What’s So Special About Vitamin E?
Do you know what makes vitamin E different from all of the rest of the vitamins?
The form of vitamin E that is most crucial for humans is alpha-tocopherol. Alpha-tocopherol is the most biologically active form of vitamin E. There are 8 vitamin E forms or tocopherols in total, but our liver usually just tosses the other 7 aside, so they can be found in low concentrations throughout our body.[1][2]
Vitamin E is fat-soluble and classified as an antioxidant. Therefore, given its antioxidant role, vitamin E acts as a buffer against any reactive oxygen species that may travel through cellular membranes or fats.[3]
Lately, dietary choices are quickly becoming a major and serious public health concern, rapidly gaining the attention of researchers. Due to the increased prevalence of obesity and the Western diet, it is clear that vitamin deficiencies are also becoming more common.
Vitamin E somehow affects many avenues of the human experience, including anxiety, cognition, and depression. The extent of just how vitamin E is involved in these domains is gradually becoming established through systematic testing and experimentation. Regardless, much remains unknown.
Vitamin E Deficiency Can Lead to Anxiety
Anxiety is one of the symptoms of Vitamin E deficiency. Such a finding is an interesting correlation and area of further study, given that humans in contemporary times are being affected by anxiety at a faster rate than ever before.
Researchers used an animal model to demonstrate ethically and establish that vitamin E deficiency can create anxiety-like behaviors.
Using an elevated plus-maze test and tissue samples to determine the animals’ levels of the alpha-tocopherol concentrations, researchers showed that anxiety behaviors and Vitamin E have an inverse relationship. In other words, as Vitamin E decreases, anxiety-like behaviors increase.[4]
To summarize the experiment, the animals that were on the vitamin E-deficient diet had different behavioral outcomes and tissue properties when compared to those of the control group. The plasma, liver, and brain samples of the young rats and older rats in the vitamin E-deficient group had significantly lower alpha-tocopherol concentration levels.
In terms of behavior, the elevated plus-maze test revealed that the experimental rats exhibited greater anxiety-like behaviors because they made significantly fewer entries in the maze’s open arms and they also spent significantly less time there. The vitamin E-deficient rats also exhibited a lesser amount of head dipping than the control group did.[4]
Treating Vitamin E Deficiency Relieves Associated Depressive-Like Behaviors
Did you know that depressive-like behaviors are noticeably decreased as diet becomes more balanced with the recommended amount of vitamin E?[5]
Depression manifests as a result of several different biological pathways, one being inflammation. Inflammation can give rise to depressive-like behaviors. A high amount of inflammatory cytokines within the central nervous system is linked to decreased serotonin production.[5] Furthermore, inflammation can influence metabolic processes and lead to neurodegeneration as a result of the presence of active inflammatory cytokines such as tumor necrosis factor-α (TNF-α).
Research has shown that depressed patients with multiple depressive episodes have low hippocampal volume, thus marking the importance of studying inflammation and its neurodegenerative properties.[6]
One research group contributed to the growing body of knowledge showing that vitamin E and depression are somehow related by using a tail suspension test, as well as western blotting and biochemical analysis of tissues, to explore the precise nature between the two variables.
The mice that had high levels of TNF-α, an animal model for depression, performed poorly in the tail suspension test, becoming immobile quite quickly. When conducting a tail suspension test, reduced immobility time is considered a success when considering antidepressive treatment whereas increased immobility is equated with depressive-like behavior. The TNF-α treated mice, upon administration of alpha-tocopherol at 30 and 100 mg/kg, showed a decrease in immobility time during the tail suspension test.
Although the exact mechanisms of such robust effects remain unknown, one possible explanation includes the involvement of the Janus kinase-signal transducers and activators of transcription (JAK/STAT) taking part within the signaling pathway of depressed rats.[7]
Alzheimer’s and Aging
Yes, there is an interplay between vitamin E, anxiety, and depression. But, it doesn’t stop there.
Vitamin E is increasingly being shown as a powerful opponent against the mild cognitive impairment and decline that accompanies Alzheimer’s disease and aging.[8]
Aging is a process that has remained a mystery to scientists. A theory that has been around since 1956 is that aging is an inevitable process that progresses due to the accumulation of damage in biomolecules from oxidative stress.[8] Given the antioxidant properties of vitamin E, it is no wonder that it has shown to be promising within the research field of aging.
To assess the effects of alpha-tocopherol in amyloid precursor protein-presenilin (APP-SPN) double transgenic mice (modeled for Alzheimer’s disease), researchers measured the mice’s behavioral performance in the Morris Water Maze and in the active/passive avoidance shuttle box before taking the mice’s tissue samples to establish the present biochemical parameters.[9]
The APP-SPN mice that had alpha-tocopherol treatment within their diets performed better at the 3-months and 7-months post-treatment trials. The control group (which was the Alzheimer’s model without any treatment) had higher levels of β-amyloid1–42 peptide accumulation than the Alzheimer’s experimental group that was treated with vitamin E nutrients. Since β-amyloid1–42 peptide is associated with the pathological effects in Alzheimer’s disease and higher levels of this molecule would indicate that the disease is progressing, lowering its levels through the administration of vitamin E implies that this antioxidant is able to alter the progression of Alzheimer’s.
