Absent a parameter of Se status reflecting both medium-term (days to weeks) Se intake and metabolic function, the clinical assessment of Se status has relied upon measurements of blood Se to indicate intake and of blood GPX activity to indicate function. Each has significant limita- tions. The Se contents of blood cells, serum or plasma are affected not only by the amount but also by the chemical species of dietary Se. For example, because selenomethionine (SeMet, e.g., in plant foods) can replace methionine in protein synthesis as well as be converted to Se- Cys, sources of SeMet enter non-specifically into blood proteins as well as specifically into SeCys-proteins, thus supporting greater blood Se values than will sources of SeCys (e.g., in animal products) at equiva- lent Se intakes. While almost all serun/plasma Se is protein-bound, most is present in two SeCys-proteins, SeP and GPX1. Hill et al (1996) cal- culated that maximal expression of these proteins contributed 80 ng/ml to plasma Se, indicating that those parameters are useful only in popula- tions with relatively low Se intakes. Nève (1995) noted that subjects with plasma/serum Se levels above 70 ng/ml show no further GPX re- sponses to Se supplementation. On the basis of these observations, the plasma/serum level of 80 ng/ml would appear to be a useful criterion of nutritional adequacy.
Fig. 3. Plasma Se responces of SePK trial subjects.
Because that is less than the plasma Se level associated with minimal cancer risk in the NPC trial, 120 ng/ml, it is appropriate to ask how much Se may be required for a given individual to reach the latter, ap- parently protective level. Results of our Se pharmacokinetics (SePK) study show that plasma Se moves from one plateau level to another
within 9-12 mos. of Se-supplementa-tion at 200 mcg/d (Fig. 3). NPC Trial subjects showed similar responces (Fig 4).
An analysis of data from the NPC trial indicated that Se dose adjusted for metabolic body size (D, ng/kg0.75) was related to the 12 mo. in- crease in plasma Se (, ng/ml) according to the following function: = 10.52 D (Fig. 5). From this relationship, the dose (D) required to reach a target plasma Se level (T, e.g., 120 ng/ml) within 12 mos. of supple- mentation for a person with a known baseline plasma Se level (B, ng/ml) can be predicted: D (T – B)/10.52. This would suggest, for example, that a 70 kg person could move from a base plasma Se level of 106 ng/ml to a level of 120 ng/ml with a daily dose of 32 mcg Se for 9+ mos.
Fig. 4. Plasma Se responses of NPC Trial subjects to 200 or 400 MCG Se/d. 0 50 100 150 200 250 300 350 0 0.5 1 2 3 4 5 6 7 8 9 10 years ng/ml placebo Se, 200 ug/d Se, 400 ug/d
y = 1 0 . 5 1 8 x R2 = 0 . 1 8 8 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 3 5 0 0 5 1 0 1 5 2 0 2 5 s u p p le m e n t a l S e , n g / k g -e x p 0 . 7 5 / d del ta ( p la s m a S e i n c r e a
Fig. 5. 12 mo. plasma Se responses of NPC trial subjects.
Conclusion
In the span of five decades, Se has moved from being thought of as a toxicant to being considered essential nutrient. The elucidation of its role in nutrition has led to fundamental discoveries in metabolic bio- chemistry (the unique metabolism of SeCys), virology (the destabiliza- tion of RNA viruses due to oxidative stress), and public health (the role in cancer risk reduction). Unlike most other nutrients, which were rec- ognized due to the fatal outcomes of their deficiencies, the conse- quences of Se deprivation appear to be largely sub-clinical in nature, requiring other precipitating factors (e.g., vitamin E deficiency, viral exposure, etc.) to reveal the effects of compromised Se-enzymes and/or essential Se-metabolites. Even after a half-century of research, much remains to learn about the metabolic bases of the roles of Se in nutrition and health.
Key words: selenium, nutrition, food, diet, intake, plasma, selenium deficiency
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