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

[tankasnowgod]

A really interesting study. In the intro, the researchers state that Retinoic Acid has shown promise in improving fatty liver, but weren't aware of the mechanism. They conducted the following study, and found that Retinoic Acid did indeed reduce both the size and fat deposits in the liver, but did not do so by acting on the liver directly. Instead, it's therapeutic effects are thought to come from acting on the fat tissue, by reducing weight of WAT, and by preventing adipogenesis.

There were three groups of mice, the control group, the High Fat Diet group, and High Fat Diet plus Retinoic Acid group. What's even more impressive about this study to me is that both HFD and HFD+RA were fed the same diet for 12 weeks. At that time, they were divided, and one group got RA (at 50 mg RA per 1 kg diet), while the other didn't. Retinoic Acid reversed the weight gain and fatty liver of the treated mice, getting their weight down similar to controls, even while still eating the same High Fat Diet.

As if that wasn't enough, the HFD+RA group also saw increased oxygen consumption, CO2 production, and energy expenditure. Since there are threads on the forum that show that Vitamin A and/or Retinoic Acid also lowers (or antagonizes) estrogen, cortisol, and TSH, while raising levels of T3 and Testosterone, it seems like Vitamin A is a great vitamin for anyone looking to lose weight or increase metabolism.

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

Results demonstrated that RA treatment for 8 weeks decreased the body weight of HFD-fed mice (Figure 1a) and no significant change in food intake was observed (Figure 1b). Compared with mice in the HFD group, those in HFD-RA group showed substantially decreased TC levels in the plasma (Figure C). Moreover, in glucose tolerance test (GTT) and insulin tolerance test (ITT), mice in the HFD-RA group showed improved glucose tolerance and insulin sensitivity (Figure 1d,F). Also, fasting glucose and HOMA-IR were significantly reduced in the HFD-RA group (Figure 1e,G). These results showed that RA treatment improved the metabolic function.

We tested the effect of RA on animal energy expenditure using a laboratory animal monitoring system (CLAMS). The metabolic analysis showed increased O2 consumption, CO2 production, and respiratory exchange ratio (RER) in the HFD-RA group compared with the HFD group during dark period (Figure 2a-C). Importantly, the protective effect of RA was associated with a significant increase in energy expenditure as evaluated by the oxygen consumption test. Further, the values of respiratory metabolism parameters were higher in the HFD-RA group than in the HFD group mainly in the dark period. These data demonstrated that the increased energy expenditure induced by RA could be the primary contributor for the prevention of obesity in NAFLD mice.

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.

 

[Grapelander]

Topical product Retin-A used to get a lot of attention. It is useful for acne and wrinkles. My guess is that it is undermarketed in favor of novel treatment$.
What's so special about Retin-A?
Retin-A, or tretinoin, is a form of vitamin A that was developed at the University of Pennsylvania in the 1960s. One of the most successful patents of all time, it revolutionized topical skin care and still has great utility today.

The most superficial cells – the keratinocytes of the epidermis – tend to become more adhesive and hang around longer. This leaves the skin looking dryer and rougher. The epidermal cells at the base also do not replicate as quickly, so the lifespan of these cells in the outer layer is much longer – and it shows. The pigmentation can become irregular and mottled because of this.

Retin-A is a topical medicine available by prescription only that is applied sparingly to the facial skin, sparing the eyelids and the corners of the nose and lips. It works at the cellular level and takes several months to see the full effect. In many ways, Retin-A can be thought of as reversing the outwards signs of aging on the skin.

The earliest effect of Retin-A is that the outer layer of keratinocytes start shedding off, leaving the skin fresher, smoother and more evenly pigmented. The next effect seen is that the epidermal cells start to replicate faster causing the skin to look and feel softer, more robust and healthier. Finally, the collagen bundles in the dermis will thicken and organize, causing the appearance of fine lines and wrinkles to lessen with time.

Retin-A improves the cosmetic appearance of the skin, but it also helps treat some functional problems of the skin such as acne and precancerous conditions, such as actinic keratoses.

 

[BlahtyBlah]

Topical product Retin-A used to get a lot of attention. It is useful for acne and wrinkles. My guess is that it is undermarketed in favor of novel treatment$.
What's so special about Retin-A?
Retin-A, or tretinoin, is a form of vitamin A that was developed at the University of Pennsylvania in the 1960s. One of the most successful patents of all time, it revolutionized topical skin care and still has great utility today.

