Fasting/exercise/lowcarb/keto may promote cancer (melanoma) metastasis

haidut

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Quite the title for this post, but I think the evidence from the study below is clear. Namely, chronic activation of the so-called "master metabolic sensor" AMPK is a key mechanism through which melanoma cells rewire their metabolism from higher into lower OXPHOS, change their physical structure and mitochondria shape/size, and become highly invasive/aggressive. Conversely, blocking AMPK reversed the aggressive melanoma phenotype back to a less aggressive, localized version. Now, AMPK has been promoted for decades all over the blogosphere (and medical journals) as the best thing next to immortality, and is proposed as the key mechanism through which "endurance" exercise, caloric restriction, low-carb diets, or even pharmaceutical lifespan extenders exert their benefits. Its main systemic effect is to increase metabolic efficiency, and switch metabolism from OXPHOS of glucose to primarily fatty acid oxidation (FAO). Speaking of lifespan extenders, the current pharmacological darling of the blogosphere (and mainstream medicine) - metformin - works primarily as an AMPPK-activator. Despite all of the purported "benefits" of AMPK, even the official Wiki page acknowledges that AMPK may have a role as a tumor promoter, ironically, by protecting cancer cells from metabolic stress induced by chemotherapy/radiation. In other words, after cancer has formed, AMPK may be strong protector of said cancer. However, the Wiki page states that there is no evidence suggesting inhibiting AMPK is prophylactic/therapeutic for cancer. Well, the study below confirms the role of AMPK as tumor promoter and provides perhaps the first contrarian evidence to the claim of the Wiki page that inhibiting AMPK is not therapeutic for cancer. The tumor in this case was metastatic melanoma (one of the deadliest cancers currently inflicting humanity). The morale of this story/study, at least for me, is that, just as in the case of autophagy, we once again see that "more is often less" when it comes to chronically promoting the activity of very basic, evolutionary ancient physiological mechanisms in humans. Oh, and for the people who are wondering - AMPK activation is one of the major activators of autophagy:): Another major finding of the study is the acknowledgement that function can drive/control structural changes, which is something the proponents of the metabolic/bioenergetic theory of disease have been saying for more than a century and medicine (especially oncology) continues to deny. As Dr. Peat often said in his articles, "structure and function cannot be separated, they are interdependent on every level", and it does seem to be so for human cells used in this study, where minor changes in the metabolic/bioenergetic processes induced major structural/skeletal modification.

Now, while the study did not mention it, I suspect the mechanism through which AMPK activation promotes metastasis is precisely through its effects of increasing FAO - a process I have written about many times, and observed in every cancer type known to medicine. If excessive FAO is at the core of metastasis, then instead of direct/specific inhibition of AMPK, one could probably achieve similar benefits by inhibiting said excessive FAO. As mentioned numerous times in the past, niacinamide, vitamin B1, vitamins A/D/E/K, aspirin, glycine/gelatin, progesterone, androgens, etc can all be viable approaches for restricting excessive FAO. For the most severe cases, the direct FAO inhibitor Meldonium/Mildronate may need to be administered in order to stop the severe metabolic derangements that sick/stressed cells experience.

AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration - Nature Communications
"...Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton."

