Background: Vitamin E is an essential micronutrient and critical human antioxidant previously tested for cancer preventative effects with conflicting clinical trial results that have yet to be explained biologically.

Methods: We examined baseline and on-trial serum samples for 154 men randomly assigned to receive 400 IU vitamin E (as alpha-tocopheryl acetate; ATA) or placebo daily in the Vitamin E Atherosclerosis Prevention Study (VEAPS), and for 100 men administered 50 IU ATA or placebo daily in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC). Over 970 metabolites were identified using ultrahigh-performance LC/MS-MS. Linear regression models estimated the change in serum metabolites of men supplemented with vitamin E versus those receiving placebo in VEAPS as compared with ATBC.

Results: Serum alpha-carboxyethyl hydrochroman (CEHC) sulfate, alpha-tocopherol, and beta/gamma-tocopherol were significantly altered by ATA supplementation in both trials (all P values ≤5.1 × 10^-5, the Bonferroni multiple comparisons corrected statistical threshold). Serum C₂₂ lactone sulfate was significantly decreased in response to the high-dose vitamin E in VEAPS (β = -0.70, P = 8.1 × 10^-6), but not altered by the low dose in ATBC (β = -0.17, P = 0.4). In addition, changes in androgenic steroid metabolites were strongly correlated with the vitamin E supplement-associated change in C₂₂ lactone sulfate only in the VEAPS trial.

Conclusions: We found evidence of a dose-dependent vitamin E supplementation effect on a novel C₂₂ lactone sulfate compound that was correlated with several androgenic steroids.

Impact: Our data add information on a differential hormonal response based on vitamin E dose that could have direct relevance to opposing prostate cancer incidence results from previous large controlled trials.

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Objective: To investigate the preventive effects of a combined antioxidant drug (N-acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect.

Design: Randomized, double-blind, sham-controlled pilot study.

Setting: Australian community.

Subjects: Adults reporting 2 to 8 migraines per month for at least a year.

Methods: After a 1-month baseline period, 35 subjects completed 3 months of treatment with NEC (n = 19) or sham (n = 16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below.

Results: For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P = 0.004) compared with 1.4 for sham (P = 0.073); there was no significant difference in these changes between the 2 groups (P = 0.052). Average monthly headache (P = 0.041) and migraine frequency (P = 0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (-3.1), moderate/severe headache days (-3.2), migraine duration, headache pain scores, and acute headache medication use.

Conclusions: This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine.

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Electronic cigarettes (e-cigarettes) are battery-operated devices to insufflate nicotine or other psychoactive e-liquid aerosols. Despite initial claims of e-cigarettes as a nicotine-cessation device, aggressive marketing of e-cigarettes has led to an explosion in adolescents’ and young adults’ use over the last few years. Coupled with a lack of adequate investigation and regulation of e-cigarettes, the USA is facing an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) starting in mid-2019. While little long-term health hazard data are available, the components and constituents of e-cigarettes may adversely impact health. Propylene glycol and glycerin are humectants (water-retaining excipients) that generate pulmonary irritants and carcinogenic carbonyl compounds (e.g., formaldehyde, acetaldehyde, and acrolein) when heated in e-cigarettes. Metals contained in heating coils and cartridge casings may leach metals such as aluminum, chromium, iron, lead, manganese, nickel, and tin. Flavoring agents are considered safe for ingestion but lack safety data for inhalational exposures. Diacetyl, a common buttery flavoring agent, has known pulmonary toxicity with inhalational exposures leading to bronchiolitis obliterans. In 2019, clusters of lung injury associated with e-cigarette use were identified in Wisconsin and Illinois. Patients with EVALI present with a constellation of respiratory, gastrointestinal, and constitutional symptoms. Radiographically, patients have bilateral ground glass opacifications. As of February 18, 2020, the Centers for Disease Control has identified 2807 hospitalized patients diagnosed with either “confirmed” or “probable” EVALI in the US. Currently, vitamin E acetate (VEA) used as a diluent in tetrahydrocannabinol vape cartridges is implicated in EVALI. VEA cuts tetrahydrocannabinol oil without changing the appearance or viscosity. When inhaled, pulmonary tissue lacks the mechanism to metabolize and absorb VEA, which may lead to its accumulation. While most EVALI patients were hospitalized, treatment remains largely supportive, and use of corticosteroids has been associated with clinical improvement. The outbreak of EVALI highlights the need for regulation of e-cigarette devices and e-liquids. Clinicians need to be aware of the health hazards of e-cigarettes and be vigilant in asking about vaping.

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