It appears that the story on vitamin E and its role in human health remains incomplete. It is apparent that vitamin E supplementation involves many variables, some of which include its uptake from the intestine, the preference for α-tocopherol, transport by tocopherol specific proteins and lipid transporters and the differential metabolism of different vitamin E isoforms. The fundamental differences within population genetics can have significant implications for the effect that dietary supplementation might have on human health. When evaluating the efficacy of vitamin E prophylactic or therapeutic use in previous and future studies, it is critical to consider dosage to be administered, form of vitamin E and source (such as whether from synthetic or purified from natural sources). Further studies are needed to determine the effects of all vitamin E isoforms on cell growth, tumorigenicity, to clarify its possible use as an adjuvant to existing chemotherapeutics. The Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study Group and Selenium and Vitamin E Cancer Prevention Trial (SELECT) studies along with the numerous studies of vitamin E should help guide the next chapter of vitamin E research.
Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients
Daud ZA, Tubie B, Sheyman M, Osia R, Adams J, Tubie S, Khosla P.
Vasc Health Risk Manag . 2013;9:747-61. doi: 10.2147/VHRM.S51710. Epub 2013 Nov 28.
Abstract
PURPOSE:
Chronic hemodialysis patients experience accelerated atherosclerosis contributed to by dyslipidemia, inflammation, and an impaired antioxidant system. Vitamin E tocotrienols possess anti-inflammatory and antioxidant properties. However, the impact of dietary intervention with Vitamin E tocotrienols is unknown in this population.
PATIENTS AND METHODS:
A randomized, double-blind, placebo-controlled, parallel trial was conducted in 81 patients undergoing chronic hemodialysis. Subjects were provided daily with capsules containing either vitamin E tocotrienol-rich fraction (TRF) (180 mg tocotrienols, 40 mg tocopherols) or placebo (0.48 mg tocotrienols, 0.88 mg tocopherols). Endpoints included measurements of inflammatory markers (C-reactive protein and interleukin 6), oxidative status (total antioxidant power and malondialdehyde), lipid profiles (plasma total cholesterol, triacylglycerols, and high-density lipoprotein cholesterol), as well as cholesteryl-ester transfer protein activity and apolipoprotein A1.
RESULTS:
TRF supplementation did not impact any nutritional, inflammatory, or oxidative status biomarkers over time when compared with the baseline within the group (one-way repeated measures analysis of variance) or when compared with the placebo group at a particular time point (independent t-test). However, the TRF supplemented group showed improvement in lipid profiles after 12 and 16 weeks of intervention when compared with placebo at the respective time points. Normalized plasma triacylglycerols (cf baseline) in the TRF group were reduced by 33 mg/dL (P=0.032) and 36 mg/dL (P=0.072) after 12 and 16 weeks of intervention but no significant improvement was seen in the placebo group. Similarly, normalized plasma high-density lipoprotein cholesterol was higher (P<0.05) in the TRF group as compared with placebo at both week 12 and week 16. The changes in the TRF group at week 12 and week 16 were associated with higher plasma apolipoprotein A1 concentration (P<0.02) and lower cholesteryl-ester transfer protein activity (P<0.001).
CONCLUSION:
TRF supplementation improved lipid profiles in this study of maintenance hemodialysis patients. A multi-centered trial is warranted to confirm these observations.
Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals
Heng, E. C., Karsani, S. A., Abdul Rahman, M., Abdul Hamid, N. A., Hamid, Z., Wan Ngah, W. Z.
2013
Objective: Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups.
METHODS: Subjects were divided into two age groups-32 +/- 2 (young) and 52 +/- 2 (old) years old. Four subjects from each group were assigned with TRF (78 % tocotrienol and 22 % tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting.
RESULTS: Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression.
CONCLUSIONS: TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.
Classification and prediction of clinical diagnosis of Alzheimer’s disease based on MRI and plasma measures of α-/γ-tocotrienols and γ-tocopherol
Mangialasche F, Westman E, Kivipelto M, et al
J Intern Med. 2013 Jan 24. doi: 10.1111/joim.12037. [Epub ahead of print]
Published
OBJECTIVES:The aim of this study was to evaluate the accuracy of combined structural magnetic resonance imaging (MRI) measures and plasma levels of vitamin E forms, including all eight natural vitamin E congeners (four tocopherols and four tocotrienols) and markers of vitamin E oxidative/nitrosative damage, in differentiating individuals with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) from cognitively intact control (CTL) subjects.
SUBJECTS AND DESIGN: Overall, 81 patients with AD, 86 with MCI and 86 CTL individuals were enrolled from the longitudinal multicentre AddNeuroMed study. MRI and plasma vitamin E data were acquired at baseline. MRI scans were analysed using Freesurfer, an automated segmentation scheme which generates regional volume and cortical thickness measures. Orthogonal partial least squares to latent structures (OPLS), a multivariate data analysis technique, was used to analyse MRI and vitamin E measures in relation to AD and MCI diagnosis.
