New Discoveries Expand Our Knowledge About Selenium's Importance
by Richard A. Passwater, Ph. D.
A lot has happened since the last time I reviewed the health benefits of selenium in this column. Unfortunately for them, the average person still hasn't even heard of the trace mineral selenium. Fortunately, most nutritionally oriented health food advocates are aware of much about selenium. This review will cover many of the important findings since "Selenium Update" and "Selenium As Food and Medicine."
Selenium is an essential trace element for humans and other animals. Selenium was named after the moon goddess, Selene, by the Swedish chemist Jons Jakob Berzelius in 1817. Dr. Klaus Schwarz established selenium as an essential nutrient for animals in 1957, but the first selenium function in humans wasn't discovered until 1973.  Dr. John Rotruck and his colleagues at the University of Wisconsin demonstrated that selenium was incorporated into molecules of an enzyme called glutathione peroxidase (GPX). This vital enzyme protects red blood cells, cell membranes and sub-cellular components against undesirable reactions with soluble peroxides.
The discovery of GPX opened the door to our understanding of how selenium is protective against cancer, heart disease, arthritis and accelerated aging. Now more scientific excitement is being generated with the recent finding that selenium is also a vital component of other mammalian enzymes.
Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPX) protects membranes against peroxides already bound to membrane surfaces.  PHGPX blocks formation of the extremely harmful alkoxyl radical and inhibits peroxidative chain branching. This activity is even of more importance in the prevention of cancer, heart disease and accelerated aging.
Now addition pathways in which selenium is involved in health are being uncovered. Selenium is a component of the enzyme that is needed to produce the most active thyroid hormone. ***Sub-optimal amounts of selenium impair thyroid hormone*** function and thus affects many body functions.
Biochemists are now studying several other selenium proteins and have classified them into four main categories. 
First there were animal studies that showed that selenium protected against chemicals and ultraviolet energy that cause cancer. [4-7] These laboratory findings were also supported by epidemiological studies (population surveys), and now large scale clinical studies are being sponsored by the U. S. government. [8-15]
Epidemiological studies have shown that persons with low-selenium diets have two-to-three times greater risk of heart disease than those eating selenium rich diets.  In a clinical study, patients with blockage of all three coronary arteries had low blood selenium levels, while those with high blood selenium levels were healthy and free of coronary heart disease.  Strikingly, those with one diseased coronary artery had the next highest blood selenium levels, and those with two blocked coronary arteries had the second lowest blood selenium levels.
Clearly, the antioxidant protection of the selenium-containing enzymes, GPX and PHGPX, protect the arteries and cholesterol-carrying lipoproteins against the damage that leads to heart disease.
Arthritic inflammation is produced by certain hormone-like compounds called prostaglandins. Selenium is involved in controlling these specific prostaglandins by controlling the free-radical damage that stimulates their production.
Norwegian physicians had noted that arthritis patients tended to have low blood selenium levels. When their arthritis ***patients were given selenium supplements, they dramatically** improved.  A Danish study has confirmed the Norwegian study. 
Selenium is a component of the enzyme that is needed to produce the thyroid hormone triiodothyronine (T3). T3 is the preponderant metabolic thyroid hormone. The selenium-containing enzyme, iodothyronine deiodinase, converts the prohormone thyroxine (T4) into T3. 
This explains the observation that selenium deficiency impairs thyroid hormone function. Impaired thyroid hormone function is called hypothyroidism and affects many body functions.
Other Areas of Study:
The role of selenium in possibly slowing the aging process has been under laboratory study for more than 25 years, but there are no known plans for clinical studies at this time. [21-3]
Studies also indicate that selenium protects against cataracts and skin damage, and is important to prostate function. A patent has even been applied for that claims selenium significantly helps Alzheimer's patients.  Several books describe the many beneficial roles of selenium in health. [23, 25-6]
Forms of Selenium Supplements:
The most efficacious and safest forms to supplement our diet with selenium is not the inorganic salt form, but the organic forms, selenium yeast and selenomethionine.
Selenium yeast is produced when selenium is naturally incorporated into the protein of growing yeast under optimum conditions. The resultant yeast has a high concentration of the selenium-containing proteins, selenomethionine and selenocysteine. Products that are created by mixing yeast with inorganic selenium are still merely inorganic selenium products.
