Wooo's "Progesterone, The Master Hormone Myth"

[Such_Saturation]

I think it's pretty clear that those who were presenting a view other than the happy, shiny, relatively healthy male pure-Peat view on progesterone have gone from this thread. I don't blame them...I would have gone, too. So even calls for "+300" to show an email exchange between Hitoshi and Peat are most likely going to go unanswered.

And by "relatively healthy male pure-Peat view" I mean that the way Ray theorizes things should work don't usually seem to, except in relatively healthy people, particularly relatively healthy males. People with complex problems really, really REALLY have to work at it to make Peat's theories work for them...if they ever work. I say this as one who has been reading and trying Peat for almost 10 years, and who still believes in his ideas even if I am utterly disgusted by the needlessly hysterical negative turn this thread took when the discussion began (and which is the reason we'll probably never see Hitoshi's email exchange with Peat).

It's a shame because exploring the reasons that things don't work for a majority of people exactly the way Peat theorizes they should is a good thing. It may scare off some people, but it's going to help others find their way. Dogmatic Peat followers shouting people into silence who don't toe the pure Peat line is one of the reasons people tend to dismiss Ray and his ideas. It's not just that Peat goes against the mainstream...it's the behavior of some of his devotees. Seen it on several different forums, and I used to hold that view, so I know.

Everything I've ever read by Ray leads me to believe he's about tolerance and letting people find their own way. That's what I saw this thread as being about...showing a valid reason why things might not work ideally for some people. Instead it turned into an ugly shouting match that I think drove some good posters away. Shame, shame, shame.

Just sayin' to present an alternative view as to why we may never get an answer to the +1's, +2's, and +3's who are calling to see the email exchange between Hitoshi and Peat. As veteran of many internet forums, I'm sure many will see Hitoshi's lack of response as proof that it doesn't exist. But my suspicion is that Hitoshi probably decided life's too short to engage here any longer.

This will probably get moderated but I'm posting anyway because IMO some people need to consider this. If they don't, it will just keep happening.

Peace out.

He was never going to post it, at least that's the impression I got.

 

[whodathunkit]

He was never going to post it, at least that's the impression I got.

The way it was demanded at the point it was originally demanded I don't really blame him. Or her. When people demand things of me in that tone I'm really not inclined to indulge the request. If the tone continues (which it did here) I usually become even more disinclined.

We can speculate all day and we'll never really know the straight of it. But it's really tangential to the point of my post, even if it was the lead-in.

The point is that the behavior that was exhibited in this thread by the "pure Peat proponents", unprovoked (remember the OP just wanted a discussion of a single alternative viewpoint brought up in a thread *on another website*), is off-putting and NOT in the spirit of enlightened, open discussion. It was the hysterical, overwhelming, semi-irrational reaction of those who feel threatened when their views are challenged.

 

[tara]

Yep, and even just focusing along the axis of immunosuppression it is clear that progesterone has often opposite effects to cortisol - i.e. progesterone raises core body temp while cortisol lowers it (body temp is crucial for proper immune response), progesterone protects the thymus while cortisol destroys it, progesterone raises the NAD/NADH ratio, while cortisol lowers it, and so on.
But hey, progesterone is immunosuppressive, be very afraid.

I have not read PakPik as saying 'be very afraid'. I'm reading an interest in seeing the detail of the various effects of progesterone in different aspects of the system rather than just an oversimplified model. PakPik has said that progesterone has a number of advantages, as well as some potential suppressive effects in particular parts of the immune system, and is not as dangerous as various other substance that have been used as immunosuppressants. She has also spoken of the advantages of using progesterone in other threads. The detail about how substances affect different parts of the immune system can be important for people who are trying to pull themselves out of severe and complex health challenges where infection and immunity are key factors - overgeneralisations clearly don't always lead to successful 'action' for everyone.

If some people feel afraid when they have health challenges and read that the body is complex, and that many substances can't be simply categorised as 'good' or 'bad', that is not surprising. I don't think it is a good reason to pretend it isn't true, though, or to stop discussion of the complex detail.

It's a shame because exploring the reasons that things don't work for a majority of people exactly the way Peat theorizes they should is a good thing. It may scare off some people, but it's going to help others find their way.
Everything I've ever read by Ray leads me to believe he's about tolerance and letting people find their own way.

I agree with this.
I also think that sometimes people attribute oversimplified views to Peat - he seems perfectly aware that things can be very complex.

The way it was demanded at the point it was originally demanded I don't really blame him.

I think it's fair to ask for a reference when someone is arguing from a source that no-one else has access to.

 

[haidut]

I have not read PakPik as saying 'be very afraid'. I'm reading an interest in seeing the detail of the various effects of progesterone in different aspects of the system rather than just an oversimplified model. PakPik has said that progesterone has a number of advantages, as well as some potential suppressive effects in particular parts of the immune system, and is not as dangerous as various other substance that have been used as immunosuppressants. She has also spoken of the advantages of using progesterone in other threads. The detail about how substances affect different parts of the immune system can be important for people who are trying to pull themselves out of severe and complex health challenges where infection and immunity are key factors - overgeneralisations clearly don't always lead to successful 'action' for everyone.

