Grant Genereux and vitamin A Pt. 2

As was mentioned in the previous article, Grant Genereux has written extensively on the topic of the ”toxicity” of vitamin A, and has, at the very least, managed to seriously question its ”essentiality”. (

From my perspective, it seems that much of the toxic effects attributed to vitamin A are really caused by the polyunsaturated fats (PUFAs). It is well known that the accumulation of PUFAs increases the need for vitamin E, which prevents their oxidation. I think this relative deficiency of vitamin E induced by the presence of the PUFAs simultaneously renders vitamin A susceptible to oxidation. Here is an audio excerpt from a Ray Peat interview where he expands on this idea of vitamin A toxicity (start around 3:08 for the most immediately relevant section):

Ray Peat comments on vitamin A toxicity (May 2019, One Radio Network)


‘’At a certain very high level, vitamin A autocatalyzes, it stimulates its own oxidation and degradation. And the symptoms of vitamin A poisoning become similar to vitamin A deficiency. Both of those are prevented by adding vitamin E which prevents the breakdown.’’ – Ray Peat

Expending on this idea, there is a particularly enlightening section in Ray’s The problem of Alzheimer’s disease as a clue to immortality – Part 2 article on his website (1):

Vitamin A’s true nature is frankly, still poorly understood. But there is clearly some interaction at play with other compounds. Grant Genereux’s work is important because it questions the fundamental ideas about what a ”vitamin” really is, and clearly highlights that vitamin A is not always beneficial, and needs to be examined within a larger context. There are conflictual reports on the physiological roles of vitamin A, especially concerning steroid (hormonal) production. Some research articles have reported that it is necessary for the conversion of pregnenolone to progesterone (2), for example, while others suggest that vitamin C (ascorbic acid) is able to compensate for deficiencies of vitamin A. (3) There is probably a fundamentally important interaction between all the vitamins, but vitamin C has been known to ”spare vitamin E in tissues by regenerating alpha-tocopherol from its oxidation products”. (4) This may mean that vitamin C protects vitamin E which in turns protects vitamin A. Whew!

To reiterate, I suspect that vitamin A can accumulate in all the tissues, if for some reason it cannot be utilized in metabolic processes (i.e. low thyroid function). The accumulation of the PUFAs will destroy and therefore increase the need for vitamin E. For the same reason that cholesterol can become elevated when thyroid is low, vitamin A might start to accumulate and oxidize and lead to different pathologies, especially in a state of vitamin E deficiency. Therefore it seems reasonable to consider vitamin A within a broader relationship with the other nutrients like vitamin E, C, K and even minerals like zinc. (5)

Beyond this, there is evidence which points towards a basic, fundamental role for vitamin A, specifically at the level of mitochondrial energy production. (6) This will be explored in a future article.



  1. Ray Peat. The problem of Alzheimer’s disease as a clue to immortality – Part 2.
  2. Junega, Murthy & Ganguly (1966). The Effect of Vitamin A Deficiency on the Biosynthesis of Steroid Hormones in Rats. Biochem. J. 9, 138
  3. Gruber et al. (2003). Vitamin A: Not required for adrenal steroidogenesis in rats. Science Vol. 191
  4. DSM in Animal Nutrition and Health. Vitamin E: Properties and Metabolism.
  5. Gropper, Smith & Groff (2009). Advanced Nutrition and Metabolism. 5th edition (p.388)
  6. Acin-Perez et al. (2009). Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis. FASEB Journal, October 2009.


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