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Selenium

Nutrient Name: Selenium.
Elemental Symbol: Se.
Related Substances: Seleocysteine, selenomethionine; selenium aspartate; sodium selenite.

Summary Table
nutrient description

Physiology and Function

Selenium is an essential trace mineral in the human body, even though it was generally considered a toxic element until the 1950s. Dietary intake of selenium largely determines selenium levels in the body, and the mineral is found in variable amounts in some foods depending on its presence in the soil. The various forms of selenium are absorbed differently in the digestive tract and are retained for different durations.L-(+)selenomethionine is most readily absorbed and exhibits a significantly slower whole-body turnover rate, especially compared with inorganic selenite. These metabolic characteristics provide for efficient use of the selenium contained in methionine.

Selenium plays a key role in numerous metabolic pathways, most notably those exerting an antioxidant action. Selenium is metabolized to methylselenium and S-methylselenocysteine, its bioactive metabolites; it then acts at the level of nuclear transcription factors, signal transduction, cell cycle checkpoints, and cellular apoptosis. Selenium also appears to act as a substitute for sulfur in key signaling enzymes such as tyrosine kinase. In the form of selenocysteine, selenium is incorporated into selenoproteins, which play a central role in cellular antioxidant defenses and serve to neutralize free radicals and reduce risk of cancer and cardiovascular disease. In particular, glutathione peroxidase (GSH-Px, GPX), a selenium-dependent enzyme containing four atoms of selenium, recycles glutathione, reducing lipid peroxidation by catalyzing the reduction of peroxides, neutralizing hydrogen peroxide, and providing anti-inflammatory properties. Within several metabolic pathways, selenium acts as a cofactor, sometimes in the form of selenocysteine. Selenium also potentiates the antioxidant effects of vitamin E. Plasma selenium concentrations influence thyroid hormone levels, particularly the conversion of thyroxine (T4) to the more active triiodothyronine (T3), through its effect on the key regulatory enzyme iodothyronine deiodinase; lowered selenium levels are associated with impaired peripheral conversion of T4to T3. Selenium's role in thyroid hormone activation exerts a special role in peripheral tissues. Thioredoxin reductase, a selenium- and NADPH-dependent flavoenzyme, is involved in intracellular reduction of substrates and appears essential to the mineral's anticancer activity. Selenium also participates in immune and detoxification functions by increasing T lymphocytes, enhancing natural killer cell activity, regulating production of immunoglobulin G (IgG) and tumor necrosis factor, and detoxifying heavy metal toxins, including mercury and cadmium.

The effects of selenium deficiency have been brought into focus through epidemiological studies in areas where the soil is particularly lacking in selenium, most notably the Chinese province of Keshan and Finland. Thus, the multifocal myocarditis of Keshan disease provides a stark study of the pathogenesis and pathology of frank selenium deficiency. Elevated rates of cancer in Finland exemplify the strong association between low dietary intake of selenium and increased risk of malignant disease. Diets high in processed foods are similarly depleted of selenium. Numerous studies have documented an association between selenium intake and serum concentrations and the risk and severity of a wide range of cancers. Other symptoms of selenium deficiency include destructive changes to the heart and pancreas, pseudoalbinism, macrocytosis, increased red blood cell (RBC) fragility, immune system dysfunction, myositis, elevated creatine kinase derived from muscles, whitening of the fingernail beds, and a peculiar form of osteoarthropathy known as Kashin-Beck disease.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Apart from treatment of deficiency patterns, selenium is most widely known and universally respected as a cancer-preventive nutrient. Although not generally considered an antioxidant per se, selenium forms an integral part of the antioxidant system related to the superfamily of antioxidant enzymes that includes glutathione perioxidase (GSH-Px). Selenium's antioxidant role is critical in many ways, but its cytotoxic and antitumor activities cannot be wholly attributable to such properties. Maximal GSH-Px activity requires only minimal amounts of selenium. Significantly higher levels of selenium, approximately 10 times as much, are necessary to reach levels at which this trace element begins to exercise its cancer prevention effects. 1

Historical/Ethnomedicine Precedent

Selenium has not been used historically as an isolated nutrient.

