Dyslipidemia

Comparative study of the effect of tocotrienols and -tocopherol on fasting serum lipid profiles in patients with mild hypercholesterolaemia: A preliminary report

Ajuluchukwu JN, Okubadejo NU, Mabayoje M, Ojini FI, Okwudiafor RN, Mbakwem AC, Fasanmade OA, Oke DA.

Niger Postgrad Med J. 2007 Mar;14(1):30-3.

Published

Objectives: This study examined the effect of tocotrienols (TOCOVIDTM Suprabio TM ) on serum lipids.

Study design: A randomised, open-label study

Subjects: Patients with mild hypercholesterolemia and one additional cardiovascular risk factor

Intervention: Tocotrienol versus vitamin E (alpha-tocopherol) 500mg daily

Primary outcome: Fasting Lipid levels

Methodology: A randomised (2:1), open-label study of patients with mild hypercholesterolaemia (= 5.18mmol/L to <7.77mmol/L) and one additional cardiovascular risk factor was carried out. Subjects received either tocotrienols (n=28) or vitamin E (alpha-tocopherol) 500mg daily (n=16). Fasting lipids were compared at baseline and after 4 weeks therapy.

Results: Following 4 weeks therapy, mean +/- SD total cholesterol declined significantly in the tocotrienol group (from 6.10+/-0.66 to 5.47+/-1.16; P=0.02) compared to the a-tocopherol group (from 5.92+/-0.52 to 5.47+/-0.76; P>0.05). Mean LDL-C levels (mmol/L) were also significantly reduced in the tocotrienol group (3.82+/-0.85 to 3.24+/-1.26; P=0.04), but not in those on a-tocopherol(3.84+/-0.75 to 3.28+/-0.94; P>0.05). There were no significant changes in HDL-C and triglycerides in both groups. The tocotrienol group experienced a net decline in TG (7.1+/-31.4 %; P>0.05) while the a-tocopherol group had a net increase at week 4 (38.6+/-61.7%; P>0.05).

Conclusion: The study adds to existing evidence of the favourable effect of tocotrienols on total cholesterol and LDL-C. However, the results need further evaluation.

Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E

Rasool AH, Yuen KH, Yusoff K, Wong AR, Rahman AR.

J Nutr Sci Vitaminol (Tokyo). 2006 Dec;52(6):473-8.

Published

Objectives: To assess the effects of 3 doses of tocotrienol-rich vitamin E (TRE) on plasma tocotrienol isomer concentration, arterial compliance, plasma total antioxidant status (TAS), aortic systolic blood pressure (ASBP), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in healthy males.

Study design: Randomised, blinded end-point, placebo-controlled

Subjects: Healthy male volunteers

Intervention: Tocotrienol-rich Vitamin E at 80 mg, 160 mg or 320 mg versus placebo

Primary outcome: Plasma tocotrienol isomer concentration, arterial compliance, plasma total antioxidant status (TAS), aortic systolic blood pressure (ASBP), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C)

Methodology: This randomised, blinded end-point, placebo-controlled clinical trial with a parallel design involved 36 healthy male subjects who took either an oral placebo or TRE at doses of 80, 160 or 320 mg daily for 2 mo. Baseline and end-of-treatment measurements of vitamin E concentration, arterial compliance [assessed by aortic femoral pulse wave velocity (PWV) and augmentation index (AI)], ASBP, plasma TAS, serum TC and LDL-C were taken.

Results: Baseline tocotrienol isomer concentrations were low and not detectable in some subjects. Upon supplementation, all TRE-treated groups showed significant difference from placebo for their change in alpha, gamma and delta tocotrienol concentrations from baseline to end of treatment. There was a linear dose and blood level relationship for all the isomers. There was no significant difference between groups for their change in PWV, AI, plasma TAS, ASBP, TC or LDL-C from baseline to end of treatment. Groups 160 mg (p = 0.024) and 320 mg (p = 0.049) showed significant reductions in their ASBP. Group 320 mg showed a significant 9.2% improvement in TAS.

Conclusion: TRE at doses up to 320 mg daily were well tolerated. Treatment significantly increased alpha, delta, and gamma tocotrienolconcentrations but did not significantly affect arterial compliance, plasma TAS, serum TC or LDL-C levels in normal subjects.

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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.

Published

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.

Published

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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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.

Effect of a Palm-Oil Vitamin E Concentrate on the Serum and Lipoprotein Lipids in Humans

Tan DT, Khor HT, Low WH, Ali A, Gapor A.

Am J Clin Nutr. 1991 Apr;53(4 Suppl):1027S-1030S.

Published

Objectives: To assess the effect of a capsulated palm-oil-vitamin E concentrate (Palmvitee) on human serum and lipoprotein lipids.

Subjects: Healthy volunteers

Intervention: Palm-oil vitamin E concentrate (18 mg tocotrienol)

Primary outcome: Serum lipids and lipoproteins

Methodology: All volunteers took one palmvitee capsule per day for 30 consecutive days. Overnight fasting blood was taken from each volunteer before and after the experiment. Serum lipids and lipoproteins were analyzed by using the enzymatic CHOD-PAP method.

Results: Our results showed that palmvitee lowered both serum total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) concentrations in all the volunteers. The magnitude of reduction of serum TC ranged from 5.0% to 35.9% whereas the reduction of LDL-C values ranged from 0.9% to 37.0% when compared with their respective starting values. Theeffect of palmvitee on triglycerides (TGs) and HDL-C was not consistent.

Conclusion: The results show that the palmvitee has a hypocholesterolemic effect.

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Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (Palmvitee)

Qureshi AA, Qureshi N, Wright JJ, Shen Z, Kramer G, Gapor A, Chong YH, DeWitt G, Ong A, Peterson DM, et al.

Am J Clin Nutr. 1991 Apr;53(4 Suppl):1021S-1026S.

Published

Objectives: The present study was carried out to assess the effect of tocotrienol-rich fraction as a dietary supplement in hypercholesterolemic human subjects.

Study design: Double-blind, crossover, 8 week study

Subjects: Subjects with elevated cholesterol levels

Intervention: Tocotrienol-rich fraction (Palmvitee) 200 mg versus placebo (300 mg corn oil capsules)

Primary outcome: To determine the cholesterol lowering effect of palmvitee

Methodology: A double-blind, crossover experimental design was used to control within-subject variability of cholesterol measurements and the effect of order of the administration of the two supplements (palmvitec and corn oil for a placebo). Subjects were radomly assigned to one of two groups. In group I, each subject was observed for 2-wk baseline period, a 4-wk palmvitee-capsule supplementation period, and a 4-wk corn-oil-capsule supplementation period. In group II, each subject was observed for a 2 wk baseline period, a 4-wk corn-oil-capsule supplementation period, and a 4-6-wk palmvitee supplementation period.

Results: Concentrations of serum total cholesterol (-15%), LDL cholesterol (-8%), Apo B (-10%), thromboxane (-25%), platelet factor 4 (-16%), and glucose (-12%) decreased significantly only in the 15 subjects given palmvitee during the initial 4 wk. The crossover confirmed these actions of palmvitee. There was a carry over effect of palmvitee. Serum cholesterol concentrations of seven hypercholesterolemic subjects (greater than 7.84 mmol/L) decreased 31% during a 4-wk period in which they were given 200 mg gamma-tocotrienol/d.

Conclusion: This indicates that gamma-tocotrienol may be the most potent cholesterol inhibitor in palmvitee capsules. The results of this pilot study are very encouraging.

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