Metabolic Efficiency And Metabolic Rate - Doubt

[BigYellowLemon]

I like the post. But here is a question. How come anti-serotonin drugs can reverse type II diabetes? Their effect is not really on improving fat oxidation but on restoring fast metabolism in general. Serotonin is the primary brake on metabolism and anything that opposes it is anti-diabetic and anti-cancer. I think it is not so much a hampered beta oxidation as it is hampered oxidation period. Removing the brake on oxidation usually reverses the pathology.

I think I agree with Yew, in that serotonin itself doesn't actually cause damage if used appropriately by the body. Why would the body ever damage itself like that? Why would it want more damage?

I think what happens is cells are damaged through some mechanism, and serotonin basically acts as a slowdown mechanism on cells, making the cells appear unhealthy, bur actually saving the cells from further damage. It's adaptive. Anti-serotonin drugs that give benefits probably do so through two ways:

1. Remove unnecessary and excess serotonin. The body sometimes prob overestimates and uses too much.

2. Makes the cell act healthy. This doesn't mean the cell is actually. In fact in the long run it prob hurts the cell. It's like forcing the cell to act a certain way when the cell clearly wants to act a different way.

Low serotonin is probably indicative of good health. Lowering serotonin through drugs however will probably not give you good health. Low serotonin is good because it means there's low stress on cells. Lowering serotonin artificially probably stresses the cells.

The reversal of diabetes isn't necessarily good. I bet diabetes is itself an adaptive change to a deeper and more subtle stressor on the organism.

This is a long way of saying: The body knows what it's doing.

 

[lollipop]

@tyw Your explanations gave me the idea of both metabolic balance AND metabolic flexibility give the open dynamic system a good chance to adjust as needed. The system itself decides what is needed for its maximum health and longevity. Like self healing electronics coming out these days. We can support that dynamic system by inputting superior nutritional substances. Have I oversimplified?

It reminds me of cat muscle fiber - relaxed and when at rest you can almost feel the bone beneath the muscle tissue - and the suddenly in a flash that resting, relaxed cat can jump from the ground to the top of a six foot fence using strong contracted fibers. The cat's fibers remain in a healthy state ready to perform whatever action is required or desired. In Yoga this ability to do any range of motion at any moment defines healthy conditioned tissue fiber.

@BigYellowLemon your last sentence - the body knows how to regulate itself was what I was trying express in the above thoughts. I think digging into the underlying cause of ill health needs more than simply biochemical understanding. We are complex layered dynamic open systems...

Even Ray talks about importance of creativity and overcoming learned helplessness. All come into the picture to support overall health...

 

[haidut]

I think I agree with Yew, in that serotonin itself doesn't actually cause damage if used appropriately by the body. Why would the body ever damage itself like that? Why would it want more damage?

I think what happens is cells are damaged through some mechanism, and serotonin basically acts as a slowdown mechanism on cells, making the cells appear unhealthy, bur actually saving the cells from further damage. It's adaptive. Anti-serotonin drugs that give benefits probably do so through two ways:

1. Remove unnecessary and excess serotonin. The body sometimes prob overestimates and uses too much.

2. Makes the cell act healthy. This doesn't mean the cell is actually. In fact in the long run it prob hurts the cell. It's like forcing the cell to act a certain way when the cell clearly wants to act a different way.

Low serotonin is probably indicative of good health. Lowering serotonin through drugs however will probably not give you good health. Low serotonin is good because it means there's low stress on cells. Lowering serotonin artificially probably stresses the cells.

The reversal of diabetes isn't necessarily good. I bet diabetes is itself an adaptive change to a deeper and more subtle stressor on the organism.

This is a long way of saying: The body knows what it's doing.

