The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
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
Abstract
BACKGROUND: Epidemiologic and case-control data suggest that increased dietary intake of omega-3 long-chain polyunsaturated fatty acids (omega3 LC-PUFAs) may be of benefit in depression. However, the results of randomized controlled trials are mixed and controversy exists as to whether either eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or both are responsible for the reported benefits. OBJECTIVE: The aim of the current study was to provide an updated meta-analysis of all double-blind, placebo-controlled, randomized controlled trials examining the effect of omega3 LC-PUFA supplementation in which depressive symptoms were a reported outcome. The study also aimed to specifically test the differential effectiveness of EPA versus DHA through meta-regression and subgroup analyses. DESIGN: Studies were selected using the PubMed database on the basis of the following criteria: (1) randomized design; (2) placebo controlled; (3) use of an omega3 LC-PUFA preparation containing DHA, EPA, or both where the relative amounts of each fatty acid could be quantified; and (4) reporting sufficient statistics on scores of a recognizable measure of depressive symptoms. RESULTS: Two hundred forty-one studies were identified, of which 28 met the above inclusion criteria and were therefore included in the subsequent meta-analysis. Using a random effects model, overall standardized mean depression scores were reduced in response to omega3 LC-PUFA supplementation as compared with placebo (standardized mean difference = -0.291, 95% CI = -0.463 to -0.120, z = -3.327, p = 0.001). However, significant heterogeneity and evidence of publication bias were present. Meta-regression studies showed a significant effect of higher levels of baseline depression and lower supplement DHAEPA ratio on therapeutic efficacy. Subgroup analyses showed significant effects for: (1) diagnostic category (bipolar disorder and major depression showing significant improvement with omega3 LC-PUFA supplementation versus mild-to-moderate depression, chronic fatigue and non-clinical populations not showing significant improvement); (2) therapeutic as opposed to preventive intervention; (3) adjunctive treatment as opposed to monotherapy; and (4) supplement type. Symptoms of depression were not significantly reduced in 3 studies using pure DHA (standardized mean difference 0.001, 95% CI -0.330 to 0.332, z = 0.004, p = 0.997) or in 4 studies using supplements containing greater than 50% DHA (standardized mean difference = 0.141, 95% CI = -0.195 to 0.477, z = 0.821, p = 0.417). In contrast, symptoms of depression were significantly reduced in 13 studies using supplements containing greater than 50% EPA (standardized mean difference = -0.446, 95% CI = -0.753 to -0.138, z = -2.843, p = 0.005) and in 8 studies using pure ethyl-EPA (standardized mean difference = -0.396, 95% CI = -0.650 to -0.141, z = -3.051, p = 0.002). However, further meta-regression studies showed significant inverse associations between efficacy and study methodological quality, study sample size, and duration, thus limiting the confidence of these findings. CONCLUSIONS: The current meta-analysis provides evidence that EPA may be more efficacious than DHA in treating depression. However, owing to the identified limitations of the included studies, larger, well-designed, randomized controlled trials of sufficient duration are needed to confirm these findings.
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Assessing the quality of reports of randomized clinical trials: Is blinding necessary?
Jadad, A. R., Moore, R. A., Carroll, D., Jenkinson, C., Reynolds, D. J. M., Gavaghan, D. J., & McQuay, H. J. (1996) · Controlled Clinical Trials · doi:10.1016/0197-2456(95)00134-4 · Cited by 17,582
Projections of Global Mortality and Burden of Disease from 2002 to 2030
Mathers, C. D., & Loncar, D. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030442 · Cited by 11,386
Sick individuals and sick populations
Rose, G. (2001) · International Journal of Epidemiology · doi:10.1093/ije/30.3.427 · Cited by 3,736
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
Sick individuals and sick populations
ROSE, G. (1985) · International Journal of Epidemiology · doi:10.1093/ije/14.1.32 · Cited by 2,701
New approaches to antidepressant drug discovery: beyond monoamines
Berton, O., & Nestler, E. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1846 · Cited by 1,589
(1994) · American Journal of Psychiatry · doi:10.1176/ajp.151.7.979 · Cited by 1,485 · cited 1×
“This, in turn, may cause women to be more vulnerable to dietary deficiencies of v3 LC-PUFAs and may also explain, at least in part, why women are at greater risk for the development of depression [74].”
BackgroundAndrade, L., Caraveo‐anduaga, J. J., Berglund, P., Bijl, R. V., Graaf, R. D., Vollebergh, W., Dragomirecka, E., Kohn, R., Keller, M., Kessler, R. C., et al. (2003) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.138 · Cited by 1,068 · cited 2×
“2 0 0 7 [4 1 ] R ec u rr en t se lf -h ar m 4 9 (2 2 /2 7 ) E P A X 5 5 0 0 1 .”
