Selenium (Se)

Se – Selenium is found in igneous rocks at 0.05 ppm; shale at 0.6 ppm; sandstone at 0.05 ppm; limestone at 0.08 ppm; fresh water at 0.02 ppm; sea water at 0.00009 ppm; soils at 0.2 ppm (not universally distributed, vast areas of Earth are deficient or even totally devoid of Se; Se is found in the humus of alkaline soils when present); marine plants at 0.8 ppm; land plants at 0.2 ppm; land animals at 1.7 ppm (highest concentrations found in liver, kidney, heart, and skeletal muscle).

Selenium is the most efficient antioxidant (anti-peroxidant) and is found at the subcellular level in the glutathione peroxidase enzyme system and metallo amino acids (selenomethionine, etc.). Selenium prevents cellular and subcellular lipids and fats from being peroxidized which literally means it prevents body fats from going rancid (seen externally as “age spots” or “liver spots” – this brown gold peroxidized lipid is known as ceroid lipofucsin).

Selenium also functions to protect cellular and organelle bi-lipid layer membranes from oxidative damage – the cover illustration is an electron photomicrograph of a selenium deficient rhesus monkey liver mitochondria magnified 126,000 times. The inner membrane of the mitochondria (made up of enzymes and RNA) has precipitated out of the normal structure to become a nonfunctioning organic crystalloid. This type of damage seen through the standard light microscope is called “age pigment”. High intakes of vegetable oils including salad dressing, margarine and cooking oils concurrent with a selenium deficiency is the quickest route to a heart attack and cancer. The polyunsaturated configuration of the oils when heated or treated with hydrogen (“trans fatty acids”) literally causes the rancidity free radical damage) of cellular fat.

Selenium Deficiency Diseases

  • HIV (AIDS)
  • Anemia (RBC fragility)
  • Age Spots” & Liver
  • Fatigue
  • Muscular weakness
  • Myalgia (muscle pain and soreness)
  • Scoliosis
  • Muscular Dystrophy (MD, White Muscle Disease, Stiff Lamb Disease)
  • Cystic Fibrosis (congenital)
  • Cardiomyopathy (Keshan Disease, Mulberry head” Disease)
  • Multiple Sclerosis (MS) – associated with Hg poisoning
  • Heart palpitations
  • Irregular heart beat
  • Liver cirrhosis
  • Pancreatitis
  • Pancreatic atrophy
  • Lou Gehrig’s Disease (ALS) – associated with Hg poisoning
  • Parkinson’s Disease – associated with Hg poisoning
  • Azheimer’s Disease – associated with high vegetable oil consumption
  • Adrenoleucodystrophy (ALD -Lorenzo’s Oil” Syndrome)
  • Infertility
  • Low birth weight
  • High infant modality
  • Sudden Infant Death Syndrome (SIDS)
  • Cancer – associated with carcinogen contact as well as high vegetable oil intake
  • Clinical AIDS (HIV infection)
  • Sickle cell anemia

The clinical diseases associated with selenium deficiency are diverse and to the uninformed (allopathic physicians) shrouded in mystery. Selenium deficiency is one of the more costly mineral deficiency complexes affecting embryos, the newborn, toddlers, teens and adults alike.

Selenium deficiency can result in infertility in both men and women. Congenital selenium deficiency during pregnancy can result in a wide variety of problems ranging from miscarriage, low birth weight, high infant mortality, cystic fibrosis muscular dystrophy and liver cirrhosis.

Selenium deficiency in growing children can result in crib death or SIDS (Sudden Infant Death Syndrome) slow growth, small size (failure to reach genetic potential for size and mass), muscular dystrophy, scoliosis cardiomyopathy (muscular dystrophy of the heart muscle or Keshan Disease), anemia, liver cirrhosis muscular weakness, lowered immune capacity and neuromuscular diseases such as ALD (Adrenoleucodystrophy or “Lorenzo’s Oil type syndromes).

In young adults, selenium deficiency appears as anemia, chronic fatigue, muscular weakness, myalgia, muscle tenderness, pancreatitis, infertility, muscular dystrophy scoliosis, cardiomyopathy (this is especially common in young athletes such as basketball players and football players at the high school, college, university and professional levels), part of the anorexia nervosa complex, multiple sclerosis (adequate Se protects against Hg poisoning), Lou Gehrig’s Disease (ALS) and liver cirrhosis.

Selenium deficiency in adults appears as reduced immune capacity, anemia, infertility, “age spots” or “liver spots),” myalgia, muscle weakness multiple sclerosis, ALS, Parkinson’s Disease, Alzheimer’s Disease, palpitations or irregular heart beat, cardiomyopathy, hypertrophy or thickening of the cardiac muscle, liver cirrhosis, cataracts and cancer.

In a review of the anti-cancer effects of selenium Dr. Gerhard N. Schrauzer, head of the Department of Chemistry, UCSD states:

Selenium is increasingly recognized as a versatile anticarcinogenic agent. Its protective functions cannot be solely attributed to the action of glutathione peroxidase. Instead, selenium appears to operate by several mechanisms, depending on dosage and chemical form of selenium and the nature of the carcinogenic stress. In a major protective function, selenium is proposed to prevent the malignant transformation of cells by acting as a “redox switch” in the activation- inactivation of cellular growth factors and other functional proteins through the catalysis of oxidation-reduction reactions of critical ~SH groups or -S-S- bonds. The growth -modulatory effects of selenium are dependent on the levels of intracellular glutathione peroxidase and the oxygen supply. In general, growth inhibition is achieved by the Se-mediated stimulation of cellular respiration (more oxygen less cancer). Selenium appears to inhibit the replication of tumor viruses and the activation of oncogenes by similar mechanisms. However, it may also alter carcinogen metabolism and protect DNA against carcinogen-induced damage. In additional functions of relevance to its anticarcinogenic activity, selenium acts as an acceptor of biogenic methyl groups, and is involved in detoxification of metals and certain xenobiotics. Selenium also has immunopotentlating properties. It is required for optimal macrophage and natural killer cell functions.

The school of pharmacy from the University of Georgia released a report in August of 1994 that concludes a human selenium deficiency is related to the onset of full blown AIDS in chronically infected HIV patients. According to their report, HIV requires large amounts of selenium for replication, and in selenium deficient patients, the virus competes with the patient for limited amounts of the essential mineral. The HIV patient actually dies of selenium deficiency encephalopathy, liver cirrhosis or cardiomyopathy. Long term HIV patients (20 years or more) that never developed full-blown AIDS had supplemented with relatively large amounts of selenium.

