Vitamin A Is A Powerful Anti-obesity Agent By Lowering Cortisol

[LeeLemonoil]

PPAR-Delta is a pro-metabolic and anti-obesity cellular pathway that gets stimulated very profoundly by RA

 

[haidut]

BUMP. Just came across some of the same studies.



Is this in reference to the first study listed? I thought the dose was mg/kg of food, not bodyweight.

There are several studies in that thread that used high dose vitamin A for obese rodents. The dose used was 129mg/kg diet, which translates to 12.9mg/kg bodyweight, which is HED of 1.8mg/kg - 2.25mg/kg bodyweight for a human. So, even higher than what my original comment said.

 

[Momado965]

But what about vitamin d levels of the participants? Also if I am going on a strickt honey diet with gekatin and whey protein for weight loss how much fat do I need for vitamin a and d for oral absorption?

 

[tankasnowgod]

Here's another recent study in support of this topic-

https://www.tandfonline.com/doi/full/10.1080/21623945.2021.2015864

It found that Retinoic Acid increased energy expenditure, increased CO2 production, and reversed weight gain from a High Fat Diet. It also reduced size and fat deposition in the liver of the mice with NAFLD. Apparently, the effect is indirect, and it did this not by targeting the liver, but adipose tissue-

RA exerts therapeutic effects by targeting the adipose tissue​

WAT functions primarily as a key regulatory centre of energy metabolism and a site for fuel storage [10]. Considering the increased energy expenditure induced by RA (Figure 2), we then evaluated the effects of RA on WAT. In general, WAT is categorized as subcutaneous WAT, dorsolumbar WAT, perigonadal WAT, retroperitoneal WAT, gluteal WAT, inguinal WAT, and mesenteric WAT. Unlike our results observed in the liver, treatment with RA significantly reduced the weight of different WATs and interscapular brown adipose tissue (BAT) in NAFLD mice (Figure 4a-H). Furthermore, as shown in H&E staining, RA treatment reversed the apparent fat cell changes caused by HFD (Figure 4i). In addition, on using the OP9 differentiation model, we found that RA significantly affected adipose differentiation (Figure 4j). These data showed that RA treatment had a direct effect on WAT, and changes in WAT by RA could be the primary contributor towards NAFLD amelioration.

Retinoic Acid was dosed at 50mg per Kilogram of diet.

HFD feed and metabolic assays​

The animal protocols followed in this study were approved by the Animal Ethics Committee of Jiangnan University, China. All experiments were performed in accordance with Chinese regulations for the administration of affairs concerning experimental animals 2017. Male C57BL/6 mice (6 weeks old) were purchased from the Xi Nuo Sai BioScience, Inc. (Suzhou, China) and randomly classified into two groups: normal diet (ND; chow diet, 10% of calories derived from fat) and high-fat diet (HFD, 60% of calories derived from fat, Research Diets, Beijing, China; D12451). After 12 weeks of modelling, the HFD group was further divided into two groups, fed with or without RA (50 mg RA per 1 kg diet). Eight mice were included in each group.

 

[Dr. B]

To offset that amount of copper you would need about 150mg zinc, doesn't seem possible. Ratio zinc:copper should be 8:1 at the very least.

That ratio is only meant for supplement users. Vitamin A itself helps utilize and offset copper. And i think other things do as well like vitamin C, taurine, zinc and even iron, which liver has all of them.

@schultz so in Rays other comment you posted, he said there were increasing benefits of vitamin A up to 100k IU a day?

Also has anyone on the forum experimented with these megadoses of vitamin A yet? It seems like even adding in 10,000 IU of retinyl palmitate causes some bone pain and hair loss…? So im not sure about safety. And some claim bone pain could be because the body is restructuring and regenerating bone? Not sure

 

[Dr. B]

Here's another recent study in support of this topic-

https://www.tandfonline.com/doi/full/10.1080/21623945.2021.2015864

It found that Retinoic Acid increased energy expenditure, increased CO2 production, and reversed weight gain from a High Fat Diet. It also reduced size and fat deposition in the liver of the mice with NAFLD. Apparently, the effect is indirect, and it did this not by targeting the liver, but adipose tissue-



Retinoic Acid was dosed at 50mg per Kilogram of diet.

