Alpha-tocotrienol, one of eight forms of vitamin E, was found to inhibit an enzyme from releasing fatty acids that eventually kill neurons, according to findings from a study with mouse brain cells published in the Journal of Neurochemistry.
The beneficial effects are observed at low levels of the nutrient, researchers from Ohio State University report following their National Institutes of Health-funded study.
“Our research suggests that the different forms of natural vitamin E have distinct functions. The relatively poorly studied tocotrienol form of natural vitamin E targets specific pathways to protect against neural cell death and rescues the brain after stroke injury,” said Professor Chandan Sen, lead researcher of the study.
“Here, we identify a novel target for tocotrienol that explains how neural cells are protected.”
“We have studied an enzyme that is present all the time, but one that is activated after a stroke in a way that causes neurodegeneration. We found that it can be put in check by very low levels of tocotrienol,” he said. “So what we have here is a naturally derived nutrient, rather than a drug, that provides this beneficial impact.”
The study’s results were welcomed by Carotech, the producer of the tocotrienol ingredient used in the study. Dr Sharon Ling, vice president, scientific affairs, sales & marketing (Europe) for Carotech Ltd (London) told NutraIngredients that the company is “very excited that tocotrienol - a natural dietary nutrient from palm oil - can be just as effective [as drugs or other therapeutic agents], if not more so, in neural protection.
“This should open up new possibilities into prevention and even treatment of stroke and other neurodegenerative diseases,” she added.
Dr Ling added that the potential neuroprotective effects of nanomolar levels of tocotrienol were first reported a decade ago. “This latest study from The Ohio State University elucidates how very low levels of tocotrienol, which are readily achievable by daily supplementation, protects the brain in artificially induced stroke,” she added.
“It shows tocotrienol inhibits the enzyme cPLA2 from releasing arachidonic acid into the brain. The release of arachidonic acid is an important step in causing neuronal death from glutamate induced state which mimics stroke,” explained Dr Ling.
The vitamin E family
There are eight forms of vitamin E: four tocopherols (alpha, beta, gamma, delta) and four tocotrienols (alpha, beta, gamma, delta). Alpha-tocopherol is the main source found in supplements and in the European diet, while gamma-tocopherol is the most common form in the American diet.
Tocotrienols (TCT) are only minor components in plants, although several sources with relatively high levels include palm oil, cereal grains and rice bran.
While the majority of research on vitamin E has focused on alpha-Toc, studies into tocotrienols account for less than one per cent of all research into vitamin E.
Sen and his co-workers looked at the effects of alpha-tocotrienol to inhibit the action of the enzyme called cystolic calcium-dependent phospholipase A2, or cPLA2. Following the trauma of blocked blood flow associated with a stroke, an excessive amount of the neurotransmitter glutamate is released in the brain. Despite playing an important role in learning and memory, too much glutamate can trigger the death of brain cells, or neurons, said to be the most damaging effects of a stroke.
By introducting excess glutamate into the brain cells of mice, the Ohio-based researchers mimicked the brain’s environment after a stroke. In the presence of excess glutamate, cPLA2 released arachidonic acid into the brain, which subsequently underwent an enzymatic chemical reaction to become toxic.
When tocotrienol was introduced to cells exposed to the high levels of glutamate arachidonic acid levels decreased by 60 per cent, said the researchers. This resulted in a cell survival rate four times higher than cells exposed to glutamate alone.
Prof Sen noted that the effects were observable with a 250 nanomolar dose of tocotrienol. This is equivalent to a concentration about 10 times lower than the average amount of tocotrienol circulating in humans who consume the vitamin regularly.
“On a concentration basis, this finding represents the most potent of all biological functions exhibited by any natural vitamin E molecule,” wrote the researchers in the Journal of Neurochemistry.
“This work provides first evidence in recognizing inducible cPLA2 activity as a key target of tocotrienol in protecting against glutamate-induced neurotoxicity,” they added.
The new findings come after seven years of collaboration between Prof Sen and Carotech, said Mr W.H. Leong, vice president of Carotech Inc.
“The science generated with Tocomin and Tocomin SupraBio for the last seven years has been amazing especially on the potent neuroprotective effect of tocotrienols,” Mr Leong told NutraIngredients. “Being the largest and only GMP-certified tocotrienol producer, it underscores Carotech’s commitment to on science and clinical trials to bring this unique form of vitamin E to our customers.”
Source: Journal of Neurochemistry
Published online ahead of print, doi: 10.1111/j.1471-4159.2009.06550.x
"Nanomolar vitamin E alpha-tocotrienol inhibits glutamate-induced activation of phospholipase A2 and causes neuroprotection"
Authors: S. Khanna, N.L. Parinandi, S.R. Kotha, S. Roy, C. Rink, D. Bibus, C.K. Sen