A key hallmark of aging is a progressive loss of muscle mass, which occurs independently of health status. Exercise and nutrition are the two main anabolic stimuli for muscle growth and its maintenance throughout the life course.[2-11]
It is clear that maintaining high physical activity and exercise levels throughout ones lifespan reduces aging related loss of muscle mass and function, compared with living a sedentary life.[12-19] However, even active older adults and master elite athletes still experience some loss of muscle and physical performance with advancing age.[8, 13, 20]
When it comes to nutrition, high protein intake [2, 3, 10, 21] and creatine supplementation [4-8, 22] are two of the best documented interventions, which together with resistance exercise training, result in greater increases muscle mass and strength in both young [21-23] and older people [2-8, 10], and prevent its loss with aging. Here I will present the relatively unknown effects of fish oil (most well-known for its cardiovascular health promoting effects) on muscle growth (anabolism) and its possible contribution to prevention of aging related loss of muscle mass and function..
Increased Muscle Growth with Fish Oil
Several studies therefore directly investigated the effect of fish oil on metabolic pathways that underlie muscle growth, with very interesting findings….
Supplementing healthy young and middle-aged (25-45 year old) men and women with 4 g per day of fish oil concentrate – providing a daily dose of 1.86 g EPA and 1.5 g DHA – for 8 weeks was found to significantly increase the anabolic response of muscle protein synthesis to amino acids and insulin. The augmented anabolic response to amino acids and insulin was shown to be due to an increased activation of the mTOR/p70S6K signaling pathway, which is considered an integral control point for muscle protein anabolism  and muscle cell growth.[26-29]
Other mechanisms probably contribute as well. The same study showed that the fish oil supplementation doubled the proportion of EPA, DPA (another less well known omega-3 fatty acid) and DHA in muscle cell membranes, at the expense of omega-6 fatty acids and mono-unsaturated fatty acids, with no change in saturated fatty acid concentrations. Thus, it is possible that fish oil supplementation may influence anabolic signaling cascades by affecting membrane lipid composition and/or fluidity.[30-33]
Fish oil supplementation also confers muscle anabolic effects in the elderly. The same research team conducted another study, using an identical research protocol (1.86 g EPA and 1.5 g DHA for 8 weeks), in healthy elderly subjects over 65 years (mean age 71 years). The results were the same as in the younger subjects ; fish oil supplementation significantly increased the muscle protein synthetic response to amino acids and insulin. Thus, fish oil seems to attenuate the anabolic resistance to protein intake that develops with aging.[35-37] The researchers were so impressed with this response that they concluded high dose fish oil may be useful for both prevention and treatment of sarcopenia. Support for this comes from a study specifically demonstrating that fish oil increases anabolic signaling in aged muscles.
Both of these studies only measured the response of muscle protein synthesis to amino acids and insulin.[24, 34] Muscle mass, which is the result of a net positive muscle protein balance over a longer time period (at least 6 months), was not measured because the interventions lasted for only 8 weeks. However, taking into consideration that changes in muscle protein metabolism precede corresponding changes in muscle mass [39-41], these results are very promising.
Indeed, recently longer term outcomes of the fish oil supplementation study in elderly were published. Compared with the placebo group (which were given identical soft gels containing corn oil), supplementing healthy elderly subjects with 1.86 g EPA and 1.5 g DHA for 6 months significantly increased thigh muscle volume by 3.6%, handgrip strength by 2.3 kg (5.1 lb), 1-RM muscle strength by 4.0%. There was also a trending increase in power output by 5.6% in the fish oil group.
The difference in muscle volume between the fish oil and the placebo group at 6 mo was +3.5%, and the difference in overall muscle strength was +6%. This suggests that 6 month of fish oil supplementation can prevent 2-3 years of normal age-related losses in muscle mass (0.5–1.0%/year) and function (w2–3%/year).[43-46] Thus, it was concluded that the fish oil fatty acids EPA and DHA may slow the common age-related decline in muscle mass and function in older adults, and that fish oil should be considered a therapeutic approach for preventing sarcopenia and maintaining physical independence in older adults.
Decreased Muscle Breakdown with Fish Oil
Another way that fish oil can promote muscle growth is by exerting anti-catabolic effects. Muscle growth occurs during periods of positive net muscle protein balance, that is, when muscle protein synthesis exceeds muscle protein breakdown. Muscle proteins undergo a continuous process of synthesis (anabolism) and breakdown (catabolism). In a healthy state, the anabolic and catabolic processes are balanced to maintain stability, or an increase muscle mass (as is observed with resistance training combined with proper nutrition and supplementation).
