Fish Oil Literature Review

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1 Fish Oil Technical Document November 2013 Fish Oils Technical Document Developed by INDI/SNIG for the Irish Sports Council 2013

2 Fish Oil Technical Document November 2013 Fish Oil Pubmed (Medline), SPORTDiscus and the Cochrane Library were searched for all human studies published in peer reviewed journals in the last 5 years. The terms: fish oils, fish oils AND exercise and fish AND exercise were used as key terms in all databases. Inclusion criteria Human studies published in English Original investigations assessing the use of fish oils and exercise Incorporated the use of an indistinguishable placebo Exclusion Criteria Studies assessing fish consumption Studies assessing the effect of fish consumption in diseased populations Qualitative studies assessing supplement use in both the general and athletic population After title and abstract review, seven original articles that assessed the use of fish oils and exercise were retrieved for review. Introduction Fish oils are made up of the long chained omega-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are synthesized from -linolenic acid and are found in the tissue of oily fish such as mackerel, sardines, herring, salmon, trout, tuna and mullet (Ruxton et al. 2004). Over time the consumption of omega-3 and omega-6 fatty acids by humans has changed substantially. Sources of omega-6 fatty acids include polyunsaturated oils - sunflower, safflower, soybean, corn and grape-seed oil, polyunsaturated margarines, nuts - brazil, walnuts, and seeds sunflower and safflower. Humans, thousands of years ago, probably consumed omega-3 to omega-6 fatty acids in a ratio of 1:1 to 1:2. Today, humans consume approximately 20-25 times more omega-6 fatty acids compared to omega-3 fatty acids. This dramatic increase in omega-6 fatty acids, from studies, is associated with an increase of proinflammatory markers (leukotrienes and prostanoids) which can cause an increase in blood thickness, blood vessel spasm, and blood vessel constriction, and decreases in bleeding time in humans (Mickleborough and Rundell 2005, Simopoulos 2007).

3 Fish Oil Technical Document November 2013 Omega-3 fatty acids possess anti-inflammatory properties along with antithrombotic, antiarrhythmic, hypolipidaemic, and vasodilatory properties (Ruxton et al. 2004). The anti-inflammatory effects appear to have a direct action on immune function through neutrophil and monocyte production of mediators, chemotactic responses, and the production of cytokines (Helenius et al. 2005). The health benefits of consuming oily fish or fish oil supplements There is a substantial amount of scientific literature demonstrating the cardiovascular benefits of regular consumption of oily fish or fish oil supplements, and their constituent omega-3 PUFA. Interest in the cardio- protective effects of consuming omega-3 fatty acids has focused around decreasing triglycerides (Harris et al. 1988, Harris et al 1997, Conner 2000, Thomas et al. 2007, Waite et al. 2008, Sadovsky et al. 2009), decreasing low density lipoprotein cholesterol (Sadovsky et al. 2009, Barter and Ginsberg 2008), decreasing blood pressure (Waite et al. 2008, Morris et al. 1993, Mori 2006), increasing high density lipoprotein cholesterol (Thomas et al. 2007); decreasing resting heart rate (Mozaffarian et al. 2005, OKeefe et al. 2006) and improving blood flow (Khan et al. 2003, Walser et al. 2006, Walser et al. 2008). The consumption of omega-3 fatty acids has also demonstrated positive outcomes for the secondary prevention of cardiovascular disease. The GISSI study (1999), the largest study involving over 11 000 subjects who had suffered acute myocardial infarction, demonstrated that subjects ingesting omega-3 PUFA supplements had a significant reduction in cardiac events over the 3.5 years in which they were observed (GISSI 1999). Apart from cardiovascular disease, favourable effects on other health conditions, such as decreasing the risk of psychiatric disorders (Jacka et al. 2004, Peet and Stokes 2005), increasing insulin sensitivity (Waite et al. 2008), decreasing the risk of metabolic syndrome (Watts et al. 2006), improving brain development (Uauy and Dangour 2006) and decreasing chronic pain in joints and the spine (Cleland et al. 2003) have been reported. A comprehensive review of the health effects of omega-3 fatty acid consumption has been published by Ruxton et al. (2004). There is emerging evidence that the consumption of oily fish or fish oil supplements can aid in the treatment of some inflammatory conditions such as rheumatoid arthritis, Crohns disease, ulcerative colitis, psoriasis, asthma, lupus and cystic fibrosis (Ruxton et al. 2004, Mickleborough et al. 2005, Cleland et al. 2009). However, to-date the scientific evidence for these inflammatory diseases is not conclusive and more research is required before conclusions can be drawn.

