Bioidentical Hormones 101 
The Book, by Jeffrey Dach MD

Chapter 30. Selenium from Toxin to Essential Mineral - Part One

 US Soil Selenium Jeffrey Dach MDChapter 30. Selenium, from Toxin to Essential Mineral - Part One

Selenium is an essential trace mineral critical for antioxidant defense, fertility, thyroid hormone metabolism, immune response, and muscle development.  First discovered in 1817, selenium was considered a toxic substance best avoided.  One hundred and forty years later, in 1957, the status of Selenium dramatically changed with a report of the first selenium deficiency disease. An obscure biochemist at the NIH, Klaus Schwarz, found that giving selenium to Vitamin E deficient mice protected them from liver degeneration.(1)

Left Image : Selenium Soil Content by Counties, with darker counties having higher selenium soil content. Courtesy of the United States Geological Survey (62)

White Marble Disease in Oregon Cattle

One year later in 1958, scientists at the University of Oregon discovered that selenium deficiency caused “white muscle disease”, causing muscle degeneration in cattle foraging grass on selenium depleted soils. They surmised that volcanic soil was low in selenium, and hot volcanic gas caused selenium depletion of the Oregon soil millions of years ago. Selenium supplementation prevented the white muscle disease.(2)  A soil selenium map of the United States shows selenium rich areas in the plains states and deficient areas in Oregon, the West coast and the South East.(62-63) 

Finland Has Low Selenium Soil

Finland is a country plagued with selenium depleted volcanic soils, and in 1984, was the first to add selenium to crop fertilizer in a mandated program of selenium enrichment.(12-13)

Keshan Disease in China Caused by Selenium Deficiency

In the 1960's and 1970's in China, government sponsored research discovered a form of cardiac muscle degeneration in humans called Keshan disease occurring in the Keshan province noted for low selenium levels in its soil.  Similar to "white muscle disease" in cattle,  Keshan disease caused the heart muscle to degenerate.  Afflicted children of the Keshan province succumbed to cardiac failure with a dilated, nonfunctional heart,  also called cardiomyopathy.  Selenium supplements were found to be preventive of the disease.(3-4)

Sudden Death From Selenium Deficient Cardiomyopathy

In the early 1980's, selenium deficiency was recognized in the United States when patients on long term artificial feeding died suddenly from cardiomyopathy (a form of heart failure) induced by selenium deficiency.  Apparently, the artificial feeding solution had not included selenium, resulting in selenium deficiency and sudden death from heart muscle degeneration. (8-10)

It's Not the Selenium, It's the Seleno-Protein

Selenium is an essential trace mineral because of the selenoproteins critical for antioxidant defense, fertility, thyroid hormone metabolism, immune responses, muscle development and function. Selenoproteins are thought involved in cancer prevention because of inverse correlation between soil selenium, selenium intake, selenium blood levels and cancer incidence. The lower the soil or blood selenium, the higher the incidence of cancer in that geographic area. (5-7)

Seleno-Proteins: When Stop Doesn't Really Mean Stop - What is Selenocysteine?

The amino acid, cysteine, normally contains a sulfur atom. However, when the sulfur atom is replaced by selenium, cysteine becomes seleno-cysteine. Subsequent incorporation of seleno-cysteine into a protein amino acid sequence is called a seleno-protein.

The DNA translation table which maps DNA codons to amino acids was completed in the 1960's. It is quite remarkable that 20 years later, it was discovered that the UGA Stop Codon sometimes is NOT a Stop Codon. The UGA stop codon can also translate as seleno-cysteine, the 21st amino acid. This was an unexpected twist which nobody expected, and biochemists were quite surprised by this new information.  Notice the translation table below has a code for START and STOP which instructs the cell when to start and stop the amino acid chain under construction. However, there is no code for seleno-cysteine which is incorporated into a seleno-protein.  This is because the STOP codon, (UGA) also serves to code for the amino acid, seleno-cysteine, whenever there is a “SECIS” instruction set present in the DNA code.

Inverse Codon Translation Table For Amino Acids

Amino acid


Amino Acid














































Dr. Vadim Gladyshev and Selenium, Correcting the Human Genome Project

The Genetic Code is a translation table which maps the code in the DNA (called codons) to one of the twenty amino acids, thereby providing the instruction set for the cell machinery to arrange long strings of amino acids into the proper sequence called a protein. The UGA Stop Codon also codes for seleno-cysteine, depending on another instruction set called the SECIS insertion sequence. Thanks to Vadim N. Gladyshev for much of our current knowledge. (Note Vadim N. Gladyshev has since moved from U Nebraska to Harvard). Based on this tricky dual translation of the UGA codon for seleno-cysteine, Gladyshev and his collaborators went about correcting the seleno-cysteine errors in the original DNA database. His new correction software is called Recode2. (14-23)

