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All-trans retinoic acid-induced hypothalamus–pituitary–adrenal hyperactivity involves glucocorticoid receptor dysregulation
Quote from
tim on February 27, 2021, 8:03 am
All-trans retinoic acid-induced hypothalamus–pituitary–adrenal hyperactivity involves glucocorticoid receptor dysregulation
Taken together, we propose that RA activates the HPA axis through (i) an increased hypothalamic CRH production, mediated via RAR-α transcriptional activation; (ii) a deficient negative feedback at the level of hypothalamic GR expression, which implicates changes in GR sensitivity to underlie RA-induced hyperactivity of the HPA axis. In humans, such maladaptive changes in the HPA axis after excessive RA treatment or vitamin A consumption may set the stage for stress-related neuropsychiatric disorders. The rapid reversal by mifepristone may hence be of interest for the development of therapeutic options for HPA-related aspects of depression.
All-trans retinoic acid-induced hypothalamus–pituitary–adrenal hyperactivity involves glucocorticoid receptor dysregulation
Taken together, we propose that RA activates the HPA axis through (i) an increased hypothalamic CRH production, mediated via RAR-α transcriptional activation; (ii) a deficient negative feedback at the level of hypothalamic GR expression, which implicates changes in GR sensitivity to underlie RA-induced hyperactivity of the HPA axis. In humans, such maladaptive changes in the HPA axis after excessive RA treatment or vitamin A consumption may set the stage for stress-related neuropsychiatric disorders. The rapid reversal by mifepristone may hence be of interest for the development of therapeutic options for HPA-related aspects of depression.
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Quote from
tim on February 27, 2021, 8:22 am
b shows levels of corticosterone which is a similar hormone to cortisol, you can see the resting amount is much higher in animals given retinoic acid
b shows levels of corticosterone which is a similar hormone to cortisol, you can see the resting amount is much higher in animals given retinoic acid
Quote from
Orion on February 27, 2021, 9:09 am
@tim-2 When I experimented years ago with cortisol(Isocort), it produced insanely oily skin and insomnia, so this makes sense when you state that RA levels are correlated to higher sebum production. Recently taking pysllium husk induced the same results as Isocort, extreme oiliness and insomnia. Makes me think pysllium husk does somehow pull VA/RA into the system from storage.
Low VA diet and other things that naturally lower cortisol might be options.
@tim-2 When I experimented years ago with cortisol(Isocort), it produced insanely oily skin and insomnia, so this makes sense when you state that RA levels are correlated to higher sebum production. Recently taking pysllium husk induced the same results as Isocort, extreme oiliness and insomnia. Makes me think pysllium husk does somehow pull VA/RA into the system from storage.
Low VA diet and other things that naturally lower cortisol might be options.
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Quote from
lil chick on February 27, 2021, 9:27 am
How is this for an idea:
I think that many of us (non-gainers) have been told by alternative practitioners that we might be adrenal insufficient, and I can see where the logic is because taking steroid helps. The body-wide inflammation of VA toxicity has the adrenal working overtime. Especially us non-gainers. We're like open wounds. We get called 'low adrenal', but the damn adrenals are doing their best to deal with the stress of the toxins on our body.
The gainers, the body is doing a better job of hiding the VA and padding it down by storing it in fat and layering on myxedema (waxy, watery swelling), however, the result is they end up with tissues that can't listen as well to all the hormones, including insulin and thyroid. It's like they have earmuffs on. The gainers end up being called diabetic and low thyroid. But again, the thyroid and pancreas are doing their best to deliver healthy amounts of the hormones.
How is this for an idea:
I think that many of us (non-gainers) have been told by alternative practitioners that we might be adrenal insufficient, and I can see where the logic is because taking steroid helps. The body-wide inflammation of VA toxicity has the adrenal working overtime. Especially us non-gainers. We're like open wounds. We get called 'low adrenal', but the damn adrenals are doing their best to deal with the stress of the toxins on our body.
The gainers, the body is doing a better job of hiding the VA and padding it down by storing it in fat and layering on myxedema (waxy, watery swelling), however, the result is they end up with tissues that can't listen as well to all the hormones, including insulin and thyroid. It's like they have earmuffs on. The gainers end up being called diabetic and low thyroid. But again, the thyroid and pancreas are doing their best to deliver healthy amounts of the hormones.
Quote from
tim on February 27, 2021, 6:03 pm
@orion
That's good information to know that cortisol had that effect. I think we are starting to have more clarity on why Accutane induces more sebum first then slows it down. It's stimulating hormone production then when the dose is high enough I think it's acting locally in the sebaceous gland.
@lil-chick
It'll be a huge discovery if it turns out that excess retinoic acid is a major cause behind various hormonal and adrenal issues.
@orion
That's good information to know that cortisol had that effect. I think we are starting to have more clarity on why Accutane induces more sebum first then slows it down. It's stimulating hormone production then when the dose is high enough I think it's acting locally in the sebaceous gland.
@lil-chick
It'll be a huge discovery if it turns out that excess retinoic acid is a major cause behind various hormonal and adrenal issues.
Quote from
Jiří on February 28, 2021, 12:08 am
@tim-2 I don't think that excess retinoic acid can be major cause behind hormonal and adrenal issues simply because I don't think that most people are vit A toxic.. There is plenty of other reason for chronic stress and hormonal issues like EMF, estrogens everywhere, another like 100 000+ chemical in our environment etc.. Most people have amalgams(mercury) most people have mineral disbalance, most people have EMF exposure, most people have chronic emotional stress due to this fast and stressful lifestyle we live in modern world etc.. But I wouldn't say most people are vit A or retinoic acid toxic.. Maybe ironically most people that are trying to "live and eat healthy" are vit A toxic, but not most people who get the bulk of their calories from white flour, vegetable oils and sugar...
