Cancer Is A State Of Chronic Stress With Elevated Lipolysis And Ketogenesis

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haidut

haidut

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“Cancer cells use glucose and the amino acid glutamine primarily for synthetic purposes, and use fats as their energy source;the growth stimulating effect of the "essential fatty acids" (Sueyoshi and Nagao, 1962a; Holley, et al., 1974) shows that depriving a tumor of those fats retards its growth. The great energetic inefficiency of the cancer metabolism, which causes it to produce a large amount of heat and to cause systemic stress, failure of immunity, and weight loss, is because it synthesizes fat from glucose and amino acids, and then oxidizes the fat as if it were diabetic.

Estrogen, which is responsible for the fact that women burn fatty acids more easily than men, is centrally involved in this metabolic inefficiency.” — Ray Peat

Thanks. Pretty much what I said, right?
 
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“Cancer cells use glucose and the amino acid glutamine primarily for synthetic purposes, and use fats as their energy source;the growth stimulating effect of the "essential fatty acids" (Sueyoshi and Nagao, 1962a; Holley, et al., 1974) shows that depriving a tumor of those fats retards its growth. The great energetic inefficiency of the cancer metabolism, which causes it to produce a large amount of heat and to cause systemic stress, failure of immunity, and weight loss, is because it synthesizes fat from glucose and amino acids, and then oxidizes the fat as if it were diabetic.

Estrogen, which is responsible for the fact that women burn fatty acids more easily than men, is centrally involved in this metabolic inefficiency.” — Ray Peat
References in absentia.
 

Wilfrid

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LOL so you mention Warburg and then say cancer eats fat? WTF Warburg couldn't have been more clear, cancer thrives on glucose. These BS studies with genetically engineered cells pale in comparison to Warburg's extremely thorough and detailed work. He would scoff at those ridiculous studies. DCA works by KILLING the cell with ROS from glucose going through the disfuctional mitochondria.
Hi rob,
You seem very knowledgeable about Warburg's work on tumor.
And I'm sure that you will probably enlighten me about what he said on paragraph 8 in his own article regarding the metabolism of tumor growth:

http://images.biomedsearch.com/19872213/519.pdf?AWSAccessKeyId=AKIAIBOKHYOLP4MBMRGQ&Expires=1515715200&Signature=aZGcyCjA2kmtczdLnNZK2ZYeUfo=

Below is what Warburg said about glucose and tumor:

" VIII. The Effect of Want of Glucose.

Silberstein, TM yon Witzleben, and Rondoni ~have published experiments which make it seem likely that relationships exist between fermentation and tumor-growth. Insulin checks the growth, glucose accelerates it. We can understand the effects if we consider that slight changes in the blood-sugar concentration affect fermentation considerably, because the tumor is badly supplied with glucose. Experiments with slices of tumor in vitro give in this respect a false picture of the sensitivity of fermentation in the body. If for example we reduce the glucose content of serum surrounding a slice of tumor from 0.1 per cent to 0.05 per cent, the aerobic fermentation of the tumor is halved. But if we vary the arterial glucose content witMn the same limits, fermentation is not halved, but, as can be easily shown, it is reduced to one-quarter, on account of the bad provision for the tumor.
Different from the question of checking tumor growth is the problem of killing off tumor cells in living animals.
Tumor cells obtain the oxygen necessary for respiration from the blood circulation. Consequently they can exist without glucose. Even if it were possible to remove the blood-sugar entirely in living animals, the life of the tumor would not be threatened.
To support this statement, we kept tumor animals at very low blood-sugar content in insulin convulsions for hours, and then measured the metabolism of pieces of tumor so treated. We found respiration and fermentation nearly normal, a proof that the main part of the tumor cells was intact. "


It seems that Warburg couldn't have been more clear about his own statement: " Tumors can exist without glucose. ", no? What do you think ?
Also could you please redirect me to an article written by Warburg himself ( much like the one I provided above ), even in german, where he clearly states that " cancer thrives on glucose " ?
Thanks in advance.
 
