The link between dietary fats and cardiovascular diseases has necessitated a growing research interest in palm oil, the second largest consumed vegetable oil in the world. Palm oil, obtained from a tropical plant, Elaeis guineensis contains 50% saturated fatty acids, yet it does not promote atherosclerosis and arterial thrombosis. The saturated fatty acid to unsaturated fatty acid ratio of palm oil is close to unity and it contains a high amount of the antioxidants, beta-carotene, and vitamin E. Although palm oil-based diets induce a higher blood cholesterol level than do corn, soybean, safflower seed, and sunflower oils, the consumption of palm oil causes the endogenous cholesterol level to drop. This phenomenon seems to arise from the presence of the tocotrienols and the peculiar isomeric position of its fatty acids. The benefits of palm oil to health include reduction in risk of arterial thrombosis and atherosclerosis, inhibition of endogenous cholesterol biosynthesis, platelet aggregation, and reduction in blood pressure. Palm oil has been used in the fresh state and/or at various levels of oxidation. Oxidation is a result of processing the oil for various culinary purposes. However, a considerable amount of the commonly used palm oil is in the oxidized state, which poses potential dangers to the biochemical and physiological functions of the body. Unlike fresh palm oil, oxidized palm oil induces an adverse lipid profile, reproductive toxicity and toxicity of the kidney, lung, liver, and heart. This may be as a result of the generation of toxicants brought on by oxidation. In contrast to oxidized palm oil, red or refined palm oil at moderate levels in the diet of experimental animals promotes efficient utilization of nutrients, favorable body weight gains, induction of hepatic drug metabolizing enzymes, adequate hemoglobinization of red cells and improvement of immune function. Howerer, high palm oil levels in the diet induce toxicity to the liver as shown by loss of cellular radial architecture and cell size reductions which are corroborated by alanine transaminase to asparate transaminase ratios which are higher than unity. The consumtion of moderate amounts of palm oil and reduction in the level of oxidation may reduce the health risk believed to be associated with the consumption of palm oil. Red palm oil, by virtue of its beta-carotene content, may protect against vitamin A deficiency and certain forms of cancer.
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Effects on the human serum lipoprotein profile of beta-glucan, soy protein and isoflavones, plant sterols and stanols, garlic and tocotrienols
Kerckhoffs DA, Brouns F, Hornstra G, Mensink RP.
J Nutr. 2002 Sep;132(9):2494-505
The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile.
Dose-dependent cholesterolemic activity of tocotrienols
Khor H Dr, Ng T, Rajendran R.
Malays J Nutr. 2002 Sep;8(2):157-166.
Tocotrienols and tocopherols are isoforms of vitamin E. Vitamin E may exhibit antioxidant, prooxidant and non-antioxidant activities depending upon circumstances. In this study, the effect of tocotrienols and a-tocopherol on the activities of HMG CoA reductase and cholesterol 7 a-hydroxylase was investigated. Pure tocotrienols were isolated from palm fatty acid distillate and pure a-tocopherol was obtained commercially. Guinea pigs were treated with different dosages of tocotrienols and a-tocopherol. After the treatment period, animals were sacrificed and liver microsomes were prepared. HMG CoA reductase and cholesterol 7a-hydroxylase were assayed using tracer techniques. Our results showed that the effects of tocotrienols and a-tocopherol on the activities of both the enzymes were dose-dependent. At low dosages, both tocotrienols and a-tocopherol exhibited an inhibitory effect on both the enzymes. Moreover, tocotrienols were a much stronger inhibitors than a-tocopherol. At high dosages, on the other hand, tocotrienols and a-tocopherol showed opposite effects on the enzymes. While tocotrienols continued to exhibit an inhibitory effect, a-tocopherol actually exhibited a stimulatory effect on both the enzymes. A possible explanation for this observation is suggested.
Tocopherols and tocotrienols are food ingredients that are believed to have a positive effect on health. The most studied property of both groups of compounds is their antioxidant action. Previously, we found that tocopherols and diverse tocopherol derivatives can inhibit the activity of human glutathione S-transferase P1-1 (GST P1-1). In this study we found that GST P1-1 is also inhibited, in a concentration-dependent manner, by alpha- and gamma-tocotrienol. The concentration giving 50% inhibition of GST P1-1 is 1.8 +/- 0.1 microM for alpha-tocotrienol and 0.7 +/- 0.1 microM for gamma-tocotrienol. This inhibition of GST P1-1 is noncompetitive with respect to both substrates CDNB and GSH. We also examined the 3D structure of GST P1-1 for a possible tocopherol/tocotrienol binding site. The enzyme contains a very hydrophobic pit-like structure where the phytyl tail of tocopherols and tocotrienols could fit in. Binding of tocopherol and tocotrienol to this hydrophobic region might lead to bending of the 3D structure. In this way tocopherols and tocotrienols can inhibit the activity of the enzyme; this inhibition can have far-reaching implications for humans.
