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Open Access Review
Vitamin E and Its Molecular Effects in Experimental
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Postgratuate Program in Health and Society, Department of Biomedical Sciences, Faculty
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Int. J. Mol. Sci. 2023, 24(13), 11191; https://doi.org/10.3390/ijms241311191
(https://doi.org/10.3390/ijms241311191)
Received: 16 May 2023 / Revised: 26 June 2023 / Accepted: 27 June 2023 /
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Published: 7 July 2023
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(This article belongs to the Special Issue Neurodegenerative Disease: From Molecular
Basis to Therapy ( /journal/ijms/special_issues/9595J0151X ))
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Abstract
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With the advancement of in vivo studies and clinical trials, the pathogenesis of
neurodegenerative diseases has been better understood. However, gaps still need to be
better elucidated, which justifies the publication of reviews that explore the mechanisms
related to the development of these diseases. Studies show that vitamin E supplementation
can protect neurons from the damage caused by oxidative stress, with a positive impact on
the prevention and progression of neurodegenerative diseases. Thus, this review aims to
summarize the scientific evidence of the effects of vitamin E supplementation on
neuroprotection and on neurodegeneration markers in experimental models. A search for
studies published between 2000 and 2023 was carried out in the PubMed, Web of Science,


Virtual Health Library (BVS), and Embase databases, in which the effects of vitamin E in
experimental models of neurodegeneration were investigated. A total of 5669 potentially
eligible studies were identified. After excluding the duplicates, 5373 remained, of which 5253
were excluded after checking the titles, 90 articles after reading the abstracts, and 11 after
fully reviewing the manuscripts, leaving 19 publications to be included in this review.
Experiments with in vivo models of neurodegenerative diseases demonstrated that vitamin E
supplementation significantly improved memory, cognition, learning, motor function, and brain
markers associated with neuroregeneration and neuroprotection. Vitamin E supplementation
reduced beta-amyloid (Aβ) deposition and toxicity in experimental models of Alzheimer’s
disease. In addition, it decreased tau-protein hyperphosphorylation and increased superoxide
dismutase and brain-derived neurotrophic factor (BDNF) levels in rodents, which seems to
indicate the potential use of vitamin E in preventing and delaying the progress of
degenerative lesions in the central nervous system.
Keywords:
experimental
models
of
neurological
diseases
(/search?
q=experimental+models+of+neurological+diseases); vitamin E (/search?q=vitamin+E);
alpha tocopherol (/search?q=alpha+tocopherol); experimental models (/search?
q=experimental+models)
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(https://pub.mdpi-res.com/ijms/ijms-24-11191/article_deploy/html/images/ijms-24-

11191-ag.png?1688711556)

Graphical Abstract
1. Introduction
Over the past few years, as a result of the steady rise in life expectancy, a significant
increase in the prevalence of neurodegenerative diseases (NDD) has been evident, which
has resulted in increased health risks and more demanding research into new and more
efficient therapies [1]. In addition, the great majority of NDD are debilitating and untreatable,
resulting in suffering for the affected patients and their families [2,3,4].
The disorders start by affecting neurons in a gradual process, resulting in degeneration
and/or death of some neurons, which might lead to impaired physical movements and
cognitive function [5]. In fact, some neurodegenerative diseases, such as Alzheimer’s disease
(AD), Parkinson’s disease (PD), and dementia with Lewy bodies, have some common clinical
manifestations such as abnormal protein deposition, inflammation, mitochondrial deficits,
intracellular Ca2+ overload, abnormal cellular transport, uncontrolled generation of reactive
oxygen species (ROS), and excitotoxicity. Thus, the existence of convergent
neurodegeneration pathways in such diseases becomes clear [6]. However, there are still no
therapeutic strategies that can prevent, reduce, or stop the progression of these diseases,
even though some drugs are able to treat only the symptoms [7].
