A review and evaluation of study design considerations for omega-3 fatty acid supplementation trials in physically trained participants.

Long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) supplements, rich in eicosapentaenoic acid and/or docosahexaenoic acid, are increasingly being recommended within athletic institutions. However, the wide range of doses, durations and study designs implemented across trials makes it difficult to provide clear recommendations. The importance of study design characteristics in LC n-3 PUFA trials has been detailed in cardiovascular disease research, and these considerations may guide LC n-3 PUFA study design in healthy cohorts. This systematic review examined the quality of studies and study design considerations used in evaluating the evidence for LC n-3 PUFA improving performance in physically trained adults. SCOPUS, PubMed and Web of Science electronic databases were searched to identify studies that supplemented LC n-3 PUFA in physically trained participants. Forty-six (n = 46) studies met inclusion. Most studies used a randomised control design. Risk of bias, assessed using the design-appropriate Cochrane Collaboration tool, revealed that studies had a predominant judgment of 'some concerns', 'high risk' or 'moderate risk' in randomised controlled, randomised crossover or non-randomised studies, respectively. A custom five-point quality assessment scale demonstrated that no study satisfied all recommendations for LC n-3 PUFA study design. This review has highlighted that the disparate range of study designs is likely contributing to the inconclusive state of outcomes pertaining to LC n-3 PUFA as a potential ergogenic aid. Further research must adequately account for the specific LC n-3 PUFA study design considerations, underpinned by a clear hypothesis, to achieve evidence-based dose, duration and composition recommendations for physically trained individuals.

DHA-Rich Fish Oil Increases the Omega-3 Index in Healthy Adults and Slows Resting Heart Rate without Altering Cardiac Autonomic Reflex Modulation.

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.

The influence of a basic military training diet on whole blood fatty acid profile and the Omega-3 Index of Australian Army recruits.

This study described the whole blood fatty acid profile and Omega-3 Index (O3I) of Australian Army recruits at the commencement and completion of basic military training (BMT). Eighty males (17-34 y, 77.4 ± 13.0 kg, 43.5 ± 4.3 mL/kg/min) and 37 females (17-45 y, 64.3 ± 8.8 kg, 39.3 ± 2.7 mL/kg/min) volunteered to participate (N = 117). Whole blood samples of each recruit were collected using a finger prick in weeks 1 and 11 (n = 82) and analysed via gas chromatography for the relative proportions of each fatty acid (mean [95% confidence interval]). The macronutrient characteristics of the diet offerings was also determined. At commencement there was a low omega-3 status (sum of omega-3; 4.95% [4.82-5.07]) and O3I (5.03% [4.90-5.16]) and no recruit recorded an O3I >8% (desirable). The omega-6/omega-3 (7.04 [6.85-7.23]) and arachidonic acid/eicosapentaenoic acid (AA/EPA) (18.70 [17.86-19.53]) ratios for the cohort were also undesirable. The BMT mess menu provided a maximum of 190 mg/day of EPA and 260 mg/day of docosahexaenoic acid (DHA). The O3I of the recruits was lower by week 11 (4.62% [4.51-4.78], p < 0.05), the omega-6/omega-3 increased (7.27 [7.07-7.47], p < 0.05) and the AA/EPA remained elevated (17.85 [16.89-18.81]). In conclusion, Australian Army recruits' omega-3 status remained undesirable during BMT and deserves nutritional attention. Novelty: Australian Army recruits' Omega-3 Index, at the commencement of BMT, was reflective of the Western-style diet. The BMT diet offered minimum opportunity for daily EPA and DHA consumption. Every recruit experienced a further reduction of their Omega-3 Index during BMT.

Emergency department care-related causal factors of in-patient deterioration.