The most superficial cells – the keratinocytes of the epidermis – tend to become more adhesive and hang around longer. This leaves the skin looking dryer and rougher. The epidermal cells at the base also do not replicate as quickly, so the lifespan of these cells in the outer layer is much longer – and it shows. The pigmentation can become irregular and mottled because of this.

Retin-A is a topical medicine available by prescription only that is applied sparingly to the facial skin, sparing the eyelids and the corners of the nose and lips. It works at the cellular level and takes several months to see the full effect. In many ways, Retin-A can be thought of as reversing the outwards signs of aging on the skin.

The earliest effect of Retin-A is that the outer layer of keratinocytes start shedding off, leaving the skin fresher, smoother and more evenly pigmented. The next effect seen is that the epidermal cells start to replicate faster causing the skin to look and feel softer, more robust and healthier. Finally, the collagen bundles in the dermis will thicken and organize, causing the appearance of fine lines and wrinkles to lessen with time.

Retin-A improves the cosmetic appearance of the skin, but it also helps treat some functional problems of the skin such as acne and precancerous conditions, such as actinic keratoses.

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.

 

[tankasnowgod]

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.

Did you notice anything mentioned in the study? Like fat loss, improved liver function, better metabolism?

I've seen some reports of people using tretinoin topically talking about localized fat loss in the area applied.

 

[Elie]

50 mg vitamin A is equivalent to 167,000 IU, isn't it? For 12 weeks? wow, seems a lot.

 

[Mauritio]

50 mg vitamin A is equivalent to 167,000 IU, isn't it? For 12 weeks? wow, seems a lot.

50mg/kilogram of food. Mice eat around 250-350g per day. So that's about 15-20mg of retinoic acid per day.

Plus vitamin A has to be converted to retinoic acid . So you'd probably have to take a much higher dosage of vitamin A to get the same effects.

"The currently accepted model postulates that RA is produced in two sequential oxidative steps: first, retinol is oxidized reversibly to retinaldehyde, and then retinaldehyde is oxidized irreversibly to RA, which is inactivated by conversion to hydroxylated derivatives. "
(RETINOIC ACID SYNTHESIS AND DEGRADATION)

 

[InChristAlone]

Retinoic acid is basically killing off the top layers of your skin revealing newer skin underneath... but is that really the best thing to be doing to your body?

Here is a paper summarizing all the studies showing neurotoxicity to the brain from retinol.

"The utilization of vitamin A or retinoids in the treatment of some types of cancer and dermatological disturbances is based on the fact that such molecules may trigger cell death or slow cell cycle progression, leading to decreased rates of tumor growth. However, it would be catastrophic if an individual with history of neurodegenerative disease in the family exceeds vitamin A intake through either supplement use or clinical administration, for example."

 

[BlahtyBlah]

Did you notice anything mentioned in the study? Like fat loss, improved liver function, better metabolism?

I've seen some reports of people using tretinoin topically talking about localized fat loss in the area applied.

I was doing a cut while taking it and now have maintained that weight since, so it's hard, if not impossible, for me to say whether it had any positive effect insofar as fat loss is concerned. I haven't tried applying it to any body parts with fat either.

 

[BlahtyBlah]

Retinoic acid is basically killing off the top layers of your skin revealing newer skin underneath... but is that really the best thing to be doing to your body?

Here is a paper summarizing all the studies showing neurotoxicity to the brain from retinol.

"The utilization of vitamin A or retinoids in the treatment of some types of cancer and dermatological disturbances is based on the fact that such molecules may trigger cell death or slow cell cycle progression, leading to decreased rates of tumor growth. However, it would be catastrophic if an individual with history of neurodegenerative disease in the family exceeds vitamin A intake through either supplement use or clinical administration, for example."

This is an article detailing possible mechanistic theories and, as far as I can read, mainly cites small experiments done on rats, not human, or solely in-vitro experiments/cultured cells. I am highly suspect of relying on any evidence that comes just from animal/rat studies and not humans. It isn't a randomized, double-blind, placebo-controlled trial done on humans taking x amounts of vitamin A. And the problem with articles detailing mechanistic theories is that they often can be wrong because of undiscovered biochemical pathways, or other mechanistic theories not accounted for. For example, we see old early 2000's articles detailing mechanistic theories as to why insulin causes obesity, but now we now know that insulin in of itself doesn't cause obesity, but type 2 diabetes/ insulin resistance is usually result of obesity, etc. But that said, in the article, even some of those experiments in cell cultures had mixed results, they admit.

