Effect of fish oil on heart rate in humans - A meta-analysis of randomized controlled trials

Background - The effect of fish oil on heart rate (HR), a major risk factor for sudden death, is not well established. We calculated this effect in a meta-analysis of randomized, double-blind, placebo- controlled trials in humans. Methods and Results - Randomized trials of fish oil that evaluated HR were identified through MEDLINE (1966 through January 2005), hand-searching of references, and contact with investigators for unpublished results. Two investigators independently extracted trial data. A pooled estimate was calculated from random-effects meta-analysis. Predefined stratified meta-analyses and meta-regression were used to explore potential heterogeneity. Of 197 identified articles, 30 met inclusion criteria. Evidence for publication bias was not present. In the overall pooled estimate, fish oil decreased HR by 1.6 bpm (95% CI, 0.6 to 2.5; P = 0.002) compared with placebo. Between-trial heterogeneity was evident (Q test, P < 0.001). Fish oil reduced HR by 2.5 bpm (P < 0.001) in trials with baseline HR >= 69 bpm (median) but had little effect (0.04-bpm reduction; P = 0.56) in trials with baseline HR >= 69 bpm (P for interaction = 0.03). Fish oil reduced HR by 2.5 bpm (P < 0.001) in trials with duration >= 12 weeks but had less effect (0.7-bpm reduction; P = 0.27) in trials with duration >= 12 weeks (P for interaction = 0.07). HR reduction with fish oil intake did not significantly vary by fish oil dose (range, 0.81 to 15 g/d), type of HR measure, population age, population health, parallel versus crossover design, type of control oil, or study quality by Delphi criteria (P for interaction > 0.25 for each). Conclusions - In randomized controlled trials in humans, fish oil reduces HR, particularly in those with higher baseline HR or longer treatment duration. These findings provide firm evidence that fish oil consumption directly or indirectly affects cardiac electrophysiology in humans. Potential mechanisms such as effects on the sinus node, ventricular efficiency, or autonomic function deserve further investigation.