Combo Metformin And Syrosingopine!!!! Looks Awesome!  

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Daniel
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09/12/2019 10:40 pm  

@manuone

Hi Manue,

Here are a few options to address lactic acidosis in case that would be seen https://emedicine.medscape.com/article/768159-overview#a5

Are you using any treatments to support your mom liver? Like Milk Thistle and/or Astragalus, and/or from time to time Alpha Lipoic Acid, and/or sometimes Hepamertz? 

Kind regards,
Daniel


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Jcancom
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10/12/2019 2:17 am  

GgE and others, I am very interested in your comments about the lactate monitor. Would this be a wise purchase for those on thread? We have already seen several instances with metabolic treatments that too much treatment power can be highly dangerous (3-BP patient 1 & 2, perhaps the Bracht patients, and likely others). Up till now too much treatment power from chemotherapy has typically not been a particularly noted problem. In fact, such incidents are usually apparently rare enough that they have been assigned journal articles to discuss the peculiarness of  such occurrences.

Having a lactate monitor on hand would allow you to keep track of lactate responses to treatment. For example, a metabolic treatment such as 3-BP that might entirely shut-down lactate production could be monitored with the lactate monitor. This would seem to me to provide extremely useful information. Why a clinic treating with powerful metabolic treatments such as 3-BP would not have such an instrument is entirely mysterious to me. The test strips only cost $2.

As has been noted on the thread elsewhere one would also be able to monitor for lactic acidosis (for relevance for the thread metformin currently has an FDA black box warning for lactic acidosis and lead to the removal from the market of phenformin which is thought to be an even more powerful anti-cancer treatment, though with even greater risk of lactic acidosis. However, even now phenformin is undergoing clinical testing for cancer with the possibility that in might be reintroduced some time in the future. It has also been mentioned that the lactic acidosis risk from metformin and phenformin is concentrated in patients with co-morbidities.). The magnitude of such risk from lactic acidosis when also blocking lactate export clearly is open to debate.  

Even beyond the safety, knowing lactate levels could be highly significant for then one has the opportunity to manipulate such levels.

 

"... demonstrated that venous outflow can be significantly inhibited using even
mild systemic acidosis. Briefly, this is because acid flow into intra-tumoural blood vessels is in part
dependent on the concentration gradient between the interstitial space and the blood. If the acid
concentration in the blood is increased, vascular outflow of acid from the tumour dramatically
decreases and the intra-tumoural pH declines precipitously. As a result, local acid concentrations
exceed the tolerance of even the tumour cells, triggering extensive tumour necrosis."

"In contrast, major increases in the levels of myokines and catecholamines are suggested to
have the potential to directly regulate tumour growth ..."  (The catecholamines are of specific interest to this thread as syrosingopine changes catecholamine biology)

"Thus, one may hypothesize that high-intensity anaerobic exercise may counteract tumour metabolism by inducing a systemic acidosis, inhibiting tumour cell glycolysis, and thus reversing theWarburg phenotype metabolism of cancer cells as proposed from a model simulation

"In the absence of lactic acidosis, cancer cells exhibited excessive glycolysis and produced large amounts
of lactate. In the presence of lactic acidosis, cancer cells exhibited low glycolytic rates and produced
negligible amounts of lactate. However, when culture conditions changed from lactic acidosis to
a regular culture, cancer cells instantly switched back to the glycolytic Warburg phenotype, indicating
the need to combine treatments." 

(Increasing systematic lactate levels (by exercise etc.) would appear to displace the lactate produced by the cancer cells!)

Glucose levels could be reduced through exercise while lactate levels could be increased. This manipulation could be of relevance in cancer management. As glucose is a non-essential nutrient one could imagine, reducing glucose intake and then monitoring as lactate levels fell as lactate --> glucose in the Cori cycle. The presence of high lactate levels is another mystery for me in cancer.  Why would not simply "burn off" this extra lactate by restricting glucose?    

From my perspecitive, the above comments provide a reasonable basis to purchase a lactate monitor in order to monitor for lactic acidosis and TLS and to manipulate lactate biology for therapeutic effect. Clinical trials have already demonstrated responses in cancer patients using this approach. Please comment!

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969185/

 

 

  (Please everyone let's go to the new thread! I realize that a thread revolt is now underway (We're not leaving!), though a new shiny thread is waiting for us.) 

