Tocotrienol: the natural vitamin E to defend the nervous system?

Ann N Y Acad Sci. 2004 Dec:1031:127-42. doi: 10.1196/annals.1331.013.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase
  • Brain / metabolism
  • CSK Tyrosine-Protein Kinase
  • Cell Death / drug effects
  • Diet
  • Dietary Supplements
  • Gene Expression / drug effects
  • Glutamic Acid / toxicity
  • Humans
  • Nervous System Physiological Phenomena*
  • Neurons / drug effects
  • Neurons / enzymology
  • Protein-Tyrosine Kinases
  • Tocotrienols* / administration & dosage
  • Tocotrienols* / analysis
  • Tocotrienols* / pharmacokinetics
  • Vitamin E / pharmacokinetics
  • Vitamin E / physiology*
  • src-Family Kinases


  • Tocotrienols
  • Vitamin E
  • Glutamic Acid
  • Arachidonate 12-Lipoxygenase
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human