The role of unsaturated fatty acids in depression treatment - international clinical guidelines and recommendation of psychiatric associations

Authors

DOI:

https://doi.org/10.12923/2353-8627/2024-0016

Keywords:

polyunsaturated fatty acids, PUFA, nutritional psychiatry, depressive disorders, omega-3 supplementation, clinical guidelines, therapeutic interventions

Abstract

Introduction: Nutritional psychiatry examines how diet and specific nutrients affect mental health and well-being. The potential role of polyunsaturated fatty acids, especially omega-3 fatty acids (n-3 PUFAs), in the treatment of major depressive disorder (MDD) has gained significant interest in recent years.

Objective: To review and present guidelines on the use of omega-3 PUFAs in the treatment of MDD and to highlight recommendations from psychiatric associations worldwide.

Method: A comprehensive literature review was conducted using articles from Web of Science, Google Scholar, Medline/ PubMed. The analysis included guidelines and recommendations from psychiatric associations published between 2014 and 2024. Keywords such as polyunsaturated fatty acids, PUFA, nutritional psychiatry, recommendations, guidelines, depressive disorders, and omega-3 were used in the search strategy. Articles in English and Polish were included.

Results: Evidence suggests that omega-3 PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (especially EPA), can serve as effective adjunctive treatments in combination with standard antidepressant medications, though they are not recommended as monotherapy. Several psychiatric associations, including the International Society of Nutritional Psychiatry Research (ISNPR), the World Federation of Societies of Biological Psychiatry (WFSBP), and the Canadian Network for Mood and Anxiety Treatment (CANMAT), have published guidelines supporting the use of n-3 PUFAs in MDD treatment, particularly in specific populations like pregnant women, the elderly, individuals with raised inflammation, with obesity.

Conclusions: The promising findings from multiple studies and the support from scientific psychiatric associations highlight the significant potential of omega-3 PUFAs as a beneficial addition to standard MDD treatments. The growing body of evidence underscores the importance of integrating dietary interventions into mental health care. With continued research and clinical application, n-3 PUFAs could play a crucial role in enhancing treatment outcomes and improving the quality of life for individuals with depressive disorders.

References

1. Marx, W., Moseley, G., Berk, M., & Jacka, F. (2017). Nutritional psychiatry: The present state of the evidence. Proceedings of the Nutrition Society, 76(4), 427-436. https://doi.org/10.1017/s0029665117002026

2. Grosso, G. (2021). Nutritional psychiatry: How diet affects brain through gut microbiota. Nutrients, 13(4), 1282. https://doi.org/10.3390/nu13041282

3. Samuthpongtorn, C., Nguyen, L. H., Okereke, O. I., Wang, D. D., Song, M., Chan, A. T., & Mehta, R. S. (2023). Consumption of ultraprocessed food and risk of depression. JAMA Network Open, 6(9). https://doi.org/10.1001/jamanetworkopen.2023.34770

4. Mac Giollabhui, N., Mischoulon, D., Dunlop, B. W., Kinkead, B., Schettler, P. J., Liu, R. T., Okereke, O. I., Lamon-Fava, S., Fava, M., & Rapaport, M. H. (2023). Individuals with depression exhibiting a pro-inflammatory phenotype receiving omega-3 polyunsaturated fatty acids experience improved motivation-related cognitive function: Preliminary results from a randomized controlled trial. Brain, behavior, & immunity -health, 32, 100666. https://doi.org/10.1016/j.bbih.2023.100666

5. Bauer, M. E., & Teixeira, A. L. (2018). Inflammation in psychiatric disorders: What comes First? Annals of the New York Academy of Sciences, 1437(1), 57-67. https://doi.org/10.1111/nyas.13712

6. Xiong RG, Li J, Cheng J, Zhou DD, Wu SX, Huang SY, Saimaiti A, Yang ZJ, Gan RY, Li HB. The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components. Nutrients. 2023 Jul 23;15(14):3258. doi: 10.3390/nu15143258. PMID: 37513676; PMCID: PMC10384867

7. Grosso, G. (2021). Nutritional psychiatry: How diet affects brain through gut microbiota. Nutrients, 13(4), 1282. https://doi.org/10.3390/nu13041282

8. Pickersgill, J. W., Turco, C. V., Ramdeo, K., Rehsi, R. S., Foglia, S. D., & Nelson, A. J. (2022). The combined influences of exercise, diet and sleep on neuroplasticity. Frontiers in Psychology, 13. https://doi.org/10.3389/fpsyg.2022.831819

