With a growing number of dietary interventions that claim to improve lipid profile, it is important to ensure that these claims are evidence based. The objective of this study was to make recommendations for dietary regimens by analyzing their effectiveness and the level of evidence. We searched MEDLINE as well as the Cochrane Database of Systematic Reviews for nutritional studies. Meta-analyses and randomized controlled trials published in English and including data on the effect on blood lipid levels were used. Randomized controlled trials were included if they were at least 4 weeks in duration and had a minimum of 50 participants. We identified 22 different dietary interventions and reviewed 136 studies published between January 1990 and December 2009 that met our inclusion criteria. Our literature review showed that to improve lipid profile, the following regimens can be recommended fully: Mediterranean and Portfolio diets; low-fat diet; diet high in soy protein, fibre, or phytosterols; whole grain foods, and omega-3 fatty acid supplementation. The consumption of nuts, a diet high in carbohydrates and protein, green tea, and red wine, as well as the supplementation with policosanol and red yeast rice extract, can be considered for improvement of the lipid profile, while the supplements of guggulipid, garlic, chromium, vitamin C, magnesium-pyridoxal-phosphate-glutamate, tocotrienols, and absorbitol cannot be recommended.
Metabolic Syndrome
Nutrapharmacology of tocotrienols for metabolic syndrome
Weng-Yew W, Brown L.
Curr Pharm Des. Volume 17, Number 21, July 2011
Metabolic syndrome is defined as a set of health risk factors that are associated with an increased chance of cardiovascular diseases and type 2 diabetes. These include abdominal obesity, hyperglycemia, impaired glucose tolerance, dyslipidemia, and hypertension. Interventions in metabolic syndrome include lifestyle interventions such as a healthy diet using functional foods together with increased physical activity to induce weight loss as the first aim of treatment. Nutraceuticals such as tocotrienols and tocopherols as members of the vitamin E family may be more targeted interventions. This review evaluates the effects of tocotrienols on the risk factors of metabolic syndrome using data from human, animal and in vitro studies. Tocotrienols improved lipid profiles and reduced atherosclerotic lesions, decreased blood glucose and glycated hemoglobin concentrations, normalized blood pressure, and inhibited adipogenesis. The differences in responses between tocopherols and tocotrienols in preventing obesity, diabetes, hypertension, artherosclerosis, ischemia, and inflammation suggest that different receptors or signaling mechanisms may be involved.
Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study
Chin, S. F.,Ibahim, J.,Makpol, S.,Abdul Hamid, N. A.,Abdul Latiff, A.,Zakaria, Z.,Mazlan, M.,Mohd Yusof, Y. A.,Abdul Karim, A.,Wan Ngah, W. Z.
Nutr Metab (Lond) 2011;8(1):42
Abstract
Background: Vitamin E supplements containing tocotrienols are now being recommended for optimum health but its effects are scarcely known. The objective was to determine the effects of Tocotrienol Rich Fraction (TRF) supplementation on lipid profile and oxidative status in healthy older individuals at a dose of 160 mg/day for 6 months.
Methods: Sixty-two subjects were recruited from two age groups: 35-49 years (n = 31) and above 50 years (n = 31), and randomly assigned to receive either TRF or placebo capsules for six months. Blood samples were obtained at 0, 3rd and 6th months.
Results: HDL-cholesterol in the TRF-supplemented group was elevated after 6 months (p < 0.01). Protein carbonyl contents were markedly decreased (p < 0.001), whereas AGE levels were lowered in the > 50 year-old group (p < 0.05). Plasma levels of total vitamin E particularly tocopherols were significantly increased in the TRF-supplemented group after 3 months (p < 0.01). Plasma total tocotrienols were only increased in the > 50 year-old group after receiving 6 months of TRF supplementation. Changes in enzyme activities were only observed in the > 50 year-old group. SOD activity was decreased after 3 (p < 0.05) and 6 (p < 0.05) months of TRF supplementation whereas CAT activity was decreased after 3 (p < 0.01) and 6 (p < 0.05) months in the placebo group. GPx activity was increased at 6 months for both treatment and placebo groups (p < 0.05).
