Testosterone and metabolism

[youngsinatra]

I've never tested my androgens and will do so soon. What are the most important markers to test?

I was thinking free and total testosterone, dht, and prolactin. Are things like cortisol and estrogen important as well? Prolactin may be a surrogate for estrogen, right?

LH, FSH, testosterone, SHBG, estradiol, prolactin gives a solid panel.

DHEA-S, cortisol can be added to see the adrenal‘s function

 

[Runenight201]

Holy ***t... I even have this myself, can't handle noise from traffic anymore and have low stress tolerance. Maybe it's the bleak future? I think it has to do with the pandemic making the obvious very obvious, people are faced with accepting reality or continuing their facade (madness), so it's forcing them out of "normie" state. If I'm correct, we will be seeing a lot of scapegoats in the near future just to avoid the ACTUAL truth. We are not ruled by benefactors, to say the least.

I also find that this stress is universal in a way, thinking, acting, working out, recovering, all is impacted. What did you do to get out of it? I'm already on testosterone and I find it a double edged sword: It provides better stress resilience, but if you stress out the price you pay is higher. Just like how women that stress out have less hair loss than men (given hair loss genetics). As a man, it is as if calmness is a duty that comes with a price, I can either be real calm or the stress will **** me up, no inbetween.

Adopting functional behaviors that are in line with good health is how you combat it. As you have witnessed, injecting testosterone makes you more resilient, so as a man, doing things that keep the androgens high and stress hormones low.

I believe Ray has mentioned before as well, but as a species, or at the least within a social sphere, we are all almost one giant organism, and collectively many of us have adopted a mindset that the world is ****88 up and we have no future because of climate change, we can't change the world because of partisan politics or capitalist/corporate greed which is unbeatable and the de facto state of affairs. This then creates in each individual a psyche that is toxic and degenerative. We need leaders who can change the public discourse and belief systems to the regenerative ones, ones in which we view humans as good, righteous, cooperative, etc...

I am a competitive amateur strength athlete (strongman), train very hard, and have a professional coach. I eat a lot of fatty meat, eggs, and milk to keep protein intake high, but in a low PUFA context, and eat organ meat and shellfish. I get carbs mostly from from potatoes and fruit.


100% agree, this is exactly the "authoritarian personality" Ray Peat talks about, and it is frustrating to see it becoming the norm even on this forum. Most of the threads on this forum are now part of that toxic drip, with, e.g. constant fear based posts about conspiracies and vaccines. If you take any one of the posts there is no depth to them... people aren't even understanding what it means to actually know something deeply in the Peat sense. How much work and curiosity that takes... how you need to keep questioning yourself and digging deeper and keeping an open mind.

Have you ever considered overtraining syndrome as a potential cause for low testosterone? Especially if you have an autistic son, you may not be recovering as well anymore as you age and the stress of raising him, but you love strongman training and force yourself to do it, which can then further damage your health since your body isn't in a generative state to build and be anabolic?

 

[CellularIconoclast]

Have you ever considered overtraining syndrome as a potential cause for low testosterone? Especially if you have an autistic son, you may not be recovering as well anymore as you age and the stress of raising him, but you love strongman training and force yourself to do it, which can then further damage your health since your body isn't in a generative state to build and be anabolic?

I took about 6mo off from training before the low T tests that led me to start TRT. I don't think it was really possible for me to train with low testosterone, I didn't have the energy, or drive. I am back to doing it, and training hard for a competition now, and loving it.

Most of my actual work and daily life is very sedentary, and I feel like the strongman training is a good counter to that. I am pretty careful to manage overtraining... much of my training sessions are more about technique than anything else. It takes a lot of mental focus and practice to use proper technique with difficult lifts under high loads.

 

[Runenight201]

I took about 6mo off from training before the low T tests that led me to start TRT. I don't think it was really possible for me to train with low testosterone, I didn't have the energy, or drive. I am back to doing it, and training hard for a competition now, and loving it.

Most of my actual work and daily life is very sedentary, and I feel like the strongman training is a good counter to that. I am pretty careful to manage overtraining... much of my training sessions are more about technique than anything else. It takes a lot of mental focus and practice to use proper technique with difficult lifts under high loads.

Ah for sure, well happy to read that you have normalized your Testosterone levels and are able to partake in an activity that brings you joy. That is truly invaluable.