9. Chen, S. H., & Goodwill, A. M. (2022). Neuroplasticity and adult learning. Third International Handbook of Lifelong Learning, 1-19. https://doi.org/10.1007/978-3-030-67930-9_43-1

10. Opinion of the panel on dietetic products, nutrition and allergies (NDA) on a requestfrom the commission related to scientific and technical guidance for the preparation and presentation of the application for authorisation of a health claim. (2007). EFSA Journal, 5(7), 530. https://doi.org/10.2903/j.efsa.2007.530

11. Kapoor, B., Kapoor, D., Gautam, S., Singh, R., & Bhardwaj, S. (2021). Dietary polyunsaturated fatty acids (pufas): Uses and potential health benefits. Current Nutrition Reports, 10(3), 232-242. https://doi.org/10.1007/s13668-021-00363-3

12. De Carvalho, C., & Caramujo, M. (2018). The various roles of fatty acids. Molecules, 23(10), 2583. https://doi.org/10.3390/molecules23102583

13. Boeldt, D. S., & Joss-Moore, L. (2023). The wide reach of fatty acids and their metabolites. Molecular and Cellular Endocrinology, 560, 111823. https://doi.org/10.1016/j. mce.2022.111823

14. Scientific opinion on dietary reference values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. (2010). EFSA Journal, 8(3). https://doi.org/10.2903/j. efsa.2010.1461

15. Sastry, P. S. (1985). Lipids of nervous tissue: Composition and metabolism. Progress in Lipid Research, 24(2), 69-176. https://doi.org/10.1016/0163-7827(85)90011-6

16. Michalak, A., Mosińska, P., & Fichna, J. (2016). Polyunsaturated fatty acids and their derivatives: Therapeutic value for inflammatory, functional gastrointestinal disorders, and colorectal cancer. Frontiers in Pharmacology, 7. https://doi.org/10.3389/fphar.2016.00459

17. Glaser, C., Heinrich, J., & Koletzko, B. (2010). Role of FADS1 and fads2 polymorphisms in polyunsaturated fatty acid metabolism. Metabolism, 59(7), 993-999. https://doi.org/10.1016/j.metabol.2009.10.022

18. Gomolka, B., Siegert, E., Blossey, K., Schunck, W.-H., Rothe, M., & Weylandt, K. H. (2011). Analysis of omega-3 and omega-6 fatty acid-derived lipid metabolite formation in human and mouse blood samples. Prostaglandins & Other Lipid Mediators, 94(3-4), 81-87. https://doi.org/10.1016/j.prostaglandins.2010.12.006

19. Powell, W. S., & Rokach, J. (2015). Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (hetes) and oxoeicosatetraenoic acids (oxo-etes) derived from arachidonic acid. Biochimica et Biophysica Acta (BBA) -Molecular and Cell Biology of Lipids, 1851(4), 340-355. https://doi.org/10.1016/j. bbalip.2014.10.008

20. Roy, J., Le Guennec, J.-Y., Galano, J.-M., Thireau, J., Bultel-Poncé, V., Demion, M., Oger, C., Lee, J. C.-Y., & Durand, T. (2016). Non-enzymatic cyclic oxygenated metabolites of omega-3 polyunsaturated fatty acid: Bioactive drugs? Biochimie, 120, 56-61. https://doi.org/10.1016/j.biochi.2015.06.010

21. Calder, P. C. (2020). Eicosanoids. Essays in Biochemistry, 64(3), 423-441. https://doi.org/10.1042/ebc20190083

22. Fiedler, P., Wolkin, A., & Rotrosen, J. (1986). Niacin-induced flush as a measure of prostaglandin activity in alcoholics and schizophrenics. Biological Psychiatry, 21(13), 1347-1350. https://doi.org/10.1016/0006-3223(86)90321-5

23. Félétou, M., Huang, Y., & Vanhoutte, P. M. (2011). Endothelium¬mediated control of vascular tone: Cox-1 and cox-2 products. British Journal of Pharmacology, 164(3), 894-912. https://doi.org/10.1111/j.1476-5381.2011.01276.x

24. Stenson, W. F. (2014). The universe of arachidonic acid metabolites in inflammatory bowel disease. Current Opinion in Gastroenterology, 30(4), 347-351. https://doi.org/10.1097/mog.0000000000000075

25. Maderna, P., & Godson, C. (2009). Lipoxins: Resolutionary road. British Journal of Pharmacology, 158(4), 947-959. https://doi.org/10.1111/j.1476-5381.2009.00386.x.

