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Background: Certain essential long-chain polyunsaturated fatty acids (LCPUFAs) are considered important for fetal growth and brain development, whereas industrial trans fatty acids (mainly 18:1trans) have been associated with negative effects. The aim of this study was to investigate associations between term birth dimensions and prenatal exposure to some of these fatty acids, reflected by neonatal fatty acid concentrations at birth., Methods: Data of up to 700 infant-mother pairs from the Maastricht Essential Fatty Acid Birth Cohort were used for the present study. Unadjusted and multivariable-adjusted linear regression analyses were performed to investigate associations between birth weight, birth length or head circumference and relative concentrations of docosahexaenoic acid (DHA), arachidonic acid (AA), dihomo-gamma-linolenic acid (DGLA) and trans-octadecenoic acids (18:1t) measured in phospholipids of the walls of umbilical arteries and veins, and in umbilical cord plasma and erythrocytes., Results: After optimal adjustment, a significant negative association was observed between birth weight and umbilical plasma DHA concentrations. Negative associations were also found for AA concentrations measured in umbilical plasma and in arterial and venous vessel walls. Birth length was negatively related to arterial vessel wall AA concentrations only. A significant negative association was observed for the relationship between 18:1t in cord erythrocytes and birth weight. For DGLA no significant associations were observed., Conclusions: Results seem to preclude a role of DHA and AA as growth factors per se. Their negative relationships with birth dimensions may result from a limited maternal-fetal LCPUFA transfer capacity. Potential effects of 18:1t and DGLA on birth dimensions are probably small or non-existing.

Lactation hampers normalization of the maternal arachidonic acid (AA) status, which is reduced after pregnancy and can further decline by the presently recommended increased consumption of (n-3) long-chain PUFA [(n-3) LCPUFA]. This may be unfavorable for breast-fed infants, because they also require an optimum supply of (n-6) LCPUFA. We therefore investigated the LCPUFA responses in nursing mothers upon increased consumption of AA and (n-3) LCPUFA. In a parallel, double-blind, controlled trial, lactating women received for 8 wk no extra LCPUFA (control group, n = 8), 200 (low AA group, n = 9), or 400 (high AA group, n = 8) mg/d AA in combination with (n-3) LCPUFA [320 mg/d docosahexaenoic acid (DHA), 80 mg/d eicosapentaenoic acid, and 80 mg/d other (n-3) fatty acids], or this dose of (n-3) LCPUFA alone [DHA + eicosapentaenoic acid group, n = 8]. Relative concentrations of AA, DHA, and sums of (n-6) and (n-3) LCPUFA were measured in milk total lipids (TL) and erythrocyte phospholipids (PL) after 2 and 8 wk and changes were compared by ANCOVA. The combined consumption of AA and (n-3) LCPUFA caused dose-dependent elevations of AA and total (n-6) LCPUFA concentrations in milk TL and did not significantly affect the DHA and total (n-3) LCPUFA increases caused by (n-3) LCPUFA supplementation only. This latter treatment did not significantly affect breast milk AA and total (n-6) LCPUFA concentrations. AA and DHA concentrations in milk TL and their changes were strongly and positively correlated with their corresponding values in erythrocyte PL (r(2) = 0.27-0.50; P

Background: Maternal n-3, n-6, and trans fatty acids are claimed to affect fetal growth, yet evidence is limited., Objective: We investigated the association between maternal n-3, n-6, and trans fatty acids measured early in pregnancy and fetal growth., Design: Amsterdam pregnant women (n = 12 373) were invited to complete a questionnaire (response 67%) and donate blood around the 12th pregnancy week for nutrient analysis. For 4336 women, fatty acid concentrations were measured in plasma phospholipids (gas-liquid chromatography). Associations of these concentrations with birth weight and small-for-gestational-age (SGA) risk were analyzed (liveborn singleton term deliveries, n = 3704)., Results: Low concentrations of individual n-3 fatty acids and 20:3n-6, the precursor of arachidonic acid (20:4n-6), but high concentrations of the other n-6 fatty acids and the main dietary trans fatty acid (18:1n-9t) were associated with lower birth weight (estimated difference in univariate analysis -52 to -172 g for extreme quintile compared with middle quintile). In general, SGA risk increased accordingly. After adjustment for physiologic, lifestyle-related and sociodemographic factors, low concentrations of most n-3 fatty acids and 20:3n-6 and high concentrations of 20:4n-6 remained associated with lower birth weight (-52 to -57 g), higher SGA risk, or both (odds ratios: 1.38-1.50). Infants of the 7% of women with the most adverse fatty acid profile were on average 125 g lighter and twice as likely to be small for gestational age., Conclusion: An adverse maternal fatty acid profile early in pregnancy is associated with reduced fetal growth, which, if confirmed, gives perspective for the dietary prevention of lower birth weight.

Background: To improve the effective prevention and treatment of obesity, it is important to focus on body weight (BW) development and its determinants during childhood., Objective: The aim of the present study was to investigate the effects of early development, parental and genetic variables, and behavioral determinants on overweight at 12 y., Design: In a Dutch cohort of 105 children, anthropometric measurements were conducted from birth until age 7 y. At age 12 y, anthropometric measurements were obtained again, as were measurements of body composition, leptin concentration, 3 polymorphisms, and physical activity, and the Three-Factor Eating Questionnaire was conducted. In addition, parental body mass indexes (BMIs, in kg/m2) and Three-Factor Eating Questionnaire scores were determined., Results: The children's mean (+/-SD) BMI at 12 y was 19.0 +/- 2.6, and 15.2% were classified as overweight. From the first year of life, BMI tracked significantly with BMI at age 12 y (r = 0.24, P < 0.05). Linear regression analyses showed that a rapid increase in BW during the first year of life, a high BMI of the father, and a high dietary restraint score of the mother were significantly associated with overweight at age 12 y (P < 0.05). No significant genetic relation was observed. In addition, overweight was positively associated with dietary restraint of the child, and percentage body fat was negatively associated with the child's activity score (P < 0.05)., Conclusions: In this homogeneous cohort of normal-weight to moderately overweight children, tracking of BMI during childhood took place from the first year of life. Overweight at age 12 y was predicted by an early rapid increase in BW and parental influences. Overweight during childhood may be maintained or even promoted by a high dietary restraint score and low physical activity.