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Fasting is the way to go Peatple.
1495168018341.gif
 
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Hi rob,
You seem very knowledgeable about Warburg's work on tumor.
And I'm sure that you will probably enlight me about what he said on paragraph 8 in his own article regarding the metabolism of tumor growth.
http://images.biomedsearch.com/19872213/519.pdf?AWSAccessKeyId=AKIAIBOKHYOLP4MBMRGQ&Expires=1515715200&Signature=aZGcyCjA2kmtczdLnNZK2ZYeUfo=


" VIII. The Effect of Want of Glucose.

Silberstein, TM yon Witzleben, and Rondoni ~have published experiments which make it seem likely that relationships exist between fermentation and tumor-growth. Insulin checks the growth, glucose accelerates it. We can understand the effects if we consider that slight changes in the blood-sugar concentration affect fermentation considerably, because the tumor is badly supplied with glucose. Experiments with slices of tumor in vitro give in this respect a false picture of the sensitivity of fermentation in the body. If for example we reduce the glucose content of serum surrounding a slice of tumor from 0.1 per cent to 0.05 per cent, the aerobic fermentation of the tumor is halved. But if we vary the arterial glucose content witMn the same limits, fermentation is not halved, but, as can be easily shown, it is reduced to one-quarter, on account of the bad provision for the tumor.
Different from the question of checking tumor growth is the problem of killing off tumor cells in living animals. Tumor cells obtain the oxygen necessary for respiration from the blood circulation. Consequently they can exist without glucose. Even if it were possible to remove the blood-sugar entirely in living animals, the life of the tumor would not be threatened.
To support this statement, we kept tumor animals at very low blood-sugar content in insulin convulsions for hours, and then measured the metabolism of pieces of tumor so treated. We found respiration and fermentation nearly normal, a proof that the main part of the tumor cells was intact.
"


It seems that Warburg couldn't have been more clear about his own statement: " Tumors can exist without glucose. ", no?
What do you think?
Thanks for the link, LOL if you think Im some expert, I would question your perception, all I know is that Warburg was a great scientist and he found that cancer ferments glucose. For your paragraph, I don't have a real refutation, but the fact still remains that 1) a culture medium with zero glucose is of course unphysiological and 2) A tumor's primary fuel is glucose, which that paragraph illustrates quite nicely.

Paragraph II : "If the provision for tumors were less complete than that of normal cells, then depression of arterial oxygen and glucose content would harm the tumor cells without affecting the better supplied normal organs. The resistance of single tumor cells is not to be compared with that of single normal cells, but rather the tumor as a whole with the organism as a whole."

Warburg didn't forget that a tumor is a macro problem for the whole body to deal with, Im just saying fasting is a method which allows the body to deal with it.
 

Wilfrid

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I understand your point but if glucose is tumor's primary fuel, how does on earth Warburg came to the following conclusion: " Even if it were possible to remove the blood sugar entirely in living animals, the life of the tumor would not be threatened. " ? The suppression of the main causal factor should have had, at least, an impact on the tumor, in vivo...but, yet, Warburg came to the inverse conclusion.
I tried in the past to read an article written by Warburg where he clearly states, himself, that cancer thrives on glucose or either, like you said, that glucose is tumor's primary fuel. Again,even a reference in german will do and I simply thought that you may have some Warburg's articles about that...but if you can't that's fine too. I will start to question my perception.
 
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I don't know about a word for word literal statement saying "cancer thrives on glucose" but I guess it is implied in his fundamental findings, even in your quoted passage above..."But if we vary the arterial glucose content witMn the same limits, fermentation is not halved, but, as can be easily shown, it is reduced to one-quarter, on account of the bad provision for the tumor."