Skin cancer rewires its energy systems to spread more efficiently, finds study
"...In the new study, published in Nature Communications, the team investigated how metastasizing cells rewire their energy systems to move quickly and efficiently on their journey to other parts of the body. The researchers examined migrating tumor cells in a special model system allowing movement in three dimensions—a departure from conventional systems that place cells on a flat surface that doesn't accurately replicate how cells move through living tissue. They found that metastasizing tumor cells adopt a style of movement known as rounded-amoeboid migration, where cells maintain a loose connection to their surroundings, enabling them to slither through the tissue. This requires far less energy than a common style of cell movement known as mesenchymal migration, where cells grip tightly onto their surroundings and drag themselves through their environment. They observed that the invasive tumor cells reshape their mitochondria to suit this efficient style of movement, opting to have many, small, fragmented mitochondria that operate in a low-power mode. This is in contrast to less-invasive cells, which have large, branching networks of mitochondria that operate in a high-power mode. "These metastatic cells are rewiring themselves to be very efficient," explains Dr. Eva Crosas-Molist, first author on the new paper. "They only need low levels of energy to move, which helps them to survive in the potentially stressful environments they are migrating to, where there may be a lack of nutrients or oxygen." Intriguingly, the team found that if they manipulate the shape of the mitochondria in their metastasizing tumor cells and force them to become more joined up, the cells lose their invasive behavior. Likewise, if they make mitochondria more disconnected in non-invasive cells, the cells start to behave like metastasizing tumor cells. The researchers discovered that a molecule called AMPK sits at the center of these processes. It senses the energy requirements of the cell and also controls the cytoskeleton, which determines how the cell moves and behaves. "That was a really surprising thing for us—we wouldn't have imagined that changing the mitochondria could affect the cytoskeleton and vice versa." Professor Sanz-Moreno explains. "By modifying these little mitochondria you create a global change, altering what the cell looks like and its whole behavior."
 
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yerrag

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Wonderful! But sadly, it confirms what I had suspected all along as to what's happened to my brother-in-law in Texas.

3 years ago, he began to get concerned about his blood pressure getting higher. Like me, he was avoiding taking blood pressure medication, but he sought to lower his blood pressure by going by going lo carb the paleo way, and mixed that in with intermittent fasting. I had no idea he had taken that route. But when I saw his picture after his doing his regimen for 2 years, I told my sister he doesn't look well. He looked better before. As my impression was formed from comparing seeing him in a before and after for 2 years, I felt my impression wasn't so much off. Yet my sister defended their approach (he follows what my sister says, as my sister thinks she knows about health matters better, as she sells a supposedly expensive brand of supplements with the Shaklee brand), telling me he looks very healthy. But when you are with someone daily, you are not able to see the changes as dramatically as someone who hasn't see someone in years.

In the past year, my BIL had a stroke in his brain, which didn't result in paralysis or anything, but no sooner was he out of that crisis was he to learn that he has very high PSA, and this set off a series of doctor visits that ended with him having prostate surgery along with 32 lymph nodes being removed because the determination was that cancer had metastasized into the lymph nodes at the hip.

Now he has to have therapy as what does one expect from having a lot of lymph nodes removed. His legs swell from edema.

Needless to say, I told my sister about Ray Peat's ideas but since Ray's ideas require a deep dive to be able to connect the dots, I gave her a summary I felt a lay person would understand to get her into doing her deep dive into it. She couldn't understand my summary at all even though she's smart and graduated with a master's in polymer chemistry years ago. But that simply reflects her intransigence towards Peat's ideas as she would complain that Peat doesn't know how to explain things the way Mercola or Dr. Axe does. I have a lot of sisters who think that way. And they are all concerned about me ironically, because my ideas are so unorthodox. But really, my ideas are just more consistent to Ray Peat's thinking and his well-documented research.

And this is not the end.

I have another sister who also has high blood pressure. She now says her blood pressure has lowered thanks to the great ideas of a doctor. This doctor also swears by intermittent fasting and goes by a program called LCIF - low carb intermittent fasting.

Oh no! Not again! I try again, but to no avail. People are like horses on blinders who can only stick on one viewpoint, and think the only way to go is in one direction. Without ever contemplating "what if I'm wrong?"

But that is the very sad part about following the crowd. Conventional wisdom is almost always wrong. And people are lemmings for following what is in popular culture, the "zeitgeist" instead of simply stepping back and thinking more critically. People get a headache for having to think deeply and instead follow the path of least resistance, which is not to think at all. It's better to be in FB, or watch a reality that gives them that vicarious pleasure, or just simply get busy with activities that yield nothing in the way of learning. And on the matter of health, great leaps of learning are needed.

I end by saying balance is needed. My siblings are all very religious Catholics. Going to mass daily and reciting the rosary daily. i prefer my time spent learning and understanding. Too much time spent praying endlessly for deliverance is not good for one's own health. Before my sister decided to take the pharma way of dealing with her husband's predicament, I told her that she has chosen the path of endless prayers. That seems to be the Catholic way, and the Christian way, or maybe even the Moslem way. Or even the Buddhist way, maybe.