Because human studies concerning the effects of stearic acid on thrombotic tendency are inconsistent, we compared the effects of stearic acid with those of its unsaturated derivatives, oleic acid and linoleic acid. In this randomized, crossover study, 45 subjects (27 women and 18 men) consumed, in random order, 3 experimental diets, each for 5 wk. Diets contained approximately 38% of energy as fat. Dietary compositions were the same except for 7% of energy from stearic, oleic, or linoleic acids. At the end of each period, ex vivo and in vitro platelet aggregation, and variables of coagulation, fibrinolysis, and hematology were evaluated. In men, ex vivo platelet aggregation time as measured by filtragometry (P = 0.036 for diet effects) was favorably prolonged during consumption of the linoleic acid diet compared with the stearic acid diet (P = 0.040), but there was no difference with consumption of the oleic acid diet (P = 0.198). In vitro platelet aggregation induced by collagen and ADP, and variables of coagulation (factor VII amidolytic activity and concentrations of fibrinogen and prothrombin fragment 1 and 2) and fibrinolysis [plasminogen activator inhibitor (PAI) activity and concentrations of tissue plasminogen activator (tPA)/PAI-1 complexes] did not differ among the 3 diets. The mean platelet volume of the subjects decreased during consumption of the stearic acid diet by 0.32 fL compared with the oleic acid diet (P < 0.001) and by 0.35 fL compared with the linoleic acid diet (P < 0.001). In conclusion, our results do not suggest that stearic acid is highly thrombogenic compared with oleic and linoleic acids.

Background: Maternal essential fatty acid status declines during pregnancy, and as a result, neonatal concentrations of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) may not be optimal., Objective: Our objective was to improve maternal and neonatal fatty acid status by supplementing pregnant women with a combination of alpha-linolenic acid (ALA, 18:3n-3) and linoleic acid (LA, 18:2n-6), the ultimate dietary precursors of DHA and AA, respectively., Design: From week 14 of gestation until delivery, pregnant women consumed daily 25 g margarine supplying either 2.8 g ALA + 9.0 g LA (n = 29) or 10.9 g LA (n = 29). Venous blood was collected for plasma phospholipid fatty acid analyses at weeks 14, 26, and 36 of pregnancy, at delivery, and at 32 wk postpartum. Umbilical cord blood and vascular tissue samples were collected to study neonatal fatty acid status also. Pregnancy outcome variables were assessed., Results: ALA+LA supplementation did not prevent decreases in maternal DHA and AA concentrations during pregnancy and, compared with LA supplementation, did not increase maternal and neonatal DHA concentrations but significantly increased eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) concentrations. In addition, ALA+LA supplementation lowered neonatal AA status. No significant differences in pregnancy outcome variables were found., Conclusions: Maternal ALA+LA supplementation did not promote neonatal DHA+AA status. The lower concentrations of Osbond acid (22:5n-6) in maternal plasma phospholipids and umbilical arterial wall phospholipids with ALA+LA supplementation than with LA supplementation suggest only that functional DHA status improves with ALA+LA supplementation.

Background: Findings about the effects of beta-glucan on serum lipoproteins are conflicting., Objective: The study investigated the effects of beta-glucan from oat bran in bread and cookies (study 1) and in orange juice (study 2) on serum lipoproteins in mildly hypercholesterolemic subjects., Design: In study 1, 48 subjects (21 men, 27 women) received for 3 wk control bread and cookies rich in wheat fiber. For the next 4 wk, by random assignment, 23 subjects continued to consume the control products, and 25 received bread and cookies rich in beta-glucan. Mean daily intake of beta-glucan was 5.9 g. Total dietary fiber intake did not differ significantly between the groups. In study 2, the same sources of control fiber and beta-glucan (5 g/d) as in study 1 were provided. For 2 wk, 25 of the original 48 subjects (10 men, 15 women) were randomly assigned to consume orange juice containing either wheat fiber (n = 13) or beta-glucan from oat bran (n = 12). After a washout period of 1 wk, dietary regimens were crossed over., Results: In study 1, the change in LDL cholesterol did not differ significantly (-0.12 mmol/L; P = 0.173) between the 2 groups. In study 2, the drink rich in beta-glucan decreased LDL cholesterol by 0.26 +/- 0.07 mmol/L (6.7 +/- 1.8%; P = 0.001) and the ratio of total to HDL cholesterol by 0.26 +/- 0.11 (5.4 +/- 2.1%; P = 0.029) compared with the other drink. HDL-cholesterol and triacylglycerol concentrations did not change significantly., Conclusions: The food matrix or the food processing, or both, could have adverse effects on the hypocholesterolemic properties of oat beta-glucan.

Background and Aim: Common variations in genes, such as apolipoprotein E (apo E) and cholesteryl ester transfer protein (CETP), are major determinants of plasma lipid and lipoprotein levels. As both apo E and CETP contribute to the reverse transport of cholesterol to the liver, the effects of variations at the CETP locus may very well interact with the apo E genotype., Methods and Results: As part of an ongoing study, the combined effects of the apo E genotype and heterogeneity at the CETP gene locus on plasma lipids and lipoproteins were studied in a birth cohort sample of 257 Dutch prepubescent boys and girls (aged 6.7-8.1 years). The children with an apo E2E3 genotype (carrying the epsilon 2 allele; arg158-->cys) had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) than those with an apo E4E3 (carrying the epsilon 4 allele; cys112-->arg) or apo E3E3 genotype (homozygous for the parent epsilon 3 allele). These associations were statistically significant in children who were homozygous (p = 0.004 for LDL; p = 0.002 for apo B) or heterozygous (p < 0.0001 for LDL and apo B) for the absence of the Taq-IB polymorphism at the CETP gene locus (B2 allele), but not in those homozygous for the presence of this variant (B1B1). The highest plasma high-density lipoprotein cholesterol (HDL-C) concentrations were observed in children with the CETP B2B2 genotype. The difference in HDL-C levels between the CETP genotype groups was statistically significant only in E2E3 carriers (p = 0.01). The LDL/HDL ratio was significantly lower in E2E3 carriers, but not when combined with a CETP B1B1 genotype., Conclusion: These findings indicate that the apo E genotype and heterogeneity at the CETP gene locus have an additive and interactive influence on plasma lipid and lipoprotein levels in children.