If some people feel afraid when they have health challenges and read that the body is complex, and that many substances can't be simply categorised as 'good' or 'bad', that is not surprising. I don't think it is a good reason to pretend it isn't true, though, or to stop discussion of the complex detail.


I agree with this.
I also think that sometimes people attribute oversimplified views to Peat - he seems perfectly aware that things can be very complex.


I think it's fair to ask for a reference when someone is arguing from a source that no-one else has access to.

To state that "progesterone is immunosuppressive. fact." as some people did earlier is both oversimplification and unwarranted as nobody really has a proper definition of immunosuppression. Not going to name names but using things like "False", "Wrong", "Definitely wrong", etc in opposition of an opinion on topic that is very far from settled is not an indication that a person wants to discuss anything openly. We had the exact same issue with the thread on Circadian Clock - i.e. an argument ensued because of the tendency of some forum members to state their opinions as the cold hard truth when in reality the evidence on the topic is at best mixed. Luckily, at least on the circadian topic I saw some posts towards the end of the discussion saying it really opened their eyes to both aspects - light and metabolism. I don't think this thread will be as beneficial. Btw, about the same events unfolded here as in the circadian thread - vocal opposition and statements of definiteness when the reality is in fact much less settled.
The word immunosuppressive is commonly used clinically and it refers to a class of drugs, which I mentioned above. All of them have the ability to lower resistance to pathogens, which is something progesterone is not definitively shown to do but rather help in many cases. The studies I posted on progesterone actually lowering viral count for the smallpox infections got promptly ignored and then the discussion was again steered towards progesterone being potentially detrimental in viral infections, which it has NOT been shown to be and is not clinically known to be such either. Hence, its absence from the list of immunosuppressive drugs and its lack of warnings and precautions from medical professionals when supplementing with it. This is in contrast to true immunosuppressants like cortisol and the rest which have blackbox warnings about causing all kinds of deadly conditions like PML (Progressive multifocal leukoencephalopathy - Wikipedia).
If the discussion was started instead as an attempt to discuss the immunomodulatory (and not the purported immunosuppressive) effects of progesterone we would have probably gotten somewhere. But when it started based on a blog post which is clear FUD and tries openly to lump progesterone with a number of testosterone derivatives which were (possibly fraudulently) officially codified as progestins and purposefully studied in many experiments with the goal of raising doubt about carcinogenicity of real progesterone, then the discussion is very likely to get derailed (as it did). I gave the example that testosterone is technically a progestin and progesterone is technically an AAS. But nobody calls them that way or starts a discussion with those definitions because it is obvious those definitions are NOT indicative of the general properties of the each steroid and how it systemically affects the organism. So, all I was trying to say is that we should not toss definitions around lightly first because the evidence is not settled, and second because labeling progesterone as something that has very specific and very bad clinical connotation is not helping elucidate its real properties, which is why people consider it as a supplement to start with.
Finally, one of the main reasons the fans of "progesterone as immunosuppressant" meme are seeing progesterone as such is its role in pregnancy (which they mentioned a few times). However, the ridiculous theory that the fetus is an antigen and a type of parasite that the mother "tolerates" for 9 months is starting to fall apart. It is a prime example of the desperate belief in "selfishness" and "genetic determinism", which sees the genetic profile of an organism as the only thing that matters and somehow that profile is locked in an eternal struggle with everything around it, including the genetic profile of its offspring. The idea is so profoundly wrong, that the only reason it survived for so long is probably that it is very convenient for the medical powers that be. It is a convenient explanation as to why women with autoimmune condition go into remission - i.e. according to the theory they are immunosuppressed during pregnancy and (surprise) progesterone is the hormone responsible for that immunosuppression. This simplistic (and wrong) explanation allows steering research away from understanding the true effects of progesterone in pregnancy and autoimmune conditions. As a convenient side benefit, even if people ask about progesterone as potential treatment for those conditions they can be easily steered away from it by saying that it is an immunosuppressant just like cortisol, so they might as well use cortisol. I interact with quite a few specialists in autoimmune conditions and they all sing the same song - pregnant women are immunosuppressed and cortisol (actually the more profitable synthetic versions like dexamethasone) is being pushed to all patients as "same as progesterone, but no risk of giving you cancer if you are a woman which is what progesterone will do".
So, both sides probably overreacted a bit but maybe if this discussion was posted in the alternative theories section or based on a less FUD-full blog post we would not have gotten carried away :)
Just my 2c.

