Hepatectomy and pancreatectomy: how we could do it.

Visible patient software provides surgeons and trainees with the opportunity to construct accurate three dimensional models of patients liver and pancreas which reflect tumour location and unique anatomical features. These can be used for operative planning, patient discussions, operative rehearsal and teaching as well as pre and postoperative briefings.

Batch-effect detection, correction and characterisation in Illumina HumanMethylation450 and MethylationEPIC BeadChip array data.

BACKGROUND: Genomic technologies can be subject to significant batch-effects which are known to reduce experimental power and to potentially create false positive results. The Illumina Infinium Methylation BeadChip is a popular technology choice for epigenome-wide association studies (EWAS), but presently, little is known about the nature of batch-effects on these designs. Given the subtlety of biological phenotypes in many EWAS, control for batch-effects should be a consideration. RESULTS: Using the batch-effect removal approaches in the ComBat and Harman software, we examined two in-house datasets and compared results with three large publicly available datasets, (1214 HumanMethylation450 and 1094 MethylationEPIC BeadChips in total), and find that despite various forms of preprocessing, some batch-effects persist. This residual batch-effect is associated with the day of processing, the individual glass slide and the position of the array on the slide. Consistently across all datasets, 4649 probes required high amounts of correction. To understand the impact of this set to EWAS studies, we explored the literature and found three instances where persistently batch-effect prone probes have been reported in abstracts as key sites of differential methylation. As well as batch-effect susceptible probes, we also discover a set of probes which are erroneously corrected. We provide batch-effect workflows for Infinium Methylation data and provide reference matrices of batch-effect prone and erroneously corrected features across the five datasets spanning regionally diverse populations and three commonly collected biosamples (blood, buccal and saliva). CONCLUSIONS: Batch-effects are ever present, even in high-quality data, and a strategy to deal with them should be part of experimental design, particularly for EWAS. Batch-effect removal tools are useful to reduce technical variance in Infinium Methylation data, but they need to be applied with care and make use of post hoc diagnostic measures.

Cardiac and vascular health in late preterm infants.

Adults who were born preterm are at increased risk of hypertension and cardiovascular disease in later life. Infants born late preterm are the majority of preterm births; however, the effect of late preterm on risk of cardiovascular disease is unclear. The objective of this study was to assess whether vascular health and cardiac autonomic control differ in a group of late preterm newborn infants compared to a group of term-born infants.A total of 35 healthy late preterm newborn infants, with normal growth (34-36 completed weeks' gestation) and 139 term-born infants (37-42 weeks' gestation) were compared in this study. Aortic wall thickening, assessed as aortic intima-media thickness (IMT) by high-resolution ultrasound, and cardiac autonomic control, assessed by heart rate variability, were measured during the first week of life. Postnatal age of full-term and late preterm infants at the time of the study was 5 days (standard deviation [SD] 5) and 4 days (SD 3), respectively.Infants born late preterm show reduced aortic IMT (574 µm [SD 51] vs. 612 µm [SD 73]) and reduced heart rate variability [log total power 622.3 (606.5) ms2 vs. 1180. 6 (1114.3) ms2], compared to term infants. These associations remained even after adjustment for sex and birth weight.Infants born late preterm show selective differences in markers of cardiovascular risk, with potentially beneficial differences in aortic wall thickness in contrast to potentially detrimental differences in autonomic control, when compared with term-born control infants. These findings provide pathophysiologic evidence to support an increased risk of hypertension and sudden cardiac death in individuals born late preterm.

Maternal dietary fatty acid composition and newborn epigenetic aging-a geometric framework approach.

BACKGROUND: Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients. OBJECTIVES: We sought to assess the collective impact of maternal dietary MUFAs, PUFAs, and SFAs on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach. METHODS: Body fatness (n = 162), aortic intima-media thickness (aIMT; n = 131), heart rate variability (n = 118), and epigenetic age acceleration (n = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered FFQ. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces. RESULTS: After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFAs, PUFAs, and SFAs (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFAs were positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFAs or PUFAs. We also demonstrate a potential beneficial association of omega-3 (n-3) PUFAs with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aIMT, heart rate variability, or body fatness. CONCLUSIONS: In this study, we demonstrated an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids.