 

[CellularIconoclast]

Ah for sure, well happy to read that you have normalized your Testosterone levels and are able to partake in an activity that brings you joy. That is truly invaluable.

Thank you, that actually means a lot. I'm shocked by the mostly negative comments, basically suggesting I go back to having debilitating fatigue. Even my doctor and endocrinologist were mostly focused on "this is a controlled substance with risks" and not really considering what it means to have my life and energy back, so I had to pay out of pocket for a clinic. It is one of the best things that has ever happened to me.

 

[CellularIconoclast]

"All Bibles or sacred codes, have been the causes of the following Errors.
1. That Man has two real existing principles Viz: a Body & a Soul.
2. That Energy, call’d Evil, is alone from the Body, & that Reason, call’d Good, is alone from the Soul.
3. That God will torment Man in Eternity for following his Energies.

But the following Contraries to these are True.
1. Man has no Body distinct from his Soul; for that call’d Body is a portion of Soul discern’d by the five Senses, the chief inlets of Soul in this age.
2. Energy is the only life and is from the Body and Reason is the bound or outward circumference of Energy.
3. Energy is Eternal Delight."
-William Blake

 

[EustaceBagge]

"All Bibles or sacred codes, have been the causes of the following Errors.
1. That Man has two real existing principles Viz: a Body & a Soul.
2. That Energy, call’d Evil, is alone from the Body, & that Reason, call’d Good, is alone from the Soul.
3. That God will torment Man in Eternity for following his Energies.

But the following Contraries to these are True.
1. Man has no Body distinct from his Soul; for that call’d Body is a portion of Soul discern’d by the five Senses, the chief inlets of Soul in this age.
2. Energy is the only life and is from the Body and Reason is the bound or outward circumference of Energy.
3. Energy is Eternal Delight."
-William Blake

What if the energies are not evil, but the environment turns it evil? Then your responsibility would not be suppressing your energies, but making good use of them. Isn't that what semen retention aims to do, not deny your urges, but use them for a higher purpose? (I'm stating this even though I can't relate).

 

[CellularIconoclast]

What if the energies are not evil, but the environment turns it evil? Then your responsibility would not be suppressing your energies, but making good use of them. Isn't that what semen retention aims to do, not deny your urges, but use them for a higher purpose? (I'm stating this even though I can't relate).

Energy in the Blake sense is a sort of all encompassing life force that also includes the concepts of passion, desire, drive, etc. It is neither good or evil, but gives you the ability to do what you choose to in life. You have the responsibility to direct that energy according to your own values and goals- and that responsibility is greater with more energy. Personally I do think addiction, harming people, etc. become greater risks with more energy, but you can also accomplish great things with that energy. It's easy to cause no harm when you never had the energy or desire in the first place, but it is impressive when someone has a massive amount of power and energy, and is able to control that to do something worthwhile.

 

[Bioenergy_Space]

Sometimes the best we can do is symptom relief. It's not optimal, but it's realistic when normal peaty interventions have failed. Human physiology is extremely complicated, and our understanding is still limited. Peat's ideas are probably the best way we have to think about health and vitality, but they are not final. We can always learn more, and indeed there is always much more to be learned.

 

[CellularIconoclast]

they are not final. We can always learn more, and indeed there is always much more to be learned.

I like to think of Peat's views on basically three different levels:

1) His personal recommendations- mostly what worked for himself, and a few people he advised personally... e.g. how much OJ he drank, what supplements he took, how much carrot salad he ate
2) His high level theory, especially the central importance of metabolism, and the general fact that it is regulated in complex ways by hormones. Also, the need to respect the incredible complexity of biological systems, and consider real world results rather than expect a simple mechanistic understanding. Our knowledge is extremely limited and reductionist.
3) His philosophy of being an independent thinker, including reading broadly and deeply on literature that most people consider unimportant or outdated, as a general toolbox for solving life problems. This stuff comes more from his experiences studying William Blake than from health or biology.

I find that about 90% of Peat's value is from #3, giving a blueprint to become an independent thinker and solve problems on our own. This is what he was trying to teach, and the health stuff was just a canvas to use as an example. Almost 10% of the value is in #2, these are useful ways to think about health that contrast with and complement what you will hear elsewhere. Virtually no value is in #1, although that ends up being the focus of forums like this, because it is easier to understand and implement. Peat tried to avoid providing much #1 level information when he could, or make it confusing on purpose, because he didn't want to think about health on this level. He wanted people to understand how he got to the solutions for his own health, as a process. At best, maybe people with debilitating health issues need some #1 ideas for a short time to get to the point where they can start with #2 and #3.

