Vitamin E Effects on Developmental Disorders in Fetuses and Cognitive Dysfunction in Adults Following Acrylamide Treatment During Pregnancy

Zeynep Erdemli, Mehmet Erman Erdemli, Yusuf Turkoz, Birgul Yigitcan, Mehmet Arif Aladag, Yilmaz Cigremis, Rumeyza Hilal Cırık, Eyup Altinoz, Harika Gozukara Bag

Biotech Histochem . 2020 Apr 29;1-9. doi: 10.1080/10520295.2020.1751880.

Abstract

We investigated the effects of acrylamide (AA) and vitamin E treatment during pregnancy on brain tissues of fetuses and on adult rats. Pregnant rats were divided into five groups: control, corn oil, vitamin E, AA, vitamin E +AA. The rats administered AA received10 mg/kg/day and those administered vitamin E received 100 mg/kg/day both by via oral gavage for 20 days. On day 20 of pregnancy, half of the pregnant rats were removed by cesarean section in each group. Morphological development parameters were measured in each fetus and histopathological, biochemical and genetic analyses were conducted on the fetuses. The remaining pregnant rats in each group gave birth to the fetuses vaginally and biochemical, histopathological, genetic and cognitive function tests were conducted when the pups were 8 weeks old. AA administration caused adverse effects on fetus number, fetal weight, crown-rump length, placenta and brain weight. AA negatively affected malondialdehyde, reduced glutathione, total oxidant and antioxidant status, brain derived neurotrophic factor (BDNF) levels, brain tissue morphology, histopathology error score and gene expression (BDNF/β-actin mRNA ratio) in fetuses. AA administration caused disruption of biochemical, histopathological and cognitive functions in adult rats. Vitamin E provided protection against neurotoxicity in both fetuses and adult rats. We conclude that exposure to AA during pregnancy should be avoided and adequate amounts of antioxidants, such as vitamin E, should be consumed.

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Trace elements homeostasis in brain exposed to 900 MHz RFW emitted from a BTS-antenna model and the protective role of vitamin E

Azimzadeh M, Jelodar G

J Anim Physiol Anim Nutr (Berl). 2020 Apr 12. doi: 10.1111/jpn.13360. [Epub ahead of print]

Abstract

Advances in telecommunication and their broad usage in the community have become a great concern from the health aspect. The object of the present study was to examine the effects of exposure to 900 MHz RFW on brain Iron (Fe), Copper (Cu), Zinc (Zn) and Manganese (Mn) concentration, and the protective role of pre-treatment of vitamin E on mentioned elements homoeostasis. Twenty adult male Sprague-Dawley rats (200 ± 20 g) randomly were divided into four groups. Control group (without any exposure, received distilled water), treatment control group (orally received 250 mg/kg BW/d vitamin E), treatment group (received 250 mg/kg BW/d vitamin E and exposed to 900 MHz RFW) and sham-exposed group (exposed to 900 MHz RFW). Animals (with freely moving in the cage) were exposed to RFW for 30 consecutive days (4 hr/day). The levels of the above mentioned elements in the brain tissue were determined on the last day using atomic absorption spectrophotometry. Exposure to 900 MHz RFW induced a significant increase in the Fe, Cu, Mn levels and Cu/Zn ratio accompanied by a significant decrease in Zn level in the sham-exposed group compare to control group. Vitamin E pre-treatment improved the level of Fe, Cu, Mn and Cu/Zn ratio, except in the Zn concentration. Exposure to 900 MHz RFW caused disrupted trace elements homoeostasis in the brain tissue and administration of vitamin E as an antioxidant and neuroprotective agent improved the situation.

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Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Antioxidative Supplements

Tadokoro K, Ohta Y, Inufusa H, Loon AFN, Abe K

Int J Mol Sci. 2020 Mar 13;21(6). pii: E1974. doi: 10.3390/ijms21061974.

Abstract

Oxidative stress plays a crucial role in Alzheimer’s disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid β (Aβ) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the Aβ cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD.

