The importance of vitamin E in reducing cardiovascular risk.
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Cardiovascular Diseases↗
Biomedical subjects
M Abbey
Publications and source records attributed to M Abbey.
Effects of supplementing with vitamin E on the uptake of low density lipoprotein and the stimulation of cholesteryl ester formation in macrophages.
Vitamin E supplementation has been reported to protect low density lipoprotein (LDL) from copper-induced oxidation and macrophage-mediated oxidation. We investigated the effect of in vitro vitamin E enrichment of LDL on the accumulation of [3H]cholesteryl ester (CE)-LDL and stimulation of cholesteryl ester formation in J774 macrophages. Vitamin E supplementation prolonged lag time (2.9-fold) before the initiation of copper-induced LDL oxidation. LDL, preincubated with 5 microM copper or with macrophages in Ham's F10 medium, accumulated in macrophages much more than did native LDL. However, following vitamin E enrichment, LDL accumulation was significantly reduced following oxidative stress. Vitamin E-enriched LDL also reduced the stimulation of cholesteryl ester formation in macrophages. Moreover, vitamin E enrichment of macrophages reduced the ability of the cells to oxidize LDL. The present results indicate that vitamin E supplementation protects LDL against copper-induced and macrophage-mediated oxidation, inhibits oxidation-dependent accumulation of LDL in macrophages, and prevents stimulation of cholesteryl ester formation in macrophages. Additionally we have provided evidence that intra-cellular enrichment with vitamin E prevents oxidative modification of LDL by macrophages.
Arteriosclerosis↗
Plasma cholesteryl ester transfer protein activity is increased when trans-elaidic acid is substituted for cis-oleic acid in the diet.
The trans isomer of oleic acid (elaidic acid) increases low density lipoprotein (LDL) cholesterol and decreases high density lipoprotein (HDL) cholesterol in man. One possible mechanism for this effect is that trans fatty acids increase plasma cholesteryl ester transfer protein (CETP) activity. We examined the effect of dietary trans fatty acids on activity of this protein in plasma from 27 men in a double blind crossover comparison. The background diet, containing 15% energy as fat from dairy products, meat, bread and cereals, was supplemented with oleic or elaidic acid providing a further 20% energy. The elaidic supplement provided about 6% energy as trans fatty acid. Activity of CETP in plasma was significantly higher (P < 0.001) after the elaidic acid-rich diet (23.95 +/- 1.26%) compared with the diet enriched with oleic acid (19.61 +/- 0.89%). A significant correlation between the change in plasma trans 18:1 fatty acids and the change in plasma CETP activity (r = 0.58, P < 0.002) was independent of changes in LDL-cholesterol. The increase in CETP activity was in turn significantly correlated with a fall in HDL-cholesterol among subjects during the elaidic acid-rich period (r = -0.57, P < 0.01). We have shown that CETP demonstrates substrate specificity and that the increase in activity with dietary trans fatty acids may contribute to a more atherogenic lipoprotein profile.
Adult↗
Partial replacement of saturated fatty acids with almonds or walnuts lowers total plasma cholesterol and low-density-lipoprotein cholesterol.
Sixteen normolipidemic male volunteers aged 41 +/- 9 y (mean +/- SD) consumed a diet providing 36% of energy as fat (92 g fat/d) for 9 wk. A daily supplement of nuts (providing half of the total fat intake) was provided against a common background diet. In the first 3-wk period the background diet was supplemented with raw peanuts (50 g/d), coconut cubes (40 g/d), and a coconut confectionary bar (50 g/d), designed to provide 47 g fat with a ratio of polyunsaturated to monounsaturated to saturated fatty acids (P:M:S) to match the Australian diet (reference diet). During the following 3 wk the background diet was supplemented with monounsaturated fatty acid-rich raw almonds (84 g/d), equivalent to 46 g fat, and during the final 3-wk period the background diet was supplemented with polyunsaturated fatty acid-rich walnuts (68 g/d), equivalent to 46 g fat. Compared with the reference diet there were significant reductions in total and LDL cholesterol, 7% and 10%, respectively, after supplementation with almonds, and 5% and 9%, respectively, after supplementation with walnuts.
