Oxidative modification of low density lipoproteins (LDL) and their unrestricted scavenger receptor-dependent uptake is believed to account for cholesterol deposition in macrophage-derived foam cells. It has been suggested that vitamin E that is transported by LDL plays a critical role in protecting against LDL oxidation. We hypothesize that the maintenance of sufficiently high vitamin E concentrations in LDL can be achieved by reducing its chromanoxyl radicals, i.e., by vitamin E recycling. In this study we demonstrate that: i) chromanoxyl radicals of endogenous vitamin E and of exogenously added alpha-tocotrienol, alpha-tocopherol or its synthetic homologue with a 6-carbon side-chain, chromanol-alpha-C6, can be directly generated in human LDL by ultraviolet (UV) light, or by interaction with peroxyl radicals produced either by an enzymic oxidation system (lipoxygenase + linolenic acid) or by an azo-initiator, 2,2′-azo-bis(2,4-dimethylvaleronitrile) (AMVN; ii) ascorbate can recycle endogenous vitamin E and exogenously added chromanols by direct reduction of chromanoxyl radicals in LDL; iii) dihydrolipoic acid is not efficient in direct reduction of chromanoxyl radicals but recycles vitamin E by synergistically interacting with ascorbate (reduces dehydroascorbate thus maintaining the steady-state concentration of ascorbate); and iv) beta-carotene is not active in vitamin E recycling but may itself be protected against oxidative destruction by the reductants of chromanoxyl radicals. We suggest that the recycling of vitamin E and other phenolic antioxidants by plasma reductants may be an important mechanism for the enhanced antioxidant protection of LDL.
Blog Archives
Individually and in combination with other oils, the tropical oils impart into manufactured foods functional properties that appeal to consumers. The use of and/or labeling in the ingredient lists give the impression that these oils are used extensively in commercially processed foods. The estimated daily intake of tropical oils by adult males is slightly more than one fourth of a tablespoon (3.8 g), 75% of which consists of saturated fatty acids. Dietary fats containing saturated fatty acids at the beta-position tend to raise plasma total and LDL-cholesterol, which, of course, contribute to atherosclerosis and coronary heart disease. Health professionals express concern that consumers who choose foods containing tropical oils unknowingly increase their intake of saturated fatty acids. The saturated fatty acid-rich tropical oils, coconut oil, hydrogenated coconut oil, and palm kernel oil, raise cholesterol levels; studies demonstrating this effect are often confounded by a developing essential fatty acid deficiency. Palm oil, an essential fatty acid-sufficient tropical oil, raises plasma cholesterol only when an excess of cholesterol is presented in the diet. The failure of palm oil to elevate blood cholesterol as predicted by the regression equations developed by Keys et al. and Hegsted et al. might be due to the dominant alpha-position location of its constituent saturated fatty acids. If so, the substitution of interesterified artificial fats for palm oil in food formulations, a recommendation of some health professionals, has the potential of raising cholesterol levels. A second rationale addresses prospective roles minor constituents of palm oil might play in health maintenance. This rationale is founded on the following observations. Dietary palm oil does not raise plasma cholesterol. Single fat studies suggests that oils richer in polyunsaturated fatty acid content tend to decrease thrombus formation. Anomalously, palm oil differs from other of the more saturated fats in tending to decrease thrombus formation. Finally, in studies comparing palm oil with other fats and oils, experimental carcinogenesis is enhanced both by vegetable oils richer in linoleic acid content and by more highly saturated animal fats. The carotenoid constituents of red palm oil are potent dietary anticarcinogens. A second group of antioxidants, the tocotrienols, are present in both palm olein and red palm oil. These vitamin E-active constituents are potent suppressors of cholesterol biosynthesis; emerging data point to their anticarcinogenic and antithrombotic activities. This review does not support claims that foods containing palm oil have no place in a prudent diet.
Nutritional and biochemical aspects of the hypolipidemic action of rice bran oil: A review
Rukmini C, Raghuram TC.
J Am Coll Nutr. 1991 Dec;10(6):593-601.
In this paper, we review the effects of rice bran oil (RBO), an unconventional oil recently introduced onto the Indian market for human use. RBO contains oleic acid (38.4%), linoleic acid (34.4%), and linolenic acid (2.2%) as unsaturated fatty acids, and palmitic (21.5%) and stearic (2.9%) acids as saturated fatty acids. The unsaponifiable fraction (4.2%) has total tocopherols (81.3 mg%), gamma-oryzanol (1.6%), and squalene (320 mg%). Oryzanol is a mixture of ferulic acid esters of triterpene alcohols such as cycloartenol (CA) (106 mg%) and 24-methylene cycloartanol (494 mg%). Studies on experimental rats demonstrated a hypolipidemic effect of RBO. The unsaponifiable fraction of RBO lowers cholesterol levels. Feeding phytosterols, CA, and 24-methylene cycloartanol in amounts present in RBO to hypercholesterolemic rats for 8 weeks indicates that CA alone reduces cholesterol and triglyceride levels significantly. Endogenous sterol excretion increases in animals given CA. The accumulation of CA in the liver inhibits cholesterol esterase activity, which in turn leads to reduction in circulating cholesterol levels. CA is structurally similar to cholesterol and may compete with the binding sites of cholesterol and sequestrate cholesterol, which is metabolized to its derivatives. RBO, which is rich in tocopherols and tocotrienols, may improve oxidative stability. Tocotrienols inhibit HMG CoA reductase, resulting in hypocholesterolemia. The hypolipidemic effect of RBO has also been established in human subjects. Thus, RBO could be a suitable edible oil for patients with hyperlipidemia.
