Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease

Abstract

A growing body of research supports that members of the vitamin E family are not redundant with respect to their biological function. Palm oil derived from Elaeis guineensis represents the richest source of the lesser characterized vitamin E, alpha-tocotrienol. One of 8 naturally occurring and chemically distinct vitamin E analogs, alpha-tocotrienol possesses unique biological activity that is independent of its potent antioxidant capacity. Current developments in alpha-tocotrienol research demonstrate neuroprotective properties for the lipid-soluble vitamin in brain tissue rich in polyunsaturated fatty acids (PUFAs). Arachidonic acid (AA), one of the most abundant PUFAs of the central nervous system, is highly susceptible to oxidative metabolism under pathologic conditions. Cleaved from the membrane phospholipid bilayer by cytosolic phospholipase A(2), AA is metabolized by both enzymatic and nonenzymatic pathways. A number of neurodegenerative conditions in the human brain are associated with disturbed PUFA metabolism of AA, including acute ischemic stroke. Palm oil-derived alpha-tocotrienol at nanomolar concentrations has been shown to attenuate both enzymatic and nonenzymatic mediators of AA metabolism and neurodegeneration. On a concentration basis, this represents the most potent of all biological functions exhibited by any natural vitamin E molecule. Despite such therapeutic potential, the scientific literature on tocotrienols accounts for roughly 1% of the total literature on vitamin E, thus warranting further investment and investigation.

Fig. 1

Chemical structure of α-tocopherol and α-tocotrienol. Three unsaturations at carbon positions 3, 7, and 11 in the isoprenoid side chain account for the structural difference in α-tocopherol and α-tocotrienol chemical structure. This seemingly small difference has large implications for bioavailability and the specific biological functions of the vitamin E isomers.

Fig. 2

Palm oil–derived natural vitamin E attenuates the arachidonic acid (AA) cascade in brain injury. Following release from the lipid membrane bilayer by phospholipase A₂ (PLA₂), the polyunsaturated fatty acid AA undergoes oxidative metabolism in nonenzymatic and enzymatic pathways. Well known for their antioxidant function, natural vitamin E isomers α-tocotrienol (αTCT) and α-tocopherol (αTOC) inhibit nonenzymatic oxidative lipid metabolism of AA. Independent of antioxidant function common to all vitamin E isomers, αTCT is a specific and potent inhibitor of cytosolic phospholipase A₂ (cPLA₂), c-Src kinase (c-Src), and 12-lipoxygenase (12-LOX) at nanomolar concentrations.