The Warburg "effect" Is, In Fact, A Direct Cause Of Cancer

[Obi-wan]

Has Anyone Tried Sodium Acetate ? (for SIBO?) nice thread by ima maniac...

 

[Mufasa]

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.

Okay, I understand what you say there, but Ray Peat mentioned that he thinks a low ratio of GSH/GSSG is good, and this study also mentions that cancer cells may survive because of the high GSH/GSSG ratio.

 

[Mufasa]

The study is actually very specific why high GSH/GSSG ratio can be bad:

- GSH inhibits respiration by keeping cytochrome C inactive by reducing the enzyme.
- GSH inhibits apoptosis by scavenging ROS (and indirectly by inhibiting ROS generation from oxidative energy metabolism)

I guess Ray Peat's reasoning is something like if oxidative energy metabolism is impaired, then GSH/GSSG becomes high because there is very little oxidative stress from oxidative phosphorylation? I'm not sure if he actually says GSH is bad, or that he means that it is a sign that electrons are not being used.

Anyway, this study seems to agree with Ray Peat views, and making the point that you can not kick start oxidative metabolism again and kill cancer if GSH is kept high.

However, the controversy remains that vitamin C and vitamin E keep GSH high and PUFA lowers GSH. This kind of feels like that adding oxidative stress may be helpful in kickstarting metabolism so that cytochrome C can get in its active oxidative state again.

 

[haidut]

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...

Instead of feeding acetic acid, why not simply reactivate the PDH and/or reduce lactic acid with something like mehylene blue? Acetic acid is dangerous because it activates the FAS and may directly feed the tumor and make ti grow. The goal is not run away from glucose because it is wasted into lactate but to ensure it is properly metabolized.

 

[Mufasa]

Some background information from wikipedia about what it means if cytrochrome C oxidase is reduced:

COX exists in three conformational states: fully oxidized (pulsed), partially reduced, and fully reduced. Each inhibitor has a high affinity to a different state. In the pulsed state, both the heme a3 and the CuB nuclear centers are oxidized; this is the conformation of the enzyme that has the highest activity. A two-electron reduction initiates a conformational change that allows oxygen to bind at the active site to the partially-reduced enzyme. Four electrons bind to COX to fully reduce the enzyme. Its fully reduced state, which consists of a reduced Fe2+ at the cytochrome a3 heme group and a reduced CuB+ binuclear center, is considered the inactive or resting state of the enzyme.

 

[Mufasa]

Here is another study talking about the redox state of cytochrome C:
The Redox State of Cytochrome C Modulates Resistance to Methotrexate in Human MCF7 Breast Cancer Cells

 

[Elephanto]

@Obi-wan Aren't most diseases and symptoms of aging characterized by states of chronic oxidative stress, and this oxidation damaging the organs contribute to the inefficiency of energy production, elevation of stress hormones and general deterioration of the hormonal state. For instance statins inhibiting the body's natural production of CoEnzyme Q10, a potent antioxidant and mitochondrial protector, is hypothesized to be the reason why they lead to diabetes. Or excess Iron, a potent oxidant, being linked to many degenerative diseases including cancer. I know that increasing ROS has been considered as a strategy to weaken tumors but generally stressors (like glucose and oxygen deprivation) tend to have the opposite effect, that is to promote tumors to metastasize more aggressively. It seems like the goal would be to create the most stress-free environment to promote efficient energy production and that would include protecting the organs from oxidative stress. Moreover, several antioxidants like Vitamin E, Selenium (depending on the form), Zinc and Lycopene have shown efficacy against prostate cancer, suggesting that oxidation plays a promoting role. Another proof would be that glucose and oxygen deprivation, which haidut mentions actually promote cancer, cause oxidative stress :
Glucose deprivation induces mitochondrial dysfunction and oxidative stress in PC12 cell line. - PubMed - NCBI

 

[Obi-wan]

Instead of feeding acetic acid, why not simply reactivate the PDH and/or reduce lactic acid with something like mehylene blue? Acetic acid is dangerous because it activates the FAS and may directly feed the tumor and make ti grow. The goal is not run away from glucose because it is wasted into lactate but to ensure it is properly metabolized.

