Low Toxin Studies "Vitamin A" not needed for steroidogenesis, contrary to Peat's claim

[youngsinatra]

I am a member of the LYL-network and have not seen that many miraculous healing stories. I’ve seen some get better, some get worse, some still struggle after multiple years on this. I am not sure this is the end-all-be-all. I see a lot of people spinning their wheels there, too.

Just thinking out loud.

 

[charlie]

I am a member of the LYL-network and have not seen that many miraculous healing stories. I’ve seen some get better, some get worse, some still struggle after multiple years on this. I am not sure this is the end-all-be-all. I see a lot of people spinning their wheels there, too.

Just thinking out loud.

Not sure how you are missing it, but there have been many. Of course some people struggle, that's just they way its going to be. They have environmental issues they are not able to overcome, personal circumstances, or just bad at following good advice. Not everyone is gonna break through. I have seen many who struggled for a while and then finally got their liver to unlock. You just have to keep chipping away at the toxicities and deficiencies until the Alchemy of the body gets flipped.

 

[Nick]

I am a member of the LYL-network and have not seen that many miraculous healing stories. I’ve seen some get better, some get worse, some still struggle after multiple years on this. I am not sure this is the end-all-be-all. I see a lot of people spinning their wheels there, too.

Just thinking out loud.

I wonder if people tend to move on from the LYL network if they get a lot better, especially with the yearly subscription fee. When the Ray Peat approach was working best for me I did not read or comment on any health information at all for many years, I was just in autopilot doing what worked well for me at the time.

 

[youngsinatra]

Not sure how you are missing it, but there have been many. Of course some people struggle, that's just they way its going to be. They have environmental issues they are not able to overcome, personal circumstances, or just bad at following good advice. Not everyone is gonna break through. I have seen many who struggled for a while and then finally got their liver to unlock. You just have to keep chipping away at the toxicities and deficiencies until the Alchemy of the body gets flipped.

I rarely check in there anymore, but sometimes I do to see what has been going on.

I personally saw a bit progress in my health at the beginning and then basically stagnated for a long time and at some point I even deteriorated more and more + my labs got worse and worse. I logged off at some point and moved on to find a better way. I started reading up studies on myself and used labs together with gut instinct to really understand what’s up with my health.

I think vitamin A toxicity contributed A LOT to my health problems, but the program just didn’t make me able to live. I was basically bedridden, extremely depressed, felt cold, pale and hypothyroid on the program, couldn’t work or exercise etc.

Now I am doing much better. I am active, feel warm most of the time, have rosy skin color, thyroid function is doing better, back to working 40h a week, able to workout, my weird labs normalized largely etc.

 

[Nick]

I rarely check in there anymore, but sometimes I do to see what has been going on.

I personally saw a bit progress in my health at the beginning and then basically stagnated for a long time and at some point I even deteriorated more and more + my labs got worse and worse. I logged off at some point and moved on to find a better way. I started reading up studies on myself and used labs together with gut instinct to really understand what’s up with my health.

I think vitamin A toxicity contributed A LOT to my health problems, but the program just didn’t make me able to live. I was basically bedridden, extremely depressed, felt cold, pale and hypothyroid on the program, couldn’t work or exercise etc.

Now I am doing much better. I am active, feel warm most of the time, have rosy skin color, thyroid function is doing better, back to working 40h a week, able to workout, my weird labs normalized largely etc.

What do you think made the biggest difference between what you do now and the Garrett Smith approach?

 

[mosaic01]

Since this "subclinical toxicity" can't be measured without obscure testing, a large theory has been created and hyped without specific verification.

You either see the connections, or you don't.

One thing that happens with vA detox, is that the serum retinol level actually increases significantly on a diet of zero vitamin A, in the first year or so.

Like here: Low Toxin Logs - Log - Anti-Vitamin A Diet - Testing out if i have been a Peatard

Autopsy studies are clear that around one third of people in western nations suffer from actual verified retinol toxicity. Just because there is not yet a standardized test beyond liver biopsies, does not mean one can't infer things based on past intake, symptoms and improvements.

The reports of people getting better should be sufficient for anyone who is still curious and interested in the truth.