Every messenger like serotoin, estrogen, prolactin, NO, etc has a physiological role. That is why it is there, as an acute state messenger. But if the stressor continues for too long (and we probably don't know exactly how long) the organism adapts and assumes this is the default environment so it continues to run like that until a very clear message is sent that the opposite it true. The process of adaptation itself is very energetically expensive and 1) does not get invoked very often for that reason 2) when invoked to adapt to bad environment the body has intertia for further adaptation in order to conserve energy. After all, once the body assumes times are bad. By adapting, I actually mean the physical changes in the cell that St. Gyorgi talked about in his various books. The "dismantling" of the oxidative metabolism aparratus or the "preference" for fats as fuel are examples of such changes. They are not irreversible though, and there is actual physical damage to the cell as far as we can see. Like you said - why would the body want to damage itself? The point 1) should immediately show you why metabolism is paramount. Without proper energy production the organism cannot adapt back to a stress-free state even if you really, really wanted it to. The anti-serotonin drugs are one such unrejectable message of good times being back, and a message that does not require much energy to process and implement. Given that development of cancer requires a serotonin receptor and so do the viral and some bacterial infections it points to serotonin actually having a pathological role. The body uses serotonin to slow down metabolism in times of famine/stress at the expense of compromised immunity, libido, higher cognitive function, etc. So, you can say that serotonin is good only if you think that living in constant subsistence state is good. So, if you don't want to be in that state either you dramatically change the environment to send your body an all-clear signal or if you cannot change your environment then you use a chemical to deliver that message. The comment about reversing diabetes not being good is misplaced IMO. If reversing pathology is not good then why are we here? Under the same logic, would you say that the 30% of breast cancer patients that actually get cured by taking an AI drug are doing a disservice to their bodies?
I also agree with @tyw that we don't know the underlying causes but I don't think this is because of lack of understanding but rather that we are looking at the wrong scientific layer. The answer will probably come from physics, or possibly a unification of biochemistry and physics, because the idea of uninterrupted electron flow and things that can interrupt it have a lot more to do with physics than chemistry. But we know enough to be able to manipulate that electron flow, and until more is known I would focus on at least that.
Just my 2c.

 

[Peater Piper]

The reversal of diabetes isn't necessarily good. I bet diabetes is itself an adaptive change to a deeper and more subtle stressor on the organism.

This is a long way of saying: The body knows what it's doing.

I think it depends on the cause of the diabetes, and how you go about reversing it. Diabetics are at significantly greater risk for just about every disease and illness, and most Type 2's remain Type 2's for life, so whether the body's trying to protect itself or not, it's not doing a very good job. In some cases simply increasing micronutrient and antioxidant status may improve insulin sensitivity by allowing the cells to appropriately handle energy and ROS. In other cases, obviously more serious intervention is needed. I don't think there's any doubt that high glucose levels are primarily a symptom of underlying issues. Metabolic derangements occur for years and sometimes even decades before glucose levels rise enough to sound an alarm.

 

[lollipop]

The answer will probably come from physics, or possibly a unification of biochemistry and physics, because the idea of uninterrupted electron flow and things that can interrupt it have a lot more to do with physics than chemistry.

@haidut I think this is an interesting direction. Be careful that you do not collapse a living system into a mechanistic worldview. This direction assumes all knowledge is had by externally observing an object and their behaviors. Each of those objects also has a subjective interior experience which these two fields you are looking at intersecting do not take into consideration. As you say: just my 2c.

 

[haidut]

@haidut I think this is an interesting direction. Be careful that you do not collapse a living system into a mechanistic worldview. This direction assumes all knowledge is had by externally observing an object and their behaviors. Each of those objects also has a subjective interior experience which these two fields you are looking at intersecting do not take into consideration. As you say: just my 2c.

Well, given my recent post about "thinking doughs" I doubt I will fall easily for a mechanistic view

 

[lollipop]

Well, given my recent post about "thinking doughs" I doubt I will fall easily for a mechanistic view :)

YaY ＼(^o^)／

I thought of quoting that in my post - lol. Hanging around and learning about Ray Peat has been one of the most interesting fields of endeavor for me recently over the past year and a half. I see some people in the larger community collapsing into this mechanistic polarity and hanging tightly.

You are one of the most interesting resources as you demonstrate a nice blend between theorizing and landing it into practical action. I selfishly want to see this resource (you) expanding out 360• so nothing gets dropped or polarized.

 

[BigYellowLemon]

@BigYellowLemon your last sentence - the body knows how to regulate itself was what I was trying express in the above thoughts. I think digging into the underlying cause of ill health needs more than simply biochemical understanding. We are complex layered dynamic open systems...

Even Ray talks about importance of creativity and overcoming learned helplessness. All come into the picture to support overall health...

Yes. It think the body knows what it's doing. I don't think fiddling directly with things such as serotonin is smart, in most cases.

