The Role of Zinc in the Pathophysiology and Treatment of Depressive Disorders: A Literature Review
DOI:
https://doi.org/10.12775/QS.2026.55.71261Keywords
depression, zinc, zinc deficiency, zinc supplementationAbstract
Background. Depression is one of the most common mental disorders worldwide and represents a major public health concern. Increasing evidence suggests that dietary factors, including trace elements such as zinc, may play a role in the development and course of depressive disorders. Zinc is involved in numerous biological processes within the central nervous system, including neurotransmission, neuroplasticity, immune regulation, and oxidative balance.
Aim. The aim of this study was to review the current literature on the role of zinc in the pathophysiology and treatment of depressive disorders, with particular emphasis on underlying biological mechanisms, clinical findings, and potential therapeutic implications.
Material and methods. The studies cited in the presented review were selected from Pubmed and Google Scholar. The search included studies between 2020 and 2026. The key words used for the search included: depression; zinc; zinc deficiency; zinc supplementation
Results. The available literature indicates that zinc deficiency is frequently observed in patients with depression and is associated with greater severity of symptoms. Experimental and clinical studies suggest that zinc influences key mechanisms implicated in depression, including NMDA receptor modulation, regulation of brain-derived neurotrophic factor (BDNF), dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and inflammatory processes. Furthermore, zinc supplementation may enhance the efficacy of antidepressant therapy and improve clinical outcomes, particularly when used as an adjunctive treatment.
Conclusions. Zinc appears to play a significant role in the pathophysiology of depression and may represent a promising target for adjunctive therapeutic strategies. However, further well-designed randomized controlled trials are required to establish optimal supplementation protocols and to better define the clinical applicability of zinc in depressive disorders.
References
Chen, X., Liu, X., Li, F. et al. Depression and health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies. Transl Psychiatry 15, 298 (2025). https://doi.org/10.1038/s41398-025-03463-8
de Sousa, R. D., Zagalo, D. M., Costa, T., de Almeida, J. M. C., Canhão, H., & Rodrigues, A. (2025). Exploring depression in adults over a decade: a review of longitudinal studies. BMC psychiatry, 25(1), 378. https://doi.org/10.1186/s12888-025-06828-x
Kim, J., Kim, I., Lee, J., Jeon, K., Kang, J., Lee, D., Choi, S., Kim, H., & Son, M. (2025). Mineral Intake and Depression: A Cross-Sectional Comparative Study Based on National Health and Nutrition Examination Surveys in Korea and the United States. Nutrients, 17(16), 2593. https://doi.org/10.3390/nu17162593
Li, Z., Liu, Y., Wei, R., Yong, V. W., & Xue, M. (2022). The Important Role of Zinc in Neurological Diseases. Biomolecules, 13(1), 28. https://doi.org/10.3390/biom13010028
Kumar, V., Kumar, A., Singh, K., Avasthi, K., & Kim, J. J. (2021). Neurobiology of zinc and its role in neurogenesis. European journal of nutrition, 60(1), 55–64. https://doi.org/10.1007/s00394-020-02454-3
Choi, S., Hong, D. K., Choi, B. Y., & Suh, S. W. (2020). Zinc in the Brain: Friend or Foe?. International journal of molecular sciences, 21(23), 8941. https://doi.org/10.3390/ijms21238941
Wang, B., Fang, T., & Chen, H. (2023). Zinc and Central Nervous System Disorders. Nutrients, 15(9), 2140. https://doi.org/10.3390/nu15092140
Thingholm, T. E., Rönnstrand, L., & Rosenberg, P. A. (2020). Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation. Cellular and molecular life sciences : CMLS, 77(16), 3085–3102. https://doi.org/10.1007/s00018-020-03473-3
Li, Y., Lu, Y., Lin, X., & Zhao, L. (2026). The role of zinc homeostasis in major depressive disorder: heterogeneous pathological mechanisms and therapeutic implications. Annals of medicine, 58(1), 2611191. https://doi.org/10.1080/07853890.2025.2611191
Gąsior, Ł., Pochwat, B., Zaręba-Kozioł, M., Włodarczyk, J., Grabrucker, A. M., & Szewczyk, B. (2025). Proteomics analysis in rats reveals convergent mechanisms between major depressive disorder and dietary zinc deficiency. Pharmacological reports : PR, 77(1), 145–157. https://doi.org/10.1007/s43440-024-00681-7
Huang, D., Lai, S., Zhong, S., & Jia, Y. (2023). Association between serum copper, zinc, and selenium concentrations and depressive symptoms in the US adult population, NHANES (2011-2016). BMC psychiatry, 23(1), 498. https://doi.org/10.1186/s12888-023-04953-z
Quan, Z., Li, H., Quan, Z., & Qing, H. (2023). Appropriate Macronutrients or Mineral Elements Are Beneficial to Improve Depression and Reduce the Risk of Depression. International journal of molecular sciences, 24(8), 7098. https://doi.org/10.3390/ijms24087098
Baddam S, Maxfield L, Shukla S, Crane JS. Zinc Deficiency. 2025 Aug 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 29630283.