Omega 3 Fatty Acids in Bipolar Disorder: A Preliminary Double-blind, Placebo-Controlled Trial
Stoll, A. L., Severus, W. E., Freeman, M. P., Rueter, S., Zboyan, H. A., Diamond, E., Cress, K. K., & Marangell, L. B. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.5.407 · Cited by 814
Burdge, G. C., & Wootton, S. A. (2002) · British Journal Of Nutrition · doi:10.1079/bjn2002689 · Cited by 812
Omega-3 Fatty Acids: Evidence Basis for Treatment and Future Research in Psychiatry
Freeman, M. P., Hibbeln, J. R., Wisner, K. L., Davis, J. M., Mischoulon, D., Peet, M., Keck, P. E., Marangell, L. B., Richardson, A. J., Lake, J., et al. (2006) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v67n1217 · Cited by 709
Lin, P.-Y., & Su, K.-P. (2007) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v68n0712 · Cited by 481
Frangou, S., Lewis, M., & McCrone, P. (2006) · British Journal of Psychiatry · doi:10.1192/bjp.188.1.46 · Cited by 309
Su, K.-P., Huang, S.-Y., Chiu, T.-H., Huang, K.-C., Huang, C.-L., Chang, H.-C., & Pariante, C. M. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0418 · Cited by 308
Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid?
Ross, B. M., Seguin, J., & Sieswerda, L. E. (2007) · Lipids in Health and Disease · doi:10.1186/1476-511x-6-21 · Cited by 275
Rogers, P. J., Appleton, K. M., Kessler, D., Peters, T. J., Gunnell, D., Hayward, R. C., Heatherley, S. V., Christian, L. M., McNaughton, S. A., & Ness, A. R. (2008) · British Journal of Nutrition · doi:10.1017/s0007114507801097 · Cited by 243
Keck, P. E., Mintz, J., McElroy, S. L., Freeman, M. P., Suppes, T., Frye, M. A., Altshuler, L. L., Kupka, R., Nolen, W. A., Leverich, G. S., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.056 · Cited by 234
Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults.
Kiecolt-Glaser, J. K., Belury, M. A., Porter, K., Beversdorf, D. Q., Lemeshow, S., & Glaser, R. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3180313a45 · Cited by 212
A systematic comparison of software dedicated to meta-analysis of causal studies
Bax, L., Yu, L.-M., Ikeda, N., & Moons, K. G. (2007) · BMC Medical Research Methodology · doi:10.1186/1471-2288-7-40 · Cited by 210
da Silva, T. M., Munhoz, R. P., Alvarez, C., Naliwaiko, K., Kiss, Á., Andreatini, R., & Ferraz, A. C. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.03.008 · Cited by 205
Rees, A.-M., Austin, M.-P., & Parker, G. B. (2008) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/00048670701827267 · Cited by 134 · cited 3×
“Regarding the assessment of compliance using RBC membrane or plasma phospholipid analyses, all 3 pure DHA studies conducted these analyses, showing significant changes in RBC membrane DHA levels as a result of supplementation [49,50,56]; all 4 mainly DHA studies conducted these analyses, showing significant increases…”
MethodResultAdvice to eat fish and mood: a randomised controlled trial in men with angina
Ness, A. R., Gallacher, J. E. J., Bennett, P. D., Gunnell, D. J., Rogers, P. J., Kessler, D., & Burr, M. L. (2003) · Nutritional Neuroscience · doi:10.1080/1028415021000056069 · Cited by 50
FUJIOKA, S., HAMAZAKI, K., ITOMURA, M., HUAN, M., NISHIZAWA, H., SAWAZAKI, S., KITAJIMA, I., & HAMAZAKI, T. (2006) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.52.261 · Cited by 36
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Shahidi, F., & Ambigaipalan, P. (2018) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-111317-095850 · Cited by 1,390
Inflammation: Depression Fans the Flames and Feasts on the Heat
Kiecolt-Glaser, J. K., Derry, H. M., & Fagundes, C. P. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15020152 · Cited by 844
Malhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G., et al. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415617657 · Cited by 842
Grosso, G., Pajak, A., Marventano, S., Castellano, S., Galvano, F., Bucolo, C., Drago, F., & Caraci, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096905 · Cited by 449
Layé, S., Nadjar, A., Joffre, C., & Bazinet, R. P. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014092 · Cited by 420
Metadata
- Authors
- Martins, J. G.
- Venue
- Journal of the American College of Nutrition
- Publisher
- Informa UK Limited
- Published
- 2009-10
- Volume
- 28
- Issue
- 5
- Pages
- 525-542
- ISSN
- 0731-5724 (ISSN-L)
- 1541-1087
- OpenAlex
- W1980568154
- Cited by
- 358
- References
- 23
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- closed
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