Some natural products exhibit a variety of neuroprotective activities, which include
targeting mitochondrial dysfunction, excitotoxicity, inflammation, apoptosis, oxidative stress,
and protein folding [8,9,10,11,12]. One of these products from natural sources with reported
neuroprotective activity is vitamin E (VE), which is formed by different fat-soluble compounds
found in plants and is divided into tocopherols and tocotrienols. Each type is formed by four
homologs according to the number and location of the methyl groups, being classified as α-,
β-, γ-, and δ-tocopherol and as α-, β-, γ-, and δ-tocotrienol [13].
The effects of α-tocopherol (α-Toc) on the central nervous system (CNS) have been
(/)
reported for over 50 years [14]. A relationship between brain health and α-tocopherol levels
searchmenu
has been hypothesized, especially in diseases associated with oxidative stress such as
ataxias, AD, and PD [15]. Therefore, VE deficiency might lead to progressive neurological
disorders such as spinocerebellar ataxia as a result of the death of peripheral nerves. Thus,
long-term α-Toc supplementation may prevent the progression of nervous system
degeneration caused by VE deficiency [16,17].
In this perspective, both tocopherol transfer protein (TTP) and vitamin E have important
functions in the CNS, as they are necessary for embryonic development, neurogenesis,
neuroprotection, and cognition [18]. Furthermore, it acts as a peroxyl-radical-scavenging
antioxidant that inhibits free radical-mediated lipid peroxidation [19]. Moreover, studies
indicate
that α-Toc reduces lipid peroxidation caused by lipopolysaccharide (LPS), microglia,


and interleukin-6 (IL-6) [20,21], in addition to having a positive effect on neuroplasticity [22].
In fact, αToc is able to break the oxidant chain found in lipoproteins and cellular
compartments such as cell membranes, preventing lipid peroxidation and thus preserving
membrane integrity [23,24].
Ambrogini et al. reported that α-tocopherol can protect against kainate-induced cell death
in the hippocampus, thereby preserving its synaptic plasticity and function [25]. Moreover,
other studies have evidenced the antioxidant activity of VE and αToc in the CNS with
significant improvements in memory and motor function, as well as a marked increase in the
levels of neuroprotective, neuroregenerative, and anti-inflammatory components [26,27].
However, there are a very limited number of reviews about the effects of VE supplementation
on animal models of neurodegenerative diseases.
Considering that the studies published so far show positive effects of VE and αToc on the
CNS, this narrative review aims to analyze the scientific evidence of the effects of VE and
αToc supplementation in animal models of neurodegenerative diseases.
2. Methodology
A search for studies published between January 2000 and April 2023 was carried out in
Medline databases through PubMed, Web of Science, Virtual Health Library (BVS), and
Embase, in which the effects of vitamin E in experimental models of neurodegeneration were
investigated. The search strategy consisted of a combination of Medical Subject Headings
(MeSH) terms “neurodegenerative diseases” and “alpha-tocopherol” (Medline and Web of
Science); “degenerative disease” and “alpha-tocopherol” (Embase); and “chronic disease”
and “alpha-tocopherol” (BVS). The search strategy performed in PubMed can be verified in
the Supplementary Material Table S1.
Studies involving the effects of VE on memory, cognition, learning, motor coordination,
neuroprotection, neuroregeneration, inflammatory markers, and biomarkers of oxidative
stress in experimental models of neurodegeneration were included in this review. Studies that
met one of the following criteria were excluded: (1) Review studies; (2) Non-peer-reviewed
(/)
studies (such as guidelines and preprints); (3) studies performed with vitamin E associated
searchmenu
with other herbal supplements, drugs, or therapies; (4) double publication: if the article
appeared more than once in one of the databases, only the original manuscript was included;
(5) experimental models other than small rodents (rats and mice) or cell culture; (6) studies
carried out with extracts of more than one oil or with the use of parts of the plant that are not
the seed, such as the stem, leaf, fruit, root, and flower.
The results of the eligible studies are described herein as a narrative synthesis that
summarizes the characteristics of the study, the studied population (animals), as well as the
type of VE and αToc supplementation used.
