Ursel Wahrburg

Effects of dietary fatty acids on the composition and oxidizability of low-density lipoprotein.

Objective: The objective of this study was to compare the effects of dietary monounsaturated fatty acids (MUFA), n-6 and n-3 polyunsaturated fatty acids (PUFA) on LDL composition and oxidizability.Design, setting and subjects: Sixty-nine healthy young volunteers, students at a nearby college, were included. Six subjects withdrew because of intercurrent illness and five withdrew because they were unable to comply with the dietary regimen.Interventions: The participants received a 2-week wash-in diet rich in saturated fatty acids (SFA) followed by diets rich in refined olive oil, rapeseed oil or sunflower oil for 4 weeks. Intakes of vitamin E and other antioxidants did not differ significantly between the diets.Results: At the end of the study, LDL oxidizability was lowest in the olive oil group (lag time: 72.6 min), intermediate in the rapeseed oil group (68.2 min) and highest in the sunflower oil group (60.4 min, P<0.05 for comparison of all three groups). Despite wide variations in SFA intake, the SFA content of LDL was not statistically different between the four diets (25.8–28.5% of LDL fatty acids). By contrast, the PUFA (43.5%–60.5% of LDL fatty acids) and MUFA content of LDL (13.7–29.1% of LDL fatty acids) showed a wider variability dependent on diet.Conclusions: Enrichment of LDL with MUFA reduces LDL susceptibility to oxidation. As seen on the rapeseed oil diet this effect is independent of a displacement of higher unsaturated fatty acids from LDL. Evidence from this diet also suggests that highly unsaturated n-3 fatty acids in moderate amounts do not increase LDL oxidizability when provided in the context of a diet rich in MUFA.Sponsorship: This work was supported by the Central Marketing Agency of the German Agricultural Industry (CMA), the German Union for the Promotion of Oil- and Protein Plants (UFOP), the Austrian Science Foundation, project F00709 (to P.M.A.) and the Brökelmann Ölmühle Company, Hamm, Germany.

Dietary α-Linolenic Acid, EPA, and DHA Have Differential Effects on LDL Fatty Acid Composition but Similar Effects on Serum Lipid Profiles in Normolipidemic Humans

Our aim was to study the effects of increased dietary intake of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) on serum lipids and LDL fatty acid compositions. To this end, a controlled parallel study was conducted in 74 healthy normolipidemic men and women aged 19-43 y. Participants were randomly assigned to 1 of 3 interventions and consumed a total intake of 4.4 g/d ALA (ALA group), 2.2 g/d EPA (EPA group), and 2.3 g/d DHA (DHA group) for 6 wk. Fatty acid ethyl esters were incorporated into margarines, which replaced the participants normal spread. The ALA, EPA, or DHA intake led to a significant enrichment of the LDL with the respective (n-3) fatty acid. In addition, LDL EPA contents in the ALA group increased by 36% (P < 0.05) with no changes in LDL DHA. The EPA intervention led to an additional enrichment with DHA (24%; P < 0.001), whereas the DHA intervention further increased the amount of EPA (249%; P < 0.001). ALA, EPA, or DHA intake did not affect fasting serum concentrations of total and LDL cholesterol, but fasting serum triacylglycerol concentrations significantly decreased in the EPA (-0.14 mmol/L) and DHA (-0.30 mmol/L) interventions and also in the ALA intervention (-0.17 mmol/L). DHA intake significantly increased serum HDL cholesterol, whereas no changes were found with ALA or EPA intake. In conclusion, the present data support the hypothesis that isolated dietary ALA, EPA, and DHA intakes lead to differential enrichment in LDL due to interconversion. Moderate amounts of ALA, EPA, and DHA are effective in improving lipid profiles of normolipidemic humans.

Mediterranean diet, olive oil and health

The traditional Mediterranean diet is characterised by an abundance of plant foods (fruits, vegetables, cereals, legumes); olive oil is the principle source of fat. Dairy products, mainly yoghurt and cheese, are eaten in low to moderate amounts, as well as fish and poultry. Red meat is eaten only in small amounts. The Mediterranean diet contains wine in moderation, usually consumed with meals. These food patterns lead to a nutrient composition with low contents of unfavourable or undesirable nutrients (saturated fatty acids, trans fatty acids, cholesterol), with high contents of desirable and health-beneficial nutrients (dietary fibre, complex carbohydrates, monounsaturated fatty acids, vitamins, minerals, minor components), and with a low energy density. Due to its specific food patterns and its favourable nutrient composition the Mediterranean diet has undoubtedly contributed to the low rates of numerous chronic diseases observed in the Mediterranean region and has been proven as a model for healthy nutrition. In particular, a large body of evidence documents the beneficial relationship between the traditional Mediterranean diet, cardiovascular risk factors, such as hyperlipidaemia, hypertension, diabetes and obesity, and coronary heart disease. Furthermore, there is evidence that the Mediterranean diet plays a role in cancer prevention.

