Re: Vit. A Poisoning from Liver - Only in the Arctic!

[Guest guest]

Hi Tom,

> So they normally have massive

> amounts of vitamin A in their livers, but I wonder what the vitamin D

> content of the livers of these animals is, knowing that the two

> vitamins are antagonists and inhibit/limit the absorption of each

> other.

This ruffles my feathers to no end every time I hear it, so I'm

wondering where you've gotten it from.

Vitamin D lowers vitamin A levels when it's supplied by UV light, and

they protect against each other's toxicity when they are delivered

through intramuscular injection. The protective effect is very

clearly not dependent on interference of intestinal absorption.

Vitamins A and D have antagonistic, additive, and synergistic roles.

Referring to them simply as " antagonists " is simply not justified by

the molecular literature.

Take, for example, osteocalcin: when osteoblasts are incubated with

retinoic acid (for the benefit of others reading, this is a vitamin A

derivative), they show a very mild increase in osteocalcin expression.

When they are incubated with calcitriol (vitamin D derivative), they

show a similarly mild increase in osteocalcin expression. When they

are incubated with retinoic acid and calcitriol together, they show a

*massive* increase in osteocalcin expression. Is this antagonism?

Recently it was shown that in order for the vitamin D receptor to

carry out its full function, the retinoid X receptor with which it

heterodimerizes (forms a complex sith) must be bound to 9-cis-retinoic

acid (another vitamin a derivative). In fact, in the presence of

9-cis-retinoic acid, even the " defective " vitamin D receptor found in

genetic vitamin D-resistant rickets became fully functional! Is this

antagonism?

In any case, you're definitely on to something by wondering about the

vitamin D content of livers. In land animals it is usually scant, but

in polar bear liver it might be high if the bears are eating a lot of

fish. And then it would, I suppose, depend on what type of fish they

eat. Not sure. There's also other toxic stuff in their livers, I've

read, like cadmium.

Chris

--

The Truth About Cholesterol

Find Out What Your Doctor Isn't Telling You:

http://www.cholesterol-and-health.com

[Guest guest]

Tom,

how much liver/week do you eat? do you eat it raw? if so, how do

you prepare it, if at all? just cut it up and eat it?

>

> Found a very informative article about vitamin A poisoning.

Take a

> look at the tables here and compare the IU per gram of liver of

the

> species listed. Here are some of them:

>

> Vit A IU per gram of food:

> Ox liver 550

> Cod liver oil 600

> Halibut liver oil 30,000

>

> Vit A IU per gram of liver:

> Man 575

> Antarctic huskies 10,570

> Polar bear 24,000-35,000

>

> In a university nutrition class I took and elsewhere, the story of

the

> (Ant)arctic explorers who ate the livers of their sled dogs and/or

> polar bears and died from vitamin A poisoning is oft-repeated.

But

> it's clear to me that it's no risk at all unless you're eating the

> liver of an article carnivore. Yet no one mentions that; the

> implication is that if you eat beef liver and/or CLO daily you're

be

> risking death, LOL.

>

> The article mentions that " Vitamin A originates in marine algae,

and

> then passes up the food chain to reach the large carnivorous

animals.

> Toxic levels of Vitamin A may accumulate in the livers of a wide

range

> of creatures such as Polar bears, seals, porpoises, dolphins,

sharks,

> whales, Arctic foxes and huskies. " So they normally have

massive

> amounts of vitamin A in their livers, but I wonder what the

vitamin D

> content of the livers of these animals is, knowing that the two

> vitamins are antagonists and inhibit/limit the absorption of

each

> other. Anyway, I thought it was interesting.

>

> The article is here:

> http://prof_anil_aggrawal.tripod.com/poiso032.html

>

> Good background on toxicity:

>

http://en.wikipedia.org/wiki/Vitamin_A#Vitamin_A_overdose_.28T

oxicity.29

>

[Guest guest]

> There's also other toxic stuff in their livers, I've

>read, like cadmium.

I actually read somewhere (I was doing a lot of reading about a year and a

half ago so it all kind of runs together and I can't remember what author,

especially since I was extremely anemic at the time so had a perpetual

brain fog going) that the symptoms of those who died after eating the polar

bear livers were nearly identical to that of cadmium poisoning.