Objective: The long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) have biophysical properties that may mediate behavioral outcome, especially cognitive development. This study examined the relationship between the LCPUFA-status at birth and cognitive development at 4 years of age., Methods: Cognitive development of 128 full-term neonates, whose umbilical venous plasma and/or red blood cell phospholipid DHA and AA levels were known, was assessed at 4 years of age. Pearson correlation coefficients were calculated between cognitive development and DHA, AA, maternal intelligence, birth weight, duration of breast-feeding and paternal educational attainment. Multiple linear regressions were employed with cognitive development as the dependent variable and whereby the above-mentioned covariables were entered in step one while each of the four LCPUFAs was entered in step two., Results: In bivariate analysis, maternal intelligence, birth weight, maternal smoking habits during pregnancy, paternal education and duration of breast-feeding showed significant correlations with cognitive development (p<0.01). The association of cognitive development with DHA and AA measured zero in bivariate analysis (plasma levels: r=0.03 and r=-0.03, respectively; erythrocyte levels: r=0.01 and r=0.05) and in multiple regression analysis (plasma DHA r=0.01, p=0.88; plasma AA r=0.02, p=0.80; erythrocyte DHA r=-0.01, p=0.95) except for erythrocyte AA (r=0.15, p=0.09)., Conclusion: No evidence was found for an association of the DHA or AA-status at birth with cognitive development at 4 years of age.

The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile.

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 (

Background: Pregnancy is associated with increased absolute amounts of docosahexaenoic acid (DHA; 22:6n-3) in plasma phospholipids. Expressed as a proportion of total fatty acids, DHA declines slightly in late pregnancy but little information is available on the normalization of DHA postpartum, which may be different in lactating and nonlactating women., Objective: The aim was to investigate maternal plasma and erythrocyte long-chain polyunsaturated fatty acids (long-chain polyenes; LCPs) postpartum, particularly DHA, in relation to lactation and dietary LCP intake., Design: Healthy pregnant women who intended to breast-feed or exclusively bottle-feed their infants were studied at 36-37 wk of pregnancy. Blood samples were collected at entry, after parturition on days 2 and 5, and 1, 2, 4, 8, 16, 32, and 64 wk postpartum. Fatty acid profiles were analyzed in plasma and erythrocyte phospholipids. Dietary intakes were assessed 4 and 32 wk postpartum with a validated food-frequency questionnaire., Results: After delivery, the percentages of plasma linoleic, arachidonic, eicosapentaenoic, and docosapentaenoic acids increased over time, whereas the percentage of docosapentaenoic acid decreased; the patterns of change did not differ significantly between the lactating and nonlactating groups. The percentage of DHA in plasma and erythrocyte phospholipid fatty acids declined significantly in the 2 groups, more so in the lactating women, and was enhanced when the lactation period was extended. Despite the apparent higher dietary intake of essential fatty acids in the lactating group at week 4, it was not significantly different from that of the nonlactating group., Conclusion: Normalization of maternal plasma and erythrocyte phospholipid n-3 LCPs differs significantly between lactating and nonlactating women postpartum but that of n-6 LCPs does not.

Background: Essential fatty acids (EFAs) in umbilical cord blood samples are associated with attained birth weight in premature infants and low-birth-weight neonates., Objective: The objective was to investigate relations between the EFA composition of cord and maternal plasma phospholipids and birth weight in term neonates., Design: This was a cross-sectional study in 627 singletons born at term. The plasma phospholipid EFA composition of the mothers was determined by gas-liquid chromatography at study entry (< or = 16 wk gestation), at delivery, and in cord plasma at birth. Birth weights were normalized to SD scores., Results: In cord plasma, the dihomo-gamma-linolenic acid concentration was positively related to weight SD scores. Both arachidonic acid (AA) and docosahexaenoic acid (DHA) were negatively related to weight SD scores. EFA-status indicators showed similar negative associations, whereas eicosatrienoic acid concentrations were positively related to neonatal size. In maternal plasma, proportions of n-3 long-chain polyenes (LCPs) and n-6 LCPs decreased during pregnancy. Larger decreases in AA, DHA, n-3 LCP, and n-6 LCP fractions were observed in mothers of heavier babies. Higher concentrations of LCPs in maternal plasma were, however, not related to a larger infant size at birth., Conclusions: A lower biochemical EFA status in umbilical cord plasma and a larger decrease in maternal plasma LCP concentrations are associated with a higher weight-for-gestational-age at birth in term neonates. Our findings do not support a growth-stimulating effect of AA or DHA; however, they do suggest that maternal-to-fetal transfer of EFAs might be a limiting factor in determining neonatal EFA status.

Background: We previously observed an inverse relation between parity and docosahexaenoic acid (DHA) status in pregnant women in the Netherlands. This implies that maternal DHA status may not fully normalize after a mature pregnancy., Objective: The objective was to investigate the relation between the essential fatty acid status (in particular the DHA status) of nonpregnant women and the number of completed pregnancies and whether the number of previous pregnancies is associated with a lower DHA status in women from the Netherlands., Design: This was a cross-sectional study of 129 healthy nonpregnant women who completed 0, 1, 2, 3, or 4 mature, uncomplicated, singleton pregnancies., Results: The relative amount of DHA in the plasma phospholipids of nulliparous women and of mothers who completed 1-4 pregnancies (duration since last pregnancy: 3.9 +/- 2.4 y) was not significantly different; a significant correlation between parity and the percentage of DHA in the phospholipids was not observed either. The percentage of DHA in the phospholipids of erythrocytes of mothers was significantly lower than the percentage in the erythrocytes of the nulliparas (P = 0.013), but no significant correlation between the percentage of DHA in the phospholipids of erythrocytes and parity was found. The time interval between the different pregnancies did not influence maternal DHA status., Conclusions: No relation was found between DHA status and parity in the nonpregnant Dutch women whose last pregnancy was completed > or = 1 y previously. Maternal DHA status, as reflected in plasma and erythrocyte phospholipids, probably normalized within 1 y after the last partus. Whether this is true for other tissues remains to be determined.

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.