Can you just drink whole milk and eat liver? Or do you need to supplement vitamin A for these effects(

 

[schultz]

That ratio is only meant for supplement users. Vitamin A itself helps utilize and offset copper. And i think other things do as well like vitamin C, taurine, zinc and even iron, which liver has all of them.

@schultz so in Rays other comment you posted, he said there were increasing benefits of vitamin A up to 100k IU a day?

Also has anyone on the forum experimented with these megadoses of vitamin A yet? It seems like even adding in 10,000 IU of retinyl palmitate causes some bone pain and hair loss…? So im not sure about safety. And some claim bone pain could be because the body is restructuring and regenerating bone? Not sure

Yah that was something Ray mentioned about a researcher. I don't know anything else about it though as I never looked into it, but I believe his name was Emmanuel Churaskin if I am remembering that correctly. I've never taken doses that high myself as I don't really trust supplements all that much, especially since there is a perfectly good source of vitamin A from beef liver. Although I do take it via milk I guess...

 

[schultz]

Yah that was something Ray mentioned about a researcher. I don't know anything else about it though as I never looked into it, but I believe his name was Emmanuel Churaskin if I am remembering that correctly. I've never taken doses that high myself as I don't really trust supplements all that much, especially since there is a perfectly good source of vitamin A from beef liver. Although I do take it via milk I guess...

I guess you can't edit anymore?

Just wanted to correct the spelling: it's Emanuel Cheraskin

 

[schultz]

This might be the research Ray was talking about...

The "ideal" daily vitamin A intake - PubMed

This approach suggests that the healthier the sample, the greater the daily vitamin A intake. Under the conditions of this experiment, approximately 33,000 I.U. of vitamin A may be designated as the "ideal" daily allowance. This is almost seven times the RDA of 5000 I.U. for the adult male and...

pubmed.ncbi.nlm.nih.gov

... But I can't find the full paper because there is no DOI

 

[xeliex]

What about taking vitamin A in the presence of fatty livers? Masterjohn seems to be saying to lose weight and ditch the fatty liver ASAP beforehand getting on high A doses.

128: Vitamin A and Fatty Liver

Watch now (5 min) | Chris Masterjohn Lite Episode 128

chrismasterjohnphd.substack.com

 

[joaquin]

What about the dude that says vitamin A is toxic and we need to deplete it and eat white bread and do everything possible to get it out our bodies? He did an experiment at home on some rats.

 

[Rinse & rePeat]

I've been thinking about Vitamin A recently and have noticed that I am a little cautious (sort of unconsciously I think) with how much vitamin A I am getting. You hear things and sometimes they just stick with you and you never give them another thought. I am thinking specifically about one of the podcasts where Ray says you can become a bit hypothyroid by eating two big servings of liver. Assuming the levels of vitamin A in beef liver don't vary tremendously, 2 servings is only like 40,000-80,000 IU's.

Ray said this in another podcast...

"The nutrition researcher dentist Emanuel Cheraskin did a survey where he found that health complaints and symptoms decreased in a nice linear relation to increasing vitamin A all the way to 100,000 units per day."

So to get to the point, as a 30 year old healthy male, is there anything wrong with eating 4oz of liver everyday? Are we too cautious on this forum with our Vitamin A intake?

Ray Peat says 4-ounces a week of liver enough, so anybody eating a big plate of liver once or more a week can’t blame Ray Peat for anything…


View: https://youtu.be/7mVXtXPW_D0?si=MQA1fzktgmVmZtQc

 

[Ideonaut]

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."

