Association between prenatal and current exposure to selected LCPUFAs and school performance at age 7.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LCPUFAs) are important for brain functioning and might, thus, influence cognition and school performance. However, research investigating LCPUFAs relationships with school performance is limited. The objective of this study was to determine the association between levels of the LCPUFAs docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and n-6 docosapentaenoic acid (Osbond acid, ObA) at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy, at partus, in umbilical cord plasma and child's plasma at age 7 and school performance scores at age 7. METHODS: Data from the Maastricht Essential Fatty Acid Birth cohort (MEFAB) were used for this study. Fatty acid levels of plasma phospholipids were measured in maternal blood plasma at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy and partus. Childs fatty acid levels of plasma phospholipids were measured a in umbilical cord blood plasma, and in blood plasma of the child at age 7. Scores on national standardised tests for spelling, reading and arithmetic at age 7 were obtained via the school (scores were available for 149, 159 and 155 children, respectively). Associations between LCPUFA levels and school performance scores were analysed with categorical regression analyses with correction for covariates (smoking, maternal education, sex, breastfeeding, maternal intelligence, birth weight and BMI at age 7). RESULTS: Significant (p<0.001) associations between DHA level at age 7 and both reading (ß=0.158) and spelling (ß=0.146) were found. Consistent significant negative associations were observed between all maternal DHA plasma levels and arithmetic scores at age 7 (all p<0.001, all ß<-0.019). Additional significant negative associations were observed between maternal LCPUFA plasma levels at study entry and both reading and spelling scores at age 7; these associations were less consistent. CONCLUSION: Plasma DHA levels at age 7 were positively associated with reading and spelling scores at age 7. Consistent significant negative associations between maternal plasma DHA levels and arithmetic scores of the child at age 7 were found. Although this is an observational study, which cannot proof causality, the consistent negative associations observed between maternal plasma DHA levels and the arithmetic scores of the children at age 7 calls upon prudence when considering DHA supplementation during pregnancy.

Relationship between DHA status at birth and child problem behaviour at 7 years of age.

Animal studies have demonstrated behavioural effects of long-chain polyunsaturated fatty acid (LC-PUFA) deficiencies and in humans, several psychiatric disorders have been linked to abnormal essential fatty acid metabolism. The aim of this study was to examine the relationship between LC-PUFA status at birth and the later development of problem behaviour. In a sample of 393 children, higher levels of docosahexaenoic acid (DHA) at birth were associated with lower levels of internalising problem behaviour at age 7 years. The association was markedly present in the infants fed with artificial formula (n=215, Beta=-0.32, P=0.000), but absent in the infants fed with human milk (n=170, Beta=0.11, P=0.325). The associations between arachidonic acid and internalising or externalising behaviour were neither large nor significant. The results suggest that perinatal DHA status may have long-term behavioural consequences. Therefore, we suggest to include measures of problem behaviour in future trials of LC-PUFA supplementation of mothers and/or infants.

Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism.

Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because their diet is low in EFAs and LCPUFAs. We have investigated the EFA and LCPUFA status of children with various amino acid metabolism disorders (not PKU) under treatment. Fatty acid profiles of plasma and erythrocyte phospholipids of 33 patients (aged 0-18 years) and 38 matched controls were determined by gas-liquid chromatography. Food-frequency questionnaires were used to assess the mean fatty acid intake. The dietary intake of the EFAs linoleic acid (LA) and alpha-linolenic acid (ALA) was comparable in both groups, while the LCPUFA intake was much lower in patients. This was associated with lower relative concentrations (% of total fatty acids) of n-3 docosahexaenoic acid (DHA) in plasma and erythrocyte phospholipids. Concentrations of arachidonic acid (AA) did not differ. The same was observed for the two EFAs LA and ALA. Thus, as compared to healthy controls, children with amino acid metabolism disorders have a lower intake of LCPUFAs and have lower concentrations of DHA but not of AA in plasma and erythrocyte phospholipids. This suggests that endogenous AA synthesis might guarantee an adequate AA status. The lower DHA status, however, warrants further investigations regarding the impact of DHA supplementation on growth and development of these children.

Dietary vegetable oil and wood derived plant stanol esters reduce atherosclerotic lesion size and severity in apoE*3-Leiden transgenic mice.