4 Fish Oil Technical Document November 2013 The athletic benefits of consuming oily fish or fish oil supplements Studies on athletic populations have demonstrated some cardiovascular benefits including: improved stroke volume and cardiac output (Walser et al. 2008), increased rate of fat oxidation while exercising (Huffman et al. 2004), and decreased heart rate during exercise (Peoples et al. 2008, Ninio et al. 2008). A recent study found no effect of an acute DHA or EPA enriched meal on cardiac output or stroke volume during exercise (Rantoyanni et al. 2012). Rantoyanni et als (2012) study indicated a DHA enriched meal promoted greater vasodilation during exercise compared to an EPA meal. Cardiopulmonary benefits, pulmonary function tests (Tartibian et al. 2010) and reduced symptoms of exercise-induced bronchoconstriction (Mickleborough et al. 2005, Mickleborough et al. 2006), have been documented in the literature. There is no conclusive evidence that consuming fish oils will enhance athletic performance. One study has indicated improved complex reaction time and efficiency time after 12 weeks of omega-3 fatty acid supplements (Guzman et al. 2011). In contrast, other studies have found no change in energy metabolism (Bortolotti et al. 2007), no effect on endurance performance (Oostenbrug et al. 1997), and no performance benefits (Raastad et al. 1997, Buckley et al. 2009) after omega-3 fatty acid supplementation. A summary of these studies can be seen in Table 1. Fish Oil consumption and muscle atrophy There is new evidence, although rather limited, to suggest that fish oil supplementation can help reduce muscle atrophy. A study, carried out by Smith and colleagues (2011), found that fish oil -derived omega 3 fatty acid supplementation stimulated muscle protein synthesis in older adults. Interestingly, recent animal studies have demonstrated that dietary supplementation of fish oils may alleviate muscle loss during immobilization (You et al. 2010, Yulan et al. 2013). These intriguing results propose relevant application of fish oil supplements in immobilised injured athletes; however, more studies using human populations are warranted for this to be more plausible. Safety concerns with fish oil consumption Fish oil supplementation does not appear to induce any clinically significant side effects, with the majority of research not reporting any adverse effects at all. Some adverse effects from consuming fish oil supplements may include a fishy aftertaste, gastrointestinal disturbances, and nausea (Kris-Etherton et al, 2002, Peet et al. 2006). Other side effects may include excessive bleeding in some individuals when fish oils supplementation is greater than 3 g of EPA and DHA (Kris-Etherton et al. 2002). Though Fish oil has not been implicated in serious adverse drug interactions, individuals with pre-existing haemorrhagic disorders

5 Fish Oil Technical Document November 2013 or those on anticoagulant treatment should seek medical advice before supplementation (Peet et al. 2006, Cleland et al. 2009). It has been deemed by the American Food and Drug Administration that fish oil supplementation up to 3g per day is generally recognised as safe for inclusion in the human diet (Kris- Etherton et al. 2002). Conclusion It is clear that omega-3 fatty acids can play an important role in the general health of the human population. These omega-3 fatty acids can be obtained from consuming oily fish, or as fish oil supplements. Though there has yet to be any research identifying a direct impact of fish oil consumption on athletic performance, indirect markers such as increases in blood flow, increased stroke volume and cardiac output, and possible increased fat oxidation during exercise are positive starting points for future research into fish oil supplementation and exercise performance. It can therefore be recommended that oily fish or fish oils be consumed for cardiovascular benefits, but not as a means for directly enhancing athletic performance.