Adult↗
Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives.
OBJECTIVE: To assess the effects of omega-3 (n-3) fatty acid supplementation on blood pressure and plasma lipids in hypertensives treated with diuretics or beta-blockers. DESIGN: Double-blind placebo-controlled cross-over trial consisting of a 4-week run-in phase and two 6-week intervention phases. PATIENTS: A total of 43 patients of either sex taking a beta-blocker only (n = 29), a diuretic only (n = 3) or a beta-blocker plus diuretic (n = 11) for hypertension were recruited from general practice. One patient from the latter group was withdrawn. METHODS: Seated blood pressure was measured every 2 weeks in the clinic with a Dinamap. After the run-in phase, participants were randomly assigned to take a supplement of either Omacor (85% n-3 fatty acid concentrate) or corn oil (four 1-g capsules/day) for 6 weeks, after which they crossed over to the other supplement. Fasted blood samples were taken at the end of each phase for lipid analysis. MAIN OUTCOME MEASURES: The within-individual differences in systolic and diastolic pressure and plasma lipids between Omacor and corn oil treatment. RESULTS: Systolic/diastolic blood pressures measured during the run-in phase were normal (132 +/- 2/76 +/- 1 mmHg, n = 42) but decreased further with n-3 fatty acid supplementation. The mean within-individual difference in blood pressure compared with corn oil supplementation was 3.1 +/- 1.0/1.8 +/- 0.6 mmHg (P < 0.01). This was accompanied by a 21% reduction in plasma triglycerides (P < 0.01) and a 15% increase in high-density lipoprotein-2 cholesterol (P < 0.01) but there were no significant differences in total or low-density lipoprotein cholesterol. CONCLUSION: The antihypertensive and hypotriglyceridaemic effects of n-3 fatty acid supplementation seen in the present study suggest that it may be a useful adjunct to antihypertensive therapy with beta-blockers or diuretics.
Adrenergic beta-Antagonists↗
The low-density lipoprotein receptor and cholesterol synthesis are affected differently by dietary cholesterol in the rat.
In the hamster and the rabbit, the low-density lipoprotein (LDL) receptor and cholesterol synthesis are coordinately downregulated by dietary cholesterol. In the rat, cholesterol synthesis is downregulated but LDL kinetic studies suggest that the LDL receptor is not. The aim of this study was to determine the effect of dietary cholesterol on the expression of the hepatic LDL receptor in the rat. Young (2 months) hooded and albino Wistar rats and older (9 months) Sprague-Dawley rats were used because of their reported different propensities to develop hypercholesterolaemia when fed cholesterol. Hepatic LDL receptor activity was measured using a dot blot assay with LDL-gold and LDL receptor mass was measured using an electroblot assay with a polyclonal antibody. Dietary cholesterol had no effect on the plasma cholesterol concentration in both strains of young Wistar rats but increased it in the older Sprague-Dawley rats. Cholesterol synthesis as measured with 3H2O or as indicated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity or the ratio of plasma lathosterol to cholesterol was effectively downregulated by dietary cholesterol (1% w/w) in all three strains. In contrast, dietary cholesterol increased both hepatic LDL receptor activity and mass in the young Wistar rats and had no effect on either receptor activity or mass in the older Sprague-Dawley rats. Increases in receptor activity occurred despite increases in hepatic cholesterol especially when cholic acid was added to the cholesterol diet. The effect was systemic because CL 277082, an inhibitor of intestinal cholesterol absorption, prevented the increase in LDL receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation.
