Zinc, Copper, and Manganese Supplementations in Rheumatic Disease: A Narrative Review

Trace elements, including zinc (Zn), copper (Cu), and manganese (Mn), play crucial roles in various biological functions, particularly in oxidative stress regulation and immune response. Their potential involvement in rheumatic diseases has been suggested, with evidence indicating altered levels of these elements in conditions such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the efficacy of supplementation remains unclear.

This narrative review aims to evaluate the available evidence on Zn, Cu, and Mn supplementation in patients with rheumatic diseases.

A comprehensive literature search was conducted in PubMed, Scielo, and LILACS databases for studies published from 1965 to April 2024. The search followed PRISMA guidelines and included randomised controlled trials (RCTs) and observational studies investigating Zn, Cu, or Mn supplementation in rheumatic diseases.

A total of four studies met the inclusion criteria, focusing on Zn and Cu supplementation. No studies on Mn supplementation were identified. Among the included studies, two evaluated Zn supplementation in RA and Behçet's disease, while two assessed Cu supplementation in RA and SLE. The mean participant age ranged from 35 to 54.3 years, with female predominance (28% to 89%). Follow-up durations varied from 4 to 24 weeks. Zn supplementation demonstrated clinical and immunological benefits, including reduced disease activity in Behçet's disease and improved inflammatory markers in RA. Conversely, Cu supplementation did not show significant therapeutic effects. Reported side effects were mild and primarily gastrointestinal, occurring in 4% to 33% of participants.

Zn supplementation appears beneficial in certain rheumatic diseases, particularly in RA and Behçet's disease, while Cu supplementation lacks significant therapeutic effects. Further high-quality RCTs are needed to establish definitive recommendations.