Chapter 31. The Case for Selenium Part Two

Chapter 31. The Case for Selenium, Part Two 

Selenium Toxicity Diagnosed by Dr. House

Selenium Toxicity from overconsumption of Brazil Nuts, called Selenosis, was "reported" on an episode of Dr. House, a medical TV show that often takes artistic liberties to enhance entertainment value. (17-20)  In reality, there has never been a reported case of Selenosis from ingesting Brazil nuts.  This in merely one example of many egregious errors and biases against natural medicine on the Dr. House series, and is to be expected, considering the massive drug company advertising supporting the show.

Evidence that Selenium Prevents Prostate Cancer

A study published by Vogt in the 2003 International Journal of Cancer evaluated selenium levels in 212 men with prostate cancer, compared with healthy controls. They found "a moderately reduced risk of prostate cancer at higher serum selenium  concentrations",  above 135 ng/ml.(1)

Selenium Prevents Prostate Cancer in Genetic Mice

Another elegant study came from the University of Illinois in the 2006 Proceedings of the National Academy of Science.  This study used mice that were genetically manipulated twice. They were genetically modified to have a selenoprotein deficiency as well as an increased risk for prostate cancer. The selenoprotein-deficient mice exhibited accelerated development of prostate cancer in the form of prostate intra-epithelial neoplasia with microinvasion.  This study clearly implicated selenoprotein deficiency as a risk factor for prostate cancer, and selenium as a preventive agent. (2)  Yet another transgenic mouse prostate cancer study published in May 2009 AACR by Wang showed inhibition of prostate cancer and increased survival in mice treated with selenium compounds.(3)

Selenium Prevents Colon Cancer in Genetic Mice

Irons published a study in the 2006 Journal of Nutrition evaluating colon cancer in genetically altered mice, deficient in selenoproteins. The mice were given dietary selenium, and the colon was studied for cancer formation. The mice supplemented with dietary selenium had reduced colon cancer, with fewer pre-neoplastic lesions of the colon,  This was true for both the seleno-protein deficient mice as well as normal mice.  (4)  A second colon cancer study in mice from India published in the 2009 World Journal of Gastroenterology showed that dietary selenium supplements reduced colon cancer tumors by 40 % in mice chemically treated with carcinogens to produce colon cancer.(5)

Selenium Levels Predict Breast Cancer Risk

A study published in 1985 in Japan Cancer Research looked at serum selenium levels in American and Japanese women with breast cancer.   Healthy Japanese women had higher selenium levels of 286 mcg/ml compared to Japanese women with breast cancer who had lower selenium levels of 195 mcg/dl.  For healthy American women, serum selenium was higher at 191 compared to American women with breast cancer who had lower selenium of 167 mcg/ml. (6) 

Evidence that Selenium Prevents Breast Cancer 

A study in Israel published in 1988 evaluated serum selenium levels in 32 breast cancer patients compared to controls.  They found significantly lower serum selenium levels in the breast cancer patients (.076 ppm) compared to controls (.119 ppm). (7)

Selenium Prevents Breast Cancer in Mice

In a 1991 publication from Cancer Research, mice with chemically induced breast cancer (using DMBA) were treated with dietary selenite. Tumor incidence correlated inversely with the quantity of selenite consumed, clearly demonstrating inhibition of breast cancer by dietary selenium consumption.(8)

 Selenium Beneficial for BRCA Gene Carriers - Reduces Breast Cancer

This may be the most convincing evidence of selenium as a cancer preventive agent.  The BRCA gene is a mutation associated with increased risk of breast and ovarian cancer. Women with the BRCA1 gene face an 80 per cent lifetime risk of breast cancer and of 40 per cent lifetime risk of ovarian cancer.  The BRCA1 gene manufactures proteins involved in repairing oxidative damage to DNA, with repair of the double-stranded DNA breaks. The BRCA gene test is available from Myriad Genetics, which holds a patent on the human gene sequence.   A March 2010 court found the patent invalid, since human gene sequences are part of nature and in the public domain. 