RESULTS: The joint evaluation of MRI and plasma vitamin E measures enhanced the accuracy of differentiating individuals with AD and MCI from CTL subjects: 98.2% (sensitivity 98.8%, specificity 97.7%) for AD versus CTL and 90.7% (sensitivity 91.8%, specificity 89.5%) for MCI versus CTL. This combination of measures also identified 85% of individuals with MCI who converted to clinical AD at follow-up after 1 year.
CONCLUSIONS: Plasma levels of tocopherols and tocotrienols together with automated MRI measures can help to differentiate AD and MCI cases from CTL subjects, and to prospectively predict MCI conversion to AD. Our results suggest the potential role of nutritional biomarkers detected in plasma – tocopherols and tocotrienols – as indirect indicators of AD pathology, and the utility of a multimodality approach. © 2013 The Association for the Publication of the Journal of Internal Medicine.
Effects of Tocotrienol-Enriched Fraction of Palm Oil of Serum Lipids in Hypercholesterolemic Subjects
David Heber, Center for Human Nutrition, UCLA
Terminated
Objective: To evaluate cholesterol-suppressive actions of tocotrienol-enriched fractions in hypercholesterolemic human subjects.
Study Type:Interventional
Study Design: Randomized, double-blind, placebo-controlled
Subjects: Hypercholesterolemic subjects
Intervention: Gamma-Delta Tocotrienol (63 mg and 127 mg; Davos Life Science Pte Ltd)
Primary Outcome:
- Fasting cholesterol levels [time frame: baseline, 4, 8, 12 weeks]
- Total body fat [time frame: baseline, 4, 8 12 weeks]
Secondary Outcome:
- Genetic biomarkers for lipid metabolism
Methodology:
The cholesterol suppressive actions of tocotrienol-enriched formulations will be assessed in 99 hypercholesterolemic subjects 37 – 70 years of age, During a two-week run-in period, subjects will be asked to follow the American Heart Association Step 1 dietary regimen and to take a placebo capsule twice daily to determine their ability to comply with the diet and pill regimen. Their fasting cholesterol levels will be tested again after the two-week run-in period.
At this point, they will be randomly assigned to take either a placebo capsule or tocotrienol twice daily. Subjects will have body weight, waist circumference, fasting lipids and other biomarkers measured at 0, 4, 8 and 12 weeks
The Effect of Supplemental Adjuvants for Intracellular Nutrition and Treatment on Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration
Nabil M Jabbour, MD, FACS M.A.R.C., West Virginia University
Ongoing
Objective: Nutritional supplements have an augmentative effect on the outcomes of standard treatment of diabetic macular edema (DME) and Neovascular Age-Related Macular Degeneration (NAMD).
Study Type: Interventional
Study Design: Randomized, Double-blind Study
Subjects: Subjects with age-related macular degeneration
Intervention:
Drug — Neutral pills with no medicinal effect
Dietary Supplement — Inosine; Tocopherols, Tocotrienol, CoQ10 combination capsule; Niacinamide SR; Viatmin C; N-acetyl Cysteine; Complete Multivitamin with all minerals
Drug: Inosine; Tocopherol, Tocotrienol, CoQ10 combination capsule; Niacinamide; Vitamin C; N-acetyl Cysteine; Complete Multivitamin with all minerals; Minocycline
Primary Outcome: Anatomic and visual outcomes
Secondary Outcome: 1) Effect on HbA1C [ Time Frame: Monthly ]
2) Effect on Blood pressure [ Time Frame: Monthly ]
3) Effect on serum uric acid [ Time Frame: Monthly ]
Methodology: It has been shown that in chronic diseases, oxidative stress results from Nitric acid reacting with oxygen to form toxins that damage both somatic and mitochondrial DNA. The potential for protecting the DNA and promoting repair by using nutritional supplements will be tested by augmenting standard treatments for DME and NAMD with such supplements. The patients will be randomized to treatment group and placebo group and followed up for a year in a double masked fashion. Anatomic and visual outcomes, as well as side effects will be assessed and analyzed. If the results are promising, this pilot study can be used to design alternative (cheaper, better and longer lasting) treatments for DME, NAMD and perhaps other chronic illnesses.
Acute Effects of Tocotrienols on Insulinaemic and Inflammatory Responses in Metabolic Syndrome Subjects
Dr Teng Kim Tiu, PhD, Universiti Malaya
Completed
Objectives: To compare the acute effects of gamma delta rich tocotrienol fractions (gd-TRF) on insulin sensitivity, metabolic risk markers and postprandial lipemia in individuals at risk for metabolic syndrome.
