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The long-chain omega-3s and depression fact or fiction?

The cardiovascular benefits associated with the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well known. What you may not be aware of is that they may provide some symptomatic relief for depression. According to the Organization for Economic Co-Operation and Development (OECD), depression is one of the most costly mental disorders, owing to the large number of persons affected and its significant impact on the labour force. In its policy brief on mental health, the OECD indicates that "21 million people in 28 European countries (4.5% of the total population) suffer from depression, with an associated cost of more than [euro]118 billion or [euro]253 per inhabitant, equivalent to 1% of the region's GDP. Direct costs were [euro]42 billion, constituted by outpatient care ([euro]22 billion), pharmaceuticals ([euro]9 billion) and hospitalization ([euro]10 billion), but indirect costs that result from work absenteeism and premature mortality accounted for [euro]76 billion, or two-thirds of the total. "


Although the body of evidence concerning the effects of long-chain omega-3s on depression has grown, it remains difficult to summarize and draw definitive conclusions because the subject pools involved in the trials were not homogenous--it is not possible to compare apples, oranges and bananas to establish whether a treatment is effective. According to the National Institute of Mental Health, there are multiple forms of depression, including major depressive disorder, dysthymic disorder, minor depression, psychotic depression, postpartum depression and seasonal affective disorder (SAD). Clearly, a lack of understanding of clinical heterogeneity has contributed to the mixed conclusions about the effectiveness of the long-chain omega-3s on these conditions. Clinical variation will cause heterogeneity if the intervention effect is affected by the factors that vary across studies--most obviously, the specific interventions or patient characteristics. Put simply, the true intervention effect will differ between studies.

Many reviews (non-systematic, systematic and meta-analysis) have been published during recent years and the review of Appleton et al. serves to illustrate the heterogeneity conundrum. The authors identified 35 randomized controlled clinical trials--the methods associated with which are detailed in a table within the publication--that investigated the effects of long-chain omega-3s on depression. In describing the methods, the authors write: "Considerable variation between studies was found in number of participants, sex and age of participants, diagnosis of participants, dose and combination of n-3 PUFAs used for supplementation, duration of supplementation, placebo used for comparison, measurement of depressed mood and trial quality as assessed in terms of blinding, adequate allocation, concealment and the use of intention-to-treat analyses." Since the publication of Appleton et al., additional trials have been published and the results and conclusions remain mixed.

An increasing amount of clinical and epidemiological evidence suggests that low dietary intake and/or tissue levels of the long-chain omega-3s are associated with depression. Although there is still insufficient data from adequately powered clinical trials to state with confidence that EPA and DHA are efficacious as therapy for the treatment of depression, there is enough favourable data to warrant further research. In the future, such research should include large, randomized, placebo-controlled trials that consider heterogeneity, down to subpopulations within the different forms of depression, to estimate the value of intervening with EPA and DHA.


Given the long history of safe use and well-documented cardiovascular benefits associated with EPA and DHA, there is no reason for consumers to wait for the scientific community to gather additional data on the potential benefits. They must make certain that they are getting enough EPA and DHA through their diet or food supplements. Although the required amount is debatable--and dependent upon current health status--a couple of points are worth noting. First, in its 2009 opinion "Scientific Opinion on Dietary Reference Values for Fats, including Saturated Fatty Acids, Polyunsaturated Fatty Acids, Monounsaturated Fatty Acids, Trans Fatty Acids and Cholesterol," the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), established an adequate intake for EPA and DHA of 250 mg/day, based on considerations of cardiovascular health. Second--and clearly ahead of its time--in its 2010 update of the recommended dietary intakes for fatty acids, the French Food Safety Agency (formerly AFSSA, now ANSES) recommended < 200-300 mg of EPA and DHA for neuropsychiatric pathologies, including depression.


(1.) K.M. Appleton, et al., "Updated Systematic Review and Meta-Analysis of the Effects of n-3 Long-Chain Polyunsaturated Fatty Acids on Depressed Mood," Am. J. Clin. Nutr. 91,757-770(2010).

