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Current discussion of the importance of food fats in the risk of coronary heart disease (CHD) often suffers from preconceptions, misunderstandings, insufficient knowledge, and selective reasoning. As a result, the sustained controversy about dietary fat recommendations can be contradictory and confusing. To clarify some of these issues, the International Expert Movement to Improve Dietary Fat Quality in cooperation with the International Union of Nutritional Sciences (IUNS) organized a symposium at the 21st meeting of the IUNS, October 17, 2017, Buenos Aires, Argentina, to summarize the key scientific evidence underlying the controversy on the relationship between the saturated and unsaturated fat consumption and CHD risk. Presenters also discussed, using examples, the rationale for and implications of the partial replacement of foods rich in saturated fats by those rich in unsaturated fats. Presentations included strategies to fit healthier fats into meals. This report summarizes the symposium presentations., (© 2018 S. Karger AG, Basel.)

Dietary fats have important effects on the risk of cardiovascular disease (CVD). Abundant evidence shows that partial replacement of saturated fatty acids (SAFA) with unsaturated fatty acids improves the blood lipid and lipoprotein profile and reduces the risk of coronary heart disease (CHD). Low-fat diets high in refined carbohydrates and sugar are not effective. Very long-chain polyunsaturated n-3 or omega-3 fatty acids (n-3 VLCPUFA) present in fish have multiple beneficial metabolic effects, and regular intake of fatty fish is associated with lower risks of fatal CHD and stroke. Food-based guidelines on dietary fats recommend limiting the consumption of animal fats high in SAFA, using vegetable oils high in monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and eating fatty fish. These recommendations are part of a healthy eating pattern that also includes ample intake of plant-based foods rich in fiber and limited sugar and salt., Competing Interests: Peter L. Zock and Wendy A.M. Blom are employed by Unilever Research & Development. Joyce A. Nettleton reports personal fees from Unilever Research & Development. Gerard Hornstra reports personal fees from MVO (Netherlands Oils and Fats Industry), EPOA (European Palm Oil Alliance), and Unilever/IUNS (International Union of Nutritional Sciences). Human and Animal Rights and Informed Consent This article does not contain any new data from studies with human or animal subjects performed by any of the authors.

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.

Previous studies have shown that energy restriction (ER) or low-fat (LF) diets have beneficial effects on high-fat (HF) diet-induced obesity and non-insulin-dependent diabetes. However, comparison between ER and low-fat diet regarding the effect on insulin resistance and lipid metabolism has not been reported. After inducing insulin resistance by HF feeding for 20 weeks, male C57BL/6J mice were divided into 3 groups. For a period of 12 weeks, group 1 received energy restriction (70% of ad libitum, HF diet), group 2 LF diet, and group 3 maintained on HF diet. Body weight and energy intake were reduced equally in ER and LF feeding. Plasma insulin levels were decreased on LF feeding, but were unchanged on ER, when compared with HF feeding. Glucose tolerance and insulin sensitivity tests revealed that insulin sensitivity was improved more efficiently by LF feeding than on ER. Plasma triglyceride (TG) levels were lower on LF feeding compared with ER and HF feeding. Measurement of hepatic very low-density lipoprotein (VLDL)-TG production revealed a lower production after LF diet feeding or ER compared with HF diet feeding. In summary, our data show that LF diet has a higher potential than ER to improve HF diet-induced insulin resistance, and that there is an association between improvement of insulin resistance and decrease of TG levels., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

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.

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.

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.

In the present intervention study we compared the effects of alpha-linolenic acid with those of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on platelet aggregation in vitro and ex vivo in healthy non-institutionalized elderly subjects. We also compared the effects of alpha-linolenic acid on platelet aggregation in elderly subjects with those in younger volunteers. During a run-in period of 3 weeks all subjects (thirty-eight elderly (> 60 years) and twelve younger volunteers (< 35 years)) received a diet rich in oleic acid. For the next 6 weeks the elderly subjects received a diet rich in oleic acid (n 11), alpha-linolenic acid (n 14) (6.8 g/d) or EPA/DHA (n 13) (1.05 g EPA plus 0.55 g DHA). The younger subjects were given a diet rich in alpha-linolenic acid. The diets did not affect ADP- or collagen-induced platelet aggregation in vitro in either platelet-rich plasma or whole blood. The ex vivo platelet aggregation as measured with filtragometry was significantly decreased in the elderly group that received EPA/DHA compared with the alpha-linolenic acid (P = 0.006) and the oleic acid (P = 0.005) diet groups. Effects of alpha-linolenic acid were not age-dependent. Our results suggest that alpha-linolenic acid and EPA/DHA do not change in vitro platelet aggregation. Compared with oleic acid, EPA/DHA, but not alpha-linolenic acid, favourably affects ex vivo platelet aggregation in healthy elderly subjects.