Somehow, people at wit's end manage to dream up scenarios that it's a matter of mind over matter. That you can meditate your way to health. Even as an atheist, people can believe that it is a simple matter. They are all guilty of crossing their fingers and hoping for the best while spinning wheels.
 
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TradClare

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Wonderful! But sadly, it confirms what I had suspected all along as to what's happened to my brother-in-law in Texas.

3 years ago, he began to get concerned about his blood pressure getting higher. Like me, he was avoiding taking blood pressure medication, but he sought to lower his blood pressure by going by going lo carb the paleo way, and mixed that in with intermittent fasting. I had no idea he had taken that route. But when I saw his picture after his doing his regimen for 2 years, I told my sister he doesn't look well. He looked better before. As my impression was formed from comparing seeing him in a before and after for 2 years, I felt my impression wasn't so much off. Yet my sister defended their approach (he follows what my sister says, as my sister thinks she knows about health matters better, as she sells a supposedly expensive brand of supplements with the Shaklee brand), telling me he looks very healthy. But when you are with someone daily, you are not able to see the changes as dramatically as someone who hasn't see someone in years.

In the past year, my BIL had a stroke in his brain, which didn't result in paralysis or anything, but no sooner was he out of that crisis was he to learn that he has very high PSA, and this set off a series of doctor visits that ended with him having prostate surgery along with 32 lymph nodes being removed because the determination was that cancer had metastasized into the lymph nodes at the hip.

Now he has to have therapy as what does one expect from having a lot of lymph nodes removed. His legs swell from edema.

Needless to say, I told my sister about Ray Peat's ideas but since Ray's ideas require a deep dive to be able to connect the dots, I gave her a summary I felt a lay person would understand to get her into doing her deep dive into it. She couldn't understand my summary at all even though she's smart and graduated with a master's in polymer chemistry years ago. But that simply reflects her intransigence towards Peat's ideas as she would complain that Peat doesn't know how to explain things the way Mercola or Dr. Axe does. I have a lot of sisters who think that way. And they are all concerned about me ironically, because my ideas are so unorthodox. But really, my ideas are just more consistent to Ray Peat's thinking and his well-documented research.

And this is not the end.

I have another sister who also has high blood pressure. She now says her blood pressure has lowered thanks to the great ideas of a doctor. This doctor also swears by intermittent fasting and goes by a program called LCIF - low carb intermittent fasting.

Oh no! Not again! I try again, but to no avail. People are like horses on blinders who can only stick on one viewpoint, and think the only way to go is in one direction. Without ever contemplating "what if I'm wrong?"

But that is the very sad part about following the crowd. Conventional wisdom is almost always wrong. And people are lemmings for following what is in popular culture, the "zeitgeist" instead of simply stepping back and thinking more critically. People get a headache for having to think deeply and instead follow the path of least resistance, which is not to think at all. It's better to be in FB, or watch a reality that gives them that vicarious pleasure, or just simply get busy with activities that yield nothing in the way of learning. And on the matter of health, great leaps of learning are needed.

I end by saying balance is needed. My siblings are all very religious Catholics. Going to mass daily and reciting the rosary daily. i prefer my time spent learning and understanding. Too much time spent praying endlessly for deliverance is not good for one's own health. Before my sister decided to take the pharma way of dealing with her husband's predicament, I told her that she has chosen the path of endless prayers. That seems to be the Catholic way, and the Christian way, or maybe even the Moslem way. Or even the Buddhist way, maybe.


Somehow, people at wit's end manage to dream up scenarios that it's a matter of mind over matter. That you can meditate your way to health. Even as an atheist, people can believe that it is a simple matter. They are all guilty of crossing their fingers and hoping for the best while spinning wheels.
I know it's hard to watch family go down a path that you think it's wrong, but please don't lump in their trendy health ideas with the Mass, the rosary, and prayers which are anything but trendy. And not given to us for meditating our way to health or granting our personal wishes. I'm sure your siblings love you regardless. Read the title of the post please
 

DennisX

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Messages
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Wonderful! But sadly, it confirms what I had suspected all along as to what's happened to my brother-in-law in Texas.