3. Results

The search strategy used in this study resulted in 5669 potentially eligible articles. After
excluding the duplicates, 5373 articles remained, of which 5253 were excluded after checking
the titles, 90 after reading the abstracts, and 11 after the complete review of the manuscripts,
leaving a total of 19 publications to be included in this review.
of
The included studies are presented in Table 1 with the following information: author, year
publication, species, control group, induction method, experimental model of
neurodegeneration, type of VE supplementation and administration method, supplementation
time and data collection, the dose used, and the main results.
Table 1. Characteristics and main findings of the studies included in this review.
3.1. Neuroprotective Mechanisms of Vitamin E in Neurodegenerative Diseases
3.1.1. Memory and Learning
The study by Alzoubi [35] was carried out using Wistar rats as the animal model, in which
they were deprived of sleep followed by oral administration of VE (100 mg/kg) for six weeks.
Such a procedure was able to prevent memory impairment (Figure 1).
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 Figure 1. Vitamin E and memory. Illustration demonstrates that sleep deprivation 
impairs cognition/memory. The role of vitamin E in memory repair after its administration
for 6 weeks in Wistar rats with sleep deprivation-induced memory impairment using the
modified multiple platform method. (Illustration performed by Dr. Francisco Irochima).
Desrumaux et al. used PLTO-KO mice that were deficient in plasma phospholipid
transfer and were induced to develop memory deficit and Alzheimer’s disease (AD) through β
25–35 administration. The animals were supplemented with vitamin E (800 mg/kg orally) for
10 days, whose effect on short-term memory impairment was considered satisfactory [36].
Wang et al. conducted their studies using APPswe/PS1dE9 transgenic mice. After
developing AD-triggering Aβ deposits, the animals received αToc, 100 mg/kg, orally for four
weeks. The authors concluded that supplementation with αToc had positive effects on
memory preservation [39].
Nesari et al. supplemented αToc (60 and 200 mg/kg) for five days after causing
proteasome inhibition and memory deficit in Wister rats through lactacystin induction. The
authors reported benefits only in those rats that received the highest doses of αToc [43].
Finally, Shadini et al. induced AD in Wistar rats through β 25–35 administration. VE
supplementation (200 mg/kg orally) for 10 days resulted in the passive avoidance of memory
impairment [44].
In addition, other studies investigated the effectiveness of VE and αToc on learning. The
experiment conducted by Conte et al. with AD-induced Tg 2576 mice investigated the
administration of 2 IU/g of VE for four weeks before repetitive concussive brain injury (RCBI),
followed by another eight weeks of vitamin supplementation after the onset of AD. The
authors reported a potential effect of VE supplementation on alleviating the learning deficit
[29].
Likewise, Annaházi et al. studied the effect of α-Toc administration in Wistar rats with
chronic cerebral hypoperfusion generated by brain injury in the bilateral common carotid
arteries. The α-Toc administration (100 mg/kg) for five days before the injury and the same
dose for another five days after the injury was able to improve the learning process [31].
3.1.2. Cognitive
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Concerning the effects of VE on cognitive functions, a study investigated the
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administration of α-Toc (100 mg/kg) for 21 days to Wistar rats subjected to streptozotocin
(ST’Z) injury for AD and cognitive deficit induction. Such a protocol was able to successfully
prevent cognitive impairment by protecting the animals’ brains against oxidative stress and
eliminating nitrosative stress and acetylcholinesterase activity [33].
Ishihara et al. obtained similar results, but with a dose of α-TOH of 1.342 mg/kg for six
months in 3 tg-AD mice with AD and cognition impairment triggered by Aβ accumulation in
the brain. This dose of α-TOH was able to reduce oxidative stress by attenuating the
expression of the brain-derived neurotrophic factor [37].