The APP-SPN mice without any treatment needed longer time to complete the Morris Water Maze at the 3-month mark than the APP-SPN mice that received the vitamin-E intervention, meaning that the mice receiving vitamin E had more intake memory functions than the non-treatment group.
The vitamin E-receiving APP-SPN mice also performed better in the active/passive avoidance shuttle box test, demonstrating a smaller amount of escape failures and a higher amount of active avoidance than the non-treated APP-SPN mice did at 3 and 7 months.
Vitamin E Relieves Memory and Learning Impairments in Temporal Lobe Epilepsy
Temporal lobe epilepsy (TLE) is the most common type of epilepsy among adults. TLE is a serious condition that causes cell death and neurodegeneration in the mesial brain structures such as the hippocampus.[10]
Due to TLEs prevalence and ability to hinder the hippocampus, a structure that is integral to the formation of long-term memories and learning, it is quite remarkable that vitamin E can also leave behind its positive influence within this clinical population.
To study the interaction between TLE and vitamin E scientists manipulated an animal model to mimic the condition. Mice were induced of TLE through “intrahippocampal unilateral injection of the excitotoxic glutamate analog kainate” which gradually hinders the animals’ performance in memory tasks.[10]
When injected with kainate, the rats had a higher rate and severity of seizures and exhibited poorer memory and learning performance in behavioral tests such as the Y-Maze task than the control groups did.
This group decided to use a Y-Maze as opposed to a Morris Water Maze. Both tests measure spatial learning and memory, but the Y-Maze does not depend on a learning component that can isolate memory performance as the Morris Water Maze does.
Vitamin E and Melatonin Buffer Against Diabetes-Induced Memory and Learning Impairment
Learning and memory impairment can be observed as a consequence of many diseases. But, is this learning and memory impairment the same, regardless of disease? For example, is the learning and memory impairment observed in obese populations the same as that in the mild cognitive impairment stages preceding Alzheimer’s?
It is important to distinguish the phenotype of research focus, just in case different pathophysiologies are involved.
One research group did exactly that by studying the memory and learning impairment specifically within a diabetes-induced rat sample by using intraperitoneal streptozotocin injections.[11]
To investigate learning and memory behaviors, a Morris Water Maze test was used. The diabetic rats exhibited more water maze test deficits in learning than the control group did.
The diabetes-induced rats had biochemical properties that indicated they had high levels of lipid peroxidation (destructive oxidative stress markers) and low concentrations of glutathione (an antioxidant). Lipid oxidation was measured in the hippocampus and the cortex. It was found to be higher in the diabetic group than in the controls. Upon combined treatment with vitamin E and melatonin, the antioxidants left a noticeable mark on the rats’ physiology by steadily reversing the rats’ levels of glutathione and lipid peroxidation.
Protective Effects of Vitamin E on Brain Tissue Injury
Brain tissue injury and brain damage are marked by high, dangerous levels of inflammation, oxidative stress, and eventual cell death or apoptosis, but it is theorized that antioxidants (such as vitamin E) can be protective against such damage.
Vitamin E has been shown to be able to counteract the deficits associated with brain damage and tissue injury in mice.[12] Such findings can have tremendous implications in the dietary management of neurotraumas such as traumatic brain injury, as well as be extended to neurotoxic conditions.
In an experiment designed to test these premises, mice brain tissues were injured through diisononyl phthalate (DINP) exposure which led to pathological alterations to the hippocampus, apoptosis, oxidative stress, and marked inflammatory responses. To test just how far the antioxidant properties of vitamin E can help injured brain tissues, behavioral measures and histological analysis were used.
The injured mice exhibited cognitive deficits and poor performance in the Morris Water Maze test. Mice from the high-injury DINP group displayed less orderly and more irregular swimming pattern routes than the control group which demonstrated more purposeful and focused swimming patterns. When the mice with DINP induced injury were treated with vitamin E, their performance on the Morris Water Maze was marked by a significant decrease in the amount of time needed to find the platform.[12]
The cognitive and behavioral problems of brain injury were counterbalanced by the administration of vitamin E, suggesting that vitamin E’s antioxidant properties can have a protective effect against some of the problems presented by brain tissue injury.
Vitamin E Supplementation Affects Purkinje Cells
The Purkinje cells and neurological functioning observed in vitamin E-deficient mice are significantly improved as a result of dietary supplementation of vitamin E.
