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Anti-Peat Grant Genereux's Theory Of Vitamin A Toxicity

tim333

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Joined
Feb 27, 2020
Messages
249
Alcohol and Tobacco Smoke in Retinoid Metabolism and Signaling: Implications for Carcinogenesis

Abstract
Considerable evidence demonstrates that retinoids (retinol, retinoic acid, and retinyl ester, which are also the important metabolites from provitamin A carotenoids), may be effective in the prevention and treatment of a variety of human chronic diseases, including cancer. Substantial work has been done investigating the mechanisms by which tobacco smoke and excessive alcohol intake interfere with retinoid metabolism and signaling. Exposure to cigarette smoke subjects tissues to increased reactive oxygen species, which can induce cytochrome P450 enzymes and result in the degradation of retinoic acid, the bioactive form of vitamin A. Further, oxidative stress can result in cleavage of Β-carotene at positions other than the central double bond, decreasing the production of retinoic acid from this vitamin A precursor. This leads to aberrant retinoid signaling through nuclear retinoid receptors, while at the same time cigarette smoke also causes dysregulated signaling through the mitogen-activated protein kinase signaling pathways. Alcohol acts as a competitive inhibitor of vitamin A oxidation to retinoic acid involving alcohol dehydrogenases and acetaldehyde dehydrogenases, induces cytochrome P450 enzymes (particularly CYP2E1) that degrade retinol and retinoic acid, and alters retinoid homeostasis by increasing vitamin A mobilization from liver to extrahepatic tissues. Moreover, this alcohol-impaired retinoid homeostasis interferes with retinoic acid signaling by decreasing target gene expression and interfering with retinoic acid cross-talk with the mitogen-activated protein kinase pathways. The overall effect of both cigarette smoke and chronic, excessive alcohol intake is dysregulated apoptosis and uncontrolled cellular proliferation, which can act to promote the process of carcinogenesis. Nutritional interventions that serve to restore normal retinoid signaling and functioning may offer protection at the cellular level and represent a means to modify cancer risk in high-risk human populations.
 

Eberhardt

Member
Joined
Apr 28, 2019
Messages
431
Alcohol and Tobacco Smoke in Retinoid Metabolism and Signaling: Implications for Carcinogenesis

Abstract
Considerable evidence demonstrates that retinoids (retinol, retinoic acid, and retinyl ester, which are also the important metabolites from provitamin A carotenoids), may be effective in the prevention and treatment of a variety of human chronic diseases, including cancer. Substantial work has been done investigating the mechanisms by which tobacco smoke and excessive alcohol intake interfere with retinoid metabolism and signaling. Exposure to cigarette smoke subjects tissues to increased reactive oxygen species, which can induce cytochrome P450 enzymes and result in the degradation of retinoic acid, the bioactive form of vitamin A. Further, oxidative stress can result in cleavage of Β-carotene at positions other than the central double bond, decreasing the production of retinoic acid from this vitamin A precursor. This leads to aberrant retinoid signaling through nuclear retinoid receptors, while at the same time cigarette smoke also causes dysregulated signaling through the mitogen-activated protein kinase signaling pathways. Alcohol acts as a competitive inhibitor of vitamin A oxidation to retinoic acid involving alcohol dehydrogenases and acetaldehyde dehydrogenases, induces cytochrome P450 enzymes (particularly CYP2E1) that degrade retinol and retinoic acid, and alters retinoid homeostasis by increasing vitamin A mobilization from liver to extrahepatic tissues. Moreover, this alcohol-impaired retinoid homeostasis interferes with retinoic acid signaling by decreasing target gene expression and interfering with retinoic acid cross-talk with the mitogen-activated protein kinase pathways. The overall effect of both cigarette smoke and chronic, excessive alcohol intake is dysregulated apoptosis and uncontrolled cellular proliferation, which can act to promote the process of carcinogenesis. Nutritional interventions that serve to restore normal retinoid signaling and functioning may offer protection at the cellular level and represent a means to modify cancer risk in high-risk human populations.
How do they turn this into vitamin A helping?? All I see is they show that alcohol and sigarett smoke being harmfull also through oxidative stress?? And yes it competes with alcohol (retinol is actually a form or alcohol, thus retin-ol, being turned into retin-aldehyde.) for detox, and actually the body uses p450 to detox retinols. But I digress - how on all earth are then anything in that quote showing the usefullness of retinol?
 