3 years ago, he began to get concerned about his blood pressure getting higher. Like me, he was avoiding taking blood pressure medication, but he sought to lower his blood pressure by going by going lo carb the paleo way, and mixed that in with intermittent fasting. I had no idea he had taken that route. But when I saw his picture after his doing his regimen for 2 years, I told my sister he doesn't look well. He looked better before. As my impression was formed from comparing seeing him in a before and after for 2 years, I felt my impression wasn't so much off. Yet my sister defended their approach (he follows what my sister says, as my sister thinks she knows about health matters better, as she sells a supposedly expensive brand of supplements with the Shaklee brand), telling me he looks very healthy. But when you are with someone daily, you are not able to see the changes as dramatically as someone who hasn't see someone in years.

In the past year, my BIL had a stroke in his brain, which didn't result in paralysis or anything, but no sooner was he out of that crisis was he to learn that he has very high PSA, and this set off a series of doctor visits that ended with him having prostate surgery along with 32 lymph nodes being removed because the determination was that cancer had metastasized into the lymph nodes at the hip.

Now he has to have therapy as what does one expect from having a lot of lymph nodes removed. His legs swell from edema.

Needless to say, I told my sister about Ray Peat's ideas but since Ray's ideas require a deep dive to be able to connect the dots, I gave her a summary I felt a lay person would understand to get her into doing her deep dive into it. She couldn't understand my summary at all even though she's smart and graduated with a master's in polymer chemistry years ago. But that simply reflects her intransigence towards Peat's ideas as she would complain that Peat doesn't know how to explain things the way Mercola or Dr. Axe does. I have a lot of sisters who think that way. And they are all concerned about me ironically, because my ideas are so unorthodox. But really, my ideas are just more consistent to Ray Peat's thinking and his well-documented research.

And this is not the end.

I have another sister who also has high blood pressure. She now says her blood pressure has lowered thanks to the great ideas of a doctor. This doctor also swears by intermittent fasting and goes by a program called LCIF - low carb intermittent fasting.

Oh no! Not again! I try again, but to no avail. People are like horses on blinders who can only stick on one viewpoint, and think the only way to go is in one direction. Without ever contemplating "what if I'm wrong?"

But that is the very sad part about following the crowd. Conventional wisdom is almost always wrong. And people are lemmings for following what is in popular culture, the "zeitgeist" instead of simply stepping back and thinking more critically. People get a headache for having to think deeply and instead follow the path of least resistance, which is not to think at all. It's better to be in FB, or watch a reality that gives them that vicarious pleasure, or just simply get busy with activities that yield nothing in the way of learning. And on the matter of health, great leaps of learning are needed.

I end by saying balance is needed. My siblings are all very religious Catholics. Going to mass daily and reciting the rosary daily. i prefer my time spent learning and understanding. Too much time spent praying endlessly for deliverance is not good for one's own health. Before my sister decided to take the pharma way of dealing with her husband's predicament, I told her that she has chosen the path of endless prayers. That seems to be the Catholic way, and the Christian way, or maybe even the Moslem way. Or even the Buddhist way, maybe.


Somehow, people at wit's end manage to dream up scenarios that it's a matter of mind over matter. That you can meditate your way to health. Even as an atheist, people can believe that it is a simple matter. They are all guilty of crossing their fingers and hoping for the best while spinning wheels.
You come off as the Ray Peat way is the only way. Aren’t you just as religious as your catholic systers but your religion is Ray Peat?
 

yerrag

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I know it's hard to watch family go down a path that you think it's wrong, but please don't lump in their trendy health ideas with the Mass, the rosary, and prayers which are anything but trendy. And not given to us for meditating our way to health or granting our personal wishes. I'm sure your siblings love you regardless. Read the title of the post please

I'm lumping them together because there is little distinction in the matter of belief involved in those two areas.

One gets used to accepting ideas and mysteries as a matter of faith, without question, and it becomes a habit that contaminates temporal areas and one becomes mired in accepting ideas that have no basis in fact when one earnestly examines the arguments and the information behind them using reason and logic. There is a coherence that makes one convinced of which road he should take.
 

