Psychiatry
META ANALYSIS
● Meta-analysis
Serum Zinc and Iron Levels Reduced in MDD; Copper Levels Elevated
Reviews on environmental health
Published March 27, 2026
Davarinejad Omran, Nasseri Zahraalsadat, Mansouri Borhan
PubMed ↗
DOI ↗
This systematic review and meta-analysis evaluated the association between serum levels of zinc, iron, and copper and Major Depressive Disorder (MDD) by analyzing data from 16 observational studies. The primary endpoint was the difference in serum concentrations of these trace elements between MDD patients and healthy controls. Results indicated that individuals with MDD had significantly lower serum zinc (SMD = -0.62; 95% CI: -0.78 to -0.46; I=68.4%) and iron levels (SMD = -0.36; 95% CI: -0.52 to -0.20; I=58.2%), while copper levels were significantly higher (SMD = +0.42; 95% CI: +0.18 to +0.66; I=67.4%). Heterogeneity was moderate to high across studies, and publication bias was noted for zinc and copper, though adjusted estimates for zinc and iron remained significant. No specific safety or adverse events were reported as the study focused on observational data. Clinically, these findings underscore the importance of considering micronutrient status in the pathophysiology and management of depression, suggesting potential avenues for nutritional interventions in psychiatric care. Further research is needed to explore the therapeutic implications of these findings.
AI Accuracy Review: 10/10
· Auto-published
This study focuses on major depressive disorder (MDD), a serious mental health condition that affects mood and daily life. Researchers reviewed 16 studies to compare the levels of important minerals—zinc, iron, and copper—in people with MDD and those without. They discovered that individuals with depression had lower levels of zinc and iron, which are important for brain health, while their copper levels were higher. This suggests that these minerals might play a role in depression. For patients, this could mean that checking and possibly improving zinc and iron levels might help with managing depression. However, it's important to note that the findings about copper were less clear, and more research is needed to understand these relationships better. Future studies could explore how nutrition might support mental health treatment.
What this means for you: Low levels of zinc and iron may be linked to major depression, highlighting the need for nutritional checks.
View Original Abstract ↓
INTRODUCTION: Trace elements such as zinc, iron, and copper are integral to neurochemical regulation, oxidative balance, and immune modulation. Their dysregulation has been increasingly implicated in the pathophysiology of Major Depressive Disorder (MDD). This systematic review and meta-analysis aimed to quantify differences in serum levels of zinc, iron, and copper between individuals with MDD and healthy controls.
CONTENT: Sixteen observational studies were included following a comprehensive search of major databases. Data on serum concentrations of zinc, iron, and copper were extracted and pooled using a random-effects model. Standardized mean differences (SMDs) with 95 % confidence intervals (CIs) were calculated. Heterogeneity was assessed using the I statistic, and publication bias was evaluated via funnel plots and Egger's regression. Sensitivity analyses were conducted to test the robustness of findings.
SUMMARY: Meta-analysis revealed serum copper levels were significantly higher in patients with MDD compared to controls (SMD = +0.42; 95 % CI: +0.18 to +0.66; I=67.4 %), while zinc (SMD = -0.62; 95 % CI: -0.78 to -0.46; I=68.4 %) and iron (SMD = -0.36; 95 % CI: -0.52 to -0.20; I=58.2 %) were lower in MDD patients. Evidence of publication bias was observed for zinc and copper, but adjusted estimates remained significant for zinc and iron.
OUTLOOK: This study demonstrates consistent reductions in serum zinc and iron among individuals with MDD, supporting their potential role in depressive pathophysiology. While copper findings were inconclusive, the stability of zinc and iron results highlights the clinical relevance of micronutrient assessment in depression. These findings provide a foundation for future research in nutritional psychiatry and adjunctive treatment strategies.