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.
Abstract
A double-blind, crossover, 8-wk study was conducted to compare effects of the tocotrienol-enriched fraction of palm oil (200 mg palmvitee capsules/day) with those of 300 mg corn oil/d on serum lipids of hypercholesterolemic human subjects (serum cholesterol 6.21-8.02 mmol/L). 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. This indicates that gamma-tocotrienol may be the most potent cholesterol inhibitor in palmvitee capsules. The results of this pilot study are very encouraging.
Dietary tocotrienols reduce concentrations of plasma cholesterol, apolipoprotein B, thromboxane B2, and platelet factor 4 in pigs with inherited hyperlipidemias
Qureshi AA, Qureshi N, Hasler-Rapacz JO, Weber FE, Chaudhary V, Crenshaw TD, Gapor A, Ong AS, Chong YH, Peterson D, et al.
Am J Clin Nutr. 1991 Apr;53(4 Suppl):1042S-1046S.
Normolipemic and genetically hypercholesterolemic pigs of defined lipoprotein genotype were fed a standard diet supplemented with 50 micrograms/gtocotrienol-rich fraction (TRF) isolated from palm oil. Hypercholesterolemic pigs fed the TRF supplement showed a 44% decrease in total serum cholesterol, a 60% decrease in low-density-lipoprotein (LDL)-cholesterol, and significant decreases in levels of apolipoprotein B (26%), thromboxane-B2 (41%), and platelet factor 4 (PF4; 29%). The declines in thromboxane B2 and PF4 suggest that TRF has a marked protective effect on the endothelium and platelet aggregation. The effect of the lipid-lowering diet persisted only in the hypercholesterolemic swine after 8 wk feeding of the control diet. These results support observations from previous studies on lowering plasma cholesterol in animals by tocotrienols, which are naturally occurring compounds in grain and palm oils and may have some effect on lowering plasma cholesterol in humans.
The bioactivities of RRR-alpha-, beta-, gamma-, and delta-tocopherol (T) and R-alpha-tocotrienol (R-alpha-TT) were determined in rat resorption-gestation tests. The ranking order was RRR-alpha-T greater than RRR-beta-T greater than RRR-gamma-T greater than or equal to R-alpha-TT greater than RRE-delta-T. Accordingly, the biopotency of a palm-oil residue was assessed and expressed as alpha-tocopherol equivalents (alpha-TEs). The release of pyruvate kinase, a variable in the nutrition-linked necrotizing myopathy, into the plasma was dose-dependently inhibited by the RRR-alpha-T standard and the corresponding alpha-TE from this residue. Prostacyclin synthesis from aorta segments induced by thrombin or ionomycin was higher than the spontaneous release. However, there was no difference between the depleted group and groups treated with RRR-alpha-T or alpha-TEs from the palm-oil residue. Quantities of IgG in plasma of vitamin E-depleted rats were the highest. Upon supplementation with RRR-alpha-T or alpha-TEs from the palm-oil residue, reduced IgG concentrations were observed, similar to those of animals on a commercial diet containing adequate amounts of vitamin E.
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.
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.
Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats
Ngah WZ, Jarien Z, San MM, Marzuki A, Top GM, Shamaan NA, Kadir KA.
Am J Clin Nutr. 1991 Apr;53(4 Suppl):1076S-1081S.
The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis.
A comparison of tocopherol and tocotrienol for the chemoprevention of chemically induced rat mammary tumors
Gould MN, Haag JD, Kennan WS, Tanner MA, Elson CE.
Am J Clin Nutr. 1991 Apr;53(4 Suppl):1068S-1070S.
Two forms of vitamin E, tocopherol and tocotrienol, were tested for chemopreventive activity in two chemically induced rat mammary-tumor models. When mammary tumors were induced by 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg), only the tocotrienol group had a statistically significant increase in tumor latency. There was no effect of either compound on tumor multiplicity. When tumors were induced by N-nitrosomethylurea (NMU, 30 mg/kg), neither analogue of vitamin E modified latency, whereas tocotrienol increased tumor multiplicity. In summary, neither vitamin analog had a major impact on mammary-tumor development after tumor induction with either DMBA or NMU.