Having read Grant Genereux's free ebook Extinguishing The Fires of Hell My eBooks , there's no way I'd take "vitamin" A. Genereux says that it CAUSES obesity: it is stored in the liver, but once the liver is full, often around age 50 for men, the body develops extra fat as a place to store it. He proves with ample evidence in his book that it is a toxin, not a vitamin -- in no way essential to health. The experiments that allegedly showed that lack of A caused deficiency disease were faulty, just like the faulty experiments with fatty acids Ray talked about that falsely showed them to be "essential". I think Genereux is completely correct, and if Haidut actually read his book, he would think so, too.

 

[Dr. B]

Having read Grant Genereux's free ebook Extinguishing The Fires of Hell My eBooks , there's no way I'd take "vitamin" A. Genereux says that it CAUSES obesity: it is stored in the liver, but once the liver is full, often around age 50 for men, the body develops extra fat as a place to store it. He proves with ample evidence in his book that it is a toxin, not a vitamin -- in no way essential to health. The experiments that allegedly showed that lack of A caused deficiency disease were faulty, just like the faulty experiments with fatty acids Ray talked about that falsely showed them to be "essential". I think Genereux is completely correct, and if Haidut actually read his book, he would think so, too.

Do all fat soluble vitamins if taken in excess cause more bodyfat or only vitamin A? Also what about vitamin A in whole milk and liver

 

[Rinse & rePeat]

.

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."

I thought Ray Peat’s aversion to the carotene version of vitamin A was because it was aging to the skin, while the retinol form was just the opposite, as long as one kept liver to no more than three ounces a week. I hadn’t heard weight issues being a concern with either form. Is the retinyl palmate taken orally or internally?

 

[mosaic01]

... But I can't find the full paper because there is no DOI

https://price-pottenger.org/pdfs/C458_2.pdf

The 1056 dentists and their wifes had a mean intake of around 19k IU, which is a lot.

There's no clear relation here in the way Peat suggests. The healthiest dentists and their wifes probably just ingest more supplements.

Peat says: "The nutrition researcher dentist Emanuel Cheraskin did a survey where he found that health complaints and symptoms decreased in a nice linear relation to increasing vitamin A all the way to 100,000 units per day."

You could just as well say: "The nutrition researcher dentist Emanuel Cheraskin did a survey where he found that those with the worst health consumed 4 times the RDA of vitamin A, but those who just added a tiny bit more discovered the fountain of youth."

Also it's not all the way to 100,000 units, it's going from 19k -> 32k. The healthiest 379 of those 1056 still only had a mean intake around 1000 IU higher than the average. That's nothing.

This survey shows that even 50 years ago health-conscious people were already oversupplementing themselves to a slow death with ever-accumulating doses of vitamin A.

 

[Ras]

https://price-pottenger.org/pdfs/C458_2.pdf

Also it's not all the way to 100,000 units, it's going from 19k -> 32k.

Reported intake ranged from 1,000 to 98,209 IU.

 

[Daniel North]

Also has anyone on the forum experimented with these megadoses of vitamin A yet?

Don’t make yourself toxic in retinol on top of that, please. That’s what I did (took 50K IUs per day for 1 year) and it’s way way more difficult to fix than hypervitaminosis D.

 

[mosaic01]

Reported intake ranged from 1,000 to 98,209 IU.

Yes, but symptoms did not decrease in a linear fashion up to 100k. Look at the table, the participant with the highest intake was in the <10 group.

The symptoms decrease in a linear fashion between 19k and 32k.

 

[schultz]

Ray Peat says 4-ounces a week of liver enough, so anybody eating a big plate of liver once or more a week can’t blame Ray Peat for anything…


View: https://youtu.be/7mVXtXPW_D0?si=MQA1fzktgmVmZtQc

Yah, he did mention stuff like that, and the idea that you can become hypothyroid temporarily by eating a lot of liver over the coarse of two days or so (the purpose of this was to temporarily lower your thyroid before a doctors appointment where your thyroid was to be tested in order to make the doctor think you either have normal or lower than normal levels. Ray was talking about how doctors get spooked when they see that you are "hyperthyroid" and then want to patient to have their thyroid removed or some such thing).

