Effect of Tocotrienols enriched canola oil on glycemic control and oxidative status in patients with type 2 diabetes mellitus: A randomized double-blind placebo-controlled clinical trial.

Vafa M, Haghighat N, Moslehi N, Eghtesadi S, Heydari I.

J Res Med Sci. 2015 Jun;20(6):540-7



Tocotrienols have been shown to improve glycemic control and redox balance in an animal study, but their effects on patients with diabetes are unknown. The study aimed to investigate whether tocotrienols improves glycemic control, insulin sensitivity, and oxidative stress in individuals with type 2 diabetes mellitus (T2DM).


This study was a double-blinded, placebo-controlled, randomized trial. A total of 50 patients, aged 35-60 years, with T2DM treated by noninsulin hypoglycemic drugs were randomly assigned to receive either 15 mL/day tocotrienols (200 mg) enriched canola oil (n = 25) or pure canola oil (n = 25) for 8 weeks. Fasting blood sugar (FBS), fasting insulin, total antioxidant capacity (TAC), malondialdehyde (MDA), and homeostatic model assessment for insulin resistance (HOMA-IR) were determined before and after the intervention. The data were compared between and within groups, before and after the intervention.


Baseline characteristics of participants including age, sex, physical activity, disease duration, and type of drug consumption were not significantly different between the two groups. In tocotrienol enriched canola oil, FBS (mean percent change: -15.4% vs. 3.9%; P = 0.006) and MDA (median percent change: -35.6% vs. 16.3%; P = 0.003) were significantly reduced while TAC was significantly increased (median percent change: 21.4% vs. 2.3%; P = 0.001) compared to pure canola oil. At the end of the study, patients who treated with tocotrienols had lower FBS (P = 0.023) and MDA (P = 0.044) compared to the pure canola oil group. However, tocotrienols had no effect on insulin concentrations and HOMA-IR.


Tocotrienols can improve FBS concentrations and modifies redox balance in T2DM patients with poor glycemic control and can be considered in combination with hypoglycemic drugs to better control of T2DM.

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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


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

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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The Acute Effects of Supplementation of Tocotrienols on Insulin Sensitivity and Metabolic Risk Markers in Individuals at Risk for Metabolic Syndrome

Dr Teng Kim Tiu, PhD, Universiti Malaya


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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The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia

Baliarsingh S, Beg ZH, Ahmad J.

Atherosclerosis. 2005 Oct;182(2):367-74. Epub 2005 Apr 20.


Objectives: In this study, we investigated the therapeutic impacts of tocotrienols on serum and lipoprotein lipid levels in type 2 diabetic patients. Based on known tocotrienol rich fraction (TRF)-mediated decrease on elevated blood glucose and glycated hemoglobin A(1C) (HbA(1C)) in diabetic rats, we have also investigated the effect of TRF on these parameters.

Study design: Randomized, double blind, placebo-controlled design

Subjects: Subjects with type 2 diabetic and hyperlipidemia

Intervention: Tocotrienol-rich fraction versus placebo

Primary outcome: Serum total cholesterol and LDL levels

Methodology: Subjects were first treated to 60 days of TRF treatment after which their serum total lipids, TC and LDL-C were measured.

Results: Subjects showed an average decline of 23, 30, and 42% in serum total lipids, TC, and LDL-C, respectively. The goal in type 2 diabetics is to reduce LDL-C levels < or = 100mg/dl. In the present investigation tocotrienols mediated a reduction of LDL-C from an average of 179 mg/dl to 104 mg/dl. However, hypoglycemic effect of TRF was not observed in these patients because they were glycemically stable and their glucose and HbA(1) levels were close to normal values.

Conclusion: Daily intake of dietary TRF by type 2 diabetics will be useful in the prevention and treatment of hyperlipidemia and atherogenesis.

Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia

Mustad VA, Smith CA, Ruey PP, Edens NK, DeMichele SJ.

Am J Clin Nutr. 2002 Dec;76(6):1237-43.


Objectives: The objective was to study the relative effect of tocotrienol supplements of different compositions (mixed alpha- plus gamma-, high gamma-, or P25-complex tocotrienol) on blood lipids, fasting blood glucose, and the excretion of 8-iso-prostaglandin F(2alpha), a measure of oxidative stress, in healthy hypercholesterolemic men and women.

Study design: Double-blind, randomized, parallel-design study

Subjects: Healthy hypercholesterolemic subjects

Intervention: Mixed tocotrienol versus placebo (safflower oil)

Primary outcome: Fasting blood lipids, fasting blood glucose, and the excretion of 8-iso-prostaglandin F(2alpha), a measure of oxidative stress.

Methodology: In this study, subjects consumed 1 of 3 commercially available tocotrienol supplements or a safflower oil placebo for 28 days. Blood and urine samples were obtained before and after the 28-d supplementation phase for analysis of fasting blood lipids, glucose, tocotrienols and tocopherols, and 8-iso-prostaglandin F(2alpha).

Results: Overall, serum tocotrienols were increased in subjects who consumed tocotrienols, which showed that the putatively active components were absorbed. No significant differences in mean lipid or glucose concentrations were observed among the 4 treatment groups at the end of the 28-dsupplementation phase. However, when the values were expressed as a percentage change from the concentrations during the presupplementation run-in phase, LDL cholesterol increased slightly (7 +/- 2%) but significantly (P < 0.05) in the group consuming the mixed alpha- plus gamma-tocotrienol supplement when compared with LDL cholesterol in the group consuming the P25-complex tocotrienol. Neither mean concentrations nor the percentage change in 8-iso-prostaglandin F(2alpha) differed significantly among treatments.

Conclusion: Supplementation with 200 mg tocotrienols/d from 3 commercially available sources has no beneficial effect on key cardiovascular disease risk factors in highly compliant adults with elevated blood lipid concentrations.

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