Low-density lipoprotein (LDL) oxidation was measured in vitro to determine intraindividual variability and to relate oxidation to linoleic acid enrichment. Intraindividual variability was determined for eight subjects on 3 consecutive days after 14 d on a fixed diet. Coefficients of variation were 7.49 +/- 1.50%, 6.58 +/- 1.16%, and 4.58 +/- 0.77% for oxidation rate, lag time, and diene concentration, respectively. In the second study 12 normolipidemic men consumed a daily diet supplement containing 35 g linoleate-rich oil in one period and 35 g oleate-rich oil in the other period (2 x 3 wk crossover). LDL oxidized faster after the linoleate diet than after the oleate diet (mean +/- SE: 16.42 +/- 0.85 and 13.16 +/- 0.68 nmol diene.mg LDL protein-1.min-1, respectively, P < 0.02) and produced more conjugated diene (416 +/- 12.60 and 379.29 +/- 11.06 nmol/mg protein, respectively, P < 0.05) in proportion to the increase in LDL linoleate (r = 0.698, P < 0.001 and r = 0.618, P < 0.01 for rate and diene concentration, respectively). Lag time before onset of oxidation was not significantly altered by the linoleate-rich diet.
Carotenoids↗
Antioxidant vitamins and low-density-lipoprotein oxidation.
Low-density-lipoprotein (LDL) oxidation was examined in 22 subjects (10 men, 12 women) after a daily dose of 18 mg beta-carotene, 900 mg vitamin C, and 200 mg alpha-tocopherol for 6 mo. Control subjects (12 men, 11 women) took no vitamin supplements. After 3-mo supplementation plasma concentrations of beta-carotene, alpha-tocopherol, and ascorbic acid increased fivefold (P < 0.001), 55% (P < 0.01), and 27% (P < 0.05), respectively. There was no difference from baseline in rate of oxidation or total amount of conjugated diene produced between subjects taking or not taking vitamins. Malondialdehyde in LDL before and after oxidation was not different between the two groups. Lag time before the onset of oxidation was significantly lengthened after antioxidant supplementation (28% and 35% after 3 and 6 mo, respectively, P < 0.001). There was a significant independent correlation between percent change in lag time and percent change in plasma alpha-tocopherol (r = 0.47, P < 0.01).
Adult↗
Dietary non-starch polysaccharides interact with cholesterol and fish oil in their effects on plasma lipids and hepatic lipoprotein receptor activity in rats.
Male rats were fed the non-starch polysaccharides pectin, methylcellulose or guar gum with corn oil or with 60% of the corn oil replaced by fish oil. They were also fed these diets with or without cholesterol (+ cholic acid). Plasma total cholesterol concentration was higher overall in rats fed cholesterol and lower in those fed fish oil or fish oil + cholesterol. Plasma triacylglycerols were lower in rats fed fish oil with or without cholesterol. Hepatic LDL receptor activity was higher overall in rats fed fish oil or fish oil + cholesterol than in those fed cholesterol. Liver HDL receptor was lower overall in rats fed fish oil or cholesterol. Type of non-starch polysaccharide influenced these dietary effects so that in cholesterol-fed rats plasma cholesterol was highest in those fed methylcellulose, intermediate in those fed guar gum and in those fed pectin was unchanged from concentrations in rats fed pectin without cholesterol. Fish oil feeding lowered plasma cholesterol concentration in rats fed pectin or methylcellulose but not in those fed guar gum. Plasma triacylglycerols were lower in rats fed fish oil and all three non-starch polysaccharides, but concentrations were similar in rats fed pectin + fish oil + cholesterol and in those fed pectin. In rats fed methylcellulose + cholesterol and any non-starch polysaccharide + fish oils, HDL receptor activity was uniformly lower than in rats fed pectin, methylcellulose or guar gum. Low density lipoprotein receptor activity was higher in rats fed pectin + fish oil or pectin + fish oil + cholesterol than in rats fed pectin.
Animals↗
Plasma cholesterol-lowering potential of edible-oil blends suitable for commercial use.