However, he also mentioned things like the Cheraskin study that I mentioned and in these instances makes it seem like 20,000IU of vitamin A per day is no problem. A 4oz serving of beef liver is only around 20,000IU's from what I remember, although that's on average and I think the actual amount can vary tremendously from cow to cow. Anyway, I was just trying to square the two statements. I assume it's just context dependent like lots of things.

I was reading a study recently about essential fatty acid deficiency and they happened to check the rats livers once the animals were killed to see their vitamin A status. The study was about visual acuity and how EFAD may affect that, and since Vitamin A tends to be associated with vision they wanted to test that as well. The control rats had levels of vitamin A between 179 IU and 204 IU of vitamin A per gram of liver and the EFAD rats had level less that 1 IU per gram. One of the EFAD rats had a level of 5.9 IU per gram (an outlier apparently). All the rats were being given supplements of vitamin A at 100 IU's per day. At 50 IU's per day a rats blood levels of vitamin A are maxed out and they start storing extra in their liver, so these rats were all getting enough of the vitamin. Off the top of my head I can of two reasons why their vitamin A would be so low (and I'm sure most people here would come to the same conclusions)...

1) The EFAD rats were on a fat free diet and therefore not absorbing the vitamin A as efficiently
2) The EFAD rats had metabolisms that caused them to burn through much more vitamin A then they were getting

Both of these make sense to me. EFAD (as well as things like hyperthyroidism) does cause a massive increase in the need for certain micronutrients, and this is well documented. The authors of the paper I mentioned say this...

"It could be due either to reduced absorption through the intestine, or to an increased rate of metabolism of the vitamin."

The authors however seemed to think that the form of the vitamin they gave the rats would have resulted in adequate absorption. Also the fat soluble vitamins were given in a small amount of tributyrin (not sure the effect that would cause, but it is a lipid).

So metabolism can surely cause a massive variation in someones need (context). EFAD animals can have metabolic rates 30% higher than normal animals, which is an insane increase, so I found it quite fascinating that the rats in the study I mentioned had basically no vitamin A left in their livers. So if you want to become deficient in Vitamin A, maybe an EFA deficiency can make that happen quite quickly.

study link

https://price-pottenger.org/pdfs/C458_2.pdf

The 1056 dentists and their wifes had a mean intake of around 19k IU, which is a lot.

View attachment 58298

There's no clear relation here in the way Peat suggests. The healthiest dentists and their wifes probably just ingest more supplements.

Peat says: "The nutrition researcher dentist Emanuel Cheraskin did a survey where he found that health complaints and symptoms decreased in a nice linear relation to increasing vitamin A all the way to 100,000 units per day."

You could just as well say: "The nutrition researcher dentist Emanuel Cheraskin did a survey where he found that those with the worst health consumed 4 times the RDA of vitamin A, but those who just added a tiny bit more discovered the fountain of youth."

Also it's not all the way to 100,000 units, it's going from 19k -> 32k. The healthiest 379 of those 1056 still only had a mean intake around 1000 IU higher than the average. That's nothing.

This survey shows that even 50 years ago health-conscious people were already oversupplementing themselves to a slow death with ever-accumulating doses of vitamin A.

Thanks for this. Hard to gleen anything from such studies as there can be a lot of uncontrolled factors. For one thing, they mentioned that the people tended to get their vitamin A from supplements if they were in the higher groups and suggested that they would also be getting other micronutrients from such supplements, so it's difficult to know which micronutrients are responsible for any perceived improvement in health. But, the higher levels didn't seem to hurt them either. I'm not sure what to make of it. I guess the only thing I can do is try increasing it myself and see if I notice improvements.