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Association of Circulating Retinol and α-TOH Levels with Cognitive Function in Aging Subject with Type 2 Diabetes Mellitus

Huang X, Guo Y, Li P, Ma X, Dong S, Hu H, Li Y, Yuan L.

J Nutr Health Aging. 2020;24(3):290-299. doi: 10.1007/s12603-020-1328-1.

Abstract

OBJECTIVES:

Malnutrition of vitamin A (retinol) and vitamin E (α-tocopherol, α-TOH) was observed in type 2 diabetes mellitus (T2DM) or dementia patients. However, how these vitamins affect cognitive function of subjects with T2DM was seldom reported. The objective of this study was to determine the association of circulating retinol and α-TOH with cognition in aging subjects with T2DM.

METHODS:

A total of 448 T2DM subjects and 448 age, gender and education matched control subjects (aged 55-75 years) were included in the study. Demographic characters of the participants were collected. Food frequency questionnaire (FFQ) method was used to collect dietary intake information. To assess the status of cognition, the MoCA test was used. Circulating retinol and α-TOH levels were compared between T2DM and non-T2DM subjects. Correlation of circulating retinol and α-TOH levels with cognitive function was analyzed in T2DM subjects. The effect of serum retinol and α-TOH levels on the risk of MCI in T2DM patients was explored.

RESULTS:

We found that T2DM-MCI subjects demonstrate lower serum retinol level than T2DM-nonMCI subjects (P < 0.01). Serum retinol level was positively correlated to cognitive function in T2DM subject (P < 0.05). T2DM subjects with higher circulating retinol level demonstrate higher cognitive scores in visual and executive, attention, language, memory and delayed recall domains (P < 0.05).

CONCLUSION:

Diminished circulating retinol predicts an increased risk of MCI in T2DM patients. Our findings provide suggestions that optimal retinol nutritional status might benefit cognition and decrease the risk of MCI in aging subjects with T2DM.

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Pharmacological correction of alterations of apoptosis of the neurons of the hypothalamus suprachiasmatic nucleus and pinealocytes during aging and stress

Khuzhakhmetova LK, Teply DL, Bazhanova ED

Adv Gerontol. 2019;32(6):915-922.

Abstract

As is known, the pineal gland plays an important role in adaptogenesis, and the hypothalamus is one of the main links of the stress-reactive system and is involved in the regulation of the involution of the whole organism. So, the study of changes in these organs during stress and aging is very interesting. The aim of the work is to study the mechanisms of apoptosis of pinealocytes and neurosecretory cells of the suprachiasmatic nucleus of the hypothalamus during aging, stress, and under the conditions of pharmacological correction of involutional processes and stress response (antioxidant alpha-tocopherol acetate, immunomodulator cycloferon). We used Wistar rats as model, young (2-4 months) and old (30 months). Age-related features of the apoptosis dynamics of pinealocytes and neurosecretory cells of the hypothalamic suprachiasmatic nucleus were studied using TUNEL and immunohistochemistry, and the possibilities of pharmacological correction of apoptotic processes are determined. An age-dependent increase of apoptosis level of cells of suprachiasmatic nucleus and epiphysis in rats was revealed. The stress effect (immobilization) led to the intensification of cell death, more significant in older animals. The pineal gland and suprachiasmatic nucleus, traditionally regarded as regulators of circadian rhythms, are at the same time actively involved in general adaptation processes. The studied drugs (α-tocopherol-acetate, cycloferon, and their combination) have a pronounced anti-apoptotic, cytoprotective effect under physiological conditions during aging, as well as during non-specific emotional stress (immobilization) in young and old animals. The regulatory effect is accomplished by activating the expression of the anti-apoptotic protein Bcl-2 in the neurosecretory cells of the suprachiasmatic nucleus and pinealocytes.

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Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels

Pirhadi-Tavandashti N, Imani H, Ebrahimpour-Koujan S, Samavat S, Hakemi MS

J Stroke Cerebrovasc Dis. 2020 Mar 6:104747. doi: 10.1016/j.jstrokecerebrovasdis.2020.104747. [Epub ahead of print]

Abstract

OBJECTIVES:

Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH.