 

[Regina]

To state that "progesterone is immunosuppressive. fact." as some people did earlier is both oversimplification and unwarranted as nobody really has a proper definition of immunosuppression. Not going to name names but using things like "False", "Wrong", "Definitely wrong", etc in opposition of an opinion on topic that is very far from settled is not an indication that a person wants to discuss anything openly. We had the exact same issue with the thread on Circadian Clock - i.e. an argument ensued because of the tendency of some forum members to state their opinions as the cold hard truth when in reality the evidence on the topic is at best mixed. Luckily, at least on the circadian topic I saw some posts towards the end of the discussion saying it really opened their eyes to both aspects - light and metabolism. I don't think this thread will be as beneficial. Btw, about the same events unfolded here as in the circadian thread - vocal opposition and statements of definiteness when the reality is in fact much less settled.
The word immunosuppressive is commonly used clinically and it refers to a class of drugs, which I mentioned above. All of them have the ability to lower resistance to pathogens, which is something progesterone is not definitively shown to do but rather help in many cases. The studies I posted on progesterone actually lowering viral count for the smallpox infections got promptly ignored and then the discussion was again steered towards progesterone being potentially detrimental in viral infections, which it has NOT been shown to be and is not clinically known to be such either. Hence, its absence from the list of immunosuppressive drugs and its lack of warnings and precautions from medical professionals when supplementing with it. This is in contrast to true immunosuppressants like cortisol and the rest which have blackbox warnings about causing all kinds of deadly conditions like PML (Progressive multifocal leukoencephalopathy - Wikipedia).
If the discussion was started instead as an attempt to discuss the immunomodulatory (and not the purported immunosuppressive) effects of progesterone we would have probably gotten somewhere. But when it started based on a blog post which is clear FUD and tries openly to lump progesterone with a number of testosterone derivatives which were (possibly fraudulently) officially codified as progestins and purposefully studied in many experiments with the goal of raising doubt about carcinogenicity of real progesterone, then the discussion is very likely to get derailed (as it did). I gave the example that testosterone is technically a progestin and progesterone is technically an AAS. But nobody calls them that way or starts a discussion with those definitions because it is obvious those definitions are NOT indicative of the general properties of the each steroid and how it systemically affects the organism. So, all I was trying to say is that we should not toss definitions around lightly first because the evidence is not settled, and second because labeling progesterone as something that has very specific and very bad clinical connotation is not helping elucidate its real properties, which is why people consider it as a supplement to start with.
Finally, one of the main reasons the fans of "progesterone as immunosuppressant" meme are seeing progesterone as such is its role in pregnancy (which they mentioned a few times). However, the ridiculous theory that the fetus is an antigen and a type of parasite that the mother "tolerates" for 9 months is starting to fall apart. It is a prime example of the desperate belief in "selfishness" and "genetic determinism", which sees the genetic profile of an organism as the only thing that matters and somehow that profile is locked in an eternal struggle with everything around it, including the genetic profile of its offspring. The idea is so profoundly wrong, that the only reason it survived for so long is probably that it is very convenient for the medical powers that be. It is a convenient explanation as to why women with autoimmune condition go into remission - i.e. according to the theory they are immunosuppressed during pregnancy and (surprise) progesterone is the hormone responsible for that immunosuppression. This simplistic (and wrong) explanation allows steering research away from understanding the true effects of progesterone in pregnancy and autoimmune conditions. As a convenient side benefit, even if people ask about progesterone as potential treatment for those conditions they can be easily steered away from it by saying that it is an immunosuppressant just like cortisol, so they might as well use cortisol. I interact with quite a few specialists in autoimmune conditions and they all sing the same song - pregnant women are immunosuppressed and cortisol (actually the more profitable synthetic versions like dexamethasone) is being pushed to all patients as "same as progesterone, but no risk of giving you cancer if you are a woman which is what progesterone will do".
So, both sides probably overreacted a bit but maybe if this discussion was posted in the alternative theories section or based on a less FUD-full blog post we would not have gotten carried away :)
Just my 2c.

"It is a prime example of the desperate belief in "selfishness" and "genetic determinism", which sees the genetic profile of an organism as the only thing that matters and somehow that profile is locked in an eternal struggle with everything around it, including the genetic profile of its offspring. The idea is so profoundly wrong..."

sigh.

 

[Hitoshi]

i dont think anyone ever suggested the fetus was foreign/antigenic/parasitic - could anyone really be that dumb?

youre right, i was hestitant to post the exchange because of the attitudes here...here is one of the more important ones
RP never says much, i guess its his way of directing further reading -_-


It is interesting, there appear to be loads of paper showing there is a clear action on the immune system toward immunosuppression
- natural progesteroneincreases viral replication Effects of Female Sex Hormones on Susceptibility to HSV-2 in Vaginal Cells Grown in Air-Liquid Interface
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376705/


There appears to be a clear increase in infection risk and mortality rate as pregnancy progresses, and this coincides with the natural and very significant rise in Progesterone, and ts ratio to estrogen. .

