Omega-3 Benefits: Omega-3 and Depression
Omega-3 benefits in depression
There is a documented, statistically significant relationship between low plasma omega-3 values and negative mood among non-psychiatric patients (1). Deficiencies in these polyunsaturated fatty acids have also been observed in attention deficit hyperactivity disorder, depression, bipolar disorder, stress, aggression and dementia (2). The omega-6/omega-3 ratio in serum and red blood cell membranes is high in depression (3, 4) and in the risk of suicide (5): serum and red blood cell membrane values of omega-3 EPA, DHA and total long-chain omega-3 polyunsaturated fatty acids are significantly lower in depressive patients compared to control subjects (6-8).
Various studies indicate that depression shares the physiopathological characteristics and risk factors of cardiovascular disease (9-12). The inflammatory hypothesis of depression stems from the observation that stress precipitates both inflammatory responses and depression, inflammatory markers are higher and inflammatory cytokines can produce depressive symptoms in humans (13, 14). High omega-3 values in the omega-6/omega-3 ratio tend to reduce eicosanoid and proinflammatory cytokine production (15) and an improvement in mood disorders is observed when anti-inflammatory agents are used as an adjuvant to conventional treatment (16).
In addition, the omega-6/omega-3 ratio could also influence the physiopathology of depression via the catecholaminergic systems (serotonin and dopamine) (17, 18).
Omega-3 as adjuvant therapy
Supplementation with omega-3 fatty acids can reduce the symptoms of perinatal depression (19-21). Although the beneficial effect of omega-3 fatty acid supplementation in depression has mainly been observed when used as adjuvant therapy (22, 23), monotherapy with omega-3 has significant therapeutic effects in major childhood depression (24), while in adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression, fish oil supplementation produced a remission in the symptoms in 40 to 100% of cases (dose dependent) (25).
Omega-3 EPA and depression
Omega-3 EPA is more effective than DHA in reducing symptoms of depression. Epidemiological and experimental studies have shown its clinical efficacy in people diagnosed with major depressive disorder and in those with depressive symptoms but not diagnosed as major depression (22, 23). The meta-analyses of clinical studies focussing on the type of omega-3 used in the treatment of depression show that the positive effect on depressive symptoms depends more on the omega-3 EPA than the DHA content of the treatment (26, 27). When comparing omega-3 EPA to DHA as adjuvants to maintenance medication in patients with depression, the response to treatment was only observed in patients treated with omega-3 EPA (28). And with major depression, effects equal to fluoxetine have been obtained with EPA, but combined administration of both produces a better result than with each separately (29).
Safety of omega-3 administration
The American Psychiatric Association recommends 1 gram of omega-3 DHA+EPA daily for the treatment of affective disorders and has proposed that the optimum proportion is 2 parts omega-3 EPA to one part DHA (30).
In psychiatric patients, in which interactions can prove a problem, supplementation with omega-3 does not represent a risk: omega-3 fatty acids are extremely safe in the long term.
1 Tiemeier H, van Tuijl HR, Hofman A et al. Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Am J Clin Nutr. 2003 Jul;78(1):40-46. // 2 Sinn N, Milte C, Howe PR. Oiling the brain: a review of randomized controlled trials of Omega-3 fatty acids in psychopathology across the lifespan. Nutrients. 2010 Feb;2(2):128-170. // 3 De Vriese SR, Christophe AB, Maes M. Lowered serum Omega-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci. 2003;73(25):3181-3187. // 4 Peet M, Murphy B, Shay J et al. Depletion of Omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 1998;43:315-319. // 5 Sublette ME, Hibbeln JR, Galfalvy H et al. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry. 2006 Jun; 163(6):1100-1102. // 6 Lina PY, Huangb SY, Su KP. A MetaAnalytic Review of Polyunsaturated Fatty Acid Compositions in Patients with Depression Biological Psychiatry 2010;68(2):140147. // 7 Adams PB, Lawson S, Sanigorski A et al. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996;31:S157-S161. // 8 Maes M, Christophe A, Delanghe J et al. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res. 1999;85:275-291. // 9 Prince M, Patel V, Saxena S et al. No health without mental health. The Lancet. 2007;370(9590):859-877. // 10 Sanchez-Villegas A, Martinez-Gonzalez MA. Diet, a new target to prevent depression? BMC Medicine. 2013;11, article 3. // 11 Machado-Vieira R, Mallinger AG. Abnormal function of monoamine oxidase-A in comorbid major depressive disorder and cardiovascular disease: pathophysiological and therapeutic implications (review). Mol Med Rep. 2012 Nov; 6(5):915-922. // 12 Do DP, Dowd JB, Ranjit N et al. Hopelessness, depression, and early markers of endothelial dysfunction in U.S. adults. Psychosom Med. 2010 Sep; 72(7):613-619. // 13 Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009 May 1; 65(9):732-741. // 14 Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006 Jan; 27(1):24-31. // 15 Calder PC. Omega-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006 Jun; 83(6 Suppl):1505S-1519S. // 16 Rosenblat JD, Cha DS, Mansur RB et al. Inflamed Moods: A Review of the Interactions between Inflammation and Mood Disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 24. pii: S0278-5846(14)00014-1. // 17 Maes M. Major depression and activation of the inflammatory response system. Adv Exp Med Biol. 1999;461:25-46. // 18 Sublette ME, Galfalvy HC, Hibbeln JR et al. Polyunsaturated fatty acid associations with dopaminergic indices in major depressive disorder. Int J Neuropsychopharmacol. 2014 Mar;17(3):383-391. // 19 Rees AM, Austin MP, Owen C et al. Omega-3 deficiency associated with perinatal depression: case control study. Psychiatr Res. 2009;166(2-3):254-259. // 20 Coletta JM, Bell SJ, Roman AS et al. Omega-3 fatty acids and pregnancy. Reviews In Obstetrics & Gynecology. 2010;3(4):163-171. // 21 Giles GE, Mahoney CR, Kanarek RB. Omega-3 fatty acids influence mood in healthy and depressed individuals. Nutr Rev. 2013 Nov;71(11):727-741. // 22 Grosso G, Galvano F, Marventano S et al. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid Med Cell Longev. 2014;2014:313570. // 23 Grosso G, Pajak A, Marventano S et al. Role of Omega-3 Fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One. 2014 May 7;9(5):e96905. // 24 Nemets H, Nemets B, Apter A et al. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry. 2006 Jun;163(6):1098-1100. // 25 McNamara RK, Strimpfel J, Jandacek R et al. Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with SSRI-Resistant Major Depressive Disorder. PharmaNutrition. 2014 Apr 1;2(2):38-46. // 26 Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids in Health and Disease. 2007;6, article 21. // 27 Martins JG. EPA but not DHA appears to be responsible for the efficacy of Omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct; 28(5):525-542. // 28 Mozaffari-Khosravi H, Yassini-Ardakani M, Karamati M et al. Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: a randomized, double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2013 Jul;23(7):636-644. // 29 Jazayeri S, Tehrani-Doost M, Keshavarz SA et al. Comparison of therapeutic effects of Omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry. 2008 Mar;42(3):192-198. // 30 Russell FD, Bürgin-Maunder CS. Distinguishing Health Benefits of Eicosapentaenoic and Docosahexaenoic Acids. Mar. Drugs 2012;10:2535-2559.