a result of complex dysregulation of multiple genes and signaling pathways. Promising oral agents like tocotrienols are bioavailable, work on multiple pathways, and are already recognized as safe.”8


In this issue we present:


• New studies suggesting that tocotrienols might protect the brain from stroke and repair stroke-induced damage.


• Groundbreaking research


showing tocotrienols can improve and often cure fatty liver disease, improve end-stage liver disease, and protect hepatic function.


(See Interview With Chandan Sen, PhD, From A Single Cell to the Human Brain, pp 9). In Sen’s words, “On a concentration ba- sis, the neuroprotective effects of nanomolar tocotrienol repre- sent the most potent biological function of all natural forms of vitamin E.”2


Uniquely, they are


biologically active in the body at concentrations far lower than that of the allied tocopherols.


Working under famed Vitamin E expert Lester Packer, PhD at The University of California at Berke-


pha-tocotrienol.9


Remarkably


even if glutathione remained de- pleted, cell death was prevented.1


Further research by Sen and col- leagues showed that alpha-to- cotrienol protected hypertensive rodents from stroke damage.10 Stroke was induced in hyperten- sive rats, and their brains were removed to measure the size of the stroke-induced lesions. Rats supplemented with alpha-tocot- rienol had significantly smaller lesions.10


• Pathways by which tocotrienols protect neurons, prevent neuronal cell death, inhibit cholesterol and beneficially alter its fractions, and


dampen inflammation.


• Studies showing that tocotrienols reduce cholesterol, and improve atherosclerosis and arterial stiffness.


Let’s Start With Stroke: Neuroprotection and Tocotrienols


If one single scientist has ad- vanced our understanding of the brain and tocotrienols, it is molecular biochemist Chandan Sen, PhD, tenured Professor of Surgery and the Executive Direc- tor of the Ohio State University Comprehensive Wound Center.


Stroke-induced lesions in tocotrienol treated dogs were significantly reduced in volume. Loss of white-matter fiber tract connectivity—the connectivity between different regions within the same hemisphere of the brain—was also reduced.


inappropriate


ley, Sen spearheaded original re- search into all eight


vitamin E


It prevented neuronal death that might otherwise have oc- curred due to excess glutamate, the most abundant neurotrans- mitter in the brain. Later in vitro research found that neuronal cells could completely recover even several hours after a glutamate challenge, when treated with al-


isomers in the late 1990’s. One vitamin E fraction stood out. “We were astonished to find that al- pha-tocotrienol was significantly more effective in preventing neu- rodegeneration in cells in vitro than any other molecule,” says Sen.1


blinded trial was conducted in dogs. Dogs were given mixed palm tocotrie- nols for 10 weeks, or a placebo. Stroke was induced and the vol- ume of brain lesions measured using high resolution MRI both


one and twenty-four hours af- ter the stroke was induced.11,12 Stroke-induced lesions in the treated dogs were significant- ly reduced in volume. Loss of white-matter fiber tract connec- tivity—the connectivity between different regions within the same hemisphere of the brain—was also reduced. Circulation to the ischemic region of the large, mid- dle cerebral artery was measured by cerebral angiogram, and was improved in the tocotrienol-sup- plemented dogs.11,12


The researchers concluded that tocotrienols improved circula- tion, inhibited


inflammatory Focus April 2013 3


Then a randomized,


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