Platelet function in stroke/transient ischemic attack patients treated with tocotrienol

Andrew Slivka, Cameron Rink, David Paoletto, Chandan K Sen

FASEB J . 2020 Jul 20. doi: 10.1096/fj.201902216RR. Online ahead of print.


The purpose of this study was to characterize the effects of tocotrienol form of vitamin E (TCT) on platelet function in patients with stroke or transient ischemic attack (TIA). A double blind, randomized, single center phase II clinical trial was conducted comparing placebo (PBO) and 400 and 800 mg TCT daily for a year in 150 patients with a sentinel ischemic stroke or TIA event in the prior 6 months. Platelet function was measured at baseline and then, at 3 month intervals for a year, using light transmission aggregometry. The incidence of aspirin resistance in aspirin-treated patients or platelet inhibition in patients on clopidogrel alone was compared between the three treatment groups. Results showed that in patients taking aspirin and clopidogrel, the incidence of aspirin resistance was significantly decreased from 40% in PBO-treated patients to 9% in the 400 mg TCT group and 25% in the TCT 800 mg group (P = .03). In conclusion, patients on aspirin and clopidogrel had a higher incidence of aspirin resistance than all patients treated with aspirin alone and TCT decreased the frequency of aspirin resistance in this group.

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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]


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.

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Effects of Tocotrienols Supplementation on Platelet Aggregation in Subjects With Metabolic Syndrome

Ju Yen Fu, PhD, Universiti Putra Malaysia


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.

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Human Blood Outcomes Following Tocotrienol Supplementation – NUTRITION Phase I and Phase IIA

Chandan K Sen, Ph.D. Andrew Slivka, MD Cameron Rink, PhD


Objective: Plan to conduct two trials (I & IIA) to determine the effects of orally supplemented TCT on platelet function and cholesterol.

Study type: Interventional

Study Design: Randomized, Double-blind

Subjects: Phase I – healthy volunteers; Phase IIa- hyperlipidemic subjects

Intervention: Tocotrienol, low dose aspirin

Primary Outcome: 1) Platelet function panel. Blood draw followed by platelet aggregometry.

2) Lipid profile. Blood lipid panel including HDL, LDL, total cholesterol

Secondary Outcome: Tape Stripping Test. HPLC vitamin E analysis of tape strips for compliance

Methodology: We plan to conduct two trials (I & IIA) to determine the effects of orally supplemented TCT on platelet function and cholesterol. Phase I subjects will be healthy volunteers, recruited by an advertisement. Phase IIA subjects will be hyperlipidemic (having high cholesterol), and will be referred to us by their Wound Care Center Physicians. Patients will be randomized to receive placebo pills, (400 or 800 mg) TCT pills, low-dose 81 mg aspirin (commonly used for secondary prevent stroke), or TCT and aspirin together. potential subjects for Phase-I who meet study criteria and agree to participate will be in the study for 6 months and have following study related procedures,blood draw total 3 times, tape stripping(non-invasive procedure) and blood pressure measurement in each visit (every month). For participants in Phase-IIA will have total 5 times blood draw, tape stripping and blood pressure measurement and participants will be in the study for 12 months.

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A Double Blind Placebo Controlled Study On The Neuroprotective And Anti-Atherogenic Effects Of Palm Tocotrienol Rich Fraction (Palm Vitamin E)

Yuen Kah Hay, Phd


Objective: The purpose of the study is to assess the neuroprotective, anti atherogenic and hepatoprotective properties of tocotrienols (palm vitamin E) supplementation as determined by white matter lesion load on serial magnetic resonance imaging (MRI), carotid artery magnetic resonance angiography (MRA) and liver ultrasound (US) as well as lipid profile analysis.

Study Type: Interventional

Study Design:  Phase 2, Randomized, Double –Blind

Subjects: Patients with cerebrovascular disorders

Intervention: Tocotrienol, placebo

Primary Outcome: Regression of white matter lesion load in terms of numbers and size in the brain [ Time Frame: 1 to 2 years ]

Secondary Outcome: 1) Regression of the carotid artery stenoses in terms of percentage [ Time Frame: 1 to 2 years ]

2) The improvement in the lipid profile other markers associated with increased cardiovascular risk [ Time Frame: 1 to 2 years ]

3) Improvement in liver echogenicity. [ Time Frame: 1 to 2 years ] [ Designated as safety issue: No ]

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