Every messenger like serotoin, estrogen, prolactin, NO, etc has a physiological role. That is why it is there, as an acute state messenger. But if the stressor continues for too long (and we probably don't know exactly how long) the organism adapts and assumes this is the default environment so it continues to run like that until a very clear message is sent that the opposite it true. The process of adaptation itself is very energetically expensive and 1) does not get invoked very often for that reason 2) when invoked to adapt to bad environment the body has intertia for further adaptation in order to conserve energy. After all, once the body assumes times are bad. By adapting, I actually mean the physical changes in the cell that St. Gyorgi talked about in his various books. The "dismantling" of the oxidative metabolism aparratus or the "preference" for fats as fuel are examples of such changes. They are not irreversible though, and there is actual physical damage to the cell as far as we can see. Like you said - why would the body want to damage itself? The point 1) should immediately show you why metabolism is paramount. Without proper energy production the organism cannot adapt back to a stress-free state even if you really, really wanted it to. The anti-serotonin drugs are one such unrejectable message of good times being back, and a message that does not require much energy to process and implement. Given that development of cancer requires a serotonin receptor and so do the viral and some bacterial infections it points to serotonin actually having a pathological role. The body uses serotonin to slow down metabolism in times of famine/stress at the expense of compromised immunity, libido, higher cognitive function, etc. So, you can say that serotonin is good only if you think that living in constant subsistence state is good. So, if you don't want to be in that state either you dramatically change the environment to send your body an all-clear signal or if you cannot change your environment then you use a chemical to deliver that message. The comment about reversing diabetes not being good is misplaced IMO. If reversing pathology is not good then why are we here? Under the same logic, would you say that the 30% of breast cancer patients that actually get cured by taking an AI drug are doing a disservice to their bodies?
I also agree with @tyw that we don't know the underlying causes but I don't think this is because of lack of understanding but rather that we are looking at the wrong scientific layer. The answer will probably come from physics, or possibly a unification of biochemistry and physics, because the idea of uninterrupted electron flow and things that can interrupt it have a lot more to do with physics than chemistry. But we know enough to be able to manipulate that electron flow, and until more is known I would focus on at least that.
Just my 2c.

I will have to think further about what you gave said. I however do not agree that these messengers are only to be used acutely. This topic is very complex. I have too many ideas to put into words here. I'm on mobile, so it's difficult to write clearly. I will try and clarify some of my ideas and get back to you. But I understand your point I think. The only thing I can say for certain is that context is the most important. Lowering serotonin might be good for one person and bad for another. Maybe one person creates more than necessary, maybe another creates the right amount. It depends. Also, I think that the "cure" we see with diabetes might just be a relievement of symptoms, the blood tests make look "better", handling of glucose may appear similar to that of a healthy person, but in reality the person is being damaged subtly by not having the adaptive mechanism that in some cases diabetes might be. I think sometimes diabetes might be adaptive, other times it may be directly harmful. It depends.

And your point about cancer patients is taken. I think for the majority of us, people who aren't in acute and life threatening situations, treatments that don't **** up the bodies signaling would be better. For someone who will die if not treated, we should treat them, but I still think they'll suffer metabolic damage, but it'll be worth it because they live. It all depends.

I think it depends on the cause of the diabetes, and how you go about reversing it. Diabetics are at significantly greater risk for just about every disease and illness, and most Type 2's remain Type 2's for life, so whether the body's trying to protect itself or not, it's not doing a very good job. In some cases simply increasing micronutrient and antioxidant status may improve insulin sensitivity by allowing the cells to appropriately handle energy and ROS. In other cases, obviously more serious intervention is needed. I don't think there's any doubt that high glucose levels are primarily a symptom of underlying issues. Metabolic derangements occur for years and sometimes even decades before glucose levels rise enough to sound an alarm.

Read what I said to haidut. As you said, it depends. Just because we relieve the symptoms and appearance of diabetes, doesn't mean we'll remove the risks associated with having diabetes.


From what I've seen on this forum as well as others, people rarely fix themselves, especially when using powerful tools such as direct agonist or antagonists of receptors, receptors with specific functions that are not to be meddled with in my opinion.

I will reply later with a more coherent (!) idea.

 

[Peater Piper]

Read what I said to haidut. As you said, it depends. Just because we relieve the symptoms and appearance of diabetes, doesn't mean we'll remove the risks associated with having diabetes.


From what I've seen on this forum as well as others, people rarely fix themselves, especially when using powerful tools such as direct agonist or antagonists of receptors, receptors with specific functions that are not to be meddled with in my opinion.

I will reply later with a more coherent (!) idea.

Well, I think a lot of the risks are related to out of control glucose and free fatty acids (especially unsaturated fatty acids). Those are the later symptoms of derangement, but they cause a lot of the damage. In that sort of case, throwing additional insulin into an insulin resistant patient increases ROS in a system that's already likely depleted of glutathione and other antioxidants, so damage is accelerated. But you can reduce the insulin resistance, thus insulin signaling improves, glutathione production increases (if diet supplies the necessary nutrients), ROS is decreased and antioxidant status is increased. The problem is modern medicine doesn't typically diagnose a problem until a substantial amount of damage has already occurred, which dramatically reduces the odds of successful treatment. Obviously there's genetic factors we can't control, but environmental factors still play a major role. Severe type 2 diabetes is rarely cured, but plenty of people overcome milder insulin resistance all the time whether it's through improved diet or a small amount of weight loss.

 

[Regina]

Yes. It think the body knows what it's doing. I don't think fiddling directly with things such as serotonin is smart, in most cases.