Biotin is a PDK inhibitor
Thiamine is a PDH upregulator
Niacinamide is a FAS inhibitor. So is Aspirin

B vitamins are made by bacteria in the digestive track or one could take Energin.

Not running away from Glycolysis just jump starting the Mitochondria machinery. I also take K2 and Lapodin

No acetate no citric acid cycle no ETC no -70 to -80 mVolt membrane potential. My quinones of choice are K2(yours) and Lapodin for the ETC...

 

[Obi-wan]

Some background information from wikipedia about what it means if cytrochrome C oxidase is reduced:

This only happens if ETC is working properly. ETC does not work without the Krebs cycle and NADH. If ETC is the engine then it does not work without the Krebs cycle which is the starter...a cell in the resting state has a -70 to -80 mvolt potential accomplished by potassium and sodium

 

[Mufasa]

This only happens if ETC is working properly. ETC does not work without the Krebs cycle and NADH. If ETC is the engine then it does not work without the Krebs cycle which is the starter...a cell in the resting state has a -70 to -80 mvolt potential accomplished by potassium and sodium

What only happens when ETC is working properly? Getting cytochrome c oxidase in its active fully oxidized state?

 

[Obi-wan]

@Obi-wan Aren't most diseases and symptoms of aging characterized by states of chronic oxidative stress, and this oxidation damaging the organs contribute to the inefficiency of energy production, elevation of stress hormones and general deterioration of the hormonal state. For instance statins inhibiting the body's natural production of CoEnzyme Q10, a potent antioxidant and mitochondrial protector, is hypothesized to be the reason why they lead to diabetes. Or excess Iron, a potent oxidant, being linked to many degenerative diseases including cancer. I know that increasing ROS has been considered as a strategy to weaken tumors but generally stressors (like glucose and oxygen deprivation) tend to have the opposite effect, that is to promote tumors to metastasize more aggressively. It seems like the goal would be to create the most stress-free environment to promote efficient energy production and that would include protecting the organs from oxidative stress. Moreover, several antioxidants like Vitamin E, Selenium (depending on the form), Zinc and Lycopene have shown efficacy against prostate cancer, suggesting that oxidation plays a promoting role. Another proof would be that glucose and oxygen deprivation, which haidut mentions actually promote cancer, cause oxidative stress :
Glucose deprivation induces mitochondrial dysfunction and oxidative stress in PC12 cell line. - PubMed - NCBI

If I did not have cancer I would take antioxidants. Normal cells can withstand a higher ROS than cancer cells. Not depriving the cells of glucose or oxygen (sitting here eating a bowl of fruit and breathing...)

 

[Obi-wan]

What only happens when ETC is working properly? Getting cytochrome c oxidase in its active fully oxidized state?

An electron transport chain (ETC) is a series of complexes that transfer electrons from electron donors to electron acceptors via redox (both reduction and oxidation occurring simultaneously) reactions, and couples this electron transfer with the transfer of protons (H+ ions) across a membrane. This creates an electrochemical proton gradient that drives the synthesis of adenosine triphosphate (ATP), a molecule that stores energy chemically in the form of highly strained bonds. The molecules of the chain include peptides, enzymes (which are proteins or protein complexes), and others. The final acceptor of electrons in the electron transport chain during aerobic respiration is molecular oxygen although a variety of acceptors other than oxygen such as sulfate exist in anaerobic respiration.

Electron transport chains are used for extracting energy via redox reactions from sunlight in photosynthesis or, such as in the case of the oxidation of sugars, cellular respiration. In eukaryotes, an important electron transport chain is found in the inner mitochondrial membrane where it serves as the site of oxidative phosphorylation through the action of ATP synthase.

In mitochondria, it is the conversion of oxygen to water, NADH to NAD+ and succinate to fumarate that are required to generate the proton gradient.