There is a clear shift away from innate immune system, as well as away from the Th1-dominant cell-mediated adaptive immune response, while increasing the more Th2-dominant / humoral immune function. This change in the immune system is likely very important in bringing a baby to partum, but would seemingly predispose the mother to a much higher infection risk.

This shift is due to Progesterone, and there is data specifically showing Progesterone that does this.

Obviously this is (for some reason) necessary for Pregnancy (otherwise we wouldn’t see this happen!) - so the only question that remains is WHY?

Might it be that it is the interest of the body to create a strong immune system for the child, at the expense of transient infection of the mother??
This immune shift may allow for both infection of more external microorganisms, and production of antibodies against those microorganisms, and then subsequent transfer of antibodies to the baby.

Perhaps accumulation of more foreign microbes in the gut of the mother, is actually leading to "immunity diversification" for the child. This seems to be important, especially when compared to caesarian section kids, who seem to have a harder time with immune system woes…

It was also brought up by a colleague on the ray peat forum that the article suggests the more pregnancies a mother has, the lower the rate of infection mortality decreases, which seems to imply an ongoing immune memory accumulation effect that happens especially strongly during pregnancy. Again, we can speculate that this is aimed at creating a stronger child, despite the risks that it may have to the mother -- the evolutionary process will permit 1 out of 10 mothers die because of this immune shift, if it means getting 9 stronger babies.

We can speculate about the lysogenic accumulation of viral DNA that is permitted by the decreased inflammatory response, which no only improves immunity down the line, but could possibly also lead to novel protein expression (aka: evolution)….



i would be keen to hear your thoughts…



RP

It is a bizarre notion, but after reading some of the links you sent, and finding some further reading - it seems to be a valid point.

Regarding your speculations, I think the idea of passage of antibodies to the developing baby to be the most likely. It is likely that viral DNA accumulation is also involved in epigenetic expressions that allow the child to adapt to the local stressors in their particular environment.

 

[Such_Saturation]

i dont think anyone ever suggested the fetus was foreign/antigenic/parasitic - could anyone really be that dumb?

youre right, i was hestitant to post the exchange because of the attitudes here...here is one of the more important ones
RP never says much, i guess its his way of directing further reading -_-


It is interesting, there appear to be loads of paper showing there is a clear action on the immune system toward immunosuppression
- natural progesteroneincreases viral replication Effects of Female Sex Hormones on Susceptibility to HSV-2 in Vaginal Cells Grown in Air-Liquid Interface
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376705/


There appears to be a clear increase in infection risk and mortality rate as pregnancy progresses, and this coincides with the natural and very significant rise in Progesterone, and ts ratio to estrogen. .

There is a clear shift away from innate immune system, as well as away from the Th1-dominant cell-mediated adaptive immune response, while increasing the more Th2-dominant / humoral immune function. This change in the immune system is likely very important in bringing a baby to partum, but would seemingly predispose the mother to a much higher infection risk.

This shift is due to Progesterone, and there is data specifically showing Progesterone that does this.

Obviously this is (for some reason) necessary for Pregnancy (otherwise we wouldn’t see this happen!) - so the only question that remains is WHY?

Might it be that it is the interest of the body to create a strong immune system for the child, at the expense of transient infection of the mother??
This immune shift may allow for both infection of more external microorganisms, and production of antibodies against those microorganisms, and then subsequent transfer of antibodies to the baby.

Perhaps accumulation of more foreign microbes in the gut of the mother, is actually leading to "immunity diversification" for the child. This seems to be important, especially when compared to caesarian section kids, who seem to have a harder time with immune system woes…

It was also brought up by a colleague on the ray peat forum that the article suggests the more pregnancies a mother has, the lower the rate of infection mortality decreases, which seems to imply an ongoing immune memory accumulation effect that happens especially strongly during pregnancy. Again, we can speculate that this is aimed at creating a stronger child, despite the risks that it may have to the mother -- the evolutionary process will permit 1 out of 10 mothers die because of this immune shift, if it means getting 9 stronger babies.

We can speculate about the lysogenic accumulation of viral DNA that is permitted by the decreased inflammatory response, which no only improves immunity down the line, but could possibly also lead to novel protein expression (aka: evolution)….



i would be keen to hear your thoughts…



RP

It is a bizarre notion, but after reading some of the links you sent, and finding some further reading - it seems to be a valid point.

Regarding your speculations, I think the idea of passage of antibodies to the developing baby to be the most likely. It is likely that viral DNA accumulation is also involved in epigenetic expressions that allow the child to adapt to the local stressors in their particular environment.

Quite stimulating. How much to release the other emails

 

[Hitoshi]

make me an offer...

 

[haidut]

i dont think anyone ever suggested the fetus was foreign/antigenic/parasitic - could anyone really be that dumb?

That is the dominant view in immunology practiced right now.
Immune tolerance in pregnancy - Wikipedia

They even call spontaneous abortion a case of "insufficient tolerance" and a type of "transplant rejection". Hence why I mentioned a mother "tolerating" a fetus earlier in the thread. Again, I am only quoting Wikipedia because it represents the official/mainstream medical view.