DennisX

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Messages
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I'm lumping them together because there is little distinction in the matter of belief involved in those two areas.

One gets used to accepting ideas and mysteries as a matter of faith, without question, and it becomes a habit that contaminates temporal areas and one becomes mired in accepting ideas that have no basis in fact when one earnestly examines the arguments and the information behind them using reason and logic. There is a coherence that makes one convinced of which road he should take.
@yerrag, as I said your religion is Ray Peat. It's seems you exclude all other health protocols as possible. Isn't this the same as being a cult member and criticizing all non cult ideas?
 

yerrag

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You come off as the Ray Peat way is the only way. Aren’t you just as religious as your catholic systers but your religion is Ray Peat?
You have no idea.

You just are in this forum without an iota of understanding of the body of work that Ray Pest has done. You haven't connected the dots. And you have the gall to lump this as a religion.

What have you read of Peat to think his ideas were about getting people to accept mysteries that aren't coherent at all but still demand people to accept them because to not believe demands they be burned at the stake or cause wars?

So unless you have anything other than a blurb to say, please stfu.
 

yerrag

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@yerrag, as I said your religion is Ray Peat. It's seems you exclude all other health protocols as possible. Isn't this the same as being a cult member and criticizing all non cult ideas?
What do you know but to assume what you don't know in all you do?
 

DennisX

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Messages
253
You have no idea.

You just are in this forum without an iota of understanding of the body of work that Ray Pest has done. You haven't connected the dots. And you have the gall to lump this as a religion.

What have you read of Peat to think his ideas were about getting people to accept mysteries that aren't coherent at all but still demand people to accept them because to not believe demands they be burned at the stake or cause wars?

So unless you have anything other than a blurb to say, please stfu.
Anger and insults are the bastion of the woke. No need to reply as I will STFU..
 

J.R.K

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Quite the title for this post, but I think the evidence from the study below is clear. Namely, chronic activation of the so-called "master metabolic sensor" AMPK is a key mechanism through which melanoma cells rewire their metabolism from higher into lower OXPHOS, change their physical structure and mitochondria shape/size, and become highly invasive/aggressive. Conversely, blocking AMPK reversed the aggressive melanoma phenotype back to a less aggressive, localized version. Now, AMPK has been promoted for decades all over the blogosphere (and medical journals) as the best thing next to immortality, and is proposed as the key mechanism through which "endurance" exercise, caloric restriction, low-carb diets, or even pharmaceutical lifespan extenders exert their benefits. Its main systemic effect is to increase metabolic efficiency, and switch metabolism from OXPHOS of glucose to primarily fatty acid oxidation (FAO). Speaking of lifespan extenders, the current pharmacological darling of the blogosphere (and mainstream medicine) - metformin - works primarily as an AMPPK-activator. Despite all of the purported "benefits" of AMPK, even the official Wiki page acknowledges that AMPK may have a role as a tumor promoter, ironically, by protecting cancer cells from metabolic stress induced by chemotherapy/radiation. In other words, after cancer has formed, AMPK may be strong protector of said cancer. However, the Wiki page states that there is no evidence suggesting inhibiting AMPK is prophylactic/therapeutic for cancer. Well, the study below confirms the role of AMPK as tumor promoter and provides perhaps the first contrarian evidence to the claim of the Wiki page that inhibiting AMPK is not therapeutic for cancer. The tumor in this case was metastatic melanoma (one of the deadliest cancers currently inflicting humanity). The morale of this story/study, at least for me, is that, just as in the case of autophagy, we once again see that "more is often less" when it comes to chronically promoting the activity of very basic, evolutionary ancient physiological mechanisms in humans. Oh, and for the people who are wondering - AMPK activation is one of the major activators of autophagy:): Another major finding of the study is the acknowledgement that function can drive/control structural changes, which is something the proponents of the metabolic/bioenergetic theory of disease have been saying for more than a century and medicine (especially oncology) continues to deny. As Dr. Peat often said in his articles, "structure and function cannot be separated, they are interdependent on every level", and it does seem to be so for human cells used in this study, where minor changes in the metabolic/bioenergetic processes induced major structural/skeletal modification.