Wang et al. reported improvement in cognitive dysfunction related to spatial memory due


to a protective effect that resulted in a reduction in lipid peroxidation and a decrease in the
release of inflammatory mediators (IL-1 and IL-6) through the oral administration of α-Toc
(100 mg/kg for four weeks) in transgenic APPswe/PS1dE9 mice previously induced to
develop AD [39].
Liu et al. used C57BL/6J transgenic mice in which PM 2.5 was administered to induce
cognitive deficit. The administration of VE (60 mg/kg/day for seven days) resulted in improved
cognitive function, which was correlated with the ability to memorize and learn on the Morris
water maze test (MWM), suggesting that it was associated with reduced oxidative stress [40].
Finally, Rana et al. used α-Toc, 5–10 mg/kg over 28 days after induction of traumatic
brain injury (TBI) in Wistar rats, resulting in reduced cognitive impairment. The use of such a
protocol of α-Toc supplementation reduced neuroinflammatory markers, restored
neurotransmitter levels, and restored oxidative stress balance [42].
3.1.3. Motor Coordination
The studies included in this section investigated whether VE and α-Toc supplementation
generated a positive impact in animal models with motor and behavioral impairments, even
though they used different experimental models.
In one study, Tg 2576 mice were induced to develop AD through repetitive concussive
brain injury (RCBI) in the left parietal-temporal region. Briefly, 2 IU/g of VE was administered
for four weeks before and eight weeks after the lesion, and an improvement in behavior
caused by RCBI was observed with cerebral lipid peroxidation secondary to brain trauma
[29].
In another study, Sprague-Dawley rats were used, and they were fed for five weeks with
α-Toc (20 mg/kg/day, orally) after being induced to develop orofacial dyskinesia and vacuum
chewing movements (MVC) by haloperidol (HAL). It was observed a reduction in the
stereotyped behavior of chewing movements after α-Toc administration [38].
Finally, Wistar rats were induced to exhibit motor impairment by a TBI lesion, whose
locomotor deficit was attenuated when supplemented with 5–10 mg/kg of α-Toc for 28 days
[42].
3.1.4. Oxidative Stress and Neurodegenerative Diseases
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VE supplementation can cause changes in the CNS and positively impact oxidative
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stress. In the study conducted by Sung et al., AD-induced Tg 2576 mice were supplemented
with vitamin E (2 IU/g) for 8 months. The authors found a reduction in lipid peroxidation as
well as a decrease in the levels of soluble Aβ and in amyloid plaque deposition [28].
Garcia-Alloza et al. carried out a study with AD-induced APPswe/PS1d9 mice. The oral
administration of VE (210 mg/kg) 1 day before and 15 days after surgery was able to reduce
AD progress, decrease oxidative stress, and reduce damage to the neurite structures [30].
In addition, Bostanci et al. administered α-Toc (100 mg/kg/day) for 10 days to Wistar rats
previously induced to neurotoxicity and oxidative stress, after which they found that the loss
of neurons was attenuated and a neuroprotective effect was observed [34].
 Singh and Chauhan induced Parkinson’s-like symptoms in Wistar rats, followed by the

administration of tocopherol (5 and 10 mg/kg) intraperitoneally for 40 days. Such a procedure
attenuated behavioral changes, in addition to improving the expression of neurotransmitters
and reducing the levels of inflammatory markers [45].
Iqbal et al. carried out a study with Swiss albino mice with PD induced by haloperidol.
Oral administration of tocopherol (5, 10, 20, and 40 mg/kg) for 23 days was able to increase
the levels of antioxidant enzymes and neurotransmitters and decrease the levels of
inflammatory cytokines and α-synuclein mRNA expression [46].
3.1.5. Neuroprotection and Neuroregeneration
VE and α-Toc have shown a neuroprotective effect in several neurodegenerative models.
Supplementation with vitamin E and α-Toc has been able to reach the entire CNS,
hippocampus, neurons, memory functions, behavior, learning, and cognition, thus protecting
from oxidative stress, which is the main cause of neurodegenerative disorders
[28,29,30,31,32,34,35,36,37,38,41,43,44].
