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From: [email protected]
Subject: Vitamin A and Infection
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
adult 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 adult male is 1,000 RE or 5,000IU of
vitamin A. For adult 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 adult 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 blood 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 alcohol(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 blood cells
and the mucosal cells get from blood) 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 blood 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 blood 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 breast 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 about vitamin A? Here are excerpts
from their book:
Vitamin A functions in vision in the forrm of retinol, it is necessay for
growth and differentation of epithelial tissue, and is required for
reproduction, embryonic development, and bone growth. Protein-calorie
malnutrition and zinc deficiency may impair the absorption, transport, and
metabolism of vitamin A. Retinaldehyde is converted to retinoic acid,
which has biological activity in growth and in cell diferentiation but not
in reproduction or vision. The most common procedure to evaluate vitamin A
status is to measure the retinol level in plasma or serum. The normal
range for vitamin A content for a child is 20 to 90ug/dl. Lower values are
indicators of deficiency or depleted body stores. Serum levels greater
than 100ug/dl are indicative of toxic levels of vitamin A. Dark adaptation
tests and electroretinogram measurements are also useful but difficult to
perform on young children. Rapidly proliferating tissues are sensitive to
vitamin A deficiency and may revert to an undifferentiated state. The
bronchorespiratory tract, skin, genitourinary system, gastrointestinal
tract and sweat glands are adversely affected. A daily intake of more than
7.5mg(about 37,000IU) of retinol is not advised and chronic use of amounts
over 20mg(100,000IU) can result in a dry and itching skin, desquamation,
erythematous dermatitis, hair loss, joint pain, chapped lips, hyperostois
(bony depositis), headaches, anorexia, edema and fatigue.
They recommend 30mg of retinol via IM injection in children for vitamin A
deficiency but do not discuss treatment for adults. Their toxic serum retinol
level is very conservative. I recommend that my students try 25,000IU in
adults that are having problems with chronic infection. They have to rule
out a zinc deficit first by getting an RBC zinc run(or if their clinical
lab can't run it, I tell them to do what Weinsier and Morgan suggest, give
them the zinc along with the vitamin A. At 25,000IU per day, toxicity
should not be a problem and you will not have to worry about pulling the
patient into the office on a regular basis to run a serum retinol.
Both Elaine and Jon found doctors who used a much higher dose of vitamin A.
Recall that the PMS papers were using 100,000IU to 200,000IU of vitamin A.
I don't suggest that my students use these high doses. If you wanted to
fill the liver up fast(as part of a clinical trial) and were monitoring the
serum retinol level, then you would be okay. But my knowledge of the
vitamin A literature suggests to me that 25,000IU for patients with a
demonstrated vitamin A deficit(dark adapatation test or serum retinol) will
provide a good and steady improvement(as long as zinc and vitamin C status
are good) without having to worry about toxicity. If they want to get more
agressive, fine if they follow my advise to check the serum retinol. But
vitamin A(retinol) should never be given in high dose to women who could
become pregnant since vitamin A shows teratogenicity towards the human
fetus. The dose needed to show this effect on the developing fetus is
18,000IU of retinol per day. Beta-carotene will never have this effect on
the human fetus.
Could just taking Beta-carotene instead of retinol supplements help? Yes
but the effect will take a long time to develop. My advise is to use
retinol to fill the liver up and then switch to beta-carotene to keep it
full. Vitamin A is probably one nutrient that is better off left to
prescription by doctors. But when we have the M.D.'s in this newsgroup
jumping all over me and other doctors that propose the use of vitamin A
supplements for treating patients with chronic sinus and GI distress, I
think that the most prudent option is to keep vitamin A in the OTC market
but require manufactors to provide package inserts to educate the general
public about the dangers of vitamin A supplementation.
Marty B.
