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Regular fish consumption, a rich source of long-chain omega-3 (ω-3) docosahexaenoic acid (DHA), modifies cardiac electrophysiology. However, human studies investigating fish oil and cardiac electrophysiology have predominantly supplemented therapeutic (high) doses of fish oil (often ω-3 eicosapentaenoic acid (EPA) rich sources). This study examined whether non-therapeutic doses of DHA-rich fish oil modulate cardiac electrophysiology at rest and during cardiovascular reflex challenges to the same extent, if at all, in young healthy adults. Participants (N = 20) were supplemented (double-blinded) with (2x1g.day−1) soy oil (Control n = 9) or DHA-rich tuna fish oil (FO n = 11) providing DHA: 560 mg and EPA: 140 mg. The Omega-3 Index (O3I; erythrocyte membrane % EPA + DHA), heart rate (HR) and HR variability (HRV) were analyzed during rest, maximal isometric handgrip and cold diving reflex challenges at baseline and following 8 weeks. The baseline O3I (Control: 5.1 ± 1.0; FO: 5.4 ± 0.9; P > 0.05), resting HR (Control: 65 ± 12bpm; FO: 66 ± 8bpm; P > 0.05) and HRV metrics did not significantly differ between the groups prior to supplementation. Relative to the control group, the O3I was increased (Control: 5.0 ± 1.1; FO: 7.8 ± 1.2; P < 0.001), and resting HR was slowed in the FO group following supplementation (Control: 66 ± 9bpm; FO: 61 ± 6bpm; P = 0.046). However, no significant (P > 0.05) between-group differences were observed in HR responsiveness or any indices of HRV during reflex challenges. In young healthy adults, dietary achievable doses of ω-3 DHA-rich fish oil exerted a direct slowing effect on resting HR, without compromising the HR response to either dominant sympathetic or parasympathetic modulation. [ABSTRACT FROM AUTHOR]

Dietary fish oil, providing docosahexaenoic acid (DHA) modulates oxygen consumption and fatigue in animal models. However, in humans predominately supplemented with high eicosapentaenoic acid (EPA), there is no evidence of endurance performance enhancement. Therefore, this study examined if DHA-rich fish oil could improve repeated bouts of physiologically stressful cycling and a subsequent time trial in a state of fatigue. Twenty-six trained males took part in a double-blind study and were supplemented with either 2 x 1g/day soy oil, Control) or DHA-rich tuna fish oil (Nu-Mega) (FO) (560mg DHA / 140mg eicosapentaenoic acid (EPA), for 8 weeks. Maximal cycling power (3 X 6s), isometric quadriceps strength (MVC), Wingate cycling protocol (6 x 30s) and a 5min cycling time-trial were assessed at baseline and eight weeks. The Omega-3 Index was not different at baseline (Control: 4.2 ± 0.2; FO: 4.7 ± 0.2%) and increased in the FO group after eight weeks (Control: 3.9 ± 0.2; FO: 6.3 ± 0.3%, p < .01). There was no effect of DHA-rich fish oil on power output of maximal 6s cycle sprinting (Control: pTe 1100 ± 49 Post 1067 ± 51; FO: Pre 1070 ± 46 Post 1042 ± 46W), during 5min time trail (Control: Pre 267 ± 19 Post 278 ± 20; FO: Pre 253 ± 16 Post 265 ± 16 W) or maximal voluntary contraction force (Control: Pre 273 ± 19 Post 251 ± 19; FO: Pre 287 ± 17 Post 283 ± 16 Nm). Nevertheless, relative oxygen consumption was reduced the FO group during the cycling time trial (Control: -23 ± 26; FO: -154 ± 59ml O2/min/100W p < .05) suggesting improved economy of cycling. We conclude that DHA-rich fish oil, successful at elevating the Omega-3 Index, and reflective of skeletal muscle membrane incorporation, can modulate oxygen consumption during intense exercise. [ABSTRACT FROM AUTHOR]

Aims: Supplementing animal diets with high-dose fish oil, rich in long chain omega-3 (ω-3) docosahexaenoic acid (DHA), enhances cardiac contractile efficiency and attenuates dysfunction, attributable to ischaemia. However, it remains unclear whether smaller doses, equivalent to what is achievable via regular fish consumption in the human diet, offer similar protection. Methods: Male Sprague–Dawley (12−15w) rats were fed isoenergetic diets (ad libitum) containing 10% fat by weight (22% energy) for 4–5w. Control diet (CON) contained 5.5% beef tallow; 2.5% ω-6 sunflower seed oil; 2% olive oil. Fish oil diets included high-DHA tuna oil exchanged for olive oil to provide 0.32% (FO1; human equivalent EPA + DHA 570 mg/d) or 1.25% (FO2; equivalent EPA + DHA 2.3 g/d) wt/wt dose of fish oil. Anaesthetised rats (pentobarbital: 60 mg/kg i.p.) were subjected to 45 min coronary artery occlusion then reperfusion in vivo as a whole animal model of regional myocardial ischaemia, with left ventricular haemodynamic function measured by conductance catheter. Results: Ischaemia-induced reductions in rate pressure product recovered faster in the FO2 group and post-ischaemic left ventricular pressure–volume loop integrity (shifted downwards and right in CON) was partially protected in both fish oil groups. Conclusion: Ischaemia-induced contractile dysfunction in rats is limited from fish oil doses equivalent to regular consumption of fish in the human diet. These observations highlight plausible and clinically relevant physiological changes that rationalise nutritional conditioning of the heart with DHA for on-going cardioprotection. [ABSTRACT FROM AUTHOR]