METHODS:

At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be “cryptogenic” (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data.

RESULTS:

All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups.

CONCLUSIONS:

In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient’s pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.

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Safety and Neuroprotective Efficacy of Palm Oil and Tocotrienol-Rich Fraction from Palm Oil: A Systematic Review

Ismail M, Alsalahi A, Imam MU, Ooi J, Khaza'ai H, Aljaberi MA, Shamsudin MN, Idrus Z

Nutrients. 2020 Feb 18;12(2). pii: E521. doi: 10.3390/nu12020521.

Abstract

BACKGROUND:

Several natural products have been reported to elicit beneficial effects against neurodegenerative disorders due to their vitamin E contents. However, the neuroprotective efficacy of palm oil or its tocotrienol-rich fraction (TRF) from the pre-clinical cell and animal studies have not been systematically reviewed.

METHODS:

The protocol for this systematic review was registered in “PROSPERO” (CRD42019150408). This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Medical Subject Heading (MeSH) descriptors of PubMed with Boolean operators were used to construct keywords, including (“Palm Oil”[Mesh]) AND “Nervous System”[Mesh], (“Palm Oil”[Mesh]) AND “Neurodegenerative Diseases”[Mesh], (“Palm Oil”[Mesh]) AND “Brain”[Mesh], and (“Palm Oil”[Mesh]) AND “Cognition”[Mesh], to retrieve the pertinent records from PubMed, Scopus, Web of Science and ScienceDirect from 1990 to 2019, while bibliographies, ProQuest and Google Scholar were searched to ensure a comprehensive identification of relevant articles. Two independent investigators were involved at every stage of the systematic review, while discrepancies were resolved through discussion with a third investigator.

RESULTS:

All of the 18 included studies in this review (10 animal and eight cell studies) showed that palm oil and TRF enhanced the cognitive performance of healthy animals. In diabetes-induced rats, TRF and α-tocotrienol enhanced cognitive function and exerted antioxidant, anti-apoptotic and anti-inflammatory activities, while in a transgenic Alzheimer’s disease (AD) animal model, TRF enhanced the cognitive function and reduced the deposition of β-amyloid by altering the expression of several genes related to AD and neuroprotection. In cell studies, simultaneous treatment with α-tocotrienols and neurotoxins improved the redox status in neuronal cells better than ϒ- and δ-tocotrienols. Both pre-treatment and post-treatment with α-tocotrienol relative to oxidative insults were able to enhance the survival of neuronal cells via increased antioxidant responses.

CONCLUSIONS:

Palm oil and its TRF enhanced the cognitive functions of healthy animals, while TRF and α-tocotrienol enhanced the cognitive performance with attenuation of oxidative stress, neuroinflammation and apoptosis in diabetes-induced or transgenic AD animal models. In cell studies, TRF and α-tocotrienol exerted prophylactic neuroprotective effects, while α-tocotrienol exerted therapeutic neuroprotective effects that were superior to those of ϒ- and δ-tocotrienol isomers.

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Vitamin E Intake Is Associated with Lower Brain Volume in Haptoglobin 1-1 Elderly with Type 2 Diabetes

Livny A, Schnaider Beeri M, Heymann A, Moshier E, Berman Y, Mamistalov M, Shahar DR, Tsarfaty G, Leroith D, Preiss R, Soleimani L, Silverman JM, Bendlin BB, Levy A, Ravona-Springer R

J Alzheimers Dis. 2020 Feb 12. doi: 10.3233/JAD-191294. [Epub ahead of print]

Abstract

BACKGROUNDS:

The efficacy of vitamin E in prevention of diabetes-related complications differs by Haptoglobin (Hp) genotype.

OBJECTIVE:

To examine the role of Hp genotype in the relationship of vitamin E intake with brain volume in cognitively normal elderly patients with type 2 diabetes.