Selenoproteins- What Do They Do? Here are a Few Selenoproteins and Their Function

1) Glutathione Peroxidase – This is a major antioxidant which works in harmony with vitamin E converting (reducing)  hydrogen peroxide to water, and preventing lipid peroxidation and oxidative cellular damage. (24)

2) Iodothyronine De-iodinase Enzyme – This is involved in thyroid function, converts thyroid hormone T4 to T3. (24).   See the Iodine Book by David Brownstein MD for an excellent summary of selenium and thyroid function.(64)

3) Thioredoxin reductase – This is an antioxidant responsible for degrading peroxides and hydroperoxides which cause cell death, DNA damage, and tissue atrophy.(24)

4) Sept 15 Selenoprotein- This is a candidate for cancer prevention. (15)

There are about 40 families of selenoproteins. Most still have unknown functions.

Selenium Deficiency and Increased Cancer Risk - The Nutritional Prevention of Cancer Trial (NPC Trial)

The NPC Trial, published in 1996 in JAMA, was the brainchild of Larry C Clark and Gerald Combs, and the first prospective double-blind, placebo-controlled, randomized trial in the Western world to test a selenium supplement on a large population for its effect on cancer prevention.  Clark chose selenized yeast containing 200 mcg selenium for residents of the southeastern United States, where soil selenium levels are the lowest in the nation. Between 1983 and 1991, seven dermatology clinics recruited 1,300 patients, with a mean age of 63 years.  All had a history of basal and/or squamous cell carcinoma (skin cancer). The NPC Trial showed selenium supplementation significantly decreased the total cancer incidence by 50 percent, and specifically dropped the incidence of lung cancer by 48 percent, prostate cancer by 63 percent, and colorectal cancer by 58 percent. Those who entered the trial with plasma selenium levels less than 106 ng/mL showed both the greatest protection from selenium and the highest rates of subsequent cancer in the control group. (26-27)

The selenized yeast tablet used in the NPC trial was called Seleno-Excell from Cypress Systems which is available at your local vitamin shop or health food store under various brand names. (Note: I have no financial interest in any selenium products mentioned)

The SELECT Study - Selenium and Vitamin E Found Useless at Cancer Prevention

The 1996 NPC trial reigned supreme until it was discredited December 2008, by the disappointing results of the 2009 SELECT study, with Time Magazine and The New York Times proclaiming that selenium and vitamin E useless at prevention of prostate cancer. (32-33) The SELECT study was a randomized, placebo-controlled trial of Selenium and Vitamin E given to 35,533 men 50 years or older, and PSA of 4.0 ng/mL or less, to determine if the vitamins reduced risk of prostate cancer. The vitamins used were 200 µg L-selenomethionine and 400 IU of synthetic vitamin E. The results showed the vitamins did not prevent prostate cancer in this group. (29)

SELECT - Why Did It Fail ?

Hatfield and Gladyshev summarize the reasons why SELECT failed and why the NPC trial and many previous studies succeeded in showing a benefit of selenium supplementation (30). Rayman and Combs also commented on the SELECT study in a JAMA editorial .(31)  The major reason for failure is the SELECT patients started with higher serum selenium levels, in the range above 135 mcg/L found not to benefit from selenium supplementation. They already had plenty.

1) SELECT used seleno-methionine whereas the NPC used selenium-enriched yeast.

2) SELECT evaluated prostate cancer. How can selenium be shown to prevent prostate cancer when PSA Screening programs rapidly remove prostate cancers from the population before they progress? The NPC evaluated all cancers in patients with underlying history of skin cancer.

3) The subjects enrolled in SELECT had higher initial plasma levels of selenium than those in the NPC trial (135 ng/ml compared to 113 ng/ml, respectively). The subjects in the NPC trial were selected, in part, on the basis of their having relatively low serum selenium levels it was in this cohort that selenium supplementation was effective in reducing cancer risks.

4) SELECT used synthetic Vitamin E (all racemic), which is clearly inferior to natural vitamin E. Results may have been different for natural vitamin E.

Blood Selenium Levels below 130 ng/ml benefit from supplementation

In agreement with Dr Rayman, a 2008 study published by Bleys in the Archives of internal medicine found an inverse correlation between serum selenium and both cancer mortality, and all cause mortality.   They found that selenium supplementation was beneficial up to a serum selenium level of 130 ng/ml. (34) Above 130 ng/ml, they found no further benefit.  (34)

Important Point

Low Selenium constitutes a health risk with increased risk for cancer, and immune dysfunction.