In this study we compared the effects of specific saturated fatty acids (lauric acid and palmitic acid) with those of a monounsaturated fatty acid (oleic acid) on coagulation and fibrinolytic parameters in healthy women and men. Eighteen women and fourteen men consumed, in random order, three experimental diets, each for six weeks. The diets consisted of solid foods and approximately 70% [28 percent of energy (En%)] of the fat calories was supplied. As determined from duplicate portions, in the lauric acid diet 7.3 En% and in the palmitic acid diet 6.1 En% of oleic acid were exchanged for lauric or palmitic acid, respectively. The lauric acid diet also contained some (average 1.8 En%) more myristic acid. Compared with the oleic acid diet, factor VIIam in the female subjects was 9% higher with the lauric acid diet (P = 0.0036; 95% CI, 3 to 14%) and 10% higher with the palmitic acid diet (P = 0.0011; 95% CI, 5 to 16%). Changes in men were not significant. Plasminogen Activator Inhibitor (PAI-1) activity was higher on the palmitic acid compared with the oleic acid diet (difference between diets of 2.3 U/ml; P = 0.0098; 95% CI, 0.4 to 4.3 U/ml) and the lauric acid diet (difference between diets of 2.2 U/ml; P = 0.0123; 95% CI, 0.2 to 4.1 U/ml). No significant differences between diets were observed for antithrombin III activity, fibrinogen concentrations, fragment 1+2 concentrations, plasminogen or alpha2-antiplasmin activity. From this study, we conclude that diets rich in lauric or palmitic acid, compared with a diet rich in oleic acid, unfavourably influence factor VIIam activity, in a gender specific manner. In addition, the plasminogen activator inhibiting capacity of the plasma is impaired with a palmitic acid rich diet compared with an oleic or lauric acid rich diet.

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.

Objectives: In two studies we have compared the effects of four different saturated fat diets (medium chain fatty acids (MCFA), and lauric, myristic and palmitic acids) with those of a monounsaturated oleic acid diet on in-vitro whole blood aggregation in healthy women and men., Design: Study 1 had a cross-over design with three diet periods of each six weeks, and studied the effects of diets enriched in lauric, palmitic or oleic acids. Study 2 had a parallel design. After a three week oleic acid run-in diet, three groups of subjects were formed which consumed either an MCFA, myristic acid or oleic acid rich diet for six weeks., Subjects: Eighteen women and 14 men in Study 1 and 37 women and 23 men in Study 2. All subjects were healthy and were aged 20-60 y., Interventions: The experimental diets were the same in nutrient composition except for on average 8 En% (Study 1) or 10 En% (Study 2) which was provided by either MCFA, lauric acid, myristic acid, palmitic acid or oleic acid. Blood samples were taken at the end of each dietary period. Whole blood platelet aggregation, anticoagulated with recombinant hirudin was assessed after administration of collagen (final concentration (fc): 0.38 microgram/mL) in Study 1 and collagen (fc: 0.22 microgram/mL) or ADP (fc: 1.25 mumol/L) in Study 2. Collagen-induced formation of thromboxane (Tx)A2, measured as thromboxane (Tx)B2, was evaluated in Study 1 only., Results: The aggregation velocity between the saturated fatty acid diets and the monounsaturated fatty acid diet did not differ. TxB2 concentrations measured in collagen activated blood samples, which correlated significantly with aggregation velocity, did not differ between the lauric or the palmitic compared with the oleic acid diet. A stepwise regression analysis indicated that collagen-induced aggregation was negatively correlated with the number of red blood cells. ADP-induced aggregation also correlated negatively with red blood cell count, and positively with platelet count., Conclusions: The exchange of 7-10 En% from oleic acid for MCFA, lauric, myristic or palmitic acid does not affect in-vitro whole blood aggregation induced by collagen. ADP-induced aggregation is not affected when 10 En% from oleic acid is exchanged for MCFA or myristic acid.

