Malaysia’s pending approval on palm tocotrienol’s antioxidant claims could help consumers gain a better understanding of the locally grown crop’s health benefits. There are 2 proposed claims: 1) TRF is an antioxidant and may help to reduce oxidative stress and 2) TRF may help to improve cognitive function. To make these claims, a product would need to contain 10mg/100g of solid TRF and 10mg/100ml of liquid TRF.
Background: Vitamin E is the most abundant lipid-soluble antioxidants present in plasma; however, the relationship between serum vitamin E and change in body mass index (BMI)-for-age Z scores in adolescents has not been well described.
Methods: This study is a cross-sectional study. Data were analyzed from 4014 adolescents who participated in the National Health and Nutrition Examination Survey. The nutritional status was calculated by BMI Z scores and was classified into normal weight, overweight, and obese. Multivariable-adjusted logistic regression was used to examine the association between serum vitamin E levels with overweight/obesity. Besides, the interaction effects between potential confounders and vitamin E on obesity were further evaluated.
Results: After adjusting potential confounders, serum vitamin E levels were negatively associated with overweight/obesity in girls but not in boys. Per standard deviation increment in vitamin E concentrations was associated with a 92% decreased risk of obesity in females. Besides, lower quartiles of serum vitamin E were associated with a higher risk of overweight/obesity in girls. Moreover, the inverse association between serum vitamin E levels and obesity was also found in most subgroups through subgroup analysis.
Conclusions: Our study supports the negative association between serum vitamin E levels and overweight/obesity in adolescents. A higher serum vitamin E level may be associated with a reduced probability of obesity in girls, but not in boys.
Non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD), can progress to cirrhosis, hepatocellular carcinoma (HCC), and hepatic failure/liver transplantation. Indeed, NASH will soon be the leading cause of HCC and liver transplantation. Lifestyle intervention represents the cornerstone of NASH treatment, but it is difficult to sustain. However, no pharmacotherapies for NASH have been approved. Oxidative stress has been implicated as one of the key factors in the pathogenesis of NASH. Systematic reviews with meta-analyses have confirmed that vitamin E reduces transaminase activities and may resolve NASH histopathology without improving hepatic fibrosis. However, vitamin E is not recommended for the treatment of NASH in diabetes, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis. Nevertheless, vitamin E supplementation may improve clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis. Further studies are warranted to confirm such effects of vitamin E and that it would reduce overall mortality/morbidity without increasing the incidence of cardiovascular events. Future clinical trials of the use of vitamin E in combination with other anti-fibrotic agents may demonstrate an additive or synergistic therapeutic effect. Vitamin E is the first-line pharmacotherapy for NASH, according to the consensus of global academic societies.
Background: Vitamin E (tocopherol) a naturally occurring mixture of antioxidants commonly used in topical skin care products, may cause allergic contact dermatitis.
Objective: The aim of this study was to characterize positive patch test reactions to tocopherol and tocopherol acetate.
Methods: This is a retrospective analysis of North American Contact Dermatitis Group patch test data to tocopherols (dl-α-tocopherol 100% and/or dl-α-tocopherol acetate 100%) from 2001 to 2016.
Results: Of the 38,699 patients patch tested to tocopherol and/or tocopherol acetate, 349 (0.9%) had positive reactions; of these, 87.6% were currently relevant. Most (51.4%) were weak (+) and/or not related to occupation (99.1%). Compared with tocopherol-negative patients, tocopherol-positive individuals were more likely to be female (72.5% vs 67.2%, P = 0.0355), have a final primary diagnosis of allergic contact dermatitis (74.2% vs 52.6%, P < 0.0001), and have dermatitis in a scattered generalized distribution (23.8% vs 18.2%, P = 0.0072); they were also less likely to have hand involvement (16.6% vs 22.3%, P = 0.0064). The most common source of tocopherol was personal care products, especially moisturizers.
Conclusions: Positive patch test reactions to tocopherols were relatively rare given their widespread use. When positive, current clinical relevance was high. Tocopherol-positive patients were more likely to be female and presented with dermatitis on the face or in a scattered generalized pattern.
Neurodegenerative disorders, such as Parkinson’s and Alzheimer’s disease, are claimed to be of major concern causing a significant disease burden worldwide. Oxidative stress, mitochondrial dysfunction and nerve damage are the main reasons for the emergence of these diseases. The formation of reactive oxygen species (ROS) is the common chemical molecule that is formed from all these three interdependent mechanisms which is highly reactive toward the neuronal cells. For these reasons, the administration of tocotrienols (T3s), which is a potent antioxidant, is proven to cater to this problem, through in vitro and in vivo investigations. Interestingly, their therapeutic potentials are not only limited to antioxidant property but also to being able to reverse the neuronal damage and act as a shield for mitochondria dysfunction. Thereby, T3s prevents the damage to the neurons. In regards to this statement, in this review, we focused on summarizing and discussing the potential therapeutic role of T3s on Alzheimer’s and Parkinson’s diseases, and their protective mechanisms based on evidence from the in vitro and in vivo studies. However, there is no clinical trial conducted to prove the efficacy of T3s for Alzheimer’s and Parkinson’s subjects. As such, the therapeutic role of T3s for these neurodegenerative disorders is still under debate.