Study Type: Interventional
Study Design: Randomized, double-blind, cross-over
Subjects: Patients at risk for metabolic syndrome
Intervention: Gamma-Delta tocotrienol, placebo
Primary Outcome: C-peptide [ Time Frame: 0, 15, 30, 60, 90, 120, 180, 240, 300, 360 min ]
Secondary Outcome: 1) Insulin sensitivity (insulin, glucose) [ Time Frame: 0, 5, 15, 30, 60, 90, 120, 180, 240, 300, 360 min ]
2) Non-esterified fatty acid (NEFA) [ Time Frame: 0, 5, 15, 30, 60, 90, 120, 180, 240, 300, 360 min ]
3) Non-esterified fatty acid (NEFA) [ Time Frame: 0, 5, 15, 30, 60, 90, 120, 180, 240, 300, 360 min ]
4) Inflammatory markers (IL-6, IL-1β, TNF-α) [ Time Frame: 0, 120, 240, 360 min ]
5) PBMC nuclear factor-κappa B (NF-κB) [ Time Frame: 0, 240, 360 min ]
Methodology: A randomised, double-blind, crossover trial will be undertaken to test the acute effects of supplementation of 200 mg, 400 mg gd-TRF vs. placebo. There are 3 occasions for subjects to attend during postprandial period and these occasions will be separated by at least one week. On the day preceding the postprandial high fat meal challenge, subjects will be asked to avoid food high in fat, alcohol, caffeine and taking part in any strenuous exercise. Subjects will be provided with a standardised low fat meal (containing < 10 g fat) on the day preceding the postprandial study days to consume as their evening meal. They will be asked to fast overnight and instructed to avoid eating or drinking anything, except water, after 10 pm. Fasting blood samples will be collected on the next day and subjects will then consume the test meal, containing 50 g test fat supplemented with gd-TRF. Further venous blood samples will be collected at regular intervals for up to 6 hours postprandially.
Effects of Tocotrienols Supplementation on Platelet Aggregation in Subjects With Metabolic Syndrome
Ju Yen Fu, PhD, Universiti Putra Malaysia
Ongoing
Objective: The objective of this study is to address the anti-thrombotic effects of tocotrienols supplementation via modulation of platelet activation, thrombotic markers, inflammatory markers and endothelial function.
Study Type: Interventional
Study Design: Randomized, Double-blind
Subjects: Volunteers with metabolic syndrome
Intervention: Tocotrienol-rich fraction 400 mg, placebo
Primary Outcome: Platelet Aggregation. Changes will be measured in between Day 0 and Day 14-fasting, and Day 14-fasting and 4hr.
Secondary Outcome: 1) Platelet activation. Changes will be measured in between Day 0 and Day 14-fasting, and Day 14-fasting and 4hr.
2) Haemostatic markers (Activated factor VII and Plasminogen activator inhibitor type 1) Changes will be measured in between Day 0 and Day 14-fasting. During Day 14, changes of markers when compared to fasting sample will be measured at 2 hours, 4 hours, and 6 hours after high fat breakfast.
3) Inflammatory markers (NF-kB, sICAM-1, and sVCAM-1) Changes will be measured in between Day 0 and Day 14-fasting, and Day 14-fasting and 4hr.
4) Lipid Profile. Changes will be measured in between Day 0 and Day 14-fasting
5) D-dimer. Changes will be measured in between Day 0 and Day 14-fasting, and Day 14-fasting and 4hr.
Methodology: A double-blind, randomized, crossover study comparing the effects of tocotrienols vs. placebo will be conducted in subjects with metabolic syndrome. Subjects will be supplemented with Tocovid Suprabio 200 mg twice daily (or placebo) for 2 weeks followed by a postprandial challenge on Day 14. During the postprandial challenge, venous blood samples will be collected during fasting. Subjects are then required to consume a high fat breakfast meal containing 50g fat and 100mL milkshake, followed by the assigned capsules. Venous blood samples will be drawn at 2, 4 and 6 hours after consumption of capsules. A washout period of at least 14 days will be in place before the commencement of the second treatment.
Efficacy Of Tocotrienol a Natural Vitamin E In Biopsy Wound
Chandan K Sen, PhD
Ongoing
Objectives: The following two objectives are proposed in healthy subjects to characterize (1) wound closure, (2) scar formation/appearance, and (3) inflammatory response:
Objective 1, (topical only – referred to as “TOP”) – Topical application of TCT vs placebo in bilateral punch biopsy
Objective 2, (oral and topical – referred to as “OTOP”) – Combined oral supplementation and topical application of TCT vs placebo in bilateral punch biopsy
Study Type: Observational
Study Design: Cohort Prospective Study
Subjects: Healthy volunteers
Intervention: Tocotrienol, placebo
Primary Outcome: Safety Issue
Methodology: Biospecimen Retention: Samples With DNA
Tissue biopsy will be collected twice in the study period.
Efficacy of Natural Vitamin E Tocotrienol on the Treatment of Surgical Scars
Chandan K Sen, PhD
Ongoing
Objective: The overall goal of this study is to determine the efficacy of tocotrienol (TCT), a natural form of vitamin E, in preventing or reducing scar formation in human skin wounds.
Study Type: Interventional
Study Design: Randomized, Double-blind Trial
Subjects: Patients with surgical scars
Intervention: Vitamin E Tocotrienol, Placebo
Primary Outcome: To determine the efficacy of TCT in improving the appearance of post-surgical scars following oral supplementation 2.To determine the efficacy of TCT in improving the appearance of post-surgical scars following topical application [ Time Frame: 4 weeks prior to surgery and 12 weeks post surgery. ]