Conclusion : The evidence is overwhelming that low selenium blood levels (below 130 ng/ml) constitute a health risk. It is suggested that selenium serum levels be routinely evaluated, and when found low, supplementation is indicated with selenium in the form of selenized yeast or L-seleno-methionine in the amount of 200 -300 mcg per day.

References for Chapter 30. Selenium, From Toxin to Essential Mineral, Part One

(1) J. Nutr. 133:3331-3342, November 2003.  History of Nutrition.  A Short History of Nutritional Science: Part 4 (1945–1985)1 Kenneth J. Carpenter. History of selenium.

WHAT’S NEW WITH SELENIUM …….FERTILIZING OREGON PASTURES By Gene Pirelli, Jim Oldfield, Wayne Mosher and Ron Hathaway - white muscle disease in Oregon

(3) Selenium: Antioxidant & Cancer Quencher From The March 1999 Issue of Nutrition Science News By Stephanie Briggs, Ph.D

(4)  The epidemiology of selenium deficiency in the etiological study of endemic diseases in China by Kei’ou Ge and Guangqi Yang .  Am J Clin Nutr February 1993 vol. 57 no. 2 259S-263S.

(5)   Selenoproteins by Jun Lu and Arne Holmgren . January 9, 2009 The Journal of Biological Chemistry, 284, 723-727.

(6) Selenium: An Essential Micronutrient Molecules 2009, 14(3), 1263-1278;  Review - Selenium as an Essential Micronutrient: Roles in Cell Cycle and Apoptosis. Huawei Zeng  

(7) Physiology, Vol. 21, No. 5, 307-315, October 2006 Selenoproteins and Their Impact on Human Health Through Diverse Physiological Pathways by Behzad Moghadaszadeh and Alan H. Beggs,

(8) Gastroenterology. 1982 Sep;83(3):689-93. Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition. by Fleming CR ET AL.

(9) Clin Pharm. 1984 Sep-Oct;3(5):531-5. Selenium deficiency and fatal cardiomyopathy in a patient receiving long-term home parenteral nutrition. Quercia RA, Korn S, O'Neill D, Dougherty JE, Ludwig M, Schweizer R, Sigman R.

(10) Med Sci Law. 2002 Jan;42(1):10-3.
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(11) Am J Clin Nutr. 1990 Sep;52(3):572-7. Cardiomyopathy associated with nonendemic selenium deficiency in a Caucasian adolescent. Lockitch G, Taylor GP, Wong LT, Davidson AG, Dison PJ, Riddell D, Massing B.

(12) The effect of nationwide selenium enrichment of fertilizers on selenium status of healthy Finnish medical students living in south western Finland Journal Biological Trace Element Research Publisher Humana Press Inc. Issue Volume 36, Number 2 / February, 1993

(13) A brief history of selenium research: From alkali disease to prostate cancer. (from poison to prevention)  J. E. Oldfield1 Oregon State University, Corvallis 97331

(14) Gerald Combs .

(15) EMBO reports 5, 2, 140–141 (2004) Finding needles in a haystack, In silico identification of eukaryotic selenoprotein genes by Donna M. Driscoll & Laurent Chavatte  Department of Cell Biology, Lerner Research Institute

Selenoproteins and selenoproteomes Vadim N. Gladyshev, University of Nebraska-Lincoln

(17) Vadim Gladyshev Lab Selenium and Redox Biology

(18) Vadim N. Gladyshev Professor Division of Genetics Department of Medicine Brigham and Women's Hospital Harvard Medical School New Research Building, Room 435 77 Ave. Louis Pasteur Boston, MA 02115

(19) Selenium research lauded Jun 2nd, 2008 BY TROY FEDDERSON,– Vadim Gladyshev, professor of biochemistry and director of the UNL’s Redox Biology Center, received the ORCA award for his research.

(20) Nucleic Acids Research Advance Access published online on September 25, 2009 . Recode-2: new design, new search tools, and many more genes BY Michaël Bekaert, Vadim N. Gladyshev et al.

(21)  Recode2.

(22) Universal genetic code late 60s

(23) Trends Biochem Sci. 1996 Jun;21(6):203-8.
Knowing when not to stop: selenocysteine incorporation in eukaryotes.Low SC, Berry al.

(24)  Selenium Biochemistry and Cancer: A Review of the Literature Lyn Patrick, ND

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(26)  NPC StudyJAMA. 2009;301(18):1876

(27)  Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin A Randomized Controlled Trial by Larry C. Clark, MPH, PhD et al. JAMA. 1996;276(24):1957-1963.