Maternal Dietary Carbohydrate Intake and Newborn Aortic Wall Thickness.

Evidence from animal models indicates that maternal diet during pregnancy affects offspring cardiometabolic health. Improving carbohydrate quality during high-risk pregnancies reduces aortic intima-medial thickness; a marker for early atherosclerosis; in the infant offspring. We sought to determine whether maternal carbohydrate quantity and quality are associated with newborn aortic intima-medial thickness in healthy pregnancies. Maternal diet throughout pregnancy was evaluated in 139 mother-child dyads using a validated food frequency questionnaire. Carbohydrate intake was expressed as quantity (% total energy), quality (fibre, glycaemic index), and glycaemic burden (glycaemic load). Aortic intima-medial thickness was measured by high-frequency ultrasound of the neonatal abdominal aorta. Neither quantity nor quality of maternal carbohydrate intake during pregnancy was associated with meaningful differences in offspring maximum aortic intima-medial thickness with the exception of fibre intake in women with overweight or obesity which was inversely associated (-8 µm [95% CI -14, -1] per g fibre, p = 0.04). In healthy pregnancy, the quantity and quality of maternal carbohydrate intake is likely not a meaningful modifiable lifestyle factor for influencing offspring vascular health. The effect of carbohydrate quality may only be evident in high-risk pregnancies, consistent with previous findings. These findings may be confirmed in prospective dietary trials in pregnancy.

Epigenetic aging in newborns: role of maternal diet.

BACKGROUND: Epigenetic aging is associated with higher risk of cardiovascular disease, cancer, and all-cause mortality and may be a mechanistic link between early-life exposures, such as maternal dietary characteristics during pregnancy, and risk of adult disease. OBJECTIVES: We sought to determine the early-life risk factors for newborn epigenetic aging, specifically maternal dietary macronutrient intake, and whether epigenetic aging is associated with cardiovascular health markers in the newborn. METHODS: Epigenetic age acceleration of 169 newborns was measured from saliva using the Horvath age calculator. Maternal diet during pregnancy was assessed using food-frequency questionnaires. RESULTS: Newborns with positive age acceleration were more likely to be female and have greater body fatness. Maternal intakes of saturated fat [6.2 wk epigenetic age acceleration (95% CI: 1.0, 11.3) per 5% of energy; P = 0.02] and monounsaturated fat [12.4 wk (95% CI: 4.2, 20.5) per 5% of energy; P = 0.003] were associated with higher epigenetic age acceleration in the newborn. The strongest association of individual fatty acids were for palmitoleic acid (25.3 wk; 95% CI: 11.4, 39.2; P = 0.0004), oleic acid (2.2 wk; 95% CI: 0.8, 3.6; P = 0.002), and palmitic acid (2.9 wk; 95% CI: 1.0, 4.9; P = 0.004) per 1% of energy intake. Vitamin D supplementation was associated with lower epigenetic age acceleration (-8.1 wk; 95% CI: -14.5, -1.7; P = 0.01). Epigenetic age acceleration was associated with aortic intima-media thickness in preterm infants [1.0 µm (95% CI: 0.2, 1.8) per week of epigenetic age acceleration; P = 0.01], but not among those born at term (P = 0.78). Epigenetic age acceleration was not associated with heart rate variability in either preterm or term born infants (both P > 0.2). CONCLUSIONS: This study provides evidence of maternal dietary characteristics that are associated with epigenetic aging in the offspring. Prospective intervention studies are required to determine whether such associations are causal.

Validation of a cuff-based device for measuring carotid-femoral pulse wave velocity in children and adolescents.