METHODS:

Brain volumes for the superior, middle, and inferior frontal gyri and for the middle temporal gyrus were generated from structural T1 MRI in 181 study participants (Hp 1-1: n = 24, Hp 2-1: n = 77, Hp 2-2: n = 80). Daily vitamin E intake was assessed using the Food Frequency Questionnaire. Analyses of covariance, controlling for demographic and cardiovascular variables was used to evaluate whether the association of daily vitamin E intake with brain volume was modified by Hp genotype.

RESULTS:

Average age was 70.8 (SD = 4.2) with 40% females, and mean Mini-Mental State Examination score of 28.17 (SD = 1.90). A significant interaction was found between vitamin E intake and Hp genotype in inferior frontal gyrus’ volume; p = 0.0108. For every 1 microgram increase in vitamin E intake, the volume of the inferior frontal gyrus decreased by 0.955% for Hp 1-1 (p = 0.0348), increased by 0.429% for Hp 2-1 (p = 0.0457), and by 0.077% for Hp 2-2 (p = 0.6318). There were no significant interactions between vitamin E intake and Hp genotype for the middle (p = 0.6011) and superior (p = 0.2025) frontal gyri or for the middle temporal gyrus (p = 0.503).

CONCLUSIONS:

The effect of dietary vitamin E on the brain may differ by Hp genotype. Studies examining the impact of vitamin E on brain-related outcomes should consider Hp genotype.

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Antioxidant phytochemicals in pulses and their relation to human health: A Review

Ciudad-Mulero M, Matallana-González MC, Cámara M, Fernádez-Ruiz V, Morales P

Curr Pharm Des. 2020 Feb 3. doi: 10.2174/1381612826666200203130150. [Epub ahead of print]

Abstract

Pulses are staple foods cultivated since ancient times, which play an important role in the human diet. From a nutritional point of view, pulses are very interesting foods as they are rich in proteins, carbohydrates and dietary fiber. Dietary antioxidants are a complex mixture of hydrophilic and lipophilic compounds usually present in foods of plant origin, including pulses. In the present study, the phytochemical composition of selected pulses (common beans, fava beans, lentils, chickpeas, peas and lupins) have been reviewed in terms of their content of antioxidant compounds. The content of hydrosoluble antioxidants (organic acids, phenolic compounds), liposoluble antioxidants (tocopherols, carotenoids) and other compounds, which exert antioxidant properties such as dietary fiber and minerals (zinc, selenium), have been studied, reporting that pulses are an interesting source of these compounds, which have important health benefits, including a preventing role on cardiovascular diseases, anticarcinogenic or neuroprotective properties. It is important to take into account that pulses are not usually consumed raw, but they must be processed before consumption in order to improve their nutritional quality and their palatability, therefore, the effect of different technological and heat treatments (germination, cooking, boiling, extrusion) on the antioxidant compounds present in pulses have been also reviewed. In this sense, it has been observed that as consequence of processing, the content of phytochemicals with antioxidant properties is usually decreased, but processed pulses maintain relevant amounts of these compounds, preserving their beneficial health effect.

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Lipophilic Antioxidants and Cognitive Function in the Elderly

Niemchick KL, Riemersma C, Lasker GA

Nutr Metab Insights. 2020 Feb 3;13:1178638820903300. doi: 10.1177/1178638820903300. eCollection 2020.

Abstract

OBJECTIVE:

To determine the relationship between blood serum lipophilic antioxidant levels and cognitive function (CF) in older adults aged 60 and above guided by the oxidative stress theory of aging.

METHODS:

Cross-sectional data from the National Health and Nutrition Examination Survey (n = 291) for older adults aged 60 and above were examined using Pearson correlation coefficient and multiple linear regression to determine whether blood serum antioxidant status predicted CF while controlling for age, sex, race, hypertension, smoking status, and body mass index.

RESULTS:

Alpha-tocopherol, retinyl palmitate, trans-lycopene, and retinyl stearate were all significantly correlated with CF. After controlling for covariates, α-tocopherol and retinyl palmitate were associated with CF. Age, sex, and current smoking status were significant predictors of CF.

CONCLUSIONS:

The benefits of antioxidants in CF may be a part of nutritional recommendations which include α-tocopherol and retinyl palmitate for delay of CI, and subsequently a better quality of life.

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