Purkinje cells have a high concentration of alpha-tocopherol, one of vitamin E’s major bioactive forms.[13] Histological analysis demonstrates that vitamin E-deficient mice exhibit Purkinje cell degeneration in the cerebellum. This is a cause for major concern since Purkinje cells are considered to be the sole output of the cerebellar cortex’s motor coordination.[14]
An experiment demonstrated the behavioral outcomes of vitamin-E deficient mice, correlating behavioral findings to histological analysis. The scientists used tests such as the rotarod test to measure motor abilities and also analyzed oxidative stress markers to determine whether vitamin E was exerting the antioxidant property that it’s assumed to have.
In this experiment, vitamin-E deficient mice performed significantly worse on the rotarod test, a test investigating movement memory and motor coordination. The vitamin E-deficient mice could not last as long on the rotarod as the control group could.[13]
Furthermore, the normal mice exhibited better performance with each subsequent trial or test attempt, an improvement that was not observed in the vitamin E-deficient mice.
Upon being given the vitamin-E dietary treatment, the once deficient mice were able to perform as well as the normal, healthy mice and were able to stay on the rotarod for as long as 3 seconds. This improvement was only seen in the mice supplemented with the 5% vitamin-E dietary concoction that the researchers created, not the 2% mix.
Using Animal Models for Studying Vitamin E Deficiency
Scientific literature has consistently established the effects between Vitamin E deficiency and behavioral problems in humans and animals.
When employing animal research to study vitamin E, it is common to use genetic strains that have the alpha-tocopherol gene knocked out, in order to mimic the vitamin E-deficient profile.
If using genetically modified animals isn’t an option, researchers moderate the animals’ diet for a prolonged period of time (about a span of 4 weeks) in order to foster two different conditions or groups that can be systematically used to compare two variables (such as a control diet and a vitamin E-deficient diet).
Conclusion
From the methods and tests used thus far to explore vitamin E’s antioxidant powers, many promising applications have been uncovered.
Both dietary control and genetic models have been used by scientists to demonstrate the relationship between vitamin E and and psychological conditions such as anxiety, depression, Alzheimer’s, mild cognitive impairment, and temporal lobe epilepsy.
Vitamin E’s antioxidant properties have protective and healing effects against the damage caused by reactive oxygen species, improving diseased models’ cognition and behavioral performance (as exhibited by improved learning and memory). Research in this area is promising and still developing with many more future applications left to be uncovered, but what has been established thus far about vitamin E has proven to be useful.
References
- Traber, Maret G. “Vitamin E regulatory mechanisms.” Annu. Rev. Nutr. 27 (2007): 347-362.
- Sen, Chandan K., Savita Khanna, and Sashwati Roy. “Tocotrienols: Vitamin E beyond tocopherols.” Life sciences78.18 (2006): 2088-2098.
- Choe, Eunok, and David B. Min. “Mechanisms of antioxidants in the oxidation of foods.” Comprehensive Reviews in Food Science and Food Safety 8.4 (2009): 345-358.
- Terada, Yuki, et al. “Dietary vitamin E deficiency increases anxiety-like behavior in juvenile and adult rats.” Bioscience, biotechnology, and biochemistry 75.10 (2011): 1894-1899.
- Manosso, Luana M., et al. “Antidepressant-like effect of α-tocopherol in a mouse model of depressive-like behavior induced by TNF-α.” Progress in Neuro-Psychopharmacology and Biological Psychiatry 46 (2013): 48-57.
- MacQueen, Glenda M., et al. “Course of illness, hippocampal function, and hippocampal volume in major depression.” Proceedings of the national academy of sciences 100.3 (2003): 1387-1392.
- Alrasheed, Nouf, et al. “Possible involvement of Janus Kinase-Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway in vitamin E-mediated anti-depressant-like effects in a rat depression model.” Parkinsonism & Related Disorders 22 (2016): e178.
- Fata, Giorgio La, Peter Weber, and M. Hasan Mohajeri. “Effects of vitamin E on cognitive performance during ageing and in Alzheimer’s disease.” Nutrients 6.12 (2014): 5453-5472.
- Wang, Shengyuan, et al. “Protective effects of dietary supplementation with a combination of nutrients in a transgenic mouse model of Alzheimer’s disease.” PloS one10.11 (2015): e0143135.
- Kiasalari, Zahra, et al. “The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats.” Indian journal of pharmacology 48.1 (2016): 11.
- Tuzcu, Mehmet, and Giyasettin Baydas. “Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats.” European journal of pharmacology 537.1-3 (2006): 106-110.
- Peng, Ling. “Mice brain tissue injury induced by diisononyl phthalate exposure and the protective application of vitamin E.” Journal of biochemical and molecular toxicology 29.7 (2015): 311-320.
- Takahashi, Toru, et al. “Rice Bran Dietary Supplementation Improves Neurological Symptoms and Loss of Purkinje Cells in Vitamin E-Deficient Mice.” Yonago acta medica 59.3 (2016): 188.
- Purves, D., et al. “Circuits within the Cerebellum.” ). Neuroscience, 2nd edition edn. Sunderland (MA): Sinauer Associates. p^ pp (2001).