 

[tankasnowgod]

50 mg vitamin A is equivalent to 167,000 IU, isn't it? For 12 weeks? wow, seems a lot.

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.

 

[InChristAlone]

Retinoic acid adverse effects:

>10%​

Headache (86%)
Fever (83%)
Bone pain (77%)
Dry mucous membranes (77%)
Malaise (67%)
URI (63%)
Shivering (60%)
Dyspnea (60%)
Hemorrhage (60%)
Elevated liver function tests (50-60%)
Hyperlipidemia (60%)
Infections (58%)
Nausea and vomiting (57%)
Rash (54%)
Peripheral edema (52%)
Leukocytosis (40%)
Pain (37%)
Abdominal pain (31%)
DIC (26%)
Respiratory insufficiency (26%)
Mucositis (26%)
GI disorder (26%)
Retinoic acid-APL syndrome (25%)
Ear ache (23%)
Diarrhea (23%)
Pleural effusion (20%)
Dizziness (20%)
Pruritus (20%)
Sweating (20%)
Anxiety (17%)
Paresthesia (17%)
Constipation (17%)
Vision changes (17%)
Dyspepsia (14%)
Rales (14%)
Depression (14%)
Insomnia (14%)
Alopecia (14%)
Skin changes (14%)
Confusion (11%)
Abdominal distention (11%)
Renal insufficiency (11%)

1-10% (selected)​

Cardiac failure (6%)
Pallor (6%)
Cardiac arrest (3%)
Cardiomyopathy (3%)
Myocarditis (3%)
Stroke (3%)
Heart murmur (3%)
Hemmorrhage (9%)
Facial edema (6%)
Intracranial hypertension (9%)
Hypotaxia (3%)
Seizure (3%)
Somnolence (3%)
Facial paralysis (3%)
Spinal cord disorder (3%)
Light reflex absent (3%)
Ulcer (3%)
Cellulitis (8%)
Hepatosplenomegaly (9%)
Dysuria (9%)
Enlarged prostate (3%)
Ascites (3%)
Hepatitis (3%)
Tremor (3%)
Bone inflammation (3%)
Hearing loss (6%)

<1%​

Arterial thrombosis
Hypercalcemia
Myositis
Pancreatitis
Thrombocytosis
Venous thrombosis
Irreversible hearing loss
Genital ulceration


There is also something called retinoic acid syndrome in patients being treated with retinoic acid for leukemia, they have fever, shortness of breath, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural or pericardial effusions, edema, and hepatic, renal, and/or multiorgan failure; this syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension.

Kinda sounds like the symptoms of covid. I do wonder how many severe covid patients have ever used retinoids (we have many on this forum for example with severe covid who have likely used retinol). And not to get too conspiracy theory on everyone but Bill Gates' favorite vitamin is vitamin A.

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.

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 a high dose of tretinoin. The study used it orally, but maybe it would work topically applied to fat deposits, or if if was injected directly into fatty areas.

Did the paper say anything about the rats not wanting to eat, because that could have been why they lost weight. Hypervitaminosis A can cause anorexia. Not exactly the way to lose weight.
Here is a paper on isotretinoin (which is the isomer of retinoic acid) causing depression:

"Bifulco reported a 52 year old woman who took daily high doses of vitamin A. She developed insomnia, loss of weight and appetite. She became “completely disinterested in her surroundings and was found to brood all the time.” One week after discontinuation of vitamin A her symptoms resolved."

"A third patient was reported to have several months of symptoms of depressed mood, irritability, aggression, agitation, decreased sleep, decreased appetite, reduced concentration, anhedonia, and early morning awakening that began during a course of isotretinoin therapy. These symptoms resulted in the breakup of her marriage."

Are you seriously considering using retinoids to lose some weight?