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(30)  Mol Interv. 2009 February; 9(1): 18–21.
The Outcome of Selenium and Vitamin E Cancer Prevention Trial (SELECT) Reveals the Need for Better Understanding of Selenium Biology Dolph L. Hatfield1 and Vadim N. Gladyshev

(31) JAMA. 2009;301(18):1876  Margaret P. Rayman; Gerald F. Combs, Jr; David J. Waters Selenium and Vitamin E Supplementation for Cancer Prevention

(32),8599,1865464,00.html Vitamins Do Not Prevent Prostate Cancer, Study Finds By Alice Park Wednesday, Dec. 10, 2008 Time Mag.

(33) October 28, 2008 Disappointing News on Vitamin E and Selenium By TARA PARKER-POPE NY Times

(34) Serum Selenium Levels and All-Cause, Cancer, and Cardiovascular Mortality Among US Adults by Joachim Bleys, MD, MPH; Ana Navas-Acien, MD, PhD; Eliseo Guallar, MD, DrPH Arch Intern Med. 2008;168(4):404-410.

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(37) Methyl-Selenium Compounds Inhibit Prostate Carcinogenesis in the Transgenic Adenocarcinoma of Mouse Prostate Model with Survival Benefit . Lei Wang et al Hormel Institute, University of Minnesota, Austin, Minnesota
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(43) Acute Selenium Toxicity Associated With a Dietary Supplement Jennifer K. MacFarquhar et al Arch Intern Med. 2010;170(3):256-261.

(44) Brazil nuts: an effective way to improve selenium status. Am J Clin Nutr. 2008 Feb. Thomson CD et al.

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(46) CYTOTOXIC MECHANISMS OF SELENIUM IN [PDF] E Olm - 2009 - Karolinska Institutet, Stockholm, Sweden

(47) FOSTER, H. D. (1986) Reducing Cancer Mortality: A Geo graphical Perspective, Western Geographical Series, vol. 23, University of Victoria, Victoria, B.C.

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(50) Biol Trace Elem Res. 1988 Jan-Apr;15:205-12. The distribution of selenium in human blood samples of Israeli population--comparison between normal and breast cancer cases. Chaitchik S et al.

(51) Cancer Causes Control. 2010 Jan 9. Toenail selenium status and DNA repair capacity among female BRCA1 mutation carriers. Kotsopoulos J et al.

(52) Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):2923-8. Selenium supplementation reduced oxidative DNA damage in adnexectomized BRCA1 mutations carriers. by Dziaman T et al.

(53) Cancer Epidemiology, Biomarkers & Prevention May 2005 14; 1302. Increased Rates of Chromosome Breakage in BRCA1 Carriers Are Normalized by Oral Selenium Supplementation by Elzbieta Kowalska et al.

(54) A Lowering of Breast and Ovarian Cancer Risk in Women with a BRCA1 Mutation by Selenium Supplementation of Diet.  Tomasz Huzarski1 , Tomasz Byrski1, Jacek Gronwald1, Elżbieta Kowalska et al.

(55),%20293-29%20c.htm Cancer Therapy Vol 1, 293-298, 2003. Allelic loss at the SEP15 locus in breast cancer by Mohamed A. Nasr et al.

(56) [Cancer Research 51, 4613-4617, September 1, 1991. Inhibition of 7,12-Dimethylbenz(a)anthracene-induced Mammary Tumors and DNA Adducts by Dietary Selenite by Jinzhou Liu et al.

(57) Selenium as a chemopreventive agent in experimentally induced colon carcinogenesis. World J Gastrointest Oncol 2009 October 15; 1(1): 74-81 by Fereshteh Ezzati Ghadi et al. Panjab University, India

(58) Int J Urol. 2006 Sep;13(9):1180-4. Selenium is inversely associated with bladder cancer risk: a report from the Belgian case-control study on bladder cancer. Kellen E, Zeegers M, Buntinx F. Belgium.

(59) Biol Trace Elem Res. 2009 Mar;127(3):200-10. Epub 2008 Oct 25.High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin's lymphoma. by Asfour IA et al.

(60) Emord Sues FDA: Selenium Claim Suppression Violates First Amendment .

(61) 2005 The American Society for Nutritional Sciences J. Nutr. 135:354-356, February 2005. The Level of Evidence for Permitting a Qualified Health Claim:
FDA’s Review of the Evidence for Selenium and Cancer and Vitamin E and Heart Disease1 Paula R. Trumbo2 Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD 20740

(62) U.S. Department of the Interior | U.S. Geological Survey. Mineral Resources On-Line Spatial Data. Selenium in Counties of the Conterminous States

(63) Selenium in Counties of the Conterminous States, U.S. Geological Survey

(64) Iodine, Why You Need It , Why You Can't Live Without It, by David Brownstein MD, Fourth Edition 2009, Medical Alternatives Press.

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