We tested semihardened blends of edible oils, suitable for commercial food manufacture, with a lower-than-conventional saturated fatty acid content, for their effects on plasma cholesterol. Twenty-six mildly hypercholesterolemic men took part in a double-blind crossover experiment in which two test blends were compared with two control dietary periods [which resembled the Australian fat intake: proportions of polyunsaturated, monounsaturated, and saturated fatty acids (PMS) 0.4:0.9:1]. PMS in the test diets was approximately 0.8:1.3:1 and resulted in significantly lower LDL-cholesterol concentrations (reductions of less than or equal to 7.7%). HDL cholesterol and plasma triglyceride were unchanged. The trans fatty acid (mainly elaidic) content of the blends was 16%, raising its contribution to energy by 4% but without apparent effect on LDL and HDL concentrations. Provided the overall ratio of linoleic acid to palmitic acid in commercial edible-oil blends exceeds that in the prevailing national diet, partial hydrogenation will not negate the LDL-lowering potential.
Adult↗
Plasma lipoprotein lipid and Lp[a] changes with substitution of elaidic acid for oleic acid in the diet.
The effect of additional dietary trans fatty acids (7% energy) on plasma lipids was assessed in a double-blind comparison of four separate diets: 1, enriched with butter fat (lauric-myristic-palmitic); 2, oleic acid-rich; 3, elaidic acid-rich; 4, palmitic acid-rich. The total dietary period was 11 weeks and comprised normal foods plus specific fat supplements. In 27 mildly hypercholesterolemic men, total and LDL cholesterol were significantly lower during the 3-week oleic acid-rich diet, and were similar during the other three diets. For the four diets LDL cholesterol levels were in mg/dl: 1, 163; 2, 151; 3, 165; 4, 161. HDL cholesterol was significantly higher with the palmitic acid-rich diet, 42 mg/dl, compared with elaidic acid, 38 mg/dl, which in turn was not lower than with oleic acid, 38 mg/dl. Plasma elaidic acid concentration rose seven-fold with the trans fatty acid diet but did not increase the vulnerability of LDL to oxidative change. The elaidic acid-rich diet led to significant elevations in the level of Lp[a] compared to all the other test diets. The Lp[a] level increased to 296 +/- 220 U/l in the elaidic acid-rich period from 235 +/- 182 (mean +/- SD) in the first ("butter") period (P less than 0.001) compared with 249 +/- 204 in the palmitic acid period (P less than 0.001) and 236 +/- 201 in the oleic acid period (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n-3 fatty acids in mildly hyperlipidemic males.
The effects of fish and fish oil on lipids, hemostasis, and blood pressure were compared in 25 mildly hyperlipidemic men who received 4.5 g eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 5 wk. Six additional subjects served as controls. Fish and fish oil lowered plasma triglycerides 20% and 28% and very-low-density-lipoprotein (VLDL) triglycerides 42% and 52%, respectively (all P less than 0.05 compared with control). High-density-lipoprotein (HDL) cholesterol increased by 10% and 9%, with 34% and 32% increases in the proportion of HDL2 particles for fish and fish oil, respectively. Changes in total cholesterol, LDL cholesterol, apolipoprotein B, and blood pressure with fish and fish oil were not significantly different from changes for the control diet. The fish lowered fibrinogen (15.7%) and thromboxane (10.5%) and increased bleeding time (10.8%) (P less than 0.05 compared with control). Eating fatty fish and fish oil produced comparable lipid and lipoprotein changes, but only the fish improved hemostatic factors.
Adult↗
Incorporation and effects of dietary eicosapentaenoate (20:5(n-3)) on plasma and erythrocyte lipids of the marmoset following dietary supplementation with differing levels of linoleic acid.