 

[tankasnowgod]

Retinoic acid adverse effects:

>10%​

Headache (86%)
Fever (83%)
Bone pain (77%)
Dry mucous membranes (77%)
Malaise (67%)
URI (63%)
Shivering (60%)
Dyspnea (60%)
Hemorrhage (60%)
Elevated liver function tests (50-60%)
Hyperlipidemia (60%)
Infections (58%)
Nausea and vomiting (57%)
Rash (54%)
Peripheral edema (52%)
Leukocytosis (40%)
Pain (37%)
Abdominal pain (31%)
DIC (26%)
Respiratory insufficiency (26%)
Mucositis (26%)
GI disorder (26%)
Retinoic acid-APL syndrome (25%)
Ear ache (23%)
Diarrhea (23%)
Pleural effusion (20%)
Dizziness (20%)
Pruritus (20%)
Sweating (20%)
Anxiety (17%)
Paresthesia (17%)
Constipation (17%)
Vision changes (17%)
Dyspepsia (14%)
Rales (14%)
Depression (14%)
Insomnia (14%)
Alopecia (14%)
Skin changes (14%)
Confusion (11%)
Abdominal distention (11%)
Renal insufficiency (11%)

1-10% (selected)​

Cardiac failure (6%)
Pallor (6%)
Cardiac arrest (3%)
Cardiomyopathy (3%)
Myocarditis (3%)
Stroke (3%)
Heart murmur (3%)
Hemmorrhage (9%)
Facial edema (6%)
Intracranial hypertension (9%)
Hypotaxia (3%)
Seizure (3%)
Somnolence (3%)
Facial paralysis (3%)
Spinal cord disorder (3%)
Light reflex absent (3%)
Ulcer (3%)
Cellulitis (8%)
Hepatosplenomegaly (9%)
Dysuria (9%)
Enlarged prostate (3%)
Ascites (3%)
Hepatitis (3%)
Tremor (3%)
Bone inflammation (3%)
Hearing loss (6%)

<1%​

Arterial thrombosis
Hypercalcemia
Myositis
Pancreatitis
Thrombocytosis
Venous thrombosis
Irreversible hearing loss
Genital ulceration

So, then don't take Retinoic Acid. Personally, I would rather take Vitamin A.

Did the paper say anything about the rats not wanting to eat, because that could have been why they lost weight. Hypervitaminosis A can cause anorexia. Not exactly the way to lose weight.

Why don't you click on the link and look at the paper? It's freely available. Anyway, the researchers stated that there was no noticable reduction in food intake, despite the weight loss.

Here is a paper on isotretinoin (which is the isomer of retinoic acid) causing depression:

"Bifulco reported a 52 year old woman who took daily high doses of vitamin A. She developed insomnia, loss of weight and appetite. She became “completely disinterested in her surroundings and was found to brood all the time.” One week after discontinuation of vitamin A her symptoms resolved."

I've seen your case studies before, and while they can happen, the two you posted in the other thread were very extreme. The first involved a 130 pound six foot man who ate several servings of liver a week and only 1400 calories a day. The second was a woman about 120 pounds averaging at least 250,000 iu of retinol a day. Neither of those people had excess fat deposits to lose, so their cases don't apply to overweight (or maybe even normal weight) people.

"A third patient was reported to have several months of symptoms of depressed mood, irritability, aggression, agitation, decreased sleep, decreased appetite, reduced concentration, anhedonia, and early morning awakening that began during a course of isotretinoin therapy. These symptoms resulted in the breakup of her marriage."

Funny, I had most of those symptoms over the summer of 2020. I don't think it was due to Vitamin A (wasn't supplementing it at the time), but instead, due to the treasonous Covid Restrictions (which, of course, were designed to create those exact symptoms). Cyproheptadine (and other anti-serotonin chemicals) have been a lifesaver in that regard.

Are you seriously considering using retinoids to lose some weight?

Retinoids like tretinoin? No. But retinol? 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.

 

[InChristAlone]

So, then don't take Retinoic Acid. Personally, I would rather take Vitamin A.

Why don't you click on the link and look at the paper? It's freely available. Anyway, the researchers stated that there was no noticable reduction in food intake, despite the weight loss.

I've seen your case studies before, and while they can happen, the two you posted in the other thread were very extreme. The first involved a 130 pound six foot man who ate several servings of liver a week and only 1400 calories a day. The second was a woman about 120 pounds averaging at least 250,000 iu of retinol a day. Neither of those people had excess fat deposits to lose, so their cases don't apply to overweight (or maybe even normal weight) people.

