Melinda Phang

Plasma n -3 polyunsaturated fatty acids are negatively associated with obesity

The objective of the present study was to investigate the relationship between plasma n-3 PUFA composition and weight status. A total of 124 adults, stratified by weight status: healthy weight (n 21), overweight (n 40) and obese (n 63) were recruited. Fasting blood samples, anthropometric measures and body composition were collected. Plasma fatty acid composition was determined by GC. BMI, waist circumference and hip circumference were inversely correlated with n-3 PUFA, EPA and DHA (P < 0.05 for all) in the obese group. Obese individuals had significantly lower plasma concentrations of total n-3 PUFA, compared with healthy-weight individuals (4.53 (SD 1.11) v. 5.25 (SD 1.43) %). When subjects were pooled and stratified into quartiles of total n-3 PUFA, a significant inverse trend was found for BMI (P = 0.002), waist circumference and hip circumference (P = 0.01 and P < 0.001 respectively). Higher plasma levels of total n-3 PUFA are associated with a healthier BMI, waist circumference and hip circumference. Our findings suggest that n-3 PUFA may play an important role in weight status and abdominal adiposity.

Inhibition of platelet aggregation by omega-3 polyunsaturated fatty acids is gender specific—Redefining platelet response to fish oils ☆

Existence of gender differences in cardiovascular disease (CVD) following long-chain omega-3 polyunsaturated fatty acid (LCn-3 PUFA) supplementation have suggested that sex hormones play a role in cardio-protection. The objective of this study was to determine gender specific responses in the efficacy of LCn-3 PUFA to inhibit platelet aggregation in vitro. Blood was analyzed for collagen-induced platelet aggregation following pre-incubation with LCn-3 PUFA in healthy adults (n=42). Eicosapentaenoic acid (EPA) was significantly more effective in reducing platelet aggregation compared with docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). When grouped by gender, this differential pattern was followed in males only. In females, DHA, DPA and EPA were all equally effective. Between group analyses (LCn-3 PUFA vs. gender) showed that both DHA and DPA were significantly less effective in males compared with females. EPA was equally effective in reducing platelet aggregation in both groups. These findings show that significant gender differences exist in platelet aggregation in response to various LCn-3 PUFA treatments.

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.

Diet and Thrombosis Risk: Nutrients for Prevention of Thrombotic Disease

An increased prothrombotic state is a major risk factor for the development of heart attacks, strokes, and venous thromboembolism. Platelet activation and aggregation play an important role in determining a prothrombotic state. Although pharmaceutical agents such as aspirin, heparin, and warfarin are able to reduce prothrombotic tendency, long-term drug treatment may produce a variety of side effects, including bleeding. Diet is generally recognized to be significantly involved in modifying the individual risk for the development of thrombotic diseases, although its influence during the treatment of these disorders is probably less important. Dietary intervention has proven effective in lowering serum lipid levels, which are otherwise essential elements in the pathogenesis of cardiovascular disease. Likewise, certain dietary components have also been proven effective in decreasing platelet activation through various mechanisms and therefore may contribute to attenuating the future risk of thrombosis. This article provides an up-to-date review of the role of nutrient and nonnutrient supplements on platelet aggregation and risk of thrombosis.

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.

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.

Combined Phytosterol and Fish Oil Therapy for Lipid Lowering and Cardiovascular Health

Prevention of atherosclerosis and its complications, both primary and secondary, is based primarily on controlling various cardiovascular risk factors. Treating combined hyperlipidemia with emphasis on reducing LDL cholesterol and triglyceride levels and increasing HDL cholesterol has been established as a highly efficacious means of reducing both morbidity and mortality from cardiovascular disease. Although statins may prove effective in the treatment for hyperlipidemia, they may not be sufficient to achieve the recommended lipid levels, in particular triglyceride goals, as set out by national governing bodies. The lipid-lowering potential of both phytosterols and omega-3 fatty acids has been well documented. Dietary supplementation with phytosterols reduces the circulating concentration of total cholesterol and LDL cholesterol, but without considerable effects on HDL cholesterol or triglycerides. Conversely, a wealth of evidence has demonstrated the triglyceride lowering, as well as anti-aggregatory, anti-inflammatory and anti-arrhythmic, properties of omega-3 fatty acids. Given the propensity of hyperlipidemia to manifest in high risk individuals, there is a plausible case for combining phytosterols and omega-3 fatty acid supplementation in the management and prevention of hyperlipidemia as well as other cardiovascular diseases.

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.

Maternal n-3 Fatty Acids and Blood Pressure in Children

High blood pressure is a major risk factor for cardiovascular and cerebrovascular diseases, and a leading cause of morbidity and mortality worldwide. There is strong evidence from epidemiological and experimental studies that hypertensive-disorders can have their origins in early life, with proposed risk factors including altered fetal growth and aspects of maternal, fetal and infant nutrition. Experimental studies have demonstrated numerous mechanistic actions through which omega-3 polyunsaturated fatty acids may improve vascular and cardiac health, and clinical trials of omega-3 polyunsaturated fatty acid intake in adults demonstrate blood pressure lowering. Omega-3 fatty acids cross the placental barrier readily, and as such it has been proposed that maternal intake of omega-3 polyunsaturated fatty acids may have similar haemodynamic effects in the offspring, and may program long term haemodynamic benefits. Such proposed improvements in haemodynamic profile may be more pronounced in children at higher risk of hypertensive-disorders due to other adverse early life risk factors or exposures. These hypotheses are supported by some observational and animal data, although high quality evidence from clinical trials is lacking.

Circulating CD36+ microparticles are not altered by docosahexaenoic or eicosapentaenoic acid supplementation ☆

BACKGROUND AND AIMS Circulating microparticles (MP) are the source of a plasma derived form of the scavenger receptor CD36, termed soluble (s)CD36, the levels of which correlate with markers of atherosclerosis and risk of cardiovascular disease. Long chain n-3 polyunsaturated fatty acids have cardioprotective effects that we have previously reported to be gender specific. The aim of this study was to determine if dietary docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) supplementation affect circulating CD36 + MP levels, and if this occurs differentially in healthy men and women. METHODS AND RESULTS Participants (43M, 51F) aged 39.6 ± 1.7 years received 4 weeks of daily supplementation with DHA rich (200 mg EPA; 1000 mg DHA), EPA rich (1000 mg EPA; 200 mg DHA), or placebo (sunola) oil in a double-blinded, randomised, placebo controlled trial. Plasma CD36 + MP were enumerated by flow cytometry and differences between genders and treatments were evaluated by Students or paired t-test and one way ANOVA. Males and females had similar levels of CD36 + MP at baseline (mean = 1018 ± 325 vs 980 ± 318; p = 0.577) and these were not significantly changed after DHA (M, p = 0.571; F, p = 0.444) or EPA (M, p = 0.361; F, p = 0.901) supplementation. Likewise, the overall percent change in these levels were not different between supplemented cohorts compared to placebo when all participants were combined (% change in CD36 + MP: DHA = 5.7 ± 37.5, EPA = -3.4 ± 35.4, placebo = -11.5 ± 32.9; p = 0.158) or stratified by gender (M, DHA = -2.6 ± 30.6, EPA = -15.1 ± 20.1, placebo = -21.4 ± 28.7, p = 0.187; F, DHA = 11.7 ± 41.5, EPA = 6.8 ± 42.9, placebo = -2.8 ± 34.7, p = 0.552). CONCLUSION The cardioprotective effects of DHA and EPA do not act through a CD36 + MP mechanism.