haidut

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The so-called "glucocorticoid resistance" is thought be behind a number of degenerative conditions including diabetes, depression, schizophrenia, chronic inflammation, autoimmune conditions, etc. The condition, similar to insulin resistance, is characterized by elevated serum cortisol levels and low suppression by synthetic glucocorticoids like dexamethasone. Agents that restore the sensitivity of the glucocorticoid receptor lead to decrease of serum cortisol levels, and are thought to be one of the most promising therapeutic agents for chronic disease.
The study below found that vitamin D is one such chemical, and confirmed its effects in humans. While the study keeps mentioning vitamin D3, the actual chemical used was calcitriol and the dose was about 20 IU daily. Given that caltiriol is not the same steroid as vitamin D3 (cholecalciferol) but rather an "activated" derivative, probably a higher dose of cholecalciferol may be needed to achieve the same effects. Conversion studies show that the effectiveness ratio of cacitriol:cholecalciferol is about 50:1 to 100:1, which means that an actual vitamin D3 dose that should achieve the same effects would be about 1,000 - 2,000 IU daily. That falls within the range Peat has recommended to people before (2,000 - 3,000 IU daily).


Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. - PubMed - NCBI
"...A proportion of asthmatic patients fails to benefit from oral glucocorticoid therapy and are thus denoted as having glucocorticoid-resistant (SR, derived from “steroid resistant”) or insensitive asthma (13). SR is associated with in vitro and in vivo alterations in cellular responses to exogenous glucocorticoids.

"...We investigated whether vitamin D3 might also act to increase GR expression since topical administration of calcitriol to patients with psoriasis has been shown to increase IL-10 locally in the skin (33). Although this was not the case (Figure (Figure6A),6A), we observed, as independently reported in certain cell lines (34), that the culture of CD4+ T cells with glucocorticoids leads to a dose-dependent decrease in GRα (Figure (Figure6B).6B). Strikingly, vitamin D3 abrogated the profound downregulation of GRα caused by dexamethasone (Figure (Figure6C),6C), suggesting a potential mechanism whereby vitamin D3 may contribute to the efficacy of dexamethasone in promoting glucocorticoid-induced IL-10 synthesis."

"...In a proof of concept study, the effect of ingestion of vitamin D3 in SR asthmatic patients was investigated. Subjects were bled prior to vitamin D3 ingestion and on days 1, 3, and 7 after ingestion of 0.5 μg vitamin D3 daily. T cells were stimulated with anti-CD3 in the presence or absence of dexamethasone for 7 days, using methodology identical to that used in earlier experiments, to determine any differences in reactivity to dexamethasone. Cell pellets were prepared at this time for mRNA extraction, or cells were recultured in the absence of drugs and analyzed for changes in IL-10 protein at 48 hours. In all SR individuals tested, IL-10 expression by CD4+ T cells was enhanced following vitamin D3 ingestion as assessed by intracellular cytokine staining, ELISA, and quantitative PCR (Figure (Figure7).7). In 2 donors (SR1 and SR2), this enhancement was sustained on days 1 and 3 as well as day 7 in SR2 over a range of dexamethasone concentrations. In the third donor, SR3, enhancement was observed on day 3 alone. Similar protein data were observed in 4 healthy individuals tested in a pilot study (Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI21759DS1 JCI - Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients; RNA not assayed in this earlier study). These preliminary data provide encouraging evidence of the capacity of vitamin D3 to promote responsiveness to glucocorticoids for the induction of IL-10 synthesis."
 

Agent207

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A great mistake to think on vitaminD as supplement, instead of the sulfated form through skin synthesis via uvb, the most effective and safe way.

People like to play roulette russe with their health with d3 supps and messing with the vdr and immune system.
 

WestCoaster

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A great mistake to think on vitaminD as supplement, instead of the sulfated form through skin synthesis via uvb, the most effective and safe way.

People like to play roulette russe with their health with d3 supps and messing with the vdr and immune system.

This is true on so many levels. It really shouldn't be called a vitamin because it's more like a steroid. Many doctors make the mistake of putting patients on both calcium and D3 supplements without boosting K2. Taking D3 will boost the need for K2 or else someone is risking calcification within the body in unwanted places over time.

IMO, it's better to forget supplementing with calcium or vitamin D, and supplement with K2 instead and get your vitamin D the old fashion way, in the sun.
 

Giraffe

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Taking D3 will boost the need for K2 or else someone is risking calcification within the body in unwanted places over time.
Everyone (who considers supplementing vitamin D) should ensure that they get adequate vitamin K, as well as magnesium and calcium.

Do you have a source for the claim that "taking D3 will boost the need for K2"?
 

Mito

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IMO, it's better to forget supplementing with calcium or vitamin D, and supplement with K2 instead and get your vitamin D the old fashion way, in the sun.