Now, while the study did not mention it, I suspect the mechanism through which AMPK activation promotes metastasis is precisely through its effects of increasing FAO - a process I have written about many times, and observed in every cancer type known to medicine. If excessive FAO is at the core of metastasis, then instead of direct/specific inhibition of AMPK, one could probably achieve similar benefits by inhibiting said excessive FAO. As mentioned numerous times in the past, niacinamide, vitamin B1, vitamins A/D/E/K, aspirin, glycine/gelatin, progesterone, androgens, etc can all be viable approaches for restricting excessive FAO. For the most severe cases, the direct FAO inhibitor Meldonium/Mildronate may need to be administered in order to stop the severe metabolic derangements that sick/stressed cells experience.

AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration - Nature Communications
"...Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton."

Skin cancer rewires its energy systems to spread more efficiently, finds study
"...In the new study, published in Nature Communications, the team investigated how metastasizing cells rewire their energy systems to move quickly and efficiently on their journey to other parts of the body. The researchers examined migrating tumor cells in a special model system allowing movement in three dimensions—a departure from conventional systems that place cells on a flat surface that doesn't accurately replicate how cells move through living tissue. They found that metastasizing tumor cells adopt a style of movement known as rounded-amoeboid migration, where cells maintain a loose connection to their surroundings, enabling them to slither through the tissue. This requires far less energy than a common style of cell movement known as mesenchymal migration, where cells grip tightly onto their surroundings and drag themselves through their environment. They observed that the invasive tumor cells reshape their mitochondria to suit this efficient style of movement, opting to have many, small, fragmented mitochondria that operate in a low-power mode. This is in contrast to less-invasive cells, which have large, branching networks of mitochondria that operate in a high-power mode. "These metastatic cells are rewiring themselves to be very efficient," explains Dr. Eva Crosas-Molist, first author on the new paper. "They only need low levels of energy to move, which helps them to survive in the potentially stressful environments they are migrating to, where there may be a lack of nutrients or oxygen." Intriguingly, the team found that if they manipulate the shape of the mitochondria in their metastasizing tumor cells and force them to become more joined up, the cells lose their invasive behavior. Likewise, if they make mitochondria more disconnected in non-invasive cells, the cells start to behave like metastasizing tumor cells. The researchers discovered that a molecule called AMPK sits at the center of these processes. It senses the energy requirements of the cell and also controls the cytoskeleton, which determines how the cell moves and behaves. "That was a really surprising thing for us—we wouldn't have imagined that changing the mitochondria could affect the cytoskeleton and vice versa." Professor Sanz-Moreno explains. "By modifying these little mitochondria you create a global change, altering what the cell looks like and its whole behavior."
Interesting find @haidut. I am in agreement with your assessment but I wonder if you might look at this idea on long COVID regarding these exact same recommendations for remylenation of oligodendtetic cells in the case of long COVID. Knowing the effects described above and how Metformin and intermittent fasting affect the body.
 
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haidut

haidut

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Interesting find @haidut. I am in agreement with your assessment but I wonder if you might look at this idea on long COVID regarding these exact same recommendations for remylenation of oligodendtetic cells in the case of long COVID. Knowing the effects described above and how Metformin and intermittent fasting affect the body.

Demyelination is mostly driven by chronic inflammation and endotoxin has a known (in research circles at least) role since TLR4 is expressed in the nervous system and repeated endotoxin injections in animals reliably causes myelin loss. So, fasting, by decreasing endotoxin, would make sense to help with remyelination but the rate of remyelination also depends on the metabolic rate, and since fasting lowers said rate the remyelination from it would probably plateau or even stop completely or even be incomplete. Pregnenolone and progesterone are both known potent remyelination agents, so I would prefer those (usually in combination with something like aspirin and/or niacinamide) than fasting. Metformin would be my last choice for any health goal.
 

