Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects

Abstract

Background: The intake of selenium needed for optimal health has not been established. Selenoproteins perform the functions of selenium, and the selenium intake needed for their full expression is not known.

Objective: This study sought to determine the intake of selenium required to optimize plasma selenoprotein P (SEPP1) and to compare SEPP1 with other plasma selenium biomarkers.

Design: A 40-wk placebo-controlled, double-blind study of selenium repletion was carried out in 98 healthy Chinese subjects who had a daily dietary selenium intake of 14 micro g. Fourteen subjects each were assigned randomly to daily dose groups of 0, 21, 35, 55, 79, 102, and 125 micro g Se as l-selenomethionine. Plasma glutathione peroxidase (GPX) activity, SEPP1, and selenium were measured. A biomarker was considered to be optimized when its value was not different from the mean value of the subjects receiving larger supplements.

Results: The SEPP1 concentration was optimized at 40 wk by the 35- micro g supplement, which indicated that 49 micro g/d could optimize it. GPX activity was optimized by 21 micro g (total ingestion: 35 micro g/d). The selenium concentration showed no tendency to become optimized.

Conclusions: The present results indicate that SEPP1 concentration is the best plasma biomarker studied for assessing optimal expression of all selenoproteins, because its optimization required a larger intake of selenium than did GPX activity. On the basis of the selenium intake needed for SEPP1 optimization with adjustments for body weight and individual variation, ap 75 micro g Se/d as selenomethionine is postulated to allow full expression of selenoproteins in US residents. This trial was registered at clinicaltrials.gov as NCT00428649.

FIGURE 1.

Mean plasma selenoprotein concentrations in 12–14 selenium-deficient subjects supplemented for 40 wk with selenium as selenomethionine or with placebo. Variation is shown in Figure 3 and in Tables S1 and S2 under “Supplemental data” in the online issue. A: Plasma glutathione peroxidase activity. One unit (U) is 1 μmol NADPH oxidized per minute. The supplemented groups were not significantly different from one another at 20 wk and at later time points. B: Plasma selenoprotein P (SEPP1) concentrations. Arrowheads indicate the last time point at which the SEPP1 value was significantly different from the mean value of subjects who received larger supplements. The statistical methods used are described in Subjects and Methods. The shaded area indicates the mean ± SD of SEPP1 concentrations in US subjects from another study (Table 2 in reference 19). The values used to construct these figures and their SDs are shown in Tables S1 and S2 under “Supplemental data” in the online issue.

FIGURE 2.

Mean plasma selenium concentrations in 12–14 selenium-deficient subjects supplemented for 40 wk with selenium as selenomethionine or with placebo. Variation is shown in Figure 3. At every time point, each group is significantly different from the mean value of subjects receiving larger supplements. The values used to construct this figure and their SDs are shown in Table S3 under “Supplemental data” in the online issue.

FIGURE 3.

A–C: Mean (±1 SD) plasma selenium biomarkers at 20 wk (□) and 40 wk (○) in 12–14 selenium-deficient subjects. Note the “optimization” of selenoprotein values with higher doses and lack of optimization of selenium concentration.

FIGURE 4.

Effect of ingested selenomethionine (Semet) on selenium pools in plasma. Semet enters the methionine pool and is incorporated into proteins at methionine positions, forming a pool of selenium in plasma (shaded area). The size of this pool depends on the amount of Semet ingested and is not subject to physiologic regulation. Selenium is released from Semet when that molecule is catabolized and enters “regulated selenium metabolism,” which produces the plasma selenoproteins selenoprotein P (SEPP1) and glutathione peroxidase-3 (GPX3). Once the synthesis of selenoproteins has been satisfied, additional selenium is excreted to regulate whole-body selenium. Forms of selenium other than selenomethionine cannot enter the methionine pool. They bypass it to enter “regulated selenium metabolism” more directly. Thus, selenium ingested as selenomethionine contributes to 2 pools of selenium in the plasma: one saturable and one not saturable. Selenium ingested in other forms contributes only to the saturable pool.