I will have to think further about what you gave said. I however do not agree that these messengers are only to be used acutely. This topic is very complex. I have too many ideas to put into words here. I'm on mobile, so it's difficult to write clearly. I will try and clarify some of my ideas and get back to you. But I understand your point I think. The only thing I can say for certain is that context is the most important. Lowering serotonin might be good for one person and bad for another. Maybe one person creates more than necessary, maybe another creates the right amount. It depends. Also, I think that the "cure" we see with diabetes might just be a relievement of symptoms, the blood tests make look "better", handling of glucose may appear similar to that of a healthy person, but in reality the person is being damaged subtly by not having the adaptive mechanism that in some cases diabetes might be. I think sometimes diabetes might be adaptive, other times it may be directly harmful. It depends.

And your point about cancer patients is taken. I think for the majority of us, people who aren't in acute and life threatening situations, treatments that don't **** up the bodies signaling would be better. For someone who will die if not treated, we should treat them, but I still think they'll suffer metabolic damage, but it'll be worth it because they live. It all depends.



Read what I said to haidut. As you said, it depends. Just because we relieve the symptoms and appearance of diabetes, doesn't mean we'll remove the risks associated with having diabetes.


From what I've seen on this forum as well as others, people rarely fix themselves, especially when using powerful tools such as direct agonist or antagonists of receptors, receptors with specific functions that are not to be meddled with in my opinion.

I will reply later with a more coherent (!) idea.

I am confused by your terms "having diabetes" and "appearance of diabetes." Diabetes seems to be an energetic state. At what point would you consider a person "cured" of diabetes?

 

[m_arch]

The amount of Thyroid related hormones is a fine balancing act. And just like my comments with Vit A, D, and Calcium, what is "high Thyroid" for one person is not necessarily considered "high" for another person.

The second paper I quoted showed analysis for Askenazi Jew showed normal T4 and a lot more TSH compared to aged matched subjects. ie: this was not just "at the end of life", and the patterns were observed even 30-40 years prior to death.

These people are different, and what consists "hypothyroid" to the mainstream establishment is not pathological to them.

----

There are enough cases of legitimately verified centenarians on Okinawa to rightfully say that it is an anomaly in terms of greater longevity.

Why? All we can say right now is that they are that way because they are born that way.




These are not necessarily mechanism that involve Metabolism, and definitely not about mechanisms that support the idea of increasing metabolism.

Firstly, I will caution against almost any study that is not a human study when discussing human longevity. We are so different to the rest of the animals out there (even primates), that any such comparison is either not very significant, or invalid.

If one really wants to see how complicated the field of Human Longevity is, I have recommended the book 'Human Longevity' by Dave Valentine before. It is expensive, but it will give a full picture about how everything from PUFA regulation to ROS regulation to oxygen restriction to select tissues, are adaptations that humans have geared towards longevity.

Another one of the reasons why I am so against animal studies, is because the Aging process has so many dependent variables depending on the organism in question.

There are the extremes of organisms that start aging the moment they are sexually mature, and then there are Humans, for which aging is controlled largely by the brain (unless there is sudden trauma to other parts of the body).

This isn't a universal mechanic, since you will find similar levels of PUFA in the brain of long-lived pigeons, and short-lived rats -- The Long Life of Birds: The Rat-Pigeon Comparison Revisited .... in other words, the brain does not set the pace of aging for Birds.

The human brain is unlike any other brain, and the regulatory mechanisms that provide for all this hormone regulation must work in concert with the rest of the body in very complex ways that we do not understand.

That is to say, the healthy aged person's brain is able to maintain their "youthful hormonal profile".

Can you replace this using exogenous means? Maybe, but there will be a lot of tweaking required, and there is risk of a hard dependency on exogenous compounds (by shutting down endogenous production or feedback pathways).

----

Unfortunately, there is no single theme that any of the mechanisms described above are converging upon.

Even something like serotonin is subject to regulation by so many uniquely-human factors, that it isn't just a simple matter of "reduce incoming serotonin from food and gut bacteria" (which doesn't answer "how do the serotonergic neurons in the CNS respond to this negative feedback")

Even something like brain responsiveness is not just about energetics, and even if it were just about "more energy is better", then one has to explain all the various mechanisms that the brain has to restrict oxygen and substrate use, and rely heavily on lactate for fuel, and then come to a conclusion as to which regions of the brain should be given more energy, at what times, for how long, etc, etc ....

The only unifying factor that I see in all this study, is "Efficiency" -- energy used when it needs to be used, just enough to deal with the incoming stimulus, and while producing as little waste products (including heat) as possible.