Electron transport chains are major sites of premature electron leakage to oxygen, generating superoxide and potentially resulting in increased oxidative stress (maybe this is why cancer wants to shut this down).

The electron transport chain consists of a spatially separated series of redox reactions in which electrons are transferred from a donor molecule to an acceptor molecule. The underlying force driving these reactions is the Gibbs free energy of the reactants and products. The Gibbs free energy is the energy available ("free") to do work. Any reaction that decreases the overall Gibbs free energy of a system is thermodynamically spontaneous.

The function of the electron transport chain is to produce a transmembrane proton electrochemical gradient as a result of the redox reactions (this is the -70 to -80 mV potential).[1] If protons flow back through the membrane, they enable mechanical work, such as rotating bacterial flagella. ATP synthase, an enzyme highly conserved among all domains of life, converts this mechanical work into chemical energy by producing ATP,[2] which powers most cellular reactions. A small amount of ATP is available from substrate-level phosphorylation, for example, in glycolysis. In most organisms the majority of ATP is generated in electron transport chains, while only some obtain ATP by fermentation ( but probably not enough to keep a -70 to -80 mVolt potential keeping the cell constantly depolarized and keeping sodium inside the cell and potassium outside the cell causing the cell to swell causing the Warburg effect..).

Most eukaryotic cells have mitochondria, which produce ATP from products of the citric acid cycle, fatty acid oxidation, and amino acid oxidation. At the mitochondrial inner membrane, electrons from NADH and FADH2 pass through the electron transport chain to oxygen, which is reduced to water. The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor will pass electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by actively "pumping" protons into the intermembrane space, producing a thermodynamic state that has the potential to do work. This entire process is called oxidative phosphorylation, since ADP is phosphorylated to ATP using the energy of hydrogen oxidation in many steps.

A small percentage of electrons do not complete the whole series and instead directly leak to oxygen, resulting in the formation of the free-radical superoxide, a highly reactive molecule that contributes to oxidative stress and has been implicated in a number of diseases and aging (@Elephanto)


Mitochondrial redox carriers[edit]
Energy obtained through the transfer of electrons down the ETC is used to pump protons from the mitochondrial matrix into the intermembrane space, creating an electrochemical proton gradient (ΔpH) across the inner mitochondrial membrane (IMM). This proton gradient is largely but not exclusively responsible for the mitochondrial membrane potential (ΔΨM). It allows ATP synthase to use the flow of H+ through the enzyme back into the matrix to generate ATP from adenosine diphosphate (ADP) and inorganic phosphate. Complex I (NADH coenzyme Q reductase; labeled I) accepts electrons from the Krebs cycle electron carrier nicotinamide adenine dinucleotide (NADH), and passes them to coenzyme Q (ubiquinone; labeled Q), which also receives electrons from complex II (succinate dehydrogenase; labeled II). Q passes electrons to complex III (cytochrome bc1 complex; labeled III), which passes them to cytochrome c (cyt c). Cyt c passes electrons to Complex IV (cytochrome c oxidase; labeled IV), which uses the electrons and hydrogen ions to reduce molecular oxygen to water (I use Vit K2 to aid this process).

Four membrane-bound complexes have been identified in mitochondria. Each is an extremely complex transmembrane structure that is embedded in the inner membrane. Three of them are proton pumps. The structures are electrically connected by lipid-soluble electron carriers and water-soluble electron carriers. The overall electron transport chain:

So the whole process of the ETC is to produce the -70 to -80 mVolt resting potential across the cell and mitochondria membrane...

Citric acid cycle

The name of this metabolic pathway is derived from the citric acid (a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH[6]) that is consumed and then regenerated by this sequence of reactions to complete the cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide as a waste byproduct (that's what I want). The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP (or membrane potential).

