The History of Vitamin A

The problem with Vitamin A is that people think it’s good for you, but almost nobody questions if it’s bad for you. That’s why people are trying to feed malnourished children with Vitamin A nanoparticles in staple foods, golden rice is engineered to have more carotenes in it, all the nutrition meals/plans such as Ensure, Soylent, Huel will include it, someone is trying to make Vitamin A enhanced ultrasonic rice, Vitamin A is added to sugar in some countries, Vitamin A is added to all low-fat milk in the USA. You get my point; I’ll stop listing things.

The difference between this and adding something like the B vitamins are that the B vitamins are water-soluble and excreted. The difference between this and chlorinating the water is that we know chlorine isn’t good for people, but we accept the necessary trade-offs for potable water. Vitamin A lies in a blind spot where although the risk of hypervitamintosis A is acknowledged, people still try to include some amount of it in foods, not aware of its accumulation in the liver over time.

Regarding the modern health crisis due to our food and environment poisoning us (increase in neoplasms, obesity, decreased testosterone, fertility, allergies, etc.), there are many culprits. The common ones: microplastics, PFAS, car emissions, tire nanoparticles, non-stick pans, pesticides. The societally-accepted-as-necessary-ones that strike a third rail for many if you disagree with them: water chlorination, fluoridation, vaccines, electromagnetic fields, x-rays. The food: Added B vitamins, antinutrients, enriched iron, processed wheat, Vitamin A, cyanocobalamin, vegetable oils.

As an individual, I don’t need to convince anyone that these common ones are bad. We need to share solutions for how to mitigate them. The societal ones are a hot political topic at this moment. There are already enough arguments why vegetable oils are bad; I think this battle is won. Of the other issues in food, I think only Vitamin A is in the very bad category yet simultaneously not talked about.

It’s also the only one that has an astoundingly easy proof: a proof by counterexample. A rat that survives and reproduces with zero serum retinol and liver stores demonstrates that it being a vitamin (something that an animal cannot grow without) is invalid.

Given that Vitamin A is known to be poisonous in high doses, this proof would move it into the realm of toxic substances and then it would no longer be added to all our foods.

Why you should stop consuming Vitamin A

Just take a look at the ingredients the next time you shop.

Vitamin A added in the form of retinyl palmitate or retinyl acetate are known as preformed Vitamin A and have no limits on systemic absorption. Provitamin A includes carotenes, such as the colors in various plants such as carrots, and are converted into preformed Vitamin A.

All of the added Vitamin A in foods tends to be preformed Vitamin A. If it were beta-carotene, it probably wouldn’t be that bad (outside of turning people orange). This means all yogurts (basically the entire Costco aisle of yogurts) created using low-fat milk (since it is federally mandated), food products that use low-fat milk (Americans eat a huge amount of processed food), and so on accumulate huge amounts of Vitamin A.

I’m going to make the historical argument too: nobody consumed large amounts of retinyl palmitate in their food 50 years ago, so why should you now?

Measurement

Vitamin A is specified as: 0.3ug retinol = 1 IU = 0.6ug beta-carotene.

History/NOTE: Following written by AI

Meta-summaries

There are two good summaries I’m aware of. The first is Multiple Functions of Vitamin A (1984) by George Wolf. The second is Vitamin A (1957) by Thomas Moore. They are good for numerous connections to the literature and seeing how the field developed.

The visual function

The oldest thread in the whole field is the eye. Night blindness (nyctalopia) and the drying-out of the cornea (xerophthalmia) were the first signs anyone tied to a missing dietary factor, long before that factor had a name. The Ebers papyrus (~1550 BC) and the Hippocratic writers both prescribed liver — eaten or squeezed onto the eye — for night blindness, the earliest recorded “treatment.” In 1816 François Magendie reported that dogs fed nutrient-poor diets developed corneal ulcers and died, the first deliberate deprivation experiment to wreck the eye.

When the fat-soluble factor was finally isolated — independently by Elmer McCollum and Marguerite Davis at Wisconsin and by Thomas Osborne and Lafayette Mendel at Yale, both in the Journal of Biological Chemistry in 1913 — the eye lesions of deficient animals were among the first hard symptoms used to track it. (Wilhelm Stepp had already shown, around 1909–1911, that the essential factor in milk was fat-soluble.)

The mechanism of the visual symptom, though, came out of a separate 19th-century line of work on the pigment of the retina:

• Zur Anatomie und Physiologie der Retina (1876–77) by Franz Boll — found that the frog retina is reddish-purple in the dark, bleaches in light, and regenerates again in the dark. He had discovered “visual purple.”
• A series of papers (1877–79) by Wilhelm Kühne — named the pigment rhodopsin (Sehpurpur), worked out its bleaching and regeneration, and even produced “optograms,” fixed images of the bleaching pattern on an excised retina.

The two threads — the dietary deficiency and the retinal pigment — were tied together by:

• Experimental contribution to the study of the relation between night blindness and malnutrition (1925) by L. S. Fridericia and Edgar Holm, American Journal of Physiology 73:63 — vitamin A–deficient rats regenerated their visual purple far more slowly after bleaching than well-fed controls. This was the first experiment to put vitamin A inside the visual mechanism rather than merely adjacent to it.

Then came George Wald, whose work is the backbone of the entire subject:

• Vitamin A in the retina (1933), Nature 132:316 — Wald identified vitamin A spectroscopically in the retinas of frog, sheep, and cattle.
• From frog retinas he isolated a new yellow carotenoid and named it retinene (today’s retinal).
• Carotenoids and the visual cycle (1935), Journal of General Physiology 19:351 — Wald showed vitamin A is both the precursor of visual purple and a product of its breakdown, concluding that “the visual processes therefore constitute a cycle.” (He travelled to Paul Karrer’s lab in Zürich to confirm the vitamin A identification.)
• Cis-trans isomers of vitamin A and retinene in the rhodopsin system (1952) by Ruth Hubbard and George Wald, Journal of General Physiology 36:269 — only the 11-cis isomer of retinene combines with opsin to form rhodopsin; light’s sole job is to isomerize it to all-trans, which is what fires the nerve signal.
• Molecular basis of visual excitation (1968), Science 162:230 — Wald’s mature synthesis, written around the 1967 Nobel Prize in Physiology or Medicine that he shared with Ragnar Granit and Haldan Keffer Hartline.

One more experiment from the same era is worth knowing because it pinned down the physical limit of the system:

• Energy, quanta, and vision (1942) by Selig Hecht, Simon Shlaer, and Maurice Pirenne, Journal of General Physiology 25:819 — the dark-adapted human eye can register a handful of photons at threshold, with a single absorbed quantum isomerizing a single rhodopsin molecule. It is the most quantitative demonstration of how sensitive the vitamin A–based pigment is.