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DiscussionLet's talk about it: The science of itReversible Hepatotoxicity

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Reversible Hepatotoxicity

#1 · May 29, 2019, 11:37 am

@ggenereux2014

Interesting case study from the 1970s linked, question came up in another forum, how the patient was able to deplete so much vitamin A, without it seems bad reactions...

https://www.gastrojournal.org/article/0016-5085(82)90132-9/pdf

"A study about vitamin a depletion in a old man who had hypervitaminosis A. It showed that RBP was greatly inhibited by protein deficiency and that eating 120 grams a protein a day causes RBP and vitamin a serum to rise. While on the high protein diet (58 days) they estimated the daily vitamin a being depleted was 226,000 iu daily."

Bella and tim have reacted to this post.

#2 · May 29, 2019, 8:20 pm

We should all start drinking protein shakes maybe.

#3 · May 30, 2019, 5:03 pm

Quote from tim on May 30, 2019, 5:03 pm
If the study isn't flawed he was losing over 1% of total liver retinol stores per day which is plausible.

The study claims he was losing this much VA eating between 4000 and 20000 IU of VA per day.

It's implying that protein consumption is more important for VA detox than VA intake, at least in this man's case. Maybe when the liver is extremely overloaded then that is true.

As his liver stores started to get lower I would speculate it would probably get harder to lower them further with that VA intake.

For some unexplained reason the man did not have fully saturated RBP and did not experience hypervitaminosis symptoms?!

He was protein deficient and when his protein consumption was increased the serum VA levels went up. He didn't get hypervitaminosis during detox though:

During his course, both serum vitamin A and RBP slowly
rose. By the tenth week serum vitamin A reached its
highest level. Retinol-binding protein was saturated at this
point, but both serum vitamin A and the vitamin A/RBP
ratio subsequently fell, and peripheral vitamin A toxicity
never appeared.

Pretty confusing why most of us probably have much lower liver stores but probably have much more RA in tissues causing harm.

I guess there are complex biochemical and genetic reasons for this difference.

I think we will find that there are genetic differences between how we process retinol in the body.

Perhaps there are genetic adaptations in some members of certain ethnicities that cause them to be more sensitive to VA. In certain areas, the vast majority of Europeans in the past were eating primarily grains and legumes for long periods of history.

https://en.wikipedia.org/wiki/Food_and_dining_in_the_Roman_Empire

Most people would have consumed at least 70 percent of their daily calories in the form of cereals and legumes.

They possibly acquired adaptations to store iron and Vitamin A more and utilize these scarce nutrients in more efficient ways.

Below is a study that discusses adaptions in retinoid metabolism in Africans to protect against disease:

https://www.sciencedirect.com/science/article/pii/S0306987713003939

In sum exposure to malaria parasites may have led to a tendency among sub-Saharan Africans in their ancestral geographic and nutritional environment to accumulate less vitamin A and to store it more efficiently in the liver than inhabitants of areas of lesser exposure, thereby rendering them less prone to DHF, and to death from yellow fever.

I think we will find there are genetic differences determining how we process different types of carotenoids, store retinol, excrete retinol and produce retinoic acid.

If the study isn't flawed he was losing over 1% of total liver retinol stores per day which is plausible.

The study claims he was losing this much VA eating between 4000 and 20000 IU of VA per day.

It's implying that protein consumption is more important for VA detox than VA intake, at least in this man's case. Maybe when the liver is extremely overloaded then that is true.

As his liver stores started to get lower I would speculate it would probably get harder to lower them further with that VA intake.

For some unexplained reason the man did not have fully saturated RBP and did not experience hypervitaminosis symptoms?!

He was protein deficient and when his protein consumption was increased the serum VA levels went up. He didn't get hypervitaminosis during detox though:

During his course, both serum vitamin A and RBP slowly
rose. By the tenth week serum vitamin A reached its
highest level. Retinol-binding protein was saturated at this
point, but both serum vitamin A and the vitamin A/RBP
ratio subsequently fell, and peripheral vitamin A toxicity
never appeared.

Pretty confusing why most of us probably have much lower liver stores but probably have much more RA in tissues causing harm.

I guess there are complex biochemical and genetic reasons for this difference.

I think we will find that there are genetic differences between how we process retinol in the body.

Perhaps there are genetic adaptations in some members of certain ethnicities that cause them to be more sensitive to VA. In certain areas, the vast majority of Europeans in the past were eating primarily grains and legumes for long periods of history.

https://en.wikipedia.org/wiki/Food_and_dining_in_the_Roman_Empire

Most people would have consumed at least 70 percent of their daily calories in the form of cereals and legumes.

They possibly acquired adaptations to store iron and Vitamin A more and utilize these scarce nutrients in more efficient ways.

Below is a study that discusses adaptions in retinoid metabolism in Africans to protect against disease:

https://www.sciencedirect.com/science/article/pii/S0306987713003939

In sum exposure to malaria parasites may have led to a tendency among sub-Saharan Africans in their ancestral geographic and nutritional environment to accumulate less vitamin A and to store it more efficiently in the liver than inhabitants of areas of lesser exposure, thereby rendering them less prone to DHF, and to death from yellow fever.

I think we will find there are genetic differences determining how we process different types of carotenoids, store retinol, excrete retinol and produce retinoic acid.

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#4 · May 31, 2019, 5:01 am

Thanks @tim-2 good perspective. I think less glyphosate in the 1970s environment probably helped as well. But yes really strange that no side effects were mentioned or discussed.

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#5 · June 2, 2019, 12:55 pm

How the heck does one eat 120 grams of protein a day? I wonder what he ate.. I struggle with getting 60+ grams a day, except for when I am having a meat frenzy which is ridivulously expensive and undoable on a daily basis 😂

Protein powder would be a logically solution. But what kind? Except maybe oat protein (fairly new here)...?

#6 · June 2, 2019, 4:45 pm

@orion thanks, yeah glyphosate is a good point.

@liz yeah I know right, 120 grams is about 1.5 chickens!

One other thing from the study:

The ingestion of
substantial amounts of sweet potatoes, carrots, peaches,
tomatoes, and dessicated beef liver accounted for this high
dietary vitamin A intake.

They didn't make the claim that carotenoids would not be converted due to sufficient liver VA stores... 😉

Does anyone know what the backing is for that assertion that is bandied about everywhere?

Reversible Hepatotoxicity

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