26. Calder, P. C. (2013). N-3 fatty acids, inflammation and immunity: New mechanisms to explain old actions. Proceedings of the Nutrition Society, 72(3), 326-336. https://doi.org/10.1017/ s0029665113001031

27. Marion-Letellier, R., Savoye, G., & Ghosh, S. (2015). Polyunsaturated fatty acids and inflammation. IUBMB Life, 67(9), 659-667. https://doi.org/10.1002/iub.1428

28. Kinney, J., & Ljungqvist, O. (2003). Evolution of nutritional science-carbohydrates. Clinical Nutrition, 22, 17-21. https://doi.org/10.1016/s0261-5614(03)00148-1

29. Haroon, E., Daguanno, A. W., Woolwine, B. J., Goldsmith, D. R., Baer, W. M., Wommack, E. C., Felger, J. C., & Miller, A. H. (2018). Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinology, 95, 43-49. https://doi.org/10.1016/j.psyneuen.2018.05.026

30. Strawbridge, R., Arnone, D., Danese, A., Papadopoulos, A., Herane Vives, A., & Cleare, A. J. (2015). Inflammation and clinical response to treatment in depression: A meta-analysis. European Neuropsychopharmacology, 25(10), 1532-1543. https://doi.org/10.1016/j.euroneuro.2015.06.007

31. Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G, Suridjan I, Kennedy JL, Rekkas PV, Houle S, Meyer JH. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry. 2015 Mar;72(3):268-75. doi: 10.1001/jamapsychiatry.2014.2427. PMID: 25629589; PMCID: PMC4836849

32. Kofod, J., Elfving, B., Nielsen, E. H., Mors, O., & Köhler-Forsberg, O. (2022). Depression and inflammation: Correlation between changes in inflammatory markers with antidepressant response and long-term prognosis. European Neuropsychopharmacology, 54, 116-125. https://doi.org/10.1016/j.euroneuro.2021.09.006

33. Guo, B., Zhang, M., Hao, W., Wang, Y., Zhang, T., & Liu, C. (2023). Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression. Translational Psychiatry, 13(1). https://doi.org/10.1038/s41398-022-02297-y

34. Henke, P. G. (1982). The telencephalic limbic system and Experimental Gastric Pathology: A Review. Neuroscience & Biobehavioral Reviews, 6(3), 381-390. https://doi.org/10.1016/0149-7634(82)90047-1

35. Torres-Platas, S. G., Cruceanu, C., Chen, G. G., Turecki, G., & Mechawar, N. (2014). Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain, Behavior, and Immunity, 42, 50-59. https://doi.org/10.1016/j.bbi.2014.05.007

36. McNamara, R. K., Jandacek, R., Rider, T., Tso, P., Stanford, K. E., Hahn, C.-G., & Richtand, N. M. (2008). Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder. Psychiatry Research, 160(3), 285-299. https://doi.org/10.1016/j.psychres.2007.08.021

37. Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., & Critchley, H. D. (2009). Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biological Psychiatry, 66(5), 407-414. https://doi.org/10.1016/j.biopsych.2009.03.015

38. Larrieu, T., & Layé, S. (2018). Food for mood: Relevance of nutritional omega-3 fatty acids for depression and anxiety. Frontiers in Physiology, 9. https://doi.org/10.3389/ fphys.2018.01047.

39. Hibbeln, J., & Salem, N. (1995). Dietary polyunsaturated fatty acids and depression: When cholesterol does not satisfy. The American Journal of Clinical Nutrition, 62(1), 1-9. https://doi.org/10.1093/ajcn/62.1.1

40. McNamara, R. K., Strimpfel, J., Jandacek, R., Rider, T., Tso, P., Welge, J. A., Strawn, J. R., & DelBello, M. P. (2014). Detection and treatment of long-chain omega-3 fatty acid deficiency in adolescents with SSRI-resistant major depressive disorder. PharmaNutrition, 2(2), 38-46. https://doi.org/10.1016/j.phanu.2014.02.002

41. Green, P., Hermesh, H., Monselise, A., Marom, S., Presburger, G., & Weizman, A. (2006). Red cell membrane omega-3 fatty acids are decreased in nondepressed patients with social anxiety disorder. European Neuropsychopharmacology, 16(2), 107-113. https://doi.org/10.1016/j.euroneuro.2005.07.005