6 Fish Oil Technical Document November 2013 Table 1 Summary of fish oil literature Reference Subjects Dose Exercise Protocol Performance Summary Enhancement Oostenbrug 24 well trained 3 weeks of FO supplementation Wmax (peak power output) and No FO did not improve endurance et al. 1997 male cyclists (6 g/day), without or with endurance cycling tests completed performance, change antioxidant vitamin E (300 IU/day) before and after supplementation. levels or LDL oxidation during Time to complete the endurance exercise. exercise test was the primary outcome measure and was completed at 70% of the pre-determined peak power output from the Wmax. Raastad et 28 well trained 10 weeks of supplementation All subjects maintained their normal No This study does not support the al. 1997 male soccer with either 5.2 g of a diet and training regimes. Maximal hypothesis that endurance players concentrated FO enriched in aerobic power, anaerobic power and athletes can improve maximal omega-3 fatty acids (1.60 running performance were the aerobic performance by omega 3- g/day EPA and 1.04 g/ day primary outcome measures. fatty acid supplementation. DHA) or 5.2 g corn oil (serving as placebo) Huffman et 7 recreationally The FO supplement Running for 60 min at 60 % Not assessed This study suggests that chronic, al. 2004 active males contained 60 % EPA, and 40 VO2max in each of the three trials. but not acute FO % DHA. Subjects Indirect calorimetry was used to supplementation enhanced the supplemented 4 g/day of FO assess oxygen consumption, contribution of lipid during for a total of 5 weeks. After 3 respiratory exchange ratio, and exercise in young active males. weeks subjects completed 3 energy expenditure from fat and exercise trials after: No meal, carbohydrate. Heart rate and rating of 4 h following a high-fat meal, perceived exertion was also assessed. or 4 h following an isocaloric high fat meal partly substituted with FO. Bortolotti et Eight healthy 7.2 g/day FO (including Energy metabolism (substrate Not assessed FO supplementation did not al. 2007 male 1.1 g/day EPA and 0.7 g/day oxidation, energy expenditure and significantly alter energy DHA) for 14 days energy efficiency) was assessed metabolism and energy efficiency during a 30 min cycling exercise at during exercise in healthy 50% VO2 max. humans.

7 Fish Oil Technical Document November 2013 Peoples et 16 well-trained 8 x 1 g capsules per day of Subjects used an electronically braked No This study reported that FO may al. 2008 male cyclists olive oil (control) or FO for 8 cycle ergometer to complete VO2 peak reduce both whole-body and weeks and sustained submaximal exercise myocardial O2 demand during tests at 55% of peak workload before exercise, without a decrement in and after supplementation. performance through lower heart rate and rate pressure product identified during the exercise tests. Walser et al. 14 healthy DHA (2 g/day) + EPA (3 20 min of cycling (10 min each at a Not assessed An increase in stroke volume and 2008 males and 7 g/day) or safflower oil for 42 low and moderate work intensity) cardiac output was seen with FO healthy females days. before and after supplementation, supplementation. This may lead with mean arterial pressure, heart to increase in oxygen delivery rate, stroke volume, cardiac output during exercise. and systemic vascular resistance assessed before exercise and during both workloads. Buckley et 25 elite male 6g/day of DHA-rich FO or Treadmill running to was assessed No Five weeks of FO al. 2009 Australian sunflower oil for 5 weeks before and after 5 weeks of team supplementation improved football players training. Erythrocyte omega-3 cardiovascular function and content, resting blood pressure, reduced cardiovascular vascular fasting serum triglycerides and heart risk factors, but did not improve rate were assessed before and after. endurance performance or recovery. Guzman et 24 elite female 3.5 g/day of DHA or olive oil Complex reaction efficiency, time and Yes Four weeks of FO al. 2011 soccer players for 4 weeks precision were assessed pre and post supplementation decreased treatment using a computerized task complex reaction time and named multiple reaction time efficiency. Tarbitan et 40 amateur 1 g /day of DHA or a Spirometry using an automated Not assessed 12 weeks of FO supplements and al. wrestlers placebo capsule for 12 weeks analyser was used before and after 12 intensive wrestling training and weeks of wrestling training to assess consumption improved FEV1, the following pulmonary variables: FIV1, MVV, FVC and FEF2575 forced expiratory volume in one however, no significant changes second (FEV1), forced vital capacity were observed in FEV1% and