Conclusion: The observed improvement of plasma cholesterol, AGE and antioxidant vitamin levels as well as the reduced protein damage may indicate a restoration of redox balance after TRF supplementation, particularly in individuals over 50 years of age.
δ-Tocotrienol and quercetin reduce serum levels of nitric oxide and lipid parameters in female chickens
Qureshi AA, Reis JC, Qureshi N, Papasian CJ, Morrison DC, Schaefer DM.
Lipids Health Dis. 2011 Feb 28;10:39.
Background: Chronic, low-grade inflammation provides a link between normal ageing and the pathogenesis of age-related diseases. A series of in vitro tests confirmed the strong anti-inflammatory activities of known inhibitors of NF-κB activation (δ-tocotrienol, quercetin, riboflavin, (-) Corey lactone, amiloride, and dexamethasone). δ-Tocotrienol also suppresses β-hydroxy-β-methylglutaryl coenzyme A (HMG-CoA) reductase activity (the rate-limiting step in de novo cholesterol synthesis), and concomitantly lowers serum total and LDL cholesterol levels. We evaluated these compounds in an avian model anticipating that a dietary additive combining δ-tocotrienol with quercetin, riboflavin, (-) Corey lactone, amiloride, or dexamethasone would yield greater reductions in serum levels of total cholesterol, LDL-cholesterol and inflammatory markers (tumor necrosis factor-α [TNF-α], and nitric oxide [NO]), than that attained with the individual compounds.
Results: The present results showed that supplementation of control diets with all compounds tested except riboflavin, (-) Corey lactone, and dexamethasone produced small but significant reductions in body weight gains as compared to control. (-) Corey lactone and riboflavin did not significantly impact body weight gains. Dexamethasone significantly and markedly reduced weight gain (>75%) compared to control. The serum levels of TNF-α and NO were decreased 61% – 84% (P < 0.001), and 14% – 67%, respectively, in chickens fed diets supplemented with δ-tocotrienol, quercetin, riboflavin, (-) Corey lactone, amiloride, or dexamethasone as compared to controls. Significant decreases in the levels of serum total and LDL-cholesterol were attained with δ-tocotrienol, quercetin, riboflavin and (-) Corey lactone (13% – 57%; P < 0.05), whereas, these levels were 2-fold higher in dexamethasone treated chickens as compared to controls. Parallel responses on hepatic lipid infiltration were confirmed by histological analyses. Treatments combining δ-tocotrienol with the other compounds yielded values that were lower than individual values attained with either δ-tocotrienol or the second compound. Exceptions were the significantly lower total and LDL cholesterol and triglyceride values attained with the δ-tocotrienol/(-) Corey lactone treatment and the significantly lower triglyceride value attained with the δ-tocotrienol/riboflavin treatment. δ-Tocotrienol attenuated the lipid-elevating impact of dexamethasone and potentiated the triglyceride lowering impact of riboflavin. Microarray analyses of liver samples identified 62 genes whose expressions were either up-regulated or down-regulated by all compounds suggesting common impact on serum TNF-α and NO levels. The microarray analyses further identified 41 genes whose expression was differentially impacted by the compounds shown to lower serum lipid levels and dexamethasone, associated with markedly elevated serum lipids.
Conclusion: This is the first report describing the anti-inflammatory effects of δ-tocotrienol, quercetin, riboflavin, (-) Corey lactone, amiloride, and dexamethasone on serum TNF-δ and NO levels. Serum TNF-δ levels were decreased by >60% by each of the experimental compounds. Additionally, all the treatments except with dexamethasone, resulted in lower serum total cholesterol, LDL-cholesterol and triglyceride levels. The impact of above mentioned compounds on the factors evaluated herein was increased when combined with δ-tocotrienol.
Comparative hypoglycemic and nephroprotective effects of tocotrienol rich fraction (TRF) from palm oil and rice bran oil against hyperglycemia induced nephropathy in type 1 diabetic rats
Siddiqui S, Rashid Khan M, Siddiqui WA.
Chem Biol Interact. 2010 Dec 5;188(3):651-8.