When VE was administered to transgenic mice APPswe/PS1d9 with induced AD, a
regenerative effect was observed, thereby slowing the progress of AD, reducing oxidative
stress, and altering structures in neurons that resulted in neuroprotection [30].
In another study, Wang et al. [39] used APPswe/Ps1dE9 mice with AD and supplemented
them with 100 mg/kg of α-Toc for four weeks, while Liu et al. [40] used C57Bl/6J mice with
induced cognitive deficit and oxidative stress and supplemented them with VE for seven days
at 50 mg/kg/day. On the other hand, Rana et al. [42] induced cognitive deficit and motor
impairment in Wistar rats by means of TBI, followed by supplementation with α-Toc for 28
days at 5–10 mg/kg. These authors reported that vitamin E and α-Toc supplementation was
able to protect and regenerate the CNS of the animals, despite the diversity of induced
neurodegenerative diseases, the doses of VE and α-Toc, and the heterogeneity in the
duration of the experiments (Figure 2).
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 Figure 2. Biochemical effects of vitamin E supplementation in rats. The groups treated 
with α-TOH (α-tocopherol) supplementation resulted in reduced levels of
malondialdehyde (MDA), nitrites, and cholinesterase, in addition to preventing the loss
of glutathione (GSH) and oxidized glutathione (GSSG) when compared to nonsupplemented animals, which had a decrease in GSH/GSSG and Catalase (Illustration
performed by Dr. Francisco Irochima).
4. Discussion
The studies analyzed in this review evidenced that VE supplementation is able to reduce
oxidative stress and lipid peroxidation as well as inhibit the brain inflammatory process in
animal models of neurodegenerative diseases. Considering that there is scientific evidence
that links oxidative stress to CNS inflammation with the onset and progression of
neurodegenerative diseases, the results of this review point to a beneficial effect of
supplementation with foods rich in α-tocopherol.
The studies included in this review showed that VE supplementation had a positive effect
on oxidative stress through a reduction in lipid peroxidation and senile plaques as a result of
its anti-inflammatory effect on the CNS. VE has the ability to regulate the gene expression of
proteins involved in the cellular redox state and, consequently, oxidative stress. In fact, the
studies demonstrate that α-Toc supplementation acts on lipid peroxidation [47]. Similarly, a
previous study reported that vitamin E has fat-soluble antioxidant capacity, efficiently
eliminating membrane lipid peroxidation and protecting against free radical damage while
maintaining membrane integrity [18]. In this perspective, a study conducted by Takatsu and
colleagues demonstrated that vitamin E improves the cognitive deficit caused by aging, not
only through its neuroprotective activity but also through its antioxidant effect [48].
Another study demonstrated the potential ability of VE to counteract the effects of
traumatic brain injury (TBI) on the molecular substrates underlying synaptic plasticity and
cognitive function in the hippocampus in rat models. The results suggested that dietary VE
supplementation may protect the brain against the effects of mild TBI on synaptic plasticity
and cognition by using molecular systems associated with long-term maintenance of synaptic
(/)
plasticity, such as BDNF and its downstream effectors in preserving activity, synaptic,
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synapsin I, CREB, and CaMKII [49]. Other studies in this review corroborate this
neuroregenerative effect, which has resulted in delaying the progression of AD, increasing
cell number, reducing cell damage, changing neurite structure, reducing oxidative stress, and
significantly improving cognitive functions [30,39,40].
Mangialasche and colleagues reported in their study that low levels of vitamin E are
found in older adults with AD and mild cognitive impairment [50]. From this perspective, the
relationship between increased levels of VE and a reduction in the incidence of cognitive
impairment cannot be ruled out. Based on these results, it is understood that high levels of
VE (α-Toc and γ-tocopherol) might play a preventive role in reducing the risk of cognitive
impairment
[51]. Therefore, it is possible to infer that the elevation of plasma α-Toc may result


in better global cognition and a reduction in total brain atrophy [52]. In fact, different authors
found similar results, showing that VE supplementation is a potential alternative to improve
the cognitive function of animals [29,31,33,35,36,37,39,42,43,44].