Dr. Dziaman from Poland published a study in Nov 2009 looking at DNA damage in BRCA gene carriers.  They measured serum and urinary products of DNA oxidation with and without selenium supplementation, finding that damaged DNA products were higher in women with BRCA mutations, and were reduced by selenium supplementation.  Their results suggest that BRCA1 deficiency contributes to oxidative damage and breaks in cellular DNA, which may be responsible for cancer development.  In addition, selenium supplementation is beneficial, because it protects from oxidative DNA damage.(9)

Strong Evidence for a Selenium as Cancer Preventive Agent 

A study of BRCA gene carriers from Kowalska in Poland in 2005 provides strong evidence for selenium as a preventive agent.  Fifty five women with the BRCA1 gene mutation were supplemented with 275 µg of sodium selenite, daily for 8 weeks.  The amount of DNA damage was assessed from blood lymphocytes showing BRCA gene carriers had twice the DNA damage compared to their normal siblings.  However, Selenium supplementation given to BRCA gene carriers reduced the DNA damage to normal levels found in their siblings.(10)  A second larger study reported by Kowalska in 2006,  verified that selenium supplementation indeed reduces cancer in women with the BRCA1 gene. After two years of selenium supplementation, expected BRCA1-associated cancers were reduced in half.(11)

Sep 15 Selenoprotein genome and breast cancer

Which seleno-protein is the best candidate for breast cancer protection?  One of the new selenoproteins discovered is the Sep15 protein, and the gene for this protein is commonly found to be damaged or lost in breast cancer tissue and other solid tumors (12)

Dietary Sources of Selenium

One of the highest dietary sources of selenium is Brazil Nuts,  which each provide 12-50 mcg of seleno-methionine. (15)  Strunza studied selenium levels in volunteers who ingested 11 Brazil nuts per day for 15 days. Serum selenium rose from 55 mcg/ML to 208 Mcg/mL at the end of the 2 week study.  There were no ill effects reported. (16) 

A Case of Selenium Toxicity Diagnosed by Dr. House

As mentioned above, Selenium overdose from Brazil nut ingestion (i.e. Selenosis) was "reported" in an episode of Dr House.  In reality, there has never been a reported case of Selenosis from ingesting Brazil nuts in the US where selenosis is exceedingly rare, and usually due to exposure to an industrial or chemical plant accident, or dietary supplement manufacturing error.(17-21)   

Toxicity of  Selenium Excess

A report of selenium toxicity in the US appeared in the 2010 Archives of Internal Medicine.  200 cases of selenosis were caused by an error in manufacturing a liquid dietary supplement, which was subsequently recalled by the FDA. (13-14)  The recalled dietary supplement contained 200 times the labeled concentration of selenium, providing 40,000 mcg per day.  The recommended dosage for selenium is 200 mcg per day.  For the 200 cases of selenosis identified in the report, the average serum selenium level was 751 mcg/ML.  Symptoms of selenium toxicity include diarrhea, fatigue, hair loss, joint pain, nail discoloration or brittleness, and nausea. In view of this report, it would appear prudent to avoid liquid selenium preparations, and stick with tablets from known reputable sources.  In addition, it is recommended that you work closely with a knowledgeable physician, for monitoring serum selenium levels prior to, and during supplementation.

Conclusion: The evidence is now overwhelming that dietary selenium is an essential mineral important for health. Selenium deficiency increases risk of cancer, and supplementation is beneficial for those with serum selenium levels below 135 mcg/ML.  Since selenium is toxic at high doses, it is recommended that you work closely with a knowledgeable physician who can monitor levels.

References for Chapter 31. Selenium, Part Two, The Case for Selenium  as Cancer Preventive

(1) http://www.ncbi.nlm.nih.gov/pubmed/12494476 Int J Cancer. 2003 Feb 20;103(5):664-70.
Serum selenium and risk of prostate cancer in U.S. blacks and whites.  Vogt TM et al.

(2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472449/ Proc Natl Acad Sci U S A. 2006 May 23; 103(21): 8179–8184.  Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model Veda Diwadkar-Navsariwala et al.

(3) http://cancerprevention.aacrjournals.org/content/2/5/484.abstract Methyl-Selenium Compounds Inhibit Prostate Carcinogenesis in the Transgenic Adenocarcinoma of Mouse Prostate Model with Survival Benefit by Lei Wang et al Hormel Institute, University of Minnesota, Austin, Minnesota Cancer Prevention Research  AACR May 2009 2; 484

(4) http://www.ncbi.nlm.nih.gov/pubmed/16614422 J Nutr. 2006 May;136(5):1311-7. Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression. Irons R, Carlson BA et al.

