Is copper deficiency a concern in celiac disease (CD) patients that can contribute to anemia?

Copper Deficiency in Celiac Disease and Its Role in Anemia

Copper deficiency is not a major concern in most celiac disease patients with anemia, but should be considered in cases of persistent anemia that doesn't respond to iron supplementation and a gluten-free diet. 1

Primary Causes of Anemia in Celiac Disease

Iron deficiency is the predominant cause of anemia in celiac disease, occurring through several mechanisms:

1. Duodenal villous atrophy: Damages the primary site of iron absorption 1
2. Chronic inflammation: Contributes to anemia of chronic disease 2
3. Malabsorption of other nutrients: Including folate (12% of patients) and vitamin B12 (5% of patients) 3