No abstract

A year-long intervention trial was conducted to characterise the responses of multiple biomarkers of Se status in healthy American adults to supplemental selenomethionine (SeMet) and to identify factors affecting those responses. A total of 261 men and women were randomised to four doses of Se (0, 50, 100 or 200 mg/d as L-SeMet) for 12 months. Responses of several biomarkers of Se status (plasma Se, serum selenoprotein P (SEPP1), plasma glutathione peroxidase activity (GPX3), buccal cell Se, urinary Se) were determined relative to genotype of four selenoproteins (GPX1, GPX3, SEPP1, selenoprotein 15), dietary Se intake and parameters of single-carbon metabolism. Results showed that supplemental SeMet did not affect GPX3 activity or SEPP1 concentration, but produced significant, dose-dependent increases in the Se contents of plasma, urine and buccal cells, each of which plateaued by 9 -12 months and was linearly related to effective Se dose (mg/d per kg 0·75 ). The increase in urinary Se excretion was greater for women than men, and for individuals of the GPX1 679 T/T genotype than for those of the GPX1 679 C/C genotype. It is concluded that the most responsive Se-biomarkers in this non-deficient cohort were those related to body Se pools: plasma, buccal cell and urinary Se concentrations. Changes in plasma Se resulted from increases in its non-specific component and were affected by both sex and GPX1 genotype. In a cohort of relatively high Se status, the Se intake (as SeMet) required to support plasma Se concentration at a target level (Se pl-target ) is: Se in ¼ ½ðSe pl2target 2 Se pl Þ=ð18:2 ng d kg 0:75 =ml per mgÞ .Key words: Selenium: Biomarkers: Selenoprotein P: Glutathione peroxidase: Genotype: Supplementation Se is an essential mineral nutrient required to support the expression of some twenty-five proteins, each of which contains selenocysteine residues as essential constituents (1) . These selenoproteins have diverse functions including antioxidant protection (2) , thyroid hormone metabolism (3) and Se transport (4) . Selenoprotein expression can be reduced by deprivation of Se. SNP can also affect selenoprotein function, as in the case of cytosolic glutathione peroxidase (GPX1) (5) . In fact, GPX1 genotype has been associated with cancer risk (6) .High Se status has been associated with reduced cancer risk, and perhaps increased risk of type 2 diabetes. The Nutritional Prevention of Cancer (NPC) Trial showed that increasing Se intake could reduce colon and prostate cancer risk (7) , at least for individuals with plasma Se levels , 106 ng/ml (8) . However, the same study indicated that Se-supplemented subjects whose plasma Se levels had increased to 180-200 ng/ml may have had increased risk of type 2 diabetes (9) . Elevated diabetes risk was observed for subjects in the upper quintile of plasma Se ($ 137·7 ng/ml) in the third National Health and Examination Survey (NHANES) (10) , and among subjects in the upper quartile of plasma Se ($ 147 ng/ml) in NHANES 2003-4 (11) . While increased diabete...

An experiment was designed to test part of the hypothesis that physiologic amounts of dietary boron enhance utilization of or, alternatively, compensate for, inadequate concentrations of active vitamin D metabolites to normalize energy substrate utilization and mineral metabolism. Day-old cockerel chicks were fed a ground corn, high-protein casein, corn oil-based diet (< or = 0.18 mg B/kg) supplemented with physiologic amounts of boron (as orthoboric acid) at 0 (non-PSB) or 1.4 (PSB) mg/kg and vitamin D3 (as vitamin D3 powder in corn endosperm carrier) at 3.13 (inadequate, IVD) or 15.6 (adequate, AVD) micrograms/kg. After 26 days, IVD decreased food consumption and plasma calcium concentrations and increased plasma concentrations of glucose, beta-hydroxybutyrate, triglycerides, triiodothyronine, cholesterol, and alkaline phosphatase activity. In the IVD chicks, PSB returned plasma glucose and triglycerides to concentrations exhibited by the AVD chicks and increased food consumption in both IVD and AVD chicks. Histologic findings suggested that PSB enhanced maturation of the growth plate. A ninefold increase in dietary boron yielded only a two-fold increase in plasma boron concentration and no increase in femur boron concentration, which suggests that boron is under homeostatic control. The findings suggest that boron acts on at least three separate metabolic sites because it compensates for perturbations in energy substrate utilization induced by vitamin D3 deficiency, enhances major mineral content in bone, and, independently of vitamin D3, enhances some indices of growth cartilage maturation.