Objective The aim of this study was to determine factors related to emergency department (ED) care causing in-patient deterioration. Methods This retrospective cohort study examined in-patient records using the human factors classification framework for patient safety in a regional health service in New South Wales, Australia, between March 2016 and February 2017. Deterioration was defined as either the initiation of a medical emergency team call, cardiac arrest or unplanned admission to the intensive care unit. Results Of the 1074 patients who deteriorated within 72 hours of admission via the ED, the care received in the ED was a contributing factor for 101 patients (9%). The most common human causal factors were poor communication between staff, medical management errors, delayed treatment, medical documentation errors, nursing management errors and unclear policies or guidelines. Communication issues occurred the most when patients had more comorbidities (P = 0.039) and were more likely to occur in the presence of a medical documentation error (odds ratio 4.4; 95% confidence interval 1.7-11.3). Unclear policies or guidelines as a factor was most frequent with a surgical diagnosis (34.5% vs 15.7% for surgical vs medical, respectively; P = 0.038) and in patients ≥80 years of age (30.0% vs 21.8% for age ≥80 vs <80 years, respectively; P = 0.027). Conclusion Quality monitoring and interventions that consider human factors are required to address preventable in-patient deterioration. What is known about the topic? The ED represents the hospital's point of contact for potentially life-threatening conditions. Adverse event rates for emergency admissions are more than double those of non-emergency admissions. Patients are at particular risk of deterioration on discharge from the ED to the ward in the first 72 hours. Predicting which patients will deteriorate following transfer to the ward remains challenging, with care in the ED hypothesised to play a role. What does this paper add? This paper reveals that in-patient deterioration relating to ED care could be reduced through the routine identification of causal factors within a human factors framework in any patient deterioration event and subsequent evidence-informed interventions to address these factors. It is also extrapolated that the implementation of any intervention should be informed by behaviour-change principles. What are the implications for practitioners? It is implied that there is a need for the clarification and revision of policies and guidelines pertaining to the management of elderly patients, education regarding the critical importance of the often clinically masked vital sign deviations in younger patients and improved communication between staff, especially regarding patients with more comorbidities. Reviews of adverse events, such as patient deterioration, should incorporate a human factors analysis. Regular collation of data following adverse events should occur, with interventions considering all aspects of the factors that led to the event.

Cardiac contractile dysfunction, during and following ischaemia, is attenuated by low-dose dietary fish oil in rats.

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.

Heart rate variability during cardiovascular reflex testing: the importance of underlying heart rate.

OBJECTIVES: Heart rate variability (HRV) is often measured during clinical and experimental cardiovascular reflex tests (CRT), as a reflection of cardiac autonomic modulation, despite limited characterization of the rapid responses that occur. Therefore, we evaluated the responsiveness of HRV indices in 20 healthy young adults (age, 27 ± 6 y; mass, 76.9 ± 16.8 kg; height, 1.79 ± 0.12 m) during four separate established CRT. METHODS: These included the [I] orthostatic challenge, [II] isometric handgrip, [III] cold pressor and [IV] cold diving reflex tests. Electrocardiogram was recorded throughout, with HRV derived from RR intervals at rest and from each CRT. On a separate day, a subgroup of participants (n=9) completed the same protocol for a second time. RESULTS: The maximal slope of heart rate change (dTdt) was significantly different between all CRT, with the orthostatic challenge producing the fastest increase (2.56 ± 0.48) and the cold pressor the fastest reduction (-1.93 ± 0.68) in heart rate. Overall HRV, reflected by Poincaré plot ratio (SD1:SD2), was significantly reduced during all CRT ([I], -0.41 ± 0.12; [II], -0.19 ± 0.05; [III], -0.36 ± 0.12; [IV], -0.44 ± 0.11; p<0.05) relative to baseline and this was reproducible in time-series. However, when HRV indices were correlated to mean-RR an exponential growth-like relationship was evident (R2 ranging from: 0.52-0.62). CONCLUSIONS: These unique outcomes demonstrate that short-term alterations in HRV are evident during CRT, while indicating the importance of adjusting for, or at least reporting, underlying heart rate when interpreting such measures.

Forearm isometric fatigue-resistance is enhanced in rock climbers compared to power lifters and aerobically-trained athletes.