Beneficial nutritional brewer's yeast (Saccharomyces cerevisiae) does not contribute to yeast infections such as Candida albicans. Food yeasts are not infectious. Nutritional yeasts are not live yeast cells. If they were, live yeast cells would actually compete with one another and nutritional yeasts would actually suppress Candida albicans yeast growth. However, selenium yeast is carefully dried after it is grown. This kills the yeast and it can no longer grow or multiply. Brewer's yeast has been a staple of the health food industry since its inception. The famous health teachers all advocated brewer's yeast in one form or another because it is rich in the B-complex vitamins and other nutrients that were not available as purified nutrients in the past. Brewer's yeast still may contain nutrients that we have yet to discover.
Selenium yeast was found to out-perform inorganic selenium in increasing the amount of selenium in the milk of lactating mothers and the blood of their infants. The researchers concluded, "Selenium yeast was safe and more effective than selenite." 
In another test, 150 micrograms daily of selenium as selenium yeast was effective in raising blood selenium levels of healthy adults, whereas the same amount of inorganic yeast failed to raise blood selenium levels.  Dr. Gerhard Schrauzer of the University of California-San Diego concludes "since a ten-fold lower oral dosage of organic selenium produced a two-fold greater increase in selenium levels in the blood, organically-bound selenium is at least twenty-fold more effective in providing the body with the trace element." 
Selenomethionine is a purified selenium-containing amino acid. There is no yeast in selenomethionine. Selenomethionine is a naturally occurring component of food. Selenomethionine is ***similar to the essential amino acid methionine but with an atom of selenium instead of an atom of sulfur.
The form of selenomethionine that the body can use is L-selenomethionine. L-selenomethionine is better absorbed and better incorporated into body components than any other known form of selenium. Experiments comparing inorganic selenium with DL-selenomethionine found that DL-selenomethionine was not as effective as the inorganic selenium .
D-selenomethionine is degraded to inorganic selenium and returned to the inorganic selenium body pool, and thus is only one-fifth as bioavailable as L-selenomethionine. 
I have been using various forms of selenium in my animal studies for thirty years and find that the selenium-containing amino acids (selenomethionine and selenocysteine) and the methylated selenides are far superior to the inorganic forms of selenium (selenite and selenate) in terms of overall health, longevity and freedom from cancer.
In studies in New Zealand, it was found that selenomethionine was at least 75 percent bioavailable, compared to 59 percent for sodium selenite. Blood selenium levels rose more quickly and didn't plateau as early with selenomethionine than with sodium selenite. [30-32]
In a Finnish study, again selenomethionine raised blood selenium levels higher and remained in the blood longer than inorganic selenium.  In a later Finnish study, it was found that as much as 3,500 micrograms of inorganic selenium had to be given to raise their blood selenium levels to match that of typical Americans. The long-term safety of such a high dose of inorganic selenium is not known.
In 1984, a MIT study determined that organic forms of selenium are able to increase the body pool size about 70 percent more effectively than inorganic selenite. 
Dr. P. Whanger of Oregon State University has spent several years studying the effectiveness of several forms of selenium supplements. He has published several papers on this subject through the years utilizing various laboratory animals and human clinical trials. His latest research was published in the MArch issue of the American Journal of Clinical Nutrition. Some of his ***findings include, "The selenium concentrations in all blood*** fractions increased at a faster rate (two- to three- fold) in women taking selenomethionine than in those taking selenate...About 95 percent of the selenium was associated with hemoglobin in women taking selenomethionine - interestingly, most of the GPX activity was also associated with hemoglobin...This suggests that selenium increases in these fractions only when selenomethionine is supplied and that the increase is restricted ***to hemoglobin." 
Selenoproteins and selenium transport:
We now know that several selenium-containing proteins exist, so selenium is essential in more ways than we knew in 1973. Earlier I discussed two new enzymes, PHGPX and iodothyronine deiodinase. Enzymes are proteins. But there are many other selenium-containing proteins, including muscle proteins and other selenium-containing enzymes. Dr. Roger Sunde of the University of Missouri-Columbia has classified selenoproteins into four distinct groups.  Table 1 lists the proteins of the selenium ion-specific selenoproteins, the selenomethionine-specific proteins, the selenocysteine-specific proteins and the selenium binding proteins.