Selenium is a trace mineral nutrient with anticancer and antiaging properties. Selenium helps protect cells against oxidative stress. As a part of the enzyme glutathione peroxidase, selenium serves as an antioxidant by destroying highly reactive chemicals that can form free radicals. Glutathione peroxidase destroys hydrogen peroxide, a naturally occurring chemical that is a powerful oxidizing agent. Hydrogen peroxide is produced for antimicrobial defense by macrophages, a type of white blood cell that engulfs foreign invaders, and it is a by-product of another antioxidant system (superoxide dismutase) that destroys a highly reactive form of oxygen called superoxide. Glutathione peroxidase neutralizes oxidative damage to lipids in cell membranes, thus limiting their damage due to free radical attack. Selenium may possess other antioxidant properties as well.

Selenium is generally recognized as an anticancer agent. In selenium-deficient experimental animals, liver cells become defective and more prone to become cancerous when activated. Studies show that populations with a low selenium intake are more prone to gastrointestinal, breast and rectal cancers. Deficiency of selenium leads to lowered glutathione peroxidase activity. Furthermore, extensive Chinese studies have suggested that selenium supplementation provides protection against hepatitis B and liver cancer. Selenium may inhibit the development of cancer by blocking the activation of certain cancer-promoting genes, by inhibiting viruses linked to cancer or by supporting healthy cell division and protecting cells against oxidative damage that could damage their DNA.

Selenium supports a healthy immune system, where it stimulates antibody production and defensive cells (lymphocytes, macrophages and natural killer cells). Some AIDS patients may be selenium deficient. Selenium can block mercury, arsenic and cadmium poisoning. Damaged heart muscle (cardiomyopathy) has occurred in patients fed intravenously mixtures that lacked selenium, and populations in areas of China characterized by regional selenium deficiency are more disease prone. Osteoarthritis in Chinese children has also been linked to selenium deficiency.

Recommended Dietary Allowances (RDA) published in 1989 proposed a selenium RDA for the first time as 70 mcg/day for men and 55 mcg for non-pregnant, non-lactating women. Obtaining adequate selenium is a growing problem in the United States. Regions like the Pacific Northwest, the Great Lakes region and some southern states (Georgia and the Carolinas) possess low soil concentrations of selenium, and vegetables and grains growing in depleted soils contain only low levels of selenium. Possibly acid rain prevents plants from taking up this mineral from soil. For insurance, some may wish to supplement with no more than 200 mcg of organic selenium per day. This doubles the average U.S. intake of about 100 mg/day.

Chemically combined selenium represents the most prevalent form of the selenium in the typical diet. Selenium can replace sulfur in the amino acids cysteine and methionine to form the analogs, selenocysteine and selenomethionine. Selenocysteine occurs in a variety of proteins including glutathione peroxidase and is found in meat. Selenomethionine cannot be synthesized by the body and is supplied in the diet by a variety of foods. It can substitute for methionine in a variety of the body’s proteins. The breakdown of methionine and selenomethionine releases cysteine and selenocysteine, respectively.

Biochemical function

Until recently, the only known metabolic role for selenium in mammals was as a component of the enzyme glutathione peroxidase which, together with vitamin E, catalase and superoxide dismutase, is a component of one of the antioxidant defense systems of the body. Recently, Burk and his colleagues have made great strides in the purification and characterization of their “selenoprotein-P”, but so far they have been unable to clarify its function in people or in animals. Several different selenium-containing enzymes have been described in microorganisms, and it is likely that selenoproteins other than glutathione peroxidase remain to be discovered in higher animals. There is, for example, growing evidence that an additional selenoenzyme protein is involved in the synthesis of the hormone triiodothyronine from thyroxine.

The Use and Importance of Selenium

By Herb Boynton

Early in December, 1988, a report in the Sacramento Bee warned that millions of Americans might be at risk of being poisoned by foods containing high levels of selenium. This story raised fears concerning the safety of the foods we eat, suggested that our regulatory agencies are lax and grossly exaggerated the toxicity of selenium.

Selenium is a rare element which has many properties resembling those of sulfur. It is widely but unevenly distributed on the earth’s crust. Because it is taken up by plants, it has always been in our food chain. Organisms not only adapted to its presence, but also through evolution they even learned how to put it to good use.

Without selenium, mammalian cells cannot grow, and life as we know it could not exist. Farmers in many parts of the United States learned this the hard way: For many years they had to face huge annual losses of livestock due to selenium deficiency diseases. These persisted until the Food and Drug Administration permitted the addition of selenium to feed.

In humans, selenium deficiency causes degenerative changes of the heart and a fatal cardiomyopathy. In China, thousands of children and young women died each year until large-scale selenium supplementation programs were instituted. Other studies have linked a lack of selenium with a diminished resistance to cancer. Several supplementation trials are underway to establish the value of selenium in cancer prevention.

The Sacramento Bee claimed, on the basis of the data it collected, that some common foods consumed by Americans are contaminated by potentially toxic levels of selenium. The FDA, which has been monitoring the selenium levels in U.S. foods on a regular basis since 1974, disagrees. It appears that some of the newspaper’s high estimates arose because of errors in the conversion of selenium levels expressed on a dry-weight basis to fresh-weight food portions.

Reliable estimates indicate that the selenium intakes of the great majority of Americans lie between 50 and 200 micrograms per day, an amount declared to be “adequate and safe” by the Food and Nutrition Board of the National Academy of Sciences. Other scientists believe that the optimal selenium intake level lies somewhere between 300 and 500 micrograms per day or at roughly twice the average U.S. intake. Selenium intakes of this magnitude are typical for adults in Japan.

In regions with locally excessive levels of selenium, toxic intake levels are occasionally reached. Symptoms of selenium poisoning appeared among the inhabitants of Enshi, a town in central China, after they had unknowingly ingested 5,000 micrograms of selenium per day for several months. This poisoning episode occurred when, as an emergency measure, seleniferous corn had to be consumed due to the failure of a rice crop.

Even at these high selenium intakes, the toxic symptoms were mild and reversible, and they disappeared after the normal diet was resumed.

The Enshi incident, which occurred about 10 years ago, shows that the threshold level of chronic selenium toxicity is about 10 to 20 times higher than the nutritional intake. The margin of safety for selenium thus is actually remarkably wide. Toxic levels are hardly ever reached since, even in the high-selenium regions of South Dakota, only a few people obtain more than 600 micrograms of selenium per day.

Author: Gerhard N. Schrauzer, Ph.D., is a professor of chemistry at the University of California, San Diego, and is one of the world’s leading authorities on selenium.