As far as pregnant women having higher mortality - I think we need more research before we can blame progesterone. The recent study on progesterone and flu is telling - while progesterone did not lower viral count, it did not increase it either, and it definitely reduced mortality from the flu. So, maybe the pregnant women who got sick and did not survive may have had insufficiently high progesterone, thyroid issues, and in general reduced fitness which got them sick in the first place. Many women nowadays are on SSRI to prevent postpartum depression (or treat existing one) and those are powerfully immunosuppressive. So I am not even sure the studies with pregnant women control for the medication these women may be taking because if a medication is approved for pregnancy use then most studies assume it is benign.
In my experience, pregnant healthy women are remarkably resilient to infections and if they succumb to something it usually happens shortly after birth when estrogen/prolactin/cortisol/oxytocin surge and progesterone drops. My take is that if the mother is healthy, the organism does not have to make trade-offs in terms of baby or mother health - both benefit.
But I like the discussion that is going on now Much more civil and informative.

 

[Amazoniac]

the organism does not have to make trade-offs in terms of baby or mother health - both benefit.

The disparity in progesterone can be to compensate for the taxing demands as the gestation progresses, not only because the mother might not be on optimal conditions (is this utopic for women during pregnancy?), but also the baby increasing his needs.

It seems to be a simple over-consumption of progesterone, which is probably a reasonable biological adaptation, preventing pregnancy during times of stress.

I think that one of your main points is that even if it has immunosupressing properties, the general effect is positive. Ray already criticized the idea that, due to pregnancy being something quite demanding, it's expected that multiple pregnancies deteriorate a woman's health. He added that up to a certain point (few pregnancies) it's something positive if you consider the overall picture in the long-term.

The idea of "nitric oxide-free meal" has appeared various times here.

Anyway, haidut, Hitoshi, PakPik and tyw, many thanks for the good points all along. You guys are coming close to Westside when it comes to persisting despite so much resistance.
Also thanks to Such for existing.

--
The healthy organism in a healthy environment,... | Ray Peat Forum

 

[haidut]

I think that one of your main points is that even if it has immunosupressing properties, the general effect is positive. Ray already criticized the idea that, due to pregancy being something quite demanding, it's expected that multiple pregnancies deteriorate a woman's health

Yes, I mentioned this earlier and in fact it is even displayed all over gyno offices around the USA in the form of fliers and brochures, even though the exact implications of this are not widely marketed as it would be considered encouraging procreation in an "already overcrowded world". Don't you know that most people should have at most 1 child and even that is one too many?? I am being sarcastic of course.
Anyways, the official message you can get even from your doctor is this - for every successful, uncomplicated pregnancy and subsequent birth the risk of female reproductive and GI cancers drop by about 15%. So, up to about 7 pregnancies/births there is very strong benefit against cancer. Along the same lines, risk of dementia and Parkinson, as well as osteoporosis drops by about 11% for every child a woman has. Finally, the risk of subsequent life threatening infection and sepsis also drops with every birth but I am currently blanking on the exact numbers.
The children also benefit - subsequent children (up to 4 I think) have higher childhood IQ (assuming the mother did not experience a bad event during pregnancy).
So, yes, I can't deny that progesterone dampens the immune response in some situations but the overall outcome is positive. That is the message (progesterone as immunomodulator) I think we should be going towards and not the message of progesterone being immunosuppressive, which for most doctors means being lumped in the same category as the glucocorticoids. But maybe that's just my preference.
Finally, I think the major role of progesterone in pregnancy is the development of the fetal brain and peripheral nervous system, as well as sexual development. Mothers with low progesterone who do manage to carry a fetus to term often have babies with profound neurological disturbances, autism, gender ambiguity, and dramatically higher risk of developing demyelinating disorders like MS later in life.
http://www.stonybrook.edu/commcms/surveys/projects/WhitakerAzmitia Lobel Moyer.pdf

That it is the maternal progesterone responsible for fetal brain development has long been disputed but recent evidence points to its vital role. So, it is the maternal and not so much fetal progesterone levels that determine fetal neurological health.
Maternal progesterone influences fetal brain development | Veterinary Sciences Tomorrow
"...In the classical brain development paradigm, fetal hormones drive the sexual differentiation of the developing brain. But Wagner now reports that maternal progesterone binds to fetal progesterone receptors. The results, Wagner says, reveal a novel role of the mother in the development of the fetal central nervous system: A possible source of progesterone receptor ligand."
"...Wagner says she believes the source of fetal PR receptor ligand is maternal ovarian progesterone, which is present in extremely high levels during pregnancy. To test this hypothesis, Wagner and her colleagues manipulated fetal and postnatal hormonal exposure. They found that prenatal testosterone treatment in females, or castration of males upon birth, abolished the sex difference in PR expression. Sex differences in PR expression were also absent in mice lacking a functional oestrogen receptor-alpha. In another finding, prenatal treatment with the aromatase inhibitor ATD reduced PR expression in both the male and female MPN. In contrast, prenatal treatment with flutamide, an androgen receptor antagonist, had no apparent effect on PR expression. Neonatal treatment with the PR antagonist RU486 also abolished subsequent sexual behaviour in most adult males and attenuated the masculinising effects of testosterone on the MPN structure in females."