This pilot study sought to determine whether a low, supplemental intake of fish oil would raise the Omega‐3 Index (O3I) and improve physical fitness in healthy older adults. Participants (70 ± 3 years) were randomised to 2 g/day of either sunola oil (control; n = 8, 62.5% female) (1700 mg/day oleic acid) or docosahexaenoic acid (DHA)‐rich fish oil (FO; n = 9, 55.6% female) [delivering 560 mg/day DHA and 140 mg/day eicosapentaenoic acid (EPA)] for 16 weeks. The O3I, physical fitness, 400 m walking speed and heart rate (HR) parameters were assessed. O3I was increased after FO (mean ± SD, control: pre 6.1 ± 0.8, post 5.9 ± 0.6; FO: pre 6.0 ± 0.6, post 8.3 ± 1.2 p < 0.05). Mean lowest overnight HR (control: pre 58 ± 6, post 58 ± 6; FO: pre 55 ± 6, post 52 ± 6 bpm, p < 0.05) and mean HR during fast walking (control: pre 120 ± 6, post 124 ± 7; FO: pre 122 ± 6, post 115 ± 6 bpm, p < 0.01) were reduced in the FO group without a change in walking speed (control: pre 1.55 ± 0.17, post 1.58 ± 0.20; FO: pre 1.59 ± 0.15, post 1.59 ± 0.18 m/s), HR variability or physical fitness. The changes in lowest resting HR and fast walking HR significantly correlated (inversely) with the changes in O3I. This nutritional approach of providing dietary achievable DHA offers a potential opportunity to reduce cardiovascular strain during physical activity in the older adult. [ABSTRACT FROM AUTHOR]

Background: 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.Objective: 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.Methods: 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.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Oxygen efficiency influences skeletal muscle contractile function during physiological hypoxia. Dietary fish oil, providing docosahexaenoic acid (DHA), reduces the oxygen cost of muscle contraction. This study used an autologous perfused rat hindlimb model to examine the effects of a fish oil diet on skeletal muscle fatigue during an acute hypoxic challenge. Male Wistar rats were fed a diet rich in saturated fat (SF), long-chain (LC) n-6 polyunsaturated fatty acids (n-6 PUFA), or LC n-3 PUFA DHA from fish oil (FO) (8 weeks). During anaesthetised and ventilated conditions (normoxia 21% O2 (SaO2-98%) and hypoxia 14% O2 (SaO2-89%)) the hindlimb was perfused at a constant flow and the gastrocnemius-plantaris-soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6-12V, 0.05 ms) to established fatigue. Caffeine (2.5, 5, 10 mM) was supplied to the contracting muscle bundle via the arterial cannula to assess force recovery. Hypoxia, independent of diet, attenuated maximal twitch tension (normoxia: 82 ± 8; hypoxia: 41 ± 2 g·g−1 tissue w.w.). However, rats fed FO sustained higher peak twitch tension compared with the SF and n-6 PUFA groups ( P < 0.05), and the time to decline to 50% of maximum twitch tension was extended (SF: 546 ± 58; n-6 PUFA: 522 ± 58; FO: 792 ± 96 s; P < 0.05). In addition, caffeine-stimulated skeletal muscle contractile recovery was enhanced in the FO-fed animals (SF: 41 ± 3; n-6 PUFA: 40 ± 4; FO: 52 ± 7% recovery; P < 0.05). These results support a physiological role of DHA in skeletal muscle membranes when exposed to low-oxygen stress that is consistent with the attenuation of muscle fatigue under physiologically normoxic conditions. [ABSTRACT FROM AUTHOR]