42. Scola, G., Versace, A., Metherel, A. H., Monsalve-Castro, L. A., Phillips, M. L., Bazinet, R. P., & Andreazza, A. C. (2018). Alterations in peripheral fatty acid composition in bipolar and Unipolar Depression. Journal of Affective Disorders, 233, 86-91. https://doi.org/10.1016/j.jad.2017.12.025

43. Hopperton, K. E., Trépanier, M.-O., Giuliano, V., & Bazinet, R. P. (2016). Brain omega-3 polyunsaturated fatty acids modulate microglia cell number and morphology in response to intracerebroventricular amyloid-β 1-40 in mice. Journal of Neuroinflammation, 13(1). https://doi.org/10.1186/s12974-016-0721-5

44. Chen, S., Zhang, H., Pu, H., Wang, G., Li, W., Leak, R. K., Chen, J., Liou, A. K., & Hu, X. (2014). N-3 PUFA supplementation benefits microglial responses to myelin pathology. Scientific Reports, 4(1). https://doi.org/10.1038/srep07458

45. Fourrier, C., Remus-Borel, J., Greenhalgh, A. D., Guichardant, M., Bernoud-Hubac, N., Lagarde, M., Joffre, C., & Layé, S. (2017). Docosahexaenoic acid-containing choline phospholipid modulates LPS-induced neuroinflammation in vivo and in microglia in vitro. Journal of Neuroinflammation, 14(1). https://doi.org/10.1186/s12974-017-0939-x

46. Shelton, R. C., Osuntokun, O., Heinloth, A. N., & Corya, S. A. (2010). Therapeutic options for treatment-resistant depression. CNS Drugs, 24(2), 131-161. https://doi.org/10.2165/11530280¬000000000-00000

47. Xiong, R.-G., Li, J., Cheng, J., Wu, S.-X., Huang, S.-Y., Zhou, D.-D., Saimaiti, A., Shang, A., Tang, G.-Y., Li, H.-B., Gan, R.-Y., & Feng, Y. (2023). New insights into the protection of dietary components on anxiety, depression, and other mental disorders caused by contaminants and food additives. Trends in Food Science & Technology, 138, 44-56. https://doi.org/10.1016/j. tifs.2023.06.004

48. Generoso JS, Giridharan VV, Lee J, Macedo D, Barichello T. The role of the microbiota-gut-brain axis in neuropsychiatric disorders. Braz J Psychiatry. 2021 May-Jun;43(3):293-305. doi: 10.1590/1516-4446-2020-0987. PMID: 32667590; PMCID: PMC8136391

49. Ortega M. A., Álvarez-Mon M. A., García-Montero C., Fraile-Martínez Ó., Monserrat J., Martinez-Rozas L., Rodríguez-Jiménez R., Álvarez-Mon M., Lahera G. (2023). Microbiota-Gut-Brain Axis mechanisms in the complex network of bipolar disorders: Potential clinical implications and translational opportunities. Molecular Psychiatry, 28(7), 2645-2673. https://doi.org/10.1038/s41380-023-01964-w

50. Bhatia N. Y., Jalgaonkar M. P., Hargude A. B., Sherje A. P., Oza M. J., & Doshi G. M. (2023). Gut-brain axis and neurological disorders-how microbiomes affect our mental health. CNS & Neurological Disorders -Drug Targets, 22(7), 1008-1030. https://doi.org/10.2174/1871527321666220822172039

51. Kennedy, P. J., Murphy, A. B., Cryan, J. F., Ross, P. R., Dinan, T. G., & Stanton, C. (2016). Microbiome in brain function and mental health. Trends in Food Science & Technology, 57, 289-301. https://doi.org/10.1016/j.tifs.2016.05.001

52. Liu, L., Wang, H., Chen, X., Zhang, Y., Zhang, H., & Xie, P. (2023). Gut microbiota and its metabolites in depression: From pathogenesis to treatment. eBioMedicine, 90, 104527. https://doi.org/10.1016/j.ebiom.2023.104527

53. Lakhan, S. E., & Vieira, K. F. (2008). Nutritional therapies for mental disorders. Nutrition Journal, 7(1). https://doi.org/10.1186/1475-2891-7-2

