In in vitro settings, different vitamin E analogs show unique effects on a number of markers of Alzheimer’s disease (AD) progression in human cells, according to a study recently published in Biochemistry and Biophysics Reports1.
The authors of the study evaluated the role that two forms of vitamin E, alpha- and gamma-tocotrienol, as well as alpha-tocopherol (a standard form of vitamin E found in many dietary supplements), in two markers of AD: beta-amyloid aggregation, and the hyperphosphorylation of tau protein to form neurofibrillary tangles in the neurons. Each of these markers is correlated to the neurodegeneration, memory deterioration, and eventual cognitive decline characteristic of this progressive disease.
In recent clinical research, vitamin E has been thought of as a nutrient of potential value in supporting structure and function of neurons in such a way that may reduce the risk of AD progression. 1-4
In the present study, a team of researchers at the Shiga University of Medical Science and Showa School of Medicine in Japan assessed the three forms of vitamin E at various concentrations on beta-amyloid aggregation, specifically looking at Aβ42 fibrils (the major component of amyloid plaques in Alzheimer's disease brains).
The two tocotrientols reduced beta-amyloid aggregation significantly at a very low concentration of 10 μM, which was not the case for the alpha-tocopherol ingredient. The two types of tocotrienols were also able to significantly disaggregate previously-formed Aβ42 fibrils while alpha-tocopherol does not at such low concentration.
This supported prior findings5-6 which suggested that gamma-tocotrienol seems to have the broadest beneficial effects as it reduces beta-amyloid aggregation, disaggregates preformed fibrils, and reduces beta-amyloid oligomerization, which, according to the authors, ultimately leads to improved neuronal functions and eventual enhanced cognitive performance.
“There is a rapid growth in the number of people suffering from Alzheimer’s disease throughout the world, and it’s the most frequent cause of dementia in Western societies. It’s important to find ways such as supplementation of tocotrienols to mitigate the progression of AD, especially at its early stage. This current research is the first to reveal that specific tocotrienol analogues such as [alpha-tocotrienol] and [gamma-tocotrienol] have a direct effect on [beta-amyloid] aggregation and fibril formation. The findings shed light on tocotrienols' possible relevance in the development of potential therapeutic agents for AD,” said Dr. Ariati Aris, scientific affairs specialist at PhytoGaia, an ingredient supplier specializing in tocotrienol ingredients.
“Tocotrienols were reported 1000 times more potent than tocopherol in protecting neuron cells from toxin challenges in 2000,” Bryan See, vice president of PhytoGaia, said. “I am encouraged to read that this new study further consolidates tocotrienols’ brain protective effect with its ability, at very low concentration to breakdown the beta-amyloid plaques while the common alpha-tocopherol doesn’t. And this could be the potential reason that explains the finding that high plasma levels of tocotrienols are associated with a reduced risk of Alzheimer’s disease in old people, published by researchers at the Karolinska Institute and Perugia University7-10. We now know that each form of vitamin E (tocopherols and tocotrienols) especially tocotrienols, is required for preserving cognitive functions, especially in the elderly. Subjects with AD and Mild cognitive impairment (MCI) have very low tocopherols and tocotrienol levels, thus further strengthening the association of full spectrum vitamin E with cognitive health.”
References
1. Ibrahim, N.F. et al. (2021). The effect of α-tocopherol, α- and γ-tocotrienols on amyloid-β aggregation and disaggregation in vitro. Biochemistry and Biophysics Reports 28.
2. Jiang, Q. et al. (2014). Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radical Biology and Medicine 72:76–90.
3. Sen, C.K. et al. (2010). Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease. The Journal of the American College of Nutrition 29, 314S–323S.
4. Naomi, R. et al. (2021). An Interactive Review on the Role of Tocotrienols in the Neurodegenerative Disorders. Frontiers in Nutrition. 8: 754086.
5. Yatin, S.M. et al. (2000). Vitamin E prevents alzheimer’s amyloid beta-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production. The Journal of Alzheimer's Disease. 123–131.
6. Yang, S. et al. (2010). α-Tocopherol quinone inhibits β-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines, Neurochemistry International. 57, 914–922.
7. Mangialasche, F. et al. (2010). High Plasma Levels of Vitamin E Forms and Reduced Alzheimer’s disease Risk in Advanced Age. Journal of Alzheimer’s Disease, 20(4), 1029-37.
8. Mangialasche, F. et al. (2012). Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiology of Aging, 33, 2282-2290.
9. Mangialasche, F. et al. (2013). 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, 273(6), 602-21.
10. Mangialasche, F. et al. (2013). Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. Experimental Gerontology, 48(12), 1428-1435.
