haidut

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This is yet another recent study showing that medicine may finally be getting on the right track. Similar to the human study with doxycycline and breast cancer I just posted, confirms again what has been known and fraudulently suppressed for almost a century. Namely, the Warburg "effect" is as much of an effect as it is actually a direct cause of cancer initiation and development. A highly controversial study with similar findings caused a lot of controversy on Reddit. However, it was completely ignored by mainstream media and the only outlet that gave it some publicity (NYT) only did do to expose the purported dangers of sugar given cancer's "addiction" to it.
The Warburg Effect drives oncogenesis: researchers at Lawrence Berkeley National Lab and in Japan show cancer really does have a sweet tooth : science

Well, the study below goes even further than the one above and shows that cancer is nothing but a cell that is kept in "proliferation" mode by its own overproduction of lactic acid, which leads to increased reductive stress, low respiration, low ROS generation, and thus lack of apoptosis. More importantly, the study showed that simply providing extra reduced glutathione (GSH) (and thus shifting the redox balance in favor of reduction) was enough to ensure the cell stays in its "proliferation" mode by inactivating cytochrome C and thus lowering respiration. Conversely, forcefully enhancing respiration triggered apoptosis, suppressed "tumor" growth, and elevated ROS production. The shift away from reduction and towards oxidation can be achieved through many dietary measures, such as niacinamide, MB, sucrose, quinones, aspirin, tetracycline antibiotics, etc. Any of the ratios such as GSSG/GSH, NAD/NADH, pyruvate/lactate, acetoacetate/hydroxybutyrate, etc can be used to rather simply and non-invasively both estimate the "cancer potential" of an organism and gauge the effectiveness of such pro-oxidation measures.

The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer

"...Additionally, the effect of glutathione as ROS scavenger was tested in a shift assay, where highly proliferative wild-type cells pregrown in liquid SCGlu media were seeded onto SCGal and SCGly plates with or without GSH. Strikingly, survival was enhanced to 50% and 55%, respectively, compared to <1% survival on plates without GSH (Fig. 4C). A similar shift of stationary cells yielded an increased survival from 50% and 60% to 75% and 77%, respectively, on GSH containing plates (data not shown). We conclude that scavenging ROS via glutathione enhances cell survival during colony development as well as during seeding on highly respiratory media. Intriguingly, it has been reported recently that in cancer cells and in neurons (that also display the Warburg effect), cytochrome c is reduced and held inactive by GSH [30]." So far, research on the Warburg effect has mainly focused on the high glycolytic flux while the accompanying repression of mitochondrial respiration was often left unattended [8], [9]."
"...Our data demonstrate that respiration triggers apoptosis during seeding and development of a cell population, providing direct experimental evidence in support of the Warburg hypothesis during initiation of tumorigenesis. The strongly decreased respiratory capacity may be crucial for tumor malignancy [12] and for resistance against inevitable fluctuating oxygenation in tumors [31], [32]. Interestingly, it has been demonstrated that yeast rho0 strains exhibit increased resistance towards certain external apoptotic stimuli such as acetic acid, which triggers death via the mitochondrial pathway [15], [17]. A similar resistance against cell death may also play a role for tumor cells in an acidic surrounding. We speculate that reprogramming of cancer cells follows an ancient mechanism present in S. cerevisiae wild-type colonies: high glycolysis in the presence of oxygen."
 

Soren

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So if I am reading this correctly, Glutathione which has been marketed by god knows how many people as a health cure all is actually very bad when supplemented and can actually cause cancer by not allowing cells to die and thus causing them to mutate and become cancerous.
 

Suikerbuik

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I don't know the long story so don't take me for facts; I am parroting here, and I don't even know his name but a quick google search suggests it might be Robert Keller. Anyways, a few years ago a story went around that 'a man' who extensively researched, promoted and supplemented GSH himself apparently died fairly young....for what's worth it.
 