Diabetic nephropathy (DN) is a serious complication confronted by patients with diabetes. Available data indicate that the development of DN is linked to hyperglycemia. Tocotrienol rich fraction (TRF) from palm oil (PO) and rice bran oil (RBO) has been shown to lower the blood glucose level in patients and preclinical animal models. This study was designed to investigate if TRF from PO and RBO could improve the renal function in DN by the virtue of their hypoglycemic and antioxidant activities. Male Wistar rats having an average body weight (bw) 250g were divided into four groups of six each .The first group served as diabetic control [injected with 55mg/kg bw of streptozotocin (STZ), intraperitoneally], while the second and third group received PO-TRF and RBO-TRF, respectively, by gavage at a dose of 200mg/kg bw/day, over a period of 8 weeks post-induction of diabetes. The fourth group comprised of age-matched male Wistar rats that received single intraperitoneal injection of normal saline only and served as control. After 8 weeks of STZ injection and TRF treatment, 24h urine was collected and animals were sacrificed. Fasting blood glucose, glycosylated hemoglobin, biochemical markers of renal function and oxidative stress were evaluated in serum, urine and kidney tissue. The results show that treatment with PO-TRF as well as RBO-TRF significantly improved the glycemic status and renal function in type 1 diabetic rats but PO-TRF afforded greater efficiency at similar dose as compared to RBO-TRF. In conclusion, PO-TRF was found to be more effective hypoglycemic and nephroprotective agent in DN than RBO-TRF.
Palm oil tocotrienol fractions restore endothelium dependent relaxation in aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats
Muharis, S. P.,Top, A. G.,Murugan, D.,Mustafa, M. R.
Nutr Res, 2010. 30(3): 209-16.
Diabetes and hypertension are closely associated with impaired endothelial function. Studies have demonstrated that regular consumption of edible palm oil may reverse endothelial dysfunction. The present study investigates the effect of palm oil fractions: tocotrienol rich fraction (TRF), alpha-tocopherol and refined palm olein (vitamin E-free fraction) on the vascular relaxation responses in the aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats (SHR). We hypothesize that the TRF and alpha-tocopherol fractions are able to improve endothelial function in both diabetic and hypertensive rat aortic tissue. A 1,1-diphenyl picryl hydrazyl assay was performed on the various palm oil fractions to evaluate their antioxidant activities. Endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxations were examined on streptozotocin-induced diabetic and SHR rat aorta following preincubation with the different fractions. In 1-diphenyl picryl hydrazyl antioxidant assay, TRF and alpha-tocopherol fractions exhibited a similar degree of activity while palm olein exhibited poor activity. TRF and alpha-tocopherol significantly improved acetylcholine-induced relaxations in both diabetic (TRF, 88.5% +/- 4.5%; alpha-tocopherol, 87.4% +/- 3.4%; vehicle, 65.0 +/- 1.6%) and SHR aorta (TRF, 72.1% +/- 7.9%; alpha-tocopherol, 69.8% +/- 4.0%, vehicle, 51.1% +/- 4.7%), while palm olein exhibited no observable effect. These results suggest that TRF and alpha-tocopherol fractions possess potent antioxidant activities and provide further support to the cardiovascular protective effects of palm oil vitamin E. TRF and alpha-tocopherol may potentially improve vascular endothelial function in diabetes and hypertension by their sparing effect on endothelium derived nitric oxide bioavailability.
Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion
Zaiden N, Yap WN, Ong S, Xu CH, Teo VH, Chang CP, Zhang XW, Nesaretnam K, Shiba S, Yap YL.
J Atheroscler Thromb. 2010 Oct 27;17(10):1019-32.
Abstract
Aim: Present study aimed to elucidate the suppression of serum lipids by gamma- and delta-tocotrienol (γδT3).
Methods: The lipid-lowering effects of γδT3 were investigated using HepG2 liver cell line, hypercholesterolemic mice and borderline-high cholesterol patients.
