The tocotrienol-rich fraction (TRF) of palm oil consists of tocotrienols and some alpha-tocopherol (alpha-T). Tocotrienols are a form of vitamin E having an unsaturated side-chain, rather than the saturated side-chain of the more common tocopherols. Because palm oil has been shown not to promote chemically-induced mammary carcinogenesis, we tested effects of TRF and alpha-T on the proliferation, growth, and plating efficiency (PE) of the MDA-MB-435 estrogen-receptor-negative human breast cancer cells. TRF inhibited the proliferation of these cells with a concentration required to inhibit cell proliferation by 50% of 180 microgram/mL whereas alpha-T had no effect at concentrations up to 1000 microgram/mL as measured by incorporation of [3H]thymidine. The effects of TRF and alpha-T also were tested in longer-term growth experiments, using concentrations of 180 and 500 microgram/mL. We found that TRF inhibited the growth of these cells by 50%, whereas alpha-T did not. Their effect on the ability of these cells to form colonies also was studied, and it was found that TRF inhibited PE, whereas alpha T had no effect. These results suggest that the inhibition is due to the presence of tocotrienols in TRF rather than alpha T.
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Response of hypercholesterolemic subjects to administration of tocotrienols
Qureshi AA, Bradlow BA, Brace L, Manganello J, Peterson DM, Pearce BC, Wright JJ, Gapor A, Elson CE.
Lipids. 1995 Dec;30(12):1171-7.
The cholesterol-suppressive actions of Palmvitee and gamma-tocotrienol were assessed in hypercholesterolemic subjects after acclimation to the American Heart Association Step 1 dietary regimen for four and eight weeks, respectively. The four-week dietary regimen alone elicited a 5% decrease (P < 0.05) in the cholesterol level of the 36 subjects. Subjects continuing on the dietary regimen for a second four-week period experienced an additional 2% decrease in their cholesterol levels. Dietary assessments based on unanticipated recalls of 24-h food intake records suggest that significant reductions in energy and fat, predominantly in saturated fat, intakes are responsible. The subjects experienced significant Palmvitee- and gamma-tocotrienol-mediated decreases in cholesterol. The group of subjects acclimated to the dietary regimen for four weeks responded to Palmvitee (a blend of tocols providing 40 mg alpha-tocopherol, 48 mg alpha-tocotrienol, 112 mg gamma-tocotrienol, and 60 mg delta-to-cotrienol/day for four weeks) with a 10% decrease in cholesterol (P < 0.05). Dietary assessments showed no further change in energy and fat intakes. alpha-Tocopherol attenuated the cholesterol-suppressive action of the tocotrienols. The second group of subjects, acclimated to the dietary regimen for eight weeks, received 200 mg gamma-tocotrienol/d for four weeks. The cholesterol-suppressive potency of this alpha-tocopherol-free preparation was calculated to be equivalent to that of the mixture of tocotrienols (220 mg) used in the prior study. Cholesterol levels of the 16 subjects in the second group decreased 13% (P < 0.05) during the four-week trial. Plasma apolipoprotein B and ex vivo generation of thromboxane B2 were similarly responsive to the tocotrienol preparations, whereas neither preparation had an impact on high density lipoprotein cholesterol and apolipoprotein A-1 levels.
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.
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.
Antioxidants may have a role in the prevention of atherosclerosis. In the present trial, the antioxidant properties of Palm Vitee, a gamma-tocotrienol-, and alpha-tocopherol enriched fraction of palm oil, in patients with carotid atherosclerosis were investigated. 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. 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. These findings suggest that antioxidants, such as tocotrienols, may influence the course of carotid atherosclerosis.
Vitamins E and C, beta-carotene, and other carotenoids as antioxidants
Sies H, Stahl W.
Am J Clin Nutr. 1995 Dec;62(6 Suppl):1315S-1321S.
Tocopherols and tocotrienols (vitamin E), ascorbic acid (vitamin C), and the carotenoids react with free radicals, notably peroxyl radicals, and with singlet molecular oxygen (1O2), which is the basis for their function as antioxidants. RRR-alpha-Tocopherol is the major peroxyl radical scavenger in biological lipid phases such as membranes or low-density lipoproteins. Ascorbic acid is present in aqueous compartments (eg, cytosol, plasma, and other body fluids) and can reduce the tocopherol radical; it also has several metabolically important cofactor functions in enzyme reactions, especially hydroxylations. These micronutrients need to be regenerated on oxidation in the biological setting, hence the need for further coupling to nonradical reducing systems such as glutathione-glutathione disulfide, dihydrolipoate-lipoate, or NADPH-NADP+ and NADH-NAD+. Carotenoids, such as beta-carotene, lycopene, and some oxycarotenoids, eg, zeaxanthin and lutein, exert antioxidant functions in lipid phases by quenching 1O2 or free radicals. There are pronounced differences in tissue carotenoid patterns, extending also to the distribution between the all-trans and various cis isomers of the respective carotenoids. Physical quenching leaves the structure intact, so that in this mode the carotenoids do not require a regeneration reaction.