~*~*~*~*~*~*~*~*~*~

Canfield

When a church jumps on the world's bandwagon, it is certain that it has

jumped out of God's will. ~ Cloud

" Be not deceived, God is not mocked; for whatsoever a man soweth, that

shall he also reap. " Galatians 6:7

[Guest guest]

> This ruffles my feathers to no end every time I hear it, so I'm

> wondering where you've gotten it from.

Well, the only thing I've read on it is a 2005 paper by DeLuca

entitled simply " All-trans Retinoic Acid Antagonizes the Action of

Calciferol and Its Active Metabolite, 1,25-Dihydroxycholecalciferol,

in Rats " , which is of course focused on the biochemistry at the

receptor level. The study attempted to elucidate the mechanism by

which the " established " antagonism occurs. The last sentence is " In

conclusion, retinol weakly antagonizes calciferol action but does not

do so by affecting the metabolism of calciferol or its active

metabolite 1,25(OH2)D3 through the CYP24 pathway. " And despite the

paper's title, they also concluded that retinyl palmitate (natural

form of A, I believe) as well as ATRA are able to antagonize the

action of ergo- and cholecalciferol in vivo. If you can't find the

paper I can look for it and send it to you.

> Vitamin D lowers vitamin A levels when it's supplied by UV light, and

> they protect against each other's toxicity when they are delivered

> through intramuscular injection. The protective effect is very

> clearly not dependent on interference of intestinal absorption.

>

> Vitamins A and D have antagonistic, additive, and synergistic roles.

> Referring to them simply as " antagonists " is simply not justified by

> the molecular literature.

>

> Take, for example, osteocalcin: when osteoblasts are incubated with

> retinoic acid (for the benefit of others reading, this is a vitamin A

> derivative), they show a very mild increase in osteocalcin expression.

> When they are incubated with calcitriol (vitamin D derivative), they

> show a similarly mild increase in osteocalcin expression. When they

> are incubated with retinoic acid and calcitriol together, they show a

> *massive* increase in osteocalcin expression. Is this antagonism?

>

> Recently it was shown that in order for the vitamin D receptor to

> carry out its full function, the retinoid X receptor with which it

> heterodimerizes (forms a complex sith) must be bound to 9-cis-retinoic

> acid (another vitamin a derivative). In fact, in the presence of

> 9-cis-retinoic acid, even the " defective " vitamin D receptor found in

> genetic vitamin D-resistant rickets became fully functional! Is this

> antagonism?

Interesting stuff...you know way more about this than I do. The

biochemistry of it is so complex as to bore me!

> In any case, you're definitely on to something by wondering about the

> vitamin D content of livers. In land animals it is usually scant, but

> in polar bear liver it might be high if the bears are eating a lot of

> fish. And then it would, I suppose, depend on what type of fish they

> eat. Not sure. There's also other toxic stuff in their livers, I've

> read, like cadmium.

>

> Chris

I see. Well, based on the " weak " antagonism and separate synergistic

effects of vits. A and D that you mentioned, it seems to me that the

only real issue is the massive amounts of vit. A in these arctic

animals' livers. I have a hard time believing there is enough

naturally occurring cadmium in a polar bear's diet to be acutely toxic

to a human consuming it. At least at the time of these explorers in

the 19th and early 20th centuries; perhaps today there's nuclear

testing or waste dumping going on up there.

Tom

[Guest guest]

Tom,

> Well, the only thing I've read on it is a 2005 paper by DeLuca

> entitled simply " All-trans Retinoic Acid Antagonizes the Action of

> Calciferol and Its Active Metabolite, 1,25-Dihydroxycholecalciferol,

> in Rats " , which is of course focused on the biochemistry at the

> receptor level. The study attempted to elucidate the mechanism by

> which the " established " antagonism occurs. The last sentence is " In

> conclusion, retinol weakly antagonizes calciferol action but does not

> do so by affecting the metabolism of calciferol or its active

> metabolite 1,25(OH2)D3 through the CYP24 pathway. " And despite the

> paper's title, they also concluded that retinyl palmitate (natural

> form of A, I believe) as well as ATRA are able to antagonize the

> action of ergo- and cholecalciferol in vivo. If you can't find the

> paper I can look for it and send it to you.