Furthermore, this review analyzed studies in which VE and α-Toc were able to cause a
significant improvement in motor activity by reducing the Bax/Bcl-2 ratio in the prefrontal
cortex, striatum, substantia nigra, and globus pallidus, in addition to restoring
neurotransmitter levels. Therefore, VE and α-Toc supplementation have demonstrated a
potential effect on motor changes caused by neurodegenerative diseases through a reduction
in stereotyped behaviors and functional decline [29,38,42,52]. In fact, previous studies have
reported that the substantia nigra is an area of the midbrain responsible for controlling motor
activity, which indicates that neurodegeneration of dopaminergic neurons in this region can
result in the genesis of Parkinson’s disease (PD) and other motor dysfunctions [53].
Ulatowski et al. reported that VE deficiency causes dysfunction in the cerebellum,
degeneration of its neurons, premature death, and ataxia [54]. Purkinje cerebellar cells also
undergo deterioration, being the main integrators of neural circuits in this region. VE-deficient
TTP null mice show a high degree of atrophy of Purkinje neurons and reduced neuronal
connectivity, highlighted by reduced neuronal arborization. In this perspective, Yokota et al.
demonstrated that α-Toc supplementation almost completely corrected the abnormalities in a
mouse model with α-TTP gene mutations that are linked to isolated LV ataxia deficiency
(AVED). These authors concluded that α-tocopherol supplementation suppressed lipid
peroxidation and almost completely prevented the development of neurological symptoms
[55].
El-Shaer et al., using an experimental model of exposure to an electromagnetic field,
evaluated the effects on the structural properties of the cerebellum and the possible
neuroprotective effects of VE. The submission to magnetism caused demyelination and
degeneration of axons in the molecular and granular layers, as well as a reduction in Purkinje
cells and pyknotic nuclei. However, supplementation with VE enabled a reduction in
neuropathological changes in all the aforementioned cerebellar areas [56].
In addition, some studies have reported that VE supplementation is able to reduce the
(/)
neurodegenerative process involved in PD. This disease is characterized by the degeneration
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of dopaminergic neurons in the substantia pars compacta in the substantia nigra. In addition,
it is associated with reduced levels of dopamine in the nigrostriatal pathway in the brain
[57,58]. Although the genesis of PD is uncertain, oxidative stress is one of the main
mechanisms involved in its underlying pathophysiology [57,59]. This review demonstrated
that VE was able to reduce the progression of the degenerative process associated with PD
through a reduction in oxidative stress. Therefore, it is believed that vitamin E causes
neuronal resistance and recovery of the atrophied neurons, thus delaying their functional
decline [32,45,46].
VE administration (α-Toc and Trolox) has the ability to reverse synaptic plasticity
abnormalities
in PINK1 -/- mice. The PINK1 haploinsufficiency precipitates mitochondrial


functioning, impairing mitophagy and energy production on demand, therefore being
responsible for the reduced release of synaptic vesicles at dopaminergic terminals and the
subsequent breakdown of corticostriatal synaptic plasticity [60,61,62,63]. In this review, Rana
and colleagues found similar results in which αToc restored altered neurotransmitter levels
after TBI induction [42]. In this study, VE and α-Toc positively interfered in inhibiting or
inactivating neuroinflammatory and neuroprotective substances, as well as markers of
oxidative stress in the CNS, through a reduction in GSH/GSSG, catalase, and superoxide
dismutase (SOD) activity, in addition to the mediators interleukin-1 beta (IL-1β), IL-6, and
tumor necrosis factor-alpha (TNF-α).