Eberhardt

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Apr 28, 2019
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431
1.5 retinol molecule per single casein molecule
@tim333 any reason you conveniently skipped over this one to post a unrelated post about the damages of alcohol and sigarettes?
1.5retinol molecules per casein molecule..
 

tim333

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Feb 27, 2020
Messages
249
You simply asked for research that shows milk has A) retinol attached to its proteins. B)contains sufficient amounts to be of concern. I am not your daddy so I expect you to have enough agency to read the research posted. What is it to debate when posted research clearly states it.

Debating if retinol is needed, sure, but just google retinol in casein yourself, there is no scientific conflict about it, and you have not presented any arguments opposing the research, you just whine about having to make any effort. Sorry dude.
BS, I've never questioned whether retinoids can bind to dairy proteins. I'm saying the amounts are dietarily insignificant. I've already stated that I read both abstracts you posted. What you've posted doesn't prove dietarily significant amounts which is why I'm asking you to quote what you believe is evidence. You're making a claim without clear and logical reasoning, I'm simply asking for clarification...

1.5 retinol molecule per single casein molecule
How does the maximum achievable molecular ratios of casein and retinoids in a lab mixture relate to the amount in mcg of retinoids in the protein component of commercially available dairy?
 

tim333

Member
Joined
Feb 27, 2020
Messages
249
How do they turn this into vitamin A helping?? All I see is they show that alcohol and sigarett smoke being harmfull also through oxidative stress?? And yes it competes with alcohol (retinol is actually a form or alcohol, thus retin-ol, being turned into retin-aldehyde.) for detox, and actually the body uses p450 to detox retinols. But I digress - how on all earth are then anything in that quote showing the usefullness of retinol?
Cigarettes and alcohol both reduce levels of retinoic acid which helps explain why both can give relief from the symptoms of Hypervitaminosis A. I quoted and highlighted the relevant parts...
 

Daniil

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Feb 13, 2021
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713
Location
Moscow
1.5 retinol molecule per single casein molecule
Thanks! So, per 100 grams of skimmed cottage cheese with a protein content of 20 grams and the casein content is 70%, there will be ~200 mcg of retinol bound to casein. Quite a lot.

Btw, VA also bind whey protein:

 

Daniil

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Feb 13, 2021
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For skimmed milk with a protein content of 3 grams, this will be 30 mcg per 100 g respectively (this is not counting what is associated with whey protein and not counting retinoic acid)
 

Belsazar

Member
Joined
May 16, 2016
Messages
108
Hey guys,

anyone measuring their Vitamin A Serum levels? And want to share their numbers? What is your rate of depletion?

My level was at 0,6mg/l at 7 and 20 week mark. Now after 45 weeks or 11 months it decreased only by 0,04mg/l. My take is that my liver was overloaded by previous supplementation, retinoid therapy, high intake from diet (liver, butter, carrots, etc) and after some months of constant level in serum (but decreasing in the liver), it finally goes down. It is still surprising to me that it has not decreased more. My target would be something around 0,3mg/l.

My diet is was quite strict for 5 months (no liver, hardly milk products (sometimes 0,1% fat greek yoghurt). At 20 week mark I measured Beta carotin level, which was way below the lower limit of the reference range, so i decided to be more free in eating some veggies again.

The most drastic change is clearing up of my skin, which I still consider a miracle after having suffered of acne for more than a decade. It could also correlate with milk intake, who knows. I am a bit concerned about calcium intake, but hopefully bone health will improve the more Vitamin A goes down. I want to discuss the connection of Vitamin A and bone health in a seperate thread, I came across a pathway never discussed in this forum - it connects retinoids with bone metabolism, cancer especially breast cancer, immunity and inflammation, hair growth and more.
 

Belsazar

Member
Joined
May 16, 2016
Messages
108
Just wanted to report. Still experiencing strong bouts of vitamin A toxicity momentarily lately.
Mostly neurological problems like dizziness, really weird vision problems (neurological fall out) yellow skin intensified, intracranial pressure and much increased blood pressure.