Carotid-femoral pulse wave velocity is associated with arterial stiffness in major elastic arteries, and predicts future cardiovascular events. However, little is known about carotid-femoral pulse wave velocity as a marker of vascular health in children. Semi-automated cuff-based devices for assessing pulse wave velocity are increasingly popular, although these utilize an algorithm developed and validated in adults. Physiological differences between adults and children may, however, reduce the accuracy of cuff-based methods. We sought to determine the accuracy of a cuff-based pulse wave velocity device in healthy children, and determine whether a novel age-appropriate algorithm increases accuracy. We recruited 29 healthy children between the ages of 2 and 20 years. Pulse wave velocity was measured both by using a tonometer on the carotid artery and an inflated cuff on the thigh, and using a tonometer on both the carotid artery and femoral artery as a reference standard. Accuracy of the cuff-based device with its standard algorithm developed in adults, and a novel age-appropriate algorithm corrected for physiological differences in leg pulse wave velocity was assessed with Regression analysis and Bland-Altman plots. Cuff-based device estimates of pulse wave velocity had excellent agreement to the reference standard (Δ = -0.26 ms-1 [SD 0.44]). The novel age-appropriate algorithm improved the accuracy of the cuff-based method (Δ = 0.02 ms-1 [SD 0.44]). The cuff-based semi-automatic approach estimates carotid-femoral pulse wave velocity with excellent agreement to the reference standard. However, adjusting the algorithm for known differences in leg pulse wave velocity further improves the accuracy of cuff-based measurement in children and adolescents.

Influence of maternal and placental factors on newborn body composition.

AIM: The objective of this study was to assess whether maternal characteristics, placental size or histological chorioamnionitis was associated with newborn body composition. Furthermore, we sought to determine whether placental weight may mediate the association between maternal pre-pregnancy weight and age with newborn body composition. METHODS: A cross-sectional study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. This study included 136 healthy, singleton, term-born newborns. Recruitment was stratified by newborn body fat percentiles (gender and gestational adjusted). Body fat was assessed by air displacement plethysmography. Placental examination was conducted by an anatomical pathologist. Maternal (chorioamnionitis) and fetal (chorionic and umbilical vasculitis, funisitis) inflammatory responses were classified according to Redline criteria. RESULTS: Maternal pre-pregnancy weight, parity, labour, placental weight and surface area were associated with newborn fat mass and fat-free mass. Gestational diabetes and maternal age were associated with newborn fat mass but not fat-free mass. There was no association between histological chorioamnionitis and newborn body composition; however, spontaneous onset of labour was strongly associated with the presence of histological chorioamnionitis. Only 25-31% of the association of maternal weight and age with newborn fat mass was mediated via the placenta. CONCLUSIONS: Maternal factors associated with newborn fat mass and fat-free mass differed, indicating that different mechanisms control fat mass and fat-free mass. Our mediation analysis suggests that placental weight partly mediates the association of maternal factors with newborn body composition. Histological chorioamnionitis was not associated with newborn body composition.

Increased α-Linolenic Acid Intake during Pregnancy is Associated with Higher Offspring Birth Weight.

BACKGROUND: The amount and type of fat in the maternal diet during pregnancy are important contributors to fetal growth. The importance of plant-based omega-3 fatty acid (α-linolenic acid, ALA) intake in fetal growth has not been previously examined. OBJECTIVE: We sought to determine the association of maternal ALA intake during pregnancy with birth weight and body composition of the offspring. METHODS: Mothers and their newborn infants (n = 224) were recruited from the Royal Prince Alfred Hospital, Australia. Maternal diet during pregnancy was assessed using a validated food frequency questionnaire. Plasma fatty acid composition was analyzed in a subset of mothers (n = 41). Newborn body composition was assessed using air-displacement plethysmography. All analyses were adjusted for gestational age, sex, physical activity, and total energy intake. RESULTS: Dietary fatty acid intakes were positively associated with plasma phospholipid fatty acids for total omega-3 fatty acids (ß = 0.452, P = 0.003), ALA (ß = 0.339, P = 0.03), linoleic acid (ß = 0.353, P = 0.03), eicosapentaenoic acid (ß = 0.407, P = 0.009), and docosahexaenoic acid (ß = 0.388, P = 0.01). Higher maternal intake of ALA (% total fat) was associated with higher offspring birth weight [189.7-g increase per 1% higher ALA (95% CI: 14, 365 g); P = .04], although individually neither newborn fat mass nor fat-free mass was significant. Birth weight increased across tertiles of maternal ALA intake (P ANOVA = 0.05), with birth weight being 221 g (95% CI: 12, 429 g) higher in those with the highest maternal ALA intake compared with those with the lowest intake (P = 0.04). Mothers of infants born small for gestational age (n = 32) had a lower ALA intake than those born appropriate for gestational age (n = 162) or large for gestational age [(n = 21); P = 0.05]. CONCLUSIONS: In otherwise healthy women giving birth at a major tertiary hospital in Australia, intake of ALA during pregnancy is associated with higher offspring birth weight. This may have implications for dietary strategies aimed at optimizing fetal growth via modification of maternal diet.