Background: Although the pattern of the essential fatty acids (EFAs) changes considerably from week 10 of pregnancy to term, no information is available on changes in EFA concentrations in the early stages of pregnancy., Objective: The main objectives were to assess the EFA status, particularly that of 22:6n-3, in women during the first 10 wk of pregnancy and to investigate the relation of EFA status to dietary EFA intake during this period., Design: Healthy women (n = 24) planning to become pregnant were recruited. The fatty acid composition of plasma and erythrocyte phospholipids was determined before and at weeks 4, 6, 8, and 10 of pregnancy. Food intake was assessed at entry into the study and at week 10 of pregnancy by using food-frequency questionnaires., Results: A small but nonsignificant increase in dietary intake of 22:6n-3 was found. The plasma phospholipid content of 22:6n-3 (% by wt) increased continuously during the first 10 wk of pregnancy. At week 10 of pregnancy, the plasma percentages of 16:0, 20:3n-6, and 20:4n-6 had increased significantly, whereas the percentages of the 18-24-carbon saturated fatty acids, 18:2n-6, and the ratio of n-6 to n-3 fatty acids had dropped significantly. The composition of erythrocyte phospholipids showed changes similar to those observed in plasma., Conclusions: Maternal plasma and erythrocyte phospholipid 22:6n-3 concentrations start to increase in very early pregnancy, which cannot be explained by changes in dietary intake alone. This rise probably represents early maternal adaptations to meet the requirements of highly proliferating and differentiating tissues at this stage of fetal development.

The two human umbilical vein endothelial cell-derived lines, ECRF24 and ECV304, differ in responsiveness to oxidative stress. In confluent monolayers of ECRF24, but not in ECV304, peroxides induce stress responses such as plasma membrane blebbing and nuclear condensation. The peroxide effect on ECRF24 was preceded by oxidation of reduced glutathione (GSH) and of NAD(P)H, and by oxidation of the redox-sensitive probe, chloromethyl 2',7'-dichlorofluorescin (DCFH). In monolayers of ECV304, peroxides induced only minimal oxidation of GSH, NAD(P)H and DCFH, which was associated with a greatly reduced GSH peroxidase activity in these cells. However, in spite of the absence of a blebbing response, ECV304 were more susceptible than ECRF24 to membrane lipid peroxidation and peroxide-induced necrosis. Only for ECV304, the culturing with high levels of polyunsaturated fatty acids increased lipid peroxidation and cellular death. Treatment of these cells with the GSH peroxidase mimic ebselen effectively reversed their decreased vitality. We conclude that, in peroxide-treated endothelial cells, cell death (necrosis) can result from lipid peroxidation by peroxide that has not been removed by GSH peroxidases, whereas extensive peroxidase activity may cause a stress response (blebbing). The data further identify ECV304 as a stress-sensitive cell line, where peroxides exert their effects independently of GSH oxidation.

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.

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.

Objective: Among white Dutch women pregnancy-induced hypertension was shown to be associated with elevated levels of the long-chain polyenes of 18:2n-6 and 18:3n-3 in combination with reduced levels of those parent essential fatty acids. This observation suggested an enhanced desaturation and elongation of the parent fatty acids. This study was performed to investigate whether this phenomenon also occurs under completely different nutritional and geographic conditions., Study Design: Plasma fatty acids of primiparous Mestizo Ecuadorian women with uncomplicated pregnancies and with pregnancy-induced hypertension were assessed at delivery and compared with similar data from white Dutch women. Neonatal values, as determined in umbilical plasma and umbilical vessel walls, were also compared., Results: In contrast to the pattern seen among white mothers, pregnancy-induced hypertension did not increase the long-chain polyene status of Mestizo mothers. Despite the absence of this compensatory mechanism, long-chain polyene status was not compromised in Mestizo neonates born after pregnancy-induced hypertension., Conclusion: Additional mechanisms may be active in maintaining the long-chain polyene status of neonates born after pregnancy-induced hypertension.

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.

Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities were measured in sera from 32 normolipidemic women and men consuming diets enriched in lauric, palmitic, or oleic acids. Serum CETP activity, measured as the rate of radiolabeled cholesteryl esters transferred from HDL toward serum apo B-containing lipoproteins, was higher with the palmitic acid diet (25.1+/-2.5%) than with the lauric acid (23.7+/-2.4%) and the oleic acid (24.0+/-2.7%) diets (P = 0.0028 and 0.0283, respectively). CETP mass concentrations, as measured with an enzyme-linked immunosorbent assay were increased after the lauric acid diet (2.57+/-0.63 mg/l) and the palmitic acid diet (2.49+/-0.64 mg/l) as compared with the oleic acid diet (2.34+/-0.45 mg/l) (P = 0.0035 and 0.0249, respectively). In contrast with CETP, serum PLTP activity, as measured as the rate of radiolabeled phosphatidylcholine transferred from liposomes toward serum HDL, was significantly higher with the lauric acid diet (23.5+/2.6%) than with the palmitic acid diet (22.5+/-2.5%) (P = 0.0013), while no significant differences were noted when comparing the saturated diets versus the oleic acid diet (23.0+/-2.3%). No significant alterations in the mean apparent diameter of LDL, and in the relative proportions of individual HDL subpopulations were observed from one dietary period to another. Nevertheless, lipid transfer activities correlated significantly with the relative abundance of HDL2b, HDL2a, HDL3b, and HDL3c, with opposite tendencies being observed for cholesteryl ester transfer and phospholipid transfer activities. In general, serum CETP activity correlated negatively with HDL cholesterol, but positively with triglyceride concentrations after the dietary interventions, and the relations with serum lipids were just the opposite for PLTP activity. In addition, CETP and PLTP activities correlated negatively when subjects consumed the standardized diets (P < 0.05 in all cases), but not when subjects consumed their habitual diet. It is concluded that serum lipid transfer activities in normolipidemic subjects can be significantly affected by the fatty acid content of the diet, with differential effects on CETP and PLTP activities.

