Hi, your friendly, local pathologist here. I'm the kind of doctor that diagnoses liver diseases, cancer, lots of infections, inflammatory processes, benign tumors, and runs the lab that a lot of other doctors use the results from to inform a lot of their other decisions.
If you really want to learn about this stuff, Robert Weinberg's The Biology of Cancer is where to start. It introduces concepts starting where a high school student could understand and carefully walks through the history of our development of knowledge until, by the end, the pithy chapters are helping novel concepts for real science flower in your brain all on their own. It's the best book of biological science I have ever read. 10/10, will read again.
Pathology... reminds me of all those studies with accident victims all over the world (and often as early as the 70s - today's numbers are likely much worse) that show 30% or half the population being liver-toxic in vitamin A (in all age groups). Lots of health problems are simply downstream from that.
Consuming lots of dairy (including fortified), lots of colorful veggies every single day year round, maybe adding multivitamins, fortified flour. Then there's the liver hype in some circles.
Your Wikipedia page references a paper in footnote 21 which says:
> "In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods"
and
> "Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons"
Google tells me that "Two pathways have been suggested for the conversion of carotenoids to vitamin A in mammals, central cleavage and excentric cleavage".
Carotene conversion cannot both be "a minor contributor" to body levels of Vitamin A and also the main way billions of people get Vitamin A. So my guess is the Wikipedia page has mistakenly taken 'excentric cleavage' to be the only conversion method. Still, ignoring carotenes entirely, the referenced paper also says:
> "observational studies suggest that more than 75% of people may be routinely ingesting more than the recommended dietary allowance (RDA) for vitamin A"
> "Dietary vitamin A is obtained from preformed vitamin A (ie, retinyl esters from animal foods, fortified foods, and pharmaceutical supplements) as well as from provitamin A carotenoids from plant sources. Preformed vitamin A is efficiently absorbed and utilized by humans at absorption rates of 70–90%. Up to 75% of dietary vitamin A in Europe, the United States, and other industrialized nations is preformed vitamin A (1, 2), which is largely derived from multivitamins, fish liver oil, and the fortification of foods such as milk, butter, margarine, breakfast cereals, and some snack foods. In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods. These are absorbed much less efficiently, at rates of 20–50%, depending on each person’s vitamin A status and other dietary and nondietary factors (3, 4). The cleavage of provitamin A carotenoids to retinal is a highly regulated step, and vitamin A toxicity from provitamin A sources is largely impossible. In contrast, absorption and hepatic storage of preformed vitamin A occur very efficiently until a pathologic condition develops."
Indeed, but they neither explain nor cite what they mean for it to be "highly regulated" or how/why that means toxicity is largely impossible.
If you take "the cleavage of provitamin A carotenoids" and Ctrl+F for 'cleavage' or 'carotene' in that paper, the only other mentions are this:
> "An acute elevation of retinoids other than retinyl esters—eg, retinoic acid—occurs after the ingestion of a large amount of vitamin A, possibly because the intestinal absorptive capacity is overwhelmed, which leads to the oxidation of retinol to retinoic acid by the intestinal enterocytes (30) and to the rapid formation of retinoic acid from retinol in certain cells (5). Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons."
That is, they only seem to be talking about excentric cleavage and not central cleavage. My limited understanding is that beta-carotene is roughly two retinoic acid molecules chained together, and cleaving them in half is what makes two retinoic acid molecules, and that non-central-cleaving would be different. See skeletal formula on right for these two pages:
(You can also wonder if beta carotene can produce 90% of circulating vitamin A in developing countries, whether getting lots of beta carotene in developed countries can raise the base level in the body, which then leads to easier overdose from preformed vitamin A)
0xWTF · · focus · HN ↗
If you really want to learn about this stuff, Robert Weinberg's The Biology of Cancer is where to start. It introduces concepts starting where a high school student could understand and carefully walks through the history of our development of knowledge until, by the end, the pithy chapters are helping novel concepts for real science flower in your brain all on their own. It's the best book of biological science I have ever read. 10/10, will read again.
<a href="https://wwnorton.com/books/9780393887655" rel="nofollow">https://wwnorton.com/books/9780393887655
hobo123 · · focus · HN ↗
Melatonic · · focus · HN ↗
hobo123 · · focus · HN ↗
theoreticalmal · · focus · HN ↗
From Wikipedia
<a href="https://en.wikipedia.org/wiki/Hypervitaminosis_A" rel="nofollow">https://en.wikipedia.org/wiki/Hypervitaminosis_A
jodrellblank · · focus · HN ↗
> "In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods"
and
> "Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons"
Google tells me that "Two pathways have been suggested for the conversion of carotenoids to vitamin A in mammals, central cleavage and excentric cleavage".
Carotene conversion cannot both be "a minor contributor" to body levels of Vitamin A and also the main way billions of people get Vitamin A. So my guess is the Wikipedia page has mistakenly taken 'excentric cleavage' to be the only conversion method. Still, ignoring carotenes entirely, the referenced paper also says:
> "observational studies suggest that more than 75% of people may be routinely ingesting more than the recommended dietary allowance (RDA) for vitamin A"
yorwba · · focus · HN ↗
> "Dietary vitamin A is obtained from preformed vitamin A (ie, retinyl esters from animal foods, fortified foods, and pharmaceutical supplements) as well as from provitamin A carotenoids from plant sources. Preformed vitamin A is efficiently absorbed and utilized by humans at absorption rates of 70–90%. Up to 75% of dietary vitamin A in Europe, the United States, and other industrialized nations is preformed vitamin A (1, 2), which is largely derived from multivitamins, fish liver oil, and the fortification of foods such as milk, butter, margarine, breakfast cereals, and some snack foods. In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods. These are absorbed much less efficiently, at rates of 20–50%, depending on each person’s vitamin A status and other dietary and nondietary factors (3, 4). The cleavage of provitamin A carotenoids to retinal is a highly regulated step, and vitamin A toxicity from provitamin A sources is largely impossible. In contrast, absorption and hepatic storage of preformed vitamin A occur very efficiently until a pathologic condition develops."
jodrellblank · · focus · HN ↗
If you take "the cleavage of provitamin A carotenoids" and Ctrl+F for 'cleavage' or 'carotene' in that paper, the only other mentions are this:
> "An acute elevation of retinoids other than retinyl esters—eg, retinoic acid—occurs after the ingestion of a large amount of vitamin A, possibly because the intestinal absorptive capacity is overwhelmed, which leads to the oxidation of retinol to retinoic acid by the intestinal enterocytes (30) and to the rapid formation of retinoic acid from retinol in certain cells (5). Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons."
That is, they only seem to be talking about excentric cleavage and not central cleavage. My limited understanding is that beta-carotene is roughly two retinoic acid molecules chained together, and cleaving them in half is what makes two retinoic acid molecules, and that non-central-cleaving would be different. See skeletal formula on right for these two pages:
<a href="https://en.wikipedia.org/wiki/%CE%92-Carotene" rel="nofollow">https://en.wikipedia.org/wiki/%CE%92-Carotene
<a href="https://en.wikipedia.org/wiki/Retinoic_acid" rel="nofollow">https://en.wikipedia.org/wiki/Retinoic_acid
(You can also wonder if beta carotene can produce 90% of circulating vitamin A in developing countries, whether getting lots of beta carotene in developed countries can raise the base level in the body, which then leads to easier overdose from preformed vitamin A)