We see this in mitochondria, where those of the longest lived organisms are those which manage to produce little ROS (through whatever means). We see this is the brain, where the most responsive to stimuli are those that are able to relax nervous system potentials and fire them very quickly at will, vs the "always on, high metabolic rate, high waste product" schizophrenic brain:
- Molecular Psychiatry - Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress
- http://www.sciencedirect.com/science/article/pii/S0925492705002052

We have no idea how to achieve this in a generalised manner . All useful strategies are purely defensive strategies, used to avoid damaging stressors when the body is not ready or able to handle them.

.....

To sum up some ideas you've been posting about, and to see if i'm interpreting it right(?), you think:

-not metabolic rate, but efficiency of cellular communication is the name of the game. disease is due to communication breakdown.
-speeding up metabolic rate can be dangerous because the body has lowered it for a reason and speeding it up will probably not lead to maximum longevity
-in general, a lot of problems are avoided by being at a lower bf %, 10-15% for men, 20~30% for women. if you have to eat less to achieve this, then thats okay. a high carb low fat diet will help lose weight, otherwise a high fat low carb diet might be the better option.. with weight gain occuring most easily with high fat and high carb in the same meal.
-if you suspect your ability to synthesize your own PUFA is compromised, 2 eggs a day should be fine to make up for this (although it seems vitamin A can be helpful)
-> strive for everything else to be PUFA free or low PUFA.
- "afternoon diabetes" is a thing, ideally eat your carbs in the first half of the day but maintaining that lower body fat will make you more insulin sensitive anyway
-infrared light is a byproduct of metabolism and enhances the cells ability to communicate with each other, which thus improves efficiency (efficiency and communication seem to be interchangeable). Red light speeds metabolism --> infrared light is a by product of metabolism (or obtained from a light source) --> infrared light is the communication channel of the cell, more infrared, better communication
- it seems like a blunt general recovery tool for people would be to bathe in infra red / red light (or just suntan when the UV rating is lower) to achieve an increase in cellular communication/efficiency (and thus promote healing).
-get your energy without causing harm (avoid food sensitivities etc)... i heard an anecdotal report that one guy healed himself from lathering himself in coconut oil and sunbathing. what are your thoughts on that? perhaps coconut oil through skin absorption is one general option of getting energy without causing harm.
- are you still into increasing the body-weight multiplier (a measure of metabolism)?

 

[haidut]

To sum up some ideas you've been posting about, and to see if i'm interpreting it right(?), you think:

-not metabolic rate, but efficiency of cellular communication is the name of the game. disease is due to communication breakdown.
-speeding up metabolic rate can be dangerous because the body has lowered it for a reason and speeding it up will probably not lead to maximum longevity
-in general, a lot of problems are avoided by being at a lower bf %, 10-15% for men, 20~30% for women. if you have to eat less to achieve this, then thats okay. a high carb low fat diet will help lose weight, otherwise a high fat low carb diet might be the better option.. with weight gain occuring most easily with high fat and high carb in the same meal.
-if you suspect your ability to synthesize your own PUFA is compromised, 2 eggs a day should be fine to make up for this (although it seems vitamin A can be helpful)
-> strive for everything else to be PUFA free or low PUFA.
- "afternoon diabetes" is a thing, ideally eat your carbs in the first half of the day but maintaining that lower body fat will make you more insulin sensitive anyway
-infrared light is a byproduct of metabolism and enhances the cells ability to communicate with each other, which thus improves efficiency (efficiency and communication seem to be interchangeable). Red light speeds metabolism --> infrared light is a by product of metabolism (or obtained from a light source) --> infrared light is the communication channel of the cell, more infrared, better communication
- it seems like a blunt general recovery tool for people would be to bathe in infra red / red light (or just suntan when the UV rating is lower) to achieve an increase in cellular communication/efficiency (and thus promote healing).
-get your energy without causing harm (avoid food sensitivities etc)... i heard an anecdotal report that one guy healed himself from lathering himself in coconut oil and sunbathing. what are your thoughts on that? perhaps coconut oil through skin absorption is one general option of getting energy without causing harm.
- are you still into increasing the body-weight multiplier (a measure of metabolism)?

All of these are valid valid thoughts, but cellular communication depends on energy. No proper/sufficient ATP production = disorganized and even harmful communication. This holds regardless of whether you believe the cellular communication is chemical or electromagnetic. When the cell is not working well there is a build up of free electrons. In a state like that the cell tends to emit chemical stress signals (NO, HIF, HSP, prolactin, serotonin, estrogen, histamine, etc) and those reach neighboring cells and probably every cell in the body. If the cells communicate with electromagnetic waves like Luc Montagnier (discoverer of HIV) recently published about, that communication process won't work well either due to the accumulation of free electrons. It is not dissimilar to the effects of geomagnetic storm on wireless communications on Earth - i.e. an excess of electrons in the cell will disrupt the electromagnetic communications between cells. The signal will get distorted and it has been shown that cells interpret even a "coherent" but distorted signal as a bad sign. For instance, the brain creates a "coherence" signal by synchronizing the phases of alpha, beta and gamma waves.
New vistas for alpha-frequency band oscillations. - PubMed - NCBI
When there is a build up of free electrons that coherence signal is hard to even form, and even if it is formed it gets distorted when it travels across the organism.
So, to me at least, we are back to metabolism.