I have the paper. It seems to me that the conclusion that vitamin A

antagonises (with respect to the specific endpoint measured) vitamin D

through some mechanism other than initiating its degradation by

stimulating its 24-hyroxylation is a giant leap away from the

conclusion that its action is mediated by interference with intestinal

absorption.

> Interesting stuff...you know way more about this than I do. The

> biochemistry of it is so complex as to bore me!

Probably bores you like looking at the medically relevant endpoints

without understanding the biochemistry bores me ;-)

> I see. Well, based on the " weak " antagonism and separate synergistic

> effects of vits. A and D that you mentioned, it seems to me that the

> only real issue is the massive amounts of vit. A in these arctic

> animals' livers. I have a hard time believing there is enough

> naturally occurring cadmium in a polar bear's diet to be acutely toxic

> to a human consuming it. At least at the time of these explorers in

> the 19th and early 20th centuries; perhaps today there's nuclear

> testing or waste dumping going on up there.

I think the amount of vitamin D *is* also relevant and I agree with

your initial observation, just not the biochemical details. Vitamin D

is highly protective against vitamin A toxicity, regardless of whether

it interferes with the intestinal absorption or not.

I have no idea whether there is sufficient cadmium or not, but it was

suggested in an article (I think on the WAPF site) so I thought I'd

throw it up for conversation.

Chris

--

The Truth About Cholesterol

Find Out What Your Doctor Isn't Telling You:

http://www.cholesterol-and-health.com

[Guest guest]

Chris-

>There's also other toxic stuff in their livers, I've

>read, like cadmium.

In fact, I've read that the symptoms of cadmium toxicity are exactly

those observed in people who supposedly suffered from vitamin A

toxicity upon eating polar bear livers. The speculation was that the

cadmium and not the vitamin A was responsible, but I have no idea

whether that's actually true.

-

[Guest guest]

Tom-

>I have a hard time believing there is enough

>naturally occurring cadmium in a polar bear's diet to be acutely toxic

>to a human consuming it. At least at the time of these explorers in

>the 19th and early 20th centuries;

Volcanos can actually spew out quite a bit of cadmium, and stuff

tends to accumulate up north.

That said, the minimum lethal dose for humans is on the order of

350mg according to this source.

<http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/group29/cadtox.htm>

Polar bear livers apparently don't contain nearly that much

cadmium.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=\

10682354 & dopt=Abstract>

I'm not sure how much a whole liver weighs, but it would take regular

consumption to reach a toxic dose. OTOH, eating some polar bear

kidneys could do the job a lot faster. While livers only had as much

as 1.98 micrograms per gram, kidneys had as much as 28.9.

There's another factor to consider, too: cadmium increases cell

membrane permeability, thus boosting transport of other toxic metals

into the cell if present. Polar bear organs also concentrate mercury

and other undesirables.

That still doesn't mean humungaloid doses of vitamin A aren't a bad

thing, though.

-

[Guest guest]

> Tom,

>

> I have the paper. It seems to me that the conclusion that vitamin A

> antagonises (with respect to the specific endpoint measured) vitamin D

> through some mechanism other than initiating its degradation by

> stimulating its 24-hyroxylation is a giant leap away from the

> conclusion that its action is mediated by interference with intestinal

> absorption.

>

So you're saying that vitamin D status (serum and liver levels?) is

what counts, not the amount of vitamin D consumed simultaneously with

vitamin A? I see your point. But unless you're focusing on a single

meal, it would seem that consuming high amounts of both vitamin A and

D will keep levels of both high enough to see some internal

antagonism. I'm not gonna try to go beyond that because my level of

knowledge isn't enough to make it worth our time.

>

> > Interesting stuff...you know way more about this than I do. The

> > biochemistry of it is so complex as to bore me!

