Selenium

Selenium salts are toxic in large amounts, but trace amounts of the element are necessary for cellular function in most, if not all, animals, forming the active center of the enzymes glutathione peroxidase and thioredoxin reductase (which indirectly reduce certain oxidized molecules in animals and some plants) and three known deiodinase enzymes (which convert one thyroid hormone to another). Selenium requirements in plants differ by species, with some plants, it seems, requiring none.[3]

Health effects and nutrition

Although it is toxic in large doses, selenium is an essential micronutrient for animals. In plants, it occurs as a bystander mineral, sometimes in toxic proportions in forage (some plants may accumulate selenium as a defense against being eaten by animals, but other plants such as locoweed require selenium, and their growth indicates the presence of selenium in soil).[3] See more on plant nutrition below.

Selenium is a component of the unusual amino acids selenocysteine and selenomethionine. In humans, selenium is a trace element nutrient that functions as cofactor for reduction of antioxidant enzymes, such as glutathione peroxidases[16] and certain forms of thioredoxin reductase found in animals and some plants (this enzyme occurs in all living organisms, but not all forms of it in plants require selenium).

The glutathione peroxidase family of enzymes (GSH-Px) catalyze certain reactions that remove reactive oxygen species such as hydrogen peroxide and organic hydroperoxides:

2 GSH + H2O2—-GSH-Px → GSSG + 2 H2O

Selenium also plays a role in the functioning of the thyroid gland and in every cell that uses thyroid hormone, by participating as a cofactor for the three known thyroid hormone deiodinases, which activate and then deactivate various thyroid hormones and their metabolites.[17] It may inhibit Hashimotos’s disease, in which the body’s own thyroid cells are attacked as alien. A reduction of 21% on TPO antibodies was reported with the dietary intake of 0.2 mg of selenium.[18]

Dietary selenium comes from nuts, cereals, meat, mushrooms, fish, and eggs. Brazil nuts are the richest ordinary dietary source (though this is soil-dependent, since the Brazil nut does not require high levels of the element for its own needs). In descending order of concentration, high levels are also found in kidney, tuna, crab, and lobster.[19][20]

The human body’s content of selenium is believed to be in the 13-20 milligram range.[21]

Indicator plants

Certain species of plants are considered indicators of high selenium content of the soil, since they require high levels of selenium to thrive. The main selenium indicator plants are Astragalus species (including some locoweeds), prince’s plume (Stanleya sp.), woody asters (Xylorhiza sp.), and false goldenweed (Oonopsis sp.)[22]

Toxicity

Although selenium is an essential trace element, it is toxic if taken in excess. Exceeding the Tolerable Upper Intake Level of 400 micrograms per day can lead to selenosis.[23] This 400 microgram (µg) Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow up study on the same five people in 1992.[24] The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to not only avoid toxicity, but also to avoid creating an imbalance of nutrients in the diet and to account for data from other countries.[25] The Chinese people who suffered from selenium toxicity ingested selenium by eating corn grown in extremely selenium-rich stony coal (carbonaceous shale). This coal was shown to have selenium content as high as 9.1%, the highest concentration in coal ever recorded in literature.[26] A dose of selenium as small as 5 milligram (5000 µg) per day can be lethal for many humans.[27]

Symptoms of selenosis include a garlic odor on the breath, gastrointestinal disorders, hair loss, sloughing of nails, fatigue, irritability, and neurological damage. Extreme cases of selenosis can result in cirrhosis of the liver, pulmonary edema, and death.[28] Elemental selenium and most metallic selenides have relatively low toxicities because of their low bioavailability. By contrast, selenates and selenites are very toxic, having an oxidant mode of action similar to that of arsenic trioxide. The chronic toxic dose of selenite for humans is about 2400 to 3000 micrograms of selenium per day for a long time.[29] Hydrogen selenide is an extremely toxic, corrosive gas.[30] Selenium also occurs in organic compounds, such as dimethyl selenide, selenomethionine, selenocysteine and methylselenocysteine, all of which have high bioavailability and are toxic in large doses. Nano-size selenium has equal efficacy, but much lower toxicity.[31]

On 19 April 2009, twenty-one polo ponies began to die shortly before a match in the United States Polo Open. Three days later, a pharmacy released a statement explaining that the horses had received an incorrect dose of one of the ingredients used in a vitamin/mineral supplement compound, with which the horses had been injected. Such nutrient injections are common to promote recovery after a match, but this mixture had been compounded by a compounding pharmacy not familiar with it. Analysis of blood levels of inorganic compounds in the supplement indicated the selenium concentrations were ten to fifteen times higher than normal in the horses’ blood samples, and 15 to 20 times higher than normal in their liver samples. It was later confirmed that selenium was the ingredient in question.[32] Selenium is active in only tiny amounts, and has a history of causing accidental poisonings in supplements when the dose that is supposed to be in micrograms is given by mistake in milligrams (1000 times as much).