Selenomethionine can furnish the required form of selenium for all four, whereas inorganic selenium has to be converted into selenomethionine or selenocysteine to be incorporated into two of the classes of selenoproteins. Notice in figure 1 that selenomethionine is incorporated directly into the selenomethionine-specific proteins. Selenomethionine can also be converted in the body into selenocysteine to form the selenocysteine-specific proteins. Also, selenomethionine can be catabolized into selenium ions to form the selenium ion-specific selenoproteins. It is easier for selenomethionine to provide selenium ions than it is for inorganic selenium to be converted into selenomethionine.
The transport protein for selenium ions is selenoprotein-P.
As discussed earlier, inorganic selenium forms (selenate and selenite) are not as well absorbed as organic selenium-containing amino acids (selenomethionine and selenocysteine). However, inorganic selenium dissolved in the drinking water of laboratory animals has been effective in preventing various cancers. However, this is not how humans normally get most of their selenium; it is in their food, nottheir water.
Inorganic selenium, at low doses, is better than no selenium at all. However, larger doses of inorganic selenium has an oxidative effect that increases undesirable lipofuscin production.  The selenium in inorganic selenite is in the plus four valance state which is very oxidative. The selenium of selenomethionine is in the minus two valance state. The lipofuscin accumulation in the liver can be accounted for by the fact that in order for selenium to go from the inorganic plus four valance state to the plus minus valance state, six electrons must be obtained from liver cells. The safety of inorganic selenium is about one-third that of selenomethionine. 
Inorganic sources of selenium do not find their way to muscle protein to an appreciable extent. If laboratory animals are fed selenomethionine, selenium soon increases in all organs, muscles, GPX and hemoglobin. When inorganic selenium is fed to animals, it accumulates in the liver, kidneys and GPX.
Inorganic selenium reacts spontaneously with sulphydryl groups to form selenotrisulfides. This can severely disrupt the structure of proteins. Inorganic selenium reacts with the sulfhydryl groups of glutathione to form selenopersulfide and free selenide. Inorganic selenium, due to its free-radical promoting oxidative nature, is mutagenic and has caused cataracts at high doses in mice.  In contrast, selenium-containing amino acids are stable, less toxic, and do not have mutagenic or oxidizing activity.
Synergism With Vitamins C and E:
Vitamin C increases the absorption of selenomethionine and organic selenium-containing yeasts. Two differing reports exist concerning vitamin C and inorganic selenite. [38,39] One report shows that vitamin C inhibits inorganic selenium absorption, while the other shows that vitamin C enhances inorganic selenium absorption. The confusion may result from the fact that if vitamin C mixes with inorganic selenium in the food, the inorganic selenium is reduced to insoluble and biologically inert metallic selenium.
Vitamin E is a partner with selenium in protecting body components against oxidative free radicals. Both vitamin E and selenium have their own specific modes of stopping free radicals, plus they have common modes. The two are "synergistic" which means that the activity of both together is greater than the sums of the activity of each by itself. It's a case of nutritionally adding one plus one and getting more than three. Vitamin E and selenium are a powerful combination and the body needs both together.
Daily intake and safety:
In 1980, the National Academy of Sciences stated that a safe and effective range for selenium intake is 50 to 200 micrograms. In 1989, a daily RDA of 75 micrograms for men and 55 micrograms for women was established. The FDA has not as yet *** set a USRDA for selenium. Conventional supplementation practices are to add 50 to 200 micrograms of selenium to the daily diet.
In my three-part 1986 series on selenium safety, I discussed that many natural diets contained more than 600 micrograms of selenium daily. [40-42] In Northern Greenland, many residents consume about 1,300 micrograms of selenium daily. And, in China, some residents were found who took 1,000 micrograms of selenium daily when they found out that it protected them from certain selenium-deficiency diseases (including Keshan disease) endemic to their area. They developed thickened fingernails and a garlic-like breath. Now we have a report that a woman took 2,400,000 micrograms of selenium daily for seventy-five days with only mild and reversible side effects.  This is 12,000 times the recommended upper limit for supplementation for healthy people.
Keep in mind that everything -- even oxygen and water -- is toxic at some level. It is the dose that makes the poison. The amount of selenium supplement that is safe and effective is the old recommended daily range of 50 to 200 micrograms daily. Yet, we continue to read the foolishness that the cancer-protecting dose is toxic. That nonsense is a disservice to everyone.