8 Fish Oil Technical Document November 2013 (FVC), forced inspiratory volume in FIV1% one second (FIV1), maximal voluntary ventilation (MVV), vital capacity (VC), forced expiratory flow from 25% to 75% (FEF2575), percentage of forced expiratory volume in one second (FEV1%) and percentage of forced inspiratory (FEV1%) Rontayanni 22 healthy male 4.7 g FO or sunflower oil in a Cardiac Output, blood pressure, mean Not assessed DHA enriched meal led to an et al. 2012 subjects high fat meal arterial pressure and heart rate were attenuated increase in MAP and a measured at fasting, 5 h post-prandial reduced SVR, at 5h and during rest, during 12 min multi-stage exercise, indicated improved exercise stress test of moderate vasodilation over EHA or intensity cycling and during 45 min sunflower enriched meal. post exercise. Systemic vascular reaction (SVR) was calculated from collected data.

9 Fish Oil Technical Document November 2013 References Barter P and Ginsbery HN. Effectiveness of combined statin plus omega-3 fatty acid therapy for mixed dyslipidemia. Am J Cardiol. (2008) 15; 102 (8):1040-5. Bortolotti M, Tappy L, Schneiter P. Fish oil supplementation does not alter energy efficiency in healthy males. Clin Nutr. 2007 Apr;26(2):225-30. Buckley JD, Burgess S, Murphy KJ, Howe PR. DHA-rich fish oil lowers heart rate during submaximal exercise in elite Australian Rules footballers. J Sci Med Sport. 2009 Jul;12(4):503-507. Cleland L, James M, Proudman S. (2003) The role of fish oils in the treatment of rheumatoid arthritis. Drugs 63, 845853. Conner WE. Importance of n-3 fatty acids in health and disease. Am J Clin Nutr 2000;71: 171S-5. GISSI (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nellInfarto miocardico. Lancet 354, 447455. Guzman JF, Esteve H, Pablos C, Pablos A, Blasco C, Villegas JA. (2011) DHA rich fish oil improves complex reaction time in female elite soccer players. J Sports Sci Med 10, 301-305. . Harris WS, Conner WE, Alam N, Illingsworth DR. Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids. J Lipid Res 1988;29:1451-60. Harris WS. Omega-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 Suppl):1645S1654S Helenius I, Lumme A, Haahtela T. Asthma, airway inflammation and treatment in elite athletes. Sports Med. 2005;35(7):565-74. Jacka FN, Pasco JA , Henry MJ, Kotowicz MA, Nicholson GC, Berk M. Dietary Omega-3 Fatty Acids and Depression in a Community Sample. Nutritional Neuroscience, Volume 7 Number 2 (April 2004), pp. 101106. Khan F, Elherik K, Bolton-Smith C, Barr R, Hill A, Murrie I et al (2003) The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects. Cardiovasc Res 59:955962.

