Vitamins and Metabolites Against Cancer: Even More Good News.
by Richard A. Passwater, Ph. D.
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 them!
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 it works.
1. Cancer: New Directions Passwater, Richard A. Amer. Lab., 5(6):10-22 (June 1973)
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