 


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Jcancom
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10/12/2019 2:18 am  

maximal lactate steady state and lactate threshold for running


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Jcancom
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10/12/2019 2:26 am  

Sorry the figure from the below url is not posting. Scroll down to where it reads: "First - there is an effort level called the ..." . Figure shows how a 4000 m run at 4.6 m/s increases lactate levels to 8 mmol. A quite rapid increase. Such exercise at varying intensity levels might be therapeutic for a range of patients.

http://lactate.com/lactate_threshold.html


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GgE
 GgE
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10/12/2019 7:15 am  
Posted by: @jcancom

comments about the lactate monitor. Would this be a wise purchase for those on thread?

Although I don't have experience with it, I agree with you that it would be a wise investment. Lactate levels are important in the management of several health concerns but it seems especially important during a syromet treatment.

I consider that the war on cancer is a war of numbers in many regards and the more relevant, precise and objective data we obtain, the less guesswork we need to do and the better decisions we make.


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Daniel
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10/12/2019 3:11 pm  

@jcancom

Hi J,

In my view a lactate measurement tool will help. I think I may have one at home too. It's always good to know what happens in the body on short term, and monitor if we see a sharp increase or drop of lactate. Of course that may indicate various mechanisms in the same way as LDH (the enzyme responsible for converting pyruvate into lactate and back) measured in the blood indicates various mechanisms. For example, a jump of LDH may often represent cellular brake-down that could be associated with a tumor breakdown, while a continuous growth of LDH during weeks would represent tumor evolution.  Coming back to lactate, a fast jump of lactate may indicate either lactic acidosis due to drugs used (which I expect to be a rare event) or a jump in glycolitic activity of the tumor (I would expect such a jump only in case of an infection). On the other hand, a drop of lactate (assuming that initially it is out of normal range) would be a good sign, indicating inhibition of fermentation and thus at least tumor growth reduction. Therefore, given the relative low cost and potential added value, I would buy a lactate meter as you suggested J.

Sorry for not being able to reply often but as you know I need to act on multiple directions at the same time. (I also think sometimes is better that I do not jump in the discussions.) 

Btw, I think it may take some time before we can switch to the "Part 3" of the tread as long as we will respond to discussions points on the first tread - the more points triggering discussions will be made in "Part 3" the more we will tend to reply to those points and as a result the switch will happen naturally.

Kind regards,
Daniel

 


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johan
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11/12/2019 3:05 am  

@daniel @jcancom

If Metformin induces the expression of UCP2 (ref) isn't that potentially a problem in cancer, many seem to overexpress UCPs?

https://www.news-medical.net/news/20111116/Human-pluripotent-stem-cells-rely-heavily-on-glycolysis-to-drive-their-metabolic-activities.aspx


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Jcancom
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11/12/2019 4:06 am  

et tu, johan? et tu?

Thank you GgE and D! Your support for the lactate monitor idea is greatly appreciated. This might wind up being one of the larger insights that we have thought of on this forum to improve outcomes for patients. Knowing that a treatment was effective (or was not effective) quickly after administration might offer us the ability to rapidly search out and find what will be helpful. Until now we have been blindly trying treatments and then waiting sometimes a month or more before receiving confirmation of efficacy. With a lactate monitor, we might attempt several anti-cancer regimens in a day. With metabolic therapy, one expects that response will be rapid. For example, syromet's shutting down NADH recycling would reasonably be detectable in the time frame of perhaps less than 3 hours.

About 95% of the time that I figure I am right and everyone is wrong, I am not in the right. It is starting to look that the lactate monitor will be one of the times that I made the right call. Lactate monitors could allow us to improve safety and enhance the overall effectiveness of treatment. This might turn out to be one of the biggest wins experienced by the forum. Detecting a response within hours (or less) all at a marginal cost of only ~$2 has to be big news! I am very anxious to see how a treatment naive syromet patient (or any other patient naive to metabolic therapy) might readout with a lactate monitor after treatment.

Happy 2020 everyone! 2019 has been another big year for us!


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johan
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11/12/2019 4:20 am  
Posted by: @jcancom

et tu, johan? et tu?

 

lol, so you must be Canadian J!


