Role of Zinc, Copper, and Vitamin D in Alopecia Areata Explored

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Affecting 0.5% to 2% of the global population, alopecia areata (AA) has increasingly been observed in younger demographics.¹ The psychological impact of AA, including anxiety and depression, is significant, and the condition is associated with comorbidities like thyroid disorders, systemic lupus erythematosus, and secondary skin infections.² The economic burden is notable; in Japan alone, the annual cost of AA is estimated at $857 million, with patients incurring average monthly medication expenses of $32.42.³

The etiology of AA is multifactorial and involves genetic predisposition, environmental triggers, and psychological stress.⁴ Recently, the role of micronutrients in AA has garnered attention, particularly the potential contributions of zinc, copper, and vitamin D (VD). Zinc is essential for hair follicle growth and repair, with deficiencies linked to impaired follicular function and hair loss.⁵ Studies have reported significantly lower serum zinc levels in patients with AA compared to healthy controls.⁶ Copper supports angiogenesis and vessel integrity, aiding hair follicle blood supply and serving as a cofactor for enzymes critical for antioxidant defense and melanogenesis. However, evidence on copper’s role in AA remains mixed, with some studies finding no significant differences in serum copper levels between patients and controls.^7-8 VD, through its receptor, regulates hair follicle cycling, with deficiencies correlating with increased AA risk.⁹

Objectives and Methodology

To better understand the relationship between serum trace elements and AA risk, a systematic review and meta-analysis was conducted.¹⁰ The study included human research retrieved from PubMed, Web of Science, EMBASE, and Cochrane Library databases until May 2024. Inclusion criteria encompassed studies involving patients with AA and healthy controls, assessing serum zinc, copper, and VD levels. Data extraction and quality assessment were performed independently by 2 researchers, with disagreements resolved by a third reviewer.

Results

Vitamin D

Twenty-three studies, encompassing 3,404 participants, showed that serum VD levels inpatients with AA were significantly lower than in controls. The meta-analysis revealed a pooled standardized mean difference (SMD) of -0.93 ng/mL (95% CI: 0.168–0.747). Additionally, VD deficiency increased AA risk (OR: 2.48; 95% CI: 1.47–4.17).

Zinc

Analysis of 10 studies with 878 participants found consistently lower serum zinc levels inpatients with AA compared to controls. The pooled SMD was -0.69 μg/dL (95% CI: -0.99 to -0.39).

Copper

The analysis found 5 studies with a total of 339 participants showed conflicting results, with no significant differences in serum copper levels betweenpatients with AA and controls (SMD: 0.27μg/dL; 95% CI: -0.49 to 1.04).

Discussion and Clinical Implications

This meta-analysis highlights the significant association between serum deficiencies in zinc and VD with increased AA risk, while the role of copper remains inconclusive. Subgroup analyses and sensitivity testing confirmed the robustness of findings for VD and zinc but indicated variability in copper-related results. Limitations included high heterogeneity across studies, reliance on cross-sectional designs, and unaccounted factors like disease severity or duration.

The findings underscore the potential of VD and zinc supplementation as adjunctive therapies for AA. Researchers suggested future research should focus on longitudinal studies to establish causal relationships and consider disease-specific factors to refine therapeutic interventions. Additionally, they stated standardized reporting of trace element levels and their correlation with disease activity is vital for advancing understanding and treatment.

Conclusion

The analysis found deficiencies in VD and zinc are significant risk factors for AA, warranting further investigation and targeted therapeutic strategies. Researchers stated comprehensive management of AA should integrate nutritional assessments and tailored supplementation to improve patient outcomes and reduce the broader healthcare burden.

References

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10. Wu R, Li Y, Peng H, et al. Association between serum trace elements level and alopecia areata: A systematic review and meta-analysis. J Cosmet Dermatol. 2025;24(1):e16740. doi:10.1111/jocd.16740