The effect of dietary eicosapentaenoic acid (EPA, 20:5(n-3), as the ethyl ester) on plasma lipid levels and the incorporation of EPA into erythrocyte and plasma lipids were investigated in the marmoset monkey. Marmosets were fed high mixed-fat diets (14.5% total fat) supplemented with or without 0.8% EPA for 30 weeks. Markedly elevated plasma cholesterol (16.4 mmol/l) was induced by an atherogenic-type diet but with EPA supplementation, plasma cholesterol increased to only 6.6 mmol/l. Plasma triacylglycerol levels were not elevated with an atherogenic type diet. Substantial EPA incorporation was evident for plasma phospholipid, triacylglycerol and cholesterol ester fractions. The proportion of docosapentaenoic acid (22:5(n-3)) but not docosahexaenoic acid (22:6(n-3)) was also elevated in these plasma lipid fractions. Greatest incorporation of EPA occurred when it was administered with an atherogenic type diet having a P:M:S (polyunsaturated:monounsaturated:saturated) fatty acid ratio of about 0.2:0.6:1.0 in comparison to the control diet of 1.0:1.0:1.0. Incorporation of EPA and 22:5(n-3)) into erythrocyte phospholipids was also apparent and this was at the expense of linoleic acid (18:2(n-6)). These results in the marmoset highlight both the cholesterol-lowering properties of EPA and the extent of its incorporation into plasma lipids and erythrocyte membrane phospholipids with far greater incorporation occurring when the level of dietary linoleic acid was reduced.
Animals↗
Effect of a high fat/cholesterol diet with or without eicosapentaenoic acid on plasma lipids, lipoproteins and lipid transfer protein activity in the marmoset.
Marmosets fed a diet supplemented with 0.2% cholesterol and 10% sheep fat (by weight) developed hypercholesterolemia with a 4-fold increase in plasma cholesterol (4.28 +/- 0.57-16.38 +/- 4.22 mmol/l, mean +/- SD, P less than 0.001). This was due mainly to a 5-fold increase in the intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fraction (d = 1.006-1.063 g/ml). The proportion of plasma cholesterol in high density lipoproteins (HDL) decreased from 56% to 25% although HDL cholesterol increased from 2.40 +/- 0.42 to 4.09 +/- 0.92 mmol/l (P less than 0.001), and HDL particle radius increased from 5.10 +/- 0.18 nm to 6.06 +/- 0.73 nm (P less than 0.05). Plasma lipid transfer protein (LTP) activity increased 2.5-fold in whole plasma and 2-fold in lipoprotein-deficient plasma. The atherogenic lipoprotein profile was attenuated by adding 0.8% eicosapentaenoic acid (EPA, 20:5 n - 3, as the ethyl ester) to the atherogenic diet. Plasma cholesterol increased only 55% to 6.64 +/- 2.55 mmol/l with only an 80% increase in lipoproteins in the d = 1.006-1.063 g/ml fraction and a more favourable proportion of plasma cholesterol in HDL (44%) than without EPA. LTP activity was reduced to 1.7-fold above control in whole plasma by addition of EPA to the atherogenic diet. There was a positive correlation between plasma cholesterol and LTP activity in whole plasma (r = 0.89, P less than 0.001) and in lipoprotein-deficient plasma (r = 0.67, P less than 0.001). EPA therefore attenuated some of the adverse effects of a 0.2% cholesterol, 10% sheep fat diet on plasma lipids and lipoproteins and induced a less atherogenic profile.
Animals↗
Effects of blocking plasma lipid transfer protein activity in the rabbit.
