Over the past few years this has been intensely debated within the alternate health spheres, particularly Ray Peat forums.

I would like to explore this deeper as a Self-Meta. Examining all sides of arguments. Mainly on the opposing view(s) by Grant Generoux and Dr. Grant Smith.

1. What is Vitamin A?
2. What is the concern?
3. Conflicting findings
4. What's in it for me?
5. Conclusion

LIVE DRAFT NOTICE

This is largely a WIP / work in progress live-draft share for public reading. Any or all mistakes including spelling errors, placeholder indicators and/or unfinished passages remains visible. However, I retain the right to temporarily unpublish this entire feature writeup, due to the complex nature of the subject, and with inevitable need for splitting these into multiple part(s). Meanwhile ~ my thoughts, on this nuanced subject remains strictly preliminary. And that I am yet to formulate any conclusions, for as long as this "Live Draft Notice" remains visible. 

Disclaimer

Since the beginning of this initiative I am absolutely not affiliated, nor do I speak for -  on behalf for any "influencer", "brand" or entity. This Self-Meta is entirely a product, concept, and initiative of my own curiosity to both purvey bespoke dialogues that are otherwise hidden amidst pedestrian or mainstream medium(s).  As general reminder once again, this Self-Meta is neither prescriptive advice nor cannot it indemnify anyone. For those new to this concept initiative, welcome! please acquaint yourselves with this starting page here. Live-it-forward, AW. 

Foreword, Context, and Rationale

Reaching close to a decade since incorporating various forms of low carbohydrate, I am an advocate of consuming most organ meats for their micronutrients. Chiefly among them ~ livers. There is a feeling of certain nourishment, quite difficult-to-describe, such that I am yet to experience nor find elsewhere from so called "superfoods".

My interest in Vitamin A also coincide within the views of Dr Ray Peat's favour. That of which, despite controversial towards high sugar, yet also liberal in saturated fats ~he is pro-Vitamin A from raw, but not cooked ~ carrots and also recommends, although in sparing amounts ~ livers and organ meats.

Despite the proclaimed anti-estrogenic attributes and all around synergy with all other key fat soluble vitamins - D, E and K2; it seems very difficult and hard to argue against Vitamin A at first. Considering their historic significance, and widely-established essentiality not only within mainstream academia, but also alternate health circles, Weston Price Foundation included.

However in recent years saw a curious, yet turbulent controversy(s) firstly stemming within Ray Peat forums. Particularly from one thread (which, names nor title shall not be mentioned) focused primarily on Grant Generoux's hypothesis that Vitamin A, is not and never should have been considered ever, to be a nutrient. The thread has attracted multitude hundred(s) of pages.

This led me to read, albeit time-restrictive ~ Grant Generoux's free to view ebook "Extinguishing The Fires of Hell.". Weighing at 430 pages, it requires careful, slow and patient reading to this day. I am yet to fully read this through, word-for-word. However, all his assertions, including the charts, well referenced citations, and the nostalgic visuals all seemingly legitimate and persuasive. But it is Grant's own N=1 experiment proving the most interesting, that is shared until in the much later Chapter(s) #25 in the book (@page 368).

Recent weeks counting months also led me to self-enquire my own dietary recalls, comparing and introspecting for differences in my WOL (way of life) from my WOE (Way of eating) specifically where and when possible ~ surrounding Vitamin A rich foods coming from predominantly carrots and my own DIY livers pate. Recalling whether or not I have indeed feeling better with lesser Vitamin A, the opposite, or perhaps still undecided. I have no conclusion as of the very publically-sharing of this Self-Meta.

Of course with all things Science ,there are those who simply are not in agreement to neither Grant's or Dr Smith's views. Several sources here, and here for instance, remains noteworthy.

In addition to the above, there is also another noteworthy reference, who shares a likewise cautionary stance with Vitamin A. Meredith Arthur ~ a dietician who is also aware of Vitamin A controversy was able to share the mechanistic backgrounds at a much detailed level She nonetheless believes that Vitamin A, at least a certain amount and type (Retinol)appears, at least in some undisclosed required amount ~ a non obligatory essential to general energy production, as well as to safeguard against Vitamin A's other conversions to the more proclaimed harmful version ~  known as "Anhydrovitamin A". (41:40). This discussion and more, will be detailed in Parts 2 and 3 of this Self-Meta.

Nevertheless, despite much controversy, this Self-Meta I hope brings together a more rounded introspection on this yet another complicated subject, just like Vitamin D.

