title: Reduction of prothrombin and Factor V levels following supplementation with omega-3 fatty acids is sex dependent: a randomised controlled study.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nutraceuticals Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
authors.forename: Melinda
authors.initials: M
authors.lastname: Phang
authors.affiliation: Hunter Haematology Research Group, Calvary Mater Newcastle, Waratah, NSW 2298, Australia.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Scorgie
authors.affiliation: Hunter Haematology Research Group, Calvary Mater Newcastle, Waratah, NSW 2298, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Seldon
authors.affiliation: Nutraceuticals Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. Electronic address: manohar.garg@newcastle.edu.au.
authors.forename: Manohar L
authors.initials: ML
authors.lastname: Garg
authors.affiliation: Hunter Haematology Research Group, Calvary Mater Newcastle, Waratah, NSW 2298, Australia.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Lincz
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects; D015992:Body Mass Index; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005165:Factor V / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011516:Prothrombin / Q000378:metabolism*; D012307:Risk Factors; D012737:Sex Factors; D013917:Thrombin / Q000378:metabolism
chemical_list: D004281:Docosahexaenoic Acids; D005165:Factor V; D011516:Prothrombin; D015118:Eicosapentaenoic Acid; D013917:Thrombin
keywords: Hemostatic markers; LCn-3PUFA; Platelets; Procoagulant activity; Sex-dependent