J.R.K

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Demyelination is mostly driven by chronic inflammation and endotoxin has a known (in research circles at least) role since TLR4 is expressed in the nervous system and repeated endotoxin injections in animals reliably causes myelin loss.
One could possibly include repeated doses of a certain experimental mRNA gene therapy vaccine in this description. The only question would be the toxicity of the shots or subsequent inflammation from the toxicity raising TLR4
Metformin would be my last choice for any health goal.
Agreed I see this drug being used by many of my circle of friends and family. Usually after a long period of a precursor such as cortisone or ACE inhibitors.
 

yerrag

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Anger and insults are the bastion of the woke. No need to reply as I will STFU..
Calling names like "woke" and "cult" wantonly makes you less and less credible. Start reading instead of making useless commentaries.
 

shakemondown

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that sucks. seems like terrible side effects of a fast. it still could have its uses, heres a older study that brought the average case of hypertension back within range.

 
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haidut

haidut

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One could possibly include repeated doses of a certain experimental mRNA gene therapy vaccine in this description. The only question would be the toxicity of the shots or subsequent inflammation from the toxicity raising TLR4

I agree, and the effect of the mRNA shots would be worse than plain endotoxin since the spike protein inhibits ACE II, thus unleashing an additional inflammatory cascade in organs that do not express TLR4.
 

J.R.K

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I agree, and the effect of the mRNA shots would be worse than plain endotoxin since the spike protein inhibits ACE II, thus unleashing an additional inflammatory cascade in organs that do not express TLR4.
A point of contention that you have mentioned that is confusing me. Is ACE ll inflammatory or anti inflammatory. I know ACE inhibitors inhibit ACE ll and presumably and logically this drug would be delivered systemically, this would be akin to the spike protein inhibiting ACE ll. Thus the newest data showing their connections to diabetes as well as kidney breakdown presumably from activating the RAAS on a continuous basis over long term usage.
But the other risk is that of lung cancer due to the reductions in ACE ll that neutralizes bradykinan.
 
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haidut

haidut

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A point of contention that you have mentioned that is confusing me. Is ACE ll inflammatory or anti inflammatory. I know ACE inhibitors inhibit ACE ll and presumably and logically this drug would be delivered systemically, this would be akin to the spike protein inhibiting ACE ll. Thus the newest data showing their connections to diabetes as well as kidney breakdown presumably from activating the RAAS on a continuous basis over long term usage.
But the other risk is that of lung cancer due to the reductions in ACE ll that neutralizes bradykinan.

There are two enzymes - ACE I and ACE II. The former is pro-inflammatory as it converts the less inflammatory angiotensin I into angiotensin II. So, you want to inhibit ACE (I) and there are many drugs that are ACE (I) inhibitors. ACE II converts the highly inflammatory angiotensin II back to antiotensin I. So you don't want to inhibit ACE II as it is beneficial, and if you inhibit it (as the spike protein does) then you you'd be increasing inflammation. Young people have less ACE and more ACE II, old people are usually the other way around. There are also drugs like losartan, which block the antiotensin II receptor 1 (AT2R1), so they block the effects of the inflammatory angiotensin II but without affecting its synthesis or degradation. A combination of ACE (I) inhibitor and an AT2R1 blocker would be synergistic for systemic inflammation or dealing with COVID-19, or the spike protein from the vaccine.
 

J.R.K

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There are two enzymes - ACE I and ACE II. The former is pro-inflammatory as it converts the less inflammatory angiotensin I into angiotensin II. So, you want to inhibit ACE (I) and there are many drugs that are ACE (I) inhibitors. ACE II converts the highly inflammatory angiotensin II back to antiotensin I. So you don't want to inhibit ACE II as it is beneficial, and if you inhibit it (as the spike protein does) then you you'd be increasing inflammation. Young people have less ACE and more ACE II, old people are usually the other way around. There are also drugs like losartan, which block the antiotensin II receptor 1 (AT2R1), so they block the effects of the inflammatory angiotensin II but without affecting its synthesis or degradation. A combination of ACE (I) inhibitor and an AT2R1 blocker would be synergistic for systemic inflammation or dealing with COVID-19, or the spike protein from the vaccine.
Thanks so much haidut! So ACE inhibitors that are prescribed to control hypertension block production of ACE ll ? Someone had posted a conversation between Anthony Fauci and someone else talking about the high levels of COVID-19 deaths in people that had hypertension and in theory a high percentage would have the condition treated presumably with ACE inhibitors in Italy, they seemed concerned that people with this prescription who came down with COVID-19 would have a higher rate of morbidity than those not on the drugs.
But the higher mortality in the elderly having less ACE ll does help explain the higher rates of poor outcomes when they were infected.
This makes sense as reduced ACE2 as a result of age or pharmaceutically lowered lead to higher morbidity in both these two groups. Thank you for your confirmation of my understanding.
 

