Background: 

g-Tocopherol (GT) traps NO by forming 5-nitro-g-tocopherol (5-NGT) and therefore might protect against damaging effects of cigarette smoke.

Aims: 

The effects of mixed tocopherol (MT, 36.8, 73.5, 147, 294 mg/d, containing 60% GT) versus a-tocopherol (AT) (294 mg/d) were investigated in a randomized, double-blind, placebo-controlled study on 41 smokers and 44 nonsmokers.

Methods: 

Before (T0) and after 4-week supplementation (T1) the nuclear factor kB (NF-kB) p65-homodimer was determined in peripheral blood mononuclear leukocytes (PBMNL) along with alpha- and gamma-tocopherol in plasma and buccal mucosal cells (BMC) and 5-NGT and biomarkers of oxidative stress and inflammation in plasma.

Results: 

AT supplementation decreased GT and 5-NGT, while MT supplementation increased GT, but had no effect on AT and 5-NGT. GT increased from T0 to T1 at a similar rate in BMC compared to plasma, while AT increased in BMC at a smaller rate. MT supplementation did not show a dose-dependent increase in 5-NGT. Formation of 5-NGT from GT was 4.7-fold higher in smokers compared to nonsmokers, which was alleviated by 4-week supplementation. In smokers (but not nonsmokers) NF-kB activation in PBMNL and malondialdehyde formation was reduced by 294 mg/d of MT, while a similar dose of AT did not have an effect.

Conclusions: 

The decrease in GT during AT supplementation with subsequent reduction of the RNS-detoxifying capacity due to decreased NGT formation constitutes an effect that might counteract the beneficial effects of AT. Supplementation with AT in combination with even small doses of GT might alleviate these unwanted effects of AT.