Body Fatness and Cardiovascular Health in Newborn Infants.

Birth weight is associated with cardiovascular disease, with those at both ends of the spectrum at increased risk. However, birth weight is a crude surrogate of fetal growth. Measures of body composition may more accurately identify high risk infants. We aimed to determine whether aortic wall thickening, cardiac autonomic control, and cardiac structure/function differ in newborns with high or low body fatness compared to those with average body fatness. 189 healthy singleton term born neonates were recruited and stratified by body fat percentiles (sex and gestation-specific). Infants with low body fat had higher aortic intima-media thickness (43 µm (95% confidence interval (CI) 7, 78), p = 0.02), lower heart rate variability (log total power, -0.5 (95% CI -0.8, -0.1), p = 0.008), and thicker ventricular walls (posterior wall thickness, 3.1 mm (95% CI 1.6, 4.6), p < 0.001) compared to infants with average body fatness. Infants with high body fat showed no differences in aortic intima-media thickness (-2 µm (95% CI -37, 33), p = 0.91) or cardiac structure compared to average body fatness, although stroke volume (-0.3 mL/kg (95% CI -0.6, -0.0), p = 0.003) and heart rate variability were lower (log total power, -0.8 (95% CI -1.1, -0.5), p < 0.001). The non-linear association of body fatness with heart rate variability was independent of birth weight. Infants born with low or high body fat have altered markers of cardiovascular health. Assessment of body fatness alongside birth weight may assist in identifying high risk individuals.

Marine Omega-3 Fatty Acids, Complications of Pregnancy and Maternal Risk Factors for Offspring Cardio-Metabolic Disease.

Marine omega-3 polyunsaturated fatty acids (n-3 PUFA) are important nutrients during periods of rapid growth and development in utero and infancy. Maternal health and risk factors play a crucial role in birth outcomes and subsequently offspring cardio-metabolic health. Evidence from observational studies and randomized trials have suggested a potential association of maternal intake of marine n-3 PUFAs during pregnancy with pregnancy and birth outcomes. However, there is inconsistency in the literature on whether marine n-3 PUFA supplementation during pregnancy can prevent maternal complications of pregnancy. This narrative literature review summarizes recent evidence on observational and clinical trials of marine n-3 PUFA intake on maternal risk factors and effects on offspring cardio-metabolic health. The current evidence generally does not support a role of maternal n-3 PUFA supplementation in altering the incidence of gestational diabetes, pregnancy-induced hypertension, or pre-eclampsia. It may be that benefits from marine n-3 PUFA supplementation are more pronounced in high-risk populations, such as women with a history of complications of pregnancy, or women with low marine n-3 PUFA intake. Discrepancies between studies may be related to differences in study design, dosage, fatty acid interplay, and length of treatment. Further prospective double-blind studies are needed to clarify the impact of long-chain marine n-3 PUFAs on risk factors for cardio-metabolic disease in the offspring.

Noninvasive assessment of autonomic function in human neonates born at the extremes of fetal growth spectrum.

