The brain acts as a control center that regulates the human body’s biological events such as respiration and metabolism processes. When compared to other organs, the brain requires higher amount of oxygen to meet metabolic demands1 but it possesses lower antioxidant capacity. Since the brain contains a high content of polyunsaturated fatty acids (PUFAs), it is very susceptible to free radical-mediated oxidative stress that affects brain health negatively.2 Therefore, lipid soluble antioxidants such as vitamin E (tocopherols and tocotrienols) are crucial to minimize oxidative stress.
Additionally, vitamin E is essential to support the brain’s ability to utilize DHA (docosahexaenoic acid), a type of PUFA that is essential for sustaining brain structure and function. A study demonstrates that a diet deficient in vitamin E-fed zebrafish is associated with 30 percent lower level of DHA-PC (docosahexaenoic acid-containing phosphatidylcholines)—a component of brain cellular membrane. Low level of DHA-PC has also been linked to increased risk of Alzheimer’s disease.3
Vitamin E Complete & Cognitive Impairment
Vitamin E complete is composed of eight different compounds—four tocopherols and four tocotrienols. Four large epidemiological studies conducted by researchers at the Karolinska Institute and Perugia University found that vitamin E complete reduces the risk of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in elderly Europeans. AD and MCI subjects in these studies demonstrated significantly lower levels of total tocotrienols, total tocopherols, and total vitamin E when compared to cognitively normal (CN) people. Hence, low plasma tocotrienols and tocopherols are strongly linked to AD and MCI, with tocotrienols having a stronger inverse correlation compared to tocopherols.4-7
Tocotrienol—Unsaturated Form of Vitamin E
Researchers have studied the role of regular vitamin E tocopherols in human health for a long time, but new scientific evidence has shown that tocotrienol exhibits 40 to 60 times stronger antioxidative activity than tocopherol and offer unique health benefits that tocopherol may not provide such as neuroprotection, cholesterol reduction, etc. Tocotrienols differ from tocopherols in the side chain, with tocotrienols possess unsaturated sidechain while tocopherols having saturated sidechain. The unsaturated side chain enables tocotrienols to penetrate into body cell membranes more efficiently than tocopherols, hence providing stronger antioxidative actions or biological effects.8 In fact, tocotrienol has shown beneficial effects in pre-stroke and post-stroke settings.
Tocotrienol & Pre-Stroke Setting
White matter lesion (WML) occurs when there is an inadequate supply of blood to the brain, and it is an independent risk factor for stroke. A randomized, double blind, placebo-controlled clinical trial with 121 MRI (magnetic resonance imaging)-confirmed WML subjects receiving bio-enhanced palm tocotrienol complex (as EVNol SupraBioTM) or placebo for 24 months. The results show that the mean WML volume in tocotrienol-supplemented and placebo groups remained unchanged and increased respectively after 24 months. The change of WML volume between the two groups was statistically significant at the end of second year. This is the first published clinical trial that shows actual brain protective effect of a natural vitamin E compound.9
Tocotrienol & Post-Stroke Setting
In another study conducted at the Ohio State University Medical Center, 20 mongrel canines were randomized into two treatment groups—one group received a daily dosage of bio-enhanced palm tocotrienol complex (EVNol SupraBio) while the other received vitamin E-deficient corn oil for 10 weeks. Tocotrienol-supplemented canines showed 20 percent and 40 percent reduced stroke-induced lesion volume at first and 24th hour compared to control. Additionally, tocotrienol-supplemented canines also demonstrated higher relative connectivity of white matter fiber tracts, improved cerebrovascular collateral circulation and increased expression of pro-arteriogenic (new blood vessels formation) genes when compared to control group. This study demonstrates that natural vitamin E tocotrienol supplementation may reduce brain injury after stroke in a preclinical setting.10
Tocotrienol & Post-Stroke Mechanisms
The first neuroprotective actions of tocotrienols were reported back in 1999 when nanomolar (10-9) concentrations of alpha-tocotrienol promoted complete recovery of neurons even when alpha-tocotrienol was introduced several hours after glutamate-induced toxicity. Hence, alpha-tocotrienol at extremely low concentration offers meaningful neuroprotection.11 Additionally, NIH (National Institutes of Health)-funded studies demonstrate tocotrienols exert neuroprotection via five identified mechanisms that modulate neuronal cell death or survival as follows:
- Reduction in c-Src kinase activation;
- Inhibition of 12-lipoxygenase phosphorylation;
- Inhibition of phospholipase A2;
- Up-regulation of Multidrug resistance-associated protein 1 (MRP1); and
- Rescued stroke-induced loss of miR-29b (microRNA-29b) and minimized lesion size.12-16
Collectively, vitamin E is an important lipid-soluble nutrient that helps to preserve brain structure and protect brain cells from degeneration. Tocotrienol has long been overlooked although it is one of the two members of vitamin E family. Due to the unsaturated side chain of tocotrienol, tocotrienol confers neuroprotection which is not shown by tocopherol. In addition, tocotrienol, together with tocopherol, helps to support healthy cognitive function especially in elderly. Hence, vitamin E complete and/or tocotrienol is an essential vitamin for brain protection and cognitive health.
CheeYen Lau, nutritionist at ExcelVite, has a master's degree in nutritional sciences. She is a health technical writer and has a passion for natural health.
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- Maret G et al. “Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics." Journal of Lipid Research. DOI: 10.1194/jlr.M058941.
- Mangialasche F et al. “High Plasma Levels of Vitamin E Forms and Reduced Alzheimer's disease Risk in Advanced Age." J Alzheimers Dis., 2010;20(4):1029-37.
- Mangialasche F et al. “Tocopherols and tocotrienols plasma levels are associated with cognitive impairment." Neurobiology of Aging, 2012;33:2282-2290.
- Mangialasche F et al. “Classification and prediction of clinical diagnosis of Alzheimer's disease based on MRI and plasma measures of α-/γ-tocotrienols and γ- tocopherol." Journal of Internal Medicine. 2013;273(6):602-21.
- Mangialasche F et al. “Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults." Exp Gerontol, 2013;48(12):1428-1435.
- Serbinova E et al. “Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol." Free Radical Biology & Medicine. 1991;10:263-275.
- Gopalan Y et al. “Clinical Investigation of the Protective Effects of Palm Vitamin E Tocotrienols on Brain White Matter Lesion." Stroke. 2014;45(5):1422-8.
- Rink C et al. “Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis." Journal of Cerebral Blood Flow & Metabolism. 2011;31;2218-2230.
- CK Sen. “Alpha-tocotrienol: A Potent Neuroprotective Natural Vitamin E." Medical Tribune. 2006.
- Sen CK et al. “Molecular Basis of Vitamin E Action: Tocotrienol potently inhibits glutamate-induced pp60c-Src kinase and death of HT4 neuronal cells." The Journal of Biological Chemistry. 2000;275(17):13049-13055.
- Khanna S et al. “Molecular Basis of Vitamin E Action: Tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration." The Journal of Biological Chemistry. 2003;278 (44):43508-43515.
- Khanna S et al. “Neuroprotective Properties of the Natural Vitamin E alpha-Tocotrienol." Stroke. 2005;36,e144-e152.
- Khanna S et al. “Nanomolar vitamin E alpha-tocotrienol inhibits glutamate-induced activation of phospholipase A2 and causes neuroprotection." Journal of Neurochemicstry. 2010;112:1248-1260.
- Khanna S et.al. “Loss of miR-29b following acute ischemic stroke contributes to neural cell death and infarct size." Journal of Cerebral Blood Flow & Metabolism. 201e3;33:1197-1206.