Treatment of hypertriglyceridemia by two diets rich either in unsaturated fatty acids or in carbohydrates: effects on lipoprotein subclasses, lipolytic enzymes, lipid transfer proteins, insulin and leptin.

BACKGROUND: There is lack of agreement on which dietary regimen is most suitable for treatment of hypertriglyceridemia, especially if high triglyceride concentrations are not due to obesity or alcohol abuse. We compared the effects on blood lipids of a diet high in total and unsaturated fat with a low-fat diet in patients with triglyceride concentrations of >2.3 mmol/l.METHODS: Nineteen non-obese male outpatients with triglycerides ranging from 2.30 to 9.94 mmol/l received two consecutive diets for 3 weeks each: first a modified high-fat diet (39% total fat, 8% SFA, 15% monounsaturated fatty acids, 1.6% marine n-3 polyunsaturated fatty acids), and then a low-fat diet (total fat 28%, carbohydrates 54%).RESULTS: The high-fat diet significantly decreased triglycerides (−63%), total cholesterol (−22%), VLDL cholesterol (−54%), LDL cholesterol (−16%), total apoC-III (−27%), apoC-III in apoB containing lipoproteins (apoC-III LpB; −31%) and in HDL (apoC-III nonLpB; −29%), apoE in serum (−33%) and apoB-containing lipoproteins (nonHDL-E; −42%), LpA-I (−16%), insulin (−36%), and leptin (−26%) and significantly increased the means of HDL cholesterol (+8%), LDL size (+6%), lipoprotein lipase (LPL, +11%), hepatic lipase (+13%), and lecithin: cholesterol acyltransferase (LCAT, +2%). The subsequent low-fat diet increased triglycerides (+63%), VLDL cholesterol (+19%), apoC-III (+23%), apoC-III LpB (+44%) apoC-III nonLpB (+17%), apoE (+29%) and nonHDL-E (+43%), and decreased HDL cholesterol (−12%), LPL (−3%), and LCAT (−3%). Changes in triglycerides correlated with changes in LPL activity and insulin levels.CONCLUSIONS: In hypertriglyceridemic patients, a modified diet rich in mono- and n-3 polyunsaturated fatty acids is more effective than a carbohydrate-rich low-fat diet in correcting the atherogenic lipoprotein phenotype.

Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers.

Objective:To compare the individual effects of dietary α-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on low-density lipoprotein (LDL) fatty acid composition, ex vivo LDL oxidizability and tocopherol requirement.Design, setting and subjects:A randomized strictly controlled dietary study with three dietary groups and a parallel design, consisting of two consecutive periods. Sixty-one healthy young volunteers, students at a nearby college, were included. Forty-eight subjects (13 males, 35 females) completed the study.Interventions:Subjects received a 2-week wash-in diet rich in monounsaturated fatty acids (21% energy) followed by experimental diets enriched with about 1% of energy of ALA, EPA or DHA for 3 weeks. The omega-3 (n-3) fatty acids were provided with special rapeseed oils and margarines. The wash-in diet and the experimental diets were identical, apart from the n-3 fatty acid composition and the tocopherol content, which was adjusted to the content of dienoic acid equivalents.Results:Ex vivo oxidative susceptibility of LDL was highest after the DHA diet, indicated by a decrease in lag time (−16%, P<0.001) and an increase in the maximum amount of conjugated dienes (+7%, P<0.001). The EPA diet decreased the lag time (−16%, P<0.001) and the propagation rate (−12%, P<0.01). Tocopherol concentrations in LDL decreased in the ALA group (−13.5%, P<0.05) and DHA group (−7.3%, P<0.05). Plasma contents of tocopherol equivalents significantly decreased in all three experimental groups (ALA group: −5.0%, EPA group: −5.7%, DHA group: −12.8%). The content of the three n-3 polyunsaturated fatty acid differently increased in the LDL: on the ALA diet, the ALA content increased by 89% (P<0.001), on the EPA diet the EPA content increased by 809% (P<0.001) and on the DHA diet, the DHA content increased by 200% (P<0.001). In addition, the EPA content also enhanced (without dietary intake) in the ALA group (+35%, P<0.01) and in the DHA group (+284%, P<0.001).Conclusions:Dietary intake of ALA, EPA or DHA led to a significant enrichment of the respective fatty acid in the LDL particles, with dietary EPA preferentially incorporated. In the context of a monounsaturated fatty acid-rich diet, ALA enrichment did not enhance LDL oxidizability, whereas the effects of EPA and DHA on ex vivo LDL oxidation were inconsistent, possibly in part due to further changes in LDL fatty acid composition.Sponsorship:This research was financially supported by the German Federal Ministry of Education and Research (BMBF) within the project ‘NAPUS 2000 – healthy foodstuffs from transgenic rapeseed’.