Cyclooxygenase (COX-1 and COX-2)- and 5-lipoxygenase (5-LOX)-catalyzed biosynthesis of eicosanoids play important roles in inflammation and chronic diseases. The vitamin E family has four tocopherols and tocotrienols. We have shown that the metabolites of δ-tocopherol (δT) and δ-tocotrienol (δTE), i.e., δT-13′-carboxychromanol (COOH) and δTE-13′-COOH, respectively, inhibit COX-1/-2 and 5-LOX activity, but the nature of how they inhibit 5-LOX is not clear. Further, the impact of tocopherols and tocotrienols on COX-1/-2 or 5-LOX activity has not been fully delineated. In this study, we found that tocopherols and tocotrienols inhibited human recombinant COX-1 with IC50s of 1-12 µM, and suppressed COX-1-mediated formation of thromboxane in collagen-stimulated rat’s platelets with IC50s of 8-50 µM. None of the vitamin E forms directly inhibited COX-2 activity. 13′-COOHs inhibited COX-1 and COX-2 enzyme activity with IC50s of 3-4 and 4-10 µM, respectively, blocked thromboxane formation in collagen- and ionophore-stimulated rats’ platelets with IC50s of 1.5-2.5 µM, and also inhibited COX-2-mediated prostaglandins in stimulated cells. Using enzyme kinetics, we observed that δT-13′-COOH, δTE-13′-COOH and δTE competitively inhibited 5-LOX activity with Ki of 1.6, 0.8 and 2.2 µM, respectively. These compounds decreased leukotriene B4 from stimulated neutrophil-like cells without affecting translocation of 5-LOX from cytosol to the nucleus. Our study reveals inhibitory effects of vitamin E forms and 13′-COOHs on COX-1 activity and thromboxane formation in platelets, and elucidates mechanisms underlying their inhibition of 5-LOX. These observations are useful for understanding the role of these compounds in disease prevention and therapy.
Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.
Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.
Self-emulsifying drug delivery systems (SEDDS) can improve the oral bioavailability of poorly water-soluble drugs. Solid self-emulsifying drug delivery systems (s-SEDDS) offer several advantages including improved drug stability, ease of administration, and production. Most compounds employed in developing s-SEDDS are solid in nature, with a high amount of surfactants added. The aim of this study was to develop an s-SEDDS using a tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The solid formulation was developed using magnesium aluminosilicate as the carrier with 70% TRF and 30% surfactants (poloxamer and Labrasol®). The formulation showed good self-emulsification efficiency with stable emulsion formed, excellent powder flowability, and small emulsion droplet size of 210-277 nm. The s-SEDDS with combined surfactants (poloxamer and Labrasol®) showed a faster absorption rate compared to preparations with only a single surfactant and enhanced oral bioavailability (3.4-3.8 times higher) compared to the non-self-emulsifying oily preparation when administered at a fasted state in rats. In conclusion, an s-SEDDS containing a high amount of TRF was successfully developed. It may serve as a useful alternative to a liquid product with enhanced oral bioavailability and the added advantage of being a solid dosage form.
Cyclooxygenase (COX-1 and COX-2)- and 5-lipoxygenase (5-LOX)-catalyzed biosynthesis of eicosanoids play important roles in inflammation and chronic diseases. The vitamin E family has four tocopherols and tocotrienols. We have shown that the metabolites of δ-tocopherol (δT) and δ-tocotrienol (δTE), i.e., δT-13′-carboxychromanol (COOH) and δTE-13′-COOH, respectively, inhibit COX-1/-2 and 5-LOX activity, but the nature of how they inhibit 5-LOX is not clear. Further, the impact of tocopherols and tocotrienols on COX-1/-2 or 5-LOX activity has not been fully delineated. In this study, we found that tocopherols and tocotrienols inhibited human recombinant COX-1 with IC50s of 1-12 µM, and suppressed COX-1-mediated formation of thromboxane in collagen-stimulated rat’s platelets with IC50s of 8-50 µM. None of the vitamin E forms directly inhibited COX-2 activity. 13′-COOHs inhibited COX-1 and COX-2 enzyme activity with IC50s of 3-4 and 4-10 µM, respectively, blocked thromboxane formation in collagen- and ionophore-stimulated rats’ platelets with IC50s of 1.5-2.5 µM, and also inhibited COX-2-mediated prostaglandins in stimulated cells. Using enzyme kinetics, we observed that δT-13′-COOH, δTE-13′-COOH and δTE competitively inhibited 5-LOX activity with Ki of 1.6, 0.8 and 2.2 µM, respectively. These compounds decreased leukotriene B4 from stimulated neutrophil-like cells without affecting translocation of 5-LOX from cytosol to the nucleus. Our study reveals inhibitory effects of vitamin E forms and 13′-COOHs on COX-1 activity and thromboxane formation in platelets, and elucidates mechanisms underlying their inhibition of 5-LOX. These observations are useful for understanding the role of these compounds in disease prevention and therapy.