Now I am doing much better. I am active, feel warm most of the time, have rosy skin color, thyroid function is doing better, back to working 40h a week, able to workout, my weird labs normalized largely etc.

What were the most important changes you made?

 

[mosaic01]

I wonder if people tend to move on from the LYL network if they get a lot better, especially with the yearly subscription fee. When the Ray Peat approach was working best for me I did not read or comment on any health information at all for many years, I was just in autopilot doing what worked well for me at the time.

People who get healthy tend to disappear from forums.

There was one member here, I suggested the low A approach to him. Two weeks later he told me his crippling OCD is gone and his life got transformed, and thats why he has stopped visiting this forum, he's gone since then.

There is simply no accurate data yet on how this approach works in people's lifes, but those who see what can happen know that it's a fundamental breakthrough in the known history of medicine and the opportunity for our entire culture to recover from it's collective depression, disease and misery before it's too late (just look at the mental health crisis in the youth and our current birthrates, civilization is at stake).

Health forums and communities give a completely screwed picture of actual reality.

 

[youngsinatra]

What were the most important changes you made?

• Low-metal diet (low in iron, zinc, copper..)
• Supplemental thyroid to optimize thyroid labs, body temperature and heart rate
• Electrolytes through coconut/mineral water (Ca, Mg, Na, K)
• Low-moderate dose B vitamin supplementation
• Low intake of plant toxins (No whole grains, beans, nuts and seeds, night shades..)
• Working on blood circulation (Sauna, exercise, walking, coffee, salt because poor blood circulation/bradycardia = hypoxia in the brain and peripheral regions = a lot of symptoms from that alone)

 

[Ras]

So far, all I can recall reading are generalized anecdotes about people who changed many things in their lifestyle, one of which was lowering carotenoid and retinyl palmitate intake. Then, proponents of this lifestyle attribute almost all of the improvements to the decreased Vitamin A intake.

Doesn't everyone see the obvious problem with this? When you stop consuming something that comprises carotenoids or retinoids, you are also changing the intake of many other things. You can't attribute all the subsequent improvements to a change in one variable, if you also changed many other things.

 

[haidut]

View attachment 61932

In his new video, Danny Roddy briefly mentions the concept of vitamin A as a toxin, and his only counter-argument is the claim that it's required for steroid production, and here he is echoing one of the arguments Ray Peat made in favor of the essentiality of retinol.

Ray Peat quotes:

"In animals, cholesterol is the basic sterol molecule, which is massively converted into other substances, including the steroid hormones. Thyroid hormone and vitamin A are required for this conversion."

"Although one of the important functions of vitamin A is its involvement in the formation of the steroids pregnenolone and progesterone (both of which moderate the effects of cortisol), it also has some hormone like actions directly on the cells of the immune system, and it stimulates production of interleukin-2 and both inhibits generation of specific suppressor cells and limits the intensity of activation of suppressor cells."

"If thyroid and vitamin A can’t be used efficiently to form steroids, a steroid imbalance is likely."

"to a very great extent, progesterone could substitute for vitamin A, meaning that a very large fraction of the vitamin A used by the body is used up in making progesterone, from which the other steroid hormones are made."

"Yes, it's definitely hard to get them coordinated when there's an imbalance in one direction or the other. For several years, when I had an extremely high metabolic rate, I needed 100,000 units per day during sunny weather to prevent acne and ingrown whiskers, but when I moved to a cloudy climate, suddenly that much was too much, and suppressed my thyroid. The average person is likely to be hypothyroid, and to need only 5,000 units per day."

Ray Peat is wrong when it comes to the involvement of retinol in steroid production. This concept has been gained from faulty rat studies.

Earlier in the Grant Genereux thread, @youngsinatra shared the following paper:

Vitamin A: Not Required for Adrenal Steroidogenesis in Rats​

As the paper from 1976 notes, "The use of an ascorbate supplement in vitamin A-depleted rats prevented all of the aforementioned symptoms."

The authors write that the idea for retinol being essential for steroid synthesis is a "controversial suject". It was (and is) by no means a settled thing within academia, but the discussion around this has probably been suppressed or ignored since the 80s.

From this data it becomes clear that the true issue here is simply a lack of ascorbic acid (in the context of diet-induced toxicity or nutrient deficiency), which we know is an anti-toxin.