In this study we investigated the effects on lipoproteins of medium chain fatty acids (MCFA) and myristic acid relative to those of oleic acid. Thirty-seven women and 23 men consumed a 3-wk run-in diet enriched in oleic acid followed by a 6-wk test diet rich in MCFA (n = 21), myristic (n = 20), or oleic acid (n = 19). Experimental fats were incorporated into solid foods. Total fat intake was 40 En% fat. The dietary compositions were the same except for 10 En%, which was provided by MCFA, myristic, or oleic acids, respectively. With the myristic acid diet, low density lipoprotein (LDL) cholesterol was 0.37 mmol/L higher compared with the oleic acid diet (P = 0.0064 for difference in changes). The MCFA diet increased LDL cholesterol, though not significantly, with 0.23 mmol/L relative to the oleic acid diet (P = 0.0752). Compared with the oleic acid diet, HDL cholesterol concentrations increased with the myristic acid diet by 0.10 mmol/L (P = 0.0273) but not with the MCFA diet. The MCFA diet slightly elevated triacylglycerol concentrations, but responses did not significantly differ between the diets. The MCFA diet significantly decreased the apoA-I to apoB ratio compared with both other diets (P < 0.02). We conclude that MCFA raise LDL cholesterol concentrations slightly and affect the apoA-I to apoB ratio unfavorably compared with oleic acid. Myristic acid is hypercholesterolemic, although less than predicted earlier, and raises both LDL and HDL cholesterol concentrations compared with oleic acid.

Objective: To examine whether dietary factors in pregnancy are related to fetal growth., Design: Prospective longitudinal study during pregnancy; midway through gestation a dietary history was obtained., Subjects/setting: Subjects (n = 372) were participants in a study on maternal essential fatty acid status during pregnancy who did not have hypertension or any metabolic, cardiovascular, neurological, or renal disorder. Only pregnant white women with the intention to give birth in one of the three hospitals involved in the study were included. All three hospitals were located in the southern part of the Netherlands., Statistical Analyses Performed: The relation between maternal nutrition and fetal growth was evaluated using multiple regression analyses., Results: Maternal intake of n-3 fatty acids plus arachidonic acid and of riboflavin were associated positively with fetal growth. A negative relation was observed between linoleic acid intake and fetal growth., Applications/conclusions: Our data suggest that the maternal diet during pregnancy is associated with fetal growth. Although this relationship ought to be more closely investigated, our results imply that much more attention should be paid to an adequate maternal diet during pregnancy, especially with respect to riboflavin and fatty acid intake.

Vitamin K is involved in the biosynthesis of a number of blood coagulation factors and bone proteins. It has been suggested that the vitamin K requirement of bone tissue is higher than that of the liver. Here we report that in rats very high doses of vitamin K affected neither the blood coagulation characteristics nor the blood platelet aggregation rate. This was observed for both phylloquinone and menaquinone-4. Both vitamers were also tested for their effects on the arterial thrombosis tendency in the rat aorta loop model. The mean obstruction times were prolonged at a high intake of menaquinone-4 (250 mg/kg body weight/day), and shortened after a similarly high phylloquinone regimen. Since (a) both vitamers only differ in their aliphatic side chains; and (b) a similar trend was observed after administration of phytol and geranylgeraniol, we conclude that the modulation of the arterial thrombosis tendency is accomplished by the side chain of vitamin K.

To study the influence of dietary fatty acids on arterial thrombosis tendency 65 groups of male rats were fed diets containing 50% of their digestible energy as fat from 32 different oils and fats. After 8 weeks their arterial thrombosis tendency was assessed by measuring the obstruction time (OT) of a loop-shaped polythene cannula inserted into the abdominal aorta. Using multiple regression analysis log10 OT was modelled as a function of the relative amounts of the various dietary fatty acids and their combinations. The best fit (R2 = 0.79) was obtained for the sums of all monoenoic and (n-6) and (n-3) polyenoic fatty acids, which appeared antithrombotic. The fit for the sum of all saturated fatty acids, which had a prothrombotic effect, was almost as good (R2 = 0.76). The ratio between dietary polyunsaturated and saturated fatty acids (P:S ratio) appeared a strong predictor of arterial thrombosis tendency (R2 = 0.77). Marine oils did not have a more powerful antithrombotic effect than could be expected on the basis of their P:S ratios. Using stepwise regression analysis myristic acid, 14:0, was shown to be the strongest prothrombotic fatty acid whereas linoleic acid, 18:2(n-6), was the strongest antithrombotic fatty acid. Since the number of marine oils was very limited the effects of the 'fish fatty acids' eicosapentaenoic acid, 20:5(n-3) and docosahexaenoic acid, 22:6(n-3), on arterial thrombus formation could not be tested reliably. The same appeared true for gamma-linolenic acid, 18:3(n-6), and stearidonic acid, 18:4(n-3), present in a few vegetable oils only.

The essential fatty acid (EFA) status of full-term infants born after an uneventful, singleton pregnancy has been reported to be marginal. If this low EFA status is caused by a limiting maternal EFA supply, the higher total fetal EFA demand associated with a multiple pregnancy would result in an even lower EFA status of the infants born after a multiple pregnancy. Therefore, we compared the EFA status at birth of 30 pairs of twins, seven sets of triplets, and one set of quintuplets with that of 94 infants (51 preterm, 43 full-term) born after a singleton pregnancy. Phospholipid-associated EFA profiles of the umbilical vessel walls, considered a longer-term reflection of the fetal EFA status, were studied. After correction for gestational age at birth, levels of n-6 and n-3 EFAs were generally lower, while levels of EFA-deficiency indicating n-9 polyunsaturated fatty acids were significantly higher both in the draining umbilical arteries and the supplying veins of infants born after a multiple pregnancy. EFA profiles of twins and triplets were similar, but the average EFA status of the set of quintuplets was lower than that of twins and triplets. In conclusion, the observation that the EFA status of infants born after a multiple pregnancy is lower than that of infants born after a singleton pregnancy supports the view that the maternal EFA supply to the fetus is limiting. Considering the importance of EFAs and their longer chain derivatives for proper growth and development, this finding warrants further studies of the adequacy of the maternal EFA intake during pregnancy.