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 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.

Objective: To study the relationships between the essential fatty acid (EFA) composition of maternal diet, maternal EFA status and the EFA status of healthy newborn infants., Methods: A prospective longitudinal study was performed in which 176 pregnant women completed a food frequency questionnaire (FFQ) before 13, at 22, and at 32 weeks of gestation, so that changes in nutrient intake throughout pregnancy could be recorded. Around 22 weeks, a dietary history was performed and a maternal blood sample was collected. Immediately after delivery, a blood sample from the umbilical vein and a piece of the umbilical cord were collected. Fatty acid compositions were determined for phospholipids (PLs) isolated from maternal and umbilical plasma and from umbilical vein and artery vessel walls., Results: No significant differences in the mean daily intake of total fat, saturated fat, mono-unsaturated fat, polyunsaturated fat and linoleic acid (18:2(n-6), LA) were observed between the three trimesters. Maternal LA intake was positively associated with LA levels in maternal and umbilical plasma and negatively associated with 20:3(n-9), 18:3(n-3), 20:4(n-3) and 22:5(n-3) levels in maternal plasma, with 20:5(n-3) levels in umbilical plasma and with 22:6(n-3) levels in umbilical vein vessel walls. Significant positive correlations for almost all (n-6) and (n-3) fatty acids were observed between maternal and umbilical plasma levels., Conclusions: The maternal dietary fat composition appears to be consistent during pregnancy. A high maternal LA intake may have a lowering effect on the maternal as well as on the neonatal (n-3) fatty acid status. Finally, neonatal EFA status is strongly related to maternal EFA status.

Unfavourable effects of trans monounsaturated fatty acid (trans-C18:1) isomers on health variables have been reported. Reports on their actual intake, however, are scarce, because of the absence in many nutrient databases of values for trans-C18:1, and the wide variation in the level of trans fatty acids between different brands of the same product. We therefore examined whether the intake of trans-C18:1 is reflected by trans-C18:1 concentrations in serum triacylglycerols or platelet phospholipids. Thirty-eight men received two diets in random order. During the first experimental period twenty men consumed a Western-type control diet for six weeks, and eighteen men consumed a modified diet in which 70% of the fat was replaced by palm oil. After a wash-out period of 3 weeks, regimens were crossed over (second experimental period). The proportion of total fatty acids from trans-C18:1 in the diet decreased from 4.7 (SEM 0.27) during the control to 2.1 (SEM 0.16) on the modified diet (P < 0.001). Trans-C18:1 in serum triacylglycerols decreased from 3.5 (SEM 0.13) to 2.8 (SEM 0.11)% (P < 0.001), and in platelet phospholipids from 1.0 (SEM 0.06) to 0.7 (SEM 0.04)% (P < 0.001). After the first experimental period trans-C18:1 in the diet correlated with trans-C18:1 in serum triacylglycerols (r 0.41; P = 0.014), and platelet phospholipids (r 0.52; P = 0.001). Also, differences in the intake between the two periods correlated with changes in the proportion of trans-C18:1 in serum triacylglycerols (r 0.56; P = 0.001) and platelet phospholipids (r 0.58; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Previously, we have reported that dietary fatty acids can modify the thromboxane A2-dependent activation of rat platelets. Here, we present evidence that this dietary effect is part of a more general effect on platelet signal transduction, putatively involving structural changes in the platelet membranes. Four experiments were performed, where Wistar rats were fed with a high-fat diet enriched in either saturated, n-6 polyunsaturated or n-3 polyunsaturated fatty acids, or with a low-fat diet enriched in n-6 polyunsaturated fatty acids. The type of diet hardly influenced mean number of double bonds in the major platelet phospholipids. Platelet membranes from the rats fed with the saturated-fat diet had phospholipids with relatively high levels of arachidonate, but were low in cholesterol/phospholipid ratio. When compared to this diet group, platelets from other groups had an arachidonate content that was 21 to 47% lower and a cholesterol/phospholipid ratio 3 to 5% higher. The saturated-fat diet resulted in platelets that, in general, were less responsive to agonists than the platelets from other groups: with thrombin, collagen and thromboxane A2 analogue U46619, both early (shape change and phospholipase C-dependent rise in [Ca2+]i) and late (exocytosis and aggregation) responses were relatively low. However, platelet activation evoked by ADP was not influenced by diet type. When the cholesterol content of rat platelets was modified in vitro, it appeared that the early and late responses to thrombin and U46619 increased with the cholesterol/phospholipid ratio. Taken together, these results suggest that in rat platelets (i) the membrane cholesterol/phospholipid ratio can be modulated by a diet rich in saturated fatty acids, explaining, at least in part, the dietary effect on phospholipase C-mediated platelet activation, and (ii) relatively small changes in cholesterol content can have a more profound effect on platelet activation than substantial changes in arachidonate level.