So the argument that vA is essential for steroid synthesis seems to have no solid foundation. Danny Roddy is just copying Ray's claims without any critical reception here. If this is his best argument, it shows he has not seriously looked into the low A approach at all.

It would be helpful for many people if Danny Roddy, and others involved, would stop treating Ray Peat like he was infallible. There are many things he got outright wrong, and he was never questioned on these things by his followers. Ray Peat, like many other scientists of the 20th century, was blinded by the newly established vitamin ideology - the idea that we need to take in lots of chemicals in exactly the right amount to be healthy, as if life is some kind of complicated puzzle to solve. A concept that is opposite of the actual truth: We need to merely stop the ingestion of toxins and the body brings back itself into balance and health. Some of those toxins are even wrongly classified as essential in large amounts, and thus act as trojan horses for an absurd level of toxicity in our culture in present times.

Now, just to diffuse any accusations that I am bashing the low-vitamin A lifestyle/diet - the comments below are not in any way related to that. People are free to eat what makes them feel best. That being said, a study was posted on vitamin A and I thought I'd chime in.
How would the low-vitamin A practitioners explain the proven fact that retinoic acid is required for male fertility and that vitamin A deficient diets reliably cause male infertility and gonadal deformities, corroborated by the recent human trials showing that retinoic acid receptor (RAR) antagonists are effective as male contraception? If lack of vitamin A causes gonadal damage, reversible by vitamin A supplementation, it does actually mean that vitamin A is required for steroidogenesis since without it, one's testicles atrophy - i.e. no viable sperm and no androgen synthesis either. The fact that RAR antagonists (or lack of RAR) can produce progressive testicular toxicity after even a single administration is especially worrying, at least to me.

A non-hormonal pill could soon expand men’s birth control options

Women have many choices for birth control, ranging from pills to patches to intrauterine devices, and partly as a result, they bear most of the burden of preventing pregnancy. But men’s birth control options — and, therefore, responsibilities — could soon be expanding. Now, scientists report a...

www.eurekalert.org

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401398/

Retinoic acid and androgens interact to regulate spermatogenesis in a non-mammalian vertebrate lacking stra8

In mammals, retinoic acid (RA) signaling is critical for spermatogonial differentiation and for entering meiosis, the latter depending on RA-induced Stra8 gene expression. Many fish species, including zebrafish, do not contain a stra8 gene, but RA signaling nevertheless is important for sperm...

www.biorxiv.org

"...The production of spermatozoa from spermatogonial stem cells (SSCs) is a developmental process that is regulated by a complex network of endocrine and local signaling pathways in the vertebrate testis. One of the local signaling systems makes use of retinoic acid (RA), the biologically active metabolite of vitamin A, which is crucial for mammalian spermatogenesis at a number of steps (reviewed by (1)). In mice, RA is first required for the transition of undifferentiated to differentiating spermatogonia (2), and again during meiotic initiation, the latter reflecting RA-triggered Stra8 (stimulated by retinoic acid 8) gene expression in the testis (3, 4). Moreover, STRA8-independent pathways fine-tune RA action in the testis as shown for SALL4A (spalt like transcription factor 4; (5)) and REC8 (REC8 meiotic recombination protein; (6)). A vitamin A (VAD) deficient diet arrested spermatogonial differentiation (7-9), which was reversed by retinoid supplementation (10, 11). Also, mice lacking different isoforms (α, β, γ) of the nuclear RA and retinoid X receptors (RARs and RXRs) showed testicular abnormalities or sterility (12) and germ cell apoptosis (13, 14). Dominant-negative mutant models of the RARα allowed further characterization of essential molecular functions of RA signaling for germ cell development (15, 16)."

BMS-189453, a novel retinoid receptor antagonist, is a potent testicular toxin - PubMed

BMS-189453 is a synthetic retinoid that acts as an antagonist at retinoic acid receptors alpha, beta, and gamma. In Sprague Dawley rats at daily oral doses of 15, 60, or 240 mg/kg for 1 month, BMS-189453 produced increases in leukocyte counts, alkaline phosphatase and alanine aminotransferase...

pubmed.ncbi.nlm.nih.gov

"...These studies indicate that retinoid antagonists can selectively produce progressive and prolonged testicular toxicity after single or repeated oral doses that are otherwise well tolerated."

