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