Anti-inflammatory properties of alpha- and gamma-tocopherol

Abstract

Natural vitamin E consists of four different tocopherol and four different tocotrienol homologues (alpha,beta, gamma, delta) that all have antioxidant activity. However, recent data indicate that the different vitamin E homologues also have biological activity unrelated to their antioxidant activity. In this review, we discuss the anti-inflammatory properties of the two major forms of vitamin E, alpha-tocopherol (alphaT) and gamma-tocopherol (gammaT), and discuss the potential molecular mechanisms involved in these effects. While both tocopherols exhibit anti-inflammatory activity in vitro and in vivo, supplementation with mixed (gammaT-enriched) tocopherols seems to be more potent than supplementation with alphaT alone. This may explain the mostly negative outcomes of the recent large-scale interventional chronic disease prevention trials with alphaT only and thus warrants further investigation.

Figure 1. Possible molecular mechanisms of the anti-inflammatory effects mediated by α- and γT

The two tocopherols can act anti-inflammatory either by affecting transcription of inflammatory genes by modulating the signaling pathways involved in upregulation of these genes, or by inhibiting the activity of enzymes involved in eicosanoid biosynthesis. αT acts primarily through inhibition of cell signaling, while γT (and its water-soluble metabolite γ-CEHC) potently inhibits COX-2-mediated biosynthesis of PGE₂. Akt, protein kinase B; p38^MAPK, p38 mitogen-activated protein kinase; PDK, phosphoinositide-dependent kinase; PI3K, phosphatidylinositol 3-kinase; PKC, protein kinase C; PLC, phospholipase C; PP2A, protein phosphatase 2A;