A high intake of trans fatty acids (TFAs) has been shown to have an undesirable effect on serum lipid profiles and lipoprotein(a) (Lpa)) levels and may thereby increase the risk for coronary heart disease (CHD). We performed a study in CHD patients, and measured the TFA concentration of the plasma phospholipid fraction. Comparison was made between a case group with angiographically documented severe CHD (> 80% stenosis in one coronary vessel, n = 83) and a control group of patients who had just minor stenosis on the coronary angiography (< 50% stenosis in all three major vessels, n = 78): All subjects were under 68 years of age and were prestratified on age, gender and smoking habits. The two groups were comparable according to the prestratification criteria, body mass index, blood pressure, number of cigarettes smoked and total fat intake. Controls had higher plasma HDL levels (P < 0.001) and lower, albeit not significantly lower, (P = 0.07) plasma LDL levels. No significant correlations were found between percentages of TFAs in plasma phospholipids and plasma LDL or HDL cholesterol levels. Of the major fatty acid classes, only the percentage of saturated fatty acids was significantly higher in cases (46.2 +/- 0.92%) than in controls (45.8 +/- 1.07% (means +/- S.D.)). The difference in total TFA content between cases and controls (0.32 +/- 0.02% versus 0.35 +/- 0.02%) was -0.03% (P = 0.2). For the specific TFAs C16:1n-7tr, C18:1n-9tr and C18: 2n-6tr, just minor differences were found. Adjusted odds ratios for tertiles of TFA percentages were 0.56 (0.25-1.23) and 0.76 (0.36-1.61) for the highest middle tertile compared to the lowest. These findings do not support an association between TFA intake and risk for coronary heart disease.

Hardly any direct information is available on the essential fatty acid (EFA) status of the fetus during intrauterine development. Therefore, we studied 86 umbilical plasma samples obtained by trans-abdominal puncture during ongoing pregnancies (18.3-39.0 weeks of gestational age). These were compared with 51 samples of umbilical cord blood, collected immediately after birth (gestational ages, 28.5-39 weeks). The total amounts of fatty acids in fetal plasma phospholipids (mg/l) did not change during gestation. The relative amounts of linoleic acid (% of total fatty acids) showed a slight increase (P = 0.03) during fetal maturation. Arachidonic acid (20:4n-6) decreased (both absolute (mg/l) and relative (% wt/wt) P < or = 0.0001), while docosahexaenoic acid (22:6n-3) increased (absolute P < 0.003, relative P < 0.0001) when pregnancy progressed. The EFA profiles of fetal samples were in general comparable with postnatal results of infants born at similar gestational ages. However, the fetal linoleic acid status was lower than the linoleic acid status of the neonates. The same was true for the overall EFA status. The results of this study indicate that the low EFA status observed in preterm infants at birth, is a developmentally related phenomenon.

The degree to which different saturated fatty acids exert their cholesterol-raising effects is still unknown. Therefore, we studied the effect on serum lipids and lipoproteins of diets rich in lauric, palmitic, or oleic acids. Eighteen women and 14 men consumed in random order three experimental diets, each for 6 wk. The diets consisted of solid foods and contained 40% of energy as fat, of which 28% was supplied by the experimental fats. The fat high in lauric acid was a mixture of palm kernel oil (75%) and a high-oleic acid sunflower oil (25%); the fat high in palmitic acid consisted of dairy fat (55%), palmstearin (36%), and sunflower oil (9%); and the fat high in oleic acid consisted of dairy fat (37%) and sunflower oil (63%). The calculated nutrient composition was the same in each diet except for approximately equal to 8.5% of energy, which was provided by lauric, palmitic, or oleic acids. With the lauric acid diet the subjects' serum total cholesterol concentration increased by 0.22 mmol/L (P = 0.0121; 95% CI: 0.02, 0.41 mmol/L) as compared with the palmitic acid diet and by 0.48 mmol/L (P < 0.0001; 95% CI: 0.29, 0.67 mmol/L) compared with the oleic acid diet. Total cholesterol concentrations with the palmitic acid diet were 0.26 mmol/L (P = 0.0012; 95% CI: 0.07, 0.46 mmol/L) higher than with the oleic acid diet. High-density-lipoprotein (HDL)-cholesterol concentrations increased by 0.12 mmol/L (P = 0.006; 95% CI: 0.04, 0.20 mmol/L) with the lauric acid compared with the palmitic acid diet and by 0.14 mmol/L (P < 0.001; 95% CI: 0.07, 0.22 mmol/L) compared with the oleic acid diet. HDL-cholesterol concentrations with the palmitic acid and the oleic acid diet were the same. No effects were seen in serum triacylglycerol and lipoprotein(a) concentrations. We conclude that both lauric and palmitic acids are hypercholesterolemic compared with oleic acid. Lauric acid raises total cholesterol concentrations more than palmitic acid, which is partly due to a stronger rise in HDL cholesterol.

To study the effect of maternal linoleic acid [18:2(n-6), LA] supplementation during pregnancy on neonatal essential fatty acid status, pregnant women with relatively low plasma linoleic acid concentrations before 16 wk of gestation (n = 21) were supplied with foods rich in linoleic acid, resulting in an additional intake of 10 g/d of linoleic acid from the 20th week of gestation until delivery. One of the two control groups consisted of pregnant women with comparably low plasma linoleic acid concentrations at the start of the study (LL-control group, n = 22); the other consisted of women with habitually high plasma linoleic acid concentrations (HL-control group, n = 21). The neonatal essential fatty acid status was assessed by determining the fatty acid composition of phospholipids (PL) isolated from umbilical plasma and umbilical vessel walls. The maternal linoleic acid status in the LA-supplemented group increased to a level comparable to that of the HL-control group, but the neonatal linoleic acid status did not differ from that of either control group. Linoleic acid supplementation did result in slightly, but significantly, higher total amounts of (n-6) long-chain polyenes in umbilical plasma and vein vessel wall phospholipids compared with the LL-control group. This increase was associated with significantly lower total amounts of (n-3) long-chain polyenes. In the HL-control group, the concentration of (n-3) long-chain polyenes in umbilical plasma and vessel walls was significantly lower than in the LA-supplemented and the LL-control group.(ABSTRACT TRUNCATED AT 250 WORDS)

The molecular species composition of plasma phosphatidylcholine (PC) was measured in sequential blood samples from 13 pregnant women from 16 weeks of gestation to delivery at term. The increased total plasma PC concentration at term was due solely to increased concentrations of individual species containing palmitate (16:0) rather than stearate (18:0) at the sn-1 position. The specific increase of PC16:0/22:6 concentration in mid-gestation suggests that adaptations to maternal hepatic PC metabolism may provide a mechanism to ensure adequate supply of 22:6(n-3) to the fetus. While cord plasma PC was comparable to liver PC composition from three stillborn term infants, the compositions of these tissues differed from maternal plasma PC, which contained significantly more PC16:0/18:2 and PC18:0/18:2. These results suggest that, although fetal acquisition of polyunsaturated fatty acids (PUFA) is dependent on the maternal lipid supply, the detailed composition of fetal plasma PC may be regulated largely by intrinsic fetal mechanisms such as placental and liver PC metabolism. Similarly, the specific alterations to maternal plasma PC composition in pregnancy, which we postulate are associated with the supply of PUFA to the fetus, were substantially independent of variations in maternal dietary lipid nutrition.

