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Biomedical subjects

M Abbey

Publications and source records attributed to M Abbey.

At least 19 recordsLinked to original sources

Moderate acute intake of de-alcoholized red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo -- results of a comparative in vivo intervention study in younger men.

Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, de-alcoholized red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of de-alcoholized red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R=-0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

Adult↗

Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods.

OBJECTIVES: To determine the efficacy on plasma cholesterol-lowering of plant sterol esters or non-esterified stanols eaten within low-fat foods as well as margarine. DESIGN: Randomised, controlled, single-blind study with sterol esters and non-esterified plant stanols provided in breakfast cereal, bread and spreads. Study 1 comprised 12 weeks during which sterol esters (2.4 g) and stanol (2.4 g)-containing foods were eaten during 4 week test periods of cross-over design following a 4 week control food period. In Study 2, in a random order cross-over design, a 50% dairy fat spread with or without 2.4 g sterol esters daily was tested. SUBJECTS: Hypercholesterolaemic subjects; 22 in study 1 and 15 in study 2. MAIN OUTCOME MEASURES: Plasma lipids, plasma sterols, plasma carotenoids and tocopherols. RESULTS: Study 1-median LDL cholesterol was reduced by the sterol esters (-13.6%; P<0.001 by ANOVA on ranks; P<0.05 by pairwise comparison) and by stanols (-8.3%; P=0.003, ANOVA and <0.05 pairwise comparison). With sterol esters plasma plant sterol levels rose (35% for sitosterol, 51% for campesterol; P<0.001); plasma lathosterol rose 20% (P=0.03), indicating compensatory increased cholesterol synthesis. With stanols, plasma sitosterol fell 22% (P=0.004), indicating less cholesterol absorption. None of the four carotenoids measured in plasma changed significantly. In study 2, median LDL cholesterol rose 6.5% with dairy spread and fell 12.2% with the sitosterol ester fortified spread (P=0.03 ANOVA and <5% pairwise comparison). CONCLUSION: 1. Plant sterol esters and non-esterified stanols, two-thirds of which were incorporated into low-fat foods, contributed effectively to LDL cholesterol lowering, extending the range of potential foods. 2. The LDL cholesterol-raising effect of butter fat could be countered by including sterol esters. 3. Plasma carotenoids and tocopherols were not reduced in this study. SPONSORSHIP: Meadow Lea Foods, Australia.

Adult↗

Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase.

Genetic linkage studies in rodents and humans have identified specific chromosomal regions harboring seizure susceptibility genes. We have identified a novel polymorphism in the human alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase (NaK-pump), a candidate gene for human temporal lobe epilepsy (TLE) based on its chromosomal location and function in ion homeostasis. The polymorphism consists of a four base pair insertion 12 base pairs upstream of the start of exon 2. We performed an association study between this polymorphism and TLE. Our study did not find a significant difference in the frequency of this polymorphism between TLE patients and controls, indicating that this variation is not a major susceptibility factor. However, since the number of patients studied so far is small and the functional consequence of the polymorphism is unknown, the variation may yet be found to play a minor role in increased risk for seizure susceptibility. In contrast to the findings in TLE patients and controls, we did find a significant difference in the frequency of the variation between African Americans and persons of European descent. This finding demonstrates the potential effect of population stratification on studies of this type and supports the growing use of parental and familial samples for controls in association studies. Further study of this polymorphism is warranted as it may be involved in other disease processes for which there are known ethnic-specific susceptibilities. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:79-83, 2000.

Base Sequence↗

Effects of n-3 fatty acids on growth and survival of J774 macrophages.

To further understand potential mechanisms underlying the protective effects of eicosapentanoic acid (EPA) against atherosclerosis, J774 macrophages were used to explore cellular responses to growth in the presence of PUFA in vitro. Clonogenic assays indicated that 15 microg/ml of EPA killed over 90% of J774 populations. Docosapentaenoic acid (DPA) was more cytotoxic than either EPA or docosahexaenoic acid (DHA). EPA was shown to be elongated to DPA. Cytotoxicity induced by EPA was not inhibited by the presence of alpha-tocopherol (a-toc) in the medium. Immunological screening for caspase enzymes and microscopic examination indicated that apoptosis was not the major cause of cell death. Proliferation assays demonstrated that total cell numbers of EPA-treated cells were not significantly different to control cells. Increasing does of EPA were correlated with increasing levels of intracellular malondialdehyde (MDA). These observations suggest that EPA may influence the growth parameters of macrophages whilst inducing moderately elevated levels of oxidative stress.