Selenium Deficiency and Increased Risk of Lung Cancer

Serum samples were taken from 21,172 Finnish men between 1968-1972. Within 11 years, lung cancer was diagnosed in 143 of these people. These cancer victims were matched by age and region with 264 control subjects. The stored serum samples of these people were then analyzed for selenium content. The subjects who eventually developed lung cancer showed lower serum selenium than did the controls.

When the group as a whole was analyzed, subjects with selenium in the lowest 20% had 3.3 times the subsequent risk of lung cancer seen in those subjects with selenium in the highest 20%.

These results are in accord with other studies strongly suggesting that poor selenium nutrition may possibly be a significant risk factor for lung cancer.

Authors: Paul Knekt, Georg Alfthan, Arop Aromaa, Matti Hakama, Timo Hakuhnen, Jouni Maatela, Richard Peto, Erkki Saxen, Lyly Teppo.

Social Insurance Institution, National Public Health Institution, Finnish Cancer Registry, Department of Public Health, University of Tampere, Tampere, Finland.

Selenium, Aflatoxin and Cancer

(Experimental Study on Selenium Blockade of Primary Hepatocarcinoma Induced by Aflatoxin in Rats)


Aflatoxin is an extremely potent carcinogen produced by molds that contaminate peanuts and other foods. It is considered to be a major cause of liver cancer in the Third World.

This study demonstrated that supplementary selenium protects rats from aflatoxin-induced liver cancer; cancer incidence was 65% in rats receiving the control diet, but only 26% in those fed extra selenium.

In addition, the onset of liver cancer was delayed in the selenium-fed group. Improved selenium nutrition may offer a practical approach to prevention of liver cancer in Third World countries and perhaps, to some extent, in developed countries as well.


Author: Li Wenguang, Shou Longqi, Qidong LiverCancer Institute, Jiangsu, China.

Selenium and Heart Function (Effect of Selenium on the Function of Cultured Rat Heart Cell)


When rat heart cells are grown in 1 culture, the addition of selenium to the medium increases the frequency and amplitude (strength) of contractions, while promoting the synthesis of nucleic acids (RNA) and enhancing membrane stability. These effects are especially marked when the cells are deprived of oxygen and glucose for 60 minutes.

Good selenium nutrition may thus help to preserve the structural and functional integrity of heart tissue subjected to a temporary loss of blood flow, as in the case of heart attack or occlusion of one or more coronary arteries.

Author: Guangyuan Li, Yingyun Ren, Wei Cheng, Institute of Integrated Traditional and Western Medicine, I Man Medical University, Xian, China.

Selenium Supplementation, Heart Attack and Stroke (Effects of Selenium Supplementa- tion on Platelet Function as As- sessed by Platelet Aggregation and Glutathione Peroxidase Activity)


Platelets are the blood cells that aggregate, or clump, to trigger blood clots. Several previous studies have suggested that good selenium nutrition helps to control platelet aggregation. In this study, young men were supplemented for four weeks with 200 mcg selenium daily as high selenium yeast. An increase in platelet glutathione peroxidase activity was observed during supplementation.

Platelet aggregation in response to the triggering agent (collagen) was decreased, as was production of the clot-promoting compound thromboxane. By helping to stabilize platelets, good selenium nutrition may promote cardiovascular health and may reduce the risk of both heart attack and stroke.

This effect is somewhat similar to that of aspirin. However, aspirin is a drug that produces a pharmacological effect, whereas selenium is a nutrient which functions to normalize platelet activity.

Authors: H.W. van der Torre, J. Veenstra, H. van de Pol, H. van Steenbrugge, S. Pelupessy and G. Schaafsma, the Ockhuizen Department of Nutrition,

TNO-CIVO Toxicology and Nutrition Institute, P.O. Box 360, 3700 Aj Zeist, The Netherlands.

Selenium, Vitamin E and Conges- tive Heart Failure (Selenium and Vitamin E Defi- ciency in Mini Pigs as an Animal Model for Keshan Disease)

Antioxidant deficiency in mini pigs is being studied as a possible model for Keshan disease, a syndrome of heart failure triggered by selenium deficiency and common in selenium-depleted regions of China.

In mini pigs, combined deficiency of selenium and vitamin E leads to inefficient functioning of the left chamber of the heart (left ventricle), with a compensatory thickening of the heart wall. This poor heart function leads to blood pooling in the liver and lungs. Heart glutathione peroxidase activity was 30% of that seen in normally fed animals.

This animal model underlines the crucial importance of antioxidant nutrition (selenium and vitamin E) to efficient heart function.

Authors: K.H. Konz, M. Haap, Y. Xia, K.E. Mill, R.A. Walsh*, and R.F. Burk, Dept. of Medicine, Vanderbilt University, Nashville, TN 37232.

The following info on Selenium is from Julian Whitaker, MD’s Health & Healing newsletter; Vol. 7, No.2, Feb 1997

The Selenium Saga Started With Skin Cancer

Selenium’s role as an anti-cancer nutrient was first published by Dr. Raymond Shamberger in 1965. Knowing that skin cancer was caused by free radical damage, he used selenium, which is a potent antioxidant, on the skin of animals subjected to ultraviolet light and reported a marked reduction in cancer incidence. This started a flurry of animal studies with selenium, which clearly demonstrated that this unique mineral could prevent carcinogens from causing cancer, and also stop the process once cancer had been introduced.

Selenium Protects You Against Cancer on Three Levels

Selenium seems to have several mechanisms of anti-cancer activity.

1. First are the antioxidant properties of selenium. It is essential for your body’s generation of glutathione, an important antioxidant that mops up hydrogen peroxide, a potent free radical produced in your body by normal metabolic processes.

2. Selenium’s ability to protect you against cancer goes beyond this. At somewhat higher levels, selenium facilitates the quick repair of free radical damage to the DNA molecule. Our current understanding of cancer is that a damaged DNA molecule replicates, carrying with it this “spark” that ignites the growth of a tumor. If adequate selenium is present, however, the DNA molecule is repaired-and normal cellular function ensues.

3. Perhaps the most dramatic property is that selenium initiates apoptosis, or cell death, in cancerous and precancerous cells. Cancer cells generally divide rapidly and die early. Selenium appears to cause cancer cells to die before they replicate, thereby short-circuiting again the generation of malignancy, tumor growth and cancer spread.

Research on Selenium and Cancer in Humans Started with Soil Analysis

Even though the research on animals was convincing and consistent, Dr. Shamberger looked for a connection between selenium with human cancers. In the early 1970s, noting that selenium’s presence in American soil varied from region to region, Dr. Shamberger demonstrated that cancer rates were significantly higher in areas of the country where soil selenium levels were lower.

