Vitamin A acts as a potent suppressor of selenoprotein P with potential relevance for multivitamin supplementation

Multivitamin supplementation is a widely used strategy to prevent disease, slow the ageing process, improve quality of life and extend life span, although recent clinical findings do not support these claims. Since selenium (Se) deficiency is associated with morbidity and mortality risk, we tested the hypothesis that certain vitamins interfere with the regular biosynthesis of the Se transporter selenoprotein P (SELENOP). Human liver cancer cells (HepG2) were treated with different concentrations of folic acid, nicotinamide, nicotinic acid, pyridoxal phosphate, thiamine, vitamin A, vitamin C, vitamin D2, vitamin D3, vitamin E, vitamin K and vitamin B12. Secreted SELENOP was quantified by ELISA and characterized by Western blot analysis. SELENOP transcript levels and promoter activity were determined, and resveratrol as a negative and thyroid hormone as a positive modulator were included for comparison. The concentration of extracellular SELENOP decreased twofold in response to micromolar concentrations of vitamin A. The SELENOP transcript concentration decreased to 70% after incubation with 1 µM vitamin A, and a moderate concomitant decrease in SELENOP core promoter activity was observed. Co-incubation experiments of vitamin A with the active thyroid hormone T3 revealed dose-dependent effects and suggested competitive activities of these two modifiers of SELENOP expression in opposite directions. We conclude that vitamin A is able to suppress hepatic SELENOP biosynthesis and secretion, which may confer health risks in self-administered or clinically indicated supplementation with retinoids, especially in individuals with marginal Se intake and status.