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Keywords = plasma α-tocotrienols

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57 pages, 2866 KB  
Review
Shifting Perspectives on the Role of Tocotrienol vs. Tocopherol in Brain Health: A Scoping Review
by Rabiatul Adawiyah Razali, Wan Zurinah Wan Ngah, Suzana Makpol, Daijiro Yanagisawa, Tomoko Kato and Ikuo Tooyama
Int. J. Mol. Sci. 2025, 26(13), 6339; https://doi.org/10.3390/ijms26136339 - 30 Jun 2025
Cited by 6 | Viewed by 9265
Abstract
Vitamin E has been extensively studied for its neuroprotective properties, with increasing evidence supporting its broader roles in brain health. This scoping review aims to systematically identify, analyze, and synthesize evidence of the existing literature over the last 10 years on tocotrienol and [...] Read more.
Vitamin E has been extensively studied for its neuroprotective properties, with increasing evidence supporting its broader roles in brain health. This scoping review aims to systematically identify, analyze, and synthesize evidence of the existing literature over the last 10 years on tocotrienol and tocopherol supplementation in humans. A systematic search was conducted across PubMed, Scopus, and EBSCOhost yielding 42 eligible articles. Findings suggest that tocopherols, especially α- and γ-forms, are associated with improved cognitive performance, reduced neuroinflammation, and preservation of synaptic proteins. Despite tocotrienol’s lower plasma bioavailability, tocotrienol availability in selective brain regions has been associated with structural protection, particularly in white matter. Both compounds exhibit complementary effects, suggesting a potential advantage of combined supplementation. However, heterogeneity in study designs, subject characteristics, dosage, duration, and assessment methods limit direct comparisons and generalizability of findings. Based on our review’s findings, further research such as dose-optimization, long-term exposures, and delivery methods on human studies should be performed. This review highlights the multifaceted roles of vitamin E in brain health and underscores the urgent need for well-designed studies to clarify the distinct and synergistic effects of tocopherols and tocotrienols, particularly in human populations. Full article
(This article belongs to the Special Issue Nutraceuticals for the Maintenance of Brain Health)
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23 pages, 877 KB  
Article
Nutritional Status of Vitamin E and Its Association with Metabolic Health in Adults
by Kacper Szewczyk, Joanna Bryś, Rita Brzezińska and Magdalena Górnicka
Nutrients 2025, 17(3), 408; https://doi.org/10.3390/nu17030408 - 23 Jan 2025
Cited by 18 | Viewed by 10022
Abstract
Background: Vitamin E is one of the key dietary antioxidants. However, current evidence remains insufficient to establish a definitive relationship between circulating vitamin E levels, body fat content, and their influence on metabolic health. This study aimed to assess and compare the vitamin [...] Read more.
Background: Vitamin E is one of the key dietary antioxidants. However, current evidence remains insufficient to establish a definitive relationship between circulating vitamin E levels, body fat content, and their influence on metabolic health. This study aimed to assess and compare the vitamin E nutritional status in adults with normal and excess body fat and its determinants. Methods: Concentrations of vitamin E isoforms (α- and γ-tocopherols, α- and γ-tocotrienols) were assessed in 127 individuals. Body fat content and other anthropometric indices, as well as biochemical markers such as lipid profile, plasma fatty acid concentration and C-reactive protein, were identified as markers of metabolic health. Participants were divided into two groups: with normal and excess body fat (defined as more than 30% in women and more than 25% in men). Results: The determinants of higher α-tocopherol concentrations were lower body fat content and higher levels of circulating lipids as HDL and LDL (R2 = 0.221, p < 0.001 in a model of multivariate linear regression). The level of circulating vitamin E isoforms correlated with the concentration of CRP (r = −0.464 for α-T, r = −0.453 for αT3, r = −0.270 for γ-T, r = −0.355 for γ-T3). Similarly, elevated concentrations of vitamin E isoforms are linked to lower adipose tissue content, which may contribute to lower inflammation and improved metabolic health (r = −0.359 for α-T, r = −0.333 for αT3, r = −0.276 for γ-T3, no significant correlation for γ-T). Conclusions: These results reveal that the vitamin E status of adults with excess body fat may be inadequate and linked to poorer metabolic health. We found that the determinants of lower plasma vitamin E were higher BF and lower TC and its fraction, with the strongest correlations being found for HDL. Full article
(This article belongs to the Special Issue Antioxidants in Diet: Metabolic Impacts and Mechanisms of Action)
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12 pages, 1616 KB  
Article
miRNAs and Alzheimer’s Disease: Exploring the Role of Inflammation and Vitamin E in an Old-Age Population
by Virginia Boccardi, Giulia Poli, Roberta Cecchetti, Patrizia Bastiani, Michela Scamosci, Marta Febo, Emanuela Mazzon, Stefano Bruscoli, Stefano Brancorsini and Patrizia Mecocci
Nutrients 2023, 15(3), 634; https://doi.org/10.3390/nu15030634 - 26 Jan 2023
Cited by 19 | Viewed by 4009
Abstract
Alzheimer’s disease (AD) is the most frequent cause of dementia worldwide and represents one of the leading factors for severe disability in older persons. Although its etiology is not fully known yet, AD may develop due to multiple factors, including inflammation and oxidative [...] Read more.