Retinoids like tretinoin? No. But retinol? 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.

Your thread was about retinoic acid which is what is in tretinoin. If you have weight to lose despite using extreme doses of vitamin A then what do you think might be going on? Do you then need to do even more extreme doses to see any weight loss?

Isotretinoin has a black box warning due to suicide risk, it isn't just a few case studies. Our body can produce it from retinol. And here is the paper showing that it can:

"The concentrations of retinoic acid compounds were monitored by a newly developed highly sensitive HPLC procedure in plasma of six volunteers who received 833 IU vitamin A per kg body weight per day during a 20-day period. There was a significant increase of alltrans-retinoic acid (two-fold), 13-cis-retinoic acid (7-fold) and 13-cis-4-oxoretinoic acid (5-fold) over endogenous plasma levels of these retinoids. The same compounds had previously been found after treatment with the teratogenic drug isotretinoin (Roaccutan, Accutane). Our results raise the possibility that high vitamin A intake may carry a teratogenic risk attributable to increased levels of retinoic acid compounds generated from retinol by metabolic processes."

 

[BlahtyBlah]

Retinoic acid adverse effects:

>10%​

Headache (86%)
Fever (83%)
Bone pain (77%)
Dry mucous membranes (77%)
Malaise (67%)
URI (63%)
Shivering (60%)
Dyspnea (60%)
Hemorrhage (60%)
Elevated liver function tests (50-60%)
Hyperlipidemia (60%)
Infections (58%)
Nausea and vomiting (57%)
Rash (54%)
Peripheral edema (52%)
Leukocytosis (40%)
Pain (37%)
Abdominal pain (31%)
DIC (26%)
Respiratory insufficiency (26%)
Mucositis (26%)
GI disorder (26%)
Retinoic acid-APL syndrome (25%)
Ear ache (23%)
Diarrhea (23%)
Pleural effusion (20%)
Dizziness (20%)
Pruritus (20%)
Sweating (20%)
Anxiety (17%)
Paresthesia (17%)
Constipation (17%)
Vision changes (17%)
Dyspepsia (14%)
Rales (14%)
Depression (14%)
Insomnia (14%)
Alopecia (14%)
Skin changes (14%)
Confusion (11%)
Abdominal distention (11%)
Renal insufficiency (11%)

1-10% (selected)​

Cardiac failure (6%)
Pallor (6%)
Cardiac arrest (3%)
Cardiomyopathy (3%)
Myocarditis (3%)
Stroke (3%)
Heart murmur (3%)
Hemmorrhage (9%)
Facial edema (6%)
Intracranial hypertension (9%)
Hypotaxia (3%)
Seizure (3%)
Somnolence (3%)
Facial paralysis (3%)
Spinal cord disorder (3%)
Light reflex absent (3%)
Ulcer (3%)
Cellulitis (8%)
Hepatosplenomegaly (9%)
Dysuria (9%)
Enlarged prostate (3%)
Ascites (3%)
Hepatitis (3%)
Tremor (3%)
Bone inflammation (3%)
Hearing loss (6%)

<1%​

Arterial thrombosis
Hypercalcemia
Myositis
Pancreatitis
Thrombocytosis
Venous thrombosis
Irreversible hearing loss
Genital ulceration


There is also something called retinoic acid syndrome in patients being treated with retinoic acid for leukemia, they have fever, shortness of breath, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural or pericardial effusions, edema, and hepatic, renal, and/or multiorgan failure; this syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension.

Kinda sounds like the symptoms of covid. I do wonder how many severe covid patients have ever used retinoids (we have many on this forum for example with severe covid who have likely used retinol). And not to get too conspiracy theory on everyone but Bill Gates' favorite vitamin is vitamin A.


Did the paper say anything about the rats not wanting to eat, because that could have been why they lost weight. Hypervitaminosis A can cause anorexia. Not exactly the way to lose weight.
Here is a paper on isotretinoin (which is the isomer of retinoic acid) causing depression:

"Bifulco reported a 52 year old woman who took daily high doses of vitamin A. She developed insomnia, loss of weight and appetite. She became “completely disinterested in her surroundings and was found to brood all the time.” One week after discontinuation of vitamin A her symptoms resolved."