Selenium poisoning of water systems may result whenever new agricultural runoff courses through normally dry, undeveloped lands. This process leaches natural soluble selenium compounds (such as selenates) into the water, which may then be concentrated in new “wetlands” as the water evaporates. High selenium levels produced in this fashion have been found to have caused certain congenital disorders in wetland birds.[33]

Deficiency

Main article: selenium deficiency

Selenium deficiency is rare in healthy, well-nourished individuals. It can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, and[34] on advanced-aged people (over 90). Also, people dependent on food grown from selenium-deficient soil are at risk. Although New Zealand has low levels of selenium in its soil, adverse health effects have not been detected.[35]

Selenium deficiency may only occur when a low selenium status is linked with an additional stress, such as chemical exposure or increased oxidant stress due to vitamin E deficiency.[36]

There are interactions between selenium and other nutrients, such as iodine and vitamin E. The interaction is observed in the etiology of many deficiency diseases in animals and pure selenium deficiency is rare. The effect of selenium deficiency on health remains uncertain, particularly in relation to Kashin-Beck disease.[37]

Controversial health effects

Cancer

Several studies have suggested a possible link between cancer and selenium deficiency.[38][39][40][41] One study, known as the NPC, was conducted to test the effect of selenium supplementation on the recurrence of skin cancers on selenium-deficient men. It did not demonstrate a reduced rate of recurrence of skin cancers, but did show a reduced occurrence of total cancers, particularly for lung, colorectal and prostate cancers (Relative Risk 0.63). There was also a significant reduction in total cancer mortality (-50 %), although without a statistically significant change in overall mortality.[42] The preventative effect observed in the NPC was greatest in those with the lowest baseline selenium levels.[43] In 2009, the 5.5 year SELECT study reported selenium and vitamin E supplementation, both alone and together, did not significantly reduce the incidence of prostate cancer in 35,000 men who “generally were replete in selenium at baseline”.[43] The SELECT trial reported vitamin E did not reduce prostate cancer as it had in the alpha-tocopherol, beta carotene (ATBC) study, but the ATBC had a large percentage of smokers, while the SELECT trial did not.[43] There was a slight trend toward more prostate cancer in the SELECT trial, but in the vitamin E only arm of the trial, where no selenium was given.

Dietary selenium prevents chemically-induced carcinogenesis in many rodent studies.[44] It has been proposed that selenium may help prevent cancer by acting as an antioxidant or by enhancing immune activity. Not all studies agree on the cancer-fighting effects of selenium. One study of naturally occurring levels of selenium in over 60,000 participants did not show a significant correlation between those levels and cancer.[45] The SU.VI.MAX study[46] concluded low-dose supplementation (with 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 µg of selenium, and 20 mg of zinc) resulted in a 30% reduction in the incidence of cancer and a 37% reduction in all-cause mortality in males, but did not get a significant result for females.[47] However, there is evidence selenium can help chemotherapy treatment by enhancing the efficacy of the treatment, reducing the toxicity of chemotherapeutic drugs, and preventing the body’s resistance to the drugs.[48] Studies of cancer cells in vitro showed that chemotherapeutic drugs, such as taxol and Adriamycin, were more toxic to strains of cancer cells when selenium was added.[49][50]

In March 2009, vitamin E (400 IU) and selenium (200 micrograms) supplements were reported to affect gene expression and can act as a tumor suppressor.[51] Eric Klein, MD from the Glickman Urological and Kidney Institute in Ohio said the new study “lend[s] credence to the previous evidence that selenium and vitamin E might be active as cancer preventatives”.[52] In an attempt to rationalize the differences between epidemiological and in vitro studies and randomized trials like SELECT, Klein said randomized controlled trials “do not always validate what we believe biology indicates and that our model systems are imperfect measures of clinical outcomes in the real world”.[52]

HIV/AIDS

Some research has indicated a geographical link between regions of selenium-deficient soils and peak incidences of HIV/AIDS infection. For example, much of sub-Saharan Africa is low in selenium. However, Senegal is not, and also has a significantly lower level of AIDS infection than the rest of the continent. AIDS appears to involve a slow and progressive decline in levels of selenium in the body. Whether this decline in selenium levels is a direct result of the replication of HIV[53] or related more generally to the overall malabsorption of nutrients by AIDS patients remains debated.

Low selenium levels in AIDS patients have been directly correlated with decreased immune cell count and increased disease progression and risk of death.[54] Selenium normally acts as an antioxidant, so low levels of it may increase oxidative stress on the immune system, leading to its more rapid decline. Others have argued T-cell-associated genes encode selenoproteins similar to human glutathione peroxidase. Depleted selenium levels in turn lead to a decline in CD4 helper T-cells, further weakening the immune system.[55]

Regardless of the cause of depleted selenium levels in AIDS patients, studies have shown selenium deficiency does strongly correlate with the progression of the disease and the risk of death.[56][57][58]

Tuberculosis

Some research has suggested selenium supplementation, along with other nutrients, can help prevent the recurrence of tuberculosis.[59]

Diabetes

A well-controlled study showed selenium levels are positively correlated with the risk of having type 2 diabetes. Because high serum selenium levels are positively associated with the prevalence of diabetes, and because selenium deficiency is rare, supplementation is not recommended in well-nourished populations, such as the U.S.[60] More recent studies, however, have indicated selenium may help inhibit the development of type 2 diabetes in men, though the mechanism for the possible preventative effect is not known.[61]

Mercury

Experimental findings have demonstrated a protective effect of selenium on methylmercury toxicity, but epidemiological studies have been inconclusive in linking selenium to protection against the adverse effects of methylmercury.[62]

{Information courtesy Wikipedia}