Antioxidant activity of tocopherols and tocotrienols against lipid peroxidation and cell death: Revisited

Vitamin E, an essential radical scavenging antioxidant, consists of tocopherol (T) and tocotrienol (T3). The relative antioxidant activity of T and T3 has been the subject of extensive studies and controversy. Chemically, T and T3 exhibit similar antioxidant effects but higher antioxidant activity of T3 than T has often been observed in cultured cells. The higher apparent activity of T3 than T is primarily because T3 is taken up by cultured cells much faster than T and, in fact, when the cellular concentrations of T and T3 are normalized, they exert substantially the same antioxidant effects. Furthermore, bioavailability of T3 in humans is much smaller than T because of significantly smaller affinity of T3 to α-tocopherol transfer protein and faster metabolism by CYP4F2 enzyme than T. Thus, biological antioxidant capacity of T3 against lipid peroxidation and related cell damage including ferroptosis is significantly smaller than T.