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johan
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11/12/2019 5:15 am  
Posted by: @jcancom

 

Happy 2020 everyone! 2019 has been another big year for us!

Happy 2020! 🍹 


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Manuone
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12/12/2019 7:51 pm  

@daniel

Thanks for the suggestions, yes, I use milk thistle..silymarin and silibinin.
I will consider Hepamerz!

kind regards


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GgE
 GgE
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13/12/2019 8:15 pm  

Hello everybody. I have some questions begging for answers. I would appreciate your thoughts, even if you are not familiar with this subject. Thanks!

Millions of patients with hormone-responsive tumors are being treated with CDK4/6 inhibitors such as palbociclib (Ibrance), avemociclib (Kisqali) or ribociclib (Verzenio) along with aromatase inhibitors such as anastrozole (Arimidex), letrazole (Femara) or exemestane (Aromasin), or other substances such as fulvestrant (Faslodex) that reduce the amount of estrogen available for the cancer cells to grow. This combo seems to work because it reduces the proliferation of cancer cells by stopping the mitosis or cell division of many such cells. This arrest can last for a long time and some (but not all) such cells die during this arrest time. But many cells survive for a long time in this state of arrest and eventually proliferate when the conditions are right. Many patients don’t respond to CDK inhibitors and those who do, stop responding usually within less than 2 years as the cells develop resistance to the CDK inhibitor. But this regimen is being used more and more often all over the world.

https://www.cancernetwork.com/breast-cancer/cdk46-inhibitors-game-changers-management-hormone-receptorpositive-advanced-breast-cancer/page/0/1

#1. I wonder if the members and guests in this web site could give here your opinions about whether the Syrosingopine + Metformin combination could be taken at the same time as a CDK4/6 inhibitor + estrogen suppressor regimen and if so, if you would expect added benefits or if you think there may be incompatibilities. If there are incompatibilities, do you any see potential solutions?

#2- A twist. Animal studies show that by adding hydroxychloroquine (HCQ) to the CDK4/6 Ibrance + letrazole the response rate was much higher; the cells whose division was stopped died irreversibly; and the cancer cells did not develop resistance to Ibrance. This beneficial effect is thought to be a result of HCQ inhibiting the cancer cells autophagy, which allows many of them to survive the CDK-induce cell cycle division arrest.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490269/

This combination with HCQ is now being tested in humans in this new trial:
https://clinicaltrials.gov/ct2/show/NCT03774472?term=Hydroxychloroquine+and erson&cond=Breast+Cancer&cntry=US&state=US%3ATX&city=Houston&rank=1

Do your answers to the first questions hold or change by the introduction of HCQ? Notice that Metformin induces autophagy while HCQ inhibits it.

If syro+metf could work together with a CDK4/6 inhibitor plus an estrogen inhibitor, can you think of any way that the addition of HCQ doesn't conflict with Metformin?

I think the answers to these questions can be highly relevant and interesting to many of us in this web site.


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Jcancom
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15/12/2019 9:34 pm  

GgE, I was also wondering whether there might be a possible combination possibility with Faslo, as you did raise the potential in an earlier post that perhaps a response to syromet while taking Faslo might be assisted by the Faslo. The next logical step, that you have suggested above,  would be that perhaps the combination itself could enhance the response. I have seen too many times that such pairings of cancer drugs can have response synergies, so I would tend now not to casually dismiss any such suggestion.

However, it might  be best to not stray too far from our metabolic focus. There are an overwhelming number of metabolic combinations that are available. I have been reviewing them on pubmed and it is almost endless. Combining and recombining treatments such as DCA/2-DG/honokiol/metformin/tocotrienol/berberine/silver nanoparticles/... ; especially when well-formulated, can result in very significant responses. It is not so much that other treatment approaches do not exist or would not be effective, though one wonders why they would be necessary with all the powerful metabolic approaches available.  

Many of these dual combinations exhibit synergies. Anyone know of any triple combinations that exhibit synergy?    

Strangely, I have been largely unaware of the excitement that has been generated for yet another metabolic therapy: Febendazole. This despite the near constant commenting that I have seen on the blog side of the comments screen. When I surfed around on the web to investigate this further I was surprised to see how viral Febendazole has went. They are out of stock of this dog dewormer? This has to be the cancer craze of 2019.