 

[Regina]

All of these are valid valid thoughts, but cellular communication depends on energy. No proper/sufficient ATP production = disorganized and even harmful communication. This holds regardless of whether you believe the cellular communication is chemical or electromagnetic. When the cell is not working well there is a build up of free electrons. In a state like that the cell tends to emit chemical stress signals (NO, HIF, HSP, prolactin, serotonin, estrogen, histamine, etc) and those reach neighboring cells and probably every cell in the body. If the cells communicate with electromagnetic waves like Luc Montagnier (discoverer of HIV) recently published about, that communication process won't work well either due to the accumulation of free electrons. It is not dissimilar to the effects of geomagnetic storm on wireless communications on Earth - i.e. an excess of electrons in the cell will disrupt the electromagnetic communications between cells. The signal will get distorted and it has been shown that cells interpret even a "coherent" but distorted signal as a bad sign. For instance, the brain creates a "coherence" signal by synchronizing the phases of alpha, beta and gamma waves.
New vistas for alpha-frequency band oscillations. - PubMed - NCBI
When there is a build up of free electrons that coherence signal is hard to even form, and even if it is formed it gets distorted when it travels across the organism.
So, to me at least, we are back to metabolism.

Lost in alphabet city. HIF? HSP??
(sorry for my ignorance)

 

[Blossom]

Lost in alphabet city. HIF? HSP??

Hypoxia-Inducible Factor
Heat Shock Proteins

 

[haidut]

Hypoxia-Inducible Factor
Heat Shock Proteins

Yes, thanks Blossom.

 

[Blossom]

Yes, thanks Blossom.

You're welcome. I figure you have enough to keep you busy so I help where I can. I corrected my typo.

 

[Regina]

Hypoxia-Inducible Factor
Heat Shock Proteins

 

[tyw]

Sorry, was relative busy the last few days .... posting this on Saturday Morning

To sum up some ideas you've been posting about, and to see if i'm interpreting it right(?), you think:

-not metabolic rate, but efficiency of cellular communication is the name of the game. disease is due to communication breakdown.

Like I've said before, I disagree with @haidut here due to my current study in Chinese Medicine. From that perspective body-wide and inter-organ communication depends on the ability for the very extensive network of Collagen meridians that are connecting those components together to remain conductive.

So long as conductivity is maintained, absolute energetic requirements are not large. Sensitivity, precision, and accuracy is required. Not large quantities of energy.

I have then written in my article debunking Cold Thermogenesis, that the conductivity of collagen is directly related to its Hydration levels. Water is the key element that enables collagen to do what it does.

I also personally believe that even the so-called Red Light communication between cells requires that there be present water around the cells that can channel charge efficiently. Only this sort of water can allow for the propagation of light signals. (Gilbert Ling calls this "polarised-oriented-multilayer water", Gerald Pollack calls it "Exclusion Zone (EZ) water" or "charge-separated water". In any case, water in this state is way way more conductive than water in the normal bulk phase)

I also personally believe that mitochondria require this sort of water in order to propagate charge, and thus become coherent (again, in the purely physical sense of "Same Frequency, Constant Phase Difference"). This is demonstrated by Douglas Wallace and colleagues in their work on Trans-mitochondrial membrane junctions, and the Inter-mitochondrial coordination that occurs -- Trans-mitochondrial coordination of cristae at regulated membrane junctions : Nature Communications

Look at this image (source -- Figure 1: Electron-dense inter-mitochondrial junctions (IMJs) link adjacent mitochondria in the heart. : Nature Communications)

And look at the huge discrepancies. There is a 50% difference in Electron Density when mitochondrial are "coherent and aligned" vs when not. Also note that there is an optimal distance between membranes where energetic flow is maximised. This is a coordination and communication problem, not a problem with absolute quantities energy.

An accurate metaphor to use is the coordination required in a game of Tug of War; the difference between everyone pulling "in phase", vs not, is tremendous. In the context of the cell, I personally view a loss of this coordination to be enough to bring a cell down to energetic levels that could trigger the "Apoptosis or Oncogenesis" decision.