References in this Self-Meta

This is a live WIP listing subject to further revision overtime.

1. Grant Generoux's Book ~ "Extinguishing the Fires of Hell". Free-to-view. Creative Commons License. For short-referencing sake, I am using  "Generoux's Book" to refer to the above book throughout this Self-Meta.
2. Nutrition with Judy podcast ~ Dr Garrett Smith (Part 1 and 2)
3. Nutrition with Judy podcast ~ Grant Generoux. 
4. The Quax Podcast ~ Grant Generoux. 
5. Weak Therefore Strong Channel ~ All Roads Lead to Anhydroretinol
6. In addition to: various current published literatures on Vitamin A's:
   1. General metabolism, background, context and history.
   2. Toxicity studies (both animal and human).

Whilst this page is published live temporarily as draft, only a few citations are listed here, subject or until time necessitates me to continue drafting on the nuanced aspects offline. Also note that in the later sections on Vitamin A's role on specific autoimmunity (particularly - AS / Anyklosing Spondyltis) feature an entire list of citations amounting to the dozens. Hence outlining each and every one of them is likely encumbering to read. 

As kind reminder, whilst videos & podcasts are persuasive and easy-to-digest mediums ~ they by no means represent permissive discount from further reading and/or research.

Lastly, unlike its predecessor,  this Self-Meta is written entirely in first person for a less-formal impression.

Questions to raise.

Besides from the main over-arching title "Should Vitamin A be avoided?" I have decided to break this down into several more layer(s) of question.

1. What is Vitamin A? And its origins of use?
2. How did Vitamin A become so pervasive in the alternative health community? 
3. What other symptoms, besides from the proclaimed / suspected auto-immune disease correlation(s) have been noted with dietary (or supplemental) Vitamin A?
4. Specifically in terms of Auto immunity ("AS" / Ankylosing Spondylitis) ~ is Vitamin A perhaps best avoided, or at least reduced either to manage or to safeguard against pending increase of symptoms associated with AS (eg. Uveitis, Dermatitis, Psoriasis, etc).    
5. If Vitamin A is and has been recognised globally through repeated scientific consensus as essential :
   1. Is it the faulty mechanism(s), be it ageing or gradual loss of regulatory processes in the individual, that may explain one's inability to handle, filter or detoxify ~ excess dietary Vitamin A?
   2. Could these faulty mechanism(s) be attributed to Genetic mutations, just like those involved Vitamin D paradox that prevents select individuals to develop Hypercalcemia?  

The Ebers Papyrus (c. 1550 BC) from ancient Egypt. (CC BY SA 3.0)

What is Vitamin A + History

“Roasted ox liver, pressed, applied (topical to the eye).” ~ Egyptian Papyrus Ebers (~1550BC)

There is no one (1) historic "event" uncovering simultaneously  ~ both the presence, and/or the function of Vitamin "A", as we know it. But there appears to be ancient evidences and/or records proclaiming that Vitamin A rich foods we've known (livers, particularly) have been used both topically and orally as medicinal nutrition.

Fast forward to 18th to 19th century saw a period of experimental models to study the effects of malnutrition on both human and animals. Commonly noted signs were volatility to infections, as well as vision loss. During these period, researchers were trying to idenitfy what key micro nutrients, apart of macronutrients (carbohydrates, proteins and fats) and minerals  that are associated with growth (bodily tissue), overall development. Between 1906 to 1920, a particular  compound (or back then, called "Accessory Factors") were found to be fat soluble,  has an "amine" group in its chemistry*, and mostly coming from milk, eggs (particularly the yolks) and cod liver oil. In 1918, these factors were then given a name "Fat-soluble-A", before then renamed as "Vitamin A" , in 1920. In 1931, organic biochemist Paul Karrer successfully extracted the compound from cod liver, and marked the first discovery of Vitamin A's structure.

Trivia: "Vitam~"ine" (before later condensed to "Vitamin") ~ was the very first suggested identity to refer to these factors.

Metabolism

Vitamin A in dietary forms come as either "preformed" (retinyl esters) from animal sources ~ eggs, liver, butter, milk and also on fortified cereals. Alternatively "provitamin" (carotenoids / Beta Caraotenes) which as one implies ~ carrots, collard greens, and squash.

Noteworthy is that caretonoids are NOT only found on bright coloured vegetables - carrots, squash, peppers and/or pumpkins. The green(s) in Kale and Brocolli for example,  as defined by their Clorophyll ~ also contain some Vitamin A. Beneath the chlorophyll exposes oranges and yellows when oxidised. These phenomenon may also explain the colour transitioning between (green) to (yellows to deep oranges) amongst fruits as they ripen.