This finding had been convincingly confirmed by studies in China. China is unique in that there are areas of the country in which the soil selenium levels are so high they’re almost toxic, and other areas where selenium ‘is almost absent.

An Analysis in China Showed a Clear Correlation

Blood levels of selenium are an excellent means of gauging selenium intake. By examining selenium blood levels in samples from blood banks in 30 different regions of China, scientists were able to classify the soils in the various regions as either 1) low, 2) medium or 3) high selenium. They then looked at the total death rates from cancer in these three defined regions and found a ratio of 3:2:1!

In other words, the cancer death rate in the high selenium regions was only one third of that in the low selenium regions. This finding, which was published in 1985, was criticized for technical reasons and, not surprisingly, received very little serious attention from scientists or the media. However, a reduction in cancer death rate of 66% is a finding that only an idiot would dismiss on technicalities.

Two Studies Provided Further Evidence…

In the 1980s, Dr. Shu-Yu Yu and colleagues at the Cancer Institute, Chinese Academy of Medical Sciences in Beijing, China set out to test these findings with more controlled research. With support from Nutrition 21, a small nutritional supplement company, they examined the effects of selenium in a double-blind, placebo-controlled trial of 226 people known to be at high risk for liver cancer because they carried the hepatitis B antigen in their blood. These patients were given either a placebo or 200 mcg of high selenium yeast (a food form of selenium) every day. At the end of four years there were five cases of liver cancer in the placebo group and none among those taking daily selenium.

Dr. Yu also recruited 2,474 family members of people who had developed liver cancer and so were judged to be at higher risk for the disease. Half received 200 mcg of high selenium yeast, and the other half received a placebo. During the two years of the study, 13 of the 1,030 controls developed liver cancer, compared to only 10 of the 1,444 on selenium. That’s a 45% reduction in cancer incidence in the selenium group.

… But No One Was Interested in These Astonishing Results…

The results of both of these studies were statistically significant, yet they failed to generate interest in the United States. Our conventional mindset toward cancer is to simply ignore the significance of nutritional elements, and consequently, no money is allocated for studies of this nature.

Again, Nutrition 21 responded by giving a small grant to Dr. Clark, chief researcher of the most recent study, who was committed to discovering the truth about selenium. All of the evidence, both animal and human, pointed to an incredibly powerful anti-cancer effect, but the acid test for American physicians–an American, double-blind, placebo-controlled trial–had not been done.

… So an American Double-Blind, Placebo-Controlled Study Was Done

Dr. Clark then recruited patients’ in several dermatology clinics who had had either squamous cell or basal cell carcinomas removed. From 1983 through 1991, 1,312 patients were enrolled and given either a placebo or 200 mcg of high selenium yeast daily. Blood selenium levels initially averaged 114 ng/ml, and remained at this level, in the placebo group. Those taking selenium experienced a 67% increase in their blood selenium, to a level of 190, which remained more or less constant throughout the test. This blood level was in the range of those of people living in areas with selenium-rich soil, and was far below the 1,000 ng/ml level identified as possibly toxic by the Environmental Protection Agency.

The Results Were Rapid and Dramatic.

Most remarkable was the rapidity with which the investigators noted a reduction in serious cancers: In fact, selenium seems to offer cancer protection almost immediately, as the study showed. The overall cancer rate in the selenium group was 37% lower than in the placebo group, and the total cancer death rate was 50% lower in the selenium group, both astoundingly high differences.

The chances of this simply being a fluke were 3 in 10,000. Without question, selenium was the reason for this dramatic reduction in the incidence of, and death rate from, cancer.

Selenium’s Protective Effects Were Clear for Certain Cancers

Selenium’s effects on specific cancers were also identified. Interestingly, skin cancers, which the study was initially designed to evaluate, showed little response to selenium. However, the selenium group had a 63% reduction in the incidence of prostate cancer, a 58% reduction in colon or rectal cancer, and a 45% reduction in lung cancer.

The Study Was Terminated Early Because the Results We re So Clear

The results were so definitive that the study was ended early. The data were not supposed to be publicly viewed or published until 1998, but the study was stopped in 1996 because of the dramatic reduction in cancer incidence and death in the selenium group. The researchers felt it would be inappropriate to allow the placebo group to continue taking an agent which did nothing, while they could be taking a supplement that would reduce their risk of serious and deadly cancers.

I can’t Emphasize Enough the Importance of These Results for You

It is difficult for me to articulate the magnitude of this study. Even if the results were only half as good as they were (25% vs. 50% reduction in death rate), you’re still looking at saving close to 100,000 lives a year, just from taking an inexpensive, completely safe (at 200 mcg a day) nutritional supplement. This is one of nature’s most powerful agents for protection against cancer.

Bioinorg Chem 1978 Apr;8(4):303-318

Selenium in human nutrition: dietary intakes and effects of supplementation.
Schrauzer GN, White DA

The dietary selenium intakes of a young couple residing in Southern California were determined to be 107 and 99 micrograms/day for the husband and the wife, respectively, on the basis of a 30 day study. For other young adult Californians, the selenium intakes were estimated from 90 to 168 micrograms/day. The highest intakes were observed in individuals subsisting on diets rich in whole wheat grain cereal products and seafoods. The selenium concentrations in whole blood of the subjects under study correlated with the dietary selenium intakes directly (P less than 0.001). The administration of 150 micrograms of selenium/day in the form of commercially available supplements increases the blood selenium concentrations. After 3 weeks of supplementation, the selenium concentrations in whole blood of our subjects reached 0.21 micrograms/ml. Prolonged supplementation at higher Se dosage levels causes further increases of the blood concentrations: Two individuals who had been ingesting 350 and 600 micrograms/day for 18 months exhibited blood selenium levels of 0.35 and 0.62 micrograms/ml. The blood selenium concentration of all subjects declined slowly after cessation of supplementation. Selenium uptake from the supplements was not affected by the joint administration of zinc supplements at 15 mg zinc/day. Glutathione peroxidase blood levels did not correlate with blood Se concentrations.

Environ Physiol Biochem 1975;5(2):107-118

A tentative recommendation for the maximum daily intake of selenium.
Sakurai H, Tsuchya K

In order to make a tentative recommendation for the maximum acceptable daily intake of selenium, relevant data were compiled from the available literature. Normal daily intake of selenium from foods was estimated as about 100 mcg, half of which comes from fish and shellfish (in an average adult Japanese). Intake of selenium from other sources was negligible. The amount of selenium excreted in the urine was found to be compatible with the estimated value of the daily oral intake. The range of the margin of safety was then estimated as 10 to 200 times the normal level on the basis of human and animal toxicity data. The variation of dietary selenium intake in the general population is discussed, leading to the conclusion that the consumers of large amounts of fish may ingest as much as 500 mcg daily. Consequently, a value of 500 mcg is proposed as the tentative maximum acceptable daily intake of selenium for the protection of human health.