BACKGROUND: Rock climbers are characterized by enhanced forearm fatigue resistance. This study compared the forearm isometric force of rock climbers (RC), strength-matched power lifters (PL) and aerobically trained (AT) athletes to determine the contribution of muscle oxygen desaturation during ischemia. METHODS: Aerobically trained athletes (N.=6, 23±1 years, 77±1 kg), power lifters (N.=7, 24±1 years, 80±3 kg) and rock climbers (N.=8, 25±2 years, 74±2 kg) took part in a controlled forearm ischemic occlusion (5 min) assessment using near infrared spectroscopy. In addition, three fatigue protocols were completed: protocol 1, sustained maximal voluntary contraction (MVC) until exhaustion; protocol 2, sustained 40% MVC for 3 mins duration; protocol 3, an intermittent 40% MVC (5-s contraction, 5-s recovery) for a duration of 3 mins. Forearm contractile fatigue was quantified as the reduction in MVC. RESULTS: MVC was equivalent between groups (P>0.05). Sustained MVC force (time to decline 50% MVC) was longer in the RC versus AT (AT: 35±5, PL: 46±6, RC: 54±4 s, P<0.05) and both AT and PL for sustained 40% MVC (AT: 56±9, RT: 62±8, RC: 87±7 s, P<0.05). Reduction in MVC was less in RC post intermittent 40% contractions (P<0.05). Oxygen desaturation half-time was longer in the RC versus AT (AT: 65±9, RT: 86±7, RC: 99±7 s, P<0.05) and this was associated with time to 50% MVC (P<0.05, r2=0.53) and time to 40% MVC task failure (P<0.05, r2=0.32). CONCLUSIONS: Rock climbers' enhanced isometric fatigue-resistance and ability to maintain MVC was associated with a lower oxygen consumption of the forearm flexors during the ischemic state. This suggests a training adaptation involving intracellular oxygen consumption.

Cardiac Arrhythmia Prevention in Ischemia and Reperfusion by Low-Dose Dietary Fish Oil Supplementation in Rats.

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.

Marine n-3 Polyunsaturated Fatty Acids and the Risk of Ischemic Stroke.

Background and Purpose- We hypothesized that total marine n-3 polyunsaturated fatty acids (PUFA), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet and in adipose tissue (biomarkers of long-term intake and endogenous exposure) were inversely associated with the risk of ischemic stroke and its subtypes. Methods- The Diet, Cancer and Health cohort consisted of 57 053 participants aged 50 to 65 years at enrolment. All participants filled in a food frequency questionnaire and had an adipose tissue biopsy taken at baseline. Information on ischemic stroke during follow-up was obtained from The Danish National Patient Register, and all cases were validated. Cases and a random sample of 3203 subjects from the whole cohort had their fatty acid composition of adipose tissue determined by gas chromatography. Results- During 13.5 years of follow-up 1879 participants developed an ischemic stroke. Adipose tissue content of EPA was inversely associated with total ischemic stroke (hazard ratio [HR], 0.74; 95% CI, 0.62-0.88) when comparing the highest with the lowest quartile. Also, lower rates of large artery atherosclerosis were seen with higher intakes of total marine n-3 PUFA (HR, 0.69; 95% CI, 0.50-0.95), EPA (HR, 0.66; 95% CI, 0.48-0.91) and DHA (HR, 0.72; 95% CI, 0.53-0.99), and higher adipose tissue content of EPA (HR, 0.52; 95% CI, 0.36-0.76). Higher rates of cardioembolism were seen with higher intakes of total marine n-3 PUFA (HR, 2.50; 95% CI, 1.38-4.53) and DHA (HR, 2.12; 95% CI, 1.21-3.69) as well as with higher adipose tissue content of total marine n-3 PUFA (HR, 2.63; 95% CI, 1.33-5.19) and DHA (HR, 2.00; 95% CI, 1.04-3.84). The EPA content in adipose tissue was inversely associated with small-vessel occlusion (HR, 0.69; 95% CI, 0.55-0.88). Conclusions- EPA was associated with lower risks of most types of ischemic stroke, apart from cardioembolism, while inconsistent findings were observed for total marine n-3 PUFA and DHA.

Substitution of Fish for Red Meat or Poultry and Risk of Ischemic Stroke.

We investigated the risk of ischemic stroke and its subtypes when red meat or poultry was substituted with fish. A total of 57,053 participants aged 50⁻65 years at baseline were included in the Danish Diet, Cancer and Health study. All participants filled in a food-frequency questionnaire at recruitment. Potential ischemic stroke cases were identified by linkage to the Danish National Patient Register, and all cases were validated and subclassified. Substitutions were investigated as 150 g/week of fish for 150 g/week of red meat or of poultry using multivariable Cox proportional hazard regression models. During 13.5 years of follow-up, 1879 participants developed an ischemic stroke. Replacing red meat or poultry with fish was not associated with the rate of total ischemic stroke, but there was a statistically significant lower rate of large artery atherosclerosis when fish replaced processed (hazard ratio (HR): 0.78; 95% confidence interval (CI): 0.67; 0.90) and unprocessed (HR: 0.87; 95% CI: 0.75; 0.99) red meat. A statistically significant higher rate of cardioembolism was found when poultry was replaced by total fish (HR: 1.42; 95% CI: 1.04; 1.93). When fatty fish replaced unprocessed red meat, a statistically significant lower rate of small-vessel occlusion was found (HR: 0.88; 95% CI: 0.77; 0.99). In conclusion, replacing red meat with fish was not associated with risk of total ischemic stroke but was associated with a lower risk of subtypes of ischemic stroke.