@Ras @CLASH

 

[BibleBeliever]

As per this quote:

"Yes, it's definitely hard to get them coordinated when there's an imbalance in one direction or the other. For several years, when I had an extremely high metabolic rate, I needed 100,000 units per day during sunny weather to prevent acne and ingrown whiskers, but when I moved to a cloudy climate, suddenly that much was too much, and suppressed my thyroid. The average person is likely to be hypothyroid, and to need only 5,000 units per day."


There is another thread where a low vitamin a user is having acne problems, wherein this very quote states Ray Peat used vitamin a to cure his acne. Vitamin a opposes estrogen strongly as per the other Ray Peat quotes.

Isn't it as the similar case of high cholesterol? If one has high cholesterol when they are given thyroid, there body converts that cholesterol into the beneficial hormones.
Thyroid converts vitamin a in the same fashion. If thyroid is high than vitamin a requirements increase. If thyroid low, than excessive vitamin a causes problems.

I have been reading the testimonies of those who notice extraordinary benefits from low vitamin a. If this is accurate, how does it line up with RayPeat's work? Can it line up?

I think many use beta carotene interchangeably with retinol (animal vitamin a) in the mainstream when speaking of vitamin a. RayPeaters and even WestonPricers state that maybe only as low as 5% of beta carotene will be converted into usable retinol, some say maybe 10-20%. This process requires sufficient thyroid stimulus and vitamin b12 stores.
In relation to this principle you can find cases of death by carotenemia (excessive unconverted beta carotene) Symptoms like diabetes also can arise from excess, besides the orange hands and feet, and many other issues.

Thus I would think it is most probable that those who find benefit from low vitamin a is due to eliminating beta carotene more so than retinol. They are most likely low thyroid and unable to properly utilize the beta carotene. A side-note vegans have no natural b12 source, so eventually once their b12 reserves run out, all beta carotene would not be able to convert to retinol.

Secondly this is in the context of the majority having excessive polyunsaturated fatty acids in their diet and stored in their tissues. As pufas inhibit thyroid to an extraordinary degree, which then would exasperate issues with beta carotene. Further even usable retinol can inhibit thyroid if in excess. Thus retinol in the context of a person with low thyroid from an unnatural excess of pufa could become more problematic; their need would greatly decrease presumably.
In other words if they did not have all this excessive polyunsaturated fatty acids than their higher thyroid would increase their need for vitamin a.

Another consideration is cytochrome c oxidase. RayPeat speaks of blue light damaging this enzyme, which is copper based. The majority of people are exposed to excessive LEDS and blue light. This amount of blue light exposure has never been seen in human history. Through the phones, computers, streetlights, hospitals, places of work, homes, etc.
In addition many demonize sunlight and get much less now than probably ever. Further even using sunglasses to block out more sun and even when driving their windows blocking it. In contrast historically people walked outside very great distances regularly and worked outside, the sunlight exposure then was much greater. Thus very little blue light in comparison to now with ample sunlight which provides sufficient red light.

The only way to regenerate this copper enzyme is through sufficient red light. Candle light provides great amounts, as all fire light does.
The sunlight provides the full light spectrum of light and thus sufficient red light.
Therefore it is probable that most of these low vitamin a testimonies may have severely damaged cytochrome c oxidase. This then inhibiting ceruloplasmin, which vitamin a is carried on. Therefore making vitamin a much more problematic.

I am only speculating possibilities to harmonize such with RayPeat's work.

 

[mosaic01]

How would the low-vitamin A practitioners explain the proven fact that retinoic acid is required for male fertility and that vitamin A deficient diets reliably cause male infertility and gonadal deformities, corroborated by the recent human trials showing that retinoic acid receptor (RAR) antagonists are effective as male contraception?

Retinoic acid and androgens interact to regulate spermatogenesis in a non-mammalian vertebrate lacking stra8

In mammals, retinoic acid (RA) signaling is critical for spermatogonial differentiation and for entering meiosis, the latter depending on RA-induced Stra8 gene expression. Many fish species, including zebrafish, do not contain a stra8 gene, but RA signaling nevertheless is important for sperm...

www.biorxiv.org

This paper mentions that "Surprisingly, androgens can partially compensate for the loss of RA signaling, and we identify a link between the endocrine system and RA signaling: follicle-stimulating hormone (Fsh) stimulates testicular RA production."

