Tocotrienol: The Natural Vitamin E to Defend the Nervous System?

Abstract

Vitamin E is essential for normal neurological function. It is the major lipid-soluble, chain-breaking antioxidant in the body, protecting the integrity of membranes by inhibiting lipid peroxidation. Mostly on the basis of symptoms of primary vitamin E deficiency, it has been demonstrated that vitamin E has a central role in maintaining neurological structure and function. Orally supplemented vitamin E reaches the cerebrospinal fluid and brain. Vitamin E is a generic term for all tocopherols and their derivatives having the biological activity of RRR-alpha-tocopherol, the naturally occurring stereoisomer compounds with vitamin E activity. 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. Often, the term vitamin E is synonymously used with alpha-tocopherol. Tocotrienols, formerly known as zeta, , or eta-tocopherols, are similar to tocopherols except that they have an isoprenoid tail with three unsaturation points instead of a saturated phytyl tail. Although tocopherols are predominantly found in corn, soybean, and olive oils, tocotrienols are particularly rich in palm, rice bran, and barley oils. Tocotrienols possess powerful antioxidant, anticancer, and cholesterol-lowering properties. Recently, we have observed that alpha-tocotrienol is multi-fold more potent than alpha-tocopherol in protecting HT4 and primary neuronal cells against toxicity induced by glutamate as well as by a number of other toxins. At nanomolar concentration, tocotrienol, but not tocopherol, completely protected neurons by an antioxidant-independent mechanism. Our current work identifies two major targets of tocotrienol in the neuron: c-Src kinase and 12-lipoxygenase. Dietary supplementation studies have established that tocotrienol, fed orally, does reach the brain. The current findings point towards tocotrienol as a potent neuroprotective form of natural vitamin E.

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

“…Some evidence has suggested that T3s have greater potential physiologic functions than TPs (7,8). T3 has been shown to mediate its activity against a variety of chronic diseases, including cardiovascular diseases, neurologic diseases, diabetes, and cancer (9)(10)(11)(12)(13)(14). T3s have shown anticancer activity against cancers such as colon, breast, liver, lung, kidney, prostate, skin, and other cancers both in vitro (15)(16)(17)(18)(19)(20) and in vivo (21)(22)(23)(24)(25).…”

Assessment of Tocopherol Metabolism and Oxidative Stress in Familial Hypobetalipoproteinemia

“…There has been considerable interest in the potential benefits of ␥-tocopherol for human health (27,28 ), and a recent analysis suggested that various forms of vitamin E may be important in the preservation of cognition in persons with Alzheimer disease (29 ). Clearly, further investigation is needed to assess the efficacy of the different forms of vitamin E and their relative effects on oxidative stress in persons with very low cholesterol.…”

“…Clearly, further investigation is needed to assess the efficacy of the different forms of vitamin E and their relative effects on oxidative stress in persons with very low cholesterol. Amid recent interest in the potential benefits of tocotrienols and neurologic function (29 ), there remains potential for different forms of vitamin E to further reduce sequelae in conditions associated with low cholesterol and oxidative stress.…”

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

“…Indeed, a-T3 in human and animal plasma usually reaches maximum 1 lmol/l irrespective of the amount supplemented (Lodge et al 2001;Mustad et al 2002). Therefore, this cytoprotection effect is mediated by physiological T3 concentrations that produced in these neuronal cells c-Src-dependent stimulation of the survival pathway MAPK-ERK, and decreased 12-LOX and eicosanoid pathway activation through a lowered depletion of intracellular glutathione (Sen et al 2004). If such a tiny T3 concentrations needed for neuronal cell protection can be reached in the human brain by feeding tocotrienols, remains to be conclusively demonstrated, but it is likely to occur (Khanna et al 2005).…”