Yet, with all such metabolic cancer crazes it is difficult to legitimately call it a craze because there is a certain reality check that occurs with metabolic treatment: responses are expected rapidly. With 3-BP, the responses have been seen within days. In the two published reports the patients felt better within hours. With syromet, we have also seen largish responses within a week. This is exactly what one might expect when shutting off NADH recycling or selectively depleting ATP. Metabolic therapies typically should produce rapid results. Febendazole is also apparently now reporting possibly a few dozen responses. Here again that is exactly what we would expect for a metabolic treatment. My suggestion of using a lactate monitor could turbocharge the entire field of metabolic therapy. If those treated with syromet, Febendazole etc. could see their lactate levels decline in real time rapidly after treatment, there could no longer be a meaningful discussion about the effectiveness of the treatment. In fact such monitoring could then be used to find the exact treatment that would be the most effective without having to wait out weeks or months between labs. One could use their own home labs as a biofeedback marker. One could then also adjust various parameters such as time of administration (chronobiology), specific combinations, dosing etc. This is very exciting! I am greatly looking forward to 2020 to see whether posters on forum see the value in this idea/      

Perhaps we should try  to amplify such breakouts for metabolic treatment, as such occurrences are one of the few times that typical mainstream society pays any attention. Those who have been on forum for a while, can recognize that the essential metabolic treatment to cancer has manifested in various guises for at least over the last ~100 years. Various diets, vitamin C, 3-BP, even syromet and many others: all have at their base the same foundational mechanism related to glycolysis, OXPHOS etc.  Few of us can even be slightly that syromet would have substantial anti-cancer effects. While the mechanism of action of Febendazole is somewhat more obscure, its effects on microtubules, and glucose uptake help to clarify its relation to metabolic theory. It is thus, also not surprising that combing with DCA or 2-DG would help to synergistically enhance FEB.  

When we recognize that Febendazole is yet another metabolic treatment, highly similar to many other such metabolic treatments, it is no longer reasonable to even argue about metabolic theory of cancer. The metabolic theory of cancer is without question correct. 


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John Pizzuto
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15/12/2019 10:52 pm  

@jcancom

Shirley objected to trying Fenbendazole, since it's made for animals, but she is ok with Mebendazole, the version made for people.  🙂

I just received a shipment of 30 pills.  $5 a pill, 500mg.  Just started giving her one every other day.

She goes for blood work tomorrow.  Should get the results by the end of the week, in time for her monthly follow up with the oncologist.

Weighed her this morning, holding steady at 127 lbs. thank God.  🙂


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GgE
 GgE
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15/12/2019 11:31 pm  
Posted by: @jpizzuto

She goes for blood work tomorrow

How many full days will she have received syromet by the time they draw her blood tomorrow?

Has she received any other drug that may be a cause for whatever results you see in tomorrow's test results?


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John Pizzuto
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16/12/2019 12:14 am  

@gge

I received the syro on Nov. 8 and started her on 2mg + 250mg quick release metformin, 2x/day.

She had some diarrhea, so she missed a couple doses here and there, so we asked for slow release metformin at her last followup.  Still only thirty pills, 500mg each.  But, I have been doubling the dose, to 500mg plus 3.8mg syro, 2x/day for the last 15 days.  Just ran out of the 30 metformin pills today, but I received a shipment from Buy Pharma a few days ago.

So far, have used 210mg syro, so 1g should last us about 5 months.

We saw her PCP last week.  I told her what we are doing, and said I would like to increase the metformin over the 500mg we are getting from the oncologist.  She mocked me, asking how long I had been practicing medicine.  She jumped down my throat, warning of the danger of renal failure, etc.  She also wants a blood test and says if her A1C is 6 she's not getting metformin, as she could be hypoglycemic.  I said she has ketones over 2.0 to make up for it but I don't know if she realizes they are a metabolite.  According to Dr. Dominic D'Agastino, he says 1mM ketone can make up for about 10% of your brain's glucose requirement.  This was said regarding alzheimer's.  This checks with Dr. George Cahill's experiments from the late 60's where he starved volunteers for 40 days.  Their ketones reached 5-7, and he determined the brain was running on 66% ketones.

 


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John Pizzuto
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16/12/2019 1:11 am  

Nope, won't last that long, as I increased the dose.  So 795mg remaining, at 7.6mg/day, equals 104 more days.