Dietary fish consumption contributes to a reduced risk of cardiac mortality. In the present study, the effect of low-dose fish oil (FO) supplementation on heart rate (HR) response to intense exercise and recovery was investigated in physically fit males. The subjects (n 26) were supplemented (double-blind, parallel design) with (2 × 1 g/d) soya bean oil (control) or tuna FO providing the long-chain n-3 PUFA DHA (560 mg) and EPA (140 mg). Erythrocyte omega-3 index (%EPA+DHA), HR, HR variability and HR recovery were analysed during rest, intense exercise and recovery at baseline and after 8 weeks of supplementation. The mean erythrocyte omega-3 index, which did not differ between the groups at baseline (control 4·2 (sem 0·2), n 13; FO 4·7 (sem 0·2), n 13), remained unchanged in the control group (3·9 (sem 0·2)), but increased in the FO group (6·3 (sem 0·3); P< 0·01). The mean HR during supine resting conditions (control 56 (sem 10); FO 59 (sem 9)) was not affected by FO supplementation. Poincaré analysis of HR variability at rest exhibited a decreasing trend in parasympathetic activity in the FO group (SD1 (standard deviation of points perpendicular to the axis of line of identity)/SD2 (standard deviation of points along the axis of line of identity): control 0·02 (sem 0·01); FO − 0·05 (sem 0·02); P= 0·18). Peak HR was not affected by supplementation. However, during submaximal exercise over 5 min, fewer total heart beats were recorded in the FO group ( − 22 (sem 6) ( = − 4·5 beats/min)), but not in the control group (+1 (sem 4)) (P< 0·05). Supine HR recovery (half-time) after cycling was significantly faster after FO supplementation (control − 0·4 (sem 1·2) s; FO − 8·0 (sem 1·7) s; P< 0·05). A low intake of FO increased the omega-3 index and reduced the mean exercise HR and improved HR recovery without compromising the peak HR. A direct influence of DHA via reductions in the cardiac intrinsic beat rate was balanced by a reciprocal decrease in vagal tone. [ABSTRACT FROM PUBLISHER]

Dietary fish oil modifies skeletal muscle membrane fatty acid composition and oxygen efficiency similar to changes in the myocardium. Oxygen efficiency is a key determinant of sustained force in mammalian skeletal muscle. Therefore, in the present study, we tested the effects of a fish-oil diet on skeletal muscle fatigue under the stress of contraction using the rat in vivo autologous perfused hindlimb model. For 8 weeks, male Wistar rats were fed a diet rich in saturated fat (SF), a diet rich in n-6 PUFA or a diet rich in long-chain (LC) n-3 PUFA DHA derived from fish oil. In anaesthetised, mechanically ventilated rats, with their hindlimbs perfused with arterial blood at a constant flow, the gastrocnemius–plantaris–soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6–12 V, 0·05 ms) to contract repetitively for 30 min. Rats fed the n-3 PUFA diet developed higher maximum twitch tension than those fed the SF and n-6 PUFA diets (P< 0·05) and sustained twitch tension through more repetitions before the tension declined to 50 % of the maximum twitch tension (P< 0·05). The n-3 PUFA group used less oxygen for tension developed and produced higher venous lactate concentrations with no difference in glycogen utilisation compared with the SF and n-6 PUFA groups. These results further support that incorporation of DHA into skeletal muscle membranes increases the efficiency of oxygen use over a range of contractile force and this is expressed as a higher sustained force and prolonged time to fatigue. [ABSTRACT FROM PUBLISHER]

Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA® 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy. [ABSTRACT FROM PUBLISHER]

Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (in- traventricular balloon) after global no-flow ischemia and reperfusion (15/30 mm), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TO, respectively (P < 0.001). The extent of mechanical recovery [rate- pressure product (RPP) = beats/mm X mmHg] of FO-fed WT and TG hearts was similar (50 ± 7% vs. 45 ± 12%, 30 mm reperfusion), and this was not significantly different from CTR-fed WT or TO. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TO (RPP, 50 ± 4% vs. 64 ± 8%) was not enhanced compared with CTR-fed mice (RPP, 60 ± 11% vs. 80 ± 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TO hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model. [ABSTRACT FROM AUTHOR]

Tests the hypothesis that in vivo antiarrhythmic effects of dietary fish oil can be attributed directly to changes in myocardial properties in adult male rats. Conclusion that dietary fish oil directly affects myocardial properties which may contribute to observed clinical reductions in cardiac mortality associated with fish consumption.

Cardio protective actions of n-3 polyunsaturated fatty acids (PUFA) suggest a preconditioning-like effect. We investigated whether modification of membrane composition by dietary fish oil protects the heart during ischemia/reperfusion compared to ischemic preconditioning. Rats were fed diets with fish oil (n-3 PUFA), sunflower seed oil (n-6 PUFA) or saturated fat (beef tallow) (SF) for 6 weeks. Isovolumic isolated perfused hearts were reperfused for 120min after 30min regional ischemia, with or without ischemic preconditioning (3x 5min cycles of global ischemia). The n-3 PUFA hearts had lower coronary flow (CF), heart rate (HR) and end diastolic pressure (EDP) at rest. In reperfusion they had less arrhythmia, better developed pressure recovery, and maximum relaxation rate, and HR, CF and EDP stayed lower. Ischemic preconditioning reduced CF, HR and EDP at rest, reduced EDP rise in ischemia and improved developed pressure recovery and reduced arrhythmia. Preconditioning was effective only in SF and n-6 PUFA hearts. Therefore, prefeeding with n-3PUFA provided cardio protection, improving recovery, reducing stunning and arrhythmia while ischemic preconditioning provided similar but no additional protection.' We conclude that dietary fish oil produces a preconditioning-like effect that is not subject to desensitisation with long-term feeding. DHA rich tuna fish oil was a gift Of NuMega Lipids Australia. [ABSTRACT FROM AUTHOR]