The hypolipidemic and anti-atherosclerotic effects of vegetable oil- and wood-based dietary plant stanol esters were compared in female apoE*3-Leiden transgenic mice at relevant plasma cholesterol levels. The plant stanol esters derived from vegetable oil (sitostanol 65.7%, campestanol 30.1%) had different contents of sitostanol and campestanol than the plant stanol esters derived from wood (sitostanol 87.6%, campestanol 9.5%) or from a mixture of vegetable oil and wood (sitostanol 73.0%, campestanol 24.7%). The mice (10 per group) received for 38 weeks a control diet or diets containing 1.0% (w/w) plant stanol esters derived from either vegetable oil, wood or a mixture of both. Vegetable oil (-46%), wood (-42%) and vegetable oil/wood (-51%) plant stanol esters decreased the plasma cholesterol levels (P<0.0001) by reducing the cholesterol content in plasma very low density-, intermediate density- and to a lesser extent in low density-lipoprotein. Plant stanol ester feeding did not change plasma triglyceride levels. Dietary plant stanol esters reduced the atherosclerotic lesion area by 91+/-13% (vegetable oil), 97+/-4% (wood) and 78+/-34% (vegetable oil/wood) (P<0.0001) and the severity from regular intimal fatty streaks/mild plaques (on average type 2--3 lesions) in controls to individual intimal foam cells (

Influence of dietary fat type on arterial thrombosis tendency.

Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by the dietary fat type. It should be recalled, however, that only after a cause-and-effect relationship has been established between the disease and a given risk indicator (called a risk factor in that case), modifying this factor can be expected to affect disease morbidity and mortality. In this review, effects of dietary lipids on cardiovascular risk are considered, with special emphasis on modification of arterial thrombosis and platelet thrombotic processes, coagulation and fibrinolysis. Although epidemiological studies do not give entirely consistent results, replacement of dietary saturated by unsaturated fatty acids generally lowers cardiovascular morbidity and mortality. The few (secondary) prevention studies reported so far confirmed this for fish oil or fish oil concentrates, as well as for vegetable oils rich in oleic-, linoleic- or a-linolenic acids. Animal thrombosis models demonstrated that dietary unsaturated fatty acids reduce arterial thrombosis tendency as compared to saturated fatty acids. Using restenosis after percutaneous transluminal coronary angioplasty (PTCA) and occlusion of coronary artery bypass grafts (CABG) as human models of arterial thrombosis, fish oil treatment has been shown to have an anti-thrombotic effect, but results are inconsistent (PTCA) or need confirmation (CABG). Major thrombotic and anti-thrombotic conditions and processes include endothelial integrity, thrombotic functions of blood platelet, coagulation, and fibrinolysis. The dietary fat type can affect endothelial integrity, but results are inconsistent and often difficult to interpret in terms of arterial thrombosis tendency. The same can be concluded for platelet aggregation, especially because results of dietary interventions often depend on the aggregation measuring technique. Novel well-validated methods are required to solve this problem. Dietary fats can affect certain factors involved in blood coagulation and fibrinolysis. Thus, Factor VII activity is increased by the fat content of the diet. However, the dietary fat type seems of less importance. Studies addressing the effect of specific fatty acids on extrinsic clotting and thrombin formation in vivo did not produce consistent results. The same holds for the dietary fatty acid effects on promoters and inhibitors of the plasma fibrinolytic potential. Although trans unsaturated fatty acids may increase cardiovascular risk, this is probably not mediated by effects on arterial thrombosis.

Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development.

UNLABELLED: This paper reports on the conclusions of a workshop on the role of long chain polyunsaturated fatty acids (LC-PUFA) in maternal and child health. The attending investigators involved in the majority of randomized trials examining LC-PUFA status and functional outcomes summarize the current knowledge in the field and make recommendations for dietary practice. Only studies published in full or in abstract form were used as our working knowledge base. CONCLUSIONS: For healthy infants we recommend and strongly support breastfeeding as the preferred method of feeding, which supplies preformed LC-PUFA. Infant formulas for term infants should contain at least 0.2% of total fatty acids as docosahexaenoic acid (DHA) and 0.35% as arachidonic acid (AA). Since preterm infants are born with much less total body DHA and AA, we suggest that preterm infant formulas should include at least 0.35% DHA and 0.4% AA. Higher levels might confer additional benefits and should be further investigated because optimal dietary intakes for term and preterm infants remain to be defined. For pregnant and lactating women we consider it premature to recommend specific LC-PUFA intakes. However, it seems prudent for pregnant and lactating women to include some food sources of DHA in their diet in view of their assumed increase in LC-PUFA demand and the relationship between maternal and foetal DHA status.