On an unrelated note, the second link above mentions once again that estrogen is responsible for masculinizing the fetal brain. Peat mentioned this in a few articles but don't think he provided a reference for it, so people kept questioning his statement. That estrogen is derived from fetal testosterone. This question about estrogen and masculinization has come up many times on the forum so I thought I'd include it here.
"...In males, fetal testosterone aromatises to oestradiol and masculinises the fetal brain. Without testosterone, the fetal brain is female. Wagner and her team previously reported that certain areas of the fetal rat brain, notably the medial preoptic nucleus (MPN) – an area that mediates sexually differentiated behaviours in adulthood – express the progesterone receptor well before birth. On the day of birth, expression of the progesterone receptor (PR) in the MPN is high in males but virtually absent in females, a difference likely produced by differential exposure to oestradiol."

 

[Drareg]

i dont think anyone ever suggested the fetus was foreign/antigenic/parasitic - could anyone really be that dumb?

youre right, i was hestitant to post the exchange because of the attitudes here...here is one of the more important ones
RP never says much, i guess its his way of directing further reading -_-


It is interesting, there appear to be loads of paper showing there is a clear action on the immune system toward immunosuppression
- natural progesteroneincreases viral replication Effects of Female Sex Hormones on Susceptibility to HSV-2 in Vaginal Cells Grown in Air-Liquid Interface
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376705/


There appears to be a clear increase in infection risk and mortality rate as pregnancy progresses, and this coincides with the natural and very significant rise in Progesterone, and ts ratio to estrogen. .

There is a clear shift away from innate immune system, as well as away from the Th1-dominant cell-mediated adaptive immune response, while increasing the more Th2-dominant / humoral immune function. This change in the immune system is likely very important in bringing a baby to partum, but would seemingly predispose the mother to a much higher infection risk.

This shift is due to Progesterone, and there is data specifically showing Progesterone that does this.

Obviously this is (for some reason) necessary for Pregnancy (otherwise we wouldn’t see this happen!) - so the only question that remains is WHY?

Might it be that it is the interest of the body to create a strong immune system for the child, at the expense of transient infection of the mother??
This immune shift may allow for both infection of more external microorganisms, and production of antibodies against those microorganisms, and then subsequent transfer of antibodies to the baby.

Perhaps accumulation of more foreign microbes in the gut of the mother, is actually leading to "immunity diversification" for the child. This seems to be important, especially when compared to caesarian section kids, who seem to have a harder time with immune system woes…

It was also brought up by a colleague on the ray peat forum that the article suggests the more pregnancies a mother has, the lower the rate of infection mortality decreases, which seems to imply an ongoing immune memory accumulation effect that happens especially strongly during pregnancy. Again, we can speculate that this is aimed at creating a stronger child, despite the risks that it may have to the mother -- the evolutionary process will permit 1 out of 10 mothers die because of this immune shift, if it means getting 9 stronger babies.

We can speculate about the lysogenic accumulation of viral DNA that is permitted by the decreased inflammatory response, which no only improves immunity down the line, but could possibly also lead to novel protein expression (aka: evolution)….



i would be keen to hear your thoughts…



RP

It is a bizarre notion, but after reading some of the links you sent, and finding some further reading - it seems to be a valid point.

Regarding your speculations, I think the idea of passage of antibodies to the developing baby to be the most likely. It is likely that viral DNA accumulation is also involved in epigenetic expressions that allow the child to adapt to the local stressors in their particular environment.

It would be helpful for anyone interested if you posted the full email exchanges, Peat articles on his website highlights how aware he is of "immune" definitions and semantics.
I find it interesting he doesn't mention thyroid or free fatty acids in this exchange.
Thanks.

 

[Drareg]

i dont think anyone ever suggested the fetus was foreign/antigenic/parasitic - could anyone really be that dumb?

youre right, i was hestitant to post the exchange because of the attitudes here...here is one of the more important ones
RP never says much, i guess its his way of directing further reading -_-


It is interesting, there appear to be loads of paper showing there is a clear action on the immune system toward immunosuppression
- natural progesteroneincreases viral replication Effects of Female Sex Hormones on Susceptibility to HSV-2 in Vaginal Cells Grown in Air-Liquid Interface
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376705/


There appears to be a clear increase in infection risk and mortality rate as pregnancy progresses, and this coincides with the natural and very significant rise in Progesterone, and ts ratio to estrogen. .