We don't all live on the WestCoast with abundant sunshine all year. Many (including Peat) agree that supplemental Vitamin D is safe as long as you regularly check your level of 25(OH)D – or vitamin D status.
 

ilikecats

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Everybody is so afraid of vitamin d here lol. I feel like it is because vitamin d supplementation is so popular in mainstream culture. Ray peat said 10000 iu is perfectly fine and would be the equivalent of 20 to 30 mins of full body sun exposure.
 

lvysaur

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Direct sunshine definitely does something that vitamin D doesn't.

Maybe it's the combination of blue and red light administered simultaneously. It feels different from red light.
 

haidut

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Nice @haidut
Interesting as usual :)

So can we do 5000 iu every other day in your opinion ?

In theory yes, but for some reason I have a feeling a lower dose every day may work better. Some people reported symptoms of hypercalcemia at 5,000+ IU daily and also blood tests showed that 5,ooo IU daily raised their blood levels less than 3,000 IU daily. So, they may be a transport saturation issue for some people. If you are taking higher dose you can try with taurine as it helps carry the fat-soluble vitamins to the cell.
Taurine Enhances Bioavailability Of Vitamins K, A, D, E
 

James ardagna

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does this mean that short term d3 supplementation could result in high cortisol symptoms i.e. high blood pressure due to improved cortisol sensitivity ?
 

ddjd

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While the study keeps mentioning vitamin D3, the actual chemical used was calcitriol and the dose was about 20 IU daily. Given that caltiriol is not the same steroid as vitamin D3 (cholecalciferol) but rather an "activated" derivative,
no chance of a Caltiriol supplement I suppose?:D
 

ddjd

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The so-called "glucocorticoid resistance" is thought be behind a number of degenerative conditions including diabetes, depression, schizophrenia, chronic inflammation, autoimmune conditions, etc. The condition, similar to insulin resistance, is characterized by elevated serum cortisol levels and low suppression by synthetic glucocorticoids like dexamethasone. Agents that restore the sensitivity of the glucocorticoid receptor lead to decrease of serum cortisol levels, and are thought to be one of the most promising therapeutic agents for chronic disease.
The study below found that vitamin D is one such chemical, and confirmed its effects in humans. While the study keeps mentioning vitamin D3, the actual chemical used was calcitriol and the dose was about 20 IU daily. Given that caltiriol is not the same steroid as vitamin D3 (cholecalciferol) but rather an "activated" derivative, probably a higher dose of cholecalciferol may be needed to achieve the same effects. Conversion studies show that the effectiveness ratio of cacitriol:cholecalciferol is about 50:1 to 100:1, which means that an actual vitamin D3 dose that should achieve the same effects would be about 1,000 - 2,000 IU daily. That falls within the range Peat has recommended to people before (2,000 - 3,000 IU daily).


Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. - PubMed - NCBI
"...A proportion of asthmatic patients fails to benefit from oral glucocorticoid therapy and are thus denoted as having glucocorticoid-resistant (SR, derived from “steroid resistant”) or insensitive asthma (13). SR is associated with in vitro and in vivo alterations in cellular responses to exogenous glucocorticoids.

"...We investigated whether vitamin D3 might also act to increase GR expression since topical administration of calcitriol to patients with psoriasis has been shown to increase IL-10 locally in the skin (33). Although this was not the case (Figure (Figure6A),6A), we observed, as independently reported in certain cell lines (34), that the culture of CD4+ T cells with glucocorticoids leads to a dose-dependent decrease in GRα (Figure (Figure6B).6B). Strikingly, vitamin D3 abrogated the profound downregulation of GRα caused by dexamethasone (Figure (Figure6C),6C), suggesting a potential mechanism whereby vitamin D3 may contribute to the efficacy of dexamethasone in promoting glucocorticoid-induced IL-10 synthesis."

"...In a proof of concept study, the effect of ingestion of vitamin D3 in SR asthmatic patients was investigated. Subjects were bled prior to vitamin D3 ingestion and on days 1, 3, and 7 after ingestion of 0.5 μg vitamin D3 daily. T cells were stimulated with anti-CD3 in the presence or absence of dexamethasone for 7 days, using methodology identical to that used in earlier experiments, to determine any differences in reactivity to dexamethasone. Cell pellets were prepared at this time for mRNA extraction, or cells were recultured in the absence of drugs and analyzed for changes in IL-10 protein at 48 hours. In all SR individuals tested, IL-10 expression by CD4+ T cells was enhanced following vitamin D3 ingestion as assessed by intracellular cytokine staining, ELISA, and quantitative PCR (Figure (Figure7).7). In 2 donors (SR1 and SR2), this enhancement was sustained on days 1 and 3 as well as day 7 in SR2 over a range of dexamethasone concentrations. In the third donor, SR3, enhancement was observed on day 3 alone. Similar protein data were observed in 4 healthy individuals tested in a pilot study (Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI21759DS1 JCI - Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients; RNA not assayed in this earlier study). These preliminary data provide encouraging evidence of the capacity of vitamin D3 to promote responsiveness to glucocorticoids for the induction of IL-10 synthesis."
are there any other substances known to improve Glucocorticoid sensitivity?
 