Zinc and selenium modulate thyroid hormone production
To explore the relationships between zinc and selenium and the metabolism of thyroid hormone, rats were fed either a zinc deficient (4 mg/kg body weight), zinc adequate (45 mg/kg), selenium deficient (0.4 mg/kg) or selenium sufficient (3 mg/kg) diets. Zinc deficiency decreased T3 and free T4 serum levels, by 30%. Total T4 concentration was unchanged. Selenium-deficient animals had lower T3 and total T4 serum levels. Analysis of liver enzymes indicated that hepatic deiodinase (DI-I) activity was lower in either zinc or selenium deficiency than in control animals fed zinc and selenium adequate diets.

Comment: Results of research on the effect of zinc deficiency on the metabolism of thyroid hormones are conflicting. In part this is due to different effects observed with severe zinc and selenium deficiencies, as compared with moderate mineral deficiencies how can zinc deficiency decrease thyroid hormone production? Zinc plays no direct role in 5′-deiodinase and inhibition of thyroid hormone processing can occur indirectly. As an example, zinc deficiency can lead to lower insulin secretion, and low DI-I activity is observed in diabetic rats. Zinc deficiency lowers thyroid stimulating hormone and thyrotropic hormone secretion and thus account for reduced free T4. Recall also that zinc stabilizes membranes to oxidative damage, and that it is an essential cofactor for the defensive enzyme, superoxide dismutase.

What about the role of selenium in the thyroid gland? The effects are also likely to be indirect. As selenocysteine, selenium is required for glutathione peroxidase, the primary mechanism for disposing of hydrogen peroxide. This oxidant is an inevitable by-product in the iodination of thyroglobulin, the precursor of thyroid hormone. Therefore selenium indirectly assures that hydrogen peroxide does not accumulate. In contrast with zinc, selenium is a component of the iodothyronine 5′-monodeiodinase, which creates T3. Thus selenium deficiency both lowered DI-I activity, and decreased the conversion of T4 to T3. It is curious that the concentration of T3 was much lower than reported for severely selenium-deficient rat.

Kralik A et al. Influence of zinc and selenium deficiency on parameters relating to thyroid hormone metabolism. Horm Metab Res 1996; 28:223-226

Biol Trace Elem Res 1996 Jan;51(1):31-41

Selenium, zinc, and thyroid hormones in healthy subjects: low T3/T4 ratio in the elderly is related to impaired selenium status.
Olivieri O, Girelli D, Stanzial AM, Rossi L, Bassi A, Corrocher R

Institute of Medical Pathology, University of Verona, Italy.

Iodothyronine 5′ deiodinase, which is mainly responsible for peripheral T3 production, has recently been demonstrated to be a selenium (Se)-containing enzyme. The structure of nuclear thyroid hormone receptors contains Zinc (Zn) ions, crucial for the functional properties of the protein. In the elderly, reduced peripheral conversion of T4 to T3 with a lower T3/T4 ratio and overt hypothyroidism are frequently observed. We measured serum Se and RBC GSH-Px (as indices of Se status), circulating and RBC Zinc (as indices of Zn status), thyroid hormones and TSH in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to avoid abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid under- or malnutrition conditions, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. Low T3/T4 ratios and reduced Se and RBC GSH-Px activity were observed only in the older group. A highly significant linear correlation between the T3/T4 ratio and indices of Se status was observed in the older group of subjects (r = 0.54; p < 0.002, for Se; r = 0.50; p < 0.002, for RBC GSH-Px). Indices of Zn status did not correlate with thyroid hormones, but RBC Zn was decreased in older as compared with younger subjects. We concluded that reduced peripheral T4 conversion is related to impaired Se status in the elderly.

Biol Trace Elem Res 1996;53(1-3):65-83

Selenium-vitamin E supplementation in infertile men. Effects on semen parameters and micronutrient levels and distribution.
Vezina D, Mauffette F, Roberts KD, Bleau G

Department of Obstetrics and Gynecology, University of Montreal, Canada.

In order to verify the hypothesis that selenium (Se) and vitamin E (Vit E) could improve male fertility, nine oligoasthenoteratozoospermic men were supplemented for a period of 6 mo. with Se and Vit E. Compared to the baseline period (presupplementation) of 4 mo., statistically significant increases were observed for Se and Vit E levels, sperm motility, percent live, and percent normal spermatozoa. These improvements are likely to be “supplementation-dependent,” since all of the parameters returned to baseline values during the posttreatment period. None of the couples reported a pregnancy during the study. The HPLC analysis conducted on the serum of one of the patients showed the existence of at least six different Se-containing peaks, whose Se content was affected by supplementation. The mechanism(s) involved in these improvements of semen parameters is presently under investigation.

Biol Trace Elem Res 1998 Mar;61(3):287-301

Influence of selenium deficiency on vital functions in rats.
Matsuda A, Kimura M, Itokawa Y

Infusion Research Department, Hoechst Marion Roussel Ltd. 1658, Shiga, Japan.

To clarify the relationship between selenium (Se) deficiency and functional disorders, the authors determined the Se concentration, anti-oxidant enzyme activity, and other parameters in rats fed a Se-deficient diet. Rats fed the Se-deficient diet showed a decrease in Se concentration and glutathione peroxidase (GSH-Px) activity in plasma, erythrocytes, heart, liver, and skeletal muscle from the first week after the initiation of the diet, an increase in heart lipid peroxide concentration from the second week, and an increase in liver glutathione S-transferase activity from the fourth week. From the twelfth week, a decrease in the growth rate in the rats fed the Se-deficient diet was observed. In spite of this growth impairment, no changes in electrocardiogram, muscle tone, degree of hemolysis, plasma biochemistry, or hematological values were detected. In summary, the authors found that a reduction of body Se is easily induced, but that the appearance of functional disorders following Se deficiency is difficult to detect in rats.

Biol Trace Elem Res 1996 Jun;52(3):241-248

Selenium status is decreased in patients with intrinsic asthma.
Kadrabova J, Mad’aric A, Kovacikova Z, Podivinsky F, Ginter E, Gazdik F

Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic.

