© Whole Foods Magazine
Selenium and Cancer Prevention:
FDA Finally Shows Some Interest
By Richard A. Passwater, Ph.D.
While reading through this special issue on the role of nutrients in reducing the incidence of major diseases such as cancer and type-2 diabetes, you may forget that it has taken the establishment more than 30 years to acknowledge what is now considered as obvious and common knowledge. The good news is that by the end of this month (May 2003), the Food and Drug Administration (FDA) is scheduled to grant health claim status to selenium as being protective against some cancers. In this column, I have been asked by Whole Foods to briefly discuss the dramatic change in direction by the FDA and to update you on recent progress in selenium and cancer prevention.
We continue to learn more about the ways in which selenium nutrients prevent cancer.
In the 1960s, when my laboratory studies elucidated that free-radicals were at the root of many cancers, it was virtually impossible to get other scientists to examine my evidence. At that time, most scientists thought viruses were the root causes of cancers. Even the concept of chemical
carcinogens was new. In the 1970s when I took my evidence directly to the public, I was called a "quack" by the American Cancer Society for even suggesting that diet was a factor in cancer. I didnít mind being called names as much as having to observe them at fund-raisers passing out sugar lollipops colored with red dye #2, which was later shown to be a carcinogen.
Later, a medical doctor filed a harassment suit against me for making the same claim that diet was a factor in cancer. When "Cancer: New Directions" was published in the June 1973 issue of American Laboratory, several scientists wrote critical letters scoffing at the idea that free-radicals were involved in the cancer process. This was in spite of my laboratory data presented in the article that showed synergistic combinations of antioxidant nutrients reduced the incidence of several types of both natural and induced cancers by 90%. One of the problems with new directions in research is that itís hard to change old ideas, so I felt compelled to present this evidence directly to the public in my 1975 book, "Supernutrition: Megavitamin Revolution."
However, one of the benefits of discovery is that your intellectual property can earn patents. As I have reported in many of my books through the years, I applied for patents in 1970 on the use of certain antioxidants and synergistic combinations of antioxidant nutrients in preventing cancer. One patent that I am especially proud of is with my colleague Dave Olson that covers the use of all selenium-containing compounds for prevention and/or treatment of cancer (US Pat. No. 6,090,414).
Today, even the National Cancer Institute (NCI) and FDA recognize that certain nutrients can reduce the risk of many types of cancers. While we couldnít get NCI interested in our research in 1980, it finally sponsored a significant study that was published in 1996 by Dr. Larry Clarkís group. Today NCI is sponsoring several follow-up studies, but what I still find troubling is that the researchers are not studying the most effective anti-cancer selenium compounds. Thousands of lives continue to be needlessly lost to cancer when, in fact, many more lives could be saved by using the more-effective anti-cancer selenium-containing nutrients. I often think of the tremendous loss of lives that has occurred since the NCI was first informed of our research in 1980.
On a brighter note, the FDA is now beginning to realize the importance of selenium nutrients in preventing cancer. But, this didnít come easily either. It took the persistent work of first-amendment attorney Jonathan W. Emord of Emord & Associates, P. C., in Washington, DC, to bring the FDA to its collective senses regarding the need to inform the public about the anti-cancer action of selenium-containing nutrients. Prior to this, in spite of the hundreds of studies around the world establishing the ability of selenium-containing nutrients to protect against cancer, it was illegal to state this fact in advertisements or on the labels of dietary supplements.
This repression of scientific fact may have been responsible for many thousands of people dying unnecessarily of cancer. In any event, in a letter dated February 21, 2003, Dr. Christine Taylor, Director of FDAís Office of Nutritional Products, Labeling and Dietary Products informed attorney Emord that "within 60 days of the date of this letter, we plan to issue the formal decision on the selenium and cancer health claim petition (Docket 02P-0457)." The FDA and the petitioners have agreed on the wording for the selenium health claims as follows:
- "Selenium may reduce the risk of certain cancers. Some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer. However, FDA has determined that this evidence is limited and not conclusive."
(2) "Selenium may produce anticarcinogenic effects in the body. Some scientific evidence suggests that consumption of selenium may produce anticarcinogenic effects in the body. However, FDA has determined that this evidence is limited and not conclusive."
