Hypolipidemic and antioxidant properties of tocotrienol rich fraction isolated from rice bran oil in experimentally induced hyperlipidemic rats

Minhajuddin M, Beg ZH, Iqbal J.

Food Chem Toxicol. 2005 May;43(5):747-53.

We investigated a dose-dependent hypolipidemic and antioxidant effect of tocotrienol rich fraction (TRF) isolated from rice bran oil on experimentally induced hyperlipidemic rats. Feeding of atherogenic diet (5% hydrogenated fat, 0.5% cholic acid and 1% cholesterol) for three weeks resulted in a significant increase in plasma triglyceride (3.3-fold) and total cholesterol (2.4-fold) levels. There was a 5-fold increase in the level of LDL cholesterol with only a small increase in HDL cholesterol. On the other hand, HMG-CoA reductase activity was significantly reduced in these animals. The formation of TBARS, thiobarbituric acid reactive substances, (86%) and conjugated dienes (78%) were also significantly higher in these rats compared to normals. After the induction of hyperlipidemia for three weeks, rats were supplemented with different doses of TRF for one week. TRF supplementation decreased the lipid parameters in a dose-dependent manner with an optimum effect at a dose of 8 mg TRF/kg/day. HMG-CoA reductase activity, which was increased after the withdrawal of atherogenic diet, remained significantly decreased during the TRF treatment. Feeding of TRF also decreased TBARS and conjugated dienes significantly. These results suggest that TRF supplementation has significant health benefits through the modulation of physiological functions that include various atherogenic lipid profiles and antioxidants in hypercholesterolemia.

Synergistic effects of tocopherol, tocotrienol, and ubiquinone in indomethacin-induced experimental gastric lesions

Nafeeza MI, Kang TT.

Int J Vitam Nutr Res. 2005 Mar;75(2):149-55.

Nonsteroidal anti-inflammatory drugs and their adverse effects on the gastric mucosa are yet another set of unresolved medical problems. This study examined the effects of various antioxidants on several gastric parameters after a single exposure to indomethacin. Forty-eight male rats of the Sprague-Dawley (200-250 g) strain were randomly divided to receive a single antioxidant (tocopherol, tocotrienol, or ubiquinone) or a combination of two (tocopherol-tocotrienol, tocopherol-ubiquinone or tocotrienol-ubiquinone) for 28 days. The rats were then challenged with a single dose of indomethacin and killed six hours later. Findings showed that the severity of gastric lesions was comparable in all groups. Only groups that received a combination of antioxidants exhibited reduced lipid peroxidation compared with all other groups (p < 0.05). The combination groups had a higher level of gastric prostaglandin E2 (PGE2) content compared with all other groups (p < 0.05). There was no significant difference among the groups in the gastric acid concentration and the glutathione/oxidized glutathione (GSH/GSSG) ratio. We conclude that although supplementation of these antioxidants in combination had desirable effects on lipid peroxidation and gastric PGE2 level, they did not reduce the lesions produced by indomethacin.

Tocotrienols: Constitutional effects in aging and disease

Sebastian Schaffer,2 Walter E. Mu¨ ller, and Gunter P. Eckert

J Nutr. 2005 Feb;135(2):151-4.

Tocotrienols, a class of vitamin E analogs, modulate several mechanisms associated with the aging process and aging-related diseases. Most studies compare the activities of tocotrienols with those of tocopherols (“classical vitamin E”). However, some biological effects were found to be unique for tocotrienols. Although the absorption mechanisms are essentially the same for all vitamin E analogs, tocotrienols are degraded to a greater extent than tocopherols. The levels of tocotrienols in the plasma of animals and humans were estimated to reach low micromolar concentrations. One hallmark in the origin of disease and aging is the overproduction of reactive oxygen species (ROS). Tocotrienols possess excellent antioxidant activity in vitro and have been suggested to suppress ROS production more efficiently than tocopherols. In addition, tocotrienols show promising nonantioxidant activities in various in vitro and in vivo models. Most notable are the interactions of tocotrienols with the mevalonate pathway leading to the lowering of cholesterol levels, the prevention of cell adhesion to endothelial cells, and the suppression of tumor cell growth. Furthermore, glutamate-induced neurotoxicity is suppressed in the presence of tocotrienols. This review summarizes the main antioxidant and nonantioxidant effects of tocotrienols and assesses their potential as health-maintaining compounds.