Animals↗

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity.

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00 +/- 0.15, 5.36 +/- 0.17 (P < 0.01), 5.63 +/- 0.13 (P < 0.05) mmol/l, respectively for total cholesterol; 4.13 +/- 0.15, 3.64 +/- 0.15 (P < 0.05), 3.82 +/- 0.12 (P < 0.05) mmol/l, respectively for LDL-cholesterol; 48.19 +/- 9.90, 26.59 +/- 5.53 (P < 0.03), 25.12 +/- 4.62 (P < 0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r = -0.27, P < 0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16 +/- 0.07 mmol/l) than in the premenopausal group (0.96 +/- 0.07) or postmenopausal group not using HRT (0.87 +/- 0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.

Analysis of Variance↗

The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro.

Oxidation of low density lipoprotein (LDL) is implicated in the development of atherosclerosis and dietary antioxidants may provide a useful therapy in the prevention of LDL oxidation and atheroma development. The aim of these experiments was to investigate the antioxidant activity of the soybean isoflavone, genistein, in in vitro models of LDL oxidation. Genistein inhibited copper-mediated oxidation of LDL in a concentration-dependent manner by lengthening the time for conjugated diene formation (54.1 +/- 5.1 min in control LDL and 107.1 +/- 1.8 min with 5 micromol/l genistein, P<0.001) and decreasing the oxidation rate (14.4 +/- 1.9 nmol conjugated diene/mg LDL protein/min in control LDL and 7.4 +/- 1.1 nmol conjugated diene/mg LDL protein/min with 5 micromol/l genistein, P<0.001). Peroxy radical (azo-initiated) oxidation of LDL was significantly inhibited by 200 micromol/l genistein as indicated by: (i) increase in the time required for malondialdehyde (MDA) formation (7 h incubation compared to 3 h incubation with control LDL), (ii) 32, 44 and 46% decreases in MDA concentration compared to control samples following 3, 4 and 5 h incubation, respectively and (iii) decrease in relative electrophoretic mobility (REM) of LDL. Incorporation of genistein into LDL and its resultant antioxidant activity was also investigated. LDL was isolated from plasma which had been pre-incubated with 25. 50 or 100 micromol/l genistein at 37 degrees C for 24 h. Approximately 3-4% of genistein present in plasma was incorporated into LDL, however copper-mediated oxidation of control LDL and LDL isolated from plasma pre-incubated with genistein was not significantly different.

Amidines↗

Lipid content and fatty acid composition of 11 species of Queensland (Australia) fish.

The fatty acid composition of 11 species of fish caught of the northeast coast of Australia was determined. No fatty acid profiles have been previously published for fish from this area nor for nine of these species. Although the percentage of polyunsaturated fatty acid (PUFA) was the same as the calculated average for Australian fish (42.3%), the percentage of n-3 fatty acids was lower (24.4 +/- 5.4% vs. 30.7 +/- 10.1%) and the n-6 fatty acids higher (16.5 +/- 4.5% vs. 11.2 +/- 5.9%), P < 0.001 in each case. The major n-3 PUFA were docosahexaenoic (15.6 +/- 6.3%) and eicosapentaenoic acid (4.3 +/- 1.1%) while the major n-6 PUFA were arachidonic (8.3 +/- 3.2%) and n-6 docosatetraenoic acid (3.1 +/- 1.3%). The second-most abundant class of fatty acid was the saturates (31.6 +/- 3.5%) while the monounsaturates accounted for 17.4 +/- 4.3% of the total fatty acids. The monounsaturate with the highest concentration was octadecenoic acid (11.8 +/- 2.6%). There was a positive correlation between the total lipid content and saturated and monounsaturated fatty acids (r = 0.675 and 0.567, respectively) and a negative correlation between the total lipid content and PUFA (r = 0.774).

Animals↗

Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro.