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Jcancom
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16/12/2019 1:20 am  

JohnnyP, I would not be able to handle a situation well; I just won't. All they can offer you is a 1% lottery on Faslo, and they are mocking you? I will reiterate my prospective prediction, I think syromet will be effective for Shirley. It clearly is only a guesstimate, I will hedge somewhat because I am sure syromet is not 100%, though I without question believe that it is not a 1 percenter either.

With all the other metabolic treatments that are out there, I see no reason why the odds couldn't be stacked even more in your favor. As I have read through the site, there are so many many treatments, that most patients should probably have on their shelves. For example, omega -3s. D noted that ~10 grams per day omega-3 resulted in complete responses; as did silver nanoparticles. There is an endless list of possibilities: Fenbendazole + DCA; Fenbendazole+ 2-DG; metformin + 2-DG; there are so many of these. I would suggest to back up the truck. Poly-pharmacy is a way to self-deal the response that you want. Basically, keep taking shots on goal until you score. The more shots the better. With a lactate monitor you would know that you were on-target. I think that it would be a wise idea to move towards a more intensive treatment plan. However, I fully understand that this can be against one's innate instincts.   

I realize that often people have spent their entire lives and have never taken much more than an aspirin and then are reluctant to engage in 24/7 dosing, though with cancer being shy of taking pharmaceuticals that have often been extensively tested is not the optimal strategy. Typically one expects that instead of making a good bet, people wind up making a less good bet when their options become restricted.  

A patient revolution is now underway. Finally patients are developing the confidence to ask the tough questions and realize that there are choices available to them. Fenbendazole is at the front of this parade. It is the biggest example of a metabolic breakout that we have seen (at least over the last 5 years). 3-BP is not an easy treatment to access for most people and was not able to achieve anything close to what we have seen with Fenbendazole. Yet with Fenbendazole anyone can buy it online without prescription. A global scale shortage appears to be emerging. Managing this narrative when so many people will have personal connection to someone who has tried it will require a great deal of exertion. 

That was funny, JohnnyP, I noticed that you responded almost immediately after I posted. I thought that perhaps that some of the posters were not posting to the thread because they were not sure how to without clicking on the latest forum posts on the side of the page. It is somewhat tricky, though another way to do this especially when the thread has been inactive for a few days is to click on the forum link on the top of the page and then scroll down to the metabolic threads; it is fairly easy to find them as they have the most views and posts listed beside them.

Best Wishes, J


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Jcancom
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16/12/2019 1:44 am  

Johan, what is your take on the lactate monitor idea? It still makes a great deal of sense to me. I wonder why this is not part of standard practice. We saw with the 3-BP tragedy that likely is not.  Having the ability to use biofeedback from a monitor could enormously change the landscape for metabolic cancer treatment. We have seen posters who have continued to take ineffective treatments sometimes for months and then had progressed beyond which they could try again. Being able to rapidly search through the massive number of metabolic treatments until the most powerful one is found would be a complete game changer. The expected outcomes would reasonably be expected to dramatically improve.


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johan
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16/12/2019 2:13 am  

@jcancom

I like it a lot, J. I'm going to buy one soon, and test it with natural compounds, as that's my "thing" 😉

 


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Jcancom
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16/12/2019 4:10 am  

Johan, this is great! I have forum thought leaders on side. I wanted to make sure before everyone spent quite a bit of money only to see it not be quite right. I suggested this a few years ago on the compass, yet no one really seemed to understand it. This could be an enormously effective strategy to amplify outcomes. 

If we had one patient with a lactate monitor and an hour later the monitor started to pick up on a sustained decrease in their lactate that would permanently change the conversation related to metabolic treatment. The connection between treatment and effect would be too apparent to even argue about. It would also be such an empowering experience for patients to see that the treatment that they had received actually meaningfully impacted on their illness. As it is now, I expect that a fair amount of the time patients are likely sliding backwards in their markers. With a lactate monitor, one could set a realistic goal of pushing back their lactate marker progressively day by day. We can look back on the threads and see that oftentimes patients only had a few shots on goal; with a lactate monitor it would be possible to dramatically increase the number of shots on goal. The more shots on goal, the greater the chance for a response. 