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Looks like another point in the right direction for medicine, indeed, even though the mainstream is all about
- loads of antioxidants,
- demonizing sugar whereas people don’t really consume lots of it,
- pushing the “low fat failure” propaganda even tho fat consumption increases decade after decade
- pushing the “high fat and cholesterol are okay” propaganda
- also pushing for even less carbs in the diet because “sugar damages arteries”, which doesn’t happen in a low fat diet (so maybe fat and cholesterol ain’t okay?)
- drugs use instead of dietary fixes
- barely mentioning electrolytes, potassium vs sodium in a world of eating out / getting food deliveries

Recently saw a video of Rhonda Patrick and Dave Attia where they babble around for one hour... and (up until the very last minute) not one single time were ROS considered as something useful for the faulty cell death. The engineering approach to biology has its limits... we’re built to produce a lot of waste and imperfections (heat, apoptosis) in order to generate a healthy system.
 

Mufasa

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So if I am reading this correctly, Glutathione which has been marketed by god knows how many people as a health cure all is actually very bad when supplemented and can actually cause cancer by not allowing cells to die and thus causing them to mutate and become cancerous.

Glutathione doesnt reach the blood when supplemented. However vitamin E, vitamin C and also glycine raise glutathione levels. Eating lots of PUFA is probably a reliable way to lower glutathione. As glutathione is needed to make sure PUFA doesnt break down in harmfull substances. Low blood glutathione levels are seen in many chronic diseases. I dont believe that Ray Peat ever said that glutathione is harmful, right @haidut?
 
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Suikerbuik

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Glutathione is really important, but the point is to get it regulated by the body and its oxidation and reduction processes instead of messing with it by unnatural means. Low glutathione is rather a result of disease and something being off (diet etc.) than a cause; although high ROS over time is certainly not unharmful.
 

Obi-wan

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This is yet another recent study showing that medicine may finally be getting on the right track. Similar to the human study with doxycycline and breast cancer I just posted, confirms again what has been known and fraudulently suppressed for almost a century. Namely, the Warburg "effect" is as much of an effect as it is actually a direct cause of cancer initiation and development. A highly controversial study with similar findings caused a lot of controversy on Reddit. However, it was completely ignored by mainstream media and the only outlet that gave it some publicity (NYT) only did do to expose the purported dangers of sugar given cancer's "addiction" to it.
The Warburg Effect drives oncogenesis: researchers at Lawrence Berkeley National Lab and in Japan show cancer really does have a sweet tooth : science

Well, the study below goes even further than the one above and shows that cancer is nothing but a cell that is kept in "proliferation" mode by its own overproduction of lactic acid, which leads to increased reductive stress, low respiration, low ROS generation, and thus lack of apoptosis. More importantly, the study showed that simply providing extra reduced glutathione (GSH) (and thus shifting the redox balance in favor of reduction) was enough to ensure the cell stays in its "proliferation" mode by inactivating cytochrome C and thus lowering respiration. Conversely, forcefully enhancing respiration triggered apoptosis, suppressed "tumor" growth, and elevated ROS production. The shift away from reduction and towards oxidation can be achieved through many dietary measures, such as niacinamide, MB, sucrose, quinones, aspirin, tetracycline antibiotics, etc. Any of the ratios such as GSSG/GSH, NAD/NADH, pyruvate/lactate, acetoacetate/hydroxybutyrate, etc can be used to rather simply and non-invasively both estimate the "cancer potential" of an organism and gauge the effectiveness of such pro-oxidation measures.