"While loss of RA signaling in germ cells clearly affects testis histology in 6 month-old transgenic males, it is not critical for sperm production and spermatogenesis recovers at 9 months of age; however, the sperm that are produced are of low quality."

I remember from Weston Price that women who wanted to get pregnant were fed retinol-containing foods like eggs and liver. It is also documented that people throughout history used liver to cure night blindness. There was someone here on the forum who went low A, reduced his blood levels to almost zero, and got eye problems that were corrected when he increased his retinol intake again. At the same time, Grant Genereux has proven that retinol is not essential for life, as otherwise he would already be dead (intake and blood levels approaching zero), and there are others as well who have achieved zero.

Despite his zero A diet, Genereux has speculated that extremely small amounts of retinol may be necessary for cell differentiation in early life and during growth, if I remember correctly.

It seems judging from historical use, that there are two areas where retinol has some function in the body - eyesight and fertility. But this function does not seem to be that of a vitamin.

Rather, it could be, that, like alluded to in the above paper, RA boosts cell differentiation in a drug-like manner, and thus overwrites normal physiological processes. In this case, RA, due to it's toxic effect of wasting stem cells and causing differentiation, has an effect on what ideally should be the responsibility of hormones like FsH.

Thus scientists have confused cause and effects here in these studies. They use retinoic acid as a drug to initiate cell differentiation in critical phases of organism development, and thus override the normal systems that are in place to regulate cell differentiation without RA.

Similar to the non-essentiality of PUFA according to Peat, another role of retinol could be in lowering the metabolic rate and masking nutrient deficiencies, like protein, b-vitamins, zinc and other minerals. Thus the organism can continue to live without symptoms in the context of a non-ideal environment.

I think this entire discussion only becomes relevant once the liver stores are completely empty and the intake is below 200-300mcg per day. Even a low A diet often has 200mcg. The EFSA notes that ingested retinol amounts over 300mcg are excreted in bile, the body wants to get rid of it. If retinol has physiological and relevant effects in the body in the form of a vitamin, the required intake must be lower than that, and everything above 300mcg acts as a toxin.

As long as the blood level is above roughly 15mcg/dl, negative effects that are ascribed to a lack of retinol should not be possible. Thus, a controlled vA detox for several years until liver is depleted should not make people worry who believe in the essentiality of retinol.

Regarding the RA-antagonists. Given Peat's criticism towards recepter theory, it seems to be possible that these RA-antagonists are simply toxins and antagonists of cell differentiation proceses and thus they block the function that certain hormones like FsH have. As I mentioned elsewhere, just because a "receptor" responds to retinoic acid, does not make it the RA receptor. Humans have given a phenomenon they observed in the body this name. It could be just a cell differentiation "receptor", and using a strong antagonist would thus block the functions of hormones on that "receptor".

Another question is whether there is really a high-quality study with mice or rats that conclusively shows the essentiality of RA in fertility. Because the problem here may simply be the problematic diet they feed to these lab animals. It may either contain hidden sources of RA, or maybe is deficient in other important nutrients. Most studies seem to be done on isolated cells and not on living animals. One would need to devise a non-toxic diet that has all relevant nutrients and feed multiple generations of mice or rats. I wonder whether his has been done before, even with the usual feed?

I think it's really important to stress that the discussion around this is mostly theoretical as long as one doesn't have serum retinol levels approaching <15 mcg/dL. For the majority in the Peat-sphere, this takes years of detox.

During the last decades, the global supplementation programs of retinol have increased, but fertility is going down, so there is clearly a negative association. Retinol kills fertility.

It's a bit funny that the country in the world with the highest fertility rate (Niger) also has the highest prevalence of "VAD". Things have been completely inverted.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912822/

https://en.wikipedia.org/wiki/List_of_countries_by_total_fertility_rate

 

[Jabuger]

I think this is an interesting paper by Mawson on the RA receptors. Antagonism and agonism of the different receptors alpha and beta have different effects. Albeit in relation to Gioma’s.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421472/

“In the case of gliomas, excessive and/or repeated exposure of the glial cells to retinoic acid due to the aforementioned risk factors, as well as traumatic brain injury, may result in alterations in the expression of retinoid receptor isotypes characterized by increased expression of RARα and reduced expression of RARβ.”