I am very excited to see how this idea will evolve in 2020. Could it go viral? Money can of course be a show stopper, though if people could access one of these devices for a modest usage fee, then there is only $2 of marginal cost to worry about. If we could move this towards $2 marginal cost, then yes this could go viral. Could be time to get the flu shot.


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GgE
 GgE
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16/12/2019 5:42 am  
Posted by: @jpizzuto

he had some diarrhea, so she missed a couple doses here and there, so we asked for slow release metformin at her last followup.  Still only thirty pills, 500mg each.  But, I have been doubling the dose, to 500mg plus 3.8mg syro, 2x/day for the last 15 days. 

Johnny, like Jcancom I also hope you and your wife see early signs of a good response very soon. But at the same time, I think you need to prepare to be in for the long haul. For this, I would take this into account.

Syro reduces, even depletes norepinephrine at peripheral neurons. It may also deplete peripheral deposits of other catecholamines. This way syro can reduce the activity of the sympathetic nervous system which controls all of the unconscious functions: breathing, blood flow, digestion, heart rate, blood pressure, and so forth. The catecholamines also control muscle strength and mental alertness. So, in addition to lowering her blood pressure syro may considerably weaken her muscles and reduce her oxygenation and alertness.

I would be alert for signs of catecholamine deficiency in her body because the above can translate into

- Weak leg muscles which can lead her to fall down, especially at night

- Weak bladder muscles which may cause her to have urinary incontinence

- Weak low back muscles which may cause low back pains.

- Weak intestinal peristaltic action which may cause her constipation. Here metf seems to counter this risk from what you’ve said.

- Weak breathing muscles which may cause her blood oxygen levels to be abnormally low which can give her headaches and lower her mental alertness, memory and balance.

and many other serious side effects that can make her life unbearable and have the potential to cause her harm and/or forcing her to stop the treatment.

Some mice studies found that the severity of some of these side effects was reduced after lowering the doses or repeating the treatments; and that they also went away after discontinuing the medication. But I am not a doctor and don't know it.

I would also consider giving her a complete vitamin B complex such as Integrative Therapeutics’ (if it is not too strong for her) and a complete protein supplement to supply her with Tyrosine and Phenylalanine, both important catecholamine precursors.


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GgE
 GgE
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16/12/2019 5:44 am  
Posted by: @jpizzuto

Nope, won't last that long, as I increased the dose.  So 795mg remaining, at 7.6mg/day, equals 104 more days

You may think of ordering again. I understand they're taking several months lately


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John Pizzuto
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16/12/2019 8:51 am  

@gge

Thanks for the heads up.

J:  It was her PCP who mocked me, not her oncologist.  Also, Mebendazole is similar to Fenbendazole.


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JulienAch
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16/12/2019 5:19 pm  

Hi All, 

I've been following this post for a while as it seems very promising ; Hope that the availibility of syro get easier to allow more people to experiment it ; 

Regarding lactate monitoring, do you guys think that it could reflect tumor status in all kind of lesion ? Only for highly glicolitic kind ? 

https://www.ncbi.nlm. https://www.ncbi.nlm.nih.gov/pubmed/26530363

This would indeed be a game changer especially for those who doesnt benefits for any specific tumor markers

 

 


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John Pizzuto
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16/12/2019 6:07 pm  

@julienach

My wife's blood work doesn't show LDH or lactate.  I asked for it to be tested last year, but that was the only time they ran it.


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GgE
 GgE
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16/12/2019 7:02 pm  
Posted by: @jpizzuto

My wife's blood work doesn't show LDH or lactate.  I asked for it to be tested last year, but that was the only time they ran it.

Posted by: @julienach

do you guys think that it could reflect tumor status in all kind of lesion ? Only for highly glicolitic kind ? 

Julien, welcome to this forum. I hope it will help you as it is helping many of us.

Johnny, breast cancers are usually highly glycolytic, especially in the metastatic stage. Could there be a reason why lactate does not show in her labs? Let me pose some quick thoughts here.