 

Wilfrid

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I don't know about a word for word literal statement saying "cancer thrives on glucose" but I guess it is implied in his fundamental findings, even in your quoted passage above..."But if we vary the arterial glucose content witMn the same limits, fermentation is not halved, but, as can be easily shown, it is reduced to one-quarter, on account of the bad provision for the tumor."
As I understand the full quote ( see Warburg's whole explanation before the: "...But if..."), he simply outlined the fact that, in vivo, glucose limitation was simply 75% less effective than in-vitro. as to halved the fermentation. Thanks to this, he desmonstrated that the 100% success observed in-vitro was simply not reproductible in a living organism ( i.e: Experiments with slices of tumor in vitro give in this respect a false picture of the sensitivity of fermentation in the body. ) and, more important, that tumor's glucose supply was not the limiting factor in tumor growth. Hence his following and final paragragh statement on the subject: " Even if it were possible to remove the blood sugar entirely in living animals, the life of the tumor would not be threatened.".
 
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" Even if it were possible to remove the blood sugar entirely in living animals, the life of the tumor would not be threatened.".
That is tumor survival, not growth. Glucose causes growth. Growth of tumors is what kills people. There will always be glucose in the blood, just that the more there is, the faster the tumor will grow.
 
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Whataboutbob

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........ “all I know is that Warburg was a great scientist and he found that cancer ferments glucose”. So very true ! But can’t we say that all cells in a compromised state prior to cancer fluctuate back and forth (fermenting glucose vs respiration) depending on the health of the person, and then as a persons becomes more stuck in chronic state (low metabolism sickness )the cells become de-differentiated .......tumor developes.....(cancer cell) of which I would call “minimalist cell” because of the cells choice to conserve energy, choosing glycolysis over oxidative respiration, and as Ray has said -i.e. that all cells will revert to growth, division and glycolysis unless mechanisms (of which high metabolism is needed and a must) for restraining that growth are working properly...@haidut.. “Glycolysis is cheaper for dividing cell” ........Cancer ferments glucose=Lactic Acid and that’s the problem this paper addresses..... http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.923.2505&rep=rep1&type=pdf

Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis......this was good but way over my head.....
 

Wilfrid

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That is tumor survival, not growth. Glucose causes growth. Growth of tumors is what kills people. There will always be glucose in the blood, just that the more there is, the faster the tumor will grow.
Thanks for taking the time to response.
That is basically what he is saying in the article: glucose accelerates the growth but insulin checks it.
According to Warburg, insulin plays a major role in checking tumor growth (@haidut has posted about insulin as a potential effective treatment against cancer in this thread and it was already proved effective in rodents: Reversal of tumor-associated hyperglucagonemia as treatment for cancer cachexia. - PubMed - NCBI ) and a steady source of glucose increases blood insulin. Insulin seems clearly protective which confirm Warburg's finding about it. The pancreas is a major organ in glucose metabolism/regulation and insulin secretion ( produces from the beta cells ). As such any substances that will act as a protective factor for the pancreas ( and especially for the beta-cells ) are likely to play a huge role against tumor growth ( and maybe by extension to tumor survival ). Cortisol, glucagon, epinephrine, norepinephrine, STH are examples of antagonists to insulin. In a fasting state as well as in cancer cachexia, a high glucagon/insulin ratio is present.
For example, in pancreatic cancer tissues ( one of the most aggressive and deadly cancer to date ), there is, also, a trend for an increased glucagon/insulin mRNA ratio. Glucagon is a water-soluble polypeptide with a fairly short half-life, and is usually excreted rapidly. However excess doses ( as to a continue secretion ) could result in metaglucagon diabetes and high blood sugar. And this medical picture is often more commonly see in women than in men, as glucagon is more concentrated in female than in male pancreas. The net result is: decreased protein and fatty acid synthesis, increased lipolysis, increased CHO glycogenolysis and very important: increased protein catabolism which further complicates the picture as @d1d2 posted, since when cancer cells are deprived of glucose they have the ability to break down muscle tissue to extract glutamine.
Ray often mentionned glucose as a regenerative substance for the beta-cells. So let's get back to what Warburg said: insulin ckecks the growth and the beta-cells of the pancreas ( in a cancer state ) are clearly damaged ( as well as adrenal ascorbic acid ) by a glucagon excess.
And since glucagon induces a catabolic effect, mainly by activating liver glycogenolysis and gluconeogenesis, which results in the release of glucose to the bloodstream, situation that should be avoid at all cost to prevent tumor growth, according to what you posted: « There will always be glucose in the blood, just that the more there is, the faster the tumor will grow.»
My question is: how could fasting or dietary glucose restriction help someone with pancreatic cancer as those approaches are all likely to produce a high glucagon/insulin ratio.
Restoring an efficient glucose oxidative state seems far more productive as to protect the major organ in insulin secretion rather than restricting glucose or doing a fast.
 
