Association between the plasma proteome and plasma α-tocopherol concentrations in humans

Vitamin E is a lipophilic antioxidant that has been inversely associated with certain chronic diseases; however, the biological processes regulated by this vitamin have not been fully elucidated. The objective of the present study was to examine the association between the most biologically active and abundant form of vitamin E in the circulation, α-tocopherol, and the plasma proteome. Subjects were from the Toronto Nutrigenomics and Health Study and included men and women (n=1,022) who completed a general health and lifestyle questionnaire and 196-item food frequency questionnaire, and provided a fasting blood sample. Plasma α-tocopherol concentrations were measured by high-performance liquid chromatography and 54 plasma proteins were assayed by a mass spectrometry-based multiple reaction monitoring method. Analysis of covariance was used to compare mean concentrations of plasma proteins across tertiles of α-tocopherol. Plasma concentrations of apolipoprotein C-III, fibrinogen alpha, beta, and gamma chains, fibronectin and fibrinopeptide A were significantly and positively associated with plasma α-tocopherol, while intermediate levels of α-tocopherol were significantly associated with higher levels of alpha-1B-glycoprotein (all P<.0009). These findings show that circulating levels of α-tocopherol are significantly associated with specific plasma proteins and suggest novel physiological effects of vitamin E.