We still have more to learn about selenium than we already know, but it is clear that selenium is extremely important to our health. It's a shame that more people don't know about selenium. In a future article on selenium, I will interview Dr. Gerhard Schrauzer of the University of California-San Diego. Perhaps Dr. Schrauzer's provocative comments will help to get the public interested in protecting their health with selenium.
1. Rotruck, J. T., et al., Science 179:588-90 (1973)
2. Ursini, F., et al., Biochim. Biophys. Acta 839:62-70 (1985)
3. Sunde, Roger A., Molecular Biology of Selenoproteins, in Annual Review of Nutrition (1990), eds. Olson, Robert E., et al., Annual Reviews, Inc., Palo Alto, Ca. (1990).
4. Passwater, Richard A., Amer. Lab. 5(6) 10-22 (1973)
5. .... Advan. in Cancer Res. 29:419 (1979)
6. .... Prevent. Med. 9:362 (1980)
7. .... Cancer Res 41:4386 (1981)
8. .... Arch. Environ. Health 31:231 (1976)
9. .... Bioinorg. Chem. 7:23 (1977)
10. .... Lancet II 130 (1983)
11. .... Amer. J. Epidem. 120:342 (1984)
12. .... Nutr. Cancer 6:13 (1985)
13. .... Fed. Proceed. 44:2584 (1985)
14. .... Brit. Med. J. 290:417 (1985)
15. .... Biolog. Tr. Element Res. 7:21 (1985)
16. .... Lancet II 175 (1982)
17. .... Clin. Chem. 30:1171 (1984)
18. Aaseth, J., et al.; Selenium in Biology and Medicine (May, 1980)
19. Tarp, U., et al., Scandinavian J. Rheumatol. 7:237-40 (1985)
20. Berry, Maria J., et al., Nature 349:438-40 (Jan 31, 1991)
21. Passwater, Richard A., Amer. Lab. 3(4) 36-40 (1971)
22. Passwater, Richard A., Amer. Lab. 3(5) 21-6 (1971)
23. Passwater, Richard A., The New Supernutrition, Pocket Books, NY (1991)
24. Birkmayer, J., Eur. Pat. Appl. EP 345,247 (Dec. 6, 1989).
25. Passwater, Richard A., Selenium as Food and Medicine, Keats Publ., New Canaan, CT (1980)
26. Passwater, Richard A., Selenium Update, Keats Publ., New Canaan, CT (1987)
27. Kumpulainen, J., et al., Amer. J. Clin. Nutr. 42 829-35 (1985)
28. Schrauzer, G., Trace Substances in Environmental Health 13:64 (1979)
29. Schrauzer, G., Bioinorganic Chem. 8:303-18 (1978)
30. Thomson, C. D., et al., Br. J. Nutr. 39:579-87 (1978)
31. Thomson, C. D., et al., Amer. J. Clin. Nutr. 36:24-31 (1982)
32. Robinson, M. F., et al., Br. J. Nutr. 39:589-600 (1978)
33. Levander, O. A., et al., Fed. Proc. 42:927 (March 1983)
34. Janghorbani, M., et al., Amer. J. Clin. Nutr. 40:208-18 (1984)
35. Butler, J. A., et al., Amer. J. Clin. Nutr. 53:748-54 (1991)
37. Foo Pan and Traver, H. Arch. Biochem. Biophys. 119:429-34 (1967)
36. Csallany, A. S. and Menken, B. Z., J. Amer. Coll. Toxic. 5(1) 79-85 (1986)
37. Clark, L. C. and Combs, G. F., J. Nutr. 116:170 (Jan. 1986)
38. Mutanen, M. and Mykkanen, H. M., Human Nutrition; Clinical Nutrition 39C 221-226 (1985)
40. Selenium: Old Horror Tales Disproved, Whole Foods 9(11) 11-12 (Nov. 1986).
41. Selenium: The Upper Limit of Safety, Whole Foods 9(10) 11-14 (Oct. 1986).
42. Selenium Safety, Part I, Whole Foods 9(9) 7-11 (Sep. 1986). 43. Here's Health p6 (April 1990)
44. Whiting, R. F. In: Selenium in Biology and Medicine, Spallholz, J. E., Martin, J. L. and Ganther, H. E., Eds. AVI Publishing, Westport, p325 (1981)
45. Thompson, H. J., et al., Cancer Res. 44(7) 2803-06 (July 1984)
All rights, including electronic and print media, to this article are copyrighted by Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).