Like all other fat solubles (Vitamins E, D and K2) the presence of fats, and optimum gall-bladder at producing enough bile (10:50) to help emulsify, packaging and transport through the small intestines. From there ~ both forms (Provitamin or Preformed) undergo their three possible (3) conversions:

1. Retinol. Interchangeable / reconvertible to Retinal. From the liver, Retinol is then bound or packaged by RBP (retinol binding protein), which then gets transported to various tissues that require Vitamin A. Any amount that is not utilised, is transported back to the liver for storage as retinyl esters. 
2. Retinal (hinted from the "~al" for aldehyde); Interchangeable / reconvertible to Retinol. The dependent enzyme on this conversion is Aldehyde Dehydrogenase, which is also required for handling / detoxifying ethanol in general.  
3. Retinoic Acid. A one way conversion. Not interchangeable to either #1 and #2.
4. (The end stages / end-destination) ~ firstly as All-trans retinal then finally ~ 11-Cis Retinal. Taught to be essential for all vision function, from colour +light recognition, but also for nightvision. In the optic nerve there are millions of rods (active during daylight) and cones (active for night vision) that rely on a protein Rhodopsin, which rely on the succesfull conversion from All-Trans Retinal.

A specific version that Generoux's Book highlighted ~ Retinol Palmitate (pg 70). This is the alcoholic form (~"ol")  bound to palmitic acid ~ a saturated fat off palm oil and often re-named in various synonyms "All-trans-retinyl", "Palmitate", and "retinol hexadecanoate" to name a few.  It is the added form throughout not only the food supply, but also in sunscreen products (pg 348).

There is also another form albeit less discussed in the alternative health circles ~ "Anhydroretinol"; a potentially yet another damaging metabolite of Vitamin A.  The Youtube® presentation by Meredith Arthur, registered dietician, explained these in quite a nuanced detail; including a discussion on the various genes and enzymes most volatile that some individuals may be inherently born with, that inevitably and adversely affect Vitamin A metabolism. Information like these can be immensely useful for those considering a nutrigenomics consultant.

How much is considered "toxic"?

Note that in Australia, the RDA for Vitamin is measured differently in mcg.

According to the NRV / nutrient reference value for Australia & NZ ~ One (1) IU  / International Unit of Activity ~ is equivalent to 0.3 of mcg.

From the above reference, the RDI / Recommended Dietary Intake were suggested as:

• For men (19 to 70+ yrs) : 900mcg or 3000 IU.
• For women (19 to 70+ yrs) : 650mcg or 2166 IU. In breast-feeding, requirements increases to 900mcg.

Elswhere suggested ~ the RDA is 900 mcg. This equates to 3000 IU. Plasma reference ranges suggests to be 18-60mg/dl.

Toxicity or upperlimits (UL) appears to vary widely.

• Official (Australian) ERV values suggests men and & women 19 years+ UL's of 3000 mcg / day or approx 10,000 IU.
• One source  ~ 25,000 IU or approx 7500 MCG per day, presumably for years.

Interestingly Beta Carotenes are widely thought to be safe, irrespective of dosage. The Australian ERV does not have any data suggesting what constitutes UL on this preformed Vitamin A, despite the warnings it did share that suggest dose-dependent correlation with lung cancers. Nevertheless, the ERV page rationale for abscence of UL on Beta carotene was simply due to "insufficient evidence" for harmful symptoms, other than "yellowing of skin".

So, what is the fuss about Vitamin A?

From what can be gathered out of a variety of research, ranging from case-studies, animal, and mechanistic ~  the two oppositions to the Vitamin A paradigm (Grant Generoux and Dr. Garrett Smith) assert two primary arguments.

1. Firstly that Vitamin A, irrespective dietary or supplemental intake is not and should not be a nutrient.
2. And secondly, Vitamin A's under-recognised correlations with auto-immunity and all-mortality risk factors.

The controversy seemingly initiated from one (1) Ray Peat forum thread. This led to gradual recognition of Grant Generoux's Book. The Ray Peat thread gathered HUNDREDs of pages. And in addition, Grant Generoux's own WordPress® discussion board also gathered several convincing arguments.

Going back in time even before this, led us to Grant's initial self-treatment of his Eczema condition, at the age of 54 years, in his first blog post in 2014. He shared many details. Notably that he has had been diagnosed within only the same year. What nutrition he kept on, for months on end. Then, affirming with pictures he journalled as evidences. All this indeed ~ prompts a very convincing read.

