Effects of Higher Doses of Vitamin E on Toxicity and Inflammation

ABSTRACT

High doses of vitamin E close to the upper limit of toxicity (UL) but still recommended and considered as harmless and beneficial, can possibly cause a number of adverse effects. In a 14-day study, in which male mice were exposed to intra peritoneal doses of 100 and 200 mg vitamin E (alpha-tocopherol)/kg bw/day, biomarkers of oxidative stress related processes (ROM, TTL), and biomakers of tissue toxicity (ALP, ALT, AST, LDH) and inflammation (MCP-1, IL-6, TNF-α, PAI-1 and resistin) were determined. Oxidative stress parameters in plasma did not change, whereas some biomarkers of inflammation were statistically significantly higher on exposure to vitamin E. In the liver, beneficial effects on tissue biomarkers were observed, whereas the inflammation biomarkers showed an U-shaped relation with the dose of vitamin E. In the kidney, the biomarkers of tissue damage showed mixed effects, whereas a substantial increase in the inflammation biomarkers was observed. In the brain, the biomarkers of tissue toxicity showed beneficial effects, whereas the inflammatory biomarkers showed an increase or an U-shaped behaviour with increasing doses of vitamin E. Especially, a dose of 200 mg of vitamin E/kg bw/day showed a number of adverse effects in several tissues. These results confirm our previous study in male mice with exposure of vitamin E by feed. Since the dose of 200 mg of vitamin E/kg bw/day is lower than the upper limit for vitamin E, the UL should be re-evaluated, in view of the effects in kidney and brain.