In most cases, anyone looking deeply with fresh eyes on modern scientific literature will greatly outperform Peat's #1 information, and even #2, because there is so much more research out there, and it is so much easier to find than when he was doing most of his work. However, this requires really looking critically and deeply, and not just on the surface. Most of the studies quoted on his forum are just pulling a quote from the abstract that agrees with peoples pre-conceived notions, and the people posting them haven't taken the time to learn how to read studies. In almost every case, you will find that the connection they are posting about is superficial, and dissolves when you look deeper. Peat wasn't educated on groupthink in internet forums, he had a PhD and spent a ton of time reading articles completely, and deeply, and forming his own opinions. To follow Peat, you have to do the same IMO. You can't just watch some conspiracy theory youtube videos and start telling everyone their health problems are all caused by vaccines, and never even take undergrad biochemistry. That isn't following Peat in any sense.

 

[Bioenergy_Space]

there is so much more research out there, and it is so much easier to find than when he was doing most of his work. However, this requires really looking critically and deeply, and not just on the surface.

Yeah, there is a lot of research out there. The problem is that much of it is noise with strange and wacky materials and methods almost designed to arrive at a predetermined result that furthers the authors career. It takes a lot of time to really dig into studies, nevermind getting the appropriate knowledge of physiology, biochem, histology (even neuroanatomy, which can be a bit frustrating) etc... I agree with you that without this rather extensive knowledge what is achievable is at best some reformulation of existing Peat knowledge. Taking it to the next level requires a lot of work just to get an understanding as deep as Peat had, so that we can integrate new studies into his framework. For example, haidut has investigated new chemicals that peat did not write about, but that are quite peaty.

My way of reading Peat is this: I ask myself "If I only had the studies that were available to Peat during his time, how would I have to think to arrive at his conclusions?" and this brings out my A-game in terms of biochem and physiology. I have to think very critically, take creative leaps, think visually etc...

 

[CellularIconoclast]

Yeah, there is a lot of research out there. The problem is that much of it is noise with strange and wacky materials and methods almost designed to arrive at a predetermined result that furthers the authors career

Yes, you have to look critically at the methods and see if it makes sense.

That said, modern molecular biology papers are a lot more careful and involved than they were in Peat's day. Nowadays, a molecular biology or biochemistry paper in a good journal will have an extremely reductionist and simple claim like "molecule X is localized within cells near molecule Y." They will then proceed to verify that in at least 3 or 4 totally different ways: typically both in vivo and in vitro, including direct imaging in both cases. Modern things light sheet fluorescence microscopy (LSFM) give real high res up close 3D video within a living cell where you can zoom and pan around what is actually happening, so are a lot harder to misinterpret than the results Peat criticizes. So you pretty much have an irrefutable paper that is about 10x as long in methods as it would have been in Peat's time, and makes a claim so simple nobody could really disagree. Outright intentional fraud still occurs as well, but it not super common, because it is too risky... a potentially career ending move for people that mostly already have tenure they could pretty much only lose through intentional fraud.

Where you run into a problem is how to interpret that in context. What does this result mean, and why is it important? Nowadays this will be buried in the discussion section, and will be carefully stated as a question or opinion, again to make it not falsifiable. But that is still the point of the paper, and why it got into the journal in the first place... so you need to see if you actually agree.

In the Peat context, people are usually looking at the methods for support of an orthogonal idea or theory, which the authors weren't even thinking about, or designing to the study to actually address. You have to be extra careful in that case, because you can't expect the authors to have put any effort into proper experimental design to test some idea they weren't even actively considering.

Truth be told, when I got into grad school more than a decade ago, my perspective from Peat, and other alternative health ideas, had me thinking there was so much stupidity and fraud, and I could work on fighting and fixing all of that from the inside. Maybe I drank the kool-aid, but it turns out I was mostly just ignorant myself. The level of intelligence, carefulness, and open mindedness is a lot more than I imagined. When I talk about 'weird' things like Peat's concepts to my colleagues, they don't get angry or defensive... they get curious, and want to discuss how it could possibly be true, or not.

