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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Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons

Park HA, Mnatsakanyan N, Broman K, Davis AU, May J, Licznerski P, Crowe-White KM, Lackey KH, Jonas EA

Int J Mol Sci. 2019 Dec 28;21(1). pii: E220. doi: 10.3390/ijms21010220.

Abstract

B-cell lymphoma-extra large (Bcl-xL) is an anti-apoptotic member of the Bcl2 family of proteins, which supports neurite outgrowth and neurotransmission by improving mitochondrial function. During excitotoxic stimulation, however, Bcl-xL undergoes post-translational cleavage to ∆N-Bcl-xL, and accumulation of ∆N-Bcl-xL causes mitochondrial dysfunction and neuronal death. In this study, we hypothesized that the generation of reactive oxygen species (ROS) during excitotoxicity leads to formation of ∆N-Bcl-xL. We further proposed that the application of an antioxidant with neuroprotective properties such as α-tocotrienol (TCT) will prevent ∆N-Bcl-xL-induced mitochondrial dysfunction via its antioxidant properties. Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both. Glutamate challenge significantly increased cytosolic and mitochondrial ROS and ∆N-Bcl-xL levels. ∆N-Bcl-xL accumulation was accompanied by intracellular ATP depletion, loss of mitochondrial membrane potential, and cell death. α-TCT prevented loss of mitochondrial membrane potential in hippocampal neurons overexpressing ∆N-Bcl-xL, suggesting that ∆N-Bcl-xL caused the loss of mitochondrial function under excitotoxic conditions. Our data suggest that production of ROS is an important cause of ∆N-Bcl-xL formation and that preventing ROS production may be an effective strategy to prevent ∆N-Bcl-xL-mediated mitochondrial dysfunction and thus promote neuronal survival.

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Tocotrienol-rich vitamin E improves diabetic nephropathy and persists 6-9 months after washout: a phase IIa randomized controlled trial

Tan GCJ, Tan SMQ, Phang SCW, Ng YT, Ng EY, Ahmad B, Palamisamy UDM, Kadir KA

Ther Adv Endocrinol Metab. 2019 Dec 25;10:2042018819895462. doi: 10.1177/2042018819895462. eCollection 2019.

Abstract

Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6-9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: -3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus -2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6-9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6-9 months post-washout.

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Nutritional Neuropathies

Gwathmey KG, Grogan J

Muscle Nerve. 2019 Dec 14. doi: 10.1002/mus.26783.

Abstract

Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Though these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.

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Tocotrienol Rich Fraction Supplementation Modulate Brain Hippocampal Gene Expression in APPswe/PS1dE9 Alzheimer’s Disease Mouse Model

Wan Nasri WN, Makpol S, Mazlan M, Tooyama I, Wan Ngah WZ, Damanhuri HA

J Alzheimers Dis. 2019;70(s1):S239-S254. doi: 10.3233/JAD-180496.

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive abilities. AD is associated with aggregation of amyloid-β (Aβ) deposited in the hippocampal brain region. Our previous work has shown that tocotrienol rich fraction (TRF) supplementation was able to attenuate the blood oxidative status, improve behavior, and reduce fibrillary-type Aβ deposition in the hippocampus of an AD mouse model. In the present study, we investigate the effect of 6 months of TRF supplementation on transcriptome profile in the hippocampus of APPswe/PS1dE9 double transgenic mice. TRF supplementation can alleviate AD conditions by modulating several important genes in AD. Moreover, TRF supplementation attenuated the affected biological process and pathways that were upregulated in the AD mouse model. Our findings indicate that TRF supplementation can modulate hippocampal gene expression as well as biological processes that can potentially delay the progression of AD.

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Modulation of Proteome Profile in AβPP/PS1 Mice Hippocampus, Medial Prefrontal Cortex, and Striatum by Palm Oil Derived Tocotrienol-Rich Fraction

Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Makpol S, Wan Ngah WZ, Damanhuri HA, Tooyama I

J Alzheimers Dis. 2019;72(1):229-246. doi: 10.3233/JAD-181171.

Abstract

Tocotrienol-rich fraction (TRF) is a mixture of vitamin E analogs derived from palm oil. We previously demonstrated that supplementation with TRF improved cognitive function and modulated amyloid pathology in AβPP/PS1 mice brains. The current study was designed to examine proteomic profiles underlying the therapeutic effect of TRF in the brain. Proteomic analyses were performed on samples of hippocampus, medial prefrontal cortex (mPFC), and striatum using liquid chromatography coupled to Q Exactive HF Orbitrap mass spectrometry. From these analyses, we profiled a total of 5,847 proteins of which 155 proteins were differentially expressed between AβPP/PS1 and wild-type mice. TRF supplementation of these mice altered the expression of 255 proteins in the hippocampus, mPFC, and striatum. TRF also negatively modulated the expression of amyloid beta A4 protein and receptor-type tyrosine-protein phosphatase alpha protein in the hippocampus. The expression of proteins in metabolic pathways, oxidative phosphorylation, and those involved in Alzheimer’s disease were altered in the brains of AβPP/PS1 mice that received TRF supplementation.

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Neuroprotective and Anti-Obesity Effects of Tocotrienols

Fukui K.

J Nutr Sci Vitaminol (Tokyo). 2019;65(Supplement):S185-S187. doi: 10.3177/jnsv.65.S185.

Abstract

Vitamin E is a natural lipophilic vitamin, and the most famous function of vitamin E is an antioxidant activity. Because we have α-tocopherol transfer protein, many vitamin E-related reports are about α-tocopherol. Recently, other vitamin E isoforms, tocotrienols are focusing. Because tocotrienols have unique biological functions such as induction of apoptosis, neuroprotective and anti-obesity effects. Tocotrienols contain in annatto, palm, whole wheat and rice bran. Rice is a typical food in the East Asian countries and Japan. Recently, intake of whole rice is a popular in young women of Japan. Previously, we demonstrated that treatment with tocotrienols on the neuronal cells shows a strong antioxidant effect compared to the tocopherols. In this review, I introduce about neuroprotective and anti-obesity effects of tocotrienols. I would like to show daily intake of whole rice is very good for our health in this review.

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