Alzheimer’s disease (AD) is the most frequent cause of dementia worldwide and represents one of the leading factors for severe disability in older persons. Although its etiology is not fully known yet, AD may develop due to multiple factors, including inflammation and oxidative stress, conditions where microRNAs (miRNAs) seem to play a pivotal role as a molecular switch. All these aspects may be modulated by nutritional factors. Among them, vitamin E has been widely studied in AD, given the plausibility of its various biological functions in influencing neurodegeneration. From a cohort of old-aged people, we measured eight vitamin E forms (tocopherols and tocotrienols), thirty cytokines/chemokines, and thirteen exosome-extracted miRNAs in plasma of subjects suffering from subjects affected by AD and age-matched healthy controls (HC). The sample population included 80 subjects (40 AD and 40 HC) with a mean age of 77.6 ± 3.8 years, mostly women (45; 56.2%). Of the vitamin E forms, only α-tocopherol differed between groups, with significantly lower levels in AD. Regarding the examined inflammatory molecules, G-CSF, GM-CSF, INF-α2, IL-3, and IL-8 were significantly higher and IL-17 lower in AD than HC. Among all miRNAs examined, AD showed downregulation of miR-9, miR-21, miR29-b, miR-122, and miR-132 compared to controls. MiR-122 positively and significantly correlated with some inflammatory molecules (GM-CSF, INF-α2, IL-1α, IL-8, and MIP-1β) as well as with α-tocopherol even after correction for age and gender. A final binary logistic regression analysis showed that α-tocopherol serum levels were associated with a higher AD probability and partially mediated by miR-122. Our results suggest an interplay between α-tocopherol, inflammatory molecules, and microRNAs in AD, where miR-122 may be a good candidate as modulating factor. Full article
(This article belongs to the Section Geriatric Nutrition)
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12 pages, 1015 KB  
Article
Hepato-Protective Effects of Delta-Tocotrienol and Alpha-Tocopherol in Patients with Non-Alcoholic Fatty Liver Disease: Regulation of Circulating MicroRNA Expression
by Muhammad Amjad Pervez, Dilshad Ahmed Khan, Sayed Tanveer Abbas Gilani, Safia Fatima, Aamir Ijaz and Sumbal Nida
Int. J. Mol. Sci. 2023, 24(1), 79; https://doi.org/10.3390/ijms24010079 - 21 Dec 2022
Cited by 17 | Viewed by 5040
Abstract
MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in [...] Read more.
MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis. Full article
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13 pages, 4767 KB  
Article
Cationic N,N-Dimethylglycine Ester Prodrug of 2R-α-Tocotrienol Promotes Intestinal Absorption via Efficient Self-Micellization with Intrinsic Bile Acid Anion
by Daisuke Watase, Shuichi Setoguchi, Nami Nagata-Akaho, Shotaro Goto, Hirofumi Yamakawa, Ayano Yamada, Mitsuhisa Koga, Yoshiharu Karube, Kazuhisa Matsunaga and Jiro Takata
Molecules 2022, 27(9), 2727; https://doi.org/10.3390/molecules27092727 - 23 Apr 2022
Cited by 2 | Viewed by 2435
Abstract
The intestinal absorption of hydrophobic compounds is severely influenced by their transportation rate through the unstirred water layer in the intestinal lumen. A member of the vitamin E family, α-Tocotrienol (α-T3) has remarkable pharmacological effects, but its intestinal absorption is hampered due to [...] Read more.