 

[Zpol]

An electron transport chain (ETC) is a series of complexes that transfer electrons from electron donors to electron acceptors via redox (both reduction and oxidation occurring simultaneously) reactions, and couples this electron transfer with the transfer of protons (H+ ions) across a membrane. This creates an electrochemical proton gradient that drives the synthesis of adenosine triphosphate (ATP), a molecule that stores energy chemically in the form of highly strained bonds. The molecules of the chain include peptides, enzymes (which are proteins or protein complexes), and others. The final acceptor of electrons in the electron transport chain during aerobic respiration is molecular oxygen although a variety of acceptors other than oxygen such as sulfate exist in anaerobic respiration.

Electron transport chains are used for extracting energy via redox reactions from sunlight in photosynthesis or, such as in the case of the oxidation of sugars, cellular respiration. In eukaryotes, an important electron transport chain is found in the inner mitochondrial membrane where it serves as the site of oxidative phosphorylation through the action of ATP synthase.

In mitochondria, it is the conversion of oxygen to water, NADH to NAD+ and succinate to fumarate that are required to generate the proton gradient.

Electron transport chains are major sites of premature electron leakage to oxygen, generating superoxide and potentially resulting in increased oxidative stress (maybe this is why cancer wants to shut this down).

The electron transport chain consists of a spatially separated series of redox reactions in which electrons are transferred from a donor molecule to an acceptor molecule. The underlying force driving these reactions is the Gibbs free energy of the reactants and products. The Gibbs free energy is the energy available ("free") to do work. Any reaction that decreases the overall Gibbs free energy of a system is thermodynamically spontaneous.

The function of the electron transport chain is to produce a transmembrane proton electrochemical gradient as a result of the redox reactions (this is the -70 to -80 mV potential).[1] If protons flow back through the membrane, they enable mechanical work, such as rotating bacterial flagella. ATP synthase, an enzyme highly conserved among all domains of life, converts this mechanical work into chemical energy by producing ATP,[2] which powers most cellular reactions. A small amount of ATP is available from substrate-level phosphorylation, for example, in glycolysis. In most organisms the majority of ATP is generated in electron transport chains, while only some obtain ATP by fermentation ( but probably not enough to keep a -70 to -80 mVolt potential keeping the cell constantly depolarized and keeping sodium inside the cell and potassium outside the cell causing the cell to swell causing the Warburg effect..).

Most eukaryotic cells have mitochondria, which produce ATP from products of the citric acid cycle, fatty acid oxidation, and amino acid oxidation. At the mitochondrial inner membrane, electrons from NADH and FADH2 pass through the electron transport chain to oxygen, which is reduced to water. The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor will pass electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by actively "pumping" protons into the intermembrane space, producing a thermodynamic state that has the potential to do work. This entire process is called oxidative phosphorylation, since ADP is phosphorylated to ATP using the energy of hydrogen oxidation in many steps.

A small percentage of electrons do not complete the whole series and instead directly leak to oxygen, resulting in the formation of the free-radical superoxide, a highly reactive molecule that contributes to oxidative stress and has been implicated in a number of diseases and aging (@Elephanto)


Mitochondrial redox carriers[edit]
Energy obtained through the transfer of electrons down the ETC is used to pump protons from the mitochondrial matrix into the intermembrane space, creating an electrochemical proton gradient (ΔpH) across the inner mitochondrial membrane (IMM). This proton gradient is largely but not exclusively responsible for the mitochondrial membrane potential (ΔΨM). It allows ATP synthase to use the flow of H+ through the enzyme back into the matrix to generate ATP from adenosine diphosphate (ADP) and inorganic phosphate. Complex I (NADH coenzyme Q reductase; labeled I) accepts electrons from the Krebs cycle electron carrier nicotinamide adenine dinucleotide (NADH), and passes them to coenzyme Q (ubiquinone; labeled Q), which also receives electrons from complex II (succinate dehydrogenase; labeled II). Q passes electrons to complex III (cytochrome bc1 complex; labeled III), which passes them to cytochrome c (cyt c). Cyt c passes electrons to Complex IV (cytochrome c oxidase; labeled IV), which uses the electrons and hydrogen ions to reduce molecular oxygen to water (I use Vit K2 to aid this process).