@tim-2 I don't think that excess retinoic acid can be major cause behind hormonal and adrenal issues simply because I don't think that most people are vit A toxic.. There is plenty of other reason for chronic stress and hormonal issues like EMF, estrogens everywhere, another like 100 000+ chemical in our environment etc.. Most people have amalgams(mercury) most people have mineral disbalance, most people have EMF exposure, most people have chronic emotional stress due to this fast and stressful lifestyle we live in modern world etc.. But I wouldn't say most people are vit A or retinoic acid toxic.. Maybe ironically most people that are trying to "live and eat healthy" are vit A toxic, but not most people who get the bulk of their calories from white flour, vegetable oils and sugar...
Quote from
tim on February 28, 2021, 12:49 am
@jiri
Yes I agree there are many other possible causes.
Garrett Smith's presentation of the evidence for Hypervitaminosis A being an epidemic is hard to refute, have you watched it? A large percentage of people have clinical Hypervitaminosis A and excess retinoic acid is a problem before it becomes clinical so I would say most people have excess levels of retinoic acid. Many of the studies he references are old too. Maybe preformed retinol consumption has gone down but beta-carotene consumption is higher now I think.
The median serum retinol level increases with age. That's not a good thing and it indicates Hypervitaminosis A is the norm.
I think most of the population now is trying to eat healthy to some extent. Many people take supplements that contain either pro vitamin A or pre formed vitamin A.
Regardless of whether we think people are eating diets higher or lower in vA the fact is is that if you biopsied everyone's liver you would find a high rate of Hypervitaminosis A.
@jiri
Yes I agree there are many other possible causes.
Garrett Smith's presentation of the evidence for Hypervitaminosis A being an epidemic is hard to refute, have you watched it? A large percentage of people have clinical Hypervitaminosis A and excess retinoic acid is a problem before it becomes clinical so I would say most people have excess levels of retinoic acid. Many of the studies he references are old too. Maybe preformed retinol consumption has gone down but beta-carotene consumption is higher now I think.
The median serum retinol level increases with age. That's not a good thing and it indicates Hypervitaminosis A is the norm.
I think most of the population now is trying to eat healthy to some extent. Many people take supplements that contain either pro vitamin A or pre formed vitamin A.
Regardless of whether we think people are eating diets higher or lower in vA the fact is is that if you biopsied everyone's liver you would find a high rate of Hypervitaminosis A.
Quote from
Jiří on February 28, 2021, 1:35 am
@tim-2 Like I said I think that most people don't have toxic amounts of vit A in the diet. But you are right too much beta carotene can be a problem especially for people who are not eating animal proteins with B vitamins, zinc etc.. For example like my brainwashed sister by some macrobiotic practitioner. Yeah her kids are eating way to much beta carotene and other plant toxins and not enough animal foods to balance it or to help detox it.. But again like I said I don't see it as Dr. Smith that vit A is big reason for why people are more sick today. It's not like most people are eating more liver, carrots and taking vit A supplements. Like I said most people eat processed foods where the bulk of their calories come from flour, vegetable oil and sugar.. I think iron in flour is bigger issue for people in US for example than vit A...
@tim-2 Like I said I think that most people don't have toxic amounts of vit A in the diet. But you are right too much beta carotene can be a problem especially for people who are not eating animal proteins with B vitamins, zinc etc.. For example like my brainwashed sister by some macrobiotic practitioner. Yeah her kids are eating way to much beta carotene and other plant toxins and not enough animal foods to balance it or to help detox it.. But again like I said I don't see it as Dr. Smith that vit A is big reason for why people are more sick today. It's not like most people are eating more liver, carrots and taking vit A supplements. Like I said most people eat processed foods where the bulk of their calories come from flour, vegetable oil and sugar.. I think iron in flour is bigger issue for people in US for example than vit A...
Quote from
Jiří on February 28, 2021, 2:14 am
@are I simply think that deficiency in key micronutrients and toxicity in all kinds of toxins is bigger issue than excessive intake of vit A.. Good analogy for this is sugar and diabetes. Sugar is not a cause of diabetes and why I think iron in foulr is bigger issue than vit A? Because people are eating shit loads of flour and it's fortified with iron not with vit A and the only effective way of lowering iron is bleeding? Iron is much more damaging and will kill you much faster than beta carotene LOL...
@are I simply think that deficiency in key micronutrients and toxicity in all kinds of toxins is bigger issue than excessive intake of vit A.. Good analogy for this is sugar and diabetes. Sugar is not a cause of diabetes and why I think iron in foulr is bigger issue than vit A? Because people are eating shit loads of flour and it's fortified with iron not with vit A and the only effective way of lowering iron is bleeding? Iron is much more damaging and will kill you much faster than beta carotene LOL...
Quote from
Jiří on February 28, 2021, 3:39 am
@are I am sure there is plenty of people doing videos about vit A deficiency and they have plenty of data as well. But hard to argue with someone who really thinks that vit A is just a toxin and is not essential for humans at all..
@are I am sure there is plenty of people doing videos about vit A deficiency and they have plenty of data as well. But hard to argue with someone who really thinks that vit A is just a toxin and is not essential for humans at all..