Possible Uses

Asthma, atherosclerosis, cardiac arrhythmia, cardiomyopathy, cataracts, childhood infectious diseases, colorectal cancer (risk reduction), depression, dermatitis herpetiformis, diabetic retinopathy, Down syndrome, food intolerance, gingivitis, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) support, hepatitis, heavy metal toxicity, hospital-acquired infections in very-low-birth-weight infants (preventive), hypothyroidism, liver cirrhosis, lung cancer (risk reduction), macular degeneration, Osgood-Schlatter disease, pancreatic insufficiency, Pap smear (abnormal), parenteral nutrition (adjunctive), phenylketonuria (if deficient), prostate cancer (risk reduction), rheumatoid arthritis, retinopathy, surgery preparation/recovery support.

Dietary Sources

Brazil nuts are the single best food source of selenium. Herring, tuna, sardines, calf liver, soybeans, yeast, garlic, and eggs are good sources. Whole grains, especially wheat, can be excellent dietary sources of selenium but provide variable amounts depending on selenium levels in soil where cultivated.

Nutrient Preparations Available

Selenomethionine, selenocysteine, selenium-rich yeast, and selenium aspartate are organic forms of selenium and are preferable. Sodium selenite is the primary inorganic form of selenium and is generally considered less bioavailable.

Dosage Forms Available

Tablet, injection.

Source Materials for Nutrient Preparations

Yeast; organic selenium, selenite.

Dosage Range

Adult

Dietary: Average U.S. daily intake: 100 µg/day.

Supplemental/Maintenance: An adult intake of 100 to 300 µg/day is often recommended, depending on exposure to environmental toxins and individual risk assessment.

Pharmacological/Therapeutic: 50 to 200 µg/day, can be up to 1000 µg/day.

Toxic: Greater than 900 µg/day.

The U.S. National Academy of Sciences recommends that selenium intake not exceed 400 µg daily, unless the higher intake is monitored. 2 Daily intakes of up to 400 to 500 µg daily appear to be safe in healthy adults, although certain increased risks may be associated.

Note: Men apparently require higher levels of selenium intake than women, possibly because stores are lost with ejaculation.

Pediatric (<18 Years)

Pharmacological/Therapeutic: Usual dosage for children: 30 to 150 µg/day, or 1.5 µg per pound of body weight.

Laboratory Values

Blood Glutathione Peroxidase Activity

Blood glutathione peroxidase (GSH-Px) activity is a sensitive assay. The GSH-Px activity of RBCs can be expressed as international units per gram of hemoglobin.

Activity less than 30 IU/g hemoglobin indicates deficiency.

Serum Selenium

  • Serum selenium levels are transient.
  • Normal range is 0.9-1.9 µmol/L.

Many clinicians consider blood and urinary levels as inadequate indicators of selenium intake and tissue levels.

safety profile

Overview

Selenium has a narrow margin of safety. Although it is generally considered safe at typical supplement levels of 100 to 200 µg/day; 800 µg/day is probably the highest long-term daily dose that can be taken without the development of toxicity in most people. There are variations in the toxic dose, as with other nutrients, but selenium must be used with caution. Daily dosages exceeding 900 µg have been associated with adverse effects in some individuals. 3 Estimates from cattle and other animals show that the toxic long-term dose is probably closer to 2.4 to 3 mg/day. This would lead to symptoms such as liver, skeletal, and cardiac muscle damage.

General Adverse Effects

High blood levels of selenium can result in a condition called selenosis .

Dosages greater than 1000 µg of selenium daily for an extended period have been associated with toxic signs that include depression, nervousness, emotional instability, lethargy, weight loss, nausea, vomiting, garlic-like breath and sweat, metallic taste in mouth, digestive irritation, peripheral neuropathies, dermatitis, hair loss, loss of teeth, and fingernail damage or loss. Rare cases of thrombocytopenia and hepatorenal dysfunction have been reported.