Leptin and phospholipid-esterified docosahexaenoic acid concentrations in plasma of women: observations during pregnancy and lactation.

BACKGROUND: The n-3 fatty acid status changes during pregnancy and lactation. Plasma leptin concentrations and gene expression have been related to n-3 fatty acids. OBJECTIVE: To investigate the relation between plasma leptin concentration and the docosahexaenoic acid (22:6n-3) content of plasma phospholipids during early pregnancy and the postpartum period. DESIGN: Leptin (radioimmunoassay) and the phospholipid fatty acid profile (capillary gas-liquid chromatography) were measured in plasma of women during two independent longitudinal observational studies. Dietary intake of n-3 fatty acids was also determined. RESULTS: Within the first 10 weeks after the last menstrual period, an almost parallel increase in leptin concentration and the 22:6n-3 content (mg/l and % wt/wt) of plasma phospholipids was seen (study 1, n = 21). During the postpartum period (study 2, n = 57), leptin levels decreased quickly, preceding the changes in 22:6n-3 concentrations. During both studies, leptin concentrations did not consistently relate to dietary intake of n-3 fatty acids or to 22:6n-3 concentrations in plasma phospholipids. Before and during early pregnancy (study 1), significant positive associations between leptin levels and the total amount of phospholipid-associated fatty acids were found. No such association was seen during late pregnancy or the postpartum period (study 2). The postpartum decrease in leptin levels did not differ between lactating and non-lactating women. CONCLUSIONS: Not the 22:6n-3 content, but the total amount of phospholipid-associated fatty acids was related to plasma leptin concentration, before and during early pregnancy but not during late pregnancy and the postpartum period.

Modulation of rat platelet activation by vessel wall-derived prostaglandin and platelet-derived thromboxane: effects of dietary fish oil on thromboxane-prostaglandin balance.

By dietary manipulation of rats with n-3 polyunsaturated fatty acids (PUFAs), platelets and endothelium-containing aortic tissue were obtained with decreased levels of arachidonate and increased levels of eicosapentaenoate and docosahexaenoate. These diet-induced changes were accompanied by a reduced formation of thromboxane A(2) (TXA(2)) and prostaglandin I(2) (PGI(2)) in platelets and aortic tissue, respectively. When platelets were incubated with autologous, aorta-derived PGI(2), the dietary modulation of PGI(2) generation had a stronger effect on the activation process than the dietary effect on TXA(2) generation. The platelet-inhibiting effect of PGI(2) was independent of the type of agonist and involved both TXA(2)-dependent and -independent activation responses. PGI(2) also inhibited the agonist-induced formation of TXA(2). In addition, the platelet-inhibitory effect of PGI(2) was more prolonged in time than the brief, stimulatory effect of TXA(2). We conclude that, in the thromboxane-prostaglandin balance of platelet activation, PGI(2) plays a more prominent role than TXA(2). Furthermore, dietary n-3 PUFAs appear to influence platelet activation more by reducing formation of endothelial PGI(2) than by decreasing autocrine-produced TXA(2). Thus, in rats, the proposed antithrombotic effect of fish oil is unlikely to be caused by an altered thromboxane-prostaglandin balance.

The effect of supplementation with docosahexaenoic and arachidonic acid derived from single cell oils on plasma and erythrocyte fatty acids of pregnant women in the second trimester.

This study was performed to investigate whether supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) to pregnant women would enhance their DHA levels, both in plasma and in erythrocyte phospholipids, without reducing the content of n-6 long-chain ployenes (LCP) usually seen when DHA is supplemented alone. Healthy pregnant women, in the second trimester, were randomly assigned to either the control group (n=12) or the intervention group (n=12). The control group received no supplements and the intervention group received daily during 4 weeks encapsulated algae-derived DHA oil (0.57 g DHA/day) and fungal-derived AA oil (0.26 g AA/day). The fatty acid compositions of plasma and erythrocyte phospholipids were determined in weekly-collected blood samples. DHA and n-6 LCP levels of the control group were unchanged after 4 weeks. Compared to the control group, DHA levels in plasma an erythrocytes of the intervention group increased significantly. No significant reductions were found in the levels of AA and total n-6 LCP. The supplement proved to be effective in increasing the DHA levels in both plasma and erythrocyte without a concomitant decline of the n-6 LCP.