 

[Nick]

Regarding the RA-antagonists. Given Peat's criticism of Peat towards recepter theory, it seems to be possible that these RA-antagonists are simply toxins and antagonists of cell differentiation proceses and thus they block the function that certain hormones like FsH have. As I mentioned elsewehere, just because a "receptor" responds to retinoic acid, does not make it the RA receptor. Humans have given a phenomenon they observed in the body this name. It could be just a cell differentiation "receptor", and using a strong antagonist would thus block the functions of hormones on that "receptor".

Exactly, the idea of a receptor just represents some particular thing the cell can do with retinol. What does it actually mean to "block" a "receptor" then? And what happens to retinol when this path is blocked? Perhaps it goes down a more destructive path, and at the very least the retinol is still there in circulation. "Blocking" a "receptor" is not the same thing as the abscence of the substance which the "receptor" acts on.

Another question is whether there is really a high-quality study with mice or rats that conclusively shows the essentiality of RA in fertility. Because the problem here may simply be the problematic diet they feed to these lab animals. It may either contain hidden sources of RA, or maybe is deficient in other important nutrients. Most studies seem to be done on isolated cells and not on living animals. One would need to devise a non-toxic diet that has all relevant nutrients and feed multiple generations of mice or rats. I wonder whether his has been done before, even with the usual feed?

I think it's really important to stress that the discussion around this is mostly theoretical as long as one doesn't have serum retinol levels approaching <15 mcg/dL. For the majority in the Peat-sphere, this takes years of detox.

During the last decades, the global supplementation programs of retinol have increased, but fertility is going down, so there is clearly a negative association. Retinol kills fertility.

It's a bit funny that the country in the world with the highest fertility rate (Niger) also has the highest prevalence of "VAD". Things have been completely inverted.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912822/

https://en.wikipedia.org/wiki/List_of_countries_by_total_fertility_rate

It seems completely theoretical once one considers how hard it is to have truly low serum retinol.

 

[mosaic01]

• Low-metal diet (low in iron, zinc, copper..)
• Supplemental thyroid to optimize thyroid labs, body temperature and heart rate
• Electrolytes through coconut/mineral water (Ca, Mg, Na, K)
• Low-moderate dose B vitamin supplementation
• Low intake of plant toxins (No whole grains, beans, nuts and seeds, night shades..)
• Working on blood circulation (Sauna, exercise, walking, coffee, salt because poor blood circulation/bradycardia = hypoxia in the brain and peripheral regions = a lot of symptoms from that alone)

Sonunds reasonable to me and a lot of this makes sense in the context of detox. Maybe with the exception of coffee, which will act like a crutch.

Regarding the low metal diet, since you got actual clinical toxicity from retinol pretty quickly, you may be pretty sensitive to build up, and maybe you actually suffered from zinc toxicity as well.

 

[youngsinatra]

Sonunds reasonable to me and a lot of this makes sense in the context of detox. Maybe with the exception of coffee, which will act like a crutch.

Regarding the low metal diet, since you got actual clinical toxicity from retinol pretty quickly, you may be pretty sensitive to build up, and maybe you actually suffered from zinc toxicity as well.

Yes. Interestingly there seems to be the possibility of zinc accumulation in the liver in cholestasis:

Excess zinc associated with severe progressive cholestasis in Cree and Ojibwa-Cree children - PubMed

The excess copper may be due to chronic cholestasis but the excess zinc is unexplained. Since three of the patients are related (shared grandparents), a genetic disorder of metal metabolism is possible, but we cannot exclude environmental factors.

pubmed.ncbi.nlm.nih.gov

Hepatic zinc in hemochromatosis - PubMed

Since an intestinal absorptive interaction between iron and zinc has been described in animals and humans, the possibility of increased accumulation of zinc as well as iron in the liver was studied in patients with hereditary hemochromatosis. Hepatic zinc was determined by atomic absorption...

pubmed.ncbi.nlm.nih.gov