Four membrane-bound complexes have been identified in mitochondria. Each is an extremely complex transmembrane structure that is embedded in the inner membrane. Three of them are proton pumps. The structures are electrically connected by lipid-soluble electron carriers and water-soluble electron carriers. The overall electron transport chain:

So the whole process of the ETC is to produce the -70 to -80 mVolt resting potential across the cell and mitochondria membrane...

Citric acid cycle

The name of this metabolic pathway is derived from the citric acid (a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH[6]) that is consumed and then regenerated by this sequence of reactions to complete the cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide as a waste byproduct (that's what I want). The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP (or membrane potential).

Good info to have.
I'm stuck in the middle. I don't have cancer but I do have poor functioning cells (and poor ETC) and high oxidative stress so even though my cells should theoretically withstand ROS, I'm leary of taking anything that will cause oxidation. My high oxidative stress is coming from deficiency of zinc and too much free copper. My doc also says I'm extremely deficient in vitamin C and glutathione. I'm so confused about all this but I have an idea though, I think consistent testing of cell membrane integrity and hydration using a Bioimpedance analyser might help so that I can try things and know if I'm on the right track.
My issue is wether to take antioxidant supp's (I already drink lots of OJ) to improve my ability to fight the infections, or use MB or something to cause oxidation to knock out the infections I have. Zinc supp's don't help.
I'm mainly posting this to see what you all think of using a Bioimpedance analysis device to determine cellular health... So we can know if we are on the right path.

 

[haidut]

Biotin is a PDK inhibitor
Thiamine is a PDH upregulator
Niacinamide is a FAS inhibitor. So is Aspirin

B vitamins are made by bacteria in the digestive track or one could take Energin.

Not running away from Glycolysis just jump starting the Mitochondria machinery. I also take K2 and Lapodin

No acetate no citric acid cycle no ETC no -70 to -80 mVolt membrane potential. My quinones of choice are K2(yours) and Lapodin for the ETC...

Actually, any of the Krebs cycle intermediates can be fed and will work just as well as if somebody was eating food. The safest one is probably succinic acid. The others, especially malic acid and oxaloacetate tend to inhibit SADH and thus lower ETC activity. Acetic acid is OK but in high amounts does shift the functioning towards fatty acid synthesis. Ingesting a lot of exogenous acetic acid is not the same as synthesizing it as a result of PDH and bound to coenzyme A. There is probably a sweet point beyond which exogenous acetic acid is risky, while getting it from food conversion through PDH is rate-limited. This is why drinking alcohol fattens up the liver - too much acetic acid that the Krebs cycle and ETC cannot handle. But adding a catalyst like MB can avoid that buildup of acetic acid and this has been confirmed in animal studies.
http://www.jbc.org/content/194/1/177.full.pdf
"...Acetic acid or a closely related 2-carbon unit is the most likely immediate precursor for fatty acids in the animal organism (1). This Cz unit can arise either directly as a product of the breakdown of the fatty acids themselves (2) and of a number of amino acids (3), or indirectly from carbohydrate by way of pyruvic acid (4)."

 

[Mito]

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.

Aren’t Vitamin E and Vitamin C important in recycling GSH back to GSSG?

 

[Mufasa]

Aren’t Vitamin E and Vitamin C important in recycling GSH back to GSSG?

As far as I know, they recycle GSSG back to GSH.

 

[Obi-wan]

Actually, any of the Krebs cycle intermediates can be fed and will work just as well as if somebody was eating food. The safest one is probably succinic acid. The others, especially malic acid and oxaloacetate tend to inhibit SADH and thus lower ETC activity. Acetic acid is OK but in high amounts does shift the functioning towards fatty acid synthesis. Ingesting a lot of exogenous acetic acid is not the same as synthesizing it as a result of PDH and bound to coenzyme A. There is probably a sweet point beyond which exogenous acetic acid is risky, while getting it from food conversion through PDH is rate-limited. This is why drinking alcohol fattens up the liver - too much acetic acid that the Krebs cycle and ETC cannot handle. But adding a catalyst like MB can avoid that buildup of acetic acid and this has been confirmed in animal studies.
http://www.jbc.org/content/194/1/177.full.pdf
"...Acetic acid or a closely related 2-carbon unit is the most likely immediate precursor for fatty acids in the animal organism (1). This Cz unit can arise either directly as a product of the breakdown of the fatty acids themselves (2) and of a number of amino acids (3), or indirectly from carbohydrate by way of pyruvic acid (4)."

