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Tocotrienol Form of Natural Vitamin E Helps Against Stroke

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Posted: 1/3/2006

COLUMBUS, Ohio – New research suggests that an alternate variety of the vitamin E most commonly known by the public – not the popular pill form – might protect against stroke and related damage, and could be delivered orally over time to offer its preventive benefits to those most at risk for certain neurological disorders.

Doctor Chandan Sen
Chandan Sen, Ph.D.

Vitamin E occurs naturally in eight different forms. The primary vitamin E on drugstore shelves is tocopherol, or TCP. But another natural form of vitamin E surfacing as a potent neuroprotective agent in repeated Ohio State University Medical Center studies is tocotrienol, or TCT. This form, while not abundant in the American diet, occurs naturally in palm oil and is a common component of the typical diet of Southeast Asians. Interestingly, that population tends to suffer fewer neurological disorders than Westerners. The TCT form of vitamin E is available as a nutritional supplement, albeit not as commonly as TCP, in American health food stores.

“One of the most striking features of these findings is that this neuroprotective property is seen in a nutrient known to be safe for human consumption,” said Chandan Sen, professor and vice chair of the department of surgery and deputy director of the Davis Heart and Lung Research Institute at OSU.

“All eight types of vitamin E share close structural similarity and therefore all have some antioxidant properties, but current studies indicate that certain members of the vitamin E family possess unique biological functions not shared by other family members,” said Sen, lead author on two new research papers reporting the findings.

“Nine out of 10 research studies performed so far to study the health implications of vitamin E have examined TCP; TCT remained neglected for decades,” he said. “Our study develops the significance of considering all members of the vitamin E family individually before general conclusions are drawn. If a particular form of vitamin E proves to be helpful or unsafe, conclusions should be properly qualified indicating the specific form of vitamin E investigated.”

Ohio State scientists recently completed two sets of studies. One identified the efficacy of tocotrienol in minimizing stroke-related damage of the brain. The other investigated the transport of orally taken TCT to vital organs in the body. The findings are published in the journals Stroke (October issue) and Free Radical Biology & Medicine (Nov. 15), respectively.

“We have discovered the molecular checkpoint where TCT works to protect neurons from toxic insults. Tocotrienol has helped us uncover novel mechanisms of stroke-related neurodegeneration,” Sen explained, referring to the research focusing on ischemic stroke, caused when a clot in a vessel stops blood flow to the brain.

In these new studies, the scientists compared hypertensive rats’ responses to TCT supplementation. One set of rats received moderate oral doses of TCT for 13 weeks before stroke was induced, and experienced a significant difference in stroke injury compared to hypertensive rats not fed with TCT.

“This suggests that the TCT form of natural vitamin E can be part of a regular diet to keep the brain enriched and more prepared to defend itself,” Sen said, “particularly for people at a high risk for stroke.”

The scientists also separately observed that the neuroprotective abilities of TCT were more effective than the popularly known TCP.

In a parallel set of studies, researchers sought to prove that this neuroprotective form of vitamin E could be taken by mouth and reach the brain and other vital organs effectively. They discovered that orally taken TCT can be carried to vital organs of the body by a mechanism that is independent of the currently known pathways involving tocopherol transfer protein (TTP). Oral TCT was efficiently transported to organs of mice deficient in TTP gene.

The same kind of defect in the TTP gene in humans causes a neurological disorder called ataxia, interfering with muscle coordination and associated with problems in speech, reflexes and sensory function.

“Based on our findings that oral TCT may be transported to vital organs in the absence of TTP, it is important to test whether TCT benefits people suffering from defects in the TTP gene,” Sen said.

TCT also restored fertility in TTP-deficient mice, which were infertile because of TCP deficiencies, suggesting that TCT reached relevant tissues and supported reproductive function.

The richest source of TCT is palm oil, commonly used for edible purposes in Southeast Asia. Because of its zero trans fat content, palm oil is fast replacing soybean derived cooking oil and now can be found in some brand-name cookies and crackers, popular candy bars and a few major health-food brands. The reason? Starting in January, food labels must start disclosing the trans fat content in the same way they now disclose other fats, cholesterol, sugar and protein.

“It would be of great value to consumers if these major health-food companies, which are now switching to palm oil for their source of fat, can prove that consuming their product would elevate the levels of TCT in vital organs. It is tricky because TCT may be broken down by the heat typically used for processing food,” Sen said.

Studies of tocotrienol in humans are not far off, and Sen and his colleagues are currently planning one. TCT is a natural nutritional vitamin, not a synthetic drug.

The National Institutes of Health supported this research. Sen co-authored the Stroke article with Ohio State colleagues Savita Khanna, Sashwati Roy, Soma Chaki and Cameron Rink of the department of surgery; Andrew Slivka and Margaret A. Notestine of the department of neurology; Tara K.S. Craft and A. Courtney DeVries of the department of psychology; and Narasimham L. Parinandi of the department of internal medicine. Co-authors of the Free Radical Biology & Medicine article were Khanna, Viren Patel, Rink and Roy, all of the OSU Laboratory of Molecular Medicine.

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Emily Caldwell
Medical Center Communications

Basic Research; OSU Medical Center; Stroke