Birth weight is associated with adult cardiovascular disease, such that those at both ends of the spectrum are at increased risk. This may be driven in part by modification to autonomic control, a mechanistic contributor to hypertension. However, birth weight is a relatively crude surrogate of fetal growth; and newborn body composition may more accurately identify the "at risk" infant. Accordingly, we sought to determine whether newborns with high or low body fat have altered autonomic control of vasomotor function and cardiac contractility. Body fat was assessed by air-displacement plethysmography <24 h postnatal. Measures of spontaneous baroreflex sensitivity (sBRS), blood pressure variability (BPV), and dP/dtmax variability were compared between newborns categorized according to established body fat percentiles: high body fat (HBF, >90th percentile, n = 7), low body fat (LBF, ≤10th percentile, n = 12), and normal body fat (control, >25th to ≤75th percentile, n = 23). BPV was similar across body fat percentiles; similarly, low frequency dP/dtmax variability was similar across body fat percentiles. sBRS was reduced in HBF compared to controls (11.0 ± 6.0 vs. 20.1 ± 9.4 msec/mmHg, P = 0.03), but LBF did not differ (18.4 ± 6.0 msec/mmHg, P = 0.80). Across the entire body fat spectrum (n = 62), there was a nonlinear association between newborn body fat and sBRS (P = 0.03) that was independent of birth weight (P = 0.04). Autonomic modulation of vasomotor function and cardiac contractility in the newborn did not differ by body fat, but newborns born with high body fat show depressed baroreflex sensitivity.

Quantity and Quality of Carbohydrate Intake during Pregnancy, Newborn Body Fatness and Cardiac Autonomic Control: Conferred Cardiovascular Risk?

The fetal environment has an important influence on health and disease over the life course. Maternal nutritional status during pregnancy is potentially a powerful contributor to the intrauterine environment, and may alter offspring physiology and later life cardio-metabolic risk. Putative early life markers of cardio-metabolic risk include newborn body fatness and cardiac autonomic control. We sought to determine whether maternal dietary carbohydrate quantity and/or quality during pregnancy are associated with newborn body composition and cardiac autonomic function. Maternal diet during pregnancy was assessed in 142 mother-infant pairs using a validated food frequency questionnaire. Infant adiposity and body composition were assessed at birth using air-displacement plethysmography. Cardiac autonomic function was assessed as heart rate variability. The quantity of carbohydrates consumed during pregnancy, as a percentage of total energy intake, was not associated with meaningful differences in offspring birth weight, adiposity or heart rate variability (p > 0.05). There was some evidence that maternal carbohydrate quality, specifically higher fibre and lower glycemic index, is associated with higher heart rate variability in the newborn offspring (p = 0.06). This suggests that poor maternal carbohydrate quality may be an important population-level inter-generational risk factor for later cardiac and hemodynamic risk of their offspring.

From the α to the ω-3: Breaking the link between impaired fetal growth and adult cardiovascular disease.

Atherosclerotic vascular disease is an important cause of premature morbidity and mortality. An extensive body of epidemiologic data links impaired fetal growth, evidenced by reductions in birth weight, with a higher risk for cardiovascular disease in adulthood. This association appears to be at least partially independent of established cardiovascular risk factors, such as hypertension and type 2 diabetes. There is currently no clinically established strategy to prevent cardiovascular events secondary to being born with poor fetal growth. This review summarizes recent evidence that suggests that ω-3 polyunsaturated fatty acids may be beneficial for this indication; in particular being associated with more marked reductions in blood pressure and subclinical atherosclerosis in people who were born with poor fetal growth, than in those with healthy birth weight. Possible mechanisms, and the evidence base required to support the implementation of dietary guidelines specific to people born with impaired fetal growth are also described.

Kinetics of omega-3 polyunsaturated fatty acids when co-administered with saturated or omega-6 fats.

OBJECTIVE: Absorption of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to be potentiated when consumed with a high fat meal. However, the effect of different dietary fats on n-3PUFA absorption and postprandial kinetics has not been previously studied. METHOD: In a randomized cross-over design intervention, postprandial incorporation of LCn-3PUFA into plasma lipids following consumption of a meal rich in either saturated fat or omega-6 polyunsaturated fatty acids (n-6PUFA) was investigated. Healthy adult male and female subjects (n=26) were fed an isocaloric meal containing equivalent amount of either butter or sunflower seed oil supplemented with 1.8grams of LCn-3PUFA (300mg eicosapentaenoic acid, 20:5n-3 and 1500mg docosahexaenoic acid, 22:6n-3). RESULTS: Postprandial plasma lipids were enriched with saturated fatty acids and linoleic acid (18:2n-6) following consumption of the butter and the sunflower oil containing meals respectively. The increase in plasma 20:5n-3 and 22:6n-3 levels over the 6hour study period was similar in both the saturated and the n-6 fat groups. CONCLUSION: These results suggest that the expected competition between LCn-3PUFA and n-6PUFA at the absorption level is unlikely; therefore competition at the enzymatic level should be primarily responsible for differences in their metabolic and clinical effects. Trial registered with the Australia New Zealand Trial registry as ACTRN12612000654853.

