Short-term animal and human studies provide promising evidence that a γ-tocopherol- enriched tocopherol supplement may mitigate neutrophil and eosinophil recruitment into the lungs and airway inflammation in eosinophilic asthma (e-asthma). The preliminary findings are clinically significant because effective, sustained treatment of e-asthma is required for prevention of irreversible lung damage, and treatment options are very limited.
Asthma is a chronic lung disease that inflames and narrows the airways. It affects an estimated 25 million people of all ages in the U.S. Moreover, about 50% of severe cases may have excessive infiltration of eosinophils and neutrophils into the lungs. Treating severe asthmatic episodes with inhalers provides “crisis management,” but laxity of proactive treatment when symptoms are less severe may lead to serious long-term, irreversible lung disease. Epidemiological studies have identified dietary vitamin E as a potential candidate for the treatment of asthma, and prior animal studies of neutrophilic inflammation have elucidated primary mechanisms by which a specific γ-tocopherol-rich mixture of tocopherols (γ-TmT) mitigates the associated pro-inflammatory, chemoattractant, and oxidative and nitrositive stress responses.
Numerous environmental factors exacerbate asthma, and lipopolysaccharide (LPS) present in airborne particles is one of the most significant triggers. A proof of concept study in rats incorporating LPS challenges preceded a double blinded, randomized, placebo controlled crossover study in 13 non-asthmatic healthy volunteers. For 7 days subjects took gel caps containing either 540 mg of γ-tocopherol (γ-T) or sunflower oil “placebo” (150 mg γ-T) prior to receiving an intranasal dose of LPS. There was a washout period between placebo and active treatment periods.
The week long active treatment (γ-TmT) more than doubled the serum level of γ-T and its end stage, bio-active metabolite up to 24 hours after the last oral dose. Active treatment also blunted the LPS-induced increase in serum 5-nitro- γ-tocopherol which is consistent with the capacity of γ-T to ameliorate nitrositive stress.
Inhaled LPS was associated with significant increases in peripheral white blood cell and absolute neutrophil counts after both placebo and active treatment; peripheral absolute eosinophil count was unaffected. However in induced sputum, γ-TmT supplementation decreased the percentage of eosinophils and almost completely blocked the LPS-induced increase of percentage of neutrophils; an apparent γ-T-induced blunted granulocyte recruitment phenomena.
Take away: Short-term supplementation with a γ-T-enriched tocopherol mixture in non-asthmatic subjects markedly reduced neutrophil recruitment into the airways after inhaled LPS, and decreased the level of a biomarker of nitrositive stress commonly associated with inflammation. Further studies are needed to determine if high-dose γ-T supplementation is in fact warranted as adjunctive therapeutic intervention for airway diseases such as e-asthma and possibly COPD. Excessive supplementation with α-tocopherol lowers serum γ-tocopherol. Direct assessment of the serum levels of both tocopherol vitamers should be considered, especially for patients diagnosed with diseases associated with airway neutrophilic inflammation.
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