Catabolism of muscle tissue is common in both clinical states (for example diabetes, renal failure, trauma and cancer) and during dieting and other stress conditions [47-52]. During these catabolic states, muscle protein degradation (catabolism) exceeds muscle protein synthesis (anabolism), which results in muscle loss and weakness.
Muscle protein catabolism is primarily caused by the ubiquitin-proteasome system [49, 52-57]. It is here fish oil enters the picture, since its fatty acid EPA significantly decreases the activity of the muscle protein catabolic (ubiquitin-proteasome) system.[48, 50, 51, 58-62]
An additional mechanism by which fish oil may exert its anti-catabolic effect is by reducing cortisol levels.[63, 64] Cortisol breaks down muscle tissue  and contributes a host of other detrimental health effects when present at chronically elevated levels (which is a topic for another article).[66-68] Thus, the cortisol lowering is a beneficial effect of fish oil beyond anti-catabolism.
Does the greater muscle anabolism and reduced catabolism translate into physical performance enhancement?
When it comes to prevention of muscle loss with aging, a paramount question is whether the beneficial muscle anabolic and anti-catabolic effects seen in short term studies translate into physical performance enhancement? Several long-term studies show promising effects.
One study in postmenopausal women found long-term (6 months) fish oil supplementation (providing 1.2g EPA + DHA]) to improve physical performance indices (such as walking speed) compared to placebo (olive oil). Moreover, during a 90-day resistance exercise training program in older women, the consumption of fish oil supplements (2 g per day) resulted in greater gains in muscle strength and functional capacity when compared with a placebo. And as outlined above, long term fish oil supplementation increases not only thigh muscle volume, but also muscle strength as well as power output.
More and more studies show that the anabolic effects of nutrients (e.g. amino acids or proteins), hormones (e.g. insulin, testosterone) and/or exercise on muscle can be enhanced by long-term fish oil supplementation. A recent review of the research literature concluded that long-term fish oil supplementation, in association with anabolic stimuli like exercise and proper nutrition, could potentially provide a safe, simple and low-cost intervention to counteract anabolic resistance and aging related loss of muscle mass, strength and performance.
In a previous article “Muscles – not just for bodybuilders!” I explained that, contrary to mainstream attitudes, muscles aren’t just for show. Your muscle mass contributes to your physical and metabolic health, which in turn paves the way for multiple health benefits.
Research shows that fish oil supplementation in both young and older adults increases muscle protein synthesis in response to anabolic stimuli like exercise and protein intake, and over time increases both muscle mass, strength and power output. It is indeed impressive that 6 month of fish oil supplementation in people who have passed their middle-age can prevent 2-3 years of normal age-related losses in muscle mass and function.
Aim for a daily fish oil intake that provides at least 1900 mg (1.9 g) EPA and 1500 mg (1.5 g) DHA. Ideally, strive to get at minimum about 4000 mg (4 g) EPA + DHA combined. At of this writing, there is not enough research data to make precise recommendations on any specific EPA-to-DHA ratio for muscle growth.
Remember to read the labels as different fish oil products provide different amounts of EPA and DHA. Don’t buy low quality fish oil products that do not specify the content of EPA and DHA individually. Look for a fish oil concentrate that provides over 50% EPA and DHA of the total fat content.
By adding fish oil supplementation to your daily regimen you will not only reap the muscle related benefits, but also a range of other health benefits (which I will cover individually in upcoming articles):
* Increased fat burning and fat loss.[64, 72-78] This, together with stimulation of muscle anabolism and reduction of muscle catabolism, will contribute to improvement of body composition and related health parameters.
* Improved brain function, cognitive performance (reaction time and memory), and prevention of dementia.[79-89]
* Multifaceted anti-inflammatory protection.[90-100]
* Cardiovascular health promotion and prevention of heart disease [101-108] and the metabolic syndrome.
For more info on how fish oil may help you get in shape, see my other article “Fish Oil for Fat Loss”
About Monica Mollica >
Monica Mollica holds a Master degree in Nutrition from the University of Stockholm / Karolinska Institue, Sweden. She has also done PhD level course work at renowned Baylor University, TX.
