Emerging Science Chronotropic effects and mechanisms of long-chain omega-3 polyunsaturated fatty acids on heartbeat: the latest insights Weiguo Zhang The roles of the resting heart rate (RHR) have been actively investigated and increasingly recognized in recent decades, because of the growing evidence that fast RHR is associated with and predicts the risk of developing cardiovascular and metabolic disorders, as well as all-cause mortality. Long-chain omega-3 polyunsat- urated fatty acids (PUFAs) (eg, eicosapentaenoic acid and docosahexaenoic acid) have been shown to have chronotropic effects on heartbeat in both healthy people and patients with various disease conditions. The aims of this review are (1) to briefly summarize the importance of elevated RHR in disease pathogenesis and mortality; (2) to provide an update on the negative chronotropic effect of omega-3 PUFAs on the heart; (3) to highlight how omega-3 PUFAs regulate heart rate through the autonomic nervous system – a central control mechanism; and (4) to highlight how omega-3 PUFAs modulate the trans-membrane ionic channels in cardiomyocytes – a fundamental mechanism of cardiac automaticity. Eicosapentaenoic acid and docosahexaenoic acid are nutrients derived from some aquatic organisms, and they can also be converted from digested oily seeds and nuts of some terrestrial plants in the body. The consumption of omega-3 PUFAs for RHR reduction represents a lifestyle modification for risk factor management and promises nutritional benefits for public health improvement. INTRODUCTION Numerous investigations have implicated that higher basal or resting heart rate (RHR) is a risk factor for both cardiovascular and all-cause mortality. 1 The risk is frequently documented in clinical patients with cardio- vascular (eg, hypertension, coronary heart disease, and heart failure) and metabolic diseases (eg, type 2 diabetes mellitus), and most importantly in the general popula- tion epidemiologically. 2–5 In a recent cohort study, in which there were 89 860 adult participants, 6 RHR was stratified into incre- mental intervals of 45–54, 55–64, 65–74, 75–84, 85–94, and 95–104 beats per minute (bpm); and metabolic syn- drome was defined as presenting 3 or more of the 5 following characteristics: abdominal adiposity, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure/hypertension, and impaired fasting glucose. The study demonstrated that the adjusted odds ratio of having metabolic syndrome in the higher RHR categories was greater in cross-sectional analysis. For instance, when the group with a RHR of 55–64 bpm was set as a reference, the adjusted odds ratio of having metabolic syndrome was 1.49 in the group with a RHR of 95–104 bpm; when 43 725 participants without meta- bolic syndrome from the same population were longitu- dinally followed up, the adjusted odds ratio in those in the higher RHR categories at baseline was yet again greater for developing metabolic syndrome. For in- stance, the adjusted odds ratio of developing metabolic Affiliation: W. Zhang is with the Las Colinas Institutes, Irving, Texas, USA Correspondence: W. Zhang, Las Colinas Institutes, Irving, TX 75039, USA. E-mail: weiguozha@yahoo.com. Key words: autonomic nervous system, cardiac pacemaker, ion channels, omega-3 fatty acids (EPA and DHA), resting heart rate, risk factors VC The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. doi: 10.1093/nutrit/nuab009 128 Nutrition Reviews VR Vol. 80(1):128–135 Downloaded from https://academic.oup.com/nutritionreviews/article/80/1/128/6219404 by guest on 29 March 2022