yerrag

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Thanks so much haidut! So ACE inhibitors that are prescribed to control hypertension block production of ACE ll ? Someone had posted a conversation between Anthony Fauci and someone else talking about the high levels of COVID-19 deaths in people that had hypertension and in theory a high percentage would have the condition treated presumably with ACE inhibitors in Italy, they seemed concerned that people with this prescription who came down with COVID-19 would have a higher rate of morbidity than those not on the drugs.
But the higher mortality in the elderly having less ACE ll does help explain the higher rates of poor outcomes when they were infected.
This makes sense as reduced ACE2 as a result of age or pharmaceutically lowered lead to higher morbidity in both these two groups. Thank you for your confirmation of my understanding.

So really from the get go, the message that hypertension is a co-morbidity and a risk factor for COVID-19 death should have been qualified. It should say that hypertensive people on ACE inhibitor medication are more at risk. And hypertensive people who don't take medication, like me, are not in this risk category.

Thanks for your line of questioning and for haidut to get a clearer picture, as I've always wondered whether my being hypertensive really puts me at risk.

So, my summation, from a person with hypertension's standpoint, is that trying to lower blood pressure, either by changing lifestyle that involves intermittent fasting and or going low carb, or by medication (especially with ACE inhibitors) redounds to greater risk, as compared to leaving the body alone to adapt to a pathological condition, usually of undetermined origin, by using an increase in blood pressure as means to compensate.
 
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haidut

haidut

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There are two enzymes - ACE I and ACE II. The former is pro-inflammatory as it converts the less inflammatory angiotensin I into angiotensin II. So, you want to inhibit ACE (I) and there are many drugs that are ACE (I) inhibitors. ACE II converts the highly inflammatory angiotensin II back to antiotensin I. So you don't want to inhibit ACE II as it is beneficial, and if you inhibit it (as the spike protein does) then you you'd be increasing inflammation. Young people have less ACE and more ACE II, old people are usually the other way around. There are also drugs like losartan, which block the antiotensin II receptor 1 (AT2R1), so they block the effects of the inflammatory angiotensin II but without affecting its synthesis or degradation. A combination of ACE (I) inhibitor and an AT2R1 blocker would be synergistic for systemic inflammation or dealing with COVID-19, or the spike protein from the vaccine.

Angiotensin and ACE (or ACE II) are not the same thing. Angiotensin is the peptide that causes vasoconstriction, raises blood pressure and causes an inflammatory response. There is angiotensin I and angiotensin II. The former is less inflammatory than the latter. The enzyme ACE (I) stands for angiotensin converting enzyme and it takes angiotensin I and converts is into the more inflammatory angiotensin II. So, inhibiting ACE (I) is usually beneficial. Once angiotensin I is converted into angiotensin II by ACE (I) then the newly formed more inflammatory angiotensin II can bind to several receptors and one of the major ones is the AT2R1 I mentioned earlier. So, if one blocks AT2R1 with a drug like losartan, blood pressure can still be lowered even if ACE (I) is not inhibited. The enzyme ACE II takes the inflammatory angiotensin II and converts it back into the less inflammatory angiotensin I. So, avoiding inhibition of ACE II or even enhancing its effects would be beneficial for both blood pressure and inflammation. Ideally, one would want to inhibit ACE (I), block AT2R1 and enhance ACE II. That would provide the maximum effect and there are studies showing giving multiple drugs to cover all of these pathways is more beneficial than a drug that only affects one of those pathways.
 
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