Having lost her father in a lifestyle induced heart attack at an age of 48, she is specializing in cardiovascular health and primordial/primary prevention. She is a strong advocate of early intervention in adolescence and young adulthood, and the importance of lifestyle habits for health promotion at all ages.
Today, Monica is sharing her solid medical research insights and real-life hands on experience and passion by offering nutrition / supplementation / exercise / health consultation services, and working as a medical writer, specializing in health promotion, fitness and anti-aging.
She is currently in the process of writing a book on testosterone, covering health related issues for both men and women.
1. Evans, W.J., What is sarcopenia? J Gerontol A Biol Sci Med Sci, 1995. 50 Spec No: p. 5-8.
2. Breen, L. and S.M. Phillips, Skeletal muscle protein metabolism in the elderly: Interventions to counteract the ‘anabolic resistance’ of ageing. Nutr Metab (Lond), 2011. 8: p. 68.
3. Wall, B.T., N.M. Cermak, and L.J. van Loon, Dietary protein considerations to support active aging. Sports Med, 2014. 44 Suppl 2: p. S185-94.
4. Brose, A., G. Parise, and M.A. Tarnopolsky, Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J Gerontol A Biol Sci Med Sci, 2003. 58(1): p. 11-9.
5. Dalbo, V.J., et al., The effects of age on skeletal muscle and the phosphocreatine energy system: can creatine supplementation help older adults. Dyn Med, 2009. 8: p. 6.
6. Gotshalk, L.A., et al., Creatine supplementation improves muscular performance in older women. Eur J Appl Physiol, 2008. 102(2): p. 223-31.
7. Gotshalk, L.A., et al., Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc, 2002. 34(3): p. 537-43.
8. Candow, D.G., Sarcopenia: current theories and the potential beneficial effect of creatine application strategies. Biogerontology, 2011. 12(4): p. 273-81.
9. Robinson, S., C. Cooper, and A. Aihie Sayer, Nutrition and sarcopenia: a review of the evidence and implications for preventive strategies. J Aging Res, 2012. 2012: p. 510801.
10. Moore, D.R., Keeping older muscle “young” through dietary protein and physical activity. Adv Nutr, 2014. 5(5): p. 599S-607S.
11. Volkert, D., The role of nutrition in the prevention of sarcopenia. Wien Med Wochenschr, 2011. 161(17-18): p. 409-15.
12. Evans, W.J. and W.W. Campbell, Sarcopenia and age-related changes in body composition and functional capacity. J Nutr, 1993. 123(2 Suppl): p. 465-8.
13. Pollock, M.L., et al., Twenty-year follow-up of aerobic power and body composition of older track athletes. J Appl Physiol (1985), 1997. 82(5): p. 1508-16.
14. Klitgaard, H., et al., Function, morphology and protein expression of ageing skeletal muscle: a cross-sectional study of elderly men with different training backgrounds. Acta Physiol Scand, 1990. 140(1): p. 41-54.
15. Peterson, M.D., A. Sen, and P.M. Gordon, Influence of resistance exercise on lean body mass in aging adults: a meta-analysis. Med Sci Sports Exerc, 2011. 43(2): p. 249-58.
16. Yarasheski, K.E., et al., Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men >/=76 yr old. Am J Physiol, 1999. 277(1 Pt 1): p. E118-25.
17. Booth, F.W. and K.A. Zwetsloot, Basic concepts about genes, inactivity and aging. Scand J Med Sci Sports, 2010. 20(1): p. 1-4.
18. Sayer, A.A., et al., The developmental origins of sarcopenia. J Nutr Health Aging, 2008. 12(7): p. 427-32.
19. Delshad, M., et al., Effect of Strength Training and Short-term Detraining on Muscle Mass in Women Aged Over 50 Years Old. Int J Prev Med, 2013. 4(12): p. 1386-94.
20. Faulkner, J.A., et al., The aging of elite male athletes: age-related changes in performance and skeletal muscle structure and function. Clin J Sport Med, 2008. 18(6): p. 501-7.
21. Campbell, B., et al., International Society of Sports Nutrition position stand: protein and exercise. J Int Soc Sports Nutr, 2007. 4: p. 8.
22. Buford, T.W., et al., International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr, 2007. 4: p. 6.
23. Helms, E.R., A.A. Aragon, and P.J. Fitschen, Evidence-based recommendations for natural bodybuilding contest preparation: nutrition and supplementation. J Int Soc Sports Nutr, 2014. 11: p. 20.