54. Yılmaz, C., & Gökmen, V. (2020). Neuroactive compounds in foods: Occurrence, mechanism and potential health effects. Food Research International, 128, 108744. https://doi.org/10.1016/j.foodres.2019.108744

55. Hepsomali, P., & Groeger, J. A. (2021). Diet, sleep, and mental health: Insights from the UK biobank study. Nutrients, 13(8), 2573. https://doi.org/10.3390/nu13082573

56. Kim, C.-S., Shin, G.-E., Cheong, Y., Shin, J., Shin, D.-M., & Chun, W. Y. (2022). Experiencing social exclusion changes gut microbiota composition. Translational Psychiatry, 12(1). https://doi.org/10.1038/s41398-022-02023-8

57. Malan-Müller, S., Valles-Colomer, M., Palomo, T., & Leza, J. C. (2023). The gut-microbiota-brain axis in a Spanish population in the aftermath of the COVID-19 pandemic: Microbiota composition linked to anxiety, trauma, and Depression Profiles. Gut Microbes, 15(1). https://doi.org/10.1080/1949097 6.2022.2162306

58. Quin, C., Vollman, D. M., Ghosh, S., Haskey, N., Estaki, M., Pither, J., Barnett, J. A., Jay, M. N., Birnie, B. W., & Gibson, D. L. (2020). Fish oil supplementation reduces maternal defensive inflammation and predicts a gut bacteriome with reduced immune priming capacity in infants. The ISME Journal, 14(8), 2090-2104. https://doi.org/10.1038/s41396-020-0672-9

59. Cao, W., Wang, C., Chin, Y., Chen, X., Gao, Y., Yuan, S., Xue, C., Wang, Y., & Tang, Q. (2019). Dha-phospholipids (DHA-PL) and EPA-phospholipids (EPA-PL) prevent intestinal dysfunction induced by chronic stress. Food & Function, 10(1), 277-288. https://doi.org/10.1039/c8fo01404c

60. Warner, D. R., Warner, J. B., Hardesty, J. E., Song, Y. L., King, T. N., Kang, J. X., Chen, C.-Y., Xie, S., Yuan, F., Prodhan, M. A., Ma, X., Zhang, X., Rouchka, E. C., Maddipati, K. R., Whitlock, J., Li, E. C., Wang, G. P., McClain, C. J., & Kirpich, I. A. (2019). Decreased ω-6:ω-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury. Journal of Lipid Research, 60(12), 2034-2049. https://doi.org/10.1194/jlr.ra119000200

61. Zeyda, M., Staffler, G., Hořejšı́, V., Waldhäusl, W., & Stulnig, T. M. (2002). Lat displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signaling by polyunsaturated fatty acids. Journal of Biological Chemistry, 277(32), 28418-28423. https://doi.org/10.1074/jbc. m203343200

62. Husson, M.-O., Ley, D., Portal, C., Gottrand, M., Hueso, T., Desseyn, J.-L., & Gottrand, F. (2016). Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids. Journal of Infection, 73(6), 523-535. https://doi.org/10.1016/j.jinf.2016.10.001

63. Guu, T. W., Mischoulon, D., Sarris, J., Hibbeln, J., McNamara, R. K., Hamazaki, K., et. al. (2019). International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder. Psychotherapy and psychosomatics, 88(5), 263-273. https://doi.org/10.1159/000502652.

64. Guu, T. W., Mischoulon, D., Sarris, J., Hibbeln, J., McNamara, R. K., Hamazaki, K., et. al. (2020). A multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder. Journal of affective disorders, 265, 233-238. https://doi.org/10.1016/j.jad.2020.01.050

65. Sarris, J., Ravindran, A., Yatham, L. N., Marx, W., Rucklidge, J. J., McIntyre, R. S., et al. (2022). Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 23(6), 424-455. https://doi.org/10.1080/15622975.2021.2013041

66. Chang, J. P., & Su, K. P. (2020). Nutritional Neuroscience as Mainstream of Psychiatry: The Evidence-Based Treatment Guidelines for Using Omega-3 Fatty Acids as a New Treatment for Psychiatric Disorders in Children and Adolescents. Clinical psychopharmacology and neuroscience: the official scientific journal of the Korean College of Neuropsychopharmacology, 18(4), 469-483. https://doi.org/10.9758/cpn.2020.18.4.469

67. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry. 2006Jun;163(6):1098-100.

Downloads

Published

2025-01-09