The long-chain polyene (LCP) status of thirty-nine premature infants (birth weight < 1800 g) was evaluated. Twenty-seven infants were fed on an artificial formula, twelve received their own mother's breast milk. Fatty acid compositions of both plasma and erythrocyte (RBC) phospholipids (PL) were determined in umbilical venous blood and in weekly postnatal blood samples until the 28th day of life. Individual fatty acid levels were expressed as absolute quantities (mg fatty acid/l plasma or RBC suspension) and as relative (mg/100 mg total fatty acids) values. The changes with time in the absolute values for 22:6n-3 and 20:4n-6 in plasma were strikingly different from those of the relative values for these fatty acids. In plasma PL the inter-group differences in the absolute postnatal values for 22:6n-3 (P < 0.0005) and 20:4n-6 (P < 0.05) and the relative values for 22:6n-3 (P < 0.02) were significant, with lower fatty acid values in the formula-fed infants. In RBC PL, no significant inter-group differences in the postnatal 22:6n-3 and 20:4n-6 values were found. Based on the assumption that it is desirable for formula-fed infants to achieve postnatal plasma LCP values at least comparable with those found in infants fed on human milk, the findings of the present study indicate that both n-3 and n-6 LCP should be added to preterm infant formulas. Moreover, the additional importance of absolute fatty acid levels was demonstrated, although analytical procedures need to be standardized to enable effective comparison of results from different research groups.

To study the influence of membrane fatty acid composition on the formation of prostanoids and hydroxy fatty acids by rat peritoneal mast cells (MC), animals were fed three different types of fatty acids: mackerel oil (MO), abundant in n-3 fatty acids; sunflower seed oil (SO), rich in linoleic acid; and hydrogenated coconut oil (HCO), mainly containing saturated fatty acids. The presence of n-3 fatty acids in the diet resulted in the incorporation of 20:5(n-3), 22:5(n-3) and 22:6(n-3) in MC phospholipids. A decrease of arachidonic acid, 20:4(n-6), was observed in MC-phospholipids of the MO-fed animals. Furthermore, increasing the relative amounts of 18:2(n-6) in the diet (SO group) led to an increased incorporation of linoleic acid, 18:2(n-6) in MC phospholipids when compared to both other dietary groups. The changes in MC phospholipid fatty acid composition were (partly) reflected in the formation of prostanoids and hydroxy fatty acids upon stimulation with the calcium ionophore A23187. The decrease in arachidonic acid content in MC phospholipids of MO-fed rats resulted in a decreased formation of PGD2 when compared to both other groups. Also, the increased amounts of 18:2(n-6) in MC phospholipids of SO-fed rats resulted in an increased formation of 9- and 13-HODE upon stimulation. The results show that modifications in the fatty acid composition of the diet influences MC membrane fatty acid composition which ultimately results in changes in prostanoid and hydroxy fatty acid synthesis by MC upon stimulation with the calcium ionophore A23187.

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 effect of dietary manipulation on eicosanoid formation in rat peritoneal macrophages was studied in relation to some of their effector functions: cellular procoagulant activity, production of reactive oxygen species (measured as chemiluminescence), and phagocytosis of antibody-coated erythrocytes. Rats were fed adequate diets for eight weeks containing mackerel oil (MO), sunflowerseed oil (SO) or hydrogenated coconut oil (HCO). The release of eicosanoids from resident macrophages stimulated by opsonized zymosan was significantly lower for the MO group as compared to the other dietary groups. Infection of the animals via intraperitoneal injection with rat cytomegalovirus resulted in a significant decrease in eicosanoid production in all groups, irrespective of dietary fat type. However, in the HCO group a partial restoration of TXB2 and HHT production could be observed at day 10 post infection. Resident macrophages obtained from the mackerel oil fed animals showed a significantly higher procoagulant activity than those from the other diet groups. Infection of the animals resulted in an increase in procoagulant activity in all groups. In contrast, no significant differences in chemiluminescence and in phagocytosis were detected between macrophages obtained from rats fed the different diet groups. It is concluded that peritoneal macrophages obtained from mackerel oil fed rats produce less eicosanoids and are more procoagulant than those from the other dietary groups, but a viral infection eradicates these differences. Therefore, a correlation between eicosanoid formation and effector functions studied could not be established.

