Tocotrienols: the emerging face of natural vitamin E

Abstract

Natural vitamin E includes eight chemically distinct molecules: alpha-, beta-, gamma-, and delta-tocopherols and alpha-, beta-, gamma-, and delta-tocotrienols. More than 95% of all studies on vitamin E are directed toward the specific study of alpha-tocopherol. The other forms of natural vitamin E remain poorly understood. 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. The tocotrienol subfamily of natural vitamin E possesses powerful neuroprotective, anticancer, 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. Recently, it has been suggested that the safe dose of various tocotrienols for human consumption is 200-1000/day. A rapidly expanding body of evidence supports that members of the vitamin E family are functionally unique. In recognition of this fact, title claims in publications 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 health 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 ε-tocopherol, is designated 5,8-dimethyltocotrienol or β-tocotrienol; R1 = H; R2 = R3 = Me, formerly known as η-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.

Figure 2. Trends in tocotrienol research and in vitamin E research as a whole

Publication data are based on PubMed entries. A, comparison of volume of all vitamin E (diamond) research and tocotrienol research (square); B, time-dependent changes in the volume of vitamin E research as a whole; C, time-dependent changes in the volume of tocotrienol research; D, tocotrienol (TCT) publications as a percent of total vitamin E publications reported; E, percent increase in tocotrienol publications and that of vitamin E as a whole over time; F, trends in NIH funding for tocotrienol research and for vitamin E research as a whole. Based on hits in the Computer Retrieval of Information on Scientific Projects (CRISP) database.