Circulating γ-Tocopherol Concentrations Are Inversely Associated with Antioxidant Exposures and Directly Associated with Systemic Oxidative Stress and Inflammation in Adults

Background: Although alpha- and gamma-tocopherol are co-consumed antioxidants, circulating gamma-tocopherol concentrations were paradoxically found to be inversely associated with total vitamin E intake and circulating alpha-tocopherol concentrations. There are limited data on this apparent paradox or on determinants of circulating gamma-tocopherol concentrations. Objective: To help clarify possible determinants of circulating gamma-tocopherol concentrations, we investigated associations of circulating gamma-tocopherol concentrations with various dietary and lifestyle factors and biomarkers of oxidative stress and inflammation. Methods: We pooled cross-sectional data from 2 outpatient, adult, elective colonoscopy populations (pooled n = 419) on whom extensive dietary, lifestyle, and medical information was collected, and the following plasma concentrations were measured: alpha- and gamma-tocopherol (via HPLC), F-2-isoprostanes (FiPs; via gas chromatography-mass spectrometry), and high-sensitivity C-reactive protein (hsCRP; via latex-enhanced immunonephelometry). Multivariable general linear models were used to assess mean gamma-tocopherol differences across quantiles of plasma antioxidant micronutrients, FiPs, and hsCRP; an oxidative balance score [OBS; a composite of anti- and pro-oxidant dietary and lifestyle exposures (a higher score indicates higher antioxidant relative to pro-oxidant exposures)]; and multiple dietary and lifestyle factors. Results: Adjusted for serum total cholesterol, mean gamma-tocopherol concentrations among those in the highest relative to the lowest tertiles of circulating alpha-tocopherol and beta-carotene, the OBS, and total calcium and dietary fiber intakes were 31.0% (P < 0.0001), 29.0% (P < 0.0001), 27.6% (P = 0.0001), 29.7% (P < 0.0001), and 18.6% (P = 0.008) lower, respectively. For those in the highest relative to the lowest tertiles of circulating FiPs and hsCRP, mean. -tocopherol concentrations were 50% (P < 0.0001) and 39.0% (P < 0.0001) higher, respectively. Conclusions: These findings support the conclusion that circulating gamma-tocopherol concentrations are inversely associated with antioxidant exposures and directly associated with systemic oxidative stress and inflammation in adults. Additional research on possible mechanisms underlying these findings and on whether circulating gamma-tocopherol may serve as a biomarker of oxidative stress, inflammation, or both is needed.