When you think about things like Association Induction vs Membrane theory for example... it seems to me that both theories are true, and not actually at odds, cells use both mechanisms. You can't say "receptors don't exist" when you can isolate, express, and study them, and know exactly what they do and how they work, and even modify them and get them to act differently and see what happens. There are also aspects of AI that are absolutely mainstream nowadays: substrate channeling for example, and the fact that cells are so dense there is actually very little free water, most is ordered on protein surfaces, and cells are not freely mixed, but carefully organized so things locate exactly where they need to.

 

[Bioenergy_Space]

When you think about things like Association Induction vs Membrane theory for example... it seems to me that both theories are true, and not actually at odds, cells use both mechanisms. You can't say "receptors don't exist" when you can isolate, express, and study them, and know exactly what they do and how they work, and even modify them and get them to act differently and see what happens. There are also aspects of AI that are absolutely mainstream nowadays: substrate channeling for example, and the fact that cells are so dense there is actually very little free water, most is ordered on protein surfaces, and cells are not freely mixed, but carefully organized so things locate exactly where they need to.

The receptor thing is something I have been thinking a lot lately. Yes, the proteins exist. As you say they can be cloned, and we have crystallographic data mapping out every atom of the protein. This much is just a given. There is affinity data, and conformational changes are well defined. What I think is going on is that most receptors are actually sensitive to an incredible array of environmental signals. My model for thinking about it is the NMDA receptor: it seems to be modulated by just about everything. Perhaps most of the polypeptide sequences that are now thought to be just "scaffolding" will turn out to be responsive to secondary messages from the environment.

As for the membrane, I think of it as a "cellular cortex". A specific phase of the cell that restricts movement and only allows lateral displacement. It makes sense that something like that would evolve, and that the outermost part of the cell would have special features, in part to localize specific proteins there. As data has been accumulating over the decades the % of protein in the membrane has been increasing, I think it's about 50% now. So perhaps the idea of the membrane as defined by phospholipids is not quite correct.

I will not hide that I come to biochem and physiology from a peaty point of view, but ultimately truth is my highest goal. I must say though, having a peaty mindset makes learning so much more fun.

 

[CellularIconoclast]

What I think is going on is that most receptors are actually sensitive to an incredible array of environmental signals. My model for thinking about it is the NMDA receptor: it seems to be modulated by just about everything.

Agreed. The old fashioned model of receptors as basically binary switches is nonsense. When you look at, for example GPCRs (G protein coupled receptors) in bioassays, they bind to *almost every* small molecule to some degree, and they have a large number of effective outputs that respond in complex non-linear ways to different structures: one ligand can strongly activate a specific output that is silent when another binds, for example. So I feel these receptors are something more along the lines of a "universal chemical sensor" than a switch triggered by a specific hormone. They provide the cell with a huge amount of data about the external chemical environment, allowing them to prepare and respond to diverse conditions appropriately.

This is probably why "rational drug design" basically does not work, and pharma has mostly stopped spending money on it. Choosing molecules that selectively bind to a target receptor rarely provides the biological response that was expected.

 

[youngsinatra]

Can you update us on your situation?

 

[youngsinatra]

A friend of mine is on testosterone aswell, but he said to me that he does not get much benefits (it at all) from it when he keeps his E2 too low. He said he likes to let his E2 run a bit higher.

I noticed that Your T and consequently E2 were very low in the beginning.

I suspect that low E2 results in low circulating ceruloplasmin/copper levels which in turn impair iron metabolism and consequently proper oxygenation of cells (through cytochrome C oxidase slowdown), which leads to lower ATP levels, which lowers SAMe synthesis (methylation) which slows down the synthesis of our neurotransmitters
(serotonin/dopamine/norepinephrine..) and so on and so forth.

Just an idea of mine.

I find it interesting that the symptoms associated with crashed E2 are similar to copper deficiency — Pale skin, depression, feeling cold, low libido, joint pain, extreme fatigue.

 

[CellularIconoclast]

Can you update us on your situation?

Sure! For the first few months I felt awesome (lots of energy, etc.) but eventually started to feel some symptoms of high estrogen- irritability, nipple sensitivity, water retention, acne. At this point my T was 1084 ng/dL, and estrogen was 47 pg/mL. I reduced my T dose from 150mg/wk to 120mg/wk and started taking 0.125mg of anastrozole (an aromatase inhibitor) 3x/week.

