Copper Supplementation with Zinc in Behçet's Disease
Yes, copper supplementation is required when using therapeutic zinc supplementation, particularly at doses used to correct hypozincemia, to prevent copper deficiency and its serious complications.
Critical FDA Warning on Zinc-Induced Copper Deficiency
The FDA explicitly warns that high doses of supplemental zinc (approximately 10 times the recommended maintenance dose of 3 mg/day) taken over extended periods can result in decreased copper absorption and copper deficiency 1. The reported complications of copper deficiency include:
If signs of copper deficiency develop during zinc treatment, interrupt zinc supplementation immediately and check zinc, copper, and ceruloplasmin levels 1.
Recommended Copper Supplementation Protocol
Based on bariatric surgery guidelines (which address therapeutic zinc supplementation protocols), concurrent copper supplementation of 2 mg daily is recommended when using therapeutic zinc doses 2. This can be provided through:
- A complete multivitamin and mineral supplement containing 2 mg copper 2
- Standalone copper supplementation if not adequately provided in multivitamin 2
Specific Considerations for Your Patient
Your patient with Behçet's disease on azathioprine and prednisone requires particular attention because:
- Azathioprine can cause myelosuppression (leukopenia occurs in 57% of patients on long-term azathioprine) 2, which overlaps with copper deficiency complications 1
- The combination of zinc-induced copper deficiency and azathioprine-related bone marrow suppression could create additive hematologic toxicity 2, 1
- Copper deficiency itself causes leukopenia, which could be misattributed to azathioprine, potentially leading to inappropriate dose adjustments 1
Monitoring Requirements
Monitor the following parameters regularly during zinc supplementation 1:
- Zinc concentrations 1
- Copper and ceruloplasmin levels 1
- Complete blood count (for anemia, leukopenia, thrombocytopenia) 1
- Neurological examination (for myeloneuropathy) 1
Common Pitfall to Avoid
Do not attribute new-onset cytopenias solely to azathioprine without checking copper levels 1. The clinical presentation of copper deficiency (anemia, leukopenia, thrombocytopenia) mimics azathioprine toxicity, but the treatments are opposite—copper deficiency requires copper supplementation and zinc discontinuation, while azathioprine toxicity requires dose reduction 2, 1.
Baseline Copper Status Consideration
Given that oxidative stress is elevated in Behçet's disease and plasma copper levels may already be altered (one study found elevated copper in BD patients) 3, obtain baseline copper and ceruloplasmin levels before initiating zinc supplementation to establish a reference point for monitoring 1.