The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer

"...Additionally, the effect of glutathione as ROS scavenger was tested in a shift assay, where highly proliferative wild-type cells pregrown in liquid SCGlu media were seeded onto SCGal and SCGly plates with or without GSH. Strikingly, survival was enhanced to 50% and 55%, respectively, compared to <1% survival on plates without GSH (Fig. 4C). A similar shift of stationary cells yielded an increased survival from 50% and 60% to 75% and 77%, respectively, on GSH containing plates (data not shown). We conclude that scavenging ROS via glutathione enhances cell survival during colony development as well as during seeding on highly respiratory media. Intriguingly, it has been reported recently that in cancer cells and in neurons (that also display the Warburg effect), cytochrome c is reduced and held inactive by GSH [30]." So far, research on the Warburg effect has mainly focused on the high glycolytic flux while the accompanying repression of mitochondrial respiration was often left unattended [8], [9]."
"...Our data demonstrate that respiration triggers apoptosis during seeding and development of a cell population, providing direct experimental evidence in support of the Warburg hypothesis during initiation of tumorigenesis. The strongly decreased respiratory capacity may be crucial for tumor malignancy [12] and for resistance against inevitable fluctuating oxygenation in tumors [31], [32]. Interestingly, it has been demonstrated that yeast rho0 strains exhibit increased resistance towards certain external apoptotic stimuli such as acetic acid, which triggers death via the mitochondrial pathway [15], [17]. A similar resistance against cell death may also play a role for tumor cells in an acidic surrounding. We speculate that reprogramming of cancer cells follows an ancient mechanism present in S. cerevisiae wild-type colonies: high glycolysis in the presence of oxygen."


THIS is what I have been talking about! but Lactic acid will continue to build until Acetyl-CoA feeds the Krebs cycle. If Pyruvate only makes Lactic acid then another source is needed. My answer is apple cider vinegar/sodium bicarbonate/potassium bicarbonate to make an acetate combined with CoA...nothing works until this is done... No Vit. E or C for more ROS...Oil of Oregano as a natural antibiotic...
 

Zpol

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THIS is what I have been talking about! but Lactic acid will continue to build until Acetyl-CoA feeds the Krebs cycle. If Pyruvate only makes Lactic acid then another source is needed. My answer is apple cider vinegar/sodium bicarbonate/potassium bicarbonate to make an acetate combined with CoA...nothing works until this is done... No Vit. E or C for more ROS...Oil of Oregano as a natural antibiotic...

Can you share with us the amounts of these substances to use, and how often to consume it?
I did see on other posts you recommend inhaling the CO2 as it fizzes.

My only concern would be the supplemental potassium could be hard on the kidneys (a problem with potassium supplements from what I've read).
 
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Indeed, I’d rather consume potassium from foods.

Baking soda+Squeezed organic lemon is helping my mother a lot against her arthritis, and my father is on that train too because he’s the hypochondriac type when it comes to cancer.
 

Obi-wan

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Can you share with us the amounts of these substances to use, and how often to consume it?
I did see on other posts you recommend inhaling the CO2 as it fizzes.

My only concern would be the supplemental potassium could be hard on the kidneys (a problem with potassium supplements from what I've read).

1/4 teaspoon each of potassium and sodium bicarbonate with 2 tablespoons of ACV in 8 ounces of water 2x per day between meals.
 

Amazoniac

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THIS is what I have been talking about! but Lactic acid will continue to build until Acetyl-CoA feeds the Krebs cycle. If Pyruvate only makes Lactic acid then another source is needed. My answer is apple cider vinegar/sodium bicarbonate/potassium bicarbonate to make an acetate combined with CoA...nothing works until this is done... No Vit. E or C for more ROS...Oil of Oregano as a natural antibiotic...
Obi, speaking of 'citric acid cycle', I was already quoting the following publications but stopped half of the way: there were many germs in them, it's better to just read them directly (especially the first one). You can offend me through PM in case you find them uninteresting.

- The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots (ref. #8 from the link below)
- Citrate in the Diagnosis of Prostate Cancer
 

Mufasa

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Glutathione is really important, but the point is to get it regulated by the body and its oxidation and reduction processes instead of messing with it by unnatural means. Low glutathione is rather a result of disease and something being off (diet etc.) than a cause; although high ROS over time is certainly not unharmful.

For what I have read, I also heard that a low GSH/GSSG ratio is seen in various diseases such as Alzheimer and Parkinson.
Ray Peat seems to think that a low GSH/GSSG ratio is good.

GSH is high in electrons, and is protective because of that it is high in electrons, and uses this to neutralize free radicals.
Molecules high in electrons are needed for oxidation to work right.
Weren't quinones good because they could deliver electrons to the oxidative system?
I don't really understand, but that is not something to ashamed of I see, quoting Ray Peat:

But Mae-Wan Ho, in her article "Cancer as a redox disease" makes the common mistake of seeing cancer as not having enough electrons.

