The effect of omega-3 fatty acids on heart rate has been observed in many different populations, both with and without cardiovascular disease. A meta-analysis of 30 randomized, double-blind, placebo-controlled trials concluded that fish oil consumption can significantly reduce heart rate (Mozaffarian et al., 2005
). In particular, the effect was greater in people whose baseline heart rate was higher: in the overall pooled estimate, fish oil decreased heart rate by 1.6 bpm compared to placebo, but reduced heart rate by 2.5 bpm in trials with a median baseline heart rate of ≥ 69 bpm. Furthermore, the ability of fish oil to reduce heart rate appeared to depend on the length of treatment. When a trial lasted for more than 12 weeks, fish oil reduced heart rate by 2.5 bpm. However, when the trial lasted for less than 12 weeks, fish oil had little effect on heart rate. Interestingly, this meta-analysis also confirmed that heart rate reduction did not vary significantly by fish oil dose (Mozaffarian et al., 2005
). Furthermore, another randomized, controlled trial on 18 men with a history of myocardial infarction and ejection fractions of <40% showed that those given omega-3 fatty acids experienced a 5 bpm reduction in resting heart rate and an improved 1-min heart rate recovery after exercise (O'Keefe et al., 2006
In addition, several large-scale, population-based studies showed that increased dietary fish and omega-3 fatty acid intake was associated with a significant reduction in heart rate. Dallongeville et al. (2003
) analyzed 2 years of data on 9758 men without coronary heart disease from France and Ireland, grouping the men into four statistical categories based on how much fish they consumed per week (less than once, once, twice, and more than twice/week). They found that heart rate decreased across the categories of fish intake and was lower in fish consumers than in non-consumers, even after adjustments for age, location, level of education, physical activity, smoking habits, alcohol consumption, body mass index, and antiarrhythmic medications (Dallongeville et al., 2003
). Studies by Mozaffarian and colleagues further examined the associations between fish intake and a variety of cardiac measures (Mozaffarian et al., 2006a
). Their results showed that high fish consumption is associated with a heart rate reduction of approximately 3.2 bpm. They also found that an estimated 1 g/day higher EPA + DHA intake was associated with a heart rate reduction of 2.3 bpm. Functionally, this improvement in heart rate (−3.2 bpm) corresponds to a ~7.5% lower risk of SCD (Mozaffarian et al., 2006b
Fish oil also effectively reduces heart rate during times of increased cardiac demand such as exercise. A study of 25 Australian football players revealed that 6g/day of fish oil reduced heart rate during submaximal exercise over a period of 5 weeks (Buckley et al., 2009
). Likewise, another randomized, placebo-controlled study of 16 exceptionally fit male cyclists taking 8g/day of fish oil for 8 weeks also found a reduction in heart rate during exercise. Heart rate during incremental workloads to exhaustion was lowered, as was peak heart rate, oxygen consumption, and heart rate during steady submaximal exercise (Peoples et al., 2008
). However, decreased heart rate from fish oil during exercise is not contingent on physical fitness; in a study of 65 sedentary, overweight volunteers who consumed tuna fish oil for 12 weeks, resting heart rate and heart rate response to submaximal exercise were decreased (Ninio et al., 2008
). Thus, fish oil reduced heart rate both at rest and during the stress of exercise, irrespective of the relative fitness level of the participant.
Another set of interesting findings comes from a population perhaps the least likely to experience cardiovascular illness: infants. Term infants treated with varying amounts of DHA in their formulas for 12 months show that DHA supplementation reduces heart rate compared to infants whose formula does not contain DHA, with no evidence of a dose response (Pivik et al., 2009
; Colombo et al., 2011
). These data are noteworthy in that they reinforce the non-specific impact of fish oil on heart rate, and suggest that almost any cohort may benefit from fish oil in this manner.
Finally, Harris and colleagues performed a small prospective study that provides a valuable indication of which mechanisms are likely to underlie the omega-3 fatty acid-driven reduction in heart rate. The group enrolled heart transplant patients, ensuring that their transplants had occurred more than three months prior and there had been no transplant-related hospitalizations (Harris et al., 2006
). The revealing aspect of this study is that transplanted hearts are functionally denervated of the vagal nerve, and thus devoid of sympathetic and parasympathetic inputs. The patients were randomly assigned to receive either a corn oil placebo or EPA/DHA for 4–6 months, and at the end of the study the patients in the omega-3 fatty acid group had heart rates on average 5.4 bpm lower than baseline, whereas the corn oil group showed no change (Harris et al., 2006
). These findings suggest that omega-3 fatty acids impact heart rate at the level of the myocardium itself, and are in particular consistent with the idea that the voltage-gated ion channels that control the pacemaker currents in the heart are influenced by omega-3 fatty acids.
Similar reductions in heart rate due to omega-3 fatty acids have been observed in animals. In a rat model, animals fed a DHA-enriched diet had lower heart rates than animals fed a control diet, a pattern that was achieved by 2 months and maintained until the end of the 32-week study (Ayalew-Pervanchon et al., 2007
). In a hyperinsulinemic model, rats fed a diet containing DHA showed lower heart rates and a shortened QT interval as compared to rats fed and EPA-rich diet (Rousseau et al., 2003
). Similarly, in rabbits fed a diet enriched with 2.5% (w/w) fish oil for three weeks, sinus cycle length and heart rate were reduced compared to animals fed a 2.5% oleic sunflower oil for the same period of time (Verkerk et al., 2009
). A series of studies by Billman and colleagues has also provided important information about omega-3 fatty acids and heart function. Omega-3 fatty acid infusions into 13 intact, conscious, exercising dogs highly susceptible to ischemia-induced ventricular fibrillation were able to prevent ventricular fibrillation in 10 of the 13 dogs tested. The antiarrhythmic effect was associated with slowing of the heart rate, shortening of the QT interval, reduction of the left ventricular systolic pressure, and prolongation of the electrocardiographic atrial-ventricular conduction time (PR interval) (Billman et al., 1997
). Additional work showed that dietary omega-3 supplementation reduces resting heart rate and increases heart rate variability in dogs with previous but healed myocardial infarction, as well as in dogs that are either susceptible or resistant to ventricular fibrillation (Billman and Harris, 2011
; Billman, 2012
). Moreover, these reductions in baseline heart rate were maintained during challenges (i.e., exercise or acute myocardial ischemia), but omega-3 did not alter the amount of change induced by challenge; these findings are consistent with the idea that omega-3 supplementation impacts intrinsic heart rate rather than autonomic regulation of the heart. Interestingly, there is also evidence that under certain conditions omega-3 may actually be pro-arrhythmic by reducing myocyte excitability during acute regional ischemia (Coronel et al., 2007
Overall, it is apparent that a wide range of human and animal subjects, with or without cardiac disease, all respond to omega-3 fatty acid supplementation with reductions in resting and stress-induced heart rates. These findings suggest a highly consistent and robust effect of omega-3 fatty acids on heart rate.