Unlike Tug of War, a cell has to coordinate thousands of mitochondria at once ...... progressive communication breakdown is what leads to progressive energetic deficits.

This is again why I say that anything that prevents communication and coordination of components, is what is the root cause of any energetic failure in the system.

I don't discriminate between communication lines that are cut due to surgery and damage to large collagen meridians, or a vaccination depositing heavy metals in a communication channel, or excessive fatty acids reducing insulin sensitivity of cells, or a bacteria embedding itself into a cell and disrupting cell-internal communication .... all of it is communication breakdown, and all of it will be reflected by relative charge discrepancies in the system.

Technical Note (not important for understanding discussion): when I say "charge discrepancies", this refers to imbalances in charge, which can be due to (a) Dys-regulation, and formation of Injury Potential, (b) Input blockage, and failure to receive upstream energy, or (c) Output blockage, and backing up of the output queue.

As a personal aside, the Actor Model (from Computer Science) is probably the best description of biology possible, and working with actor and (true-)object based Software Systems probably helped me the most in understanding biology -- History of Actors (eighty-twenty news)​

Treatment in Chinese Medicine is always about "Purge. Tonify. Balance". The first step must be to remove the stressors that are causing communication breakdown, and given the many many modalities that this can occur, will lead to many different methods for purgation as well.

Trying to Tonify / Enhance without first Purging will lead to imbalances. This may make the patient feel better, and perform better on higher level measures, but if the fundamental stressor is not removed, this is like permanently walking on crutches, and upgrading the crutches to deal with different types of terrain as needed ...

-----

As a final aside, when it comes to Mitochondrial Energetics, I have somewhat sloppily used the term "Efficiency" to describe the state:

(1) Accurately matched Inputs to Demands
(2) Maximisation of Yield (of ATP) from Inputs
(3a) Minimisation of Waste Products
(3b) Ability to Cleanup Waste Products

Technically, "efficiency" in the traditional sense would refer to (1) and (2). It is clear that some organisms manage to get away with (3a) and (3b). What I need now is a single word that describes all of the above. Until then, I will abuse the word "Efficiency".

Now, on to the other points.

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-in general, a lot of problems are avoided by being at a lower bf %, 10-15% for men, 20~30% for women. if you have to eat less to achieve this, then thats okay. a high carb low fat diet will help lose weight, otherwise a high fat low carb diet might be the better option.. with weight gain occuring most easily with high fat and high carb in the same meal.

To be specific, the term "Body Composition" is probably more accurately used, since this reflects the ratio of body fat to lean tissue. I won't go into why preservation of lean tissue mass is a good thing.

But yes, I think a lot of problems are avoided by having good body composition.

But being a fundamental pessimist, all I care is about is to avoid the problems that will kill you. Good body composition isn't going to help you with many of the communication problems described above.

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The point about macronutrient manipulation and weight loss is a separate issue, and I am of the opinion that:

(a) it doesn't really matter if the patient is obese -- an obese person who is successfully losing weight, is by definition, using a ton of fatty acids for fuel. They are on a "high fat diet" no matter what they eat on that (successful) diet.

(b) everyone is going to be different anyway. Though I share Masterjohn's opinion that it is not wise to remove carbs unless they cause major dysfunction (see the rare case of perma-keto ItsTheWoooo).

-if you suspect your ability to synthesize your own PUFA is compromised, 2 eggs a day should be fine to make up for this (although it seems vitamin A can be helpful)
-> strive for everything else to be PUFA free or low PUFA.

Would generally agree with this.

- "afternoon diabetes" is a thing, ideally eat your carbs in the first half of the day but maintaining that lower body fat will make you more insulin sensitive anyway

Agree with this.

-infrared light is a byproduct of metabolism and enhances the cells ability to communicate with each other, which thus improves efficiency (efficiency and communication seem to be interchangeable). Red light speeds metabolism --> infrared light is a by product of metabolism (or obtained from a light source) --> infrared light is the communication channel of the cell, more infrared, better communication
- it seems like a blunt general recovery tool for people would be to bathe in infra red / red light (or just suntan when the UV rating is lower) to achieve an increase in cellular communication/efficiency (and thus promote healing).

Yes, given all the caveats about the communication infrastructure mentioned above.

-get your energy without causing harm (avoid food sensitivities etc)... i heard an anecdotal report that one guy healed himself from lathering himself in coconut oil and sunbathing. what are your thoughts on that? perhaps coconut oil through skin absorption is one general option of getting energy without causing harm.

Cannot comment on said person who "healed himself" unless I actually asses the person and their relative deficiencies.

I have no clue how much coconut oil can be absorbed through the skin.

- are you still into increasing the body-weight multiplier (a measure of metabolism)?