Essential fatty acids in mothers and their neonates.

Essential fatty acids (EFAs) and their long-chain polyenes (LCPs) are indispensable for human development and health. Because humans cannot synthesize EFAs and can only ineffectively synthesize LCPs, EFAs need to be consumed as part of the diet. Consequently, the polyunsaturated fatty acid (PUFA) status of the developing fetus depends on that of its mother, as confirmed by the positive relation between maternal PUFA consumption and neonatal PUFA status. Pregnancy is associated with a decrease in the biochemical PUFA status, and normalization after delivery is slow. This is particularly true for docosahexaenoic acid (DHA) because, on the basis of the current habitual diet, birth spacing appeared to be insufficient for the maternal DHA status to normalize completely. Because of the decrease in PUFA status during pregnancy, the neonatal PUFA status may not be optimal. This view is supported by the lower neonatal PUFA status after multiple than after single births. The neonatal PUFA status can be increased by maternal PUFA supplementation during pregnancy. For optimum results, the supplement should contain both n-6 and n-3 PUFAs. The PUFA status of preterm neonates is significantly lower than that of term infants, which is a physiologic condition. Because the neonatal DHA status correlates positively with birth weight, birth length, and head circumference, maternal DHA supplementation during pregnancy may improve the prognosis of preterm infants. In term neonates, maternal linoleic acid consumption correlates negatively with neonatal head circumference. This suggests that the ratio of n-3 to n-6 PUFAs in the maternal diet should be increased. Consumption of trans unsaturated fatty acids appeared to be associated with lower maternal and neonatal PUFA status. Therefore, it seems prudent to minimize the consumption of trans fatty acids during pregnancy.

Relationship between vitamin E requirement and polyunsaturated fatty acid intake in man: a review.

Vitamin E is the general term for all tocopherols and tocotrienols, of which alpha-tocopherol is the natural and biologically most active form. Although gamma-tocopherol makes a significant contribution to the vitamin E CONTENT in foods, it is less effective in animal and human tissues, where alpha-tocopherol is the most effective chain-breaking lipid-soluble antioxidant. The antioxidant function of vitamin E is critical for the prevention of oxidation of tissue PUFA. Animal experiments have shown that increasing the degree of dietary fatty acid unsaturation increases the peroxidizability of the lipids and reduces the time required to develop symptoms of vitamin E deficiency. From these experiments, relative amounts of vitamin E required to protect the various fatty acids from being peroxidized, could be estimated. Since systematic studies on the vitamin E requirement in relation to PUFA consumption have not been performed in man, recommendations for vitamin E intake are based on animal experiments and human food intake data. An intake of 0.6 mg alpha-tocopherol equivalents per gram linoleic acid is generally seen as adequate for human adults. The minimum vitamin E requirement at consumption of fatty acids with a higher degree of unsaturation can be calculated by a formula, which takes into account the peroxidizability of unsaturated fatty acids and is based on the results of animal experiments. There are, however, no clear data on the vitamin E requirement of humans consuming the more unsaturated fatty acids as for instance EPA (20:5, n-3) and DHA (22:6, n-3). Studies investigating the effects of EPA and DHA supplementation have shown an increase in lipid peroxidation, although amounts of vitamin E were present that are considered adequate in relation to the calculated oxidative potential of these fatty acids. Furthermore, a calculation of the vitamin E requirement, using recent nutritional intake data, shows that a reduction in total fat intake with a concomitant increase in PUFA consumption, including EPA and DHA, will result in an increased amount of vitamin E required. In addition, the methods used in previous studies investigating vitamin E requirement and PUFA consumption (for instance erythrocyte hemolysis), and the techniques used to assess lipid peroxidation (e.g. MDA analysis), may be unsuitable to establish a quantitative relation between vitamin E intake and consumption of highly unsaturated fatty acids. Therefore, further studies are required to establish the vitamin E requirement when the intake of longer-chain, more-unsaturated fatty acids is increased. For this purpose it is necessary to use functional techniques based on the measurement of lipid peroxidation in vivo. Until these data are available, the widely used ratio of at least 0.6 mg alpha-TE/g PUFA is suggested. Higher levels may be necessary, however, for fats that are rich in fatty acids containing more than two double bonds.