I take 2 tablespoonfuls 2 to 3 times a day which is the recommended dosage by Bragg plus take Lapodin and Aspirin to inhibit FAS. I noticed in the study it was saturated fat that they were talking about. I take Cocoa powder in coffee for stearic acid...I will try 2 drops of Oxidal in orange juice with my 10 drops of Lapodin.

Interesting:

Several of the citric acid cycle intermediates are used for the synthesis of important compounds, which will have significant cataplerotic effects on the cycle.[36] Acetyl-CoA cannot be transported out of the mitochondrion. To obtain cytosolic acetyl-CoA, citrate is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion).[39] The cytosolic acetyl-CoA is used for fatty acid synthesis and the production of cholesterol. Cholesterol can, in turn, be used to synthesize the steroid hormones, bile salts, and vitamin D. -Wikipedia

 

[Sourdoughbanana]

I hadn't realized Peat discusses Warburg briefly in one of my favorite articles of his:

Glucose and sucrose for diabetes.

The ability of the mitochondria to oxidize pyruvic acid and glucose is characteristically lost to some degree in cancer. When this oxidation fails, the disturbed redox balance of the cell will usually lead to the cell's death, but if it can survive, this balance favors growth and cell division, rather than differentiated function. This was Otto Warburg's discovery, that was rejected by official medicine for 75 years.

Cancer researchers have become interested in this enzyme system that controls the oxidation of pyruvic acid (and thus sugar) by the mitochondria, since these enzymes are crucially defective in cancer cells (and also in diabetes). The chemical DCA, dichloroacetate, is effective against a variety of cancers, and it acts by reactivating the enzymes that oxidize pyruvic acid. Thyroid hormone, insulin, and fructose also activate these enzymes. These are the enzymes that are inactivated by excessive exposure to fatty acids, and that are involved in the progressive replacement of sugar oxidation by fat oxidation, during stress and aging, and in degenerative diseases; for example, a process that inactivates the energy-producing pyruvate dehydrogenase in Alzheimer's disease has been identified (Ishiguro, 1998). Niacinamide, by lowering free fatty acids and regulating the redox system, supporting sugar oxidation, is useful in the whole spectrum of metabolic degenerative diseases.

(I'm glad I'm done with starch from now on. Better late than never)

 

[Inaut]

great thread here. I wish i had more to offer then just that but thanks all. keep posting :)

 

[Elephanto]

I hadn't realized Peat discusses Warburg briefly in one of my favorite articles of his:

Glucose and sucrose for diabetes.



(I'm glad I'm done with starch from now on. Better late than never)

This isn't an argument for starch avoidance or even high fructose intake. The fact that Fructose has beneficial functions (many that can be achieved at low doses) doesn't imply that it is beneficial in unlimited amount. High Fructose intake has been shown to potently increase lipogenesis.

While both sugars increased ChREBP-β, fructose supplementation uniquely increased SREBP1c and downstream fatty acid synthesis genes, resulting in reduced liver insulin signaling.

Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. - PubMed - NCBI

Fructose induced lipogenesis: from sugar to fat to insulin resistance. - PubMed - NCBI

Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity. - PubMed - NCBI

INCREASED FRUCTOSE CONSUMPTION IS ASSOCIATED WITH FIBROSIS SEVERITY IN PATIENTS WITH NAFLD

Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH.

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. - PubMed - NCBI
High Fructose intake can increase gut permeability which would explain its effect on endotoxemia. Endotoxins also being a cause of liver damage.
Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease