Monthly Archives: December 2012

Completed

Objective: Despite the emerging interest in tocotrienols, the absorption of tocotrienols in humans remains unclear especially with different fat diets. This study aimed at evaluating the absorption and distribution of tocotrienols in plasma and lipoproteins in associations with high and low fat diets. Different fat level will affect the absorption and distribution of tocotrienols.

Study Type: Interventional

Study Design: Randomized, single blind, cross-over

Subjects: Healthy Volunteers

Intervention: Tocotrienol

Primary Outcome:

  • Plasma, chylomicron, and HDL level of tocotrienol [Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 24 hours after tocotrienol administration and intake of designated meal ]

Methodology: Not available

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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.

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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.

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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.

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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.

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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. ]

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Effect of Mixed-Tocotrienols in Hypercholesterolemic Subjects

Kah Hay Yuen, Jia Woei Wong, Ai Beoy Lim, Bee Hong Ng, Wai Peng Choy

Functional Foods in Health and Disease: 3:106-117

Published

Objectives: Aims to investigate the cholesterol lowering activity of tocotrienols.

Study design: Randomized, double blind study

Subjects: Hypercholesterolemic patients

Intervention: Mixed tocotrienol 300 mg versus placebo (soya bean oil 300 mg)

Primary outcome: Tocotrienol and tocopherol concentrations and serum cholesterol levels

Methodology: Thirty-two hypercholesterolemic subjects were randomly assigned to orally receive either 300 mg of mixed tocotrienols capsules daily or placebo capsules containing 300 mg of soya bean oil for a period of 6 months. The subjects were monitored before supplementation and monthly thereafter for their serum cholesterol as well as tocotrienol and tocopherol concentrations.

Results: The serum total cholesterol and low density lipoprotein (LDL) cholesterol of the subjects in the tocotrienol supplementation group were decreased significantly by 8.9 ± 0.9% and 12.8 ± 2.6% respectively after 4 months of supplementation and the reduction persisted till the end of the 6-month study, with a reduction of 10.8 ± 1.0% and 17.3 ± 1.8%, respectively from baseline. Moreover, there was a 22fold increase in the total tocotrienol concentrations from baseline during supplementation compared to the placebo group, while the concentration of α-tocopherol recorded only a modest increase. On the other hand, the serum cholesterol, total tocotrienol and α-tocopherol concentrations of subjects in the placebo group remained essentially unchanged.

Conclusion: Supplementation with mixed tocotrienols at dose of 300 mg per day resulted in the lowering of the serum total and LDL cholesterol levels after 5 months of supplementation.

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Tocotrienol Emerges a Winner Among the Vitamin E Family Constituents For Its Role In Maintaining Lipid Balance

Vanessa Y. Lacuesta, Fong Chee Wai

WHO report states that cardiovascular disease (CVD) remains a leading cause of death and disability worldwide. Though preventable, an  expected 23.6 million people will die mainly from CVD by 2030. To help support cardiovascular health, the majority of nutraceuticals are directed towards promoting heart and blood vessel health through reduction in the level of body lipids such as cholesterol and triglyceride.

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Delta-tocotrienol suppresses Notch-1 pathway by upregulating miR-34a in nonsmall cell lung cancer cells

Ji, X., Wang, Z., Geamanu, A., Goja, A., Sarkar, F. H., Gupta, S. V.

Int J Cancer. 2012 Dec 1;131(11):2668-77.

MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in regulating various cellular functions by transcriptional silencing. miRNAs can function as either oncogenes or tumor suppressors (oncomirs), depending on cancer types. In our study, using miRNA microarray, we observed that downregulation of the Notch-1 pathway, by delta-tocotrienol, correlated with upregulation of miR-34a, in nonsmall cell lung cancer cells (NSCLC). Moreover, re-expression of miR-34a by transfection in NSCLC cells resulted in inhibition of cell growth and invasiveness, induction of apoptosis and enhanced p53 activity. Furthermore, cellular mechanism studies revealed that induction of miR-34a decreased the expression of Notch-1 and its downstream targets including Hes-1, Cyclin D1, Survivin and Bcl-2. Our findings suggest that delta-tocotrienol is a nontoxic activator of mir-34a which can inhibit NSCLC cell proliferation, induce apoptosis and inhibit invasion, and thus offering a potential starting point for the design of novel anticancer agents.

A Phase I Dose-Escalation Study Evaluating the Pharmacokinetics, Safety and Tolerability of Oral Gamma-Delta-Tocotrienol (GDT) in Patients with Castration-Resistant Prostate Cancer (CRPC)

Prof Azad Hassan A. Razack, University of Malaya Medical Centre, Malaysia

Ongoing

Objective:  In this study, we intend to determine Gamma-Delta Tocotrienol’s (GDT) safety and tolerability in patients with castrate-resistant prostate cancer (CRPC). In addition, GDT’s pharmacokinetic profile in this cohort of patients will be investigated.

Study Type: Interventional

Study Design: Dose-escalation, pharmacokinetics study

Subjects: Castrate-resistant prostate cancer patients

Intervention: Gamma-Delta Tocotrienol (GDT; Davos Life Science Pte Ltd)

Primary Outcome:

  • Safety and tolerability
  • GDT isomer plasma concentration [ time frame: 0, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours ]

Secondary Outcome: Circulating tumor cell (CTC) levels and inflammatory biomarkers (IL-8, MCP-1, MIP-1 alpha, IFN-gamma, IL-1B, IL-4, IL-6, IL-10, IL-12 (p70), IL-17A, Il-23, IL-27, TNF-alpha, MIP-3 alpha, CRP) [time frame: baseline and day 22]

Methodology: During pharmacokinetic evaluation wherein GDT will be taken as a single dose, participants will receive oral GDT for 21 days at 400, 800, 1600, 2400 and 3200 mg/day for 21 days. Pharmakokinetic and safety profiles will be evaluated on the 8th, 15th and 22nd day.