The oxidative modification of low density lipoproteins (LDL) has been implicated in the development of atherosclerosis. This study examined the effect of red wine, ethanol and red wine stripped of phenols on copper-mediated and azo-initiated LDL oxidation. Red wine containing phenolic compounds (0.025-20 mg/l gallic acid equivalents) increased the lag time of conjugated diene formation, inhibited the generation of thiobarbituric acid reactive substances (TBARS) and decreased the relative electrophoretic mobility of LDL in a concentration-dependent manner. These changes were not apparent in LDL incubated with ethanol or red wine stripped of phenols. In other experiments, red wine (75 mg/l gallic acid equivalents) was incubated with plasma at 37 degrees C for 3 h. The LDL isolated from this plasma displayed a 60% increase in lag time following copper-mediated oxidation. Uptake of this LDL by cultured J774 macrophages was three-fold lower than control LDL. Red wine was fractionated into phenolic acids (fraction 1), catechins and monomeric anthocyanidins (fraction 2), flavonols (fraction 3) and polymeric anthocyanidins (fraction 4). All red wine fractions prolonged the time before LDL oxidation. Fraction 2 displayed a significantly greater antioxidant activity than fractions 3 and 4 (but not fraction 1) in at least one pro-oxidant model. In conclusion we have shown that antioxidant compounds in red wine can associate with LDL particles following an incubation in whole plasma, can exert an antioxidant effect and, in so doing, can inhibit the uptake of the lipoprotein by macrophages. This antioxidant effect of red wine was apparent in most of the phenolic fractions separated from wine, particularly catechins, monomeric anthocyanidins and phenolic acids.

Amidines↗

Direct gene transfer into human epileptogenic hippocampal tissue with an adeno-associated virus vector: implications for a gene therapy approach to epilepsy.

PURPOSE: Virus vectors capable of transferring genetic information into human cells provide hope for improved therapy in several neurological diseases, including epilepsy. We evaluated the ability of an adeno-associated virus (AAV) vector to transfer and cause expression of a lacZ marker gene in brain slices obtained from patients undergoing temporal lobectomy for control of medically intractable seizures. METHODS: Human brain slices were injected with an AAV vector (AAVlacZ) encoding Escherichia coli beta-galactosidase and incubated for as long as 24 h. The presence of lacZ mRNA. beta-galactosidase protein and enzymatic activity were assayed by reverse transcriptase polymerase chain reaction (rtPCR), immunocytochemistry, and the X-Gal technique, respectively. RESULTS: AAVlacZ directed the expression in human epileptogenic brain of E. coli beta-galactosidase that had functional activity. Expression was observed in < or =5 h and was sustained for as long as the slices were viable. Morphological analysis indicated that neurons were preferentially transfected, and there was no evidence of cytotoxicity. CONCLUSIONS: Our results confirm the feasibility of using AAV vectors to transfer genes into the human CNS and in particular, into neurons. Replacement of the lacZ gene with a functional gene modulating hippocampal neuronal physiology, might allow a localized genetic intervention for focal seizures based on the stereotaxic or endovascular delivery of such a vector system into the appropriate brain region.

Dependovirus↗

Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women.

The possibility that the heightened cardiovascular risk associated with the menopause, which is said to be ameliorated by soybeans, can be reduced with soy isoflavones was tested in 21 women. Although several were perimenopausal, all have been included. A placebo-controlled crossover trial tested the effects of 80-mg daily isoflavones (45 mg genistein) over 5- to 10-week periods. Systemic arterial compliance (arterial elasticity), which declined with age in this group, improved 26% (P < .001) compared with placebo. Arterial pressure and plasma lipids were unaffected. The vasodilatory capacity of the microcirculation was measured in nine women; high acetylcholine-mediated dilation in the forearm vasculature was similar with active and placebo treatments. LDL oxidizability measured in vitro was unchanged. Thus, one important measure of arterial health, systemic arterial compliance, was significantly improved in perimenopausal and menopausal women taking soy isoflavones to about the same extent as is achieved with conventional hormone replacement therapy.

Adult↗

Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability.

The compliance or elasticity of the arterial system, an important index of circulatory function, diminishes with increasing cardiovascular risk. Conversely, systemic arterial compliance improves through eating of fish and fish oil. We therefore tested the value of high intake of alpha-linolenic acid, the plant precursor of fish fatty acids. Fifteen obese people with markers for insulin resistance ate in turn four diets of 4 weeks each; saturated/high fat (SHF), alpha-linolenic acid/low fat (ALF), oleic/low fat (OLF), and SHF. Daily intake of alpha-linolenic acid was 20 g from margarine products based on flax oil. Systemic arterial compliance was calculated from aortic flow velocity and aortic root driving pressure. Plasma lipids, glucose tolerance, and in vitro LDL oxidizability were also measured. Systemic arterial compliance during the first and last SHF periods was 0.42 +/- 0.12 (mean +/- SD) and 0.56 +/- 0.21 units based on milliliters per millimeter of mercury. It rose significantly to 0.78 +/- 0.28 (P < .0001) with ALF; systemic arterial compliance with OLF was 0.62 +/- 0.19, lower than with ALF (P < .05). Mean arterial pressures and results of oral glucose tolerance tests were similar during ALF, OLF, and second SHF; total cholesterol levels were also not significantly different. However, insulin sensitivity and HDL cholesterol diminished and LDL oxidizability increased with ALF. The marked rise in arterial compliance at least with alpha-linolenic acid reflected rapid functional improvement in the systemic arterial circulation despite a rise in LDL oxidizability. Dietary n-3 fatty acids in flax oil thus confer a novel approach to improving arterial function.