Read Full Article Here

Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not?

Barry Halliwell, Joseph Rafter, and Andrew Jenner

Am J Clin Nutr. 2005 Jan;81(1 Suppl):268S-276S.

Foods and beverages rich in phenolic compounds, especially flavonoids, have often been associated with decreased risk of developing several diseases. However, it remains unclear whether this protective effect is attributable to the phenols or to other agents in the diet. Alleged health-promoting effects of flavonoids are usually attributed to their powerful antioxidant activities, but evidence for in vivo antioxidant effects of flavonoids is confusing and equivocal. This may be because maximal plasma concentrations, even after extensive flavonoid intake, may be low (insufficient to exert significant systemic antioxidant effects) and because flavonoid metabolites tend to have decreased antioxidant activity. Reports of substantial increases in plasma total antioxidant activity after flavonoid intake must be interpreted with caution; findings may be attributable to changes in urate concentrations. However, phenols might exert direct effects within the gastrointestinal tract, because of the high concentrations present. These effects could include binding of prooxidant iron, scavenging of reactive nitrogen, chlorine, and oxygen species, and perhaps inhibition of cyclooxygenases and lipoxygenases. Our measurements of flavonoids and other phenols in human fecal water are consistent with this concept. We argue that tocopherols and tocotrienols may also exert direct beneficial effects in the gastrointestinal tract and that their return to the gastrointestinal tract by the liver through the bile may be physiologically advantageous.

Read Full Article Here

Lack of oxidative stress in a selenium deficient area in Ivory Coast–potential nutritional antioxidant role of crude palm oil

Tiahou G, Maire B, Dupuy A, Delage M, Vernet MH, Mathieu-Daudé JC, Michel F, Sess ED, Cristol JP.

Eur J Nutr. 2004 Dec;43(6):367-74. Epub 2004 Oct 20.

BACKGROUND:Previous studies have described an important selenium deficiency in a mountain region (Glanle) in the west of Ivory Coast.

AIM OF THE STUDY:To assess the antioxidant capacity of subjects from a selenium deficient area in Ivory Coast (Glanle region).

METHODS:This study involved 57 subjects, 18 to 69 years old, living in the Glanle region and 56 healthy controls living in the southern coastal region (Bodou). In the Glanle region families consume basically a vegetarian and crude palm oil diet, whereas in the Bodou region, families eat a fish-based diet with principally refined palm oil. Fasting blood samples were collected to assess the following parameters: lipid status (plasma total lipids; total-, HDL and LDL-cholesterol; triglycerides; phospholipids; fatty acid composition), plasma protein status (total protein, albumin, transthyretin, orosomucoid, CRP, transferrin), antioxidant capacity (plasma selenium, uric acid, retinol, alpha-tocopherol and tocotrienols levels, plasma seleno-glutathione peroxidase (GSHPx) activity) and oxidative stress markers (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)).

RESULTS:The mountain region samples (Glanle) were characterized by significantly lower plasma albumin, total-, HDL- and LDL-cholesterol, retinol and selenium levels, plasma PUFA content and GSHPx activity, but significantly higher alpha-tocopherol index and total tocotrienol level, than controls from the coastal area (Bodou). These results suggest a higher exposure risk to oxidative stress for the mountain region subjects. However, the absence of oxidative damage in this group provides evidence of a selenium independent protection mechanism against oxidative stress. This protection is related to lower plasma LDL cholesterol and PUFA content, and to higher alpha-tocopherol index, delta and total tocotrienols.

