Do tocotrienols have potential as neuroprotective dietary factors?

Tocotrienols (T3) belong to the family of vitamin E compounds (α-, β-, γ-, δ-tocopherols and -tocotrienols) and have unique biological properties that make them potential neuroprotective dietary factors. In addition to their antioxidant activity, T3 at micromolar concentrations exert cholesterol-lowering activities in cells, animal models and some, but not all, human studies by means of inhibition of the activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. At lower concentrations (∼10 nmol/L), T3 modulate signalling pathways involved in neuronal cell death in cell culture experiments. Targets of T3 include prenyl transferases, non-receptor tyrosine kinase, phospholipase A2, 12-lipoxygenase, cyclooxygenase-2, and nuclear factor κB. The low bioavailability and rapid excretion of T3 represents a major hurdle in their preventive use. Fasting plasma concentrations, even after supplementation with high doses, are below 1 μmol/L. T3 bioavailability may be enhanced by ingestion with a high-fat meal, self-emulsifying drug delivery systems, or phytochemicals that inhibit T3 metabolism and excretion. T3 have no known adverse effects when consumed as part of a normal diet and the studies reviewed here support the notion that they may have potential as neuroprotective agents. However, experiments in relevant animal models and randomised human intervention trials addressing the neuroprotection mediated by T3 are scarce and, thus, highly warranted.

► Tocotrienols (T3) are natural vitamin E compounds with low bioavailability.
► Bioavailability is affected by dietary fat and ingestion of phytochemicals.
► T3 are antioxidants, hypocholesterolemic agents, and alter cell signalling.
► Cellular targets include enzymes and transcription factors.
► T3 are safe and have potential as neuroprotective dietary factors.