Graduate Medicine, School of Medicine, University of Wollongong, Wollongong, Australia.
Centre for Medical and Exercise Physiology, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, Australia.
J Nutr. 2020 Dec 10;150(12):3086-3093. doi: 10.1093/jn/nxaa256.
Supplementing animal diets with fish oil increases myocardial omega-3 polyunsaturated fatty acids [ω-3 (n-3) PUFA], lowers heart rate, and prevents malignant cardiac arrhythmias. In contrast to epidemiological reports, results of some human clinical trials and of unphysiologically high doses employed in animal studies call into question the application of dietary ω-3 PUFA for cardioprotection.
This study tested the hypothesis that low ω-3 PUFA dietary thresholds for myocardial incorporation in rats, equivalent in dose to what humans derive from eating fish, can reduce heart rate and arrhythmia vulnerability.
Male Sprague-Dawley rats (12-15 wk old) were fed isoenergetic diets containing 10% fat for 4-5 wk. The control diet (CON) contained 5.5% beef tallow, 2.5% sunflower seed oil, and 2% olive oil. Fish oil diets contained high-DHA tuna oil, exchanged for olive oil: 0.31% [fish oil group 1 (FO1)] (human equivalent EPA + DHA 570 mg/d); 1.25% [fish oil group 2 (FO2)] (equivalent EPA + DHA 2.3 g/d). Anaesthetized rats (pentobarbital, 60 mg/kg intraperitoneally) were subjected in vivo to 15-min cardiac ischemia by left coronary artery occlusion and then reperfusion, with arrhythmias detected by electrocardiogram.
Fish oil dose dependently modulated myocardial membrane fatty acids (DHA mean ± SEM: CON, 5.0 ± 0.2%; FO1, 13.1 ± 0.9%; FO2, 18.3 ± 0.4%; n = 4-5; P-trend < 0.001 ANOVA); resting heart rate (CON, 453 ± 6; FO1, 432 ± 4; FO2, 422 ± 5 bpm; n = 15-18; P-trend < 0.001); reduced ventricular fibrillation (VF) (CON, 89%; FO1, 60%; P = 0.052; FO2, 50%; n = 15-18; P = 0.013 chi square); and total arrhythmia severity (arrhythmia score: CON, 6.1 ± 0.4; FO1, 4.6 ± 0.5; FO2, 3.1 ± 0.7; n = 15-18; P-trend < 0.01) during ischemia and reperfusion (VF: Con, 86%; FO1, 22% P = 0.011; FO2, 8% P = 0.001; n = 7-12); (arrhythmia score: CON, 4.6 ± 0.3; FO1, 3.1 ± 0.3; FO2, 1.3 ± 0.3; n = 7-12; P-trend < 0.001).
Ventricular arrhythmias were prevented and heart rate was slowed by lower ω-3 PUFA intake in rats than previously reported, equivalent to human fish consumption and associated with increased myocardial DHA. The efficacy of low-dose fish oil demonstrates biological plausibility for nutritional ω-3 fatty acid-mediated cardioprotection and suggests that effectiveness in human clinical trials may be obscured by failure to exclude fish eaters.
在动物饲料中添加鱼油可以增加心肌中的 ω-3 多不饱和脂肪酸[ω-3（n-3）PUFA]，降低心率，并预防恶性心律失常。与流行病学报告相反，一些人体临床试验和动物研究中使用的非生理高剂量的结果对饮食 ω-3 PUFA 用于心脏保护提出了质疑。
本研究检验了这样一个假设，即大鼠心肌中 ω-3 PUFA 的低膳食阈值相当于人类从食用鱼类中获得的剂量，可以降低心率和心律失常易感性。
雄性 Sprague-Dawley 大鼠（12-15 周龄）喂食含有 10%脂肪的等能量饮食 4-5 周。对照饮食（CON）含有 5.5%的牛脂、2.5%的葵花籽油和 2%的橄榄油。鱼油饮食含有高 DHA 金枪鱼油，用橄榄油替代：0.31%[鱼油 1 组（FO1）]（人类等效 EPA+DHA 570mg/d）；1.25%[鱼油 2 组（FO2）]（等效 EPA+DHA 2.3g/d）。麻醉大鼠（戊巴比妥，60mg/kg 腹腔内注射）通过左冠状动脉闭塞和再灌注进行 15 分钟的体内心肌缺血，通过心电图检测心律失常。
鱼油剂量依赖性地调节心肌膜脂肪酸（DHA 平均值±SEM：CON，5.0±0.2%；FO1，13.1±0.9%；FO2，18.3±0.4%；n=4-5；P-趋势<0.001 ANOVA）；静息心率（CON，453±6；FO1，432±4；FO2，422±5 bpm；n=15-18；P-趋势<0.001）；减少室颤（VF）（CON，89%；FO1，60%；P=0.052；FO2，50%；n=15-18；P=0.013 卡方）；总心律失常严重程度（心律失常评分：CON，6.1±0.4；FO1，4.6±0.5；FO2，3.1±0.7；n=15-18；P-趋势<0.01）在缺血和再灌注期间（VF：Con，86%；FO1，22% P=0.011；FO2，8% P=0.001；n=7-12）；（心律失常评分：CON，4.6±0.3；FO1，3.1±0.3；FO2，1.3±0.3；n=7-12；P-趋势<0.001）。
与先前报道的大鼠相比，较低的 ω-3 PUFA 摄入量可预防心室性心律失常并降低心率，这相当于人类的鱼类摄入量，并与心肌 DHA 增加有关。低剂量鱼油的疗效证明了营养 ω-3 脂肪酸介导的心脏保护的生物学合理性，并表明在人体临床试验中可能因未能排除鱼类食用者而掩盖了有效性。
