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

Abstract

BACKGROUND:

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).

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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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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.

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Suppression of Nitric Oxide Production and Cardiovascular Risk Factors in Healthy Seniors and Hypercholesterolemic Subjects by a Combination of Polyphenols and Vitamins

Qureshi AA, Khan DA, Mahjabeen W, Papasian CJ, Qureshi N.

J Clin Exp Cardiolog. 2012 Jun 7;S5:8.

Published

Objectives: To determine whether serum nitric oxide (NO) levels increase with age in humans, and whether the combined cholesterol-lowering and inflammation-reducing properties of resveratrol, pterostilbene, morin hydrate, quercetin, δ-tocotrienol, riboflavin, and nicotinic acid would reduce cardiovascular risk factors in humans when used as nutritional supplements with, or without, other dietary changes.

Subjects: Healthy Seniors and Hypercholesterolemic Subjects

Intervention: δ-tocotrienol, resveratrol, pterostilbene, Morin hydrate, quercetin, riboflavin, and nicotinic acid

Primary outcome: Serum NO, C-reactive protein (CRP), γ-glutamyltransferase (γ-GT) activity, uric acid, total antioxidant status (TAS), total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides levels

Methodology: Elderly human subjects were stratified into two groups based on total serum cholesterol levels. Initial total serum cholesterol levels were normal and elevated in Group 1 and 2 subjects, respectively. Baseline serum NO, C-reactive protein (CRP), γ-glutamyltransferase (γ-GT) activity, uric acid, total antioxidant status (TAS), total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides levels were established over a four week period. Group 1 subjects subsequently received nutritional supplementation with one of two different combinations (NS-7 = 25 mg of each, resveratrol, pterostilbene, quercetin, δ-tocotrienol, nicotinic acid, morin hydrate or NS-6 = morin hydrate replaced with quercetin, 50 mg/capsule). Group 2subjects also received these nutritional supplements (two capsules/d), but an AHA Step-1 diet was also implemented. After these interventions were administered for four weeks, the above parameters were re-measured and changes from baseline levels determined. Nitric acid (NO) levels in children, young adults, and seniors were also compared.

Results: The key results of the current study were: 1) that serum NO levels were significantly increased in seniors compared to both children (~80%) and young adults (~65%); 2) that the intake of two capsules/d of NS-7 or NS-6 for four weeks significantly (P < 0.05) decreased serum NO (39%, 24%), CRP (19%, 21%), uric acid (6%, 12%) levels, and γ-GT activity (8%, 6%), respectively in free-living healthy seniors; 3) that serum NO (36%, 29%), CRP (29%, 20%), uric acid (6%, 9%) γ-GT activity (9%, 18%), total cholesterol (8%, 11%), LDL-cholesterol (10%, 13%), and triglycerides (16%, 23%) levels were significantly (P < 0.02) decreased in hypercholesterolemic subjects restricted to AHA Step-1 diet plus intake of SN-7 or SN-6 (two capsules/d), respectively; 4) that TAS was increased (3%, 9%; P < 0.05) in free-living healthy seniors receiving NS-7 or NS-6 alone, and in hypercholesterolemic subjects plus AHA Step-1 diet (20%, 12%; P < 0.02) with either of the combinations tested.

Conclusions: Serum NO levels are elevated in elderly humans compared to children or young adults. Diet supplementation with combinations of resveratrol, pterostilbene, morin hydrate, quercetin, δ-tocotrienol, riboflavin, and nicotinic acid reduce cardiovascular risk factors in humans when used as nutritional supplements with, or without, other dietary changes.

Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis

Tomeo AC, Geller M, Watkins TR, Gapor A, Bierenbaum ML.

Lipids. 1995 Dec;30(12):1179-83.

Published

Objectives: Antioxidants may have a role in the prevention of atherosclerosis. In the present trial, we investigate the antioxidant properties of a gamma-tocotrienol (Palmvitee), and alpha-tocopherol enriched fraction of palm oil, in patients with carotid atherosclerosis.

Subjects: Patients with carotid atherosclerosis

Intervention: Gamma-Tocotrienol

Primary outcome: Serum lipids, fatty acid peroxides, platelet aggregation and changes in carotid artery stenosis (duplex ultrasonography)

Methodology:  In the present trial, we investigated the antioxidant properties of gamma-tocotrienol and alpha-tocopherol enriched fraction of palm oil, in patients with carotid atherosclerosis. Serum lipids, fatty acid peroxides, platelet aggregation and carotid artery stenosis were measured over an 18-month period in fifty patients with cerebrovascular disease. Change in stenosis was measured with duplex ultrasonography. Ultrasound scans were done at six months, twelve months, and yearly thereafter.

Results: Bilateral duplex ultrasonography revealed apparent carotid atherosclerotic regression in seven and progression in two of the 25 tocotrienol patients, while none of the control group exhibited regression and ten of 25 showed progression (P < 0.002). Serum thiobarbituric acid reactive substances, an ex vivo indicator of maximal platelet peroxidation, decreased in the treatment group from 1.08 +/- 0.70 to 0.80 +/- 0.55 microM/L (P < 0.05) after 12 mon, and in the placebo group, they increased nonsignificantly from 0.99 +/- 0.80 to 1.26 +/- 0.54 microM/L. Both tocotrienol and placebo groups displayed significantly attenuated collagen-induced platelet aggregation responses (P < 0.05) as compared with entry values. Serum total cholesterol, low density lipoprotein cholesterol, and triglyceride values remained unchanged in both groups, as did the plasma high density lipoprotein cholesterol values.

Conclusion: These findings suggest that antioxidants, such as tocotrienols, may influence the course of carotid atherosclerosis.

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