I've sent Gordon R. my posts on protein, vitamin C and vitamin A prior to
posting on internet as a professional courtesy.  Somehow I've managed to
delete my vitamin A post from my text file.  Gordon R. had promised to send
it back to me but he's pretty mad at me right now so I'll just retype it.
Since digging through all my references is very time consuming(took me all
day for that PMS post), I'm not going to cite any references(Gordon R. has
them).  I'm going to include some of the material from Weinsier and
Morgan's new Nutrition textbook(which was not in my original material) to
point out that what I'm going to say has some support in the medical
community.

Diet has been know to affect the immune system of man for a very, very long
time.  Protein has always had the biggest role in infection and I've
already covered the role of protein in protecting you against infection.
Now I'm going to hit what I consider to be the most important nutrient in
the U.S. as far as infection is concerned(vitamin A).

When vitamin A was originally discovered, it was commonly referred to as
the anti-infection vitamin.  Many people(Linus Pauling being one) have
decided to take this title away from vitamin A and give it to vitamin C
(which I've already covered).  Big mistake(in my opinion).  Vitamin A is
also getting a reputation as an anti-cancer vitamin(with good reason).
The NCI currently has numerous clinical trials in progress to see if
vitamin A can not only prevent cancer but cure it as well.  It's role in
both cancer and infection is almost identical(but not quite).

Vitamin A comes in two completely different forms(retinol and
beta-carotene).  Retinol is the animal form and it's toxic, beta-carotene
is the plant form and it's completely nontoxic.  Both retinol and beta-
carotene display good absorption in the human gut if bile is present
(60-80%).  The liver stores all of your retinol and doles it out for other
tissues to use by synthesizing retinol binding protein(RBP).  A normal human
{*filter*} liver should have 500,000IU to 1,000,000IU of retinol stored.  We
are born with 10,000IU in our liver.  U.S. autopsy has shown that about
30% of Americans die with the same(or less) amount of vitamin A as they
were born with.  If you don't believe that nutritional reserves(like that
of retinol in the liver) are important, then this low vitamin A reserve is
not going to affect you.  But if you believe(like I do) that the nutrient
reserves are important, then there is a problem with vitamin A in the U.S.

The U.S. RDA for vitamin A in an {*filter*} male is 1,000 RE or 5,000IU of
vitamin A.  For {*filter*} feamles its 800 RE or 4,000IU of vitamin A.  Diet
surveys show that most Americans are getting this amount of vitamin A
(either retinol or Beta-carotene) from their diet.  But the NRC(National
Research Council) was going to release a new RDA table in 1985 that had the
RDA for both vitamin A and vitamin C raised(C to 90mg per day and A to
7,500IU per day for {*filter*} males).  That report and it's recommendations was
killed.  Why? Concern over the increasing supplementation was the main
reason.  RDAs are set to prevent clinical disease, not to keep nutrient
reserves full.  Many scientist in the U.S. feel that the time has come to
move away from the prevention of clinical pathology concept and move
towards the promotion of optimum health concept, especially since we have
some very good data now that show that nutrient reserves are extremely
important during periods of stress.  The nutritonal concervatives won that
battle and a new group of scientist were collected to come out with the
1989 RDA list which lowered the RDA for several nutrients and moved the
dietary guidelines back to where they were when we first started in the
1940's(get enough to prevent clinical pathology, but not enough to fill
the reserves).

We know from autopsy that only about 10% of Americans have a liver with a
normal vitamin A reserve(500,000IU to 1,000,000IU).  I preach nutrient
reserves to my students and tell them to measure them in their patients.
But for vitamin A, only a liver biopsy(or autopsy data) will tell you how
much somebody has stored.  We can tell very easily if someone has
overfilled his or her liver with vitamin A by measuring the serium retinol
level(levels above 450ug/dl are highly suggestive that you have filled your
liver with vitamin A and it's time to stop taking retinol).  The normal
range of serum retinol will be 20-100ug/dl.  Hypervitaminosis A is
diagnosed with a serum retinol level of 2,000ug/dl or higher(Interpretation
of Diagnostic Test, Wallach, M.D., a Little Brown Series book).  This level
of vitamin A in {*filter*} means that medical attention is necessary due to
vitamin A toxicity.  Weinsier and Morgan take a much more conservative
approach to vitamin A toxicity than does Wallach, as you will see later in
this post.  Between 450ug/dl and 2,000ug/dl you should have plenty
of warning that it's time to eliminate the retinol from your diet(headache,
redness of the skin, hair loss, joint pain).

I tell all my students that will use vitamin A in their practice that they
had better monitor the serum retinol level and stop when there are clear
signs that the liver is full.  You will never really know if the patient
needs the vitamin A(because you can not measure the pool in liver) but you
will always know when it's time to stop(just like in those vitamin A for
PMS studies).