Needed my parents to come get me home from work because I was unable to drive my car this morning. Will go to the clinic today.. I am scared that I might not fix this problem alone..
I am quite sure some people here including me warned you several times of the danger of supplements especially fat solubles. Please get blood work done, check your liver - yellow skin could be an indication already. Good luck.
 

Apollo

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Joined
Apr 15, 2015
Messages
618
I wanted to throw a couple comments in here from the last 30 pages or so. This comment above was interesting. I have noticed that since I went low vitamin A a few years ago, I have had a lot more hair loss then before that period. I attribute this to increased bone density and mass. My teeth also became much stronger and whiter over these years. I imagine my skull has also had mass added to it, and this could account for the hair loss. Although others will probably say lack of metabolism or something from low VA. I don't really care...the depression, chaos, and awful feeling I get from Vitamin A is a fine trade for some hair.
Did you consume lots of red meat since you went low vitamin A ?
 

Eberhardt

Member
Joined
Apr 28, 2019
Messages
431
Thanks! So, per 100 grams of skimmed cottage cheese with a protein content of 20 grams and the casein content is 70%, there will be ~200 mcg of retinol bound to casein. Quite a lot.

Btw, VA also bind whey protein:

:). and about whey. yeah I know - it just didnt say in the one I posted. Its only that casein are the dominant protein in milk but you are right and yes that makes whey problemtic from that perspective as well.
Btw. I think you mean bind TO whey protein :). - not meaning to be picky just clarifying in case people dont read the abstract :)
 

tim333

Member
Joined
Feb 27, 2020
Messages
249
Thanks! So, per 100 grams of skimmed cottage cheese with a protein content of 20 grams and the casein content is 70%, there will be ~200 mcg of retinol bound to casein. Quite a lot.

Btw, VA also bind whey protein:

LOL, just stop.
 

tim333

Member
Joined
Feb 27, 2020
Messages
249
Hey guys,

anyone measuring their Vitamin A Serum levels? And want to share their numbers? What is your rate of depletion?

My level was at 0,6mg/l at 7 and 20 week mark. Now after 45 weeks or 11 months it decreased only by 0,04mg/l. My take is that my liver was overloaded by previous supplementation, retinoid therapy, high intake from diet (liver, butter, carrots, etc) and after some months of constant level in serum (but decreasing in the liver), it finally goes down. It is still surprising to me that it has not decreased more. My target would be something around 0,3mg/l.

My diet is was quite strict for 5 months (no liver, hardly milk products (sometimes 0,1% fat greek yoghurt). At 20 week mark I measured Beta carotin level, which was way below the lower limit of the reference range, so i decided to be more free in eating some veggies again.

The most drastic change is clearing up of my skin, which I still consider a miracle after having suffered of acne for more than a decade. It could also correlate with milk intake, who knows. I am a bit concerned about calcium intake, but hopefully bone health will improve the more Vitamin A goes down. I want to discuss the connection of Vitamin A and bone health in a seperate thread, I came across a pathway never discussed in this forum - it connects retinoids with bone metabolism, cancer especially breast cancer, immunity and inflammation, hair growth and more.
Congrats on improving your skin.

My results:

Serum retinol @ 12 months: 51 mcg/dL

Serum retinol @ 18 months: 51 mcg/dL

I've been following a low vitamin A diet for over 2.5 years now. Seb derm improved quickly but took over 2 years to be almost nonexistent.

If your serum retinol is now 56 mcg/dL after 11 months then you may have another 2 or 3 years ahead of you to get down to 30 mcg/dL. If you're consuming high carotenoid vegetables that may slow down or stop depletion.
 

youngsinatra

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Joined
Feb 3, 2020
Messages
935
Age
23
Location
Frankfurt, Germany
I am quite sure some people here including me warned you several times of the danger of supplements especially fat solubles. Please get blood work done, check your liver - yellow skin could be an indication already. Good luck.
I don’t want to blame anyone but myself, but I got inspired by some prominent posts here about the usage of retinol for TLR4 antagonism, leukemia treatment and so on.

I’ll get blood work done on thursday. I am still signed off sick by my doctor for this week.
It sucks that there seems to be no quick solution to this problem.

Was tempted to go straight to the hospital but you typically wait for 8-10h there, if it‘s not an emergency. However if I get extreme dizzy and get visual problems again, I‘ll definitely call the ambulance.

Btw, this is how my hands look like at the moment.
 

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ursidae

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Feb 12, 2020
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I don’t want to blame anyone but myself, but I got inspired by some prominent posts here about the usage of retinol for TLR4 antagonism, leukemia treatment and so on.

I’ll get blood work done on thursday. I am still signed off sick by my doctor for this week.
It sucks that there seems to be no quick solution to this problem.

Was tempted to go straight to the hospital but you typically wait for 8-10h there, if it‘s not an emergency. However if I get extreme dizzy and get visual problems again, I‘ll definitely call the ambulance.

Btw, this is how my hands look like at the moment.

This looks like Raynaud’s rather than carotenemia?
 

youngsinatra

Member
Joined
Feb 3, 2020
Messages
935
Age
23
Location
Frankfurt, Germany
This looks like Raynaud’s rather than carotenemia?
Well the coloration gets way worse if I consume even just a little bit of carotene, then it actually gets severly orange. But I stopped all dietary vitamin A around 5-6 weeks ago. I have a friend of mine who overdid retinol too and did not really eat vegetables or dietary carotene and he has similar manifestation. The sad thing is he already got liver tested and has severely elevated enzymes - the doc actually thought he was abusing alcohol and drugs like crazy - but he does not consume any of those..

If I understand correctly Raynaud‘s is more a lack lf blood reaching your fingers, which causes them to become very cold and so on.
 
Last edited:

PaRa

Member
Joined
Nov 18, 2019
Messages
316
I don’t want to blame anyone but myself, but I got inspired by some prominent posts here about the usage of retinol for TLR4 antagonism, leukemia treatment and so on.

I’ll get blood work done on thursday. I am still signed off sick by my doctor for this week.
It sucks that there seems to be no quick solution to this problem.

Was tempted to go straight to the hospital but you typically wait for 8-10h there, if it‘s not an emergency. However if I get extreme dizzy and get visual problems again, I‘ll definitely call the ambulance.

Btw, this is how my hands look like at the moment.
I get the exact same hands when i do a high dairy/retinol diet
 

Belsazar

Member
Joined
May 16, 2016
Messages
108
Congrats on improving your skin.

My results:

Serum retinol @ 12 months: 51 mcg/dL

Serum retinol @ 18 months: 51 mcg/dL

I've been following a low vitamin A diet for over 2.5 years now. Seb derm improved quickly but took over 2 years to be almost nonexistent.

If your serum retinol is now 56 mcg/dL after 11 months then you may have another 2 or 3 years ahead of you to get down to 30 mcg/dL. If you're consuming high carotenoid vegetables that may slow down or stop depletion.
It seems to be a long journey. Any idea why your level stayed basically the same? How is your diet? For me the diet got really boring, so I had to put in more variation again. Do you take caffeine, taurine, aspirin or anything?


I don’t want to blame anyone but myself, but I got inspired by some prominent posts here about the usage of retinol for TLR4 antagonism, leukemia treatment and so on.

I’ll get blood work done on thursday. I am still signed off sick by my doctor for this week.
It sucks that there seems to be no quick solution to this problem.

Was tempted to go straight to the hospital but you typically wait for 8-10h there, if it‘s not an emergency. However if I get extreme dizzy and get visual problems again, I‘ll definitely call the ambulance.

Btw, this is how my hands look like at the moment.
Yes, I know what you are talking about, for me it was the acne related postings and publications. At some point it was pure ignorance from my side: completely ignoring the massive data that is out there that speaks against Vitamin A, which I read way before I have read Grant`s books, ignoring all the negative reviews out there and completely ignoring the side effects. Anyway it is surprising to me how people can even tolerate such crazy high amounts without pain.

The main problem imho is the concept of "lacking something" - a vitamin, a mineral or even think about materialist things. The concept of having too much of something at a given timepoint or an overload is rarely discussed.
 
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