- Title
- Differential effects of long chain omega-3 polyunsaturated fatty acids on platelet aggregation and hemostatic variables in healthy male versus female subjects
- Creator
- Phang, Melinda
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2013
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Thrombosis is a critical event that accounts for considerable morbidity and mortality in the Western world. Thrombosis is associated with arterial diseases including, myocardial infarction, stroke, and peripheral occlusive disease as well as with venous thromboembolic disorders. Consequently, the primary goal for the prevention of arterial and venous thrombosis to combat disease progression is to limit thrombus extension. Platelet activation and aggregation is considered to be central to thrombus production; thus anti-thrombotic treatments to inhibit platelet activity have been a major drug target to retard the thrombotic and atherosclerotic processes. Despite extensive resource investment in cardiovascular research and treatment, the current pharmacological strategies for the inhibition of platelet aggregation, although effective, may present limitations and adverse health effects have been reported. Given the toll taken by thrombotic complications, a safe and efficacious non-pharmacological approach may be paramount for the prevention and management of thrombotic disease. While a wealth of evidence supports that fish oil provides preventative or ameliorative effects against thrombotic disease, the mechanisms responsible for this association are not understood and are further complicated by contrasting reports. Fish oils are a rich source long chain omega-3 polyunsaturated fatty acids including eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), however it is not clear whether the anti-thrombotic effects are due to EPA or DHA or whether both are equally effective. In the available literature relating fish oil and platelet aggregation, wide variability in terms of dosage, concentration ratios, study design, subject characteristics and gender inequality are apparent, hence there is discrepancy regarding the effect of fish oils on platelet activity. Consequently, the anti-thrombotic potential of fish oil supplementation is controversial and largely disregarded by the medical community. This dissertation investigated the independent effects of EPA and DHA on platelet and coagulant activity. A series of three controlled studies were undertaken to elucidate the mechanisms by which EPA and DHA influence hemostatic parameters with the hope to resolve the existing controversy. The ultimate and unifying theme of these studies was to provide a safe and efficacious approach to optimise cardio-protection via anti-thrombotic potential of EPA versus DHA. Firstly, an in vitro investigation was carried out that compared the effects of EPA with DHA on platelet aggregation in healthy male and female subjects. The inhibition of platelet aggregation by EPA/DPA/DHA was equally effective and correlated with lag time; however most strikingly the results were influenced in a gender-specific manner. These observations suggest that interactions between sex hormones and fish oils exist to influence platelet response differentially. With a new perspective of gender bias effects, an acute supplementation study monitored the platelet responses up to 24 hours after consumption of a single dose of an EPA versus DHA-rich oil capsule in thirty male and female subjects. The kinetics of the EPA and DHA supplement on platelet activity was examined according to gender stratified treatment. Subgroup gender analysis showed that the anti-aggregatory effects of EPA were predominately evident in males while female platelets were more responsive to DHA. The marked decrease in platelet aggregation with EPA supplementation was paralleled with a reduction in platelet microparticle activity in the male subjects only, and an inverse relationship between testosterone levels and platelet responses were observed. Findings from this study reflected the in vitro observations and suggest that EPA and DHA inhibit platelet aggregation via independent pathways compounded by sex hormonal influences. Confirmation of gender-specific platelet responses with omega-3 fatty acid supplementation was achieved in a chronic supplementation study involving ninety-four healthy male and female subjects. Subsequently, this four week dietary intervention trial demonstrated that the anti-thrombotic potential is apparent with longer term exposure to EPA/DHA and explored the mechanistic pathways. Significant interactions between gender and treatment were observed; the effects of EPA were specific in reducing platelet aggregation and specific coagulation factors in males, whereas no effects were observed in the female cohort. Conversely, the effects of DHA were unique to females with a similar decrease in platelet aggregability. Interactions between sex hormones with coagulation factors and retention of EPA and DHA in plasma were also observed.In conclusion, the study findings presented in this thesis provide evidence that the effects of EPA and DHA on platelet aggregation are apparent; the effects are neither shared nor complementary, rather they are gender-specific. Furthermore, the results herein may explain the existing controversy between fish oils, platelets and thrombosis that have intrigued clinical investigators for several decades. With respect to thrombotic disease risk, males would likely benefit more from supplementation with EPA while females are more responsive to DHA. The significance of these findings allows optimal cardio-protection tailored for both gender groups offering a safe and efficacious non-pharmacological approach.
- Subject
- thrombosis; omega-3 fatty acids; platelet aggregation; fish oil; EPA; DHA; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/938766
- Identifier
- uon:12674
- Rights
- Copyright 2013 Melinda Phang
- Language
- eng
- Full Text
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| View Details Download | ATTACHMENT02 | Thesis | 2 MB | Adobe Acrobat PDF | View Details Download |