Postprandial lipid responses do not differ following consumption of butter or vegetable oil when consumed with omega-3 polyunsaturated fatty acids.

Dietary saturated fat (SFA) intake has been associated with elevated blood lipid levels and increased risk for the development of chronic diseases. However, some animal studies have demonstrated that dietary SFA may not raise blood lipid levels when the diet is sufficient in omega-3 polyunsaturated fatty acids (n-3PUFA). Therefore, in a randomised cross-over design, we investigated the postprandial effects of feeding meals rich in either SFA (butter) or vegetable oil rich in omega-6 polyunsaturated fatty acids (n-6PUFA), in conjunction with n-3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG)] and n-3PUFA incorporation into plasma lipids over a 6-h period. The incremental area under the curve for plasma cholesterol, LDL-C, HDL-C, TAG and n-3PUFA levels over 6 h was similar in the n-6PUFA compared to SFA group. The postprandial lipemic response to saturated fat is comparable to that of n-6PUFA when consumed with n-3PUFA; however, sex-differences in response to dietary fat type are worthy of further attention.

Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation.

BACKGROUND: Recent studies have demonstrated a relationship between fructose consumption and risk of developing metabolic syndrome. Mechanisms by which dietary fructose mediates metabolic changes are poorly understood. This study compared the effects of fructose, glucose and sucrose consumption on post-postprandial lipemia and low grade inflammation measured as hs-CRP. METHODS: This was a randomized, single blinded, cross-over trial involving healthy subjects (n=14). After an overnight fast, participants were given one of 3 different isocaloric drinks, containing 50 g of either fructose or glucose or sucrose dissolved in water. Blood samples were collected at baseline, 30, 60 and 120 minutes post intervention for the analysis of blood lipids, glucose, insulin and high sensitivity C-reactive protein (hs-CRP). RESULTS: Glucose and sucrose supplementation initially resulted in a significant increase in glucose and insulin levels compared to fructose supplementation and returned to near baseline values within 2 hours. Change in plasma cholesterol, LDL and HDL-cholesterol (measured as area under curve, AUC) was significantly higher when participants consumed fructose compared with glucose or sucrose (P<0.05). AUC for plasma triglyceride levels however remained unchanged regardless of the dietary intervention. Change in AUC for hs-CRP was also significantly higher in subjects consuming fructose compared with those consuming glucose (P<0.05), but not sucrose (P=0.07). CONCLUSION: This study demonstrates that fructose as a sole source of energy modulates plasma lipids and hsCRP levels in healthy individuals. The significance of increase in HDL-cholesterol with a concurrent increase in LDL-cholesterol and elevated hs-CRP levels remains to be delineated when considering health effects of feeding fructose-rich diets. REGISTRATION NUMBER FOR CLINICAL TRIALS: ACTRN12614000431628.

Reduction of prothrombin and Factor V levels following supplementation with omega-3 fatty acids is sex dependent: a randomised controlled study.

BACKGROUND: LCn-3PUFA comprised of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) offer cardioprotection involving a decrease in coagulant activity; however, the evidence is equivocal. We have previously demonstrated that the acute (24 h) effects and chronic (4 weeks) effects of LCn-3PUFA supplementation on platelet aggregation in human subjects are sex specific. This study investigated the mechanisms of the sex-dependent effects of LCn-3PUFA with 4 weeks supplementation of EPA-rich vs. DHA-rich oils on procoagulant and platelet activity in healthy subjects. DESIGN: A double-blinded, placebo-controlled randomised trial was conducted in 94 healthy adults: male (n=41) and female (n=53). Platelet coagulation parameters including factors I, II, V, VII, VIII, IX, X, vWF:Ag and endogenous thrombin potential were measured at baseline and 4 weeks postsupplementation with EPA-rich or DHA-rich oil capsules. RESULTS: We have previously reported that platelet aggregation is specifically reduced by supplementation with EPA in males and DHA in females. This sex-specific effect was also observed for decreases in plasma levels of Factor II (-7.9 ± 3.8%, P=.026), Factor V (-6.5 ± 4.5%, P=.022) and vWF:Ag (-7.3 ± 2.1%, P=.034) and was most pronounced in males supplemented with EPA. In contrast, DHA-mediated reduction in platelet aggregation in females was not accompanied by any significant changes in the coagulation parameters tested. CONCLUSION: Significant interactions between sex and specific LCn-3PUFA exist to reduce procoagulant activity differentially in males vs. females and could have profound effects on managing risk of thrombotic disease.