CONCLUSION:The long-term consumption of crude palm oil could be considered as an effective protective factor against oxidative stress.

Vitamin E: Underestimated as an antioxidant

Pfluger P, Kluth D, Landes N, Bumke-Vogt C, Brigelius-Flohé R.

Redox Rep. 2004;9(5):249-54.

Some 80 years after its discovery, vitamin E has experienced a renaissance which is as surprising as it is trivial. Although vitamin E is essential for reproduction, in rats at least, and deficiency causes neurological disorders in humans, the main interest in the last decades has concentrated on its antioxidant functions. This focus has highly underestimated the biological importance of vitamin E, which by far exceeds the need for acting as a radical scavenger. Only recently has it become clear that vitamin E can regulate cellular signaling and gene expression. Out of the eight different tocols included in the term vitamin E, alpha-tocopherol often exerts specific functions, which is also reflected in its selective recognition by proteins such as the alpha-tocopherol transfer protein and alpha-tocopherol-associated proteins. Vitamin E forms other than alpha-tocopherol are very actively metabolised, which explains their low biopotency. In vivo, metabolism may also attenuate the novel functions of gamma-tocopherol and tocotrienolsobserved in vitro. On the other hand, metabolites derived from individual forms of vitamin E have been shown to exert effects by themselves. This article focuses on the metabolism and novel functions of vitamin E with special emphasis on differential biological activities of individual vitamin E forms.

DNA chip analysis of comprehensive food function: Inhibition of angiogenesis and telomerase activity with unsaturated vitamin E, tocotrienol

Nakagawa K, Eitsuka T, Inokuchi H, Miyazawa T.

Biofactors. 2004;21(1-4):5-10.

Inhibition of angiogenesis and telomerase activity with vitamin E compounds, especially for tocotrienol (T3), has been investigated. Nutrigenomic tools have been used for elucidating the bioactive mechanisms of T3. In the cell culture experiments, T3 reduced the vascular endothelial growth factor (VEGF)-stimulated tube formation by human umbilical vein endothelial cells (HUVEC). Among T3 isomers, delta-T3 appeared the highest activity. The T3 inhibited the new blood vessels formation on the growing chick embryo chorioallantoic membrane (CAM assay for an in vivo model of angiogenesis). In contrast, tocopherol did not. The findings suggested that the T3 has potential use for reducing angiogenic disorder. DNA chip analysis revealed that T3 specifically down-regulates the expression of VEGF receptor (VEGFR) in endothelial cells. It is well-known that VEGF regulates angiogenesis by binding to VEGFR. Therefore, T3 could block the intracellular signaling of VEGF via down-regulation of VEGFR, which resulted in the inhibition of angiogenesis. On the other hand, DNA chip analysis also revealed that T3 down-regulates the expression of protein kinase C (PKC) in the cultured HUVEC. Since PKC is involved with the control of telomerase activity, T3 has potential to act as anti-telomerase inhibitor via PKC inhibition. In this manner, DNA chip technology provides efficient access to genetic information regarding food function and its mechanism.

Effect of dietary tocopherols and tocotrienols on the antioxidant status and lipid stability of chicken

Lanari MC, Hewavitharana AK, Becu C, de Jong S.

Meat Sci. 2004 Oct;68(2):155-62.

We determined the effect of dietary tocopherols and tocotrienols on the lipid stability of pre-cooked chicken breast and thigh. The birds were supplemented with one of two doses of a commercial mixture of tocopherols and tocotrienols (Oryza1, Oryza2) or one of two doses of all-rac α-tocopherol acetate (Toc1, Toc2). Diets were formulated so that Oryza1 and Toc1 and Oryza2 and Toc2 contained similar tocopherol concentrations. No quantifiable amounts of tocotrienols were found in either breast or thigh muscles. Tocotrienols present in the diet reduced muscle α-tocopherol concentration. The effect of Oryza1 on the tocopherol content in muscle and on its lipid stability was not significant. The Oryza2, Toc1 and Toc2 diets increased the α- and γ-tocopherol in breast and thigh muscles and enhanced their lipid stability. This improvement was only due to the antioxidant action of the tocopherols. Lipid stability of pre-cooked chicken was not enhanced by adding tocotrienols to a tocopherol supplement.