Beta-carotene can be taken to fill up your liver with retinol and you will
never have to worry about toxicity because the conversion of beta-carotene to
retinol that occurs in both your gut and your liver will slow down(stops in the
liver and slows down in the gut) when your liver is full of retinol.  But
taking Beta-carotene as the source of retinol takes a very long time to
fill the liver up(I've seen estimates of 20-30 years) if you are in the 30%
that only has as much as you were born with in your liver(10,000IU).  One
other problem with beta-carotene, if you have a zinc deficit, you will not
convert as much beta-carotene to retinol in the gut or the liver because the
enxzyme that does this conversion requires zinc.  In addition, the release of
retinol from the liver is a zinc dependent process so a zinc deficit will
cause a vitamin A deficit even if your liver has plenty of vitamin A.

Now what does vitamin A do in cancer and infection protection?  The body
uses vitamin A(retinol) for many different things.  Vision(the first to be
nailed down and where you see overt clinical pathology) uses the aldehyde
(retinal) and {*filter*}(retinol) form of vitamin A.  Reproduction uses the
retinol form  and some retinal.  Infection and cancer protection uses
retinoic acid.  How do you convert retinol(which your white {*filter*} cells
and the mucosal cells get from {*filter*}) to retinoic acid?  You use enzymes,
one of which requires vitamin C(this is why Pauling has tried to pull the
title of anti-infection vitamin away from vitamin A).  Vitamin C does play
a role in infection(interferon production for example) but it's biggest role
is the conversion of retinol to retinoic acid.  If you increase your intake
of vitamin C, you will increase your formation of retinoic acid.  But
retinoic acid can not be converted back to retinol(as retinal can) and once
it's formed, it's used and then lost to the body.  This is why the 1985 NRC
group wanted to increase both vitamin C and vitamin A RDA's.

Most people taking large amounts of vitamin C really think that they are
helping themselves.  If they don't have much vitamin A in their liver and
they are not also increasing their intake of vitamin A, they actually do
themselves more harm than good.

Retinoic acid functions in white {*filter*} cells to promote antibody formation.
In the mucus membrane, it is the main factor in promoting good mucus
production and a good epithelial cell barrier to prevent infectious agents from
entering the {*filter*} system.  The mucus membrane is referred to as the "first
line" defense against infection.  For cancer, retinoic acid has been shown
to act as a cell brake(it counteracts the effect of cell promoters which
stimulate cells to divide).  Cancer has two distinct steps, DNA alteration
and cell promotion.  For cells that normally divide all the time, promoters
are not that important.  But for lung and {*filter*} tissue which does not
normally divide, promoters are real important in the malignant process.
This is the major reason why the NCI has so many different clinical trials
in progress using retinol and/or beta-carotene.

Chronic infection(irritation) of the mucus membranes is a signal that
vitamin A may not be adequate.  I tell my students that any patient who
walks into their office with a complaint of chronic infection has to be
worked up for vitamin A(along with the other factors that medicine already
has on it's list of causes for chronic infection).  I drive this home in my
course at the Osteopathic College in Tulsa, when I teach at the allopathic
medical school in Tulsa(OU's branch campus) and when I give CME lectures.

Dark adaptation is the best clinical test for vitamin A status since night
vision is impacted when liver reverves drop to 50,000IU of retinol.  The
serum level of retinol can also be used, but it does not drop until liver
reserves drop below 10,000 to 20,000IU.  Asking a patient if they have
trouble seeing at night is a good initial screen(if cataracts are ruled
out).  In one study done on U.S. Spanish-Americans where serum retinol levels
were measured, 25% of the sample population had a serum retinol level below
20ug/dl.

As more studies are done on serum retinol levels in population groups of
the U.S. that have had a history of high infection rates, we will probably
see a much stonger correlation between infection incidence rates and low
serum retinol levels.

What do Weinsier and Morgan have to say ...

read more »

The conservative approach is best.  Vitamin A is not a drug you
can safely push to toxicity.  Permanent visual damage can occur
prior to the development of headache in some persons.  Headache
may not develop before the intracranial pressure gets to double
the normal values.  I would not recommend anyone mess with
megavitamin dosages of vitamin A without strict medical supervision.
This is the most common vitamin overdose we see.  More people
are hospitalized for this than for any vitamin deficiency except
thiamine in {*filter*}ics.
--
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Gordon Banks  N3JXP      | "Skepticism is the chastity of the intellect, and

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So the patient saw the physician for advice only, not treatment?
Did the patient object when the prescription was written?

How is the pharmacist supposed to know it is a placebo?

I suppose a homeopath assumes the patient would not have
come unless they believed in homeopathy.

Some of them are.

Caveat emptor.