Diets containing high levels of monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids were fed to Wistar rats. This resulted in decreases in the arachidonate content in platelet phospholipids to 91%, 79% and 51% respectively of the level found after feeding a diet rich in saturated fatty acids. In the presence of CaCl2, collagen- and thrombin-induced aggregation of washed platelets from the saturated-fat dietary group (with highest level of arachidonate) was low compared with that of platelets from the other dietary groups, despite a relatively high production of thromboxane B2. On the other hand, n-3 polyunsaturated fatty acids in the diet resulted in platelets aggregating actively, but producing low levels of levels of thromboxane B2. When indomethacin-treated rat platelets were activated with the thromboxane A2 analogue U46619, the presence of a second agonist such as collagen. ADP or thrombin was necessary for aggregate formation. U46619-induced aggregation in combination with either co-activator was relatively low in arachidonate-rich platelets, and was higher in platelets with a low arachidonate content. Similarly, phospholipase C-catalysed formation of L-myo-inositol phosphates was higher in platelets with a low arachidonate content. We conclude that the ability of platelets to react with thromboxane A2 is modified by diet in such a way that a decreased substrate-limited generation of thromboxane A2 is compensated for by an increased response to thromboxane, and vice versa. No significant differences were detected in the binding of U46619 or SQ29548 to platelets from the various dietary groups. Therefore the changed response seems not to be caused by modified properties of the thromboxane A2/prostaglandin H2 receptors, but by altered transduction of the thromboxane signal.

Dietary mackerel causes the increase of timnodonic acid (eicosapentaenoic acid) in all platelet phospholipid classes, at the expense of arachidonic acid. Because of these fatty acid changes, the potency of platelets to produce cyclo oxygenase products from the 2-series is greatly reduced. However, upon mild platelet triggering, changes in TxB2 formation are hardly significant, strongly depend on dietary compliance and require a high fish intake. The reduced formation of 2-series prostanoids is only partly compensated for by the increased formation of timnodonic acid-derived products. Urinary PGI metabolites suggest that dietary fish is associated with the enhanced turnover of PGI3 without a concomitant reduction in PGI2 formation. Since the site of PGI formation is not known, and an effect of dietary fish on the prostanoid metabolic routes cannot be excluded, the physiological relevance of these results is uncertain.

The total urinary excretion of tetranor prostaglandin metabolites, measured as tetranorprostanedioic acid (TPD), was quantified in traditionally living Greenland Eskimos (E) and compared with that in Caucasian Danes (D). TPD excretion (microgram/24h) was not significantly different between both groups, neither for males (331 +/- 62.4 (E) vs. 331 +/- 25.7 (D), mean +/- SEM, n = 9 and 10) nor for females (190 +/- 31.7 (E) vs. 264 +/- 27.4 (D), n = 11 and 10, P2 greater than 0.05). Since urinary prostaglandin metabolites are thought to reflect the total prostaglandin turnover in vivo, these results suggest that a long-term intake of relatively large amounts of polyunsaturated fatty acids of the (n-3) family does not alter total prostaglandin turnover in vivo. This is in contrast to stimulated prostanoid formation in vitro, and thus suggests a different regulatory role of dietary and tissue fatty acids for 'stimulated' and 'basal' prostaglandin production.

We conclude that dietary changes can have a profound influence on prostaglandin and thromboxane synthesis of organ systems. A better insight into underlying mechanisms is necessary before more definite advice with respect to feeding a linolenic acid and very long-chain polyunsaturated fatty acids as found in fish oils can be given.

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.