Plasma C-reactive protein concentrations in active and passive smokers: Influence of antioxidant supplementation

Gladys Block, PhD, Christopher Jensen, PhD, Marion Dietrich, PhD, Edward P. Norkus, PhD, Mark Hudes, PhD, and Lester Packer, PhD

J Am Coll Nutr. 2004 Apr;23(2):141-7.

Objective: C-reactive protein (CRP) may directly affect the progression of atherosclerosis, and therefore, may be a target for reducing disease risk. The objective was to determine whether antioxidant supplementation reduces plasma CRP in active and passive smokers.

Design: Randomized, double-blind, placebo-controlled, parallel group trial with 2 months exposure to study supplements.

Setting: Berkeley and Oakland, California.

Subjects: Healthy adult men and women, consuming <4 daily servings of fruits and vegetables, and who were actively or passively exposed to cigarette smoke. Analysis was limited to participants with detectable baseline CRP concentrations and no evidence of inflammation associated with acute illness at baseline or follow-up as reflected in CRP elevations (≥10.0 mg/L). A total of 1393 individuals were screened, 216 randomized, 203 completed the study, and 160 were included in the analysis.

Interventions: Participants were randomized to receive a placebo or vitamin C (515 mg/day) or antioxidant mixture (per day: 515 mg vitamin C, 371 mg α-tocopherol, 171 mg  γ-tocopherol, 252 mg  mixed tocotrienols, and 95 mg α-lipoic acid).

Measures of Outcome: Change in plasma CRP concentration.

Results: Vitamin C supplementation yielded a 24.0% reduction (95% confidence interval, -38.9% to-5.5%, p =0.036 compared to control) in plasma CRP, whereas the antioxidant mixture and placebo produced a nonsignificant 4.7% reduction (-23.9% to 19.3%) and 4.3% increase (-15.1% to 28.2%), respectively. Results were adjusted for baseline body mass index and CRP concentrations.

Conclusions: Plasma CRP itself may serve as a potential target for reducing the risk of atherosclerosis, and antioxidants, including vitamin C, should be investigated further to confirm their CRP-lowering and anti-inflammatory effects.

Dietary antioxidant intake and risk of type 2 diabetes

Montonen J, Knekt P, Järvinen R, Reunanen A.

Diabetes Care. 2004 Feb;27(2):362-6.

Objective: The intake of antioxidants was studied for its ability to predict type 2 diabetes.

Research Design & Methods: A cohort of 2,285 men and 2,019 women 40-69 years of age and free of diabetes at baseline (1967-1972) was studied. Food consumption during the previous year was estimated using a dietary history interview. The intake of vitamin C, four tocopherols, four tocotrienols, and six carotenoids was calculated. During a 23-year follow-up, a total of 164 male and 219 female incident cases occurred.

Results: Vitamin E intake was significantly associated with a reduced risk of type 2 diabetes. The relative risk (RR) of type 2 diabetes between the extreme quartiles of the intake was 0.69 (95% CI 0.51-0.94, P for trend = 0.003). Intakes of alpha-tocopherol, gamma-tocopherol, delta-tocopherol, and beta-tocotrienol were inversely related to a risk of type 2 diabetes. Among single carotenoids, beta-cryptoxanthin intake was significantly associated with a reduced risk of type 2 diabetes (RR 0.58, 95% CI 0.44-0.78, P < 0.001). No association was evident between intake of vitamin C and type 2 diabetes risk.

Conclusion: This study supports the hypothesis that development of type 2 diabetes may be reduced by the intake of antioxidants in the diet.