title: A Small Cohort Omega-3 PUFA Supplement Study: Implications of Stratifying According to Lipid Membrane Incorporation in Cardiac Surgical Patients.
abstract: BACKGROUND
  Epidemiological studies and randomised clinical trials (RCTs) report disparate findings in relation to omega-3 polyunsaturated fatty acids (n-3 PUFA) benefit for cardiac patients. With RCTs interpretation is potentially confounded by background n-3 PUFA intake. The goal of this pilot, small cohort, pre-surgical supplementation study was to evaluate postoperative atrial fibrillation (AF) and cardiac molecular expression profiles employing two data analysis approaches - by treatment randomisation and by stratification using measured n-3 PUFA.
  
  
  METHODS
  Patients (n=20) received 3g/day of fish or placebo oil (FO vs PO) in a double blind randomised protocol prior to elective coronary artery graft and valve surgery. Groups were matched for age, gender, and mean treatment duration (∼20 days). Resected atrial myocardium was sampled for assay of viability metabolic markers, and blood obtained for erythrocyte membrane lipid measurement.
  
  
  RESULTS
  There was substantial overlap of cell membrane n-3 PUFA content across PO and FO groups, and no group treatment effects on AF incidence or myocardial molecular marker levels were detected. In contrast, data stratification using membrane n-3 PUFA content (at 8% total membrane lipid) achieved significant separation of patients (by n-6:n-3 PUFA ratio), a significant differential cardiac expression of the marker peroxisomal proliferator-activated receptor, but no difference in AF incidence.
  
  
  CONCLUSIONS
  This small n-3 PUFA case study demonstrates that the same cohort may yield differing findings when evaluated using randomisation or stratification approaches based on direct molecular measures in cell membranes.
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Melbourne, Vic, Australia.
authors.forename: Wendy T K
authors.initials: WTK
authors.lastname: Ip
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Melbourne, Vic, Australia.
authors.forename: Chanchal
authors.initials: C
authors.lastname: Chandramouli
authors.affiliation: Department of Cardiothoracic Surgery, Monash Health, Monash University, Melbourne, Vic, Australia; Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Vic, Australia.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Smith
authors.affiliation: Graduate School of Medicine, Centre for Human Applied Physiology, University of Wollongong, Sydney, NSW, Australia.
authors.forename: Peter L
authors.initials: PL
authors.lastname: McLennan
authors.affiliation: Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Vic, Australia. Electronic address: salvatore.pepe@mcri.edu.au.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Melbourne, Vic, Australia.
authors.forename: Lea M D
authors.initials: LMD
authors.lastname: Delbridge
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000601:surgery*; D006348:Cardiac Surgical Procedures; D019587:Dietary Supplements; D004910:Erythrocyte Membrane / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008563:Membrane Lipids / Q000097:blood*; D008875:Middle Aged
chemical_list: D015525:Fatty Acids, Omega-3; D008563:Membrane Lipids
keywords: Atrial fibrillation; Bax; Bcl2; Omega-3 polyunsaturated fatty acids (PUFA); Peroxisomal proliferator-activated receptor (PPAR)