Selenium

Selenium is an essential mineral and micronutrient. It is fundamental to human health and found in many foods often a function of levels of selenium in soils. It is found in meat, seafood (hence selenium levels are high in populations with high intake of seafood, like the Inuit population ¹), grain cereals, egg yolk, milk, mushrooms and garlic. ² Selenoproteins are important constituents of a number of enzymes with a range of functions including antoxidant function, thyroid hormone metabolism, male fertility and immune mechanisms. A decline in blood selenium levels in the United Kingdom and other European countries has raised concern about possible public health implications, particularly in relation to cancer and cardiovascular disease.³ Whilst there is some understanding of the role of these proteins in health and disease (and some interesting theories and research), there are many unanswered questions and much debate about supplementation. More research is repeatedly called for.² Deficiency is linked with Keshan disease but excessive intake can have toxic effects and may even be carcinogenic.⁴

The recommended daily selenium intake (the RDA) is 40-55 mcg/ day.⁵ Intake in children should not exceed 60 mcg/ day. Some are recommending supranutritional supplements of 200 mcg/ day to 800 mcg/day. Toxic effects occur at around 40x the RDA.

Serum selenium levels can be measured. Erythrocyte, serum and tissue levels of glutathione peroxidase can be measured to assess selenium status. Selenium in hair and nails can be measured. Discuss with your laboratory before deciding which method to use.

Dietary recommendations were made over 15 years ago on the basis of blood levels of glutathione peroxidase. This intracellular enzyme converts hydroxyl radicals or hydrogen peroxide into water and this requires selenium as a cofactor. Levels of this enzyme have thus been taken to correlate with selenium levels. Since then over 30 new selenoproteins have been identified and about half of these have an identified biological function.² These selenoproteins include:

• Four glutathione peroxidase (GP) enzymes, a major class of functionally important selenoproteins and the first to be characterised:
  • Classical GPx1
  • Gastrointestinal GPx2
  • Plasma GPx3
  • Phospholipid hydroperoxide GPx4
• Thioredoxin reductase (TR), a seleno-cysteine containing enzyme important in regulating metabolic activity.
• Selenoprotein P (60% of plasma selenium is held in this form) may have a role in the transport of selenium but also may have other functions.
• Several iodothyronine deiodinase enzymes. These are responsible for conversion of the prohormone thyroxine to the active thyroid hormones (triiodothyronine or T3).
• Sperm capsule selenoprotein which may be responsible for maintaining integrity of the sperm flagella (and hence motility of sperm).
• Selenoprotein W. This is involved in muscle metabolism.

Deficiency of selenium may cause a variety of problems, but the health implications of a decline in Selenium levels in the United Kingdom over the last 25 years have not been systematically investigated.² In general selenium is thought to be important in a number of varied aspects of health (for a healthy immune system, for a protective effect against some forms of cancer, to maintain and enhance male fertility, for a reduction in cardiovascular mortality and to regulate inflammatory markers in asthma). Research is in progress and there is a lot of interest in the results of this research. Although there are still many unanswered questions, so far selenium has been linked with:

• Keshan disease or Keshan-Beck disease. This is a disease associated with selenium deficiency.^6,7,8
• Counteracting the development of virulence and inhibiting HIV progression to AIDS.⁹ Trials are small and results mixed but more research is called for.¹⁰
• Enhancing sperm motility. Selenium deficient rats have immotile deformed sperm and infertility. Although there is a rationale for this¹¹ one RCT was not able to show such an effect.¹²
• A possible role in preventing pre-eclampsia, although the Cochrane review suggests more trials are necessary.
• A possible relationship between mood disturbance and selenium deficiency
• A possible association between elevated selenium intake and reduced cancer risk.The association between selenium status and cancer risk remains enigmatic and epidemiological studies have failed to consistently link low selenium levels with increased cancer risk in men and women.¹³ It is possible that there may be gender differences in susceptibility to cancer risk with men being more susceptible to the risk of low selenium.¹³ In the Nutritional Prevention of Cancer Trial daily supplementation of selenium significantly reduced prostate cancer in men.^14,15 It is thought that the greatest benefit from selenium supplementation will be in low selenium status populations, although the biggest primary and secondary prevention trials (SELECT Trials) are underway in the United States (where selenium status is good).¹⁶ Some are predicting that when the SELECT trial results come out in 2013 they will show benefit!¹⁷
• Asthma. Although a number of trials suggest supplementation with selenium may help symptoms of chronic asthma, only one small trial, according to the cochrane review, showed evidence of this.
• Cardiovascular disease. Deficiency is associated with cardiomyopathy.¹⁸ The hypotheses that low selenium concentrations are associated with increased cardiovascular disease and that selenium supplements prevent coronary heart disease are unproven. Selenium supplementation cannot currently be recommended for cardiovascular disease prevention.¹⁹
• Deficiency in trauma and burns patients. One study reports improved recovery with selenium supplementation in trauma and burns patients.²⁰

Risk factors include:

• Poor dietary intake
• Smoking. Smokers have lower levels of selenium compared to non-smokers.²¹
• Socioeconomic status. Lower levels have been found in people receiving state benefits or with lower educational attainment.²¹
• Elderly living in residential or nursing homes had lower levels of selenium²¹ as did elderly hospital patients²² when compared with 'free-living' elderly patients.
• The elderly, particularly in areas where low intake common.
• Where you live:
  • Areas with a low selenium soil environment are associated with deficiency. Such areas include parts of China, Croatia ²³, New Zealand ²⁴, the Slovak Republic²⁵The elderly in such areas are particularly at risk and one study from New Zealand recently demonstrated suboptimal levels of selenium in a significant proportion of 103 elderly New Zealand women.²⁴
  • The levels of selenium are higher in the south of England than the north.²¹ The selenium status may vary within countries according to factors such as the selenium in the local soil but is also affected by the levels of selenium in imported crops.
• Patients on total parenteral nutrition (TPN).^26,27,28
• Trauma and burns patients.²⁰
• Vegetarians in countries with low selenium status.²⁹

Those at high risk of deficiency should have their selenium status measured. If deficient in selenium such patients should certainly be given supplements. As with many nutritional components distinction must be drawn between the basic nutritional requirement to prevent deficiency and supplementation to prevent, for example, chronic disease and cancer.^30,31,32 According to recent research in the United States 99% of over 17,000 subjects were 'selenium replete' according to plasma selenium levels and not in need of routine supplementation.³³ There is widespread questioning of the use of recommended dietary amounts (RDAs) and some questioning of methods of assessing deficiency in this as in other areas of nutrition.^34,30,35,36 Evidence of benefit at supra-nutritional levels of dietary intake is needed to support what has been called the 'nutraceutical' approach to supplementation. Further studies are needed and are being undertaken to support such beneficial effects.³² If such evidence is forthcoming then health professionals will need to use dietary and clinical assessment methods to ensure that those at risk of cancer, inflammatory or infectious disease are appropriately advised about selenium intake.³²