Telemedicine in remote Australia: The Royal Flying Doctor Service (RFDS) Medical Chest Program as a marker of remote health.

INTRODUCTION: Remote communities across Australia lack the ready access to medical care generally afforded to metropolitan populations. The Royal Flying Doctor Service (RFDS) medical chest program provides medical resources to these communities allowing medications to be dispensed in conjunction with a telehealth consulting service. More than 3000 medical chests are located throughout Australia and each year the Queensland RFDS conducts approximately 20 000 telehealth consultations. The aim of this study was to review the use of the medical chest model within the state of Queensland and to analyse changes in the medical chest program from 10 years earlier to evaluate the changing healthcare needs of remote Australian populations. METHODS: All telehealth consultations and items dispensed from the medical chests were reviewed over a 1-year period from 1 July 2013 and 30 June 2014. Items dispensed were categorised and compared to those in 2005-06 in absolute terms by one-way ANOVA and proportionately by χ2 with Fisher's exact test. Consultations using the medical chest were categorised and compared to those in 2005-06 by χ2 with Fisher's exact test. RESULTS: The number of telehealth consultations conducted in 2013-14 (N=20 707) was not different to the number conducted in 2005-06 (N=21 470). Fewer items were dispensed from the medical chests in 2013-14 (3936 total items) than in 2005-06 (8607 total items; p<0.0001). In the specific categories of 'burns and other dressings' and 'antihistamines', the number of individual items dispensed increased. Resources from the medical chest were used more for genitourinary system consultations and less for consultations involving specific infectious diseases; the circulation, respiratory and abdominal systems; skin diseases; injury; symptoms without a diagnosis; and following other contact with a health service. CONCLUSIONS: The medical chests remain a vital tool for medical care of remote populations and the need for telehealth medical advice remains unchanged, although fewer items are being dispensed. The use of the medical chest for each diagnostic category of consultation has shown some variation over the past 10 years, reflective of changing patterns of accident, injury and disease.

DHA-rich Fish Oil Increases the Omega-3 Index and Lowers the Oxygen Cost of Physiologically Stressful Cycling in Trained Individuals.

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 × 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 × 6s), isometric quadriceps strength (MVC), Wingate cycling protocol (6 × 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: Pre 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.

Dietary fish oil delays hypoxic skeletal muscle fatigue and enhances caffeine-stimulated contractile recovery in the rat in vivo hindlimb.

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.

A Small Cohort Omega-3 PUFA Supplement Study: Implications of Stratifying According to Lipid Membrane Incorporation in Cardiac Surgical Patients.

BACKGROUND: Epidemiological studies and randomised clinical trials (RCTs) report disparate findings in relation to omega-3 polyunsaturated fatty acids (n-3 PUFA) benefit for cardiac patients. With RCTs interpretation is potentially confounded by background n-3 PUFA intake. The goal of this pilot, small cohort, pre-surgical supplementation study was to evaluate postoperative atrial fibrillation (AF) and cardiac molecular expression profiles employing two data analysis approaches - by treatment randomisation and by stratification using measured n-3 PUFA. METHODS: Patients (n=20) received 3g/day of fish or placebo oil (FO vs PO) in a double blind randomised protocol prior to elective coronary artery graft and valve surgery. Groups were matched for age, gender, and mean treatment duration (∼20 days). Resected atrial myocardium was sampled for assay of viability metabolic markers, and blood obtained for erythrocyte membrane lipid measurement. RESULTS: There was substantial overlap of cell membrane n-3 PUFA content across PO and FO groups, and no group treatment effects on AF incidence or myocardial molecular marker levels were detected. In contrast, data stratification using membrane n-3 PUFA content (at 8% total membrane lipid) achieved significant separation of patients (by n-6:n-3 PUFA ratio), a significant differential cardiac expression of the marker peroxisomal proliferator-activated receptor, but no difference in AF incidence. CONCLUSIONS: This small n-3 PUFA case study demonstrates that the same cohort may yield differing findings when evaluated using randomisation or stratification approaches based on direct molecular measures in cell membranes.

'Involve Me and I Learn': Development of an Assessment Program for Research and Critical Analysis.

