Gamma-tocopherol, a major form of vitamin E in diets: Insights into antioxidant and anti-inflammatory effects, mechanisms, and roles in disease management

gamma-Tocopherol (gamma T) is a major form of vitamin E in the US diet and the second most abundant vitamin E in the blood and tissues, while alpha-tocopherol (alpha T) is the predominant vitamin E in tissues. During the last >25 years, research has revealed that gamma T has unique antioxidant and anti-inflammatory activities relevant to disease prevention compared to alpha T. While both compounds are potent lipophilic antioxidants, gamma T but not al' can trap reactive nitrogen species by forming 5-nitro-gamma T, and appears to show superior protection of mitochondrial function. gamma T inhibits ionophore-stimulated leukotrienes by blocking 5-lipoxygenase (5-LOX) translocation in leukocytes, decreases cyclooxygenase-2 (COX-2)-catalyzed prostaglandins in macrophages and blocks the growth of cancer cells but not healthy cells. For these activities, gamma T is stronger than ca. Moreover, gamma T is more extensively metabolized than gamma T via cytochmme P-450 (CYP4F2)-initiated side-chain oxidation, which leads to formation of metabolites including 13'-carboxychromanol (13'-COOH) and carboxyethyl-hydroxychroman (gamma-CEHC). 13'-COOH and gamma-CEHC are shown to be the predominant metabolites found in feces and urine, respectively. Interestingly, gamma-CEHC has natriuretic activity and 13'-COOH inhibits both COX-1/-2 and 5-LOX activity. Consistent with these mechanistic findings of gamma T and metabolites, studies show that supplementation of gamma T mitigates inflammation and disease symptoms in animal models with induced inflammation, asthma and cancer. In addition, supplementation of gamma T decreased inflammation markers in patients with kidney diseases and mild asthma. These observations support that gamma T may be useful against inflammation-associated diseases.