The authors of the study evaluated the role that two forms of vitamin E, alpha- and gamma-tocotrienol, as well as alpha-tocopherol (a standard form of vitamin E found in many dietary supplements), in two markers of AD: beta-amyloid aggregation, and the hyperphosphorylation of tau protein to form neurofibrillary tangles in the neurons. Each of these markers is correlated to the neurodegeneration, memory deterioration, and eventual cognitive decline characteristic of this progressive disease.
In recent clinical research, vitamin E has been thought of as a nutrient of potential value in supporting structure and function of neurons in such a way that may reduce the risk of AD progression. 1-4
In the present study, a team of researchers at the Shiga University of Medical Science and Showa School of Medicine in Japan assessed the three forms of vitamin E at various concentrations on beta-amyloid aggregation, specifically looking at Aβ42 fibrils (the major component of amyloid plaques in Alzheimer's disease brains).
The two tocotrientols reduced beta-amyloid aggregation significantly at a very low concentration of 10 μM, which was not the case for the alpha-tocopherol ingredient. The two types of tocotrienols were also able to significantly disaggregate previously-formed Aβ42 fibrils while alpha-tocopherol does not at such low concentration.
This supported prior findings5-6 which suggested that gamma-tocotrienol seems to have the broadest beneficial effects as it reduces beta-amyloid aggregation, disaggregates preformed fibrils, and reduces beta-amyloid oligomerization, which, according to the authors, ultimately leads to improved neuronal functions and eventual enhanced cognitive performance.
“There is a rapid growth in the number of people suffering from Alzheimer’s disease throughout the world, and it’s the most frequent cause of dementia in Western societies. It’s important to find ways such as supplementation of tocotrienols to mitigate the progression of AD, especially at its early stage. This current research is the first to reveal that specific tocotrienol analogues such as [alpha-tocotrienol] and [gamma-tocotrienol] have a direct effect on [beta-amyloid] aggregation and fibril formation. The findings shed light on tocotrienols' possible relevance in the development of potential therapeutic agents for AD,” said Dr. Ariati Aris, scientific affairs specialist at PhytoGaia, an ingredient supplier specializing in tocotrienol ingredients.
“Tocotrienols were reported 1000 times more potent than tocopherol in protecting neuron cells from toxin challenges in 2000,” Bryan See, vice president of PhytoGaia, said. “I am encouraged to read that this new study further consolidates tocotrienols’ brain protective effect with its ability, at very low concentration to breakdown the beta-amyloid plaques while the common alpha-tocopherol doesn’t. And this could be the potential reason that explains the finding that high plasma levels of tocotrienols are associated with a reduced risk of Alzheimer’s disease in old people, published by researchers at the Karolinska Institute and Perugia University7-10. We now know that each form of vitamin E (tocopherols and tocotrienols) especially tocotrienols, is required for preserving cognitive functions, especially in the elderly. Subjects with AD and Mild cognitive impairment (MCI) have very low tocopherols and tocotrienol levels, thus further strengthening the association of full spectrum vitamin E with cognitive health.”
References
1. Ibrahim, N.F. et al. (2021). The effect of α-tocopherol, α- and γ-tocotrienols on amyloid-β aggregation and disaggregation in vitro. Biochemistry and Biophysics Reports 28.
2. Jiang, Q. et al. (2014). Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radical Biology and Medicine 72:76–90.
3. Sen, C.K. et al. (2010). Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease. The Journal of the American College of Nutrition 29, 314S–323S.
4. Naomi, R. et al. (2021). An Interactive Review on the Role of Tocotrienols in the Neurodegenerative Disorders. Frontiers in Nutrition. 8: 754086.
5. Yatin, S.M. et al. (2000). Vitamin E prevents alzheimer’s amyloid beta-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production. The Journal of Alzheimer's Disease. 123–131.
6. Yang, S. et al. (2010). α-Tocopherol quinone inhibits β-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines, Neurochemistry International. 57, 914–922.
7. Mangialasche, F. et al. (2010). High Plasma Levels of Vitamin E Forms and Reduced Alzheimer’s disease Risk in Advanced Age. Journal of Alzheimer’s Disease, 20(4), 1029-37.
8. Mangialasche, F. et al. (2012). Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiology of Aging, 33, 2282-2290.
9. Mangialasche, F. et al. (2013). 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, 273(6), 602-21.
10. Mangialasche, F. et al. (2013). Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. Experimental Gerontology, 48(12), 1428-1435.
