Hi J, indeed its very interesting and this is why some weeks ago I added the above reference on Syrosingopine to the pH strategy https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ since the mechanism behind anti-cancer action may also be the acidification of the cytosol (both Syro and Met are known cell acidifies). Anyway, Syro is a good one to keep in mind and add on our list of metabolic inhibitors.

Sorry D, I just noticed that you posted this one. I think it is a good idea, though perhaps that we bring this one out more visibly.

In the past some of the truly amazing ideas on our forum and elsewhere get completely lost. I felt badly when I saw my old post from April 13, 2017 on the vitamin C thread and realized that it took us over a year to get this to out to help our friends on the forum. From there it took most of us a few more months to realize what we had stumbled upon.

Turning an idea into a clinically applied treatment in less than 2 years is actually very impressive, though  we should do what we can do to make the turn as short as is possible.

The metformin-syrosingopine combo might be a good example where the above lesson could be applied. "Complete loss of the cell's NAD+ recycling capacity"? Are they kidding? A cancer cell could not survive very long without NAD+ recycling!! This is one of its main weaknesses: namely, it is in an overctive-glycolytic state of roughly 20 times normal cells.  Possibly this crisis could be amplified by going to peroxisomal beta-oxidation where large amounts of NADH is generated. If this could be trapped as NADH, the recycling might even be worse.   

"combined metformin-syrosingopine treatment results in complete loss of the cell’s NAD+ recycling capacity. The depletion of NAD+ in turn leads to cell death, as the cancer cells are no longer able to produce sufficient energy."

Perhaps by communicating in a more direct and colorful manner others on the forum can recognzie how important this latest Metformin-Syrosingopine research likely is.

Hi J, there is no point for saying sorry. You are doing a great job uncovering valuable pieces of research. I think it is good you highlighted this one and it makes me think that before we create a new post on metabolic and more specific glyco inhibitors, I can create a topic on the Forum where we add all our findings like this. After that, we consolidate them into a post on the main page.

I will create now a new topic (Metabolic Inhibitors) and will move this post under that.

Btw, this combo of Syro + Met is a similar idea like Vit C + Doxycicline combo that was published a few years ago.

Thanks for pointing out the metformin doxycycline connection! Yes, I am beginning to integrate more and more of these linkages, so that the various protocols start to consolidate into a broadly metabolic treatment approach. When you perceive these linkages you realize how much more difficult it is to challenge the foundational concept. Some might question the research evidence for 3-BP, as there are only 2 published patient reports. Yet, then there is vitamin C which has decades of evidence supporting it, and citrate, and ketogenic diet ... . There is simply too much supporting research to make far-reaching denials of the efficacy of the metabolic strategy.

Here's another great one. It has been known for a long time that removing the primary often merely seems to encourage the development of secondaries. Metastasis is to a large extent the central problem of cancer. Apparently, meta-tyrosine is a chemical that the body uses to suppress metastasis!

http://www.medicinabuenosaires.com/PMID/25637892.pdf

This combo has an incredible potential,but apart from the study that supports, the procedure we should also try to discover where syrosyngopin can be obtained for example because it is discontinued in many countries,I at least I have not found it

Yes, marcos the only reasonable suppliers that I see are Chinese. Resperine is very chemically similar to Syrosingopine. The articles mentioned this connection, though they did not seem to discuss how effective resperine might be in the place of it.

Intresting connection of Syrosingopine with an alternative cancer treatment:

Syrosingopine is derived from Reserpine.

(It is known that Syrosingopine (Singoserp) is pharmacologically and therapeutically similar to Reserpine.  Therefore, there is a very good chance that Reserpine has similar anticancer effects.)

Reserpine is extracted e.g. from Rauwolfia Vomitoria plant  http://www.indo-world.com/reserpine/reserpine.htm

Rauwolfia vomitoria extract is an alternative cancer treatment, marketed and available online as Rovol V  https://www.beljanski.org/engl/mirko-beljanski-extracts/rauwolfia-vomitoria/
However, the plant extract is not containing Reserpine, but Alstonine which seems to be the main anticancer ingredient in the Rovol V product. 

Reserpine has been removed due to side effects from the extract above. However note that Reserpine is a drug that is used for the treatment of high blood pressure, so the side effects should be manageable.