Lowered selenium (Se) status has been observed in asthma patients. An increased production of reactive oxygen species (ROS) owing to inflammatory condition has also been found in these patients and thus antioxidant properties of Se via glutathione peroxidase (GPx) activity are of great importance. Concentrations of Se in plasma and erythrocytes as well as erythrocyte GPx activity in 22 intrinsic asthma patients (five patients; all women were aspirin-sensitive) were compared with those of 33 control subjects. Se concentrations in both plasma and erythrocytes and GPx activity were decreased in intrinsic asthma patients. There were no significant differences in investigated parameters of Se status between aspirin-tolerant and aspirin-intolerant patients within intrinsic asthma group. Significantly high positive correlation between plasma and erythrocyte Se concentrations was found when regarding all subjects as a whole. Se supplementation might be beneficial to patients with intrinsic asthma, which may be at risk of Se deficiency.


Selenium & Viruses
In his search for biochemical and environmental factors that decrease the severity and incidence of viral disease, Ethan Will Taylor, PhD, Associate Professor of Medicinal Chemistry at the University of Georgia College of Pharmacy, came across selenium. Chinese studies have shown that selenium deficiency may actually induce Hepatitis B and coxsackievirus infection (related to the polio family and the common cold virus). Selenium supplementation decreased the incidence of these diseases. Large doses of selenium, given during a 1993 study, reduced the death rate from 100% to 30% in cases of “incurable” viral hemorrhagic fever (similar to Ebola virus). Taylor has suggested that, when selenium is present, some viruses manufacture selenoproteins that repress their own reproduction -making them less virulent. Research by an Atlanta colleague indicates that HIV may be one such virus.

Selenium deficiency apparently encourages viruses to mutate into more dangerous forms. Researchers put a benign strain of coxsackievirus into a selenium-deficient mouse virus mutated into a more virulent form that did more damage. When the mutated virus infected other mice, it remained virulent, even though the mice were not selenium-deficient. Taylor says: “If selenium deficiency increases the virulence of some viruses, it could be a factor contributing to the apparent emergence of more serious ‘new’ viral diseases.”
“Exclusive Interview: Viral Modification and Control with Selenium -Ethan Will Taylor, PhD” Dr. Jonathan V. Wright’s Nutrition & Healing with Alan R. Gaby, MD June 1996. For subscription information, call 800-528-0559 or 602252-4477.

Biol Trace Elem Res 1997 Jan;56(1):117-124

Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong.
Yu SY, Zhu YJ, Li WG

Cancer Institute, Chinese Academy of Medical Sciences, Peking Union Medical
College, Beijing, China.

High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr. showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect.


Preventing hepatitis with selenium
The effect of selenium supplementation on the incidence of hepatitis was investigated in Qidong County of Jiangsu Province in China, where the carrier rate of hepatitis B surface antigen (HBsAg) is 15% or higher in some townships. Table salt fortified with 15 ppm of anhydrous sodium selenite (corresponding to 6.7 ppm selenium) was distributed for three years to 20,847 individuals living in one township of Qidong County, while six surrounding townships received normal table salt (control group).

Prior to and during the first year of the study, there were no significant differences between the selenium and control groups in the annual incidence of viral hepatitis. During the second year of the study, the incidence of hepatitis was significantly lower in the selenium group than in the control group (1.20 vs. 2.96 per 1,000; 59.4% reduction, p < 0.001). A similar reduction in incidence was seen during the third year (4.52 vs. 10.48 per 1,000; 56.8% reduction, p < 0.002). Selenium supplementation was associated with a reduced risk of both hepatitis A and hepatitis B.
COMMENT: This study demonstrated that fortification of table salt with selenium significantly reduced the incidence of infectious hepatitis (A and B) in an area of China with a high carrier rate of HBsAg. During the past several years, selenium has been shown to have activity against a wide range of pathogenic viruses. This antiviral activity appears to be attainable in vivo with “nutritional” doses of selenium, although higher amounts may exert a more pronounced effect (at least against some viruses). Of course, excessive amounts of selenium can cause toxicity, so (as usual) more research is needed to determine the optimal intake of selenium for prevention and treatment of various viral illnesses. At the present time, long-term supplementation with 200 mcg/day appears to be safe.

Yu S-Y, et al. Chemoprevention trial of human hepatitis with selenium supplementation in China. Biol Trace Elem Res 1989;20:15-22.

J Am Diet Assoc 1986 Nov;86(11):1576-1577

Dietary selenium intake of preschool children.
Costello HE, Kalinowski M, Thompson HJ

The results of this investigation indicate that the range of selenium intakes of the preschool children who were studied was in the acceptable range of adequate and safe as suggested by the Food and Nutrition Board. The majority of the selenium in the diets of the subjects came from grains. Although the amount of selenium consumed was within normal limits, the concentration in the diet was estimated to be 70% of the expected value for mixed diets, i.e., 0.1 microgram/gm.

Biol Trace Elem Res 1996 Mar;51(3):225-234

Evidence for altered structure and impaired mitochondrial electron transport function in selenium deficiency.
Rani P, Lalitha K

Department of Chemistry, Indian Institute of Technology, Madras, India.

Selenium (Se) deficiency in the experimental models, Coturnix coturnix japonica and Corcyra cephalonica, resulted in impaired mitochondrial substrate oxidations and lowered thiol levels. Studies with respiratory inhibitors confirmed reduced mitochondrial electron transport enzyme activities, especially at cytochrome c oxidase (COX), the terminal segment. Enhanced mitochondrial lipid peroxidation in Se deficiency was more pronounced in the heart tissue of the quail compared to other tissues. Glutathione peroxidase (GSH-Px) activity toward H2O2 and cumene hydroperoxide were generally low in the insect muscle tissue and activity toward H2O2 was maximal in the quail heart mitochondria that was not very sensitive to Se status. Lowered COX activity in Se deficiency was more directly correlated with the increased level of lipid peroxidation than with the GSH-Px activity measured, suggestive of Se mediated protective mechanisms independent of GSH-Px. Electron microscopic observations revealed structural changes such as loss of cristae on the mitochondria with proliferative and degenerative changes of the mitochondria in Se deficiency. Involvement of Se in maintaining structure and functional efficiency of mitochondria is evident from the present study.

Biol Trace Elem Res 1998 Jun;62(3):265-280

Tissue and concentration-dependent effects of sodium selenite on muscle contraction.
Turan B, Koc E, Hotomaroglu O, Kiziltan E, Yildirim S, Demirel E

Department of Biophysics, Faculty of Medicine, University of Ankara, Turkey.