Arteries↗

Enhanced capacity of n-3 fatty acid-enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins.

We have investigated possible mechanisms by which n-3 fatty acid-enriched macrophages enhance the oxidation of low density lipoprotein (LDL), and the ability of antioxidant vitamins to prevent this. Macrophages were enriched with n-3 fatty acids (eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid) following incubation with fish oil. These macrophages produced large amount of TBARS in medium containing metals, and showed enhanced capacity to oxidize LDL (3-4 fold increase compared to control cells) and to accumulate the modified LDL. 5,8,11,14-eicosatetraynoic acid (ETYA, 15-lipoxygenase inhibitor) and superoxide dismutase (SOD) did not inhibit the enhanced capacity of n-3 fatty acid-enriched cells to oxidize LDL. However antioxidants, (vitamin E-enriched macrophages or vitamin C in the medium), inhibited this enhanced capacity. Medium conditioned by n-3 fatty acid-enriched cells had pro-oxidant effects on metal-initiated LDL oxidation. We conclude that n-3 fatty acid-enriched macrophages display increased oxidant capacity which is not inhibited by ETYA or SOD, and that antioxidant vitamins inhibit the enhanced capacity to oxidize LDL.

5,8,11,14-Eicosatetraynoic Acid↗

Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women.

OBJECTIVE: Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post-menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. DESIGN: Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium-dependent dilatation (flow-mediated dilatation). PATIENTS: We investigated 135 healthy women; 40 were pre-menopausal (mean +/- SD age/26 +/- 6 years, group 1), 40 were post-menopausal and had never taken HRT (aged 58 +/- 3 years; group 2) and 55 were age-matched post-menopausal women who had taken HRT for > or = 2 years, from within 2 years of the menopause (aged 57 +/- 4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen-only HRT. RESULTS: In group 2, flow-mediated dilatation was significantly reduced compared with group 1 (4.4 +/- 3.4 vs 9.6 +/- 3.6%, P < 0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow-mediated dilatation was significantly better than group 2 (6.2 +/- 3.3 vs 4.4 +/- 3.4%, P = 0.01), suggesting a protective effect of HRT. Flow-mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5 +/- 2.8 vs 6.5 +/- 3.4%, P = 0.40). CONCLUSIONS: Long-term HRT is associated with improved arterial endothelial function in healthy post-menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.

Adolescent↗

Dietary supplementation with orange and carrot juice in cigarette smokers lowers oxidation products in copper-oxidized low-density lipoproteins.

OBJECTIVE: Our objective was to evaluate the effect of daily supplementation with foods high in vitamin C and beta carotene on plasma vitamin levels and oxidation of low-density lipoprotein (LDL) in cigarette smokers. SUBJECTS: Fifteen normolipidemic male cigarette smokers who did not usually take vitamin supplements were recruited into the study. INTERVENTIONS: Throughout the study, subjects consumed a diet rich in polyunsaturated fatty acids, which provided 36% of energy as fat: 18% from meat, dairy products, vegetable oils, and fat spreads and 18% from walnuts (68 g/day). Subjects consumed a vitamin-free drink daily for 3 weeks; then for 3 weeks they consumed daily supplements of orange juice (145 mg vitamin C) and carrot juice (16 mg beta carotene). RESULTS: Vitamin-rich food supplements raised plasma levels of ascorbic acid (1.6-fold; P < .01) and beta carotene (2.6-fold; P < .01). Malondialdehyde, one end product of oxidation, was lower in copper-oxidized LDL after vitamin supplementation (mean +/- standard error = 65.7 +/- 2.0 and 57.5 +/- 2.9 mumol/g LDL protein before and after supplementation, respectively; P < .01). Rate of LDL oxidation and lag time before the onset of LDL oxidation were not affected by antioxidant supplementation. CONCLUSIONS: In habitual cigarette smokers, antioxidant vitamins, which can be feasibly provided from food, partly protected LDL from oxidation despite a diet rich in polyunsaturated fatty acids.