--
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Gordon Banks  N3JXP      | "Skepticism is the chastity of the intellect, and

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Gordon, I agree 100%.  It's too bad that vitamin A has such potential in
dealing with a number of different disease processes and the lay press
jumps on any announcement of a nutrient effect on human disease.  Without
any education or medical supervision, serious, irreversible damage can be
done by a number of nutrients when taken in pharmacological(megadose)
rather than physiological amounts.  Vitamin A has always scared the heck
out of me( along with vitamin D) and my main concern has always been careful
monitoring if high dose retinol is going to be used.  But anybody can run down
to their grocery store and buy a bottle of 10,000IU retinol pills and start
popping to their hearts content.  I'd heard through the grapevine(so to speak)
that vitamin A toxicity was getting to be a real serious medical problem.  I
hope that the people reading this newsgroup have enough common sense to
avoid megadose retinol even if they think that it may help them.  If you
think that you may need more vitamin A, you are better off going with beta-
carotene.  If you need a quick infusion of retinol, find a doctor who can
monitor you and who believes that vitamin A may help you.  The NCI does
have a fairly large number of clinical trials in progress which may show
that vitamin A is useful in both preventing and treating cancer.  Once
these trial hit the lay press, I think that we will see a rush on vitamin A
supplements.  This is one that I would not mind seeing being restricted to
perscription only.  Especially since beta-carotene will always be around.  
If it is restricted, Doctors will have to become more aware of it's
usefullness and more willing to prescribe it.

Marty B.

NI> I would like to know if their is any medical consensus
NI> (or consensus within this group) regarding the ethics
NI> of the following:

NI>   1: Prescription of placebo medications when the patient
NI>      did not specifically request any sort of treatment.

Ethical, but rarely of benefit.  One possible instance: a patient is
suspected of having psychogenic seizures and is referred for an EEG.
The patient does not have any events during the tracing.  The
physician injects the patient with saline, claiming that it can
induce a brief seizure.  The patient then has a typical event that
looks like a psychogenic seizure, with the EEG tracing to prove it.
(I was able to diagnose psychogenic seizures on one occasion with
this procedure.)

NI>   2: Selling a placebo medication for a profit.

Highly unethical, with a few exceptions.

Placebos are routinely given in "blinded" research studies,
following detailed informed consent.  These studies are not usually
performed for "profit".  However, profit making, placebo-controlled
research could still be ethical if the profits, and the placebos,
were disclosed.

Virtually all physicians occasionally give *active* placebos -
substances that have actions, but are unlikely to themselves
produce the result the patient is expecting.  Multivitamins for a
patient complaining of fatigue is one example.

Physicians can decrease their ethical entanglements, and the
perception of conflict of interest, by not "selling" any
medications.  Pharmaceuticals, in most cases, should be dispensed
by pharmacists.

NI>   3: Prescribing homeopathic remedies without advising
NI>      a patient of their "controversial nature".

NI>   4: Representing homeopathic remedies as "over the counter"
NI>      medications.

I do not believe that homeopathic and other harmless, worthless
practices are unethical, *provided that* they are not represented as
medical treatments.
---

When I was a kid, my dermatologist prescribed Retin-A and vitamin A
capsules (50,000 I.U.).  I suppose it did dome good, I don't really
remember.

Anyway, the vitamin A needed a prescription.  When and why (especially
if there is so much potential for abuse) did Vitamin A supplements become available over the counter?

--
Doug Bank                       Private Systems Division

-*----

My understanding is that the RDA is 5000 IU.  Is twice this
amount really dangerous?  Or is the concern with people who
take multiple pills a day?

Russell

In Europe, I believe, placebos are more commonly prescribed.
I recall when I was in England they were running studies on
exactly what the placebo tablets should look like.  They
found that large red capsules and tiny blue pills were the
most effective.  The least effective were white tablets about
the size of an aspirin.  European medicine tends to be more
paternalistic in general than does US medicine.
(I think some of the drug companies must have read that study,
since soon after, extra-strength Tylenol capsules came out.
They were big and red and worked a lot better than the same
dose of acetaminophen in tablet form.)

--
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Gordon Banks  N3JXP      | "To the intelligent, life is infinitely mysterious.

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The toxic dose is considered to be 50,000IU(10 times the RDA).  But this is
highly variable.  Some people can take this dose each day all their life
and never have a problem while others will.  Anyone with liver disease is
going to show a greater sensitivity to retinol(toxicity) than someone with
normal liver function.  Weinsier, M.D. and Morgan, M.D. in their new
Clinical Nutrition book take a conservative approach and recommend that the
daily dose of retinol should not exceed 37,000IU.  I tell my students not
to use more than 25,000IU per day.  I've thought a lot about vitamin A
since posting this material and I'm tending to agree with Gordon Banks that
retinol really shouldn't be used at all unless it's being given under a
doctor's care.  There is just so much potential for permanent damage
occuring.  Some of the D.O's at my College are seeing patients with vitamin
A toxicity and Gordon Banks has pointed out that it is also occuring with a
fairly high degree of frequency on the M.D. side of the medical fence too.
I'm really starting to worry about what is going to happen when the news of
some of these NCI clinical cancer trials strats getting leaked to the
press.  I think that both vitamin A(retinol) and vitamin D need to be taken
off the OTC market.  There is just too much potential for very serious
harm(and potential death) if either is abused.  Other than iron(it's
replaced aspirin as the leading cause of infant poisioning deaths), most
other OTC supplements are less toxic than vitamin A or D.  Beta-carotene
really is a much safer way to get your vitamin A.

Marty B.