"A third patient was reported to have several months of symptoms of depressed mood, irritability, aggression, agitation, decreased sleep, decreased appetite, reduced concentration, anhedonia, and early morning awakening that began during a course of isotretinoin therapy. These symptoms resulted in the breakup of her marriage."

Are you seriously considering using retinoids to lose some weight?

These anecdotes of a few patients do not prove cause and effect of the vitamin A itself. We would need a controlled trial with placebo to show that. Someone can have side effects taking high doses of Vitamin A and it may be because they're not eating enough Vitamin D/K and it is therefore displacing those other vitamins. It may be a result of that or something similar than the Vitamin A itself. Or it could be a coincidence of a health issue that was manifest at the time of taking the Vitamin A. You have reports of side effects with almost any supplement as well. This is not uncommon.

 

[InChristAlone]

These anecdotes of a few patients do not prove cause and effect of the vitamin A itself. We would need a controlled trial with placebo to show that. Someone can have side effects taking high doses of Vitamin A and it may be because they're not eating enough Vitamin D/K and it is therefore displacing those other vitamins. It may be a result of that or something similar than the Vitamin A itself. Or it could be a coincidence of a health issue that was manifest at the time of taking the Vitamin A. You have reports of side effects with almost any supplement as well. This is not uncommon.

Did you read the paper? They put a black box warning for suicide risk on Accutane, it's not just a few reports. Hypervitaminosis A is well documented. You can't just take D and K to avoid it especially since it's well documented from cod liver oil and liver which has many fat solubles.

 

[BlahtyBlah]

Did you read the paper? They put a black box warning for suicide risk on Accutane, it's not just a few reports. Hypervitaminosis A is well documented. You can't just take D and K to avoid it especially since it's well documented from cod liver oil and liver which has many fat solubles.

Drug companies put warning on labels even when there is barely any evidence of said side effects to cover themselves agaisnt frivolous and unsubstantiated claims. This has happened with many drugs in the past where even studies were done showing no side effects as claimed by some, and they still put it on the warning label just to protect themselves because, believe it or not, the no placebo effect is real, and some people look to sue companies just for money as well, so from a business perspective it gives some insurance. Even no evidence has shown clinically that Accutane causes suicides. That would be extremely hard to prove because there are many variables in one's life that may increase suicide risk as well, so no way could someone weed those factors out from a drug they're taking it as causing it unless there was a very expensive and controlled trial, double-blinded, etc. I have been taking this form of vitamin A for years and never had any thoughts of suicide as well. It's a widely used and old medicine that has been shown to be fairly safe.

 

[tankasnowgod]

Your thread was about retinoic acid which is what is in tretinoin. If you have weight to lose despite using extreme doses of vitamin A then what do you think might be going on? Do you then need to do even more extreme doses to see any weight loss?

Retinoic Acid is a Vitamin A metabolite. The first sentence of the linked study literally states this. If you read my original post, I also mention how there are studies with Vitamin A posted to the forum that show positive metabolic changes that would tend to lead to weight loss, like the study in humans using vitamin A that lowered TSH and raised T3-

The Effect Of Vitamin A Supplementation On Thyroid Function In Premenopausal Women

http://www.ncbi.nlm.nih.gov/pubmed/23378454 Abstract OBJECTIVE: Vitamin A and its retinoid derivates play an important role in regulation of normal growth and development. Vitamin A has been shown to regulate thyroid hormone metabolism and inhibit thyroid-stimulating hormone (TSH) secretion...

raypeatforum.com

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.

Isotretinoin has a black box warning due to suicide risk, it isn't just a few case studies.

Are you aware of how "black box" warnings come about? Usually, it is a small number of cases. Even in the case for the J&J Demonvax Black Box warning for Guillan Barre, it was 100 cases out of 13 Million recipients.

Our body can produce it from retinol. And here is the paper showing that it can:

"The concentrations of retinoic acid compounds were monitored by a newly developed highly sensitive HPLC procedure in plasma of six volunteers who received 833 IU vitamin A per kg body weight per day during a 20-day period. There was a significant increase of alltrans-retinoic acid (two-fold), 13-cis-retinoic acid (7-fold) and 13-cis-4-oxoretinoic acid (5-fold) over endogenous plasma levels of these retinoids. The same compounds had previously been found after treatment with the teratogenic drug isotretinoin (Roaccutan, Accutane). Our results raise the possibility that high vitamin A intake may carry a teratogenic risk attributable to increased levels of retinoic acid compounds generated from retinol by metabolic processes."

