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

Abstract

γ-Tocopherol (γ-T) scavenges reactive nitrogen species (RNS) to form 5-NO2-γ-tocopherol (NGT). However, α-T supplementation decreases circulating γ-T, which could limit its RNS scavenging activities. We hypothesized that α-T supplementation would mitigate NGT accumulation by impairing γ-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-α-tocopheryl acetate for 6 d. Plasma α-T, γ-T, γ-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. α-T supplementation increased plasma α-T, and decreased γ-T, in both groups and these returned to Pre concentrations on Post 6 regardless of smoking status. Plasma γ-CEHC increased after the first dose of supplementation in both groups, suggesting that α-T supplementation decreased plasma γ-T in part by increasing its metabolism. Plasma NGT and nitrate/nitrite at Pre were greater in smokers, indicating greater nitrative stress due to cigarette smoking. Plasma NGT 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 γ-T. Plasma NGT was more strongly correlated (P<0.05) with γ-T in smokers (R=0.83) compared to non-smokers (R=0.50), supporting that α-T-mediated decreases in γ-T reduces NGT formation. These data indicate that α-T supplementation limits γ-T scavenging of RNS in smokers by decreasing γ-T availability.

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

“…is effective in scavenging peroxyl radicals. The biologically most efficient forms of vitamin E are α-tocopherol, which is effective in trapping peroxyl radicals and protecting membranes, and γ-tocopherol, very efficient in deactivating nitrogen-based radicals (RNS) (Pei et al 2015 ). Vitamin E has the capacity to delay neuronal death caused by inflammation.…”

Analytical strategies to assess the functional metabolome of vitamin E

“…CEHC metabolites have been reported to possess chemical and biological properties that may support and even strengthen the biological roles of vitamin E. In a close functional analogy with ␥-T [41], ␥-CEHC can scavenge NOx through either electron donation or NO 2 addition in position 5 of the chroman ring [60], a process that may have relevance in case of a sustained metabolism of ␥-T in both the plasma and urinary compartment. Moreover, ␥-CEHC has moderate natriuretic properties [7,61,62].…”

“…Accordingly, such a constitutive selectivity of capture and tissue transferring mechanisms in liver cells has been demonstrated to have important functional implications limiting the systemic bioavailability of non-␣-forms. In fact, human high-dose supplementation protocols based on the sole administration of ␣-T cause a massive depletion of blood ␥-T by stimulating its enzymatic metabolism [7,40,41], a condition that may cause health harms for instance by limiting the capability of scavenging NO-derived species in smokers [41] or in other groups at risk of developing nitrosative stress such as chronic kidney disease patients [42] and others as reviewed in [7].…”