Dr. Passwater’s research with selenium as a cancer preventative began more than four decades ago, and over the decades, thousands of mechanistic studies, hundreds of animal studies, dozens of epidemiological (population) studies, and at least three published clinical supplementation trials have verified his findings.
On December 25, 1996, Dr. Larry Clark and his colleagues published their large, prospective, randomized, placebo-controlled, double-blind Nutritional Prevention of Cancer (NPC) clinical study in the Journal of the American Medical Association (JAMA 1996; 276:1957-1963). This landmark research effort showed that daily supplementation of diets with 200 micrograms of selenium yeast cut the cancer death rate in half. That is cancer mortality was reduced 50 percent (p=0.002). Lung cancer deaths were reduced 53% (p=0.03)
Total cancer incidence was reduced 37 percent (p=0.001) and the total carcinoma incidence was reduced 45%. In addition, the three leading sites of cancer had significantly lower incidence; lung cancer incidence was reduced 46 percent (p=0.04), prostate cancer incidence was reduced 63 percent (p=0.002) and colon cancer incidence was reduced 58 percent (p=0.03). There was a 17% reduction in all cause mortality (p=0.14), which when adjusted for sex, current smoking and age yielded a 21% reduction in deaths from all causes (p=0.07). (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8971064&dopt=Abstract)
Throughout all of the mechanistic, animal and clinical studies of selenium it has been observed that not only is the incidence reduced, but also the severity and death rate have been even more greatly reduced suggesting that tumors are being destroyed, not just prevented. At the very least, the progress is delayed.
A large 2003 French study called SU.VI.MAX incorporated 100 micrograms of selenium as selenomethione in its regimen that also included vitamins C and E, beta-carotene and zinc. It found that the supplements reduced cancer deaths by 37% and cancer incidence 30%. (In press)
In Qidong County, China, a four-year study involving 226 hepatitis B antigen carriers demonstrated the protective effects of selenium supplementation. An equal number of participants were given either a supplement containing 200 micrograms of selenium or a placebo containing no selenium. None of the selenium-supplemented participants developed hepatocellular carcinoma, whereas seven participants receiving the placebo without selenium did. (Yu, S. Y. et al., Biol. Trace Elem. Res. 1997)
Another clinical intervention trial involving 130,000 Chinese in five townships also showed that selenium supplementation was protective against cancer. Selenium was added to the table salt in one of the five townships in close proximity to the other four townships. The result was that there was a 35% reduction in hepatocellular carcinoma in the township receiving the selenium supplementation. (Yu, S. Y. 1997)
From March 1986 through May 1991, a randomized nutritional intervention trial called the General Population Trial was conducted with over 30,000 people in Linxian, China. The participants who received 50 micrograms of selenium, beta-carotene, and vitamin E had significantly lower cancer mortality rates than those who did not. After supplements were given for 5.25 years in the clinical trial, significant reductions (P = .03) in total mortality [relative risk (RR) = 0.91] and cancer mortality (RR = 0.87) were observed in subjects receiving beta-carotene, alpha-tocopherol, and selenium, with the reduced risk beginning to arise about 1-2 years after the start of supplementation By the last six months of the trial, the degree of cancer reduction was approaching 100%.
Further clinical studies are underway in the U. S. including: the Negative Biopsy Trial (NBT) for men at high risk of Prostate Cancer because of a persistent elevation in PSA above 4 ng/ml and had a negative biopsy; the Watchful Waiting Trial: for men diagnosed with Prostate Cancer and under 'Watchful Waiting' of a physician for their disease; the Preprostatectomy Trial (PREP): for men who have been diagnosed with non-metastatic prostate cancer that have not yet had a radical prostatectomy; the Selenium and Lung Trial for former tobacco smokers. (See http://www.selenium.arizona.edu/Introduction.htm ) And the Selenium and Vitamin E Cancer Prevention Trial (SELECT) will confirm the Clark results for selenium and determine if these two dietary supplements together result in greater synergistic protection than either alone against prostate cancer, the most common form of cancer, after skin cancer, in men. The study will include a total of 32,400 men. The selenium used is selenomethionine at the dosage level equivalent to 200 micrograms of elemental selenium.
The Prevention of Cancer by Intervention with Selenium (PRECISE) clinical trial, a study of 33,000 European individuals from the UK, Denmark and Sweden is at the pilot study stage.
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. 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. A selenoprotein (a protein that purposely incorporates selenium as opposed to a protein that merely incorporates selenium by accident) identified in 1998 called Sep15 has now been shown to have redox function. The selenium-containing nutrient, selenomethionine has been shown to regulate the tumor suppresser p53 by the redox factor refl-dependent redox mechanism. 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 could block mutated cells from progressing to cancer. Methylseleninic acid has been shown to inhibit NF-kappa B and regulate I kappa B in prostate cancer cells. A representative of the hydrogen selenide metabolic pool has been found to protect liver cells against damage to DNA.
Studies continue to confirm that people with higher levels of selenium in their blood have lower 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)