>

> Probably bores you like looking at the medically relevant endpoints

> without understanding the biochemistry bores me ;-)

>

Probably. I suspect that there are two main types of scientists (or

scientifically minded people): those who revel in the minutiae and

intricacies of life since they are more concrete, and those who love

seeing the big picture and making new connections and coming to

greater understanding based on the emergent properties that appear

with the sum of the parts. I am one of the latter type. To pre-empt

your response, I wouldn't be surprised if you see yourself as both,

but if you're that interested in biochemical pathways and mechanisms,

you are one of the former type IMO. Both types of people, of course,

are important and it's merely a generalization.

> I think the amount of vitamin D *is* also relevant and I agree with

> your initial observation, just not the biochemical details. Vitamin D

> is highly protective against vitamin A toxicity, regardless of whether

> it interferes with the intestinal absorption or not.

>

> I have no idea whether there is sufficient cadmium or not, but it was

> suggested in an article (I think on the WAPF site) so I thought I'd

> throw it up for conversation.

>

> Chris

Hmm, I really don't remember specifying that I thought the antagonism

was intestinal in nature. But I'm too lazy to go back and check. Sorry

if I gave that impression; I was trying to get at a general antagonism

at some point in the body. I certainly don't pretend to know the details.

Tom

[Guest guest]

On 9/22/06, Tom Jeanne <tjeanne@...> wrote:

> > I have the paper. It seems to me that the conclusion that vitamin A

> > antagonises (with respect to the specific endpoint measured) vitamin D

> > through some mechanism other than initiating its degradation by

> > stimulating its 24-hyroxylation is a giant leap away from the

> > conclusion that its action is mediated by interference with intestinal

> > absorption.

> So you're saying that vitamin D status (serum and liver levels?) is

> what counts, not the amount of vitamin D consumed simultaneously with

> vitamin A?

Well yes that's most likely to be true, but no that's not what I was

saying. The 24-hydroxylase (CYP24 or whatever they called it)

" degrades " calcitriol (the active form of vitamin D) into

1,24,25-(OH)3-D, although it is controversial whether or not this form

is truly " inactive. " Some had speculated, from rather poor evidence,

that vitamin A stimulates this enzyme and that it " antagonizes "

vitamin D by inducing its degradation. DeLuca et al. found that

unlikely to be the cause of the " antagonism " observed in their study.

This does NOT mean that they inhibit each other's absorption! There

is no connection there whatsoever. " Vitamin A does not antagonize

vitamin D by stimulating it's degradation, therefore, it inhibits its

intestinal absorption. " The latter is not in any way whatsoever a

corollary of the former.

> I see your point. But unless you're focusing on a single

> meal, it would seem that consuming high amounts of both vitamin A and

> D will keep levels of both high enough to see some internal

> antagonism. I'm not gonna try to go beyond that because my level of

> knowledge isn't enough to make it worth our time.

You will see antagonism as well as cooperative action, synergism, and

so on. The description of them as " antagonists " was what I was

objecting to in the first place.

> Probably. I suspect that there are two main types of scientists (or

> scientifically minded people): those who revel in the minutiae and

> intricacies of life since they are more concrete, and those who love

> seeing the big picture and making new connections and coming to

> greater understanding based on the emergent properties that appear

> with the sum of the parts. I am one of the latter type.

I don't think there are two types of scientists, but maybe those are

two types of science. I think that any scientist would fall somewhere

on a spectrum of enjoying one, the other (the two poles of the

spectrum), or both to varying degrees (the large area in the middle).

> To pre-empt

> your response, I wouldn't be surprised if you see yourself as both,

> but if you're that interested in biochemical pathways and mechanisms,

> you are one of the former type IMO. Both types of people, of course,

> are important and it's merely a generalization.

So long as you're making up the definitions, I suppose I can't object

to my placement within them.

> > I think the amount of vitamin D *is* also relevant and I agree with

> > your initial observation, just not the biochemical details. Vitamin D

> > is highly protective against vitamin A toxicity, regardless of whether

> > it interferes with the intestinal absorption or not.

> > I have no idea whether there is sufficient cadmium or not, but it was

> > suggested in an article (I think on the WAPF site) so I thought I'd

> > throw it up for conversation.