Does someone here really understand why Ray Peat think a low GSH/GSSH ratio is a good thing?
 

Obi-wan

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Obi, speaking of 'citric acid cycle', I was already quoting the following publications but stopped half of the way: there were many germs in them, it's better to just read them directly (especially the first one). You can offend me through PM in case you find them uninteresting.

- The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots (ref. #8 from the link below)
- Citrate in the Diagnosis of Prostate Cancer


The studies state that cancer cells have a lower citrate and zinc concentration due to citrate being oxidized. I found THIS interesting on Wikipedia:

Pyruvate molecules produced by glycolysis are actively transported across the inner mitochondrial membrane, and into the matrix where they can either be oxidized and combined with coenzyme A to form CO2, acetyl-CoA, and NADH,[28] or they can be carboxylated (by pyruvate carboxylase) to form oxaloacetate. This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle, and is therefore an anaplerotic reaction (from the Greek meaning to "fill up"), increasing the cycle’s capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g. in heart and skeletal muscle) are suddenly increased by activity.[37] In the citric acid cycle all the intermediates (e.g. citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that that additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence the addition of oxaloacetate (or malate) greatly increases the amounts of all the citric acid intermediates, thereby increasing the cycle's capacity to metabolize acetyl CoA, converting its acetate component into CO2 and water, with the release of enough energy to form 11 ATP and 1 GTP molecule for each additional molecule of acetyl CoA that combines with oxaloacetate in the cycle.[37]


Apple cider vinegar is rich in malate...combined with a base (bicarbonate) is an acetate forming acetyl CoA converting the acetate component to Carbon dioxide opposing lactic acid build up...a double whammy! Now some K2 for the ETC...
 
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Spokey

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Glutathione doesnt reach the blood when supplemented. However vitamin E, vitamin C and also glycine raise glutathione levels. Eating lots of PUFA is probably a reliable way to lower glutathione. As glutathione is needed to make sure PUFA doesnt break down in harmfull substances. Low blood glutathione levels are seen in many chronic diseases. I dont believe that Ray Peat ever said that glutathione is harmful, right @haidut?

I think this is a context thing. Reduced Glutathione is an antioxidant, less will be used when other antioxidants are in play (vitamins E,C) and PUFA will lower glutathione by being pro-oxidant. Uncontrolled oxidation is likely the issue there, not the stuff going on in cells to generate energy.

It's the difference between having a controlled sequence of explosions in the engine block of your car, to having an out of control fire in the back seat. Water for the back seat is good, in the engine not so much. You could drop your car in the ocean to put out that fire, but the engine wont be too happy about it.
 

Obi-wan

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I think this is a context thing. Reduced Glutathione is an antioxidant, less will be used when other antioxidants are in play (vitamins E,C) and PUFA will lower glutathione by being pro-oxidant. Uncontrolled oxidation is likely the issue there, not the stuff going on in cells to generate energy.

It's the difference between having a controlled sequence of explosions in the engine block of your car, to having an out of control fire in the back seat. Water for the back seat is good, in the engine not so much. You could drop your car in the ocean to put out that fire, but the engine wont be too happy about it.

GSH is not good for cancer ROS is...
 

Obi-wan

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Sweet thanks.

This morning 10 minutes after consumption...higher state of clarity and energy...little nervous energy (maybe K2 which I put on my hips 10 drops, 5 each hip...idea labs stuff.. trying to make bones stronger in that area due to androgen depravation therapy)...makes me want to accomplish things...work...
 

Obi-wan

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Just for clarity to all (…) in my comments means sometimes I know a lot sometimes I know nothing (nice disclaimer). That's how I roll...See what I mean @Zpol ...my brain starts working in multiple directions. brain is faster than my fingers as I type... no brain fog(no lactic acid)… want to run up and down stairs... want to clean the house...want to mow the lawn...eyelids are high and eyes are nice and big...is this the beginning of a novel @Amazoniac...favorite saying "Woah Dog"...
 
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