Adult↗

Body fat distribution is a determinant of the high-density lipoprotein response to dietary fat and cholesterol in women.

We have conducted a dietary trial that addressed the factors influencing the variability in plasma lipids in response to dietary fat and cholesterol with a focus on the effects of gender and body fat distribution. Sixty-seven women and 53 men were selected so that overall men and women had a similar mean age, LDL cholesterol, and body mass index. After a 2-week low-fat period subjects were given two liquid supplements for 3 weeks each, one that contained 31 to 40 g fat and 650 to 845 mg cholesterol, and one that was fat free. Measurements included plasma lipids and lipoproteins, glucose, insulin, hepatic triglyceride lipase activity, apolipoprotein E polymorphism, and three indexes of body fat (body mass index, waist girth, and waist-hip ratio). In response to dietary fat and cholesterol supplementation only the changes in HDL cholesterol, especially in HDL2, differed between the sexes. Although on univariate analysis lipoprotein changes were predicted by baseline lipoprotein levels, body mass index, waist girth, waist-hip ratio, hepatic triglyceride lipase activity, and insulin, multiple regression showed only waist-hip ratio to predict changes in HDL2 cholesterol in women and body mass index and baseline HDL2 cholesterol in men. Changes in LDL were predicted by baseline LDL cholesterol in women and apolipoprotein E phenotype and age in men. These studies explain much of the variability that individuals show in lipoprotein changes, especially in the more desirable changes in cholesterol transport in HDL2, in response to eating saturated fat and cholesterol.

Adipose Tissue↗

Restriction fragment length polymorphism of the apolipoprotein B gene and response to dietary fat and cholesterol.

OBJECTIVE: The relationship between response to dietary fat and cholesterol, and the EcoRI restriction fragment length polymorphism (RFLP) of the apolipoprotein B(apoB) gene was examined. DESIGN: Forty-nine free-living subjects took part in a prospective double-blind crossover dietary intervention study. The apoB EcoRI cutting site was present in five women and 18 men (E+) and absent in 15 women and 11 men (E-). INTERVENTION: Subjects consumed a low fat (25% energy), low cholesterol (less than 200 mg/day) diet. After two weeks on this background diet (baseline) subjects were randomly assigned to consume a liquid supplement for three weeks which was either fat and cholesterol free or which contained fat (30 to 36 g) and cholesterol (650 to 780 mg). After the first three-week period subjects switched to the other supplement. Blood samples were collected for plasma lipid analysis after an overnight fast on two consecutive days at the end of baseline and on three consecutive days after each three-week supplement period. RESULTS: There was no significant difference in response to diet between the RFLP groups. Changes in plasma total, low density lipoprotein (LDL), high density lipoprotein(HDL), HDL2 and HDL3 cholesterol or plasma triglyceride were not different between the two RFLP groups. There was a significant difference between RFLP groups for baseline HDL2-cholesterol (0.31 +/- 0.04 and 0.16 +/- 0.02 mmol/L for E- and E+ subjects, respectively) which was independent of sex and apoE genotype (P = 0.032). CONCLUSIONS: These results indicate that the EcoRI RFLP of the apoB gene is not associated with response to dietary fat and cholesterol.

Apolipoproteins B↗

Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages.

The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein (LDL) oxidation was examined in 20 treated hypertensive subjects. The randomized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil. Fish oil significantly (-24%, P < 0.01) reduced plasma triglyceride, and increased LDL-cholesterol (+6%, P < 0.01 compared to corn oil). LDL particles were larger (P < 0.01) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride (P < 0.001) both before and after fish oil supplementation, and positively correlated with high density lipoprotein cholesterol (P < 0.01). Fish oil reduced lag time before onset of copper-induced LDL oxidation (-25%, P < 0.001) and significantly increased production of thiobarbituric acid-reactive substances (TBARS) during oxidation, compared with corn oil. Corn oil had no significant effect on lag time and oxidation rate. Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL. Corn oil was without effect. Additionally, macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly (P < 0.001) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids. We conclude that from the standpoint of atherosclerosis, fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable.

Aged↗