Raymond Peat
Member
- Aug 3, 2024
- 13
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The study below is one perhaps the most comprehensive review published to date, challenging the medical dogma that cancer is a genetic/mutation disease. As the study aptly explains, the evidence, spanning as far back as Otto Warburg’s original work on this disease, is overwhelmingly in support of cancer being entirely metabolic in origin. Warburg stated that the metabolic defects seen in cancer are “irreversible”, but that does not mean they are of genetic origin! To the contrary – the accumulated evidence strongly suggests that any genetic mutations observed in “cancer” cells are secondary and downstream effects of those cells’ deranged metabolism. When Warburg said the metabolic changes are “irreversible”, apparently he meant that in a strictly “functional” context – i.e. irreversible for as long as the factor driving them is still present. Remove that factor and the “cancer” cells likely revert to normal behavior/metabolism. So, what is that mysterious prima causa of cancer, causing initially its functional derangement (e.g. Warburg Effect) and subsequently its structural changes (genetic mutations)? Well, as the article convincingly demonstrates, (excessive) fatty acid oxidation (FAO), also known as β-oxidation, through the reductive state (lowered mitochondrial NAD/NADH ratio) it leads to is both a necessary and sufficient factor for the initiation, growth and metastasizing of cancer. Thus, FAO is likely that prima causa medicine has been searching for more than century. Conversely, inhibiting FAO is likely the most promising avenue for truly curing that disease, and likely other metabolic (all?) diseases. Speaking of other diseases, as the study demonstrates, there does not seem to be some critical, specific threshold beyond which FAO becomes detrimental. The pathological effects of FAO are basically on a spectrum – the more it is increased the more reductive the redox state of the cell becomes, and the more deranged its metabolism becomes in desperate attempt to allow the cell to survive in this pseudo-hypoxic environment. As such, the “seeds” of cancer development can be seen even in states that medicine considers perfectly normal, and even desirable. Namely, glucose deprivation (through fasting and/or low-carb diets), acute/chronic stress (e.g. exhaustive exercise), or even administration of “beneficial” drugs such as metformin. Any activity or substance that shifts the so-called Randle Cycle in favor of FAO will likely lead to pathology, and the severity of that pathology can vary from mild elevations of blood glucose, to insulin resistance, to diabetes, and ultimately to CVD, liver disease, and even cancer depending on to what degree the Randle Cycle has been shifted in favor of FAO and for how long that state has persisted. Btw, one of the most effective metabolic inhibitors that is consumed by people every day is PUFA. Ironically, as the study explains, the initial process of FAO actually favors PUFA as a substrate. So, PUFA seem to have a unique role as not only a universally-consumed metabolic inhibitor, but also as the preferred fuel of cancer.
If this hypothesis is correct, simple, cheap and widely available interventions may be able to truly cure cancer in many/most cases, as well as most/all other diseases (assuming they are all metabolic in origin). Namely, aspirin, quinine, niacinamide, thiamine, progesterone, pregnenolone, androgens, vitamin D, baking soda, methylene blue, vitamin K, tetracycline antibiotics, anti-serotonin chemicals, etc all have a role as therapies (especially for cancer) and their combination is likely to be even more effective than using any of those on its own. For very advanced or highly aggressive cancers, high doses of drugs such as Meldonium (Mildronate) may be needed to sufficiently restrict FAO, and adding aspirin would be highly synergistic as several studies on Meldonium/aspirin for heart disease have already demonstrated. Equally important would be practices such as avoiding dietary PUFA (and other metabolic inhibitors such as raw vegetables), limiting stress, and performing exercise that is mostly of concentric origin (biking, swimming, climbing stairs, jumps, etc) and only within the so-called glycogen-bound state (i.e. only until glucose stores are depleted and then the person must stop and replenish glycogen stores so that the person does not end up in state where FAO takes over within the Randle cycle).