The essential fatty acid (EFA) composition of umbilical vessel walls is increasingly being studied as a longer-term reflection of the fetal EFA status. We evaluated the EFA content of umbilical artery and vein vessel walls in 43 preterm infants and compared it with that of 43 full-term cord vessels. In addition, relations among cord vessel wall fatty acid composition, gestational age (GA) at birth, and anthropometric parameters at birth (weight, head circumference, and length) were explored in the preterm infants. Generally, n-6 and n-3 EFA levels were lower, while levels of EFA deficiency markers were higher in preterm than in term cords, both in the walls of the draining arteries and the supplying vein. In preterm cords, significant correlations were observed between GA at birth and levels of n-6 and n-3 EFAs (positive) and EFA deficiency markers (negative). Birth weight showed significant (P < or = 0.01), positive correlations with n-6 and n-3 EFA levels in the cord artery walls of preterm infants, all after correction for GA at birth. In conclusion, substantial differences between the EFA profiles of preterm and full-term cord vessel walls indicate a lower biochemical EFA status of the preterm than of the term fetus. This lower preterm EFA status might be a reflection of a physiologically lower EFA demand for growth and development of the preterm fetus than of the term fetus.

Objective: Our purpose was to investigate, in a prospective way, whether the altered essential fatty acid status observed in pregnancy-induced hypertension is a consequence of the disease or may contribute to its cause., Study Design: Pregnant women healthy at the start of the study were asked to give a blood sample before 16 weeks, at 22 weeks, and at 32 weeks of gestation. After delivery a blood sample from the umbilical vein, a piece of the umbilical cord, and a maternal blood sample were collected. Fatty acid compositions were determined of the phospholipids isolated from plasma and umbilical arterial and venous vessel walls. The nutrient intake of the pregnant women was assessed by use of the dietary history method and food frequency questionnaires. The results of each woman with pregnancy-induced hypertension were compared with the results of three matched healthy controls., Results: During pregnancy (16 to 32 weeks) no significant differences were observed in nutrient intake and maternal plasma fatty acid composition between the group with pregnancy-induced hypertension (n = 52) and the control group (n = 156). After delivery the relative amounts of 18:2(n-6) and 18:3(n-3) in maternal plasma were significantly lower in pregnancy-induced hypertension than in normal pregnancy. This was associated with significantly higher levels of (n-6) long-chain polyenes and cervonic acid (22:6[n-3]). In comparison with the situation at 32 weeks, the postpartum cervonic acid status increased in pregnancy-induced hypertension, whereas it decreased in normal pregnancy. The cervonic acid levels in umbilical plasma phospholipids were significantly higher after pregnancy-induced hypertension than after normal pregnancy. No significant differences were observed for the fatty acid content in umbilical vessel walls., Conclusion: The results indicate that the altered essential fatty acid status in pregnancy-induced hypertension is a late phenomenon and is therefore unlikely to have contributed to the pathogenesis of pregnancy-induced hypertension. Moreover, the neonatal essential fatty acid status is not negatively affected by pregnancy-induced hypertension.

A highly sensitive and rapid high-performance liquid chromatographic assay for the determination of histamine and 3-methylhistamine in biological samples using 1-methylhistamine as the internal standard is described. Samples were purified and concentrated on cation-exchange columns and derivatized with fluorescamine. The lower detection limit was 20 pg on-column. Linearity was demonstrated up to 20 ng on-column. The samples could be derivatized simultaneously before injection and were stable for 7 days. The method was used for the determination of histamine and related compounds in coronary perfusates, extracts of homogenized rat hearts, and supernatants of stimulated peritoneal mast cells.

Human umbilical vein endothelial cells were cultured in various fatty acid-modified media until equilibrium conditions were reached (7-8 days). The effects on the fatty acid composition of phospholipid classes and on the metabolism of arachidonic acid (20:4(n-6)) were studied. The results showed that in every phospholipid class large changes in fatty acid composition, including 20:4(n-6) content, were induced by long-term modification with unsaturated as well as saturated fatty acids. However, the mean levels of saturated and unsaturated fatty acids per phospholipid class remained relatively constant, except for cells modified with oleic acid, which showed an increase in monounsaturated fatty acids at the expense of both saturated and polyunsaturated fatty acids. The rate of incorporation of radiolabeled 20:4(n-6) in endothelial lipids was not influenced by long-term fatty acid modification. Cells modified with 20:4(n-6) (having a high 20:4(n-6) content) tended to "store" excess 20:4(n-6) as the elongated product 22:4(n-6) mainly in phosphatidylserine and ethanolamine phospholipids. On the other hand, endothelial cells modified with 20:5(n-3) (having a low 20:4(n-6) content) differed typically from other fatty acid-modified cells by a relatively high level and high incorporation rate of 20:4(n-6) in phosphatidylinositol, with a low extent of elongation. These results indicate extensive homeostatic control of membrane unsaturation in each phospholipid class and economical control of 20:4(n-6) content in all modified endothelial cells, irrespective of a considerable variation of 20:4(n-6) levels in cellular lipids. Moreover, the observed maintenance of a critical level of 20:4(n-6) in phosphatidylinositol, when 20:4(n-6) supply was strongly decreased, may be important for maintaining proper signal transduction upon endothelial cell stimulation.