Changes in hemostasis during treatment of hypertriglyceridemia with a diet rich in monounsaturated and n-3 polyunsaturated fatty acids in comparison with a low-fat diet.

High levels of fibrinogen, factor (F) VIIc, plasminogen activator inhibitor-1 (PAI-1), and plasma viscosity are associated with an increased coronary risk. As positive correlations of these parameters with triglycerides have been shown, the increased coronary risk associated with high levels of triglycerides may be assumed to be due to alterations within the hemostatic system. To reduce the coronary risk to which hypertriglyceridemic patients are exposed, dietary treatment is recommended; the optimal composition of such a diet is, however, a matter of debate. With regard to the effects on hemostasis, we compared in a sequential approach two diets for treatment of 25 nonobese male patients (age, mean+/-S.D., 40.4+/-8.7 years) with fasting triglycerides >2.3 mmol/l. The first diet (high fat) was rich in monounsaturated fatty acids (MUFA) and marine n-3 polyunsaturated fatty acids (PUFA), whereas the second diet (low-fat) was rich in complex carbohydrates and dietary fiber. The high-fat diet induced a significant lowering of FIIc, FIXc, FXc, FVIIc, FVIIa, FXIIa, PAI-1, plasma viscosity, and platelet activity, but led to an increase in fibrinogen, whereas the low-fat diet lowered FXIIc values and induced a nonsignificant decrease in fibrinogen. Probands on this diet had a slightly higher FVIIa and platelet activity than those on the high-fat diet. However, as all changes appeared to be within the normal range of each hemostatic parameter, it remains to be clarified whether the likely beneficial effects of the high-fat diet on most hemostatic factors are outweighed by the small increase in fibrinogen levels.

Effects of Dietary α-Linolenic Acid, Eicosapentaenoic Acid or Docosahexaenoic Acid on Parameters of Glucose Metabolism in Healthy Volunteers

Aim: To investigate the effects of α-linolenic acid (ALA) and purified eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on fasting concentrations of glucose, insulin, fructosamine, on glycosylated haemoglobin (HbA1c) and on insulin sensitivity. Methods: A randomized strictly controlled dietary study in 48 healthy volunteers (13 males, 35 females) of normal body weight (mean age 25.9 years) with three dietary groups (ALA, EPA and DHA) and a parallel design, consisting of two consecutive periods. Subjects received a 2-week wash-in diet rich in monounsaturated fatty acids followed by experimental diets enriched with equal amounts of ALA, EPA, or DHA for 3 weeks. Mean dietary intake of ALA in the ALA group was 6.0 g/day (2.5% of energy intake), mean intake of EPA in the EPA group was 2.8 g/day (1.1% of energy intake) and mean intake of DHA in the DHA group was 2.9 g/day (1.1% of energy intake). Results: Fasting serum concentrations of insulin and fructosamine and of HbA1c did not change significantly after consuming the ALA, EPA or DHA diet. Fasting serum glucose levels did not change significantly following either the ALA or DHA diet. During the EPA diet, fasting glucose concentration slightly increased by 0.15 mmol/l (p < 0.05). All measured values of all subjects were in the reference ranges for healthy adults. No effects on insulin sensitivity indicated by the HOMA insulin resistance index could be observed. Conclusions: Except for the minor effect of EPA on fasting glucose levels, the moderate amounts of dietary ALA, EPA or DHA administered in this study did not significantly affect blood concentrations of glucose, insulin, fructosamine and HbA1c in healthy normal-weight men and women over a time course of 3 weeks.

Margarines Fortified with α-Linolenic Acid, Eicosapentaenoic Acid, or Docosahexaenoic Acid Alter the Fatty Acid Composition of Erythrocytes but Do Not Affect the Antioxidant Status of Healthy Adults

We aimed to investigate the effects of increased intake of α-linolenic acid (ALA), EPA, or DHA incorporated into a food matrix on the fatty acid composition of erythrocytes and on biomarkers of oxidant/antioxidant status. To this end, a controlled dietary study was conducted in 74 healthy men and women. The participants were randomly assigned to 1 of 3 interventions in which margarines fortified with either 10 weight percent ALA, EPA, or DHA ethyl esters replaced their normal spread for 6 wk. The total intakes of ALA, EPA, and DHA were 4.4, 2.2, and 2.3 g/d, respectively. Consuming EPA increased the erythrocyte proportion of EPA (394%) and the omega-3 index (sum of EPA and DHA, 38%). Consumption of DHA increased erythrocyte DHA (91%), the omega-3 index (98%), and EPA (137%). The omega-3 index increased to a significantly greater extent in the DHA group than in the EPA group. ALA did not increase erythrocyte EPA or the omega-3 index. We found no change in plasma uric acid or antioxidant capacity in any of the groups. Plasma malondialdehyde (MDA) increased with the EPA and DHA interventions. All 3 interventions decreased erythrocyte linoleic acid hydroperoxides but did not affect their MDA concentrations. In conclusion, the intake of both isolated EPA and DHA incorporated into margarine resulted in an enhanced incorporation of EPA and DHA into erythrocytes. Our findings indicate that DHA is quantitatively superior to EPA in view of the EPA+DHA tissue incorporation and also that 4 g/d ALA is not sufficient to increase the omega-3 index over a 6-wk period.

Influence of Menopause and Lifestyle Factors on High Density Lipoproteins in Middle-Aged Women

The risk of cardiovascular diseases in women is low until menopause, but increases considerably afterward. Data on changes in high density lipoproteins caused by menopause are controversial. The aim of this investigation was to establish the influence of various endogenous (age, body mass index, blood pressure, sex hormones) and exogenous (dietary habits, smoking and drinking behavior, physical activity) factors on variables associated with high density lipoprotein metabolism. One thousand twenty-one working female participants of the DRECAN Study aged between 36 and 65 years were investigated. Two-thirds of the study population were premenopausal and one-third were postmenopausal. High density lipoprotein cholesterol and apolipoprotein AI concentrations did not correlate with age and did not change significantly as a consequence of menopause. Postmenopausal women without hormone replacement therapy showed significantly higher values of age-, body mass index-, and blood pressure-adjusted ratios of triglycerides/high density lipoprotein cholesterol, low density lipoprotein cholesterol/ high density lipoprotein cholesterol, and apolipoprotein B/apolipoprotein AI as compared with premenopausal women not using oral contraceptives. The current use of oral contraceptives or of hormone replacement therapy was associated with a lower low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio. These changes were caused mainly by increased serum concentrations of triglycerides, total cholesterol, and apolipoprotein B and not by changes in high density lipoprotein concentrations. Cigarette smoking decreased high density lipoprotein cholesterol. Apolipoprotein AI concentration was directly influenced by the amount of daily energy intake. A high caloric diet rich in cholesterol and saturated fatty acids increased high density lipoprotein 2 cholesterol. There was no influence of higher alcohol intake or physical activity at leisure time on variables of high density lipoprotein metabolism. A higher level of physical activity at the workplace lowered the ratio of triglycerides/high density lipoprotein cholesterol. In premenopausal women, the use of oral contraceptives increased apolipoprotein AI concentrations.

Electrophoretic screening for human apolipoprotein C-II variants: repeated identification of apolipoprotein C-II(K19T).

Screening for apolipoprotein (apo) C-II variants in the plasma of 400 students, 600 patients of a cardiological rehabilitation center, and 1200 patients of an outpatient lipid clinic by isoelectric focusing and subsequent anti-apo C-II immunoblotting led to the identification of four individuals whose plasma samples contained an apo C-II isoform with an abnormal isoelectric point. In all cases direct sequencing of PCR-amplified DNA assessed a heterozygous A to C transversion in codon 19 of the apo C-II gene which leads to the replacement of lysine with threonine. Two of the four index patients presented with moderate hypertriglyceridemia; one suffered from severe hyperlipidemia, with triglyceride levels ranging between 180 and 1900 mg/dl, depending on dietary changes. Sequencing of this probands lipoprotein lipase gene showed no alteration compared to the wildtype sequence. A study in his family revealed that heterozygosity for apo C-II(K19T) is not associated with differences in mean lipid and lipoprotein concentrations. In conclusion, apo C-II(K19T) occurs in Germany at a frequency of approximately 1 in 550. Although this variant is not sufficient to cause hypertriglyceridemia, it may be possible that apo C-II(K19T) causes hypertriglyceridemia in the presence of additional as yet unidentified environmental and/or genetic factors.