https://www.hindawi.com/journals/omcl/2022/2339584/
“…The main aspect of these pioneering studies is the increased mitochondrial ratios of NADH/NAD+, acetyl-CoA/CoA and ATP/ADP, and the accumulation of citrate in the mitochondria [70] (Figure 5). Currently, the study of antagonism between mFAO and glycolysis and accumulation of acetyl-CoA from fatty acid oxidation seems to have been forgotten. Even less attention is paid to the increased NADH/NAD+ ratio [83]. The increase in NADH has not been explained and has also been forgotten. The Krebs cycle could be inhibited by elevated NADH concentrations. High amount of NADH inhibits the PDH and Krebs cycle dehydrogenases and decreases combustion of pyruvate and glucose [87]. This is normal regulation when the amount of ATP is at the upper threshold in the cell, which decreases glucose combustion. Does this regulation also work for mFAO to decrease fatty acid combustion? The answer seems to be positive, given that the Krebs cycle can be inhibited by high concentrations of NADH.
“…However, mFAO consists of two parts—β-oxidation and the Krebs cycle. ATP does not apply the same force to β-oxidation, which precedes the Krebs cycle. We are accustomed to accept that at rest, the energy metabolism is self-regulating on the principle of feedback and the NADH/NAD+ ratio in mitochondria may vary depending on the utilization of ATP. Sahlin and Katz reported that mitochondrial NADH in skeletal muscles at rest is between 36% and 60%, while in the heart muscles it is between 4.2% and 13% [88]. So, that must be the difference in the redox state of the mitochondrial matrix between highly active tissues and tissues in rest. In rest, ATP has a feedback effect on all metabolic processes associated with its production. This also applies to the Krebs cycle.”
If this hypothesis is correct, simple, cheap and widely available interventions may be able to truly cure cancer in many/most cases, as well as most/all other diseases (assuming they are all metabolic in origin). Namely, aspirin, quinine, niacinamide, thiamine, progesterone, pregnenolone, androgens, vitamin D, baking soda, methylene blue, vitamin K, tetracycline antibiotics, anti-serotonin chemicals, etc all have a role as therapies (especially for cancer) and their combination is likely to be even more effective than using any of those on its own. For very advanced or highly aggressive cancers, high doses of drugs such as Meldonium (Mildronate) may be needed to sufficiently restrict FAO, and adding aspirin would be highly synergistic as several studies on Meldonium/aspirin for heart disease have already demonstrated. Equally important would be practices such as avoiding dietary PUFA (and other metabolic inhibitors such as raw vegetables), limiting stress, and performing exercise that is mostly of concentric origin (biking, swimming, climbing stairs, jumps, etc) and only within the so-called glycogen-bound state (i.e. only until glucose stores are depleted and then the person must stop and replenish glycogen stores so that the person does not end up in state where FAO takes over within the Randle cycle).
https://www.hindawi.com/journals/omcl/2022/2339584/
“…The main aspect of these pioneering studies is the increased mitochondrial ratios of NADH/NAD+, acetyl-CoA/CoA and ATP/ADP, and the accumulation of citrate in the mitochondria [70] (Figure 5). Currently, the study of antagonism between mFAO and glycolysis and accumulation of acetyl-CoA from fatty acid oxidation seems to have been forgotten. Even less attention is paid to the increased NADH/NAD+ ratio [83]. The increase in NADH has not been explained and has also been forgotten. The Krebs cycle could be inhibited by elevated NADH concentrations. High amount of NADH inhibits the PDH and Krebs cycle dehydrogenases and decreases combustion of pyruvate and glucose [87]. This is normal regulation when the amount of ATP is at the upper threshold in the cell, which decreases glucose combustion. Does this regulation also work for mFAO to decrease fatty acid combustion? The answer seems to be positive, given that the Krebs cycle can be inhibited by high concentrations of NADH.
“…However, mFAO consists of two parts—β-oxidation and the Krebs cycle. ATP does not apply the same force to β-oxidation, which precedes the Krebs cycle. We are accustomed to accept that at rest, the energy metabolism is self-regulating on the principle of feedback and the NADH/NAD+ ratio in mitochondria may vary depending on the utilization of ATP. Sahlin and Katz reported that mitochondrial NADH in skeletal muscles at rest is between 36% and 60%, while in the heart muscles it is between 4.2% and 13% [88]. So, that must be the difference in the redox state of the mitochondrial matrix between highly active tissues and tissues in rest. In rest, ATP has a feedback effect on all metabolic processes associated with its production. This also applies to the Krebs cycle.”