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Injecting insulin will rapidly lower blood glucose, maybe that transiently stresses the tumor, but the low glucose triggers cortisol and reactive hyperglycemia, leading to a large and sustained increase in blood glucose.
Whether it is exogenous or endogenous insulin, it will always create large undulations in your metabolism, which is favorable for anabolic growth ( I think of insulin as the first domino of the anabolic cascade) not favorable for immune activity.
 

Whataboutbob

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........ “all I know is that Warburg was a great scientist and he found that cancer ferments glucose”. So very true ! But can’t we say that all cells in a compromised state prior to cancer fluctuate back and forth (fermenting glucose vs respiration) depending on the health of the person, and then as a persons becomes more stuck in chronic state (low metabolism sickness )the cells become de-differentiated .......tumor developes.....(cancer cell) of which I would call “minimalist cell” because of the cells choice to conserve energy, choosing glycolysis over oxidative respiration, and as Ray has said -i.e. that all cells will revert to growth, division and glycolysis unless mechanisms (of which high metabolism is needed and a must) for restraining that growth are working properly...@haidut.. “Glycolysis is cheaper for dividing cell” ........Cancer ferments glucose=Lactic Acid and that’s the problem this paper addresses.....

Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis......this was good but way over my head.....
 
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........ “all I know is that Warburg was a great scientist and he found that cancer ferments glucose”. So very true ! But can’t we say that all cells in a compromised state prior to cancer fluctuate back and forth (fermenting glucose vs respiration) depending on the health of the person, and then as a persons becomes more stuck in chronic state (low metabolism sickness )the cells become de-differentiated .......tumor developes.....(cancer cell) of which I would call “minimalist cell” because of the cells choice to conserve energy, choosing glycolysis over oxidative respiration, and as Ray has said -i.e. that all cells will revert to growth, division and glycolysis unless mechanisms (of which high metabolism is needed and a must) for restraining that growth are working properly...@haidut.. “Glycolysis is cheaper for dividing cell” ........Cancer ferments glucose=Lactic Acid and that’s the problem this paper addresses..... http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.923.2505&rep=rep1&type=pdf

Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis......this was good but way over my head.....
Nice studies, I agree with your basic premises.

Clearly the lactate is both a sign of fermentation and destabilizing agent in its own right. It's a lot harder on the kidneys and liver to maintain Ph and general homeostasis if there is massive amounts of lactate pouring into the blood. Even in a healthy person, large sugar feedings will transiently increase lactate. That first study pointed to lactate interfering with lymphocyte production, which goes in line with what I said earlier about the immune system and trying not to interfere with it, best way is through Gerson/fasting. Haidut is getting caught up in all the cancer research, easy mistake to make for a smart guy.
 