In this study, we demonstrated that sodium selenite with high doses (> or = 10(-3) M) were potent in inducing a contracture type effect on heart and smooth muscles. Selenite (Se), at a concentration of 10(-3) M, caused a contracture effect in heart preparations. Also, low Se concentrations did not have any significant effect. Although low concentrations of Se (> or = 10(-5) M) had a biphasic effects on acetylcholine (ACh) induced and spontaneous ileum contractions, 10(-3) M selenite enhanced once more a contracture effect similar to that of the heart preparations. Replacing Ca2+ concentration of the bathing solution by twofold Ca2+ or Ca2+-free did not change the effects of selenite (10(-5) M) on contractility of ileum preparations. In vascular smooth muscle, low concentration of selenite (< 10(-4)) had no significant effects on KCl, and phenylephrine-induced contractions and acethylcholine-induced endothelium-dependent relaxations of isolated rabbit aorta. However, the contractions induced by phenylephrine and the relaxations induced by acetylcholine in rabbit aorta were depressed significantly by high concentration of selenite (10(-3) M). The results obtained by selenite exposure from these three different types of tissue preparations first suggest that the high concentration of selenite exposure induces some alterations in the functions of muscles and endothelium in a tissue- and dose-dependent manner. Second, this observed irreversible type of dysfunction of tissues induced by 10(-3) M selenite is not directly dependent on the Ca2+ entrance into the cytosol, but might be induced by the increase of intracellular Ca2+ with the disturbance of Ca2+ regulation.

J Trace Elem Med Biol 1998 Mar;12(1):28-38

Trace elements and cardioprotection: increasing endogenous glutathione peroxidase activity by oral selenium supplementation in rats limits reperfusion-induced arrhythmias.
Tanguy S, Boucher F, Besse S, Ducros V, Favier A, de Leiris J

Physiopathologie Cellulaire Cardiaque, CNRS ESA 5077, Universite J. Fourier,
Grenoble, France.

Oxyradicals have been implicated as a possible cause of reperfusion-arrhythmias (RA). However, the use of diverse exogenous oxyradical scavengers designed to reduce RA has given contradictory results. The aim of the present study was to determine whether enhancing the activity of the main endogenous enzyme involved in peroxide elimination in cardiac cells, namely glutathione peroxidase, may limit RA in isolated heart preparations by increasing their antioxidant status. For this purpose, a group of 15 male Wistar rats received a selenium enriched diet for ten weeks (1.5 mg Se/kg diet). Control animals (n = 15) received a standard diet containing 0.05 mg Se/kg diet. The incidence of early ventricular arrhythmias was investigated during the reperfusion period following 10 min regional ischemia induced ex-vivo by left coronary artery ligation. Our results show that selenium-supplementation significantly increased the global selenium status of the animals. In the isolated heart preparations, the selenium supplementation induced a significant reduction of the severity of RA as assessed by the arrhythmia score and the limitation of the incidence of both ventricular tachycardia (control: 91% vs selenium: 36%, p < 0.05) and irreversible ventricular fibrillation (control: 45% vs selenium: 0%, p < 0.05). These effects were associated with a significant increase in cardiac mitochondrial and cytosolic glutathione peroxidase activities in both the left and the right ventricles. These results illustrate the potential protective effect of selenium against ischemia-reperfusion injury and suggest that peroxides might play a key role in the genesis of some aspects of the reperfusion syndrome.

Biol Trace Elem Res 1994 Apr;41(1-2):115-127

Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells.
Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G

New York University Dental Center, New York.

This study examined the effect of dietary (200 micrograms/d for 8 wk) supplementation with selenium (as sodium selenite) on the ability of human peripheral blood lymphocytes to respond to stimulation with alloantigen, develop into cytotoxic lymphocytes, and to destroy tumor cells, and on the activity of natural killer cells. The participants in the study were randomized for age, sex, weight, height, and nutritional habits and given selenite or placebo tablets; all participants had a selenium replete status as indicated by their plasma Se levels prior to supplementation. The data indicated that the supplementation regimen resulted in 118% increase in cytotoxic lymphocyte-mediated tumor cytotoxicity and 82.3% increase in natural killer cell activity as compared to baseline values. This apparently was related to the ability of the nutrient to enhance the expression of receptors for the growth regulatory lymphokine interleukin-2, and consequently, the rate of cell proliferation and differentiation into cytotoxic cells. The supplementation regimen did not produce significant changes in the plasma Se levels of the participants. The results indicated that the immunoenhancing effects of selenium in humans require supplementation above the replete levels produced by normal dietary intake.

Biol Trace Elem Res 1996;53(1-3):51-56

Plasma selenium levels in rheumatoid arthritis.
Kose K, Dogan P, Kardas Y, Saraymen R

Department of Biochemistry, Erciyes University, Faculty of Medicine, Kayseri, Turkey.

The plasma selenium (Se) levels were determined in patients with rheumatoid arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found to be significantly lower than those in 60 normal, healthy controls (p < 0.001). Similar significant differences were determined in sex-matched comparisons between patients and controls (p < 0.001) but there was no significant difference in plasma Se levels in sex-matched comparisons in both groups (p > 0.05). Our results suggest that Se is an important factor in RA.

Biol Trace Elem Res 1997;59(1-3):87-92

Inhibition of lipid peroxidation.
Sun E, Xu H, Wen D, Zuo P, Zhou J, Wang J

Chemistry Department, Huazhong University of Science and Technology Wuhan, People’s Republic of China.

Lipid peroxy radicals (ROO.) were detected by electron spin resonance (ESR) at low temperature after formation by addition of H2O2 into a suspension of mice lymphocytes. If lymphocytes were treated with selenomethionine (Se-Met) prior to addition of H2O2, ROO. formation was inhibited in a fashion that was dependent on Se-Met concentration. Formation of ROO. in the spleen of mice was induced by 60Co irradiation. Animals that were supplemented with Na2SeO3 prior to irradiation exhibited a lower ROO. concentration than that of nontreated animals. Based on our experiments, we have concluded that Se has an oxygen-free radical scavenging effect. This should be a protective effect against lipid peroxy radical cellular attack.

Biol Trace Elem Res 1998 Apr;62(1-2):1-6

Symptomatic treatment of brain tumor patients with sodium selenite, oxygen, and other supportive measures.
Pakdaman A

Klinik fur komplimentare Onkologie und Immuntherapie im Gesundheitspark Beelitz, Beelitz-Heilstatten, Germany.