Eicosapentaenoic and docosahexaenoic acid supplementations reduce platelet aggregation and hemostatic markers differentially in men and women.

Although long-chain n3 polyunsaturated fatty acids [n3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have been reported to reduce platelet aggregation, the available evidence on this is equivocal. We previously demonstrated that the acute effects of n3 PUFA supplementation on platelet aggregation are sex specific. We aimed to determine if this gender bias is maintained during long-term n3 PUFA supplementation and whether this translates to other hemostatic markers. A double-blinded, randomized, placebo controlled trial was conducted in 94 healthy men and women. Platelet aggregation, thromboxane (TX) B2, P-selectin (P-sel), von Willebrand factor (vWF), and plasminogen activator inhibitor-1 were measured at baseline and 4 wk postsupplementation with EPA-rich (1000 mg EPA:200 mg DHA) or DHA-rich (200 mg EPA:1000 mg DHA) oil capsules daily. The effects of n3 PUFA on platelet activity were compared between men and women. In men and women combined, EPA and DHA reduced platelet aggregation following 4 wk of supplementation relative to placebo (-11.8%, P = 0.016; and -14.8%, P = 0.001, respectively). In subgroup analyses, in men, only the EPA treatment reduced platelet aggregation by -18.4% compared with placebo (P = 0.005) and women (P = 0.011). In contrast, in women, only the DHA treatment reduced platelet aggregation (-18.9%) compared with placebo (P = 0.001) and men (P = 0.017). Significant sex × treatment interactions were also observed on hemostatic markers and uptake of n3 PUFAs. The significant interactions between sex and specific, supplemental, long-chain n3 PUFAs result in platelet aggregation being differentially affected in men and women. With respect to thrombotic disease risk, men are more likely to benefit from supplementation with EPA, whereas women are more responsive to DHA.

Acute supplementation with eicosapentaenoic acid reduces platelet microparticle activity in healthy subjects.

BACKGROUND: Dietary supplementation with omega-3 fatty acids has been associated with reduced incidence in thrombotic events. In addition, administration of n-3 polyunsaturated fatty acids (PUFAs) has been shown to rectify elevated platelet microparticle (MP) number and procoagulant activity in post myocardial infarction patients. However, it is unknown whether supplementation can alter these parameters in healthy individuals and if such effects are immediate or require long-term supplementation. We have previously demonstrated a gender-specific effect of LCn-3PUFA supplementation on platelet aggregation in healthy human subjects. Here we extend these findings to include the acute effects of supplementation with EPA- or DHA-rich oils on circulating MP levels and activity in healthy subjects. DESIGN: A placebo-controlled trial was conducted in healthy males and females (n=30). MP activity, MP levels and platelet aggregation were measured at 0 and 24 h postsupplementation with either a placebo or EPA- or DHA-rich oil. RESULTS: Both EPA and DHA effectively reduced platelet aggregation at 24 h postsupplementation relative to placebo (-13.3%, P=.006 and -11.9%, P=.016, respectively), but only EPA reduced MP activity (-19.4%, P=.003). When grouped by gender, males showed a similar reduction in both platelet aggregation and MP activity (-20.5%, P=.008; -22%, P=.008) following EPA, while females showed significantly reduced platelet aggregation (-13.7%, P=.04) but not MP activity after DHA only. CONCLUSION: EPA and DHA exert gender-dependent effects on platelet aggregation and platelet MP activity, but not on MP levels. With respect to thrombotic disease risk, males may benefit more from EPA supplementation.