Selenium Distribution Status Assays and Dietary Reference Values

In an adequately supplied adult male human subject, the total body selenium content is on the order of 30-60 mg, of which one-third is found in the skeleton and two-thirds in the soft tissues. A substantial fraction of kidney selenium is retained even when selenium at other sites is severely depleted during deficiency, and renal selenium is more constant between human populations than selenium in other tissues or body fluids. Regulation of selenoprotein synthesis at the transcription level appears to ensure a hierarchy of preservation of individual seleno-proteins at critical sites. The cytosolic glutathione peroxidase (GPx I) and selenoprotein P can donate selenium to other sites whenever overall depletion occurs. Selenium crosses the placenta readily, and breast milk selenium concentration is responsive to changes in maternal selenium intake. In the United States, breast milk Se concentrations are generally in the range of 0.19-0.25 mmol/l, but colostrum has levels that are two or three times higher than those of mature breast milk.

Selenium status can be measured in several ways. One recently developed and effective approach toward selenium concentration measurement is the use of inductively coupled plasma mass spectrome-try. Older assays are based on the generation of selenium hydrides or fluorescent derivatives of selenium. Selenium status can be measured by its concentration in plasma or serum; in whole blood (a result that can be recalculated to provide red cell selenium concentrations); or in platelets, hair, or nails. The platelet concentration is considered to be a reliable medium-term index, whereas hair and nail concentrations can integrate selenium status, and hence intakes, over a longer term.

Glutathione peroxidase enzymatic assay in plasma or red cells is another frequently used approach to status measurement. In situations of severe to marginal deficiency, this has proven to be a sensitive and responsive index, varying consistently with variations in the selenium supply. However, once an adequate supply is achieved, there is no further capacity for increases in enzyme synthesis, and a plateau of activity is reached that does not respond to further increases in selenium intake. Therefore, if a population exhibits a strong correlation between plasma (or red cell) selenium concentrations and glutathione peroxidase activity in blood fractions, or there is a major increase in GPx activity after selenium supplementation, this can be taken as evidence of suboptimum selenium status in the population. If there is little evidence of such a correlation or of a response to supplementation, then the population is likely to be adequately supplied. The absolute values of GPx activity are more difficult to interpret because there are many different versions of the assay in use in different laboratories, and interlaboratory harmonization has rarely been undertaken for this assay. Recent reappraisal has suggested that the plasma glutathione peroxidase (GPx III) assay may be more reliable than the blood cytosolic (GPx I) enzyme assay because haemoglobin tends to interfere with the reaction in erythrocyte extracts.

A summary of reference values and recommended intakes of selenium from three publications is presented in Table 2. Dietary reference values for

Table 2 Reference values for intakes of selenium (mg/day)a

Population group

UK

UK RNI

USAI/

WHO/

LRNI

RDAb

FAO RNI

0-6 months

4-5

10-13

AI:15

6

7-12 months

5-6

10

AI:20

10

1-3 years

7

15

RDA:20

17

4-6 years

10

20

30

22

7-10 years

16

30

30-40

21-26

11-18 years, male

25-40

45-70

40-55

32

11-18 years,

25-40

45-60

40-55

26

female

19-65 years, male

40

70

55

34

19-65 years,

40

60

55

26

female

65 + years, male

40

70

55

33

65 + years, female

40

60

55

25

Pregnant

40

60

60

26-30

Lactating

55

75

70

35-42

aWhere a range of values is given, the population group described in this table overlapped across more than one population group in the source table.

bThe first two age groups are AI; the remainder are RDA.

LRNI, Lower Reference Nutrient Intake; RNI, Reference Nutrient

Intake; AI, Adequate Intake; RDA, Recommended Dietary

Allowance.

Sources: UK: Department of Health (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom, Report on Health and Social Subjects No. 41. London: HMSO. USA: Food and Nutrition Board, Institute of Medicine (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids. Washington, DC: National Academy Press. WHO/FAO: WHO/FAO (2002) Human Vitamin and Mineral Requirements. Report of a Joint FAO/WHO Expert Consultation, Bangkok, Thailand. Rome: WHO/FAO.

selenium in the United Kingdom, set in 1991, were based on a number of criteria, including the facts that no evidence of deficiency was detectable in populations with intakes of 40 mg/day and that saturation of GPx in Chinese males occurred at an intake of approximately 41 mg/day (equivalent to 50 mg/day for a UK male based on a body weight comparison). On this basis, the UK Lower Reference Nutrient Intake (LRNI) was set at 40 mg/day for both male and female adults, and the corresponding RNI values were set at 75 mg/day for males and 60 mg/day for females, with lower values, proportional to body weight, for children. No extra increment was considered necessary for pregnancy, but for lactating women an additional 15 mg/day was added to both the LRNI and the RNI.

More recently, selenium recommendations or reference values have been slightly lower. The US committee that set Dietary Reference Intakes in 2000 interpreted the Chinese estimate of 41 mg/day needed to saturate GPx in adult men, and data from New Zealand indicating selenium intake adequacy at 38 mg/day, as supporting an Estimated Average Requirement (EAR) of 45 mg/day for adults of both sexes, and hence an Recommended Dietary Allowance (RDA) (with 10% CV of requirements) of 55 mg/ day for both sexes, increasing to 60 mg/day for pregnant and lactating women. However, RNI values set by an FAO/WHO committee, published in 2002, were much lower, at only 26 mg/day for women and 34 mg/day for men, based on the premise that full saturation of GPx is unnecessary and two-thirds saturation is probably adequate. Clearly, there has been considerable divergence of opinion between different committees, and this divergence underlies the current uncertainty about the overall adequacy of selenium intakes in many European countries, including the United Kingdom. In the United Kingdom, selenium intakes have declined considerably during the past 25 years because of the substitution of North American wheat imports by European wheat with a much lower selenium content. In contrast, selenium intakes in New Zealand have increased as a result of grain imports from Australia.

There are also recommendations for the upper limit of safe intake of selenium. For the United Kingdom, it was noted that evidence of toxicity was detectable at intakes of approximately 750-900 mg/day, and the UK panel recommended a maximum safe intake of 450 mg for adults (6 mg/kg body weight/day), which was confirmed as an official safe upper level (SUL) in 2003. In the US Dietary Reference Intakes, the upper level of 400 mg/day was based on a no adverse effect level of 800 mg/day divided by an uncertainty (i.e., safety) factor of 2. The FAO/ WHO committee also set an SUL of 400 mg/day for adults. In humans, at intakes of >3mg/day, overt signs of selenosis include damage to nails and hair, skin and nerve lesions, mottling of teeth, nausea, weakness, and diarrhea. Urinary selenium excretion is high, and a garlic odour may be apparent in the breath.

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