India is the second largest producer of rice in the world and has the high potential to produce rice bran oil (RBO), a by-product of the rice milling industry. Since RBO is, an unconventional oil, the chemical composition, nutrient evaluation and toxicological safety were assessed. The fatty acid composition RBO is very close to that of groundnut oil (GNO). Though RBO has high unsaponifiable matter (4.2%), it is rich In minor constituents such as phytosterols, triterpene alcohols, tocopherols and tocotrienols. Experimental as well as human studies have demonstrated the hypolipidaemic effects of RBO. Further, It was established that minor constituents present in unsaponifiable fraction of RBO were responsible for its hypolipidaemic effects. Nutritional evaluation studies, carried out with 10 per cent RBO and 20 per cent protein, indicated that growth, feed efficiency and mineral balance were comparable to GNO-fed animals. Toxicological studies had shown that there were no abnormalities In animals fed either RBO or GNO. The reproductive performance was also found to be normal as compared with that of GNO-fed animals in all three generations. In addition, neither RBO nor the foods deepfried in it showed any mutagenicity as judged by Ames test. In view of its safety and hypolipidaemic activity, RBO could be considered as an alternative source of edible oil.
Tocotrienols from palm oil as potent inhibitors of lipid peroxidation and protein oxidation in rat brain mitochondria
Kamat JP, Devasagayam TP.
Neurosci Lett. 1995 Aug 11;195(3):179-82.
The tocotrienol-rich-fraction (TRF) from palm oil, being tried as a more economical and efficient substitute for alpha-tocopherol, significantly inhibited oxidative damage in vitro to both lipids and proteins in rat brain mitochondria induced by ascorbate-Fe2+, the free radical initiator azobis(2-amidopropane)dihydrochloride (AAPH) and photosensitisation. The observed inhibitory effect was both time- and concentration-dependent. At a low concentration of 5 microM, TRF can significantly inhibit oxidative damage to both lipids and proteins. The inhibitory effect of TRF seems to be mainly due to gamma-tocotrienol and to a lesser extent alpha- and delta-tocotrienols. TRF was significantly more effective than alpha-tocopherol. This fraction from palm oil can be considered a natural antioxidant supplement capable of protecting the brain against oxidative damage and thereby from the ensuing adverse alterations.
New analytical data of Finnish foods were utilized in calculating the intakes of 8 different carotenoids, 6 retinoids, 4 tocopherols and tocotrienols in a Finnish population sample (5403 men and 4750 women) forming a basis for prospective studies on the associations of diet and chronic diseases. Data on habitual food consumption referring to the preceding year were collected by a dietary history interview method in 1967-1972. Beta-carotene, lutein and lycopene, mainly provided by different vegetables, were the most abundant carotenoids. Alltrans retinol was a predominant retinoid compound. A major proportion of total vitamin A (85% in men and 74% in women) was attributed to dietary retinoids. Alpha-tocopherol accounted for approximately half of the total tocopherols and tocotrienols of diet, and made up approximately 85% of total vitamin E. Intakes of different tocopherols and tocotrienols were mainly associated with the consumption of cereal products and/or margarine and oils, but alpha-tocopherol and vitamin E had several other food sources. It is suggested that these more specific measures for carotenoids and tocopherols would increase the accuracy of estimating health impacts of antioxidant vitamins in the study population.
Coupling the cholesterol- and tumor-suppressive actions of palm oil to the impact of its minor constituents on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity
Elson CE, Qureshi AA.
Prostaglandins Leukot Essent Fatty Acids. 1995 Feb;52(2-3):205-7.
The impact of palm oil on cardiovascular disease and cancer may be explained by the mevalonate-suppressive action of constituent isoprenoid end products of plant secondary metabolism. Assorted monoterpenes, sesquiterpenes, carotenoids and tocotrienols down regulate, post-transcriptionally, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity thereby modestly decreasing cholesterol synthesis and concomitantly decreasing LDL cholesterol. The reductase activity in tumor tissues differs from that of liver in being resistant to sterol feedback regulation. Tumor reductase activity retains sensitivity to the post-transcriptional regulation. As a consequence, the isoprenoid-mediated suppression of mevalonate synthesis depletes tumor tissues of two intermediate products, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are incorporated post-translationally into growth control-associated proteins.
Protection by tocotrienols against hypercholesterolaemia and atheroma
Teoh MK, Chong JM, Mohamed J, Phang KS.
Med J Malaysia. 1994 Sep;49(3):255-62.
Antioxidants such as tocotrienols may protect against atherosclerosis since tissue injury from free radicals is a final common pathway of damage in arterial disease. In this study, the effects of tocotrienols on serum cholesterol, lipid peroxides, and aorta atheroma were assessed in rabbits fed an atherogenic diet for 12 weeks. Tocotrienols were more effective than tocopherols in preventing increases in serum LDL (p = 0.03) and total cholesterol (p = 0.008) levels in the cholesterol-fed rabbits. Elevation of serum lipid peroxides was effectively suppressed by tocotrienols (p = 0.01). Both tocopherols and tocotrienols offered significant protection against atheroma in the rabbit aorta, but tocotrienols had a stronger hypolipidaemic effect.