A novel pathway for neuroprotection mediated by tocotrienol – found in vitamin E – in primary hippocampal neurons has been discovered in a collaborative study by researchers from Yale University and the University of Alabama, both in the US. The new paper details that tocotrienol exerts its protective effect on the brain via a novel pathway that involves both antioxidant and non-antioxidant functions. The researchers note that tocotrienol may be a novel nutritional strategy to prevent reactive oxygen species (ROS) formation in neuronal mitochondria and, therefore, protect neuronal cell death.
The study was also well received by ExcelVite, the largest producer of natural full spectrum tocotrienol and tocopherol complexes including products such as EVNol and EVNol SupraBio.
ExcelVite’s nutritionist Diyanah Roslan was interested in the study results, she tells “This is a novel and additional mechanism for tocotrienol in protecting neuron cells, especially the antioxidant and non-antioxidant pathway. Additionally, the study was carried out on hippocampal neurons, which is the region responsible for learning and memory. These two areas were not studied before and therefore significantly add to the mechanism and understanding of how tocotrienols confer neuroprotection, as well as why tocotrienols are more potent than the regular tocopherol vitamin E in neuroprotection,” she explains.
ExcelVite’s ingredients include EVNol SupraBio, a self-emulsifying palm tocotrienol complex that ensures optimal tocotrienols oral absorption and EVTene, which is a natural palm mixed-carotene, a source of vitamin A and a natural coloring agent.
“In the year 2000, d-alpha-tocotrienol was first reported to be 1,000 times more potent than d-alpha-tocopherol in protecting neuronal cell death upon glutamate toxicity. This study shows that tocotrienol could act via the antioxidant pathway and competitive inhibition as well in protecting neurons especially hippocampal neurons against excitotoxicity. The study highlights that tocotrienol could exert neuroprotection effects via both antioxidant and non-antioxidant pathways,” explains Bryan See, Business Development Manager of ExcelVite.
However, the specifics are still not clear regarding dosage and regulatory issues. “This is the first study conducted on hippocampal neurons. In order to understand the optimal dose per day, an actual human clinical trial is required,” See tells.
“Obtaining a cognitive or brain health claim is challenging. At the moment, there are two human clinical studies of EVNol SupraBio in relation to brain health published, but more clinical trials are required and there are three or four on-going clinical trials right now,” he adds.
These trials are critical to the R&D of ExcelVite’s complexes, which come in several forms, such as oil extracts, bio-enhanced suspensions, beadlets and powders. This allows for varied applications in supplements and food and beverages, according to See.
He also highlights that the study was carried out with hippocampal neurons, which are linked to learning and memory. “Hippocampal dysfunction has been associated with the pathogenesis of neurodegenerative diseases and age-related cognitive impairment. This new study underscores EVNol SupraBio or EVNol as a potential well-rounded and natural therapeutic agent for brain protection and cognitive health.”
Delving into the study
The new study further adds to the foundation of the non-antioxidant pathway elucidated by Dr. Chandan Sen of Indiana University in the past two decades. Mitochondrial ROS, which are linked to cell death, are produced in hippocampal neurons during excitotoxic conditions such as after glutamate toxicity. This typically occurs during injuries such as stroke or trauma to the head.
This study investigated the role of alpha-tocotrienol (the most neuroprotective isoform of tocotrienol) in protecting primary hippocampal neurons against excitotoxicity. The study shows that glutamate-induced excitotoxicity increases hippocampal neuronal death, whereas the application of alpha-tocotrienol before the induction of excitotoxicity protects hippocampal neurons against excitotoxic stimulation. In addition to that, alpha-tocotrienol is able to significantly attenuate generation of oxidative stress and therefore prevent ROS-induced neuronal death signaling.
Alpha-tocotrienol is able to scavenge ROS, thus indirectly reducing the formation of ΔN-Bcl-xL in neurons via its strong antioxidant activity. Notably, this study also reported another novel pathway in that alpha-tocotrienol plays an important role in blocking the binding of ΔN-Bcl-xL and Bax through competitive inhibition.
The binding of ΔN-Bcl-xL with Bax will eventually lead to neuronal mitochondrial apoptosis. However, in the presence of alpha-tocotrienol, it competitively binds with ΔN-Bcl-xL and consequently prevents mitochondrial death.
Moreover, a study from May 2019, also highlighted by ExcelVite, linked Alzheimer’s disease with low levels of vitamin E tocotrienols and tocopherols, further pointing to their brain-boosting benefits.