I know some people on the forum struggle with high cortisol, as well as its accompanying side effects such as weight gain, muscle loss, etc. It looks like vitamin A may be able to help, and it can do so even in people with Cushing disease whose cortisol levels are VERY high. Here is some info on that:
viewtopic.php?f=116&t=8130
In the obesity and insulin resistance studies below, the minimum effective dose of vitamin A for obesity was a human equivalent of 1.4mg/kg of retinyl palmitate. The effects were statistically significant at the end of second month, while the full study lasted 5 months. This means that a dose of about 200,000 IU daily is needed to replicate the findings of the study. While this dose may seem high, a human study found that much publicized toxicity of natural vitamin A is greatly overblown and vitamin A in doses as high as 500,000 IU daily for months appears to be safe for humans with acne. Here is more info on that:
viewtopic.php?f=116&t=8128
Finally, Ray has cautioned that high doses of vitamin A may inhibit thyroid activity, but this study with a daily dose of 25,000 IU found exactly the opposite - i.e. vitamin A suppressed TSH and increased T3.
viewtopic.php?f=116&t=8131 [ moderator edit: correct link ]
The main mechanism of action of vitamin A was the inhibition of the enzyme 11b-HSD1, which is responsible for the synthesis of cortisol. As forum members undoubtedly know, elevated cortisol has been implicated as a cause in diabetes, heart disease, osteopenia, muscle loss, skin atrophy, mental disease, and host of other degenerative conditions. Cortisol also inhibits thyroid gland function and the conversion of T4 into T3. Finally, cortisol pormotes the synthesis of estrogen, which then drives the production of more cortisol. In summary, cortisol is something best kept at bay.
The inhibition of 11b-HSD1 by vitamin A is very similar to the activity of DHEA, which also inhibits 11b-HSD1 at doses of 5mg+. So, combining the two may be synergistic and thus require less vitamin A to limit the risk of side effects even more.
Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats
Mitochondriogenesis and apoptosis: possible cause of vitamin A-mediated adipose loss in WNIN/Ob-obese rats. - PubMed - NCBI
Vitamin A as a key regulator of obesity & its associated disorders: Evidences from an obese rat model
Vitamin A supplementation induces adipose tissue loss through apoptosis in lean but not in obese rats of the WNIN/Ob strain. - PubMed - NCBI
From the first study above:
"...Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα), the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα), a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes."
"...This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly contribute to visceral fat loss in these obese rats. Studying the role of various nutrients on the regulation of 11β-HSD1 activity and expression will help in the evolving of dietary approaches to treat obesity and insulin resistance."
"...In summary, we showed for the first time that supra-physiological dose of vitamin A through diet decreases 11β-HSD1 activity in visceral fat and liver of WNIN/Ob obese rat. The observed vitamin A-mediated reduction in 11β-HSD1 activity in the visceral fat of obese rats may contribute to the decreased visceral fat mass in this model. Further research is needed to understand the mechanisms involved in the regulation of 11β-HSD1 by various nutrients in tissues like liver and visceral fat in order to develop appropriate dietary interventions to prevent the development of obesity and insulin resistance."
viewtopic.php?f=116&t=8130
In the obesity and insulin resistance studies below, the minimum effective dose of vitamin A for obesity was a human equivalent of 1.4mg/kg of retinyl palmitate. The effects were statistically significant at the end of second month, while the full study lasted 5 months. This means that a dose of about 200,000 IU daily is needed to replicate the findings of the study. While this dose may seem high, a human study found that much publicized toxicity of natural vitamin A is greatly overblown and vitamin A in doses as high as 500,000 IU daily for months appears to be safe for humans with acne. Here is more info on that:
viewtopic.php?f=116&t=8128
Finally, Ray has cautioned that high doses of vitamin A may inhibit thyroid activity, but this study with a daily dose of 25,000 IU found exactly the opposite - i.e. vitamin A suppressed TSH and increased T3.
viewtopic.php?f=116&t=8131 [ moderator edit: correct link ]
The main mechanism of action of vitamin A was the inhibition of the enzyme 11b-HSD1, which is responsible for the synthesis of cortisol. As forum members undoubtedly know, elevated cortisol has been implicated as a cause in diabetes, heart disease, osteopenia, muscle loss, skin atrophy, mental disease, and host of other degenerative conditions. Cortisol also inhibits thyroid gland function and the conversion of T4 into T3. Finally, cortisol pormotes the synthesis of estrogen, which then drives the production of more cortisol. In summary, cortisol is something best kept at bay.
The inhibition of 11b-HSD1 by vitamin A is very similar to the activity of DHEA, which also inhibits 11b-HSD1 at doses of 5mg+. So, combining the two may be synergistic and thus require less vitamin A to limit the risk of side effects even more.
Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats
Mitochondriogenesis and apoptosis: possible cause of vitamin A-mediated adipose loss in WNIN/Ob-obese rats. - PubMed - NCBI
Vitamin A as a key regulator of obesity & its associated disorders: Evidences from an obese rat model
Vitamin A supplementation induces adipose tissue loss through apoptosis in lean but not in obese rats of the WNIN/Ob strain. - PubMed - NCBI
From the first study above:
"...Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα), the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα), a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes."
"...This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly contribute to visceral fat loss in these obese rats. Studying the role of various nutrients on the regulation of 11β-HSD1 activity and expression will help in the evolving of dietary approaches to treat obesity and insulin resistance."
"...In summary, we showed for the first time that supra-physiological dose of vitamin A through diet decreases 11β-HSD1 activity in visceral fat and liver of WNIN/Ob obese rat. The observed vitamin A-mediated reduction in 11β-HSD1 activity in the visceral fat of obese rats may contribute to the decreased visceral fat mass in this model. Further research is needed to understand the mechanisms involved in the regulation of 11β-HSD1 by various nutrients in tissues like liver and visceral fat in order to develop appropriate dietary interventions to prevent the development of obesity and insulin resistance."
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