Koveras

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I am posting this study because it invalidates one of the central dogmas of modern oncology - i.e. that cancer is a localized, organ-specific disease that is best handled by attacking/destroying/removing the affected organ/tissue. Most doctors would flatly deny/reject the statement that a cancer patient is under chronic systemic stress as a result of their disease, and as such they see no problem with subjecting the patient to even more systemic stress as a result of radiation, chemotherapy and surgery.
This study shows that all organisms with a tumor burden experience increased lipolysis and ketogenesis. Mainstream medicine recognizes these metabolic abnormalities in cancer patients but claims that they are the result of poor appetite and anorexia in the patient. This study found that it is the tumor presence and not dietary abnormalities that change the patient's metabolism from carbohydrates to fatty acids. Perhaps more importantly, just as Peat has said, the brain plays a central role in directing this change of metabolic fuel preference. Given the recent studies I published that blocking fat metabolism can treat cancer, I think it confirms once again one of Peat's main points - any prolonged stress skews metabolism in favor of fatty acids, and conversely elevated lypolysis/ketogenesis/NEFA are a sign of systemic stress and not something that is desirable to maintain long term.
Just as an additional example, diverse conditions like depression, diabetes, schizphrenia, dementia/Alzheimer, Parkinson, ALS, liver disease, kidney disease, infection, etc are all also characterized by increased fatty acid level and metabolism and consequently reduced glucose oxidation. It is really all one disease under different names, and it comes down to blockade of proper oxidation of glucose. So, anything that improves glucose oxidation should be therapeutic regardless of the specific named "condition" a person has been diagnosed with.

[Activation of lipolysis and ketogenesis in tumor-bearing animals as a reflection of chronic stress states]. - PubMed - NCBI
"...In order to elucidate the peculiarities of brain metabolism in tumour-bearing organisms, the arterio-venous (A-V) content of glucose, acetoacetate (Ac-Ac), beta-hydroxybutyrate (beta-HB) and non-esterified fatty acids (NEFA) in growing Zajdela ascite hepatoma (ZAH) and solid hepatoma 27 (H-27) was compared. Analysis of metabolic patterns of healthy, starving and fed recipients (ZAH and H-27) revealed the inadequacy of the concepts on anorexia as being the cause of carbohydrate-lipid metabolic disturbances. In tumour-bearing organisms lipolysis and ketogenesis reflect the tumour-induced chronic stress. Absorption of beta-HB and release of Ac-Ac by brain were observed at all stages of malignant growth. This is probably due to a partial switch-over of brain metabolism to non-carbohydrate energy sources. Besides, certain stages of tumour growth are associated with active assimilation of NEFA by brain. A correlation between the A-V difference with respect to glucose and Ac-Ac as well as between the glucose and NEFA contents was established. It was assumed that the A-V difference in glucose is the main regulator of ketone body metabolism."

Ketone bodies as a predictor of prognosis of hepatocellular carcinoma after transcatheter arterial chemoembolization

"Increase of venous ketone bodies is negatively correlated with survival."
 
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Thanks. Since you mentioned HCC - not sure if you know but the drug sorafenib used as core therapy for HCC is actually a niacinamide derivative. In fact, it is just 3 niacinamide molecules plus some fluorine. Aside from the toxic effects of fluorine I wonder if the benefits of that drug for HCC are not mostly due to lowering FFA and thus ketone bodies...
Sorafenib - Wikipedia
 

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best way is through Gerson/fasting
Gerson and fasting seem very different to me. My reading of Gerson is that he was keen to have people drink juice regularly enough to maintain blood sugars, and to live on a very high carb low fat (and high mineral and vitamin) diet during treatment - and plenty of it, no drinking water, since this would displace necessary nourishment. This seems contrary to my reading of your arguments. You did not seem to favour supplying abundant sugars.
 
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Gerson and fasting seem very different to me. My reading of Gerson is that he was keen to have people drink juice regularly enough to maintain blood sugars, and to live on a very high carb low fat (and high mineral and vitamin) diet during treatment - and plenty of it, no drinking water, since this would displace necessary nourishment. This seems contrary to my reading of your arguments. You did not seem to favour supplying abundant sugars.
Gerson is calorie restriction, lol try getting enough calories drinking veggie juice. Protein restriction combined with calorie restriction has many similar effects to fasting. I personally believe the calorie/protein restriction is more important than the high potassium/low sodium but I would love to see a study done comparing CR high potassium +low/high sodium.
 

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