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BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV(1))] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV(1) was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGA(ex)). We used mixed-effects linear regression modeling to examine the ∆vitE–FEV(1) association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P

BackgroundGiven its antioxidant activity, vitamin E is hypothesized to attenuate the age-related decline in pulmonary function.ObjectiveWe investigated the association between change in plasma vitamin E (ΔvitE) and pulmonary function decline and examined genetic and non-genetic factors associated with ΔvitE.DesignWe studied 1,144 men randomized to vitE in the Selenium and Vitamin E Cancer Prevention Trial. ΔvitE was calculated as the difference between baseline and year 3 vitE concentrations measured with gas chromatography-mass spectrometry. Pulmonary function (forced expiratory volume in the first second [FEV1]) was measured longitudinally with spirometry. We genotyped 555 participants (vitE-only arm) using the Illumina MEGAex array. We examined the association of ΔvitE with annual change in FEV1 using mixed-effects linear regression. We also examined the association of previously reported genetic and non-genetic factors with ΔvitE.ResultsGreater ΔvitE was associated with attenuated FEV1 decline, with stronger effects in adherent supplement responders: a 1 SD higher ΔvitE (+4 µmol/mmol free-cholesterol-adjusted α-tocopherol) attenuated FEV1 decline by ∼8.9 mL/year (P=0.014). This effect size is ∼1/4 of the effect of one year of aging, but in the opposite direction. The ΔvitE-FEV1 association was positive in never and current smokers (9.7 and 11.0 mL/year attenuated FEV1 decline, respectively), but there was little to no association in former smokers. Greater ΔvitE was associated with lower baseline α-tocopherol, higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (vs. African ancestry) (all PCYP4F2 (rs2108622-T) (2.4 µmol/L greater ΔvitE; P=0.0032).ConclusionsGreater response to vitE supplementation was associated with attenuated FEV1 decline, and this response was differed by rs2108622 such that individuals with the C allele may need a higher vitE intake dose to reach the same plasma level, compared to the T allele.

Background The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to the risk of chronic obstructive pulmonary disease (COPD). Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported. Methods A post hoc analysis of 38 597 women without chronic lung disease at baseline was conducted in the Women9s Health Study (WHS) to test the effect of vitamin E on the risk of incident chronic lung disease. The WHS is a randomised double-blind placebo-controlled factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged ≥45 years. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported physician-diagnosed chronic lung disease was evaluated. Results During 10 years of follow-up (376 710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared with 846 in the placebo arm (HR 0.90; 95% CI 0.81 to 0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use or dietary vitamin E intake (minimum p for interaction=0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70 to 4.70; vs. never smokers). Conclusions In this large randomised trial, assignment to 600 IU vitamin E led to a 10% reduction in the risk of chronic lung disease in women.

Antioxidant nutritional status is hypothesized to influence chronic obstructive pulmonary disease (COPD) susceptibility and progression. Although past studies relate antioxidants to gene expression, there are no data in patients with COPD. This study investigated the hypothesis that antioxidant status is compromised in patients with COPD, and antioxidant-responsive genes differentially express in a similar pattern. Lung tissue samples from patients with COPD were assayed for vitamin E and gene expression. Selenium and vitamin E were assayed in corresponding plasma samples. Discovery based genome-wide expression analysis compared moderate, severe, and very severe COPD (GOLD II-IV) patients to mild and at-risk/normal (GOLD 0-I). Hypotheses-driven analyses assessed differential gene expression by disease severity for vitamin E-responsive and selenium-responsive genes. GOLD II-IV COPD patients had 30% lower lung tissue vitamin E levels compared to GOLD 0-I participants (p = 0.0082). No statistically significant genome-wide differences in expression by disease severity were identified. Hypothesis-driven analyses of 109 genes found 16 genes differentially expressed (padjusted < 0.05) by disease severity including 6 selenium-responsive genes (range in fold-change -1.39 to 2.25), 6 vitamin E-responsive genes (fold-change -2.30 to 1.51), and 4 COPD-associated genes. Lung tissue vitamin E in patients with COPD was associated with disease severity and vitamin E-responsive genes were differentially expressed by disease severity. Although nutritional status is hypothesized to contribute to COPD risk, and is of therapeutic interest, evidence to date is mainly observational. The findings reported herein are novel, and support a role of vitamin E in COPD progression.