Plasma lipid transfer protein activity was completely blocked in rabbits for up to 48 h by infusion with goat antibody to rabbit lipid transfer protein. Lipid transfer protein activity in plasma of control animals, infused with antibody from a non-immune goat, decreased during the experiment but was never less than 50% of pre-infusion levels. During the period that lipid transfer protein activity was completely blocked, there were changes in high-density lipoprotein composition (expressed as % by weight) with a reduction in triacylglycerol from 8.4 +/- 2.4% to 1.0 +/- 0.2% (P less than 0.05) and an increase in esterified cholesterol from 10.7 +/- 1.7% to 14.5 +/- 0.3% (P less than 0.1). In conjunction with the observed changes in high-density lipoprotein composition, there was an increase in high-density lipoprotein particle size from a mean radius of 4.7 to 5.4 nm. The change in composition and particle size was not observed in high-density lipoproteins from control animals. There was a change in the distribution of plasma cholesterol in control animals, with a fall in the proportion of cholesterol in high-density lipoproteins (P less than 0.02) and consequently an increase in the proportion of cholesterol in low-density lipoproteins (P less than 0.02). However, the distribution of plasma cholesterol in animals in which lipid transfer protein activity was inhibited was maintained at original levels during the period of inhibition. Consequently, in these animals, there was a less atherogenic distribution of cholesterol during the period of lipid transfer protein inhibition when compared with control animals. The changes observed in lipoproteins, in the absence of lipid transfer protein activity, demonstrate that lipid transfer protein modifies lipoproteins in vivo and appears to contribute to a more atherogenic lipid profile.
Animals↗
D-galactosamine induced hepatitis in the rabbit: effect on lecithin:cholesterol acyltransferase activity, plasma lipid transfer protein activity and high density lipoproteins.
Hepatitis was induced in rabbits by a single intraperitoneal injection of D(+)-galactosamine-HCl (750 mg/kg body wt). Plasma lecithin:cholesterol acyltransferase activity fell to 5% and lipid transfer protein activity to 50% of control values 48 hr after injection. Discoid high density lipoprotein began to appear in plasma of treated rabbits 36 hr after injection, along with populations of high density lipoprotein (HDL) which were both smaller (radius 3.7 nm) and larger (radius 5.9 nm) than the original HDL population (radius 4.8 nm).
Alanine Transaminase↗
Immunoprecipitation of lipid transfer protein activity by an antibody against human plasma lipid transfer protein-I.
Two lipid transfer proteins, designated lipid transfer protein-I (Mr 69 000) and lipid transfer protein-II (Mr 55 000), each of which facilitates the transfer of radiolabelled cholesteryl ester, triacylglycerol and phosphatidylcholine between plasma lipoproteins, were purified from human plasma. Immunoglobulin G was prepared from goat antiserum to human lipid transfer protein-I (i.e., anti-human LTP-I IgG). The progressive addition of anti-human LTP-I IgG to buffered solutions containing either a highly purified mixture of human lipid transfer protein-I and lipid transfer protein-II, or highly purified rabbit lipid transfer protein (Abbey, M., Calvert, G.D. and Barter, P.J. (1984) Biochim. Biophys. Acta 793, 471-480) resulted in specific immunoprecipitation and the removal of increasing amounts, up to 100%, of cholesteryl ester, triacylglycerol and phosphatidylcholine transfer activities. However, similar precipitation studies on human and rabbit lipoprotein-free plasma resulted in the progressive removal of all cholesteryl ester and triacylglycerol transfer activities but only 30% (human) or 20% (rabbit) of phosphatidylcholine transfer activity. In all cases more anti-human LTP-I IgG was required to precipitate rabbit lipid transfer activity than human lipid transfer activity. These results suggest that lipid transfer protein-I and lipid transfer protein-II have antigenic sites in common, allowing precipitation of both proteins by specific antibody to lipid transfer protein-I. Most plasma phosphatidylcholine transfer activity is mediated by a protein (or proteins) other than lipid transfer protein-I and lipid transfer protein-II. In lipoprotein-free plasma all cholesteryl ester and triacylglycerol transfer activity, and some phosphatidylcholine transfer activity, is mediated by lipid transfer protein-I (or lipid transfer protein-I and an antigenically similar protein, lipid transfer protein-II.
Animals↗
Plasma lipoproteins, apolipoproteins, and proteins concerned with lipid metabolism.
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Animals↗