I assume that her tumors are medium to big size. If so, they have a dense, hypoxic core which must get its energy from glycolysis, as it has scanty access to oxygen due to its high density that squeezes its inadequate blood vessels to the max. This glycolysis produces a lot of intracellular lactate which must be pushed out of the cells to avoid their death. This lactate does not go into the blood vessels because they are squashed and can barely carry any blood. The pushed out lactate goes into the intratumoral space where the tight packing of the cells squeezes it towards the outer tumor areas. Here, the cancer cells are not so dense yet and have access to oxygen. They eagerly absorb the lactate and use it as energy source (through oxidation) and as a material source to make more cancer cells. The end result of this theory is that a blood test would not show any abnormal lactate level as most of the lactate gets absorbed very close to its source. A lactate monitor thus would not help monitor untreated regular cancer progress.

Comes a successful metabolic treatment and let us think if things change. Let's talk about syromet. The hypoxic core cells get choked up on their own lactate because syro does not let them push it out of their insides. They start dying. The outer cells use up all the lactate they find but run out of it. They start oxidizing glucose, and if it is not available lipids or proteins for energy and protein synthesis but their mitochondria gets jammed up by metformin and they start dying also.

As the core cells dye, their membranes rupture and their innards get spilled out, including the lactate that had been choking them. But now there is no outer cancer cells to take it in, so the lactate eventually oozes out of the tumor and is carried away by the blood. If this happens in large quantities then a lactate monitor could detect it and give an indication of what is happening.

If your wife's test results of today show a positive response, you might want to get her tested for lactate again ASAP, even if you have to pay it from out of your pocket. I think it costs around $60 from an online lab such as walkinlab.com. If the test results show a high lactate level then you might want to repeat it soon to see if you can use frequent lactate monitoring as a marker of syromet's effectiveness, as J proposes.

This is just a theory. Maybe D, J, and the great minds that visit our pages can chime in.


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John Pizzuto
(@jpizzuto)
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16/12/2019 10:51 pm  

@gge

I don't think she has large tumors.  She has at least a hundred lesions on her bones, primarily in her back and some on her hips.  I think she may have a tumor in her lymph system, in her chest.


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Daniel
(@daniel)
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17/12/2019 12:51 am  

@gge

Hi GgE,

I think your explanation sounds very good. Another dimension to consider is the tumor type and the aggressiveness. When tumors develop slower, the LDH increase (and lactate) may not be visible - but when they move fast there will be large necrotic areas formed and the related cellular breakdown will induce an increase in LDH and probably an increase of lactate too since the absorption of lactate by the oxidative cells will not be compensated anymore. However, the lactate that get's into the blood will be converted into glucose by the liver- this wold be another mechanism that would lower the blood lactate - this may make lactate blood level look normal, unless the patient is using Hydrazine to block gluconeogenesis. Actually, Metformin is also blocking gluconeogenesis https://www.cancertreatmentsresearch.com/addressing-gluconeogenesis/ and this may lead to an increase of lactate in the blood, that could also lead to lactic acidosis. Therefore, for patients with fast developing tumors who also use gluconeogenesis inhibitors such as Metformin, lactate could be a relevant parameter.

Kind regards,

Daniel


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Jcancom
(@jcancom)
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17/12/2019 2:32 am  

Julien, thank you for joining the discussion. The lactate monitor is still somewhat in the beta stage, though we are slowly working through the issues involved. I am glad that D has now mentioned that hydrazine and metformin block gluconeogenesis; I was trying to remember where I had read that. What I have thought is if someone did not even have cancer they might take metformin etc. in order to see how much lactate they were producing. The problem might be that for someone with a low tumor burden (especially if they were pre-detection stage) the cancer would be there but the liver would be converting it to glucose and this would hide the lactate. Shutting down lactate processing would let you see it, even if it were otherwise undectable.

I am very excited about this idea and I can hardly wait to see how it might develop in the new year. I was surprised, though, that the walkin lab that GgE noted charges ~$70 for a lactate reading. The lactate monitor has strips that only cost ~$2 per reading. Do people actually spend $70 (instead of $2) ?  

I am sure that you are aware that the blog is somewhat fixated on a metabolic interpretation of cancer. It would be a good idea to think along these lines as well. The Nature article that D noted on his Fen page, found a strong synergy between Fen and 2-DG, and Fen and DCA. These dual metabolic combos can be powerful. We have started to see some large responses with metabolic approaches (For example, metronomic 2-DG and now syromet). I understand that many of these treatments are unfamiliar, yet many of them appear to offer significant potential; this will likely become even more clear when we see the responses with the lactate monitor.  J


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