Retinoic Acid (Vitamin A Metabolite) reverses Fatty Liver by targeting White Adipose Tissue

[InChristAlone]

Here's a review of the reports of depression and suicide that come from isotretinoin-

Isotretinoin, depression and suicide: a review of the evidence

There is currently considerable controversy regarding a proposed causal relationship between the use of isotretinoin and depression and suicide. A search was made of the MEDLINE, EMBASE and PsychINFO databases using the search terms ‘isotretinoin’, ...

www.ncbi.nlm.nih.gov

That's not many total cases (although the suicides are tragic), and the article goes onto state that over 8 Million patients had used it by 1998.

However.... was it isotretonin that caused these?



So, this could have been a serious reaction between drugs, not the direct action of isotretonin itself. LSD and cannabis are well known to cause mood and behavior changes.

I appreciate your concern, but I think you are overstating risk (especially since I am using retinol, and not isotretonin or tretinoin). Of course, if anyone is considering any course of action, it's always best to do a well informed analysis of potential risks and benefits, ideally with the help of a well trained medical professional.

Welp if you don't think it applies to this discussion because you aren't using it and that some cases might be a drug interaction then you probably won't believe this paper either about men developing breasts after isotretinoin: https://sci-hub.hkvisa.net/10.3109/15569527.2012.705406

"There are few studies that showed the effect of isotretinoin on androgen metabolism. In a study after 3 months of treatment with isotretinoin, both testosterone and LH levels were decreased (3). In another study, testosterone and androstenedion are found to be lower after 12 weeks of treatment with isotretinoin."

I mean I could go on and on. I will always advise caution with any retinol/retinoid drug or supplement and even with liver. For every study showing some small benefit there are 10 showing harm. I don't think there are any other supplements or drugs that have such a long history of harm when overdoing it. Accutane may change a teenager's life for the better if they have their severe acne cured, but they are routinely monitored and told not to get pregnant because it is toxic, it is working as a chemical agent. I classify that similar to using chemo for cancer. Sure it may result in remission, but at what long term cost?

 

[tankasnowgod]

Welp if you don't think it applies to this discussion because you aren't using it and that some cases might be a drug interaction then you probably won't believe this paper either about men developing breasts after isotretinoin: Sci-Hub | Gynecomastia: a rare complication of isoretinoin? | 10.3109/15569527.2012.705406

"There are few studies that showed the effect of isotretinoin on androgen metabolism. In a study after 3 months of treatment with isotretinoin, both testosterone and LH levels were decreased (3). In another study, testosterone and androstenedion are found to be lower after 12 weeks of treatment with isotretinoin."

Well, again, it doesn't apply, because I am not taking Isotretonin. It was also just a single case study of a 20 year old with mid range testosterone. What about the studies posted to this forum that show Testosterone increases in a dose dependent manner when vitamin A is taken?

I mean I could go on and on.

Lol. You already have!

I will always advise caution with any retinol/retinoid drug or supplement and even with liver. For every study showing some small benefit there are 10 showing harm.

So, again, read the studies and see which ones were better conducted and/or more applicable to your situation, and make your own decisions. I think most people on this forum are good at such a thing. I enjoy the freedom to make decisions in this capacity, and I take full responsibility at the same time.

I don't think there are any other supplements or drugs that have such a long history of harm when overdoing it.

Not sure if you are referring to Isotretonin, or Vitamin A here. I think the case studies you have shown for Hypervitaminosis A have either been extreme in nature, or poorly conducted. And none seem to be applicable to how I plan on using it (and have used it successfully in the past).

Accutane may change a teenager's life for the better if they have their severe acne cured, but they are routinely monitored and told not to get pregnant because it is toxic, it is working as a chemical agent. I classify that similar to using chemo for cancer. Sure it may result in remission, but at what long term cost?

I agree with this, I don't think Accutane is the best choice. I think a lot of people who had success with Grant Generaux's protocol had a history with Accutane, and maybe depleting all the retinoids in all their forms is a good plan, as an intervention diet (some of the studies he mentioned back up this idea).

 

[pastanagueta]

Real Vitamin A? Yes. I will say from personal experience, I have taken up to 100,000 iu of retinol a day for several months, and never noticed any side effects. Health was quite positive at the time.

Were you taking the vitamin A as a supplement, and if so, would you mind sharing which one? I’m looking for a good quality one and it’s not easy to find.

Thanks

 

[tankasnowgod]

Were you taking the vitamin A as a supplement, and if so, would you mind sharing which one? I’m looking for a good quality one and it’s not easy to find.

Thanks

Currently, I am using the NOW brand Vitamin A, which has both A from fish liver and Retinyl Palmitate. I don't have any issue with Palmitate or Acetate. I have also had success with the Carlson brand in the past. I think it's important for it to be in oil (olive oil likely being the best, although I would be fine with sunflower, too). I have used Retinyl Palmitate in powder and "dry" versions before (including thorne, when they made it), and it didn't seem to have the effect that A in oil did. I have some of Health Natura's A in MCT oil, and that seems okay, too (though I think something with longer chain fats is better, as per Peat's suggesting in this regard). I am using the rest of that bottle topically now.

 

[username]

I eat about 25 grams of beef liver per day. Any reason to dial it back?

 

[pastanagueta]

Currently, I am using the NOW brand Vitamin A, which has both A from fish liver and Retinyl Palmitate. I don't have any issue with Palmitate or Acetate. I have also had success with the Carlson brand in the past. I think it's important for it to be in oil (olive oil likely being the best, although I would be fine with sunflower, too). I have used Retinyl Palmitate in powder and "dry" versions before (including thorne, when they made it), and it didn't seem to have the effect that A in oil did. I have some of Health Natura's A in MCT oil, and that seems okay, too (though I think something with longer chain fats is better, as per Peat's suggesting in this regard). I am using the rest of that bottle topically now

Very helpful thanks

 

[Amazoniac]

There are a lot of conversions you have to do, first, calculating the mg/kg bodyweight, then Human Equivalent dose, and then figuring out the A to Retinoic Acid conversion.

The mice on the HFD-RA diet ate about 3 grams of food a day, which means they took in about 0.15 mg of Retinoic Acid a Day. Their weight when they started getting the RA was about 42 grams, so about 3.57mg/kg of bodyweight a day. You then divide that by 12.3 to get the Human Equivalent dose, so that would be 0.29mg/kg. So, for a 100 kg man, that would be about 29 mg of Retinoic Acid to replicate the study. This would likely put you in the high area of 200,000-300,000 iu of Vitamin A a day, which is quite a bit. Although some of the doses used for Acne have gone up to 500,000 iu a day for a few months, so these doses have been tried before in humans.

However, this part of the study was only 8 weeks, and the mice dropped about 25% of their weight. Can a 300 pound man drop to 225 in 2 months? That's a tall order, I don't know if that happens outside of "The Biggest Loser." However, big drops in weight (say, 20 pounds in a week or something like 30 over a month) can happen, usually from excess water weight, but that pace usually doesn't last. But, if spread out over 6-8 months, I think this sort of weight loss is very possible. There are other studies that suggest RA leads to a dose dependent drop in weight (like this one- Remodeling of White Adipose Tissue after Retinoic Acid Administration in Mice), so a more reasonable (but still high) dose of something like 50,000-100,000 iu might work over a longer time period. There are other studies on the forum showing that doses in this range (and even at 25,000 iu) can have positive effects on the things I mentioned in the first post (like on cortisol, TSH and T3).

Or, maybe someone with a lot of fat to lose wants to try the HED does of tretinoin. The study used Retinoic Acid orally, but maybe it would work topically applied to fat deposits, or if if was injected directly into fatty areas.

I thought that once you arrived on the leukemic dose of poisonoic acid after extrapolation, it would shy you away from conceiving replicating it with poisonol.

If a supraphysiological dose is consumed, it tends to be mishandled, in excess is disruptive to cells. The fraction that's not absorbed can be unexpectedly high and may not be inert.

Those models can differ from real life conditions. In liver disease, subjects can have the enzymes that metabolize poisonal to poisonoic acid inhibited, while storage, mobilization and conjugation (for direct elimination) may be compromised. On a chronic basis, it would be a complicated situation to put yourself in.

Topical conversion is inefficient as well, doesn't seem promising.
- Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes

I wouldn't gamble with extreme doses, it's not worth the risk.

I also discussed the dosing earlier in the thread. And "extreme" is relative. The RDA for Vitamin A used to be 25,000 iu a day, and Peat himself has discussed taking doses of up to 100,000 iu.

Regarding previous dietary recommendations and that of different countries, I couldn't find anything close to what you and Jorge mention. Do you know when and where? It would be an outlier:

- The Vitamins: Fundamental Aspects in Nutrition and Health (978-0-12-802965-7)

Spoiler

- Current micronutrient recommendations in Europe: towards understanding their differences and similarities

If I remember it right, Raj's justification for his stunt was intense metabolism and light exposure. A person that claims to be using up poison A at such rate has to be worried about what's happening to the reserves of actual nutrients that are more labile, the ongoing purification of the liver wouldn't be a priority.

Someone like Abram Hoffer could get away with an excess, but he was stuffing himself with various other "nutrients".

Well, again, it doesn't apply, because I am not taking Isotretonin.

If you think that poisonol is a feasible molecule to derive pharmacological amounts of poisonoic acid from, why isotretinoin has no relevance? It's partially metabolized to poisonoic acid and it's also a metabolite of poisonol when the latter is consumed in large doses.

 

[username]

@Amazoniac Are you calling retinol poisonol? Why?

I may be wrong, but I feel like I've read some other posts by you that were anti-meat. Am I remembering correctly?

 

[Tim Lundeen]

Supplemental retinoic acid is HIGHLY toxic. It doubtless works by poisoning cells, giving the illusion of better health through the magic of surrogate markers. Our cells do make it, but in a highly controlled manner and in extremely low concentrations.

 

[Tansia]

I have been using this RX for well over a few years now with very good results. It's one of the very few, cost effective products that actually work and have a lot of science backing it. Good diet, on top of this, and using a very good natural sun block to protect skin from long periods of sun exposure (I get about 20-30 min of it without sunblock every morning, but other than that, I think too much of a good thing (sun) on skin can age it fast) are what have worked for me. People constantly comment on my skin and how I look. I had some eye lines starting to creep up with age and they're not even notable anymore. I also like to rub cold pressed organic olive oil on my skin, which I am a big believer in. Gelatin and liver also helps.

Could you share the product you used? Is it OTC or prescription only?

 

[tankasnowgod]

Supplemental retinoic acid is HIGHLY toxic. It doubtless works by poisoning cells, giving the illusion of better health through the magic of surrogate markers. Our cells do make it, but in a highly controlled manner and in extremely low concentrations.

Then how do you explain the improved fatty liver of the mice? That is not a "surrogate marker." If it were truly as toxic as you are suggesting, you would see worse liver function, not improved liver function.

Also, do you really think higher oxygen consumption, higher CO2 production, and higher levels of uncoupling protein are just illusory markers?

 

[FitnessMike]

bump

 

[Dr. B]

Then how do you explain the improved fatty liver of the mice? That is not a "surrogate marker." If it were truly as toxic as you are suggesting, you would see worse liver function, not improved liver function.

Also, do you really think higher oxygen consumption, higher CO2 production, and higher levels of uncoupling protein are just illusory markers?

the stuff youre saying on vitamin A is all true for a fact, i dont know about supplemental A. but I know its true because of the massive benefits I got from dropping oral vitamin D3 usage entirely. prior to that I was using 10000 IU vitamin D3 and getting 5000 IU of A daily from whole milk and liver.
im not sure if I should supplement A due to the risks involved... but dropping D3 supplements seems to have improved everything even within just a week.
is it worth supplementing A if youre getting 5000Iu from the diet, and not getting much sunlight and not using vitamin d3?
does grass fed milk contain significant vitamin D3, k2, E, omega 3 or omega 6?