There is a clear shift away from innate immune system, as well as away from the Th1-dominant cell-mediated adaptive immune response, while increasing the more Th2-dominant / humoral immune function. This change in the immune system is likely very important in bringing a baby to partum, but would seemingly predispose the mother to a much higher infection risk.

This shift is due to Progesterone, and there is data specifically showing Progesterone that does this.

Obviously this is (for some reason) necessary for Pregnancy (otherwise we wouldn’t see this happen!) - so the only question that remains is WHY?

Might it be that it is the interest of the body to create a strong immune system for the child, at the expense of transient infection of the mother??
This immune shift may allow for both infection of more external microorganisms, and production of antibodies against those microorganisms, and then subsequent transfer of antibodies to the baby.

Perhaps accumulation of more foreign microbes in the gut of the mother, is actually leading to "immunity diversification" for the child. This seems to be important, especially when compared to caesarian section kids, who seem to have a harder time with immune system woes…

It was also brought up by a colleague on the ray peat forum that the article suggests the more pregnancies a mother has, the lower the rate of infection mortality decreases, which seems to imply an ongoing immune memory accumulation effect that happens especially strongly during pregnancy. Again, we can speculate that this is aimed at creating a stronger child, despite the risks that it may have to the mother -- the evolutionary process will permit 1 out of 10 mothers die because of this immune shift, if it means getting 9 stronger babies.

We can speculate about the lysogenic accumulation of viral DNA that is permitted by the decreased inflammatory response, which no only improves immunity down the line, but could possibly also lead to novel protein expression (aka: evolution)….



i would be keen to hear your thoughts…



RP

It is a bizarre notion, but after reading some of the links you sent, and finding some further reading - it seems to be a valid point.

Regarding your speculations, I think the idea of passage of antibodies to the developing baby to be the most likely. It is likely that viral DNA accumulation is also involved in epigenetic expressions that allow the child to adapt to the local stressors in their particular environment.

I'm not sure what question you sent to Peat,the formulation of your post implies it's before the RP.
This post was posted by tyw on Tuesday ,you claimed to have emailed Peat in your first post,you sent the link to the scribble pad to Peat,later you claimed to have a good back and forth with him yet the question above is after all of this.

Perhaps you can clarify,thanks.

 

[Such_Saturation]

"Tolerance" of the fetus (or rather, sameness with the mother) is probably electromagnetic in its primary nature. Again, the fights in this thread are almost pointless in the context of Ray Peat.

 

[whodathunkit]

I think it's fair to ask for a reference when someone is arguing from a source that no-one else has access to.

So do I. Absolutely. But in the context of what happened here...I wouldn't have been inclined to share much, either. My point was not the demand (which was a reasonable request, out of the context of this thread) but simply the antagonistic atmosphere in which the demand was placed, and then putative causes of the subsequent lack of response.

But...since I see @Hitoshi is back, I'll stop with the scolding. I just think such deliberately antagonistic behavior as was exhibited in this thread should be more karmically painful in an immediate sense...then maybe it would stop.

 

[Drareg]

Some quotes from Ray Peat,as we know he is always open to change,all hail Peat!

"High quality protein, thyroid, pregnenolone and progesterone tend to correct the underlying pathology. These are antiinflammatory, but they are not immunosuppressive or catabolic".

Below quote is good to consider when feeding for 2,in the third world food isn't exactly a luxury. Increasing progesterone can lead to increased thyroid output,more fuel needed. Not checking thyroid in these studies is farcical imo.
"The simplest illustration of how inflammation relates to the organism's resources was an experiment in which blood glucose was varied, while an animal was exposed to chemicals that varied from mildly irritating to potentially deadly. When the animal had very low blood sugar, the mildest irritant could be deadly, but when its blood glucose was kept very high, even the deadly antigens were only mildly irritating. Varying the blood sodium concentration had similar, but weaker, effects."

"There is a tendency to see inflammation not only as a normal part of immunity, but to see it as being proportional to the nature of the antigen, except when the immune system has been primed for it by previous contact, in which case the organism will either not react at all (because it has become immune), or it will react much more violently than it did on the first exposure, because it has become allergic. But, in reality, the mere concentration of glucose and sodium in the blood (and of thyroid, and many other substances that aren't considered to be part of the immune system) can make a tremendous difference in the degree of "immunological" reaction".

"Adrenaline increases in hypoglycemia, and, if the adrenaline fails to convert glycogen into glucose, it will provide an alternative fuel by liberating free fatty acids from fat cells".

"If the liberated fatty acids are unsaturated, they will cause serotonin to be secreted, and both serotonin and the unsaturated fatty acids will suppress mitochondrial respiration, exacerbating the hypoglycemia. They will stimulate the release of cytokines, activating a variety of immunological and inflammatory processes, and they will cause blood vessels to become leaky, creating edema and starting the first stages of fibrosis. Both adrenaline and serotonin will stimulate the release of cortisol, which mobilizes amino acids from tissues such as the large skeletal muscles. Those muscles contain a large amount of cysteine and tryptophan, which, among other effects, suppress the thyroid. The increased tryptophan, especially in the presence of free fatty acids, is likely to be converted into additional serotonin, since fatty acids release tryptophan from albumin, increasing its entry into the brain. Free fatty acids and increased serotonin reduce metabolic efficiency (leading to insulin resistance, for example) and promote an inflammatory state".