RayPeatFan777

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are there any other substances known to improve Glucocorticoid sensitivity?
Was just scrolling down this thread ready to ask the very same thing... did you find an answer?

@haidut is very busy these days but if you see this Haidut and have a minute could you please just list the known substances and ill research them further. thanks.

I think P5p might be one. I am in my current poor state of health because of oral steroids. This perspective could be a game-changer for me.
 
Last edited:

Astolfo

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Aug 12, 2018
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are there any other substances known to improve Glucocorticoid sensitivity?

I wonder this too, is there a safer way to improve G sensitivity? I'm 17, and apperantly, the sun exposure is not enought to improve my situation.
 

lampofred

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Feb 13, 2016
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I wonder this too, is there a safer way to improve G sensitivity? I'm 17, and apperantly, the sun exposure is not enought to improve my situation.

I am just guessing but I think CO2 would be the most important thing that improves sensitivity to glucocorticoids.
 

ddjd

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Joined
Jul 13, 2014
Messages
3,776
The so-called "glucocorticoid resistance" is thought be behind a number of degenerative conditions including diabetes, depression, schizophrenia, chronic inflammation, autoimmune conditions, etc. The condition, similar to insulin resistance, is characterized by elevated serum cortisol levels and low suppression by synthetic glucocorticoids like dexamethasone. Agents that restore the sensitivity of the glucocorticoid receptor lead to decrease of serum cortisol levels, and are thought to be one of the most promising therapeutic agents for chronic disease.
The study below found that vitamin D is one such chemical, and confirmed its effects in humans. While the study keeps mentioning vitamin D3, the actual chemical used was calcitriol and the dose was about 20 IU daily. Given that caltiriol is not the same steroid as vitamin D3 (cholecalciferol) but rather an "activated" derivative, probably a higher dose of cholecalciferol may be needed to achieve the same effects. Conversion studies show that the effectiveness ratio of cacitriol:cholecalciferol is about 50:1 to 100:1, which means that an actual vitamin D3 dose that should achieve the same effects would be about 1,000 - 2,000 IU daily. That falls within the range Peat has recommended to people before (2,000 - 3,000 IU daily).


Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. - PubMed - NCBI
"...A proportion of asthmatic patients fails to benefit from oral glucocorticoid therapy and are thus denoted as having glucocorticoid-resistant (SR, derived from “steroid resistant”) or insensitive asthma (13). SR is associated with in vitro and in vivo alterations in cellular responses to exogenous glucocorticoids.

"...We investigated whether vitamin D3 might also act to increase GR expression since topical administration of calcitriol to patients with psoriasis has been shown to increase IL-10 locally in the skin (33). Although this was not the case (Figure (Figure6A),6A), we observed, as independently reported in certain cell lines (34), that the culture of CD4+ T cells with glucocorticoids leads to a dose-dependent decrease in GRα (Figure (Figure6B).6B). Strikingly, vitamin D3 abrogated the profound downregulation of GRα caused by dexamethasone (Figure (Figure6C),6C), suggesting a potential mechanism whereby vitamin D3 may contribute to the efficacy of dexamethasone in promoting glucocorticoid-induced IL-10 synthesis."

"...In a proof of concept study, the effect of ingestion of vitamin D3 in SR asthmatic patients was investigated. Subjects were bled prior to vitamin D3 ingestion and on days 1, 3, and 7 after ingestion of 0.5 μg vitamin D3 daily. T cells were stimulated with anti-CD3 in the presence or absence of dexamethasone for 7 days, using methodology identical to that used in earlier experiments, to determine any differences in reactivity to dexamethasone. Cell pellets were prepared at this time for mRNA extraction, or cells were recultured in the absence of drugs and analyzed for changes in IL-10 protein at 48 hours. In all SR individuals tested, IL-10 expression by CD4+ T cells was enhanced following vitamin D3 ingestion as assessed by intracellular cytokine staining, ELISA, and quantitative PCR (Figure (Figure7).7). In 2 donors (SR1 and SR2), this enhancement was sustained on days 1 and 3 as well as day 7 in SR2 over a range of dexamethasone concentrations. In the third donor, SR3, enhancement was observed on day 3 alone. Similar protein data were observed in 4 healthy individuals tested in a pilot study (Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI21759DS1 JCI - Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients; RNA not assayed in this earlier study). These preliminary data provide encouraging evidence of the capacity of vitamin D3 to promote responsiveness to glucocorticoids for the induction of IL-10 synthesis."
haidut is it your opinion that insulin resistance is closely related to HPA axis dysfunction?
 
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