Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial

Abstract

Background: Dietary recommendations for selenium differ between countries, mainly because of uncertainties over the definition of optimal selenium status.

Objective: The objective was to examine the dose-response relations for different forms of selenium.

Design: A randomized, double-blind, placebo-controlled dietary intervention was carried out in 119 healthy men and women aged 50-64 y living in the United Kingdom. Daily placebo or selenium-enriched yeast tablets containing 50, 100, or 200 microg Se ( approximately 60% selenomethionine), selenium-enriched onion meals ( approximately 66% gamma-glutamyl-methylselenocysteine, providing the equivalent of 50 microg Se/d), or unenriched onion meals were consumed for 12 wk. Changes in platelet glutathione peroxidase activity and in plasma selenium and selenoprotein P concentrations were measured.

Results: The mean baseline plasma selenium concentration for all subjects was 95.7 +/- 11.5 ng/mL, which increased significantly by 10 wk to steady state concentrations of 118.3 +/- 13.1, 152.0 +/- 24.3, and 177.4 +/- 26.3 ng/mL in those who consumed 50, 100, or 200 microg Se-yeast/d, respectively. Platelet glutathione peroxidase activity did not change significantly in response to either dose or form of selenium. Selenoprotein P increased significantly in all selenium intervention groups from an overall baseline mean of 4.99 +/- 0.80 microg/mL to 6.17 +/- 0.85, 6.73 +/- 1.01, 6.59 +/- 0.64, and 5.72 +/- 0.75 microg/mL in those who consumed 50, 100, or 200 microg Se-yeast/d and 50 microg Se-enriched onions/d, respectively.

Conclusions: Plasma selenoprotein P is a useful biomarker of status in populations with relatively low selenium intakes because it responds to different dietary forms of selenium. To optimize the plasma selenoprotein P concentration in this study, 50 microg Se/d was required in addition to the habitual intake of approximately 55 microg/d. In the context of established relations between plasma selenium and risk of cancer and mortality, and recognizing the important functions of selenoprotein P, these results provide important evidence for deriving estimated average requirements for selenium in adults. This trial was registered at clinicaltrials.gov as NCT00279812.

FIGURE 1

Trial profile. Numbers of volunteers who were screened and took part in the intervention trial.

FIGURE 2

Dose response of plasma selenium concentrations over a range of selenium-enriched yeast supplement doses and comparison with the food intervention groups at week 10, when selenium status had reached steady state. The box plots show the median and interquartile range for the placebo (n = 20), 50 μg Se-yeast/d (n = 18), 100 μg Se-yeast/d (n = 20), 200 μg Se-yeast/d (n = 23), 0 μg Se/d unenriched onion meal (n = 16), and 50 μg Se-enriched onion meal/d (n = 17) groups. The significant changes over the dose range are shown, including the comparison between the two 50-μg/d groups (selenium-yeast compared with selenium-enriched onions). Data were analyzed by using a single mixed-effects model, and Tukey's honestly significant difference test was used to assess pairwise differences between groups. There was a significant effect of time (P < 0.001), treatment (P < 0.001), and time × treatment interaction (P < 0.001) on plasma selenium concentrations. The box plots displaying the food intervention group data are shaded gray to distinguish them from the supplement and food groups.

FIGURE 3

Relation between plasma selenium and selenoprotein P concentrations from a joinpoint regression analysis (29) of data from weeks 0, 6, and 10 (when data were available for both biomarkers, n = 340). The mean values for each 10-ng/mL increase in plasma selenium concentration are shown for both biomarkers, and the 2 lines represent a joinpoint regression fit to the data. A single joinpoint gave the best fit to the data, with a linear slope from >50 ng/mL up to a mean plasma selenium concentration of 124 ng/mL (P < 0.001 for the test of the null hypothesis that the first slope was equal to zero), followed by a plateau, with the line >124 ng/mL displaying no significant change (P = 0.24 for the test of the null hypothesis that the second slope was equal to zero).

FIGURE 4

Dose response of plasma selenoprotein P concentrations over a range of selenium-enriched yeast supplement doses and comparison with the food intervention groups. Data shown are from week 10 data when selenium status had reached steady state. The box plots show the median and interquartile range for the placebo (n = 20), 50 μg Se-yeast/d (n = 18), 100 μg Se-yeast/d (n = 21), 200 μg Se-yeast/d (n = 23), 0 μg Se/d unenriched onion meal (n = 17), and 50 μg Se-enriched onion meal/d (n = 18) groups. The significant changes over the dose range are shown, including the comparison between the two 50-μg/d groups (selenium-yeast compared with selenium-enriched onions). Data were analyzed by using a single mixed-effects model, and Tukey's honestly significant difference test was used to assess pairwise differences between groups. There was a significant effect of time (P < 0.001), treatment (P < 0.001), and time × treatment interaction (P < 0.001) on plasma selenoprotein P concentrations. The box plots displaying the food intervention group data are shaded gray to distinguish them from the supplement and food groups.