Because the chemical structure of Alstonine and Reserpine is somewhat similar to that o Syrosingopine, we could speculate there is a chance that both Reserpine and Alstonine will inhibit the MCT transporters as Syrosingopine did in the study cited by J.

Btw, the plant also contains type II topoisomerase inhibitors such as Serpentine.  Chemotherapeutic agent Doxorubicin is such an inhibitor.

This appears to be a more than 2,000 year old ethno-medicine. Perhaps simply start with the traditional dosing and then go from there.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196640/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898180/

Yes, J. We now use science of the last 10-20 years to explain effectiveness of traditional medicine coming since >1000-2000 years ago. There are so many examples of recent science explaining the effectiveness of folk medicine that makes me conclude that any solution used by more than 1000 years, can be effective at least in some cases. I am thinking to coin this "the rule of 1000 years".  ? 

D, have you been able to work through the dosing of syrosingopine? The 2016 article used 5 micromol Syro. From what I can tell human dosing with Syro was on the scale of 3-4 mg in humans. What does this give us in human pharmacokinetic molarity?  If metformin is only being used to inhibit NADH subunit 1, then moving to MG might be a reasonable substitute.

Good question J. I will have a look tomorrow. Now I go to sleep as it is 3:39 am on my side. I just finished the article I published a few minutes ago. Let me know what you think about it. Please have a look at the included case reports in humans as they are impressive.

Bonjour.

Je suis intéressée par la combinaison Metformine-Syrosingopine. Maman a un leiomyosarcome au stade terminal et je voulais essayer cette thérapie alternative.

Je me suis procurée de la syrosingopine (sous forme de poudre) mais je ne sais pas le protocole à suivre pour le dosage.

Avez-vous une idée ? 

Je serai très reconnaissante 

Dear Hanen,

I did a quick reserach for you, and based on the references cited below, the dose that seems to be suitable/day is between 1mg to 3mg/day. People are taking the powder under the tongue to increase absorption. Also there is a pharmacy in Switzerland that seems to make the capsules on request.

I would start with the lower dose first (1mg/day). Please note that Syrosingopine is a drug used to treat hypertension, so make sure your mom has a heart condition that can deal with anti hypertensive drugs.

I hope this helps. Please share with us your findings if you decide to go forward with this treatment approach.

Kind regards,
Daniel

References:

In group 3 the dosage used (3 mg. of syrosingopine per day) maintained the desired antihypertensive effect without nightmares, nasal congestion, or other significant side-effects.
Reference: https://jamanetwork.com/journals/jama/article-abstract/325703

After the initial control measurements were performed, syrosingopine was administered intramuscularly every six hours over a seven-day period. The amount, usually limited by postural hypotension or other symptoms related to the drug's administration, ranged from 1.5 to 6 mg./day and averaged 4.S mg./day. The total dose varied between 0.3 and 0.9 mg./Kg. and averaged 0.6 mg./Kg.
Reference: https://www.ahajournals.org/doi/pdf/10.1161/01.RES.9.5.989

I found this on another website, taht is very helpfull:

"I have contact with Dr.Ben Benjamin for his study about Metformin and Syrosingopine.1mg Syrosingopine dayly ist enough combined with Metformin 2x 800 mg to help killing the stammcells of cancer.Syrosingopine you can order in Switserland :1000 capsules from 1mg cost 5000,- Euro.I hoop i can help you a Little bit.No guarantee that will help humans cancer!!!But sometimes is no other way.Greetings from Germany.Volksapotheke Schaffhausen ,Switzerland"
"you can get it in Switzerland on the Volksapotheke in Schaffhausen.1000 Tablets of capsules kost 5000,-Euro.Give a call and the will produceed for you!!"

Reference: https://healthunlocked.com/advanced-prostate-cancer/posts/139563286/antihypertensive-drug-syrosingopine-enhances-metformins-anti-cancer-efficacy.

One man taking it "3mg syrosingopine powder under the tong to dissolve"/day
Reference: https://www.inspire.com/groups/american-lung-association-lung-cancer-survivors/discussion/syrosingopine-and-metaformin-kills-cancer-any-body-try/?page=2#replies

D, there is a wave of new posters on the forum! We are so blessed! We were out in the wilderness for years and years. Nothing seemed to help that much... and then all of a sudden we turned a corner and now positives are popping up all everywhere and we seem to be seeing successes. I am grateful that we are offerring suggestions to our friends on forum that truly appear to be helping them. We appear to have entered into a positive feedback cycle, in which success produces yet more success!