Signs and symptoms of severe overdose include fever, increased respiratory rate, gastrointestinal (GI) distress, paralysis, myelitis, and, potentially in extreme cases, death.

There have been no reports of death attributed to selenium toxicity in humans; however, fatal overdoses have been reported in livestock. Reports of selenium overdose in humans indicate resolution of adverse effects on cessation of intake.

Limited secondary research suggests that supplemental intake of selenium, 200 µg/day, for 7.7 years (average) may be associated with an increased risk of developing type 2 diabetes mellitus. 3a

Contraindications

Individuals with low thyroid function or iodine deficiency–induced goiter are reported to be at an increased risk of symptom exacerbation with selenium supplementation. 4 Selenium supplementation in individuals with a history of nonmelanoma skin cancer may raise the risk of squamous cell cancer. 5

High hair selenium levels in children have been associated with learning disabilities and behavioral problems.

interactions review

Strategic Considerations

The wide-ranging roles of selenium in healthy human physiology and the well-known adverse effects of selenium deficiency warrant our attention as a valuable agent in health optimization and disease prevention, as well as a potentially critical ally in disease management using conventional pharmacology. In particular, clinicians must consider the selenium depletion patterns associated with many pathologies and suspected to be aggravated by some pharmacological agents. Selenium’s role in cancer prevention has always suggested to clinicians that it might prove to be of therapeutic benefit as a component of cancer therapy. Although the direct treatment of cancer using selenium within an integrative model is just emerging, the use of selenium coadministration within a chemotherapeutic regimen has been the subject of extensive, but still often inconclusive, research. It has been widely demonstrated that alterations in selenium levels directly affect the concentration and activity of glutathione peroxidases. Results from animal experiments indicate that selenium compounds, as well as other antioxidant nutrients such as vitamin E, are protective against lethality and other radiation effects, although to a lesser degree than some synthetic protectors. 6 Further, the strong association recognized between selenium deficiency and cardiomyopathy suggests use of this crucial trace mineral in limiting known cardiotoxic effects of medications such as doxorubicin.

Many of the issues discussed reveal a need for human clinical trials, first to ascertain efficacy and then, on confirmation, to flesh out the particulars of integrative care models using the knowledge, skills, and experience of clinicians experienced in both conventional pharmacology and nutritional therapeutics. Researchers may find value in looking to studies such as the Polish clinical trial investigating selenium deficiency and concomitant administration of selenium (200 µg/day) and antioxidant nutrients for 3 months in women with ovarian cancer undergoing multidrug chemotherapy. Selenium nutrient coadministration was associated with significantly increased serum and hair concentrations of selenium and significantly higher activity of GSH-Px. 7 Further, Last et al. 8 retrospectively analyzed total selenium content in 100 sera of patients with aggressive B-cell non-Hodgkin's lymphoma who had received anthracycline-based chemotherapy, radiotherapy, or both. They determined that serum selenium concentration at presentation is a prognostic factor, predicting positively for dose delivery, treatment response, and long-term survival. The authors concluded that selenium supplementation might offer a novel therapeutic strategy in the treatment of aggressive non-Hodgkin's lymphoma.

nutrient-drug interactions
Chemotherapy (Cytotoxic Agents)
Cisplatin
Clozapine
Corticosteroids, Oral
Doxorubicin and Related Anthracycline Chemotherapy
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)
Valproic Acid
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Bleomycin

Bleomycin (Blenoxane).

Recent research indicates that selenium might interfere with the antineoplastic action of bleomycin, an antibiotic used in the treatment of various cancers. Bleomycin is known to damage DNA by free-radical mechanisms. In two rat studies published in 2001, Desai et al. 53,54 found that selenium may inhibit the therapeutic action of bleomycin, most likely by enhancing the catalytic function of glutathione peroxidase.

HMG-CoA Reductase Inhibitors (Statins)
nutrient-nutrient interactions
S -adenosylmethionine (SAMe)
Total Parenteral Nutrition (TPN)
Vitamin E
herb-nutrient interactions
Milk Thistle (Silybum marianum) and Alpha-Lipoic Acid
Citations and Reference Literature
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