are speaking mainly about supplements and FDA approved drugs - the safety profile of those and the interaction with other drugs is relatively well known - such risks are much higher when it comes to typical treatments for cancers, including immunotherapies and chemo.

I find this discussion very relevant and I think just with a few messages will be difficult to align our thoughts, since our views and believes here are relative to the reference points we have in our life. But at least we shared a little of our views here.

I was always the adept of small steps and no mistake. And I am still the adept of that. But after all these years, I concluded that regardless of the cancer type, when it comes to aggressive/advanced cancers, in general, wait and see doesn't work. Instead, we need to be informed, have positive expectations, think beyond, take small steps when the territory is uncharted but move.

I hope this makes sense to you. 

Kind regards,
Daniel

 


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GgE
 GgE
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@jpizzuto

You say Steve's dosage translates to 3.2mg for your wife. Is this 3.2mg a day or twice a day? If she is petite or very thin, then 3.2 mg a day might be enough. If so, 1.6 mg 2 times a day or even 1.1 mg 3 times a day might be enough. This should cause less severe drops in her blood pressure and as a result she might feel less drowsy, her guts might be more active and she might better process and tolerate the metformin. Just a suggestion for your consideration.


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John Pizzuto
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@gge

Steve weighs 70kg, and takes 4mg twice a day.  My wife is 57kg, so a similar dose would be 3.2mg twice a day. 

I posted a short video of my scales and process:  https://www.youtube.com/watch?v=GSNe0VTJ3Mk


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GgE
 GgE
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Posts: 240
 

@daniel

You are correct, Daniel. My comments addressed JPizzuto’s case specifically, not cases that are more aggressive, more advanced, or which have no chance of responding to StevenK’s protocol. Sorry if I didn’t make it clear. As you state, oftentimes these other cases cannot afford to wait for long.

Our discussions and thoughts regarding Johnny’s case come from the concerns we all share for them and our desire to help them succeed.

I think we all agree that once you choose a treatment because you believe it has a good chance to succeed, that it is a good thing to follow it cautiously before changing it or adding things might mess it up.

Also, one has to keep in mind that the circulatory system and organs of someone bedridden for 18 months may be weaker and more prone to serious reactions than healthy people's. Her gut motility and overall metabolism may be sluggish and so she may react in different ways than healthy people would. This calls out for extra precautions.

Your comments always make a lot of sense, and so did this time as well. Your web site is a priceless incubator of great ideas which can help millions of cancer patients all over the world, each one with their own set of health problems, now and in the foreseeable future. I have followed it for about a year and I learn something new about fighting cancer every time I visit it.

The brilliant collaborators in this forum brain storm with each other on a daily basis and produce promising strategies that advance cancer knowledge for the rest of us. I consider it to be at par with many cancer research centers. Except that unlike most of them, you guys share your ideas with the rest of us. For this we all are thankful. I hope that you guys continue your good work until cancer is a thing of the past.


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NA
 NA
(@j)
Joined: 3 years ago
Posts: 531
 

@gge

Indeed, and it probably can't be said enough: above all, do no harm. Even with supplements, always be careful.

Very interesting thread!

 


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Jcancom
(@jcancom)
Joined: 4 years ago
Posts: 535
Topic starter  

41 of 56 patients received 6-12 mg per day of syro (average 9.2) {Unfortunately they were not clear about how long treatment lasted nor the daily schedule for the dosing.} While 43% of the patients developed side effects, these side effects largely consisted sedation, nasal congestion and nervousness.

https://www.ncbi.nlm.nih.gov/pubmed/?term=14408654

Syrosingopine appears to be a well-tolerated treatment, and considering that hypertension needs to be continuously managed, syrosingopine has been tested in the context of metronomic dosing (which is of particular importance in cancer) and found to be safe for this purpose.   

 

 

 

 

 


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