24. Smith, G.I., et al., Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. Clin Sci (Lond), 2011. 121(6): p. 267-78.
25. Drummond, M.J., et al., Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis. J Physiol, 2009. 587(Pt 7): p. 1535-46.
26. Bodine, S.C., et al., Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol, 2001. 3(11): p. 1014-9.
27. Rommel, C., et al., Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol, 2001. 3(11): p. 1009-13.
28. Baar, K. and K. Esser, Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise. Am J Physiol, 1999. 276(1 Pt 1): p. C120-7.
29. O’Neil, T.K., et al., The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol, 2009. 587(Pt 14): p. 3691-701.
30. Mansilla, M.C., C.E. Banchio, and D. de Mendoza, Signalling pathways controlling fatty acid desaturation. Subcell Biochem, 2008. 49: p. 71-99.
31. Stillwell, W. and S.R. Wassall, Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids, 2003. 126(1): p. 1-27.
32. Armstrong, V.T., et al., Rapid flip-flop in polyunsaturated (docosahexaenoate) phospholipid membranes. Arch Biochem Biophys, 2003. 414(1): p. 74-82.
33. Stillwell, W., et al., Docosahexaenoic acid affects cell signaling by altering lipid rafts. Reprod Nutr Dev, 2005. 45(5): p. 559-79.
34. Smith, G.I., et al., 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(2): p. 402-12.
35. Cuthbertson, D., et al., Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J, 2005. 19(3): p. 422-4.
36. Guillet, C., et al., Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J, 2004. 18(13): p. 1586-7.
37. Rasmussen, B.B., et al., Insulin resistance of muscle protein metabolism in aging. FASEB J, 2006. 20(6): p. 768-9.
38. Kamolrat, T., S.R. Gray, and M.C. Thivierge, Fish oil positively regulates anabolic signalling alongside an increase in whole-body gluconeogenesis in ageing skeletal muscle. Eur J Nutr, 2013. 52(2): p. 647-57.
39. Hawley, J.A., K.D. Tipton, and M.L. Millard-Stafford, Promoting training adaptations through nutritional interventions. J Sports Sci, 2006. 24(7): p. 709-21.
40. Hawley, J.A., et al., Nutritional modulation of training-induced skeletal muscle adaptations. J Appl Physiol, 2011. 110(3): p. 834-45.
41. Rennie, M.J., et al., Control of the size of the human muscle mass. Annu Rev Physiol, 2004. 66: p. 799-828.
42. Smith, G.I., et al., Fish oil-derived n-3 PUFA therapy increases muscle mass and function in healthy older adults. Am J Clin Nutr, 2015.
43. Fielding, R.A., et al., Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc, 2011. 12(4): p. 249-56.
44. Cruz-Jentoft, A.J., et al., Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing, 2010. 39(4): p. 412-23.
45. Goodpaster, B.H., et al., The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci, 2006. 61(10): p. 1059-64.
46. Skelton, D.A., et al., Strength, power and related functional ability of healthy people aged 65-89 years. Age Ageing, 1994. 23(5): p. 371-7.
47. Bailey, J.L., X. Wang, and S.R. Price, The balance between glucocorticoids and insulin regulates muscle proteolysis via the ubiquitin-proteasome pathway. Miner Electrolyte Metab, 1999. 25(4-6): p. 220-3.
48. Ross, J.A., A.G. Moses, and K.C. Fearon, The anti-catabolic effects of n-3 fatty acids. Curr Opin Clin Nutr Metab Care, 1999. 2(3): p. 219-26.
49. Ventadour, S. and D. Attaix, Mechanisms of skeletal muscle atrophy. Curr Opin Rheumatol, 2006. 18(6): p. 631-5.
50. Whitehouse, A.S., et al., Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res, 2001. 61(9): p. 3604-9.
51. Whitehouse, A.S. and M.J. Tisdale, Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in acute starvation. Biochem Biophys Res Commun, 2001. 285(3): p. 598-602.
52. Wing, S.S. and A.L. Goldberg, Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting. Am J Physiol, 1993. 264(4 Pt 1): p. E668-76.
53. Attaix, D., et al., Ubiquitin-proteasome-dependent proteolysis in skeletal muscle. Reprod Nutr Dev, 1998. 38(2): p. 153-65.
