α-Tocopherol supplementation reduces 5-nitro-γ-tocopherol accumulation by decreasing γ-tocopherol in young adult smokers

gamma-Tocopherol (gamma-T) scavenges reactive nitrogen species (RNS) to form 5-NO2-gamma-T (NGT). However, alpha-T supplementation decreases circulating gamma-T, which could limit its RNS scavenging activities. We hypothesized that alpha-T supplementation would mitigate NGT accumulation by impairing gamma-T status. Healthy smokers (21 +/- 1 y, n = 11) and non-smokers (21 +/- 2 y, n = 10) ingested 75 mg/d each of RRR- and all-rac-alpha-tocopheryl acetate for 6 d. Plasma alpha-T, gamma-T, gamma-carboxyethyl hydroxychromanol (CEHC), NGT, and nitrate/nitrite were measured prior to supplementation (Pre), the morning after 6 consecutive evenings of supplementation (Post 1), and on the mornings of d 6 (Post 6) and d 14 (Post 14) during the post-supplementation period. alpha-T supplementation increased plasma alpha-T, and decreased gamma-T, in both groups and these returned to Pre concentrations on Post 6 regardless of smoking status. Plasma gamma-CEHC increased after the first dose of supplementation in both groups, suggesting that alpha-T supplementation decreased plasma gamma-T in part by increasing its metabolism. Plasma NGT and nitrate/nitrite concentrations at Pre were greater in smokers, indicating greater nitrative stress due to cigarette smoking. Plasma NGT concentration was lowered only in smokers on Post 1 and Post 6 and was restored to Pre levels on Post 14. Plasma nitrate/nitrite tended (P = 0.07) to increase post-supplementation only in smokers, supporting decreases in RNS scavenging by gamma-T. Plasma NGT concentration was more strongly correlated (P < 0.05) with gamma-T in smokers (R = 0.83) compared with non-smokers (R = 0.50), supporting that alpha-T-mediated decreases in gamma-T reduces NGT formation. These data indicate that alpha-T supplementation limits gamma-T scavenging of RNS in smokers by decreasing gamma-T availability.