Vitamin A is the beginning of a story: the vitamin-story! I also experienced my own vitamin A story which you can read later if you want. Man-kind has explored vitamin A since nearly a century ago. A brief assessment of how much research has been done to understand vitamin A so far is condensed in the graph below. Check out the total number of articles about vitamin A that were published world-wide by scientists each year. It is not coincidental that in 1997 the biggest number of vitamin A articles were published, about 1300. Vitamin A was still of interest later on, but it seems to have lost some “wow” as the decades went by – see why below.

The graph shows the number of publications each year that investigated vitamin A as indexed by PubMed.gov. Explore the graph to learn more about the publication history of vitamin A.

Topics

What is vitamin A?

Don’t feed your cat carrots hoping to improve its night vision! That won’t work…

Vitamin A is an essential nutrient needed in optimal amounts for adequate visual system function, growth and development, cell integrity, immune function, and reproduction. Our body is able to derive vitamin A from a wide range of animal and vegetable sources in the form of precursor molecules that are metabolized to make active vitamin A. For this reason, when referring to “vitamin A intake” most sources count the intake of precursor molecules as vitamin A intake, despite their “precursor” status. Vitamin A, more specifically the precursor molecules, sourced from food are retinyl palmitate and β-carotene. Retinyl palmitate comes from animal sources and β-carotene is absorbed from vegetables (but also from β-carotene enriched foods such as fish meat (especially salmon), cereals, etc). Retinyl palmitate is packed in what are called fat micro-micelles (something like a biological submarine that easily passes through the wall of our gut) can pass through the intestinal mucosa and either get deposited in the liver as retinyl esters or get converted into retinol on the spot for immediate use. Retinol is the actual active form of vitamin A and remains as fat-soluble as retinyl palmitate originally was. It is the wonder of the retinol molecule that it can then travel all the way to the eye and bind to proteins in the eye called opsins to form rhodopsin, the marvelous light-absorbing molecule that is essential for our night vision! Retinol also reaches our skin and integuments contributing to their healthy elasticity and integrity – this is the reason behind an expansive cosmetics market advertising retinol.

From a vegetable source perspective, the orange & yellow carotenoid pigments (namely alpha-, beta-, and gamma-carotene) are all provitamins of vitamin A. To some extent beta-cryptoxanthin is also such a pigment. However, there is something very interesting about these pigments. A certain enzyme called beta-carotene dioxygenase is required to cut the beta-carotene into two molecules of retinol, thus making it usable by the body. Interesting enough, this enzyme is only present in the intestines of herbivores and omnivorous animals. With this in mind, I’d say: “Don’t feed your cat carrots hoping to improve its night vision! That won’t work…” – a cat is a carnivore, it doesn’t have the dioxygenase enzyme.  Chicken liver would work much-much better for the night vision of your purring friend!

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How big is vitamin A?

Retinol is the active form of vitamin A and is composed of 20 carbon atoms, 30 hydrogen atoms and one oxygen atom (C20H30O). The volume of one hydrogen atom is 6.2 x 10-22mm3, the volume of one carbon atom is 1.9 x 10-21mm3, and the volume of an oxygen atom is 9.1 x 10-22mm3. So, assuming inter-molecular forces don’t exist and atoms pack together into perfect spheres, we could add together the volumes of 20 carbon atoms, 30 hydrogens and one oxygen to estimate the volume of one retinol (Vretinol), we get:

20 x 1.9 x 10-21 + 30 x 6.2 x 10-22 + 9.1 x 10-22 =
200 x 1.9 x 10-22 + 30 x 6.2 x 10-22 + 9.1 x 10-22 =
(200 x 1.9 + 30 x 6.2 + 9.1) x 10-22 =
(380 + 186 + 9.1) x 10-22 =
575.1 x 10-22 =
Vretinol = 5.751 x 10-20 mm3

That is about 5.75 hundredths of a millionth of a trillionth of 1 mm3. Which means one retinol molecule is still ~100 times bigger than one atom of hydrogen. So, if I were to compare the size of a retinol molecule to the tip of a sewing needle – which, according to needle manufacturers, is supposed to have a diameter of 0.1mm – retinol would be to a needle tip what a big whale would be to the entire volume of Indian Ocean.

If we would take 6.023 x 1023 molecules, also called a mole, of retinol, they would weigh a combined grand total of ~286.45 grams, a little more than 1/2 a pound.

About the other forms of vitamin A, like retinal or retinoic acid, we can safely estimate their volume is within a similar size ball-park as retinol. The exception would be beta-carotene which basically counts as two molecules of pre-retinol. Therefore, its volume would be about twice that of retinol. So, Beta-carotene will be to the needle tip what 2,000 people swimming together would be to the Indian Ocean.

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Does vitamin A impact cancer risk?

The history of vitamin A studies in cancer is a sad one. Since the day scientists proved its antioxidant properties, lots of hope was invested in vitamin A. Since cancer occurrence has been attributed mostly to reactive oxygen species, clinicians and researchers thought that an antioxidant molecule such as vitamin A will be an ideal cancer prevention agent! Although known for over 50 years, vitamin A did not enter the spot-light until the 1980s together with vitamin E (another antioxidant vitamin). For nearly two decades, the number of published articles studying vitamin A in cancer sky-rocketed to the maximum ever reached: just over 600 in a single year, back in 1994. That year was not just any year in vitamin A research history. It was the year when the first and biggest chemoprevention prospective study, the ATBC clinical trial, released its very first set of information. Closed in 1993, the ATBC study not only yielded itself a considerable wave of publications but also triggered a considerable wave from others. But the news of beta-carotene – a vitamin A precursor – increasing lung cancer risk in male smokers led to a decrease in research related to vitamin A or retinol in relationship to cancer. The bar graph below stands as clear proof to the progressive decrease in the research efforts related to vitamin A and cancer. One may easily notice that last year (2016), less than 300 paper articles were published on this topic, meaning less than half of the number of reports published two decades ago.

In a way, vitamin A fell in disgrace. I will discuss more about the strong and the weak reasons behind the impact generated by the ATBC study on the world-wide research investigating vitamin A: follow my posts to learn more!

The graph shows the number of publications each year that investigated the effect of vitamin A on cancer as indexed by PubMed.gov. Explore the graph to learn more about the publication history of vitamin A’s effect on cancer.

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Does vitamin A impact type II diabetes mellitus?

Type II diabetes mellitus, also known as acquired diabetes, is a common condition that affects hundreds of millions of people around the world.

The graph shows the number of publications each year that investigated the effect of vitamin A on type II diabetes mellitus as indexed by PubMed.gov. Explore the graph to learn more about the publication history of vitamin A’s effect on diabetes mellitus.

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Global Vitamin A deficiency monitoring as reported by WHO

The map shows the global vitamin A deficiency surveillance as indexed by the World Health Organization. Click or hover over any country on the map to learn more about the studies conducted in the respective country that year. Provided legend shows the normal vitamin A range in green.

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