So, this justifies the concept.

 

[tankasnowgod]

Hypervitaminosis A is well documented. You can't just take D and K to avoid it especially since it's well documented from cod liver oil and liver which has many fat solubles.

Without specifics, this is just silly to say.

First off, there is no claim that Cod Liver Oil has significant amounts of any Vitamin K, 1 or 2. Second, the amount of A and D can vary widely from batch to batch. And lastly, the vast majority of people in history who have taken cod liver oil (well over 99%) have NOT developed Hypervitaminosis A.

 

[tankasnowgod]

They put a black box warning for suicide risk on Accutane, it's not just a few reports.

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

Case reports​

A number of case reports and case series linking isotretinoin to depression or suicide have appeared in the medical and psychological literature since 1982.10-19 Between 1982 and 2000 the FDA has received reports of 394 cases of depression, and 37 suicides occurring in patients exposed to isotretinoin.7,20 It is the fifth most common drug reported to the US Adverse Event Reporting System (AERS) in association with depression, and the tenth most common (and the only non-psychotropic drug) in suicide reports.7 In Canada, psychiatric adverse effects in patients taking isotretinoin have been reported to Health Canada21 — 56 events between 1983 and 2003.22 Forty-two psychiatric reactions were reported to the British Medicines Control Agency between 1982 and 1998,23 including a small number of suicides.24 In Australia from 1995 to 1998 the Adverse Drug Reactions Advisory Committee received 12 reports of depression in patients taking isotretinoin.25 Two cases were described as severe, in four there were psychotic features, in three there was suicidal ideation and there were three suicide attempts (with one completed suicide).

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?

But pitfalls inherent in making inferences of causality from case reports or case series are illustrated by the case reported by Kovacs and Mallory.26 They describe a 17-year-old Korean boy who developed mood and behaviour changes while taking isotretinoin. Symptoms resolved with isotretinoin withdrawal, but re-emerged with rechallenge, and the boy's psychological morbidity was attributed to isotretinoin. It later emerged that the boy's symptoms also coincided with periods of recreational LSD and cannabis use.

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.

 

[InChristAlone]

Without specifics, this is just silly to say.

First off, there is no claim that Cod Liver Oil has significant amounts of any Vitamin K, 1 or 2. Second, the amount of A and D can vary widely from batch to batch. And lastly, the vast majority of people in history who have taken cod liver oil (well over 99%) have NOT developed Hypervitaminosis A.

It does come down to dose as always. But the theory that vitamin D or K would protect you from extremely high doses needs to be proven as well. Weston A Price did find high vitamin butter oil to be protective of the toxic effects of cod liver oil, but we are talking about 100,000 IU's, the dosages he used of cod liver oil were extremely small (and still found it to be toxic).

Here is another paper showing high doses might be the cause of chronic liver disease diagnosable by liver biopsy.

Right off the bat they say: "Although vitamin A-induced systemic and liver toxicity have been recognized now for more than a century,"...

"A precise appraisal of drug consumption was obtained in 29 cases. Among them the total cumulative intake was the highest in patients with cirrhosis (423 +/- 103 x 10(6) IU) and significantly lower in those with noncirrhotic liver disease (88.5 +/- 41; P less than 0.02). The smallest continuous daily consumption leading to cirrhosis was 25,000 IU during 6 years, whereas higher daily doses (greater than or equal to 100,000 IU) taken during 21/2 years resulted in similar histological lesions. It was concluded that at least in some western countries chronic vitamin A consumption might represent an appreciable cause of chronic liver disease, the recognition of which mainly relies on expert liver biopsy interpretation. The data also indicate that prolonged and continuous consumption of doses in the low "therapeutic" range can result in life-threatening liver damage."

Liver disease is a slow death, you won't know it until very late. If anyone is reading this and considering using excessive doses to try to somehow force their body to be healthy (have never seen someone do this without also using lots of thyroid and other supporting nutrition because it will cause hypothyroidism- even Peat acknowledges this) please routinely screen for liver disease and other abnormalities in organ function.