Evidence-based medical practice is best achieved by developing research understanding in medical practitioners. To this end, medical councils worldwide increasingly recognise the importance of medical schools graduating students with well-developed research skills and research capacity. To meet this need, the principles of programmatic assessment were implemented in designing a research and critical analysis curriculum and assessment program that aimed to enhance the research and critical analysis skills of medical students. The program was developed by mapping assessment tasks to a research capabilities framework that was in turn scaffolded to different levels of Miler's pyramid. The curriculum and assessments were integrated with the science, clinical, and professional aspects of the medical course. The progressive longitudinal development of research skills, with feedback and academic mentoring, culminated in the students' capacity to undertake an independent research project. Designing an assessment program for learning encouraged students to develop their research capacity by involving them in their learning.

Dietary omega-6 fatty acid replacement selectively impairs cardiac functional recovery after ischemia in female (but not male) rats.

A definitive understanding of the role of dietary lipids in determining cardioprotection (or cardiodetriment) has been elusive. Randomized trial findings have been variable and sex specificity of dietary interventions has not been determined. In this investigation the sex-selective cardiac functional effects of three diets enriched by omega-3 or omega-6 polyunsaturated fatty acids (PUFA) or enriched to an equivalent extent in saturated fatty acid components were examined in rats after an 8-wk treatment period. In females the myocardial membrane omega-6:omega-3 PUFA ratio was twofold higher than males in the omega-6 diet replacement group. In diets specified to be high in omega-3 PUFA or in saturated fat, this sex difference was not apparent. Isolated cardiomyocyte and heart Langendorff perfusion experiments were performed, and molecular measures of cell viability were assessed. Under basal conditions the contractile performance of omega-6 fed female cardiomyocytes and hearts was reduced compared with males. Omega-6 fed females exhibited impaired systolic resilience after ischemic insult. This response was associated with increased postischemia necrotic cell damage evaluated by coronary lactate dehydrogenase during reperfusion in omega-6 fed females. Cardiac and myocyte functional parameters were not different between omega-3 and saturated fat dietary groups and within these groups there were no discernible sex differences. Our data provide evidence at both the cardiac and cardiomyocyte levels that dietary saturated fatty acid intake replacement with an omega-6 (but not omega-3) enriched diet has selective adverse cardiac effect in females. This finding has potential relevance in relation to women, cardiac risk, and dietary management.

Up-Regulation of Mitochondrial Antioxidant Superoxide Dismutase Underpins Persistent Cardiac Nutritional-Preconditioning by Long Chain n-3 Polyunsaturated Fatty Acids in the Rat.

Reactive oxygen species paradoxically underpin both ischaemia/reperfusion (I/R) damage and ischaemic preconditioning (IPC) cardioprotection. Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are highly susceptible to peroxidation, but are paradoxically cardioprotective. This study tested the hypothesis that LCn-3 PUFA cardioprotection is underpinned by peroxidation, upregulating antioxidant activity to reduce I/R-induced lipid oxidation, and the mechanisms of this nutritional preconditioning contrast to mechanisms of IPC. Rats were fed: fish oil (LCn-3 PUFA); sunflower seed oil (n-6 PUFA); or beef tallow (saturated fat, SF) enriched diets for six weeks. Isolated hearts were subject to: 180 min normoxic perfusion; a 30 min coronary occlusion ischaemia protocol then 120 min normoxic reperfusion; or a 3 × 5 min global IPC protocol, 30 min ischaemia, then reperfusion. Dietary LCn-3 PUFA raised basal: membrane docosahexaenoic acid (22:6n-3 DHA); fatty acid peroxidisability index; concentrations of lipid oxidation products; and superoxide dismutase (MnSOD) activity (but not CuZnSOD or glutathione peroxidase). Infarct size correlated inversely with basal MnSOD activity (r² = 0.85) in the ischaemia protocol and positively with I/R-induced lipid oxidation (lipid hydroperoxides (LPO), r² = 0.475; malondialdehyde (MDA), r² = 0.583) across ischaemia and IPC protocols. While both dietary fish oil and IPC infarct-reduction were associated with reduced I/R-induced lipid oxidation, fish oil produced nutritional preconditioning by prior LCn-3 PUFA incorporation and increased peroxidisability leading to up-regulated mitochondrial SOD antioxidant activity.

Intrinsic heart rate recovery after dynamic exercise is improved with an increased omega-3 index in healthy males.

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.