We have recently reported that gamma tocopherol (γT) reduces allergen and zymosan-induced inflammation using rodent models. As an initial step in extending these observations to humans, we conducted an open-label, Phase I dosing study of two doses (one or two capsules/daily for one week) of a gamma tocopherol rich preparation containing 623mg of γ tocopherol, 61.1mg of d-α-tocopherol, 11.1 mg of d-β-tocopherol (11.1mg), and 231 mg of d-σ-tocopherol per capsule. Endpoints for this study include serum levels of 5-nitro-gamma tocopherol, as a marker of oxidative stress, and changes in serum gamma, alpha and delta tocopherol and γ-2′-carboxyethyl-6-hydroxychroman (CEHC) six and 24 hours after the first dose and after 1 week of treatment. To assess biological activity of this treatment, we obtained peripheral blood mononuclear cells at baseline and after 1 week of treatment with 2 capsules of a gamma tocopherol rich preparation/day, and examined the inflammatory cytokine response of these cells in culture to ex-vivo endotoxin/LPS (0.01 ng/ml) challenge. We also monitored a number of safety endpoints to examine how well this preparation is tolerated in 8 normal volunteers (4 allergic and 4 non-allergic) and 8 allergic asthmatics. We further obtained human monocytes from a subset of these volunteers and treated them ex vivo with γT, αT,γ-CEHC and α-CEHC and assessed their actions on LPS induced degradation of IkBα, and JNK signaling and ROS generation. As detailed herein, this open label study demonstrates that gamma tocopherol enriched supplementation decreased systemic oxidative stress, increased serum levels of gamma tocopherol, and inhibited monocyte responses to LPS without any adverse health effects. Further,in vitro treatment of human monocytes with γ-CEHC and α-CEHC inhibits ROS generation and LPS-induced degradation of IκB and JNK activation