10 Fish Oil Technical Document November 2013 Kris-Etherton PM, Harris WS, Appel LJ. (2002): Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 106, 27472757. Mickleborough TD, Rundell KW. Dietary polyunsaturated fatty acids in asthma- and exercise-induced bronchoconstriction. Eur J Clin Nutr. 2005 Dec;59(12):1335- 46. Mickleborough TD, Lindley MR, Ionescu AA, Fly AD. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest. 2006 Jan;129(1):39-49. Mori TA. Omega -3 fatty acids and hypertension in humans. Clinical and Experimental Pharmacology and Physiology (2006) 33, 842846. Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta- analysis of controlled trials. Circulation. 1993;88:523533. Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB (2005) Effect of Fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation 112:19451952. Ninio DM, Hill AM, Howe PR, Buckley JD, Saint DA. Docosahexaenoic acid-rich fish oil improves heart rate variability and heart rate responses to exercise in overweight adults. Br J Nutr. 2008 Nov;100(5):1097-103. OKeefe JH Jr, Abuissa H, Sastre A, Steinhaus DM, Harris WS. (2006) Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions. Am J Cardiol 97:11271130 Oostenbrug GS, Mensink RP, Hardeman MR, De Vries T, Brouns F, Hornstra G. Exercise performance, red blood cell deformability, and lipid peroxidation: effects of fish oil and vitamin E. J. Appl. Physiol. 83(3):746752, 1997. Peet M, Stokes C. Omega-3 Fatty Acids in the Treatment of Psychiatric Disorders. Drugs 2005; 65 (8): 1051-1059. Peoples GE, McLennan PL, Howe PR, Groeller H. Fish oil reduces heart rate and oxygen consumption during exercise. J Cardiovasc Pharmacol. 2008 Dec;52(6):540-7. Raastad T, Hostmark AT, Stromme SB. Omega-3 fatty acid supplementation does not improve maximal aerobic power, anaerobic threshold and running

11 Fish Oil Technical Document November 2013 performance in well-trained soccer players. Scand J Med Sci Sports. 1997 Feb;7(1):25-31 Rontoyanni VG, Hall WL, Pombo-Rodrigues S, Appleton A, Chung R, Sanders TAB (2012). A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA. 3, 108, 492-499. Ruxton, CHS, Reed SC, Simpson MJA, Millington KJ. The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. J Hum Nutr Dietet, (2004) 17, pp. 449459. Simopoulos AP. Omega-3 Fatty Acids and Athletics. Current Sports Medicine Reports 2007, 6:230-236. Sadovsky R, Kris-Etherton P. Prescription omega-3-Acid Ethyl Esters for the treatment of Very High Triglycerides. Postgraduate Medicine, Volume 121, Issue 4, July 2009. Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 2011;93:40212. Tartibian B, Maleki BH, Abbasi A (2010) The effect of omega-3 supplementation on pulmonary function of young wrestlers during intensive training. J Sci Med. 13, 281-286. Thomas TR. Liu, Y. Linden, MA. Rector, RS. Interaction of exercise training and n-3 fatty acid supplementation on postprandial lipemia. Appl. Physiol. Nutr. Metab. 32: 473480 (2007). You JS, Park MN, Song W, Lee YS, Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats. Applied Physiology, Nutrition & Metabolism Jun2010, Vol. 35 Issue 3, p310 8p Yulan L, Chen F, Odle J, Lin X, Zhu H, Shi H, Hou Y, Yin J. Fish Oil Increases Muscle Protein Mass and Modulates Akt/FOXO, TLR4, and NOD Signaling in Weaning Piglets After LPS Challenge..Nutr. 2013 jn.113.176255; first published online June 5, 2013.

12 Fish Oil Technical Document November 2013 Waite N, Lodge J, Robertson MD, Badley E, Burton S, Hart K. Do fish-oil supplements affect insulin sensitivity? A pilot intervention study. J Hum Nutr Diet, 2008, 21, pp. 280289. Walser B, Giordano RM, Stebbins CL (2006) Supplementation with omega-3 polyunsaturated fatty acids augments brachial artery dilation and blood flow during forearm contraction. Eur J Appl Physiol 97:347354 Walser B, Stebbins CL. Omega-3 fatty acid supplementation enhances stroke volume and cardiac output during dynamic exercise. Eur J Appl Physiol (2008) 104:455461. Uauy R, Dangour AD. Nutrition in Brain Development and Ageing: Role of Essential Fatty Acids. Nutrition Reviews, Vol. 64, No. 5.

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