A tocotrienol (T3) mixture was intragastricaly administered to Sprague-Dawley rats, and the T3 levels in various tissues were measured 0, 4, 8 and 24 hr after the administration. In blood clots, brain, thymus, testes, vice-testes and muscles, T3 homologues were not detected at all. In epididymal adipose, renal adipose, subcutaneous adipose and brown adipose tissues and in the heart, the T3 levels were maintained or increased for 24 hr after the administration. In the serum, liver, mesenteric lymph node, spleen and lungs, the T3 levels were highest 8 hr after the T3 administration. These results suggest that the distribution and metabolism of T3 in the rat vary considerably among different tissues.
We have shown that sesame lignans added to rat diet resulted in significantly greater plasma and tissue concentrations of alpha- and gamma-tocopherol concentrations in supplemented rats than in rats without supplementation. In the present studies we examined whether sesaminol, a sesame lignan, enhances tocotrienol concentrations in plasma and tissues of rats fed diets containing a tocotrienol-rich fraction of palm oil (T-mix). In Experiment 1, effects of sesaminol on tocotrienol concentrations in plasma, liver, and kidney were evaluated in rats fed diets containing 20 mg/kg of T-mix (20T) and 50 mg/kg of T-mix (50T) with or without 0.1% sesaminol. Although the T-mix contained 23% alpha-tocopherol, 22% alpha-tocotrienol, and 34% gamma-tocotrienol, alpha-tocopherol constituted most or all of the vitamin E in plasma and tissue (from 97% in kidney to 100% in plasma), with no or very little alpha-tocotrienol and no gamma-tocotrienol at all. Addition of sesaminol to the T-mix resulted in significantly higher plasma, liver, and kidney alpha-tocopherol concentrations compared to values for T-mix alone. Further, T-mix with sesaminol resulted in significantly higher alpha-tocotrienol concentrations in kidney, although the concentration was very low. In Experiment 2, we examined whether sesaminol caused enhanced absorption of alpha-tocopherol and alpha-tocotrienol in a dosage regimen supplying T-mix and sesaminol on alternating days and observed significantly higher levels of alpha-tocopherol and alpha-tocotrienol in rats fed sesaminol, even without simultaneous intake, compared to those in rats without sesaminol. In Experiment 3, alpha-tocopherol was supplied to the stomach with and without sesaminol, and alpha-tocopherol concentrations in the lymph fluid were measured. a-Tocopherol concentrations were not different between groups. These results indicated that sesaminol produced markedly higher alpha-tocopherol concentrations in plasma and tissue and significantly greater alpha-tocotrienol concentrations in kidney and various other tissues, but the concentrations of alpha-tocotrienol were extremely low compared to those of a-tocopherol (Exps. 1 and 2). However, the sesaminol-induced increases of a-tocopherol and a-tocotrienol concentrations in plasma and tissue were not caused by their enhanced absorption since sesaminol did not enhance their absorption.
Development and validation of oxygen radical absorbance capacity assay for lipophilic antioxidants using randomly methylated beta-cyclodextrin as the solubility enhancer
Huang D, Ou B, Hampsch-Woodill M, Flanagan JA, Deemer EK.
J Agric Food Chem. 2002 Mar 27;50(7):1815-21.
We recently reported the improved oxygen radical absorbance capacity (ORAC) assay using fluorescein (FL) as the fluorescent probe. The current ORAC(FL) assay is limited in hydrophilic antioxidant due to the aqueous environment of the assay. Lipophilic antioxidants mainly include the vitamin E family and carotenoids, which play a critical role in biological defense systems. In this paper, we expanded the current ORAC(FL) assay to lipophilic antioxidants. Randomly methylated beta-cyclodextrin (RMCD) was introduced as the water solubility enhancer for lipophilic antioxidants. Seven percent RMCD (w/v) in a 50% acetone-H(2)O mixture was found to sufficiently solubilize vitamin E compounds and other lipophilic phenolic antioxidants in 75 mM phosphate buffer (pH 7.4). This newly developed ORAC assay (abbbreviated ORAC(FL-LIPO)) was validated through linearity, precision, accuracy, and ruggedness. The validation results demonstrate that the ORAC(FL-LIPO) assay is reliable and robust. For the first time, by using 6-hydroxy-2,5,7,8-tetramethyl-2-carboxylic acid as a standard (1.0), the ORAC values of alpha-tocopherol, (+)-gamma-tocopherol, (+)-delta-tocopherol, alpha-tocopherol acetate, tocotrienols, 2,6-di-tert-butyl-4-methylphenol, and gamma-oryzanol were determined to be 0.5 +/- 0.02, 0.74 +/- 0.03, 1.36 +/- 0.14, 0.00, 0.91 +/- 0.04, 0.16 +/- 0.01, and 3.00 +/- 0.26, respectively. The structural information of oxidized alpha-tocopherol obtained by liquid chromatography/mass spectrometry reveals that the mechanism for the reaction between the vitamin E and the peroxyl radical follows the hydrogen atom transfer mechanism, which is in agreement with the notion that vitamin E is the chain-breaking antioxidant.