(2.) M.H. Bloch, et al., "Omega-3 Fatty Acids for the Treatment of Depression: Systematic Review and Meta-Analysis," Mol. Psychiatry[Epub ahead of print] doi: 10.1038/mp.2011.100.(2011).

(3.) EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA), "Scientific Opinion on Dietary Reference Values for Fats, Including Saturated Fatty Acids, Polyunsaturated Fatty Acids, Monounsaturated Fatty Acids, Trans Fatty Acids and Cholesterol," EFSA Journal 8(3), 1461(2010).

(4.) M.P.Freeman, et al., "Omega-3 Fatty Acids for Major Depressive Disorder Associated with the Menopausal Transition: A preliminary Open Trial," Menopause 18, 279-284 (2011).

(5.) French Food Safety Agency, "Opinion of the French Food Safety Agency on the Update of French Population Refrence Intakes (ANCs) for Fatty Acids," Request No. 2006-SA-0359 (2010); http;//

(6.) L.A. Jans, et al., "The Efficacy of n-3 Fatty Acids DHA and EPA (Fish Oil) for Perinatal Depression," Br.J. Nutr. 104, 1577-1585 (2010).

(7.) K.Kendall-Tackett, "Long-Chain Omega-3Fatty Acids and Wonen's Mental Health in the Perinatal Period and Beyond," J.Midwifery Women's Health 55, 561-567 (2010).

(8.) N.V. Kragulijac, et al., "Efficacy of Omenga-3 Fatty Acids in Mood Disorders--A Systematic Review and Metaanalysis," Psychopharmacol. Bull. 42, 39-54 (2009).

(9.) F.Lesperance, et al., "The Effcacy of Omega-3 Supplementation for Major Depression: A Randomized Controlled Trial," J. Clin. Psychiatry 72, 1054=1062 (2011).

(10.) B.Levant, "N-3 (Omega-3) Fatty Acids in Postpartum Depression: Implications for Prevevntion and Treatment," doi: 10.115/2011/4673490.

(11.) P.Y.Lin, et al., "A Meta-Analytic Rveview of Polyunsaturated Fatty Acid Compositions in Patients with Depression," Biol. Psychiatry 68, 140-147 (2010).

(12.) JG Martins, "EPA but not DHA Appears to be Respinsile for theEffcacy of Omega-3 Loong Chan Polyunsatrated Faeey Acid eiplementation in deprdsstion:Evidence from a Meta-Analysis fo Eandomixd Controlled Trial," J.Am. Coll.Nutr. 28, 525-542 (2009).

(13.) National Instisute of Mental Health, US Department of Health and Human Services, National Institutes of Health, NIH Publication No. 11-3561 (2011).

(14.) W.H. Oddy, et al., "Dietary Intake of Omega-3 Fatty Acids and Risk of Depressive Symptoms in Adolescent," Depress. Anxiet 28, 582-588 (2011).

(15.) Organization for Economic Co-Operation and Development, "Policy Brief: Mental Health in OECD Countries," (2008):

(16.) M. Rondanelli. et al., "Effect of Omega-3 Ftty Acids Supplementation on Depressive Symptoms and on Health-Related Quality of Life in the Treatment of Elderly Women with Depression: a Double-Blind, Placebo-Controlled, Randomized Clinical Trial," J.Am. Coll. Nutr. 29, 55-64 (2010).

(17.) M.E. Sublette, et al., "Meta-Analysis of the Effects of Eicosapentaenoic Acid (EPA) in Clinical Trials in Depression," J.Clin. Psychiatry 72, 1577-1584 (2011).

(18.) J.M. Wojcicki, "Maternal Omega-3 Fatty Acid Supplementation and Risk for Perinatal Maternal Depression," J. Matern. Fetal Neonatal.Med.24, 680-686 (2011).

For more information

Dr Harry B.Rice VP, Regulatory Scientific Affairs Global Organization for EPA and DHA Omega-3s (GOED)1075 East Hollywood Avenue Salt Lake City, Utah 84105, USA Tel. +18017461413
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Title Annotation:mood and brain health
Publication:Nutraceutical Business & Technology
Geographic Code:1USA
Date:Mar 1, 2012
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