(5) http://www.wjgnet.com/1948-5204/pdf/v1/i1/74.pdf 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

(6) http://www.ncbi.nlm.nih.gov/pubmed/3924710 Jpn J Cancer Res. 1985 May;76(5):374-7. Selenium in the blood of Japanese and American women with and without breast cancer and fibrocystic disease. Schrauzer GN, Molenaar T, Mead S, Kuehn K, Yamamoto H, Araki E.

(7) http://www.ncbi.nlm.nih.gov/pubmed/2484517 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, Shenberg C, Nir-El Y, Mantel M. Elias Sourasky Medical Center Tel-Aviv, Israel.

(8) http://cancerres.aacrjournals.org/cgi/content/abstract/51/17/4613  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. University of Illinois

(9) http://www.ncbi.nlm.nih.gov/pubmed/19843683 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. Poland.

(10) http://cebp.aacrjournals.org/content/14/5/1302.long 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.

Although our sample size was small, our results were highly significant; in every case, selenium supplementation resulted in a reduced frequency of chromosome breaks.

(11) http://www.hccpjournal.com/content/4/1/58 A Lowering of Breast and Ovarian Cancer Risk in Women with a BRCA1 Mutation by Selenium Supplementation of Diet by Tomasz Huzarski , Tomasz Byrski1, Jacek Gronwald1, Elżbieta Kowalska et al. Pomeranian Medical University, Szczecin, Poland in Hereditary Cancer in Clinical Practice 2006, 4:58

(12) http://www.cancer-therapy.org/CT1A/HTML/34%20%20Diamond%20et%20al,%20293-29%20c.htm Cancer Therapy Vol 1, 293-298, 2003. Allelic loss at the SEP15 locus in breast cancer by Mohamed A. Nasr, Ya Jun Hu, and Alan M. Diamond Department of Human Nutrition, University of Illinois at Chicago, Chicago, IL

(13)  http://archinte.ama-assn.org/cgi/content/abstract/170/3/256 Acute Selenium Toxicity Associated With a Dietary Supplement Jennifer K. MacFarquhar et al Arch Intern Med. 2010;170(3):256-261.

(14) http://www.bt.cdc.gov/agent/selenium/supplements2008.asp Toxic Levels of Selenium in Dietary Supplements The US Food and Drug Administration and Total Body Essential Nutrition, Inc, have recalled approximately 1000 bottles of diet supplements “Total Body Formula” and “Total Body Mega Formula.”

(15) http://www.ajcn.org/cgi/content/abstract/87/2/379 Brazil nuts: an effective way to improve selenium status. Am J Clin Nutr. 2008 Feb. Thomson CD, Chisholm A, McLachlan SK, Campbell JM. Department of Human Nutrition, University of Otago, Dunedin, New Zealand.

(16) http://www.vianutricia.com.br/imagens/naMidiaViaNutricia-Nutrition_Research.pdf
Brazil nut ingestion increased plasma selenium but had minimal effects on lipids, apolipoproteins, and high-density lipoprotein function in human subjects from Nutrition Research 28 (2008) 151–155 by Célia C. Strunza et al. São Paulo, Brazil

(17) http://www.imdb.com/title/tt1123416/quotes House M.D." Whatever It Takes (2007)

(18) http://en.wikipedia.org/wiki/Whatever_It_Takes_(House) Whatever It Takes" is the sixth episode of the fourth season of House and the seventy-sixth episode overall. It aired on November 6, 2007.

(19) http://www.politedissent.com/archives/1800 November 6th, 2007 House – Episode 6 (Season 4): “Whatever It Takes”

(20) http://hightechsurvivor.blogspot.com/2007/11/brazil-nut-overdose.html Brazil Nut OverDose

(21) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002502/pdf/westjmed00108-0050.pdf 
Fan AM, Kizer KW: Selenium-Nutritional, toxicologic, and clinical aspects.  West J Med 1990 Aug; 153:160-167

(22) https://www.myriadpro.com/  Myriad Genetics Web Site.

author: Dr Dach

Jeffrey Dach MD