Patients (16 women and 16 men) with brain tumors previously treated conservatively by surgery, radiation, and/or chemotherapy with typical symptoms of increased intracranial pressure were consecutively enrolled to test the effects of pharmacological dosages of sodium selenite (selenase) in conjunction with other supportive therapies (biological response modifiers, detoxification, chemotherapy, immunotherapy, oxygen therapy). The rationale for the use of sodium selenite was that the whole-blood selenium levels were subnormal in 70% of the patients on admission. Patients also frequently presented abnormal levels of other minerals, especially lowered sodium and elevated potassium levels, which appears to be characteristic of brain tumor patients. Sodium selenite was administered by infusion at dosages of 1000 mcg Se in physiological saline/d for 4-8 wk. In 76% of the patients, a definite, and in 24% a slight improvement of the general condition and a decrease in symptoms, such as nausea, emesis, headache, vertigo, unsteady gait, speech disorders, and Jacksonian seizures, were observed. In all treated patients, improvements of erythrocyte, hemoglobin, and thrombocyte counts were observed. Additional beneficial effects were noted in the patients receiving the oxygen therapy. It is concluded that the sodium selenite can be employed with oxygen therapy and other supportive measures in the management of brain tumor patients.

Br J Urol 1998 May;81(5):730-4

Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial.
Clark LC, Dalkin B, Krongrad A, Combs GF Jr, Turnbull BW, Slate EH, Witherington R, Herlong JH, Janosko E, Carpenter D, Borosso C, Falk S, Rounder J

Arizona Cancer Center, College of Medicine, University of Arizona, Tucson 85716, USA.

OBJECTIVE: To test if supplemental dietary selenium is associated with changes in the incidence of prostate cancer. PATIENTS AND METHOD: A total of 974 men with a history of either a basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 mcg of selenium or a placebo. Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years. RESULTS: Selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence during 1983-93. There were 13 prostate cancer cases in the selenium-treated group and 35 cases in the placebo group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843 patients with initially normal levels of prostate-specific antigen (< or = 4 ng/ml), only four cases were diagnosed in the selenium-treated group and 16 cases were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26 P=0.009). There were significant health benefits also for the other secondary endpoints of total cancer mortality, and the incidence of total, lung and colorectal cancer. There was no significant change in incidence for the primary endpoints of basal and squamous cell carcinoma of the skin. In light of these results, the ‘blinded’ phase of this trial was stopped early. CONCLUSIONS: Although selenium shows little protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin, the selenium-treated group had substantial reductions in the incidence of prostate cancer, and total cancer incidence and mortality that demand further evaluation in well-controlled prevention trials.

J Trace Elem Med Biol 1998 Mar;12(1):28-38

Trace elements and cardioprotection: increasing endogenous glutathione peroxidase activity by oral selenium supplementation in rats limits reperfusion-induced arrhythmias.
Tanguy S, Boucher F, Besse S, Ducros V, Favier A, de Leiris J

Physiopathologie Cellulaire Cardiaque, CNRS ESA 5077, Universite J. Fourier, Grenoble, France.

Oxyradicals have been implicated as a possible cause of reperfusion-arrhythmias (RA). However, the use of diverse exogenous oxyradical scavengers designed to reduce RA has given contradictory results. The aim of the present study was to determine whether enhancing the activity of the main endogenous enzyme involved in peroxide elimination in cardiac cells, namely glutathione peroxidase, may limit RA in isolated heart preparations by increasing their antioxidant status. For this purpose, a group of 15 male Wistar rats received a selenium enriched diet for ten weeks (1.5 mg Se/kg diet). Control animals (n = 15) received a standard diet containing 0.05 mg Se/kg diet. The incidence of early ventricular arrhythmias was investigated during the reperfusion period following 10 min regional ischemia induced ex-vivo by left coronary artery ligation. Our results show that selenium-supplementation significantly increased the global selenium status of the animals. In the isolated heart preparations, the selenium supplementation induced a significant reduction of the severity of RA as assessed by the arrhythmia score and the limitation of the incidence of both ventricular tachycardia (control: 91% vs selenium: 36%, p < 0.05) and irreversible ventricular fibrillation (control: 45% vs selenium: 0%, p < 0.05). These effects were associated with a significant increase in cardiac mitochondrial and cytosolic glutathione peroxidase activities in both the left and the right ventricles. These results illustrate the potential protective effect of selenium against ischemia-reperfusion injury and suggest that peroxides might play a key role in the genesis of some aspects of the reperfusion syndrome.

Title: Selenium and sulfur in antioxidant protective systems: relationships with vitamin E and malaria.
Author(s): Levander OA

Address: U.S. Department of Agriculture, Beltsville Human Nutrition Research, Center, Maryland 20705-2350.

Source: Proc Soc Exp Biol Med 1992 Jun;200(2):255-9

Abstract: The metabolic relationships among the antioxidant nutrients selenium, sulfur, and vitamin E are particularly close. Selenium and vitamin E have long been known to spare one another in certain nutritional diseases of animals, and selenium has been considered to have a key antioxidant defense function as a component of glutathione peroxidase. However, the antioxidant role of glutathione peroxidase has been questioned and new proteins containing selenium have been identified: phospholipid hydroperoxide glutathione peroxidase, selenoprotein P, and iodothyronine deiodinase. Glutathione peroxidase activity independent of selenium resides in the glutathione S-transferases. Glutathione participates in both enzymatic and nonenzymatic antioxidant defense systems. Some low-molecular weight selenium compounds (e.g., ebselen) exhibit glutathione peroxidase-like action. Certain low molecular weight thiols decompose peroxides nonenzymatically (e.g., the ovothiols). Murine malaria appears to be a useful experimental model for investigating interrelationships of selenium and vitamin E. Vitamin E deficiency protects against the parasite, especially when the mice are concurrently fed peroxidizable fat such as fish or linseed oils. Selenium deficiency, on the other hand, has little or no protective effect against the parasite. Any practical utility of pro-oxidant diets in combating human malaria remains to be determined.

Selenium Summary
Selenium inhibits many types of carcinogen-induced cancer in animals including skin, liver, and the fat-sensitive breast and colon cancer. In addition, selenium inhibits mutagenesis in bacterial test systems and reduces human chromosome breakage. Epidemiological studies seem to indicate that where selenium occurs in the environment or in large amounts in the blood, there is decreased cancer mortality, especially of the fat sensitive cancers such as breast and colon cancer. More epidemiological studies would be desirable in this regard.

Epidemiological studies in the 1980’s have provided consistent evidence of an association between low serum selenium resulting from dietary selenium deficiency and the risk of cancer whereas the evidence of the relationship of dietary selenium with the risk of ischemic heart disease is still inconclusive although indicative of an inverse relationship in certain conditions. New epidemiological studies on the role of selenium in IHD are still needed to confirm or negate the previous findings. These should consider confounding and effect modification by other nutrients, especially fatty acids and other antioxidants, and other risk factors. The mechanisms through which selenium deficiency could increase the risk of IHD need to be established in experiments in animals and humans.