The intestinal absorption of hydrophobic compounds is severely influenced by their transportation rate through the unstirred water layer in the intestinal lumen. A member of the vitamin E family, α-Tocotrienol (α-T3) has remarkable pharmacological effects, but its intestinal absorption is hampered due to its hydrophobicity. Here, we prepared three ester derivatives of 2R-α-T3, and we selected a suitable prodrug compound using rat plasma and liver microsomes. The micellization profile of the selected compound in the presence of taurocholic acid (TCA) was evaluated. After gastrostomy administration of the prodrug candidate or α-T3 solution containing TCA, AUC values were determined for α-T3 in plasma obtained from bile duct-ligated rats. Among the three types in the efficiency of the reconversion to the parent drug, α-T3 N,N-dimethylglycinate (α-T3DMG) was the best prodrug; α-T3DMG formed mixed micelles via ion pairs with anionic TCA. The solubility of α-T3DMG in n-octanol/water depended on its ratio to TCA. The AUC after α-T3DMG administration to ligated rats was 2-fold higher than that after α-T3 administration, suggesting a smooth interaction with intrinsic bile acids. In conclusion, utilization of the prodrug synthesized using N,N-dimethylglycine ester may be a beneficial approach to promote intestinal absorption of α-T3 via self-micellization with intrinsic bile acid. Full article
(This article belongs to the Special Issue The Role of Bile Acids in Metabolic Control)
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18 pages, 4495 KB  
Article
Effects of Palm Oil Tocotrienol-Rich Fraction (TRF) and Carotenes in Ovalbumin (OVA)-Challenged Asthmatic Brown Norway Rats
by Zaida Zainal, Afiqah Abdul Rahim, Huzwah Khaza’ai and Sui Kiat Chang
Int. J. Mol. Sci. 2019, 20(7), 1764; https://doi.org/10.3390/ijms20071764 - 10 Apr 2019
Cited by 29 | Viewed by 6246
Abstract
Synthetic therapeutic drugs for asthma, a chronic airway inflammation characterised by strong eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness, exhibit numerous side effects. Alternatively, the high antioxidant potential of palm oil phytonutrients, including vitamin E (tocotrienol-rich fractions; TRF) and [...] Read more.
Synthetic therapeutic drugs for asthma, a chronic airway inflammation characterised by strong eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness, exhibit numerous side effects. Alternatively, the high antioxidant potential of palm oil phytonutrients, including vitamin E (tocotrienol-rich fractions; TRF) and carotene, may be beneficial for alleviating asthma. Here, we determined the therapeutic efficacy of TRF, carotene, and dexamethasone in ovalbumin-challenged allergic asthma in Brown Norway rats. Asthmatic symptoms fully developed within 8 days after the second sensitization, and were preserved throughout the time course via intranasal ovalbumin re-challenge. Asthmatic rats were then orally administered 30 mg/kg body weight TRF or carotene. TRF-treated animals exhibited reduced inflammatory cells in bronchial alveolar lavage fluid. TRF- and carotene-treated rats exhibited notable white blood cell reduction comparable to that from dexamethasone. TRF- and carotene-treatment also downregulated pro-inflammatory markers (IL-β, IL-6, TNF-α), coincident with anti-inflammatory marker IL-4 and IL-13 upregulation. Treatment significantly reduced asthmatic rat plasma CRP and IgE, signifying improved systemic inflammation. Asthmatic lung histology displayed severe edema and inflammatory cell infiltration in the bronchial wall, whereas treated animals retained healthy, normal-appearing lungs. The phytonutrients tocotrienol and carotene thus exhibit potential benefits for consumption as nutritional adjuncts in asthmatic disease. Full article
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18 pages, 3840 KB  
Article
The Ameliorative Effects of a Tocotrienol-Rich Fraction on the AGE-RAGE Axis and Hypertension in High-Fat-Diet-Fed Rats with Metabolic Syndrome
by Hong Sheng Cheng, So Ha Ton, Joash Ban Lee Tan and Khalid Abdul Kadir
Nutrients 2017, 9(9), 984; https://doi.org/10.3390/nu9090984 - 7 Sep 2017
Cited by 30 | Viewed by 6810
Abstract
The clinical value of tocotrienols is increasingly appreciated because of the unique therapeutic effects that are not shared by tocopherols. However, their effect on metabolic syndrome is not well-established. This study aimed to investigate the effects of a tocotrienol-rich fraction (TRF) from palm [...] Read more.
The clinical value of tocotrienols is increasingly appreciated because of the unique therapeutic effects that are not shared by tocopherols. However, their effect on metabolic syndrome is not well-established. This study aimed to investigate the effects of a tocotrienol-rich fraction (TRF) from palm oil in high-fat-diet-treated rats. Male, post-weaning Sprague Dawley rats were provided high-fat (60% kcal) diet for eight weeks followed by a TRF (60 mg/kg) treatment for another four weeks. Physical, metabolic, and histological changes were compared to those on control and high-fat diets respectively. High-fat feeding for eight weeks induced all hallmarks of metabolic syndrome. The TRF reversed systolic and diastolic hypertension, hypercholesterolemia, hepatic steatosis, impaired antioxidant defense, and myeloperoxidase hyperactivity triggered by the high-fat diet. It also conferred an inhibitory effect on protein glycation to reduce glycated hemoglobin A1c and advanced glycation end products (AGE). This was accompanied by the suppression of the receptor for advanced glycation end product (RAGE) expression in the liver. The treatment effects on visceral adiposity, glycemic control, triglyceride level, as well as peroxisome proliferator-activated receptor α and γ expression were negligible. To conclude, treatment with a TRF exhibited protective effects on the cardiovascular and liver health in addition to the amelioration of plasma redox imbalance and AGE-RAGE activation. Further investigation as a therapy for metabolic syndrome is therefore worthwhile. Full article
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