54. Attaix, D., et al., The ubiquitin-proteasome system and skeletal muscle wasting. Essays Biochem, 2005. 41: p. 173-86.
55. Jagoe, R.T. and A.L. Goldberg, What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? Curr Opin Clin Nutr Metab Care, 2001. 4(3): p. 183-90.
56. Mitch, W.E. and A.L. Goldberg, Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med, 1996. 335(25): p. 1897-905.
57. Tisdale, M.J., The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting. J Support Oncol, 2005. 3(3): p. 209-17.
58. Fearon, K.C., et al., Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut, 2003. 52(10): p. 1479-86.
59. Smith, H.J., N.A. Greenberg, and M.J. Tisdale, Effect of eicosapentaenoic acid, protein and amino acids on protein synthesis and degradation in skeletal muscle of cachectic mice. Br J Cancer, 2004. 91(2): p. 408-12.
60. Smith, H.J., J. Khal, and M.J. Tisdale, Downregulation of ubiquitin-dependent protein degradation in murine myotubes during hyperthermia by eicosapentaenoic acid. Biochem Biophys Res Commun, 2005. 332(1): p. 83-8.
61. Smith, H.J., M.J. Lorite, and M.J. Tisdale, Effect of a cancer cachectic factor on protein synthesis/degradation in murine C2C12 myoblasts: modulation by eicosapentaenoic acid. Cancer Res, 1999. 59(21): p. 5507-13.
62. Smith, H.J. and M.J. Tisdale, Induction of apoptosis by a cachectic-factor in murine myotubes and inhibition by eicosapentaenoic acid. Apoptosis, 2003. 8(2): p. 161-9.
63. Delarue, J., et al., Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Diabetes Metab, 2003. 29(3): p. 289-95.
64. Noreen, E.E., et al., Effects of supplemental fish oil on resting metabolic rate, body composition, and salivary cortisol in healthy adults. J Int Soc Sports Nutr, 2010. 7: p. 31.
65. Rooyackers, O.E. and K.S. Nair, Hormonal regulation of human muscle protein metabolism. Annu Rev Nutr, 1997. 17: p. 457-85.
66. Juster, R.P., B.S. McEwen, and S.J. Lupien, Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosci Biobehav Rev, 2010. 35(1): p. 2-16.
67. Seeman, T.E., et al., Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. Proc Natl Acad Sci U S A, 2001. 98(8): p. 4770-5.
68. Seeman, T.E., et al., Price of adaptation–allostatic load and its health consequences. MacArthur studies of successful aging. Arch Intern Med, 1997. 157(19): p. 2259-68.
69. Hutchins-Wiese, H.L., et al., The impact of supplemental n-3 long chain polyunsaturated fatty acids and dietary antioxidants on physical performance in postmenopausal women. J Nutr Health Aging, 2013. 17(1): p. 76-80.
70. Rodacki, C.L., et al., Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr, 2012. 95(2): p. 428-36.
71. Di Girolamo, F.G., et al., Omega-3 fatty acids and protein metabolism: enhancement of anabolic interventions for sarcopenia. Curr Opin Clin Nutr Metab Care, 2014. 17(2): p. 145-50.
72. Couet, C., et al., Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes Relat Metab Disord, 1997. 21(8): p. 637-43.
73. Delarue, J., et al., Effects of fish oil on metabolic responses to oral fructose and glucose loads in healthy humans. Am J Physiol, 1996. 270(2 Pt 1): p. E353-62.
74. Huffman, D.M., J.L. Michaelson, and T. Thomas, R. , Chronic supplementation with fish oil increases fat oxidation during exercise in young men. . JEPonline, 2004. 7(1): p. 48-56.
75. Kabir, M., et al., Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr, 2007. 86(6): p. 1670-9.
76. Hill, A.M., et al., Combining fish-oil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors. Am J Clin Nutr, 2007. 85(5): p. 1267-74.
77. Kunesova, M., et al., The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women. Physiol Res, 2006. 55(1): p. 63-72.
78. Thorsdottir, I., et al., Randomized trial of weight-loss-diets for young adults varying in fish and fish oil content. Int J Obes (Lond), 2007. 31(10): p. 1560-6.
79. Yurko-Mauro, K., et al., Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement, 2010. 6(6): p. 456-64.
80. Narendran, R., et al., Improved working memory but no effect on striatal vesicular monoamine transporter type 2 after omega-3 polyunsaturated fatty acid supplementation. PLoS One, 2012. 7(10): p. e46832.