I look at this as a revolutionary first step by the FDA. I am an avid supporter of the need for a strong FDA, but the agency must be scientific, not prejudiced. The FDA is starting to catch up with the science. Unfortunately, the scientific community as a whole is not as well informed about selenium research as it should be. The general scientific community still has to deal with several misconceptions. There is still the misconception that all selenium-containing nutrients have equal effect. There is still the misconception that the anti-cancer effect of selenium-containing nutrients is related to their nutritional value or toxicity. And, there is another problem, too: faulty assumptions have been used to set astonishingly low estimates of the recommended dietary requirements for selenium-containing nutrients.
Since my last update two years ago, research on the ways in which selenium-containing compounds prevent cancer formation and/or destroy cancer cells has progressed on several fronts. Inhibition of cell invasion, DNA repair, and stimulation of transforming growth factor beta signaling are of recent interest. The effect of selenium-containing compounds on gene expression is of special interest. A large number of selenium-responsive genes with diverse biological functions have now been identified (Dong, Y., et al., Cancer Res. 2003 1;63(1):52-9) These genes fall into 12 clusters of distinct kinetics patterns. The expression changes of 10 genes known to be critically involved in cell cycle regulation have been noted so far. Selenium compounds also inhibit signaling enzymes such as protein kinase C (PKC) that play crucial roles in tumor promotion. (Gopalakrishma, R. and Gundimeda, U. J. Nutr. 2002 132;(12):3819S-3823S)
A selenium-containing protein identified in 1998 called Sep15 has now been shown to have redox function. (Wu, H. J., et al., Ai Zheng 2003;22(2):119-22) The selenium-containing nutrient, selenomethionine has been shown to regulate the tumor suppresser p53 by the redox factor refl-dependent redox mechanism. (Seo, Y. R., et al., Proc. Natl. Acad. Sci 2002; epub Sep 19)
Studies continue to support evidence that one important pathway is that many selenium-containing nutrients can be converted in the body to methylselenol. Methylselenol has been shown to block expansion of pre-malignant cells forming into fully developed cancers. Several pathways have been proposed that could explain how selenium-containing compounds can block mutated cells from progressing to cancer. (Ip, C. et al., Cancer Metastasis Rev. 2002;21(3-4):281-9)
Methylseleninic acid has been shown to inhibit NF-kappa B and regulate I kappa B in prostate cancer cells. (Gasparian, A. V., et al., Mol. Cancer Ther. 2002;1(12):1079-87; Jiang, C., et al., Mol. Cancer Ther. 20021(12):1059-66)
A representative of the hydrogen selenide metabolic pool was found to protect liver cells against damage to DNA. (Thirunavukkarasu, C. and Sakthisekaran, D., J. Cell Biochem. 2003;88(3):578-88).
Studies continue to confirm that people with lower levels of selenium in their blood have higher rates of prostate and lung cancers. (Vogt, T. M., et al., Int. J. Cancer 2003;103(5):664-70). A new study confirms that selenium supplementation reduces damage to DNA in prostate cells (Waters, D. J., et al., J. Natl. Cancer Inst. 2003;95(3):237-41)
Continued studies in China confirm that those with low levels of selenium before selenium supplementation had significantly lowered incidence of lung cancer due to selenium supplementation. (Reid, M. E., et al., Cancer Epidemiol. Biomarkers Prev. 2002;(11):1285-91). This finding is also supported by a Finnish study showing that low selenium levels lead to an increased incidence of lung cancer. (Hartman, T. J., et al., Cancer Causes Control 2002;13(10):923-8).
In the Netherlands, former smokers with high levels of selenium experienced half as many bladder tumors as their counterparts with low selenium levels. An Indian study found that those with low levels of selenium have significantly more head and neck cancers than those with higher selenium levels. (Yadav, S. P., et al., J. Otolaryngol. 2002;31(4):216-9)
It is important to note, too, that the reduced levels of prostate specific antigen (PSA), a commonly used marker for prostate cancer, observed with selenium supplementation is due entirely to the effect of selenium on the cancer cells and not due to selenium interfering with the production of PSA for any reason other than a decrease in cancer cells. "Changes in serum PSA levels in an individual during selenium supplementation is not an effect specific for PSA secretion, but rather is a useful indicator for changes in the disease progression in individual patients." (Bhamre, S., et al., Prostate 2003;54:315-21)
There is much more yet to come regarding the selenium anticancer story. Please stay tuned. In the meantime, please be sure you are well nourished with selenium. WF
© 2003 Whole Foods Magazine and Richard A. Passwater, Ph.D.
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