There many reasons, albeit only chiefly-ones we can gather here ~ at speculating the why behind this controversy.

Firstly ~ the confusions surrounding its nuanced mechanism that interacts widely with so many other confounders. Notable to add to the difficulty of toxicity diagnosis this is that Vitamin A toxicity and symptoms seems to have a "U" curve. Unfortunately, studies examining this phenomenon have not been found, unlike Vitamin D.

Then, the difficulty at asssessing Vitamin A toxicity indications. Serum Vitamin A, as Grant asserts in his book is not a reliable marker for overall Vitamin A status. Several other research literature(s) appears to agree, particularly one (Kristina Penniston KL & Tanumihardjo SA 2006).that looked at individuals who express Vitamin A toxicity symptoms, paradoxically also showed serum normal levels

Then, the already prevalent and ubiqutuious nature of Vitamin A throughout our Food supply, thus prompting sheer difficulty when and if anyone is prescribed to eliminate all sources.

Certainly there's more to uncover. But at the time of drafting this Self-Meta ~ succinctly rewriting these for concise lay reading are enormously difficult and time consuming.

The Oppositions' Highlighted Proclamations.

From observing, reading and listening through all the main references, including podcasts and guest interviews in various channels as listed in the beginning of this Self-Meta:

1. Vitamin A is not and should not be classified - as essential nutrient.
2. Vitamin A appears to be already consumed well and beyond the RDAs in many developed nations. This research appears to agree (Kristina Penniston KL & Tanumihardjo SA 2006).
3. Vitamin A, particularly as it gets broken down as into the retinoic acid potentially disrupts various protein synthesis, in general (7:43 onwards).
4. Vitamin A is also potentially addictive. There has actually been multiple case studies on this (Sansone A et al 2012), (Kaplan R 1996). This gained traction on New York Times, The Independent UK, and even amongst reddit forums.
5. Low serum Vitamin A is NOT and should NOT be a signal for deficiency. Case studies seem to suggest that there is some time required for the liver to "detox", or "shed" its own excess stored Vitamin A, back to the serum / circulation.
6. The copper content coinciding in many Vitamin A rich foods likewise also pose numerous health risk. This view I concur somewhat, from an earlier noteworthy podcast I shared sometime ago; particularly in context of copper's role in psychiatric malaises.
7. Another opposition, albeit from highly nuanced standpoint by  Meredith Arthur ~ proclaims that we do need, inevitably, some amount of Retinol; in order to safeguard against the unintended conversion to another damaging metabolite known as "Anhydroretinol" .
8. Vitamin A in sunscreen products (pg 348) have also been suspected to play a role to skin cancer development.
9. Vitamin A toxicity, can be reached even amongst modest of doses well below RDAs.
10.  Following from point #1 - human body can live up to ten years virtually free of Vitamin A intakes without signs or symptoms of deficiencies.
11. (From very strong N=1 case points from both authors) ~ Vitamin A abstinence greatly help reduce eczema.
12. Lastly, and perhaps an interesting reminder it pays for us all to think twice from all figures we all followed ~ Dr. Weston Price ~ had some mixed views on Vitamin A. Despite proclaiming that Vitamin A was not deemed a "toxin", he did raise a number of observational concerns amongst children, who became sick when supplemented or dieted with Vitamin A. This was proclaimed within the podcast I'm sharing below. 

Other interesting notes indirect to Vitamin A, lead us to Carnivore Diets and how it has recently grained fame for addressing auto-immune conditions. The famous 2021 study from Harvard (Lennerz BS et al. 2021) observed improvements amongst 2029 participants. Looking at the "perceived" symptoms documented ~ all eye health related concerns appears generally "improved" or "stable", with the diet. Noteworthy however is that throughout carnivore sphere in general, including Shawn Baker ~ all consider organ meats as only optional. An article by Optimising Nutrition examining Shawn Baker's micronutrients input ~ all appears to be very low on Vitamin A. This mildly suggests, only hypothetically that a lowered Vitamin A intake may have likely a part of, or a contributing factor ~ that led to relieve many of symptoms above.

Symptoms

Generoux's Book primarily focuses around Vitamin A's correlations with auto-immunity. For context ~ Autoimmune disease is a highly complicated stream of condition(s). There are over (possibly more than) eighty (80) thus-far known separate disorder(s). Each affecting anywhere from psychology to physiology. A possible list, though of course high level suggest the following as surrogate effects:

• osteoporosis & hip fractures,
• abdominal pain,
• anxiety,
• blurry vision,
• bone pain,
• confusion,
• depression,
• fatigue,
• dry rough skin.