81. Nilsson, A., et al., Effects of supplementation with n-3 polyunsaturated fatty acids on cognitive performance and cardiometabolic risk markers in healthy 51 to 72 years old subjects: a randomized controlled cross-over study. Nutr J, 2012. 11: p. 99.
82. Dangour, A.D. and R. Uauy, N-3 long-chain polyunsaturated fatty acids for optimal function during brain development and ageing. Asia Pac J Clin Nutr, 2008. 17 Suppl 1: p. 185-8.
83. Swanson, D., R. Block, and S.A. Mousa, Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr, 2012. 3(1): p. 1-7.
84. Yurko-Mauro, K., Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline. Curr Alzheimer Res, 2010. 7(3): p. 190-6.
85. Stonehouse, W., et al., DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr, 2013. 97(5): p. 1134-43.
86. Sinn, N., et al., Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br J Nutr, 2012. 107(11): p. 1682-93.
87. Stonehouse, W., Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Evidence from clinical trials. Nutrients, 2014. 6(7): p. 2730-58.
88. Titova, O.E., et al., Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly. Age (Dordr), 2013. 35(4): p. 1495-505.
89. Cederholm, T., N. Salem, Jr., and J. Palmblad, omega-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr, 2013. 4(6): p. 672-6.
90. Zhang, M.J. and M. Spite, Resolvins: anti-inflammatory and proresolving mediators derived from omega-3 polyunsaturated fatty acids. Annu Rev Nutr, 2012. 32: p. 203-27.
91. Serhan, C.N., N. Chiang, and T.E. Van Dyke, Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol, 2008. 8(5): p. 349-61.
92. Serhan, C.N., et al., Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med, 2000. 192(8): p. 1197-204.
93. Serhan, C.N., et al., Anti-microinflammatory lipid signals generated from dietary N-3 fatty acids via cyclooxygenase-2 and transcellular processing: a novel mechanism for NSAID and N-3 PUFA therapeutic actions. J Physiol Pharmacol, 2000. 51(4 Pt 1): p. 643-54.
94. Kelley, D.S., et al., DHA supplementation decreases serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men. J Nutr, 2009. 139(3): p. 495-501.
95. Micallef, M.A., I.A. Munro, and M.L. Garg, An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur J Clin Nutr, 2009. 63(9): p. 1154-6.
96. Kapoor, R. and Y.S. Huang, Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Curr Pharm Biotechnol, 2006. 7(6): p. 531-4.
97. Wang, X., H. Lin, and Y. Gu, Multiple roles of dihomo-gamma-linolenic acid against proliferation diseases. Lipids Health Dis, 2012. 11: p. 25.
98. Simopoulos, A.P., Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr, 2002. 21(6): p. 495-505.
99. Bouwens, M., et al., Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr, 2009. 90(2): p. 415-24.
100. de la Puerta, R., V. Ruiz Gutierrez, and J.R. Hoult, Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil. Biochem Pharmacol, 1999. 57(4): p. 445-9.
101. Ueshima, H., et al., Food omega-3 fatty acid intake of individuals (total, linolenic acid, long-chain) and their blood pressure: INTERMAP study. Hypertension, 2007. 50(2): p. 313-9.
102. Liu, J.C., et al., Long-chain omega-3 fatty acids and blood pressure. Am J Hypertens, 2011. 24(10): p. 1121-6.
103. Visioli, F. and C. Galli, Antiatherogenic components of olive oil. Curr Atheroscler Rep, 2001. 3(1): p. 64-7.
104. Harris, W.S., Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor. Pharmacol Res, 2007. 55(3): p. 217-23.
105. Harris, W.S. and C. Von Schacky, The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med, 2004. 39(1): p. 212-20.
106. von Schacky, C., Omega-3 index and cardiovascular health. Nutrients, 2014. 6(2): p. 799-814.
107. Delgado-Lista, J., et al., Long chain omega-3 fatty acids and cardiovascular disease: a systematic review. Br J Nutr, 2012. 107 Suppl 2: p. S201-13.
108. Jump, D.B., C.M. Depner, and S. Tripathy, Omega-3 fatty acid supplementation and cardiovascular disease. J Lipid Res, 2012. 53(12): p. 2525-45.
109. Poudyal, H., et al., Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action. Prog Lipid Res, 2011. 50(4): p. 372-87.