The apparent steady-state fluorescence anisotropy of DPH- or TMA-DPH-labeled washed rat platelets is strongly affected by factors that also influence the turbidity by these platelet suspensions. Sonicated preparations from platelet lipids have a low turbidity and give anisotropy values which are hardly affected by the experimental conditions. We studied the effect of four high-fat diets on membrane fluidity, lipid composition and activation tendency of washed platelets. The diets contained 50 energy% of oils with different levels of saturated and (poly)unsaturated fatty acids. Only small diet-induced differences in DPH fluorescence anisotropy were found, which were comparable for intact platelets and platelet lipids. These differences were unrelated to the degree of saturation of the dietary fatty acids. Platelets from rats fed mainly saturated fatty acids differed significantly from other diet groups in a higher unsaturation degree of phospholipids and a lower cholesterol/phospholipid ratio, but this was not detected by DPH in terms of decreased anisotropy. These platelets aggregated less than other platelets in response to thrombin or collagen. The lower response to collagen persisted in indomethacin-treated platelets activated with the thromboxane A2 mimetic U46619, indicating a different sensitivity of these platelets for thromboxane A2. We conclude that in rat platelets: (a) the overall membrane fluidity and phospholipid unsaturation degree are subject to strong homeostatic control; (b) steady-state anisotropy with DPH or TMA-DPH label is inadequate to reveal subtile changes in lipid profile; (c) changes in platelet responsiveness to thrombin and thromboxane A2, rather than (plasma) membrane fluidity, determine the effect of dietary fatty acids on platelet aggregation.

Dietary fats have a pronounced effect on arterial thrombosis: in rats, long-chain saturated fatty acids are thrombogenic, oleic acid is neutral, and linoleic acid is anti-thrombotic. These effects are likely to be mediated, at least in part, by changes in platelet fatty acid composition and--consequently--platelet function. Blood coagulability and differences in vitamin E intake seem of no (or minor) importance. In man, dietary linoleic acid inhibits platelet aggregation and other parameters of platelet activation. Dietary fat effects on vascular prostacyclin formation have not yet been found.

In rats, diets rich in polyunsaturated fatty acids of the (n-6) and (n-3) families (P) lower arterial thrombosis tendency, whereas long-chain saturated fatty acids (S) are prothrombotic. Monounsaturated fatty acids seem to behave neutrally as to arterial thrombus formation. Consequently, the P/S ratio is an important determinant of the thrombogenicity of a dietary fat, the effect of which is probably mediated by an influence on platelet aggregability. In man, the dietary fat type also affects platelet aggregation. Methodological problems, however, resulted in equivocal results, especially with respect to diets enriched with fish oil. Thus, more research is required with methods that are able to quantify thrombotic risk in a reliable way. Nonetheless, the available evidence already justifies an active policy to increase the consumption of (poly)unsaturated fatty acids at the expense of long-chain saturated fatty acids.

Epidemiological studies indicate that dietary saturated fats are implicated in coronary heart disease (CHD). Human prospective studies have shown that diets low in long chain saturated fatty acids and enriched in linoleic acid are beneficial in CHD-prevention. Experiments in animals have shown that such diets diminish atherosclerosis and the tendency to arterial thrombosis; they also lower the ability of platelets to aggregate in animals and in man. The mechanisms by which these diets produce these effects are not yet completely understood. Platelets and vascular prostaglandin-like substances may be involved as well as platelet membrane fluidity and platelet coagulant activities. On the basis of the available evidence, measures to decrease the intake of long chain saturated fatty acids (concomitant with an enhanced consumption of linoleic acid-rich products) are justified. Although certain marine oils may also have anti-thrombotic properties the possibility of undesirable side effects compels extensive investigation before their wide-spread use can be recommended.

In rats, diets rich in polyunsaturated fatty acids of the (n-6) and (n-3) families (P) reduce the tendency to arterial thrombosis, whereas diets containing long-chain saturated fatty acids (S) are prothrombotic. Monounsaturated fatty acids seem to have a neutral influence on arterial thrombus formation. Consequently, the P/S ratio is an important determinant of the thrombogenicity of a dietary fat, the effect of which is probably mediated by an influence on platelet aggregability. In man, the type of dietary fat also affects platelet aggregation. Methodological problems, however, have resulted in equivocal results from studies, especially with respect to diets enriched with fish oil. Therefore, more research is required with methods than can quantify thrombotic risk in a reliable way. Nevertheless, the available evidence already justifies an active policy to increase people's consumption of (poly)unsaturated fatty acids at the expense of long chain saturated fatty acids.