After a month or so again, I lost all of the benefits of testosterone, and started to feel fatigued again. I did blood tests again, and T was down to 777 ng/dL, and E down to 23.3 pg/mL. At that point, I kept the T dose lower, but stopped the anastrozole. About 3 weeks later, the nipple sensitivity came back. So I restarted the anastrozole but at a much lower dose of 0.125mg/week split into two doses. So far seem to be doing great.

This overall, reflects what you are saying- it seems both low and high estrogen cause me fatigue, so I need to tune it carefully to the right range. My Dr. says his TRT patients usually feel best with estrogen in the 25-35 pg/mL range, possibly up to 40 pg/mL, so this is also consistent with what I have seen- where I felt fatigue both above and below that range.

My Dr. prescribing the T also suggests I am likely also hypothyroid in addition to low T and is putting me on Armour NDT. This is the only Dr. I have ever met that beleives in using NDT, and in treating by symptoms, in a Peat consistent manner. I will update on how it goes... I tried NDT a few years back and didn't notice any benefits so quit.

I also have pretty low vitamin D- 28.2 ng/mL, and am trying to get it back up with both sunlight, and supplementation, but keep forgetting to take the supplement for some reason.

 

[Wolf]

Sure! For the first few months I felt awesome (lots of energy, etc.) but eventually started to feel some symptoms of high estrogen- irritability, nipple sensitivity, water retention, acne. At this point my T was 1084 ng/dL, and estrogen was 47 pg/mL. I reduced my T dose from 150mg/wk to 120mg/wk and started taking 0.125mg of anastrozole (an aromatase inhibitor) 3x/week.

After a month or so again, I lost all of the benefits of testosterone, and started to feel fatigued again. I did blood tests again, and T was down to 777 ng/dL, and E down to 23.3 pg/mL. At that point, I kept the T dose lower, but stopped the anastrozole. About 3 weeks later, the nipple sensitivity came back. So I restarted the anastrozole but at a much lower dose of 0.125mg/week split into two doses. So far seem to be doing great.

This overall, reflects what you are saying- it seems both low and high estrogen cause me fatigue, so I need to tune it carefully to the right range. My Dr. says his TRT patients usually feel best with estrogen in the 25-35 pg/mL range, possibly up to 40 pg/mL, so this is also consistent with what I have seen- where I felt fatigue both above and below that range.

My Dr. prescribing the T also suggests I am likely also hypothyroid in addition to low T and is putting me on Armour NDT. This is the only Dr. I have ever met that beleives in using NDT, and in treating by symptoms, in a Peat consistent manner. I will update on how it goes... I tried NDT a few years back and didn't notice any benefits so quit.

I also have pretty low vitamin D- 28.2 ng/mL, and am trying to get it back up with both sunlight, and supplementation, but keep forgetting to take the supplement for some reason.

Have you thought about supplemental boron? My vitamin D supplementation tends to actually bring blood levels up(and energy!) when I couple it with 3-6mg of boron glycinate. Haven’t had much luck with mineral complexes.

 

[feedandseed]

A friend of mine is on testosterone aswell, but he said to me that he does not get much benefits (it at all) from it when he keeps his E2 too low. He said he likes to let his E2 run a bit higher.

I noticed that Your T and consequently E2 were very low in the beginning.

I suspect that low E2 results in low circulating ceruloplasmin/copper levels which in turn impair iron metabolism and consequently proper oxygenation of cells (through cytochrome C oxidase slowdown), which leads to lower ATP levels, which lowers SAMe synthesis (methylation) which slows down the synthesis of our neurotransmitters
(serotonin/dopamine/norepinephrine..) and so on and so forth.

Just an idea of mine.

I find it interesting that the symptoms associated with crashed E2 are similar to copper deficiency — Pale skin, depression, feeling cold, low libido, joint pain, extreme fatigue.

My anecdotal experience supports this. I don't think Ray was very bullish on copper supplementation, but in my experience it alleviated "low estrogen" symptoms from AI usage. Also many estrogen blockers coincidentally lowers ceruloplasmin. Methylene Blue is an example of this. Coffee also seems to alleviate "low estrogen" symptoms despite in theory being anti estrogenic, and if your theory is correct then the anti-iron effect of caffeine explains this.

 

[CellularIconoclast]

Have you thought about supplemental boron? My vitamin D supplementation tends to actually bring blood levels up(and energy!) when I couple it with 3-6mg of boron glycinate. Haven’t had much luck with mineral complexes.

Any info on why boron should be helpful in this case? I haven't looked into it.