Kunugi H. (2023). Depression and lifestyle: Focusing on nutrition, exercise, and their possible relevance to molecular mechanisms. Psychiatry and clinical neurosciences, 77(8), 420–433. https://doi.org/10.1111/pcn.13551
Bagarić, T., Mihaljević-Peleš, A., Skočić Hanžek, M., Živković, M., Kozmar, A., & Rogić, D. (2024). Serum Levels of Zinc, Albumin, Interleukin-6 and CRP in Patients with Unipolar and Bipolar Depression: Cross Sectional Study. Current issues in molecular biology, 46(5), 4533–4550. https://doi.org/10.3390/cimb46050275
Aoki, C., Imai, K., Owaki, T., Kobayashi-Nakano, T., Ushida, T., Iitani, Y., Nakamura, N., Kajiyama, H., & Kotani, T. (2022). The Possible Effects of Zinc Supplementation on Postpartum Depression and Anemia. Medicina (Kaunas, Lithuania), 58(6), 731. https://doi.org/10.3390/medicina58060731
Rafało-Ulińska, A., Pochwat, B., Misztak, P., Bugno, R., Kryczyk-Poprawa, A., Opoka, W., Muszyńska, B., Poleszak, E., Nowak, G., & Szewczyk, B. (2022). Zinc Deficiency Blunts the Effectiveness of Antidepressants in the Olfactory Bulbectomy Model of Depression in Rats. Nutrients, 14(13), 2746. https://doi.org/10.3390/nu14132746
Bederska-Łojewska, D., Szczepanik, K., Turek, J., Machaczka, A., Gąsior, Ł., Pochwat, B., Piotrowska, J., Rospond, B., & Szewczyk, B. (2024). Dietary Zinc Restriction and Chronic Restraint Stress Affect Mice Physiology, Immune Organ Morphology, and Liver Function. Nutrients, 16(22), 3934. https://doi.org/10.3390/nu16223934
Li, J., Cao, D., Huang, Y., Chen, B., Chen, Z., Wang, R., Dong, Q., Wei, Q., & Liu, L. (2022). Zinc Intakes and Health Outcomes: An Umbrella Review. Frontiers in nutrition, 9, 798078. https://doi.org/10.3389/fnut.2022.798078
Xu, Y., Zeng, L., Zou, K., Shan, S., Wang, X., Xiong, J., Zhao, L., Zhang, L., & Cheng, G. (2021). Role of dietary factors in the prevention and treatment for depression: an umbrella review of meta-analyses of prospective studies. Translational psychiatry, 11(1), 478. https://doi.org/10.1038/s41398-021-01590-6
Ekinci, G. N., & Sanlier, N. (2023). The relationship between nutrition and depression in the life process: A mini-review. Experimental gerontology, 172, 112072. https://doi.org/10.1016/j.exger.2022.112072
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Aleksandra Przygoda, Aleksandra Skowron, Jakub Orzeł, Patrycja Pelczar
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 13
Number of citations: 0