I am also glad to see that posters are digging into back posts on the forum (for example syrosingopine)! With metabolic medicine we still do not have an easy off the shelf recipe; it is still important that there are explorers on the frontier, though on the frontier there are dangers that we need to be mindful of.    

Wahoo! If we could take this syrosingopine into a chitosan formulation that could be a turbo-charger. I am generally quite concerned when we change things up with combinations because even when things look fine on paper you can never be sure that something unpleasant might pop up. Chitosan gives you a targeting mechanism that can let you down dose and increase safety and increase efficacy all at the same time.

The patenese is so convoluted in the below url that I have no idea what they are trying to say, though chitosan and syrosingopine did make it onto the same page. I start I suppose. 

It would be such a help if regulators could at some level acknowledge that formulating with chitosan should typically be understood to be GRAS. 

https://patents.google.com/patent/WO2003030818A2/en

(Thank you for the Like Johan. Like you back!

It was tough on the threads and on the forum for quite a few years. Whenever we lost a friend, it was difficult for everyone. I was not sure whether I was making a positive contribution. Yet, together we made it through. We are seeing patient after patient that it is reasonable to suggest have benefited from metabolic strategies. Now there are all these new explorers on forum who can see value in what we have done and are going to search out new discoveries. With metabolic treatment there are so many combinations to try. When we hit the right combo, the entire puzzle could unlock. But you don't know what the combo is until you give it a try.

It is very gratifying to see that our efforts might be help to them.) 

Great contribution J!

I keep working on mitohonokiol. I'm close to getting it. It is possible that by considering it well access other formulations.
I will expand information.
It may be a good idea to exchange opinions by mail? To have more "privacy" on some sensitive topics ... what do you think about this?

kind regards

Manuone, you made my day!  (Actually my year!)

I know that it can be difficult to make arrangements for synthing (especially when people typically do not have reach into the chemical lab community). However, as you can see (most particularly with mito-HK and others) there can be a very large boost in efficacy and reduction in risk when the proper formulation is adminstered.

I am slightly unsure of the wording you used above, though I believe you said that you might then be able to access other options. Yes! That would certainly be fantastic. There are so many of these formulations that have been written up and hidden away in libraries. Many of them appear to be simpler than mito-HK to synth. Once you get the feel for it, you could open up a great number of possibilities.  

As you noted, it is exciting to see that others on forum have picked up on syrosingopine. Shutting down NADH recycling? Wow! This is a central mechanism of cancer. The entire glycolytic overdrive of cancer is heavily dependent on this process; I am not entirely sure how cancer cells could carry on for long without it.

Gerat thinking about going off thread. I've asked D to help us out on this, so we should be in contact soon.

Wishing you and yours the best, Jcancom   

Manuone, I have been rereading the literature on POH. This sounds great! On the compass thread there is a recent post that talks of bumping up intranasal daily dosing to over 1,000 mg per day ( dose is divided into 4 4 equal doses through the day. Guess this might qualify as metronomic.) Hundreds of patients have been treated in Brazil and also some in the US. According to Right to Try legislation, this treatment could be available now. Given the results, it would be a good one to look into further. Research found that benefit was extended yet more by adding in ketogenic diet. Best Wishes.

What would happen if you add something like quercetin, simvastatin and (local?)hyperthermia in the mix?

Dear Jcancom,

I've become comfortable writing in English and the google translator is sometimes crazy!
Use intranasal poh for over a year and it was not effective. It is also an invasive therapy for my mother's current conditions.
I will update the news about mitohonokiol quickly. If I get a good amount and the price is high, I may look for patients interested in acquiring it.
Now I need to think about an important issue such as the supposed cerebral edema of my mother. She improves rapidly with corticosteroids in doses of 2 to 4 mg but I need to remove them as soon as possible.
Daniel and other contacts suggested DMSO IV ... the problem is that I can not find enough information about its intravenous use. I find some old study but they are restricted access. I have seen that it is not as innocuous as it is spoken and can cause side effects such as hemolysis, nausea, vomiting and elevations of liver values ​​.....
It is true that a dose of 2ml of dmso dissolved in saline solution of 100ml is a very low concentration.
I would appreciate it if you shared with me information about dmso iv especially dose and number of bolus in a week.
I do not know if it would be compatible with the other therapies, you know that I handle a very wide cocktail.
I would appreciate help and information friends

kind regards

Hi Manu,

Regarding DMSO, while waiting for the response of J to your questions, I also like to add the following:

