A Small Cohort Omega-3 PUFA Supplement Study: Implications of Stratifying According to Lipid Membrane Incorporation in Cardiac Surgical Patients

Wendy T K Ip, Chanchal Chandramouli, Julian A. Smith, Peter Leslie McLennan, Salvatore Pepe, Lea M Durham Delbridge

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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 3 g/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.

Original languageEnglish
Pages (from-to)846-855
Number of pages10
JournalHeart Lung and Circulation
Issue number8
Publication statusPublished - 1 Aug 2017


  • Atrial fibrillation
  • Bax
  • Bcl2
  • Omega-3 polyunsaturated fatty acids (PUFA)
  • Peroxisomal proliferator-activated receptor (PPAR)

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