> Hmm, I really don't remember specifying that I thought the antagonism

> was intestinal in nature. But I'm too lazy to go back and check.

Having Gmail, I will spend the three seconds required of me:

" So they normally have massive

amounts of vitamin A in their livers, but I wonder what the vitamin D

content of the livers of these animals is, knowing that the two

vitamins are antagonists and inhibit/limit the absorption of each

other. "

I assume that by " inhibit/limit the absorption of each other " you mean

at the intestinal level, which is what one would usually mean by the

phrase.

> Sorry

> if I gave that impression; I was trying to get at a general antagonism

> at some point in the body. I certainly don't pretend to know the details.

What " ruffles my feathers " is the assumption that because they protect

against each other's toxicity they " antagonize " each other. They do,

in fact, antognize each other in certain respects, but they act

additively and synergistically in other respects. What bothers me

about the assumption that because they protect against each other's

toxicity they must inhibit each other's activity is that it is stuck

in the paradigm that the toxicity is due to " too much " of either, per

se.

Of course, I believe you can get too much of anything. But you start

seeing toxicity with either vitamin long before you reach what I would

believe to be the point of " too much. " If you add vitamin D to

vitamin A, you will not simply inhiibit vitamin A's activity. In some

respects, you are going to dramatically increase vitamin A's activity.

Yet you still protect against the toxicity. Since many of their

functions are cooperative -- i.e. you need both to get some given

thing done -- some of their toxicity is probably attributable to

imbalance, rather than " too much " per se. So in those cases you can

protect against toxicity through synergism rather than antagonism.

Chris

--

The Truth About Cholesterol

Find Out What Your Doctor Isn't Telling You:

http://www.cholesterol-and-health.com

[Guest guest]

> I don't think there are two types of scientists, but maybe those are

> two types of science. I think that any scientist would fall somewhere

> on a spectrum of enjoying one, the other (the two poles of the

> spectrum), or both to varying degrees (the large area in the middle).

Point taken; a continuum is the best way to picture it.

> What " ruffles my feathers " is the assumption that because they protect

> against each other's toxicity they " antagonize " each other. They do,

> in fact, antognize each other in certain respects, but they act

> additively and synergistically in other respects. What bothers me

> about the assumption that because they protect against each other's

> toxicity they must inhibit each other's activity is that it is stuck

> in the paradigm that the toxicity is due to " too much " of either, per

> se.

>

> Of course, I believe you can get too much of anything. But you start

> seeing toxicity with either vitamin long before you reach what I would

> believe to be the point of " too much. " If you add vitamin D to

> vitamin A, you will not simply inhiibit vitamin A's activity. In some

> respects, you are going to dramatically increase vitamin A's activity.

> Yet you still protect against the toxicity. Since many of their

> functions are cooperative -- i.e. you need both to get some given

> thing done -- some of their toxicity is probably attributable to

> imbalance, rather than " too much " per se. So in those cases you can

> protect against toxicity through synergism rather than antagonism.

I'm afraid at the start of our discussion I had a foggy idea of the

interactions between the two vitamins, and so I used the term

" antagonism " to describe what I was recalling from your A & D articles

in Wise Traditions. I used that word because I'd recently read that

paper and it seemed apt, but it was anything but. You've succinctly

shown that their interactions are much more complex than mere

antagonism or synergism.

Sorry that I'm not up to speed with discussion on NN most of the time

and my word choice usually ends up being more informal and careless

than you'll let me get away with. But thanks, your last two paragraphs

quoted above are very informative. The idea of imbalance seems to be

at the heart of it.

Tom

[Guest guest]

Tom,

> Sorry that I'm not up to speed with discussion on NN most of the time

> and my word choice usually ends up being more informal and careless

> than you'll let me get away with. But thanks, your last two paragraphs

> quoted above are very informative. The idea of imbalance seems to be

> at the heart of it.

No need for an apology. I was just trying to set the record straight

on that particular point.

Chris

--

The Truth About Cholesterol

Find Out What Your Doctor Isn't Telling You:

http://www.cholesterol-and-health.com