Long-chain polyunsaturated fatty acids, pregnancy, and pregnancy outcome.

During pregnancy, essential long-chain polyunsaturated fatty acids (LCPUFAs) play important roles as precursors of prostaglandins and as structural elements of cell membranes. Throughout gestation, accretion of maternal, placental, and fetal tissue occurs and consequently the LCPUFA requirements of pregnant women and their developing fetuses are high. This is particularly true for docosahexaenoic acid (DHA; 22:6n-3). The ratio of DHA to its status marker, docosapentaenoic acid (22:5n-6), in maternal plasma phospholipids decreases significantly during pregnancy. This suggests that pregnancy is associated with maternal difficulty in coping with the high demand for DHA. The DHA status of newborn multiplets is significantly lower than that of singletons; the same is true for infants of multigravidas as compared with those of primigravidas and for preterm compared with term neonates. Because the LCPUFA status at birth seems to have a long-term effect, the fetus should receive an adequate supply of LCPUFAs. Data from an international comparative study indicated that, especially for n-3 LCPUFAs, the fetus is dependent on maternal fatty acid intake; maternal supplementation with LCPUFAs, their precursors, or both increased LCPUFA concentrations in maternal and umbilical plasma phospholipids. However, significant competition between the 2 LCPUFA families was observed, which implies that effective supplementation requires a mixture of n-6 and n-3 fatty acids. Further research is needed to determine whether higher LCPUFA concentrations in plasma phospholipid will have functional benefits for mothers and children.

Early nutrition, essential fatty acid status and visual acuity of term infants at 7 months of age.

OBJECTIVE: In term infants the relationship between visual acuity and dietary fatty acid composition is not consistent, possibly due to confounders, which were mostly neglected in the studies concerned. In the current study, therefore, the influence of the essential fatty acid status and potential confounders on the visual acuity was investigated. DESIGN: The essential fatty acid status was determined at 7 months of age in red blood cell and plasma phospholipids of breastfed and formula-fed infants, born at term. Visual acuity was measured with Teller Acuity Cards. Information about potential confounding factors was obtained during an interview and with a retrospective questionnaire. RESULTS: This study, like others, showed that the concentrations of docosahexaenoic acid (DHA, 22:6n-3) are lower in plasma and red blood cell phospolipids of formula-fed infants compared to that of breastfed infants. However, no differences in visual acuity could be found between the two groups. Moreover, no significant relationship was found between the amounts of docosahexaenoic acid in plasma and red blood cell phospholipids and the visual acuity. Although dummy (pacifier) use showed a significant positive correlation with visual acuity, it did not influence the relationship between the essential fatty acids in the infant diet and visual acuity. There was also no confounding influence of smoking habits and alcohol use during pregnancy, socioeconomic background and other potential confounders. CONCLUSIONS: At 7 months of age no influence of fatty acid status, infant diet or potential confounders on visual acuity was found.

A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations.

BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations.

Functional food science and the cardiovascular system.

Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by dietary means. It should be recalled, however, that only after a cause-and-effect relationship has been established between the disease and a given risk indicator (called a risk factor in that case), can modifying this factor be expected to affect disease morbidity and mortality. In this paper, effects of diet on cardiovascular risk are reviewed, with special emphasis on modification of the plasma lipoprotein profile and of hypertension. In addition, dietary influences on arterial thrombotic processes, immunological interactions, insulin resistance and hyperhomocysteinaemia are discussed. Dietary lipids are able to affect lipoprotein metabolism in a significant way, thereby modifying the risk of cardiovascular disease. However, more research is required concerning the possible interactions between the various dietary fatty acids, and between fatty acids and dietary cholesterol. In addition, more studies are needed with respect to the possible importance of the postprandial state. Although in the aetiology of hypertension the genetic component is definitely stronger than environmental factors, some benefit in terms of the development and coronary complications of atherosclerosis in hypertensive patients can be expected from fatty acids such as alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid. This particularly holds for those subjects where the hypertensive mechanism involves the formation of thromboxane A2 and/or alpha 1-adrenergic activities. However, large-scale trials are required to test this contention. Certain aspects of blood platelet function, blood coagulability, and fibrinolytic activity are associated with cardiovascular risk, but causality has been insufficiently proven. Nonetheless, well-designed intervention studies should be initiated to further evaluate such promising dietary components as the various n-3 and n-6 fatty acids and their combination, antioxidants, fibre, etc. for their effect on processes participating in arterial thrombus formation. Long-chain polyenes of the n-3 family and antioxidants can modify the activity of immunocompetent cells, but we are at an early stage of examining the role of immune function on the development of atherosclerotic plaques. Actually, there is little, if any, evidence that dietary modulation of immune system responses of cells participating in atherogenesis exerts beneficial effects. Although it seems feasible to modulate insulin sensitivity and subsequent cardiovascular risk factors by decreasing the total amount of dietary fat and increasing the proportion of polyunsaturated fatty acids, additional studies on the efficacy of specific fatty acids, dietary fibre, and low-energy diets, as well as on the mechanisms involved are required to understand the real function of these dietary components. Finally, dietary supplements containing folate and vitamins B6 and/or B12 should be tested for their potential to reduce cardiovascular risk by lowering the plasma level of homocysteine.