"When a tissue is injured or stressed, antibodies are formed in response to the altered components of that tissue. Therefore, we could call a bruise or a sprain an autoimmune condition, but there are no commercial tests for bruised-shin antibodies. The availability of tests for specific antibodies seems to be the essential factor in classifying a condition as autoimmune, as in "autoimmune thyroiditis." Unfortunately, this way of using language is nested in a culture that is full of unrealistic ideas of causality, and thousands of people build their careers on the search for the "mutated genes that are responsible for the disease," and for the drugs that will correct the defect".

"I believe that an important aspect of the intolerance for heat so often reported in people with MS could be the tendency of relative hyperthermia to release increased amounts of free fatty acids into the blood stream. Women, because of estrogen's effects, usually have much higher levels of free fatty acids in the blood than men do. Estrogen increases the release of free fatty acids from stored fat, and the unsaturated fats synergize with both estrogen and prolactin, increasing their effects".

"The thyroid hormone is ultimately responsible for maintaining cells' energy and structure, and responsiveness, but if it is increased suddenly without allowing all the other factors to adjust, it will raise the temperature too suddenly. It needn't take a long time, but all the factors have to be present at the same time".

For anyone lost in this thread here is the article Multiple sclerosis, protein, fats, and progesterone
There are many more like it on there to give a broader context rather than cherry picked contexts and semantics backed with cherry picked studies.

 

[Giraffe]

I would like to add one quote:

" [...] an entirely different view of the immune system was taking over the medical culture just as Koch began his research. Mechnikov’s morphogenic view, in which the essential function of “the immune system” was to maintain the integrity of the organism, was submerged by Ehrlich’s approach, which emphasized killing pathogens [...] "

Cascara, energy, cancer and the FDA's laxative abuse.

 

[Hitoshi]

^ bang on.

 

[Giraffe]

Estradiol Regulates Susceptibility following Primary Exposure to Genital Herpes Simplex Virus Type 2, while Progesterone Induces Inflammation
> With an inoculation dose of 105 PFU, the saline- and P4-treated mice were found to be highly susceptible to genital HSV-2 infection
> Both groups had extensive pathology and high viral titers in vaginal secretions, and 100% of mice succumbed by day 4 postinfection.
> E2-treated mice were protected from HSV-2 infection at the same dose and did not display any vaginal pathology or viral shedding.
> An analysis of the genes in the vaginal tissue showed that inflammation in the P4-treated group correlated with local induction of chemokines and chemokine receptors that were absent in the E2-treated mice and in uninfected P4-treated mice.

(P4 is progesterone. E2 is estrogen. HSV-2 is Herpes Simplex Virus 2)

One of the possible mechanisms discussed in the study:

The mechanism by which E2 made mice nonsusceptible is not clear. One well-accepted mechanism is that during estrus and under the influence of estradiol, the vaginal epithelium is several layers thick and keratinized in superficial layers, making it impermeable to viral entry (18).

.....

I found these two papers that seem to give a balanced / agenda-free view:

Role of Progesterone in HIV and Parasitic Infections

Thus, protective or permissive effects of P4 depend on the parasite and the host, among other factors [40].

You could also say that you will always find a species that suits you to prove your point.


The Role of Sex Steroids in the Host-Parasite Interaction

This paper discusses the so-called sexual dimorphism (SD) in parasitic infections, and host-parasite interactions. The authors suggest that some parasites use the host's sex steroids for their own purposes, and some modulate the host's hormones.

.....

This brings us back to the question: In which context would progesterone be bad? When would we prefer to have a immune reaction that emphazises to kill the pathogen at the cost of collateral damage to the tissue?

One more quote:

Emerging functions of amphiregulin in orchestrating immunity, inflammation and tissue repair

Similarly, in the context of bacterial-viral co-infections, mice that had been previously infected with Influenza rapidly succumb to a consecutive bacterial infection in the lungs (Jamieson et al., 2013). This effect is not due to an overwhelming pathogen burden but is instead associated with impaired tissue integrity and immunopathology.

 

[haidut]

This brings us back to the question: In which context would progesterone be bad?

Wow, I can't thank you enough for that post! This is what I have been trying to convey all along. If you look at one of my first posts this is what I said:

Calling progesterone immunosuppressive and raising vague doubts about its role in viral infections (where the evidence is mixed) is neither actionable nor beneficial (IMO). Again, if we have specific information about doses, conditions, and contraindications then this is probably what we should be discussing.

But not only did my request get ignored, it apparently is seen as a way of suppressing dissent. As if I had any power to suppress anybody here...
Oh well, I've been misunderstood in worse ways before