The effects of various commercial hydrothermal processes (steaming, autoclaving, and drum drying) on levels of selected oat antioxidants were investigated. Steaming and flaking of dehulled oat groats resulted in moderate losses of tocotrienols, caffeic acid, and the avenanthramide Bp (N-(4′-hydroxy)-(E)-cinnamoyl-5-hydroxy-anthranilic acid), while ferulic acid and vanillin increased. The tocopherols and the avenanthramides Bc (N-(3′,4′-dihydroxy-(E)-cinnamoyl-5-hydroxy-anthranilic acid) and Bf (N-(4′-hydroxy-3′-methoxy)-(E)-cinnamoyl-5-hydroxy-anthranilic acid) were not affected by steaming. Autoclaving of grains (including the hulls) caused increased levels of all tocopherols and tocotrienols analyzed except beta-tocotrienol, which was not affected. Vanillin and ferulic and p-coumaric acids also increased, whereas the avenanthramides decreased, and caffeic acid was almost completely eliminated. Drum drying of steamed rolled oats resulted in an almost complete loss of tocopherols and tocotrienols, as well as a large decrease in total cinnamic acids and avenanthramides. The same process applied to wholemeal made from groats from autoclaved grains resulted in less pronounced losses, especially for the avenanthramides which were not significantly affected.
Palm oil is an excellent choice for food manufacturers because of its nutritional benefits and versatility. The oil is highly structured to contain predominantly oleic acid at the sn2-position in the major triacylglycerols to account for the beneficial effects described in numerous nutritional studies. Oil quality and nutritional benefits have been assured for the variety of foods that can be manufactured from the oil directly or from blends with other oils while remaining trans-free. The oxidative stability coupled with the cost-effectiveness is unparalleled among cholesterol-free oils, and these values can be extended to blends of polyunsaturated oils to provide long shelf-life. Presently the supply of genetic-modification-free palm oil is assured at economic prices, since the oil palm is a perennial crop with unparalleled productivity. Numerous studies have confirmed the nutritional value of palm oil as a result of the high monounsaturation at the crucial 2-position of the oil’s triacylglycerols, making the oil as healthful as olive oil. It is now recognized that the contribution of dietary fats to blood lipids and cholesterol modulation is a consequence of the digestion, absorption, and metabolism of the fats. Lipolytic hydrolysis of palm oil glycerides containing predominantly oleic acid at the 2 position and palmitic and stearic acids at the 1 and 3 positions allows for the ready absorption of the 2-monoacrylglycerols while the saturated free fatty acids remain poorly absorbed. Dietary palm oil in balanced diets generally reduced blood cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides while raising the high-density lipoprotein (HDL) cholesterol. Improved lipoprotein(a) and apo-A1 levels were also demonstrated from palm oil diets; an important benefits also comes from the lowering of blood triglycerides (or reduced fat storage) as compared with those from polyunsaturated fat diets. Virgin palm oil also provides carotenes apart from tocotrienols and tocopherols that have been shown to be powerful antioxidants and potential mediators of cellular functions. These compounds can be antithrombotic, cause an increase of the prostacyclin/thromboxane ratio, reduce restenosis, and inhibit HMG-CoA-reductase (thus reducing) cholesterol biosynthesis). Red palm oil is a rich source of beta-carotene as well as of alpha-tocopherol andtocotrienols.
Antioxidants in dietary oils: Their potential role in breast cancer prevention
Sylvester PW Dr, Shah S.
Malays J Nutr. 2002 Mar;8(1):1-11.
Edible oils contain variable amounts of natural antioxidants such as vitamin E. Antioxidants act not only to prevent lipid peroxidation and free-radical production, but also display potent anticancer activity. The vitamin E family of compounds is divided into two subgroups called tocopherols and tocotrienols, but only tocotrienols display potent anticancer activity at treatment doses that have little or no effect on normal cell growth or viability. Palm oil contains the highest concentrations of natural tocotrienols. Tocotrienols induced apoptosis or programmed cell death in breast cancer cells. Morphological and biochemical characteristics of apoptosis, such as nuclear and cytoplasmic condensation and DNA fragmentation, are mediated by the activation of cysteine proteases called caspases. Apoptosis is triggered by the activation of initiator caspases (caspase-8 or 9) that subsequently activate effector caspases (caspase-3, 6, and 7). Studies were conducted using the highly malignant +SA mouse mammary epithelial cell line to determine if tocotrienol-induced programmed cell death is mediated through the caspase-8 or caspase-9 pathway. Treatment with cytotoxic doses of tocotrienol resulted in a large increase in caspase-8 and caspase-3, but not caspase-9 activity. Combined treatment of tocotrienol with selective caspase-8 or caspase-3 inhibitors completely blocked tocotrieno-linduced apoptosis and activation of caspase-8 and caspase-3, respectively. These findings demonstrate that tocotrienol-induced apoptosis in highly malignant mammary epithelial cells is mediated through caspase-8 activation, and may provide essential information necessary for understanding the potential health benefits of these compounds in preventing and/or reducing the risk of breast cancer in women.