Tocotrienols: Vitamin E beyond tocopherols

Abstract

In nature, eight substances have been found to have vitamin E activity: alpha-, beta-, gamma- and delta-tocopherol; and alpha-, beta-, gamma- and delta-tocotrienol. Yet, of all papers on vitamin E listed in PubMed less than 1% relate to tocotrienols. The abundance of alpha-tocopherol in the human body and the comparable efficiency of all vitamin E molecules as antioxidants, led biologists to neglect the non-tocopherol vitamin E molecules as topics for basic and clinical research. Recent developments warrant a serious reconsideration of this conventional wisdom. Tocotrienols possess powerful neuroprotective, anti-cancer and cholesterol lowering properties that are often not exhibited by tocopherols. Current developments in vitamin E research clearly indicate that members of the vitamin E family are not redundant with respect to their biological functions. alpha-Tocotrienol, gamma-tocopherol, and delta-tocotrienol have emerged as vitamin E molecules with functions in health and disease that are clearly distinct from that of alpha-tocopherol. At nanomolar concentration, alpha-tocotrienol, not alpha-tocopherol, prevents neurodegeneration. On a concentration basis, this finding represents the most potent of all biological functions exhibited by any natural vitamin E molecule. An expanding body of evidence support that members of the vitamin E family are functionally unique. In recognition of this fact, title claims in manuscripts should be limited to the specific form of vitamin E studied. For example, evidence for toxicity of a specific form of tocopherol in excess may not be used to conclude that high-dosage "vitamin E" supplementation may increase all-cause mortality. Such conclusion incorrectly implies that tocotrienols are toxic as well under conditions where tocotrienols were not even considered. The current state of knowledge warrants strategic investment into the lesser known forms of vitamin E. This will enable prudent selection of the appropriate vitamin E molecule for studies addressing a specific need.

Figure 1. Vitamin E: variations and nomenclature

A, R1 = R2 = R3 = Me, known as α-tocopherol, is designated α-tocopherol or 5,7,8-trimethyltocol; R1 = R3 = Me; R2 = H, known as, β-tocopherol, is designated, β-tocopherol or 5,8-dimethyltocol; R1 = H; R2 = R3 = Me, known as γ-tocopherol, is designated γ-tocopherol or 7,8-dimethyltocol; R1 = R2 = H; R3 = Me, known as δ-tocopherol, is designated δ-tocopherol or 8-methyltocol. B, R1 = R2 = R3 = H, 2-methyl-2-(4,8,12-trimethyltrideca-3,7,11-trienyl)chroman-6-ol, is designated tocotrienol; R1 = R2 = R3 = Me, formerly known as ζ1 or ζ2-tocopherol, is designated 5,7,8-trimethyltocotrienol or α-tocotrienol. The name tocochromanol-3 has also been used; R1 = R3 = Me; R2 = H, formerly known as ɛ-tocopherol, is designated 5,8-dimethyltocotrienol or β-tocotrienol; R1 = H; R2 = R3 = Me, formerly known as γ-tocopherol, is designated 7,8-dimethyltocotrienol or γ-tocotrienol. The name plastochromanol-3 has also been used; R1 = R2 = H; R3 = Me is designated 8-methyltocotrienol or δ-tocotrienol (Liebecq, 1992).