To name a few. For a full list, reading Generoux's book is highly recommended (pg 88). 

Other more metabolic health specific symptoms (Olson JM et al. 2023) include the following though not exclusively limited:

• Hypertriglyceridemia (through supplement use - oral Retinoid)
• Hypothyroidism (through supplement use - Bexarotene)

For pathology / blood panels ~ liver function tests (particularly for the below two enzymes), in addition to complete blood count (CBC) seems recommended.

• AST (reference range 14.0-59.0 U/L)
• ALTV (reference range 1.0-50.0 U/L)

Noteworthy is that serum Vitamin A  (normally suggested as 1-3 picoMol/L) may not be realiable indicators for toxicity. As there are multiple case studies strongly suggesting toxicity symptoms do manifests, despite normal serum readings (Penniston KL & Tanumihardjo SA 2006). 

Which form of Vitamin A is more or less considered "toxic"?

As Vitamin A gets catabolized originating from the dietary or supplemental ~ Preformed (Retinyl Esteres) or Provitamin (Carotenoids / Beta-carotenes),

1. Retinoic Acid. The end stage of conversions, considered to be the most toxic as firstly proclaimed by the Opposition.
2. Retinol. The alcohol version.
3. Retinal. The aldehyde version.
4. The dietary / precursor wholefood forms ~ retinyl esters and carotenoids. Obviously, as the oppositions argued - so long as they're not ingested or limited in their consumption.

General knowledge suggests that beta-carotenes, the most familiar form of caretonoids in brightly coloured fruits and starchy vegetables have been proclaimed safe, and cannot be overdosed at any level. Yet other research suggest that more insight is needed. For instance "Caretonosis" has been a well documented symptom notably through yellowing and/or orange pigmentations; usually on hands. One meta-analysis (Zhang Y et al 2023)  suggests that Beta-carotenes supplementation may be associated, albeit within sub-group analysis ~ with worsening state of lung cancer.  And two more meta-analysis, one in 2022 (Yang J et al 2022) and previously in 2010 (Latino-Martel P et al. 2010) ~ found likewise associations with not only lung cancer, but also in the 2010 analysis ~ worsening CVD / cardiovascular disease association.

Furthermore in 2022, there was an article on The Conversation on this topic. Attentive and convincing in the title, it reads "An expert panel has recommended against taking vitamin E or beta carotene supplements for the prevention of cancer and cardiovascular disease – here’s why". 

So what is the mechanism that led to all the above damage or concern?

At the very least from what we may take away from the above video references thus far:

1. "RBP" or retinol binding protein is thought to be protective throughout the  Vitamin A conversion and their mobilisation. It keeps the Vitamin A bound and to keep unbound in their so called "free form". A defect or an error somewhere during the Vitamin A conversion may cause malhandling or production of this protein, which serve a hypothetical discussion that unbound Vitamin A is the contributing cause of the oxidative stress cascade in the mitochonrdria, which consequent/prompts the release of superoxide (H202 / hydrogen peroxide) in hte process. 
2. Vitamin A requires many other co-factors and nutrients in order to be "safely" utilised. Zinc-copper balance, Vitamin D, Magnesium to name a few.
3. In highly more technical explanation ~ Meredith Arthur's presentation examines the critical metabolic processes of Vitamin A. Specifically, it is the metabolite of Vitamin A (Anhydroretinol) which is argued to be the most damaging as it impacts the entire energy production cycle (Krebs and ETC chain) and inevitably cell death / apoptosis. To ensure that this metabolite conversion (to Anhydroretinol) does NOT occur, it is suggested (from the cited research) that some presence of Retinol was nonetheless vital ~ to safeguard the entire Vitamin A metabolism without oxidative stress (10:45). Specifically, the gene "PKCO" remains chronically activated during oxidative stress were there is little to no presence of Retinol.

Obviously the above only a grossly summarised attempt at providing a high level explanation. Therefore is not a permission to discount further reading.

<Draft WIP progress>

(Draft WIP in progress)

This is a Live-Draft WIP in Progress article. Embarrasments, non-sequitor's and the like are all in the show. Without shame. However I still retain the right to continue drafting elsewhere. And that this may be subject for complete (albeit temporary) omission altogether until I am confident or ready for their public release.

Nutritional Science carries "science" in the end for a reason. Such is what I believe to be open-ended for readers own introspection.

Live-It-forward

AW.