Our understanding of how vitamins and their metabolites protect us against
cancer moves ever onward. You might think that I would tire of writing about
this subject, but the news continues to be so exciting that I can’t wait
to share it with you. And, of course, this is not a rehash of anything else
I have written, it’s just that there is so much supporting research going
on that there always seems to be minor breakthroughs on several fronts.
In this article, I will discuss the news concerning the roles of certain
vitamin metabolites against cancer. Metabolites are smaller compounds made
by the body from a larger compound as the body processes the larger compound.
As an example, L-threonic acid is a metabolite of Ascorbic acid, whereas
calcium ascorbate is a salt of ascorbic acid. The difference being that
both ascorbic acid and calcium ascorbate are forms of vitamin C, whereas,
L-threonic acid is a completely different compound entirely.
Of particular interest is that the riddle of how increased dietary levels
of vitamin A protects against cancer without raising the amount of vitamin
A in the blood may have been solved. Some Scientists have used the fact
that the liver limits the amount of vitamin A circulating in the blood as
an argument against any possible role for vitamin A in quantities above
those needed to prevent deficiency. Now we understand how extra dietary
vitamin A may increase our protection.
When I did my cancer prevention animal studies in the early 1970’s, I couldn’t
fully explain all of my results.  With most of the antioxidant nutrients,
I could show that the increased blood levels of the vitamins significantly
decreased free radical activity for very long periods of time and thus protected
body components against cancer. However, with vitamin A, the amounts circulating
in the blood were raised only for four to six hours. The liver would remove
vitamin A for storage and thus maintain a normal level.
It was easy to explain how extra vitamin A would give long term protection
when there were existing deficiencies, because the blood level of vitamin
A would be raised from low levels to normal levels.
I’m sure you can guess from the title that the answer has something to do
with a vitamin A metabolite. Congratulations, you’ve hit the jackpot. But,
before we look at the role of vitamin A metabolites, let’s review the scope
of human clinical studies that are now going on.
In my earlier books, I discussed my animal studies and those of others,
and the supporting epidemiological studies, that demonstrate a protective
effect of the antioxidant nutrients against cancer. [2,3] In my latest book,
“The New Supernutrition,” I mention that the U. S. government
is sponsoring several human clinical studies of the role of antioxidant
nutrients against cancer. 
The list is impressive. To paraphrase that infamous ad, this research has
come a long way, baby! Thanks to Sharon Landvik, MS, RD of the Vitamin E
Research and Information Service, you can see for yourself just how many
and what type of human studies are underway. Table 1 lists 24 studies sponsored
by the National Cancer Institute that were underway by 1987. Hurray for
Table 2 nicely summarizes 24 major epidemiological studies of the protective
effect of the antioxidant nutrients against cancer. As with any research,
epidemiological studies do not prove anything and they usually point out
areas needed for further study. However, you can see how generally supportive
these studies are.
But, how can “extra” vitamin A increase cancer protection if the
liver removes the extra amount from the blood. (Also, keep in mind that
too much vitamin A is toxic to the liver for that very reason. 
Vitamin A Metabolites
Drs. G. Tang and R. Russell have shown that the much researched cancer “drug,”
13-cis-retinoic acid (isotretinoin) is actually a normal metabolite of vitamin
A. [6,7] They have shown that both all-trans-retinoic acid and 13-cis-retinoic
acid are metabolites of retinol. Retinol, of course, is the chemical name
for vitamin A.
Dr. M. E. Huang has shown that all-trans-retinoic acid puts acute myeloid
leukemia in complete “remission.”  Drs. W. K. Hong and S. Lippman
have shown that high doses of 13-cis-retinoic acid have effectively “suppressed”
squamous cell carcinomas of the head and neck.  The researchers noted
that “second primary tumors are the chief cause of treatment failure
and death in patients (with head and neck cancers). After a year of treatment
of 49 patients with 13-cis-retinoic acid and 51 patients with placebos,
four percent had second primary tumors in the 13-cis-retinoic acid group,
as opposed to twenty-four percent in the placebo group.
Of course, there are many other studies that show the same effect. Isn’t
it nice to know that these metabolites are normally in the blood and they
can be increased with dietary intakes of vitamin A above that needed to
prevent vitamin A deficiency. Again, remember that there is a limiting rate
of return as vitamin A becomes toxic at higher levels.
In a study by Dr. Huang, after consuming vitamin A in the form used commonly
in supplements, retinyl palmitate, the blood level of retinol remained relatively
unchanged, whereas the level of retinyl palmitate increased forty times.
While the level of retinyl palmitate was elevated, the body converted significant
quantities to all-trans-retinoic acid and 13-cis-retinoic acid. These metabolites
persisted for significant periods of time, whereas the retinyl palmitate
eventually was cleared from the blood after six hours.
So now we understand a little bit more about how vitamin A protects us against
cancer. There is other research showing that metabolites of vitamin C protects
against cancer, and I have earlier found that metabolites of vitamin E –
including the tocotrienols – are protective.  The neat thing about empirical
research is that sometimes we find out that things work many years before
theoretical or more sophisticated empirical research elucidates how or why
1. Cancer: New DirectionsPasswater, Richard A.Amer. Lab., 5(6):10-22 (June
2. Supernutrition: Megavitamin RevolutionPasswater, Richard A.Dial Press,
3. Cancer and Its Nutritional TherapiesPasswater, Richard A.Keats Publ.,
New Canaan, (1978)
4. The New SupernutritionPasswater, Richard A.Pocket Books, p89, NY (1991)
5. Vitamin A Can be ToxicPasswater, Richard A.Whole Foods (1985?)
6. 13-Cis-retinoic acid is an endogenous compound in humanserum.Tang, G.
and Russell, R. M.J. Lipid Res. 31:175-82 (1990)
7. Formation of all-trans-retinoic acid from retinyl palmitatein humans.Tang,
G. and Russell, R. M.J. Nutr. Biochem. 2:210-3 (1991)
8. Use of all-trans-retinoic acid in the treatment of acutepromyelocytic
leukemia.Huang, M. E., et al.Blood 72:567-72 (1988)
9. Prevention of second primary tumors with isotretinoin insquamous-cell
carcinoma of the head and neck.Hong, W. K., et al.New Engl. J. Med. 323:795-801
10. Antitumoric potentiality of some ascorbate derivatives.Omura, Hirohisa,
et al.J. Fac. Agr., Kyushu Univ., 18:181-9 (1974)11 – 34 (See separate sheet
National Cancer Institute Supported Chemoprevention Studies.
(Reprinted with permission from Landvik, Sharon; VERIS (Sep 1991)
Human Epidemiological Studies of Antioxidant Levels and Cancer
(Reprinted with permission from Landvik, Sharon; VERIS (Sep 1991)
All rights, including electronic and print media, to this article are copyrighted
by Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).