Omega-3 fatty acid (n-3 FA) consumption has been linked to reductions in the risk of death from coronary heart disease and, recently, to lower heart rates (HRs). The investigators previously observed a reduction of 5 beats/min in HR in patients with coronary heart disease given n-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) for 4 months. Reductions in HR may be explained by enhanced vagal tone, influences on cardiac voltage-gated ion channels, or both. The hypothesis that n-3 FAs would affect HR independent of vagal input was investigated by studying the effects of n-3 FA supplementation on HR in patients with denervated hearts after orthotopic heart transplantation. Electrocardiographic data obtained in 2 prospective trials in which 18 heart transplant recipients received n-3 FA supplementation (1 to 3.4 g/day) for 4 to 6 months were collected. Patients were studied 4.4 +/- 2.6 years after transplantation. HR, QRS complex, and QTc duration were determined before and after treatment. Pretreatment HR was reduced from 88 +/- 14 to 83 +/- 13 beats/min after n-3 FA treatment (p = 0.016). QRS duration increased from 107 +/- 24 to 117 +/- 25 ms (p = 0.001). QTc duration remained unchanged from baseline (427 +/- 34 ms) to study end (424 +/- 39 ms). In conclusion, n-3 FA supplementation reduced HR and prolonged QRS duration in heart transplant recipients who were presumably devoid of vagal innervation. These findings suggest that n-3 FAs may modify electrophysiologic properties of the myocardium itself.