1. It would be good to start another topic with title DMSO
2. DMSO IV is used at Germany clinics several times/week
3. At doses of a few to several ml DMSO/day IV, I haven't heard of any special reaction other than the unpleasant smell from the patient for 12-24h after IV. Some have used even more than 10ml/IV but we never used more than a few to several ml
4. When DMSO was used in combo with Curcumin IV, the dose of Curcumin IV had to be lowered at half the normal dose, as the reaction to Curcumin +DMSO would be very intensive. The conclusion was that DMSO may increase the effectiveness of some drugs. This is why when using DMSO IV I would lower the dose of the drugs used to maybe half, and increase them back towards normal dose step by step. 

Apologizes if there is any repetition, and any of the above statements have been made in my previous comments.

Kind regards,
Daniel

Thank you Daniel for your answer!
I'm less worried about being like that. I hope to handle the situation well and be able to handle the therapy well again.
I am going to introduce lomustine at very low doses on days of 2dg metronomic 30mg / day x 2 days. I will combine it with high doses of DHA that according to one study increases the efficacy of lomustine.
The cocktail looks like this:
- lomustine 30mg + 2dg metronomic + DHA + empty liposomes loaded with 20mg of parthenolide.
- sodium phenylbutyrate 5g
- tamoxifen 60mg
-metformin 1700mg
-doxycycline 200mg
- canagliflozin (far from 2dg)
-simvastatin 20mg
- dca 700mg
-fenfendazole 1g x 3 days
-vitaminad3
- milk thristle 3g
-salinomycin iv
- vitamin c iv
- dmso iv 2-5ml (reducing the amount of drugs)
- mitohonokiol I hope to use it soon.

How is the cocktail?

Thanks for everything!

Hi Manuel,

Have you considered melatonin? 

https://www.researchgate.net/publication/330346531_Melatonin_and_its_anti-glioma_functions_A_comprehensive_review

Amazing cocktail, there's no doubt your mother is alive today b/c of your exceptional care.

Regards

Johan

Melatonin May Increase Anticancer Potential of Pleiotropic Drugs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320927/

"The results from our laboratory showed that MEL has the potential to elevate the anti-cancer effects of statins. "

MEL  anti-inflammatory effects:

https://www.ncbi.nlm.nih.gov/pubmed/29902071

Hi Manuel, 

You are always very welcome! The cocktail looks very good indeed.

We discussed sometime ago the following:

Dear Daniel,

Thank you for your continued help and opinions.
The problem with acetozolamide is its supposed interaction with other drugs and NSAIDs.
I share the list of interactions and I would appreciate your opinion.
https://www.drugs.com/interactions-check.php?interaction_list_id=183194368&drug_list=2145-3709,2092-0,1463-3511,1573-0,940-505,2067-0,3465-0,810-3297,1481- 0.1633-0.1690-1051,1115-0,560-284,894-0,1548-10148,86-0
I have to carefully study syrosingopine and steripentol.

kind regards

Thousands of thanks Johan!
We used it some time ago and I think it can be helpful again

Hi Manuel,

I checked the list of drugs you shared above with Acetazolamide. According to this there may be moderate interaction with Metformin, Dexamethasone, Canagliflozine. My understanding is that this interaction is related to potential Acetazolamide modulation of blood glucose and blood pH. Acetazolamide can both increase or decrease blood glucose levels. So if I would introduce Acetazolamide I would have an eye on these two, specifically blood glucose levels, and I would introduce it step by step. 

I would also be careful in case it is used and removed at a latter point. I can imagine that the brain tumours may be extra sensitive to Acetazolamide as it is known to modulate cerebral edema, e.g.:

https://www.karger.com/Article/FullText/445170

https://www.frontiersin.org/articles/10.3389/fneur.2019.00273/full

Kind regards,

Daniel