Results: In-vitro results demonstrated two modes of action. First, γδT3 suppressed the upstream regulators of lipid homeostasis genes (DGAT2, APOB100, SREBP1/2 and HMGCR) leading to the suppression of triglycerides, cholesterol and VLDL biosyntheses. Second, γδT3 enhanced LDL efflux through induction of LDL receptor (LDLr) expression. Treatment of LDLr-deficient mice with 1 mg/day (50 mg/kg/day) γδT3 for one-month showed 28%, 19% reduction in cholesterol and triglyceride levels respectively, whereas HDL level was unaltered. The lipid-lowering effects were not affected by alpha-tocopherol (αTP). In a placebo-controlled human trial using 120 mg/day γδT3, only serum triglycerides were lowered by 28% followed by concomitant reduction in the triglyceride-rich VLDL and chylomicrons. In contrast, total cholesterol, LDL and HDL remained unchanged in treated and placebo groups. The discrepancies between in-vitro, in-vivo and human studies may be attributed to the differential rates of post-absorptive γδT3 degradation and LDL metabolism.
Conclusion: Reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting γδT3 in human.
Protective effects of vitamin E analogs against carbon tetrachloride-induced fatty liver in rats
Yachi R, Igarashi O, Kiyose C.
J Clin Biochem Nutr. 2010 Sep;47(2):148-54. Epub 2010 Aug 6.
Recently, it has been reported that α-tocopherol (α-Toc) is effective for amelioration of liver damage. However, it is unknown whether other vitamin E analogs are effective. In this study, we investigated the effects of γ-tocopherol (γ-Toc) and tocotrienols (T3) in rats with fatty liver. Rats fed a vitamin E-deficient diet for four weeks were divided into eight groups: Control, carbon tetrachloride (CCl(4)), α-Toc, α-Toc + CCl(4), γ-Toc, γ-Toc + CCl(4), T3 mix, T3 mix + CCl(4). After a 24 h fast, the rats were administered 20 mg of each of the vitamin E analogs, respectively. Moreover, the CCl(4) group were given 0.5 ml/kg body weight corn oil preparation containing CCl(4) 6 h after vitamin E administration. We measured the activities of aspartate aminotransferase and alanine aminotransferase (ALT) in plasma, and the contents of triglyceride (TG), total cholesterol (T-Chol) and vitamin E analogs in the liver. Also, we determined the hepatic expression of mRNA for inflammatory cytokines. The liver TG content in the γ-Toc + CCl(4) and T3 mix + CCl(4) groups was decreased in comparison with the CCl(4) group. Moreover, ALT activity in the T3 mix + CCl(4) group was significantly lower than CCl(4) group. These findings suggest that γ-Toc and T3 are effective for amelioration of fatty liver.
Vitamin E for Nonalcoholic Steatohepatitis: Ready for Prime Time?
Sanyal AJ, Chalasani N, Kowdley KV, McCullough A,Diehl AM, Bass NM, et al.
Hepatology. 2010 Aug;52(2):789-92.
Recent results show that alpha-tocopheryl succinate (alpha-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of alpha-TOS with lower number of methyl substitutions on the aromatic ring were less active than alpha-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on alpha-TOS and delta-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. alpha-tocotrienol (alpha-T3 H) failed to induce apoptosis, while gamma-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of gamma-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.
Tocotrienol enriched palm oil prevents atherosclerosis through modulating the activities of peroxisome proliferators-activated receptors
Li F, Tan W, Kang Z, Wong CW.
Atherosclerosis. 2010 Jul;211(1):278-82. Epub 2010 Jan 25.
Palm oil is enriched in vitamin E in the form of alpha-, gamma-, and delta-tocotrienols. Dietary tocotrienol supplements have been shown to prevent atherosclerosis development in patients and preclinical animal models. However, the mechanistic basis for this health beneficial effect is not well established. Peroxisome proliferator-activated receptors alpha, gamma, and delta (PPARalpha, PPARgamma, and PPARdelta) are ligand regulated transcription factors that play essential preventive roles in the development of atherosclerosis through regulating energy metabolism and inflammation. In this study, we presented data that the tocotrienol rich fraction (TRF) of palm oil activated PPARalpha, PPARgamma, and PPARdelta in reporter based assays. Importantly, TRF attenuated the development of atherosclerosis in ApoE-/- mice through inducing PPAR target gene liver X receptor alpha (LXRalpha) and its down-stream target genes apolipoproteins and cholesterol transporters, suggesting that modulating the activities of PPARs is a key aspect of the in vivo action of tocotrienols.