The antioxidant system has other important components, such as SOD, which plays a
fundamental role in protecting cells against the deteriorating and ROS scavenging effects
[64,65], portraying the function of SOD as having the ability to catalyze the conversion of
superoxide radicals to hydrogen peroxide and molecular oxygen, whereas CAT catalyzes the
breakdown of toxic H2O2 into water and oxygen. In addition, there are other enzymes that
inactivate hydrogen peroxide, a potent ROS that has the ability to convert into a stable
product, such as glutathione peroxidase (GPx) [66]. Ward and colleagues [67] stated that the
aging process causes different cellular changes, such as increased intracellular Ca2+ levels,
which cause low-grade inflammation in the CNS and peripheral systems. Furthermore, they
reported that low-grade inflammation causes the release of IL-1β, IL-6, and TNF-α. However,
it has been reported that VE and/or LTB supplementation decreases TNF-α and IL-6 levels,
reducing DNA fragmentation and MAPK signaling pathways. Thus, VE supplementation was
able to inhibit oxidative damage in vivo in systemic vasculitides [68,69].
In addition, Celikoglu et al. [70] demonstrated that VE alleviated the oxidative stress
induced by mercury, causing increased activities of SOD, catalase, and glutathione
peroxidase. Furthermore, α-Toc supplementation resulted in a protective effect against
oxidative brain damage through a reduction in lipid peroxidation and improved brain
antioxidant capacity by increasing GSH levels [71,72].
Studies carried out using elderly rodents have shown that the BDNF system is affected
(/)
at several levels with aging, which includes reduced transcription, synthesis, and protein
searchmenu
processing [73]. These reductions are related to hippocampal shrinkage [74], spatial memory
decline [75], and neuronal atrophy [76]. However, VE was able to promote an enhancement
in cognition mediated by BDNF through its ability to regulate the production of CaMK in the
hippocampus, whereas α-Toc was able to increase the molecular factors associated with
memory consolidation such as BDNF, CREB, and synapsin I, all of which can be affected by
oxidative stress [49,77,78].
Although the studies with animal models of neurodegenerative diseases that underwent
supplementation with VE or α-Toc have shown potential in preventing and controlling the
progression of these diseases, there are limitations in this review that may compromise the
extrapolation
of results. The diversity found in the amount of supplementation used, as well


as in the administration route and in the heterogeneity of the evaluation of the effects on the
CNS, are limitations that need to be pointed out. In addition, it is important to emphasize that
only in vivo studies were included in this review, and even with scientifically validated
evidence, there is a conviction that the results cannot yet be fully extrapolated to humans.
5. Conclusions
VE and α-Toc have the potential to significantly improve cognition, memory, learning,
motor function, and disease progression in animal models of neurodegenerative diseases,
playing a preventive role.
Therefore, the promising results shown in the in vivo studies indicate that vitamin E can
reduce oxidative stress and lipid peroxidation and inhibit the brain inflammatory process,
whose mechanisms are present in different neurodegenerative diseases. However, there is a
need to confirm these findings in controlled clinical trials that assess the efficacy of vitamin E
supplementation in humans with such CNS pathologies.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/arti
cle/10.3390/ijms241311191/s1 (https://www.mdpi.com/article/10.3390/ijms241311191/s1).
Funding
CAPES code 001.
Acknowledgments
The authors thank the Brazilian agencies the National Council for Scientific and
Technological Development (CNPq) and the Coordination for the Improvement of Higher
Education Personnel (CAPES) for fellowships and financial support.
Conflicts of Interest
(/)
The authors declare no conflict of interest.
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da Cunha Germano, B.C.; de Morais, L.C.C.; Idalina Neta, F.; Fernandes, A.C.L.; Pinheiro,
F.I.; do Rego, A.C.M.; Araújo Filho, I.; de Azevedo, E.P.; de Paiva Cavalcanti, J.R.L.; Guzen,
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Diseases. Int. J. Mol. Sci. 2023, 24, 11191. https://doi.org/10.3390/ijms241311191
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da Cunha Germano BC, de Morais LCC, Idalina Neta F, Fernandes ACL, Pinheiro FI, do
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International Journal of Molecular Sciences. 2023; 24(13):11191.
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