Preliminary studies indicated that the EFA status of normal neonates is marginal, if not insufficient. Since a better knowledge of the physiology of maternal-fetal essential fatty acid transfer is relevant for nutritional recommendations during pregnancy, we investigated the course of the fetal EFA status during fetal development by analysing the absolute (micrograms/g dry fetal tissue) and relative (% of total fatty acids) fatty acid composition of phospholipids in human fetal tissue, (n = 40, gestational age 5-15.2 weeks). The total content of fatty acids (mg/g dry fetal tissue) increased with gestational age. The absolute amount of virtually all fatty acids increased with maturation. Linoleic acid (18:2n-6, LA), however, was an exception. A highly significant, negative correlation between gestational age and the relative amount of LA in fetal tissue was observed during this first trimester of pregnancy. Our results show that the fetal-maternal difference in linoleic acid content observed at birth, initiates early in pregnancy. Since the fetus completely depends on the mother for its EFA supply, the maternal EFA status was measured simultaneously by analysing the fatty acid composition of phospholipids, isolated from plasma and red blood cells. Significant positive correlations between maternal rbc and fetal tissue were found for the relative amounts of LA. Similar relationships were observed between maternal plasma and fetal tissue for the relative amounts of cervonic acid (22:6n-3), the most abundant essential fatty acid in brain and retina. The relation between maternal and fetal EFA in phospholipids is significantly more pronounced after 10 weeks of gestation than before. This might be connected with the increased importance of the placenta with respect to maternal-fetal fatty acid transfer after 10 weeks of gestation.

Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a control diet high in saturated fatty acids for 17 days. For the next 36 days, 6.5% of total energy intake from saturated fatty acids was replaced by monounsaturates plus polyunsaturates (monounsaturated fatty acid diet; n = 29) or by polyunsaturates alone (polyunsaturated fatty acid diet; n = 29). Both diets caused a slight, nonsignificant, increase in median Lp[a] levels, with no difference between diets. In Expt. II, 10% of energy from the cholesterol-raising saturated fatty acids (lauric, myristic, and palmitic acid) was replaced by oleic acid or by trans-monounsaturated fatty acids. Each of the 59 participants received each diet for 3 weeks in random order. The median level of Lp[a] was 26 mg/l on the saturated fatty acid diet; it increased to 32 mg/l (P less than 0.020) on the oleic acid diet and to 45 mg/l (P less than 0.001) on the trans-fatty acid diet. The difference in Lp[a] between the trans-fatty acid and the oleic acid diets was also highly significant (P less than 0.001). Expt. III involved 56 subjects; all received 8% of energy from stearic acid, from linoleic acid, or from trans-monounsaturates, for 3 weeks each. All other nutrients were equal.(ABSTRACT TRUNCATED AT 250 WORDS)

The essential fatty acid (EFA) status of neonates was compared with that of their mothers by determining the fatty acid compositions of phospholipids (PL), isolated from umbilical arterial and venous tissue, blood cells (BC) and plasma, from maternal venous plasma and BC, and from non-infarcted placental tissue. The PL of umbilical arterial tissue (efferent fetal vessels) contained fewer fatty acids of the (n-6) family and more of the (n-9) family than umbilical venous tissue (afferent fetal vessel). The relative amounts of (n-6) and (n-3) fatty acids were less in arterial than in venous plasma. Mead acid, 20:3(n-9), the presence of which indicates a poor EFA status, was 5 times higher in the efferent than in afferent cord vessels. In neonatal plasma and BC it was twice as high as compared with maternal levels. In general, the fatty acid composition of the placenta PL showed a comparable pattern as neonatal venous plasma PL. These findings demonstrate that the biochemical EFA status of neonates after a normal pregnancy is not optimal. The significant correlations between neonatal and maternal EFAs indicate that the neonatal EFA status depends on the EFA content of the maternal diet.

In Maastricht and Zeist, The Netherlands, and Tromsø, Norway, a well-controlled study was performed on the effect of a fish-enriched diet on serum lipids, apolipoproteins A-1 and B, and fatty acid compositions of serum triglycerides and cholesterol esters. For 6 wk healthy male volunteers were given a daily dietary supplement consisting of 135 g mackerel paste (experimental group, n = 42) or meat paste (control group, n = 42). Dietary adherence was calculated on the basis of urinary excretion of a standard amount of lithium added to the supplements. Average compliance was 80%. Low-density-lipoprotein (LDL) and total serum cholesterol concentrations were unaffected. High-density-lipoprotein (HDL) cholesterol increased to a comparable degree in both groups. Triglyceride content of serum decreased in the fish group. Apolipoproteins A-1 and B (both in Maastricht subjects only) were only slightly affected. In the mackerel group the n-3 fatty acids increased significantly in serum cholesterol esters and triglycerides; the n-6 fatty acids decreased in cholesterol esters only.

To clarify whether the inverse relation between habitual fish consumption and cardiovascular mortality in the Dutch town of Zutphen could be explained by changes in platelet function or fibrinolysis, 40 healthy elderly men were selected from the Zutphen study population on the basis of their fish consumption over the last 26 years. In the high-fish group (n = 25) fish consumption was on average 33 g per person per day; in the low-fish group (n = 15) it was on average 2 g per person per day. This difference was reflected by significant differences in the concentrations of timnodonic acid (20:5n - 3) and cervonic acid (22:6n - 3) in the serum phospholipids of the participants. Between both groups no significant differences were observed in cutaneous bleeding time, platelet number, and collagen-induced platelet aggregation and ATP-release in whole blood. The same holds for the actual as well as the potential thromboxane B2 formation of activated platelets and for the activity of the plasminogen activator inhibitor. For most of the platelet-related variables a trend was found for a lower activity in the high-fish group. Therefore changes in platelet function might not explain, but may have slightly contributed to the inverse relationship between coronary heart disease and fish consumption, as observed in Zutphen.

The effect of dietary fatty acids on the formation and growth of intra-arterial occlusive thrombi in rats was investigated. It appeared that fats containing a large amount of saturated fatty acids promote arterial thrombus formation, whereas dietary linoleic acid has a specific anti-thrombotic effect. Oleic acid on its own does not seem to act as an anti-thrombotic substance. However, the replacement of thrombogenic fatty acids by oleic acid results in a decrease of the dietary thrombogenic potency. Moreover, the results indicated that the thrombogenicity of the saturated fatty acids increases with their chain length. As for the anti-thrombotic effect of cis fatty acids and their trans isomers, no obvious differences have been observed. Almost identical results were obtained when thrombogenicity was related to either absorption or to composition of the dietary fatty acids. Further research can therefore be restricted to this latter criterion. For the majority of the fats tested, thrombosis tendency and ADP-induced platelet aggregation were closely associated. It is therefore highly probable that platelet aggregation is involved in the mechanism by which dietary fats affect arterial thrombus formation.