This statement complects using a body-weight multiplier for calorie intake as a measurement tool, and as a success metric.

Yes, use it as a measurement tool, but not as a metric for success. I don't see how aiming to increase this beyond what is normative (based on personal measurements) is going to be productive

The exception would be people for whom all signals for determining food intake are broken (eg: anorexics, people with gastric bypass surgery). In such cases, tracking needs to be done.

If not, eating to satiety is enough, and if caloric needs change over time, then they change over time. This is just information.

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[papaya]

The amount of Thyroid related hormones is a fine balancing act. And just like my comments with Vit A, D, and Calcium, what is "high Thyroid" for one person is not necessarily considered "high" for another person.

The second paper I quoted showed analysis for Askenazi Jew showed normal T4 and a lot more TSH compared to aged matched subjects. ie: this was not just "at the end of life", and the patterns were observed even 30-40 years prior to death.

These people are different, and what consists "hypothyroid" to the mainstream establishment is not pathological to them.

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There are enough cases of legitimately verified centenarians on Okinawa to rightfully say that it is an anomaly in terms of greater longevity.

Why? All we can say right now is that they are that way because they are born that way.




These are not necessarily mechanism that involve Metabolism, and definitely not about mechanisms that support the idea of increasing metabolism.

Firstly, I will caution against almost any study that is not a human study when discussing human longevity. We are so different to the rest of the animals out there (even primates), that any such comparison is either not very significant, or invalid.

If one really wants to see how complicated the field of Human Longevity is, I have recommended the book 'Human Longevity' by Dave Valentine before. It is expensive, but it will give a full picture about how everything from PUFA regulation to ROS regulation to oxygen restriction to select tissues, are adaptations that humans have geared towards longevity.

Another one of the reasons why I am so against animal studies, is because the Aging process has so many dependent variables depending on the organism in question.

There are the extremes of organisms that start aging the moment they are sexually mature, and then there are Humans, for which aging is controlled largely by the brain (unless there is sudden trauma to other parts of the body).

This isn't a universal mechanic, since you will find similar levels of PUFA in the brain of long-lived pigeons, and short-lived rats -- The Long Life of Birds: The Rat-Pigeon Comparison Revisited .... in other words, the brain does not set the pace of aging for Birds.

The human brain is unlike any other brain, and the regulatory mechanisms that provide for all this hormone regulation must work in concert with the rest of the body in very complex ways that we do not understand.

That is to say, the healthy aged person's brain is able to maintain their "youthful hormonal profile".

Can you replace this using exogenous means? Maybe, but there will be a lot of tweaking required, and there is risk of a hard dependency on exogenous compounds (by shutting down endogenous production or feedback pathways).

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Unfortunately, there is no single theme that any of the mechanisms described above are converging upon.

Even something like serotonin is subject to regulation by so many uniquely-human factors, that it isn't just a simple matter of "reduce incoming serotonin from food and gut bacteria" (which doesn't answer "how do the serotonergic neurons in the CNS respond to this negative feedback")

Even something like brain responsiveness is not just about energetics, and even if it were just about "more energy is better", then one has to explain all the various mechanisms that the brain has to restrict oxygen and substrate use, and rely heavily on lactate for fuel, and then come to a conclusion as to which regions of the brain should be given more energy, at what times, for how long, etc, etc ....

The only unifying factor that I see in all this study, is "Efficiency" -- energy used when it needs to be used, just enough to deal with the incoming stimulus, and while producing as little waste products (including heat) as possible.

We see this in mitochondria, where those of the longest lived organisms are those which manage to produce little ROS (through whatever means). We see this is the brain, where the most responsive to stimuli are those that are able to relax nervous system potentials and fire them very quickly at will, vs the "always on, high metabolic rate, high waste product" schizophrenic brain:
- Molecular Psychiatry - Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress
- http://www.sciencedirect.com/science/article/pii/S0925492705002052

We have no idea how to achieve this in a generalised manner . All useful strategies are purely defensive strategies, used to avoid damaging stressors when the body is not ready or able to handle them.

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it sounds like it might be best to not mess with thyroid meds at all considering it sounds like the body regulates itself regardless & nobody seems to truly know what normal thyroid level really should be if it's so individual(or maybe by ancestry?). do you take thyroid meds? what supplements, if any do you take? btw, thank u so much for your brilliant posts! i've been trying to read through all of them but my add has been really bad lately, do u know of anything i can try instead of adderall?

 

[ATP]

@tyw From what I read it seems you don't agree with a lot of Ray Peat's ideas. I am interested in what you think is an optimal diet then?
All of Peat's ideas are about raising metabolism, clearly you're not in favor of that. Then what would be your approach to disease prevention and vitality?
Does is it all come from complimentary medicine (TCM)?