Tocotrienols: Mother Nature's Gift to the Brain

Vitamin E is essential for neurological function. Eight substances are known to have vitamin E activity in nature, namely α-, β-, δ-, and γ-tocopherol and α-, β-, δ-, and γ-tocotrienol. Tocotrienols are similar to tocopherols except that they have an isoprenoid tail with three unsaturation points instead of a saturated phytyl tail. Abundantly found in palm oil, tocotrienols made up less than 1% of all papers on vitamin E listed in PubMed for several decades. Recent developments have shown that tocotrienols possess powerful neuroprotective effects and play a central role in maintaining neurological structure and function. Indeed, such potent antioxidative and anti-inflammatory properties are often not exhibited by tocopherols. Orally supplemented tocotrienols could effectively reach the brain and the cerebrospinal fluid. At nanomolar concentration, alpha-tocotrienol—not alpha-tocopherol—prevents neurodegeneration and safeguards neurons by an antioxidant-independent mechanism. It shields the brain against oxidative insult as well as glutamate-induced injury. Its strong antioxidant properties could also help in protecting the nerve cells while delaying cognitive deterioration in Alzheimer’s disease. Though the role of tocotrienol in preventing Parkinson’s disease is conflicting, recent evidence about its antioxidative and non-oxidative mechanism in mitigating Parkinson’s disease is promising. With regard to ischaemic stroke, tocotrienols were shown to induce TIMP1 expression and consecutively adaptive atherogenesis in response to focal cerebral ischemia. Similarly, they could help attenuate brain lesion volume and retard the progression of white matter lesion (WML). Oral administration of tocotrienols minimises infarct volume and protects against stroke-induced lesion in the brain of hypertensive animal models. Another effect of tocotrienols is in preventing brain cancer; this is achieved through a variety of mechanisms such as its antiproliferative effects, induction of apoptosis, and cell cycle arrest. It is now proven that tocotrienols induce apoptosis via a mechanism of action different from that of tocopherols. Moreover, tocotrienol works on aggressive tumours such as glioblastomas via its potential antiangiogenetic activity and apoptosis induction in endothelial cells. Additionally, it downregulates vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF). Though the role of tocotrienols in traumatic brain injury (TBI) remains to be defined, tocotrienols have been postulated to counteract the effects of oxidative insult in TBI. For all its merits, it would be a fitting tribute to qualify tocotrienol as mother nature’s gift to the brain.