Hypocoagulant and lipid-lowering effects of dietary n-3 polyunsaturated fatty acids with unchanged platelet activation in rats.

We investigated the effects of dietary polyunsaturated fatty acids (PUFAs) on blood lipids and processes that determine hemostatic potential: platelet activation, coagulation, and fibrinolysis. For 8 to 10 weeks, Wistar rats were fed a high-fat diet containing various amounts (2% to 16%) of n-3 PUFAs derived from fish oil (FO) or a diet enriched in n-6 PUFAs from sunflower seed oil (SO). Only the FO diets caused a reduction in mean platelet volume, platelet arachidonate level, and formation of thromboxane B2 by activated platelets, but neither of the diets had a measurable effect on platelet activation. The FO-rich diets decreased the plasma concentrations of triglycerides and cholesterol, whereas the SO diet reduced triglycerides only. Parameters of fibrinolysis and standard coagulation times, ie, activated partial thromboplastin time and prothrombin time, were only marginally influenced by these diets. In contrast, dietary FO, but not SO, led to decreased levels of the vitamin K-dependent coagulation factors prothrombin and factor VII, while the level of antithrombin III was unchanged. The endogenous thrombin potential (ETP) was measured with an assay developed to detect the hypocoagulable state of plasma. After activation with tissue factor and phospholipids, the ETP was reduced by 23% or more in plasma from animals fed a diet with >4% FO. No significant effect of the SO diet on ETP was observed. Control experiments with plasma from warfarin-treated rats indicated that the ETP was more sensitive to changes in prothrombin concentration than in factor VII concentration. Taken together, these results indicate that in rats, prolonged administration of n-3 but not n-6 PUFAs can lead to a hypocoagulable state of plasma through a reduced capacity of vitamin K-dependent thrombin generation, with unchanged thrombin inactivation by antithrombin III.

Exercise performance, red blood cell deformability, and lipid peroxidation: effects of fish oil and vitamin E.

Previous studies have indicated that fish oil supplementation increases red blood cell (RBC) deformability, which may improve exercise performance. Exercise alone, or in combination with an increase in fatty acid unsaturation, however, may enhance lipid peroxidation. Effects of a bicycle time trial of approximately 1 h on RBC characteristics and lipid peroxidation were, therefore, studied in 24 trained cyclists. After 3 wk of fish oil supplementation (6 g/day), without or with vitamin E (300 IU/day), trial performance, RBC characteristics, and lipid peroxidation were measured again. RBC deformability appeared to decrease during endurance exercise. After correction for hemoconcentration, plasma total tocopherol concentrations decreased by 0.77 micromol/l (P = 0. 012) or 2.9% and carotenoid concentrations by 0.08 micromol/l (P = 0. 0008) or 4.5%. Endurance exercise did not affect the lag time and rate of in vitro oxidation of low-density lipoproteins (LDLs), but the maximum amount of conjugated dienes formed decreased by 2.1 +/- 1.0 micromol/mmol LDL cholesterol (P = 0.042) or 1.2%. Fish oil supplementation with and without vitamin E did not affect RBC characteristics or exercise performance. Both supplements decreased the rate of LDL oxidation, and fish oil supplementation with vitamin E delayed oxidation. The amount of dienes, however, was not affected. The supplements also did not change effects of exercise. We conclude that the changes observed during endurance exercise may indicate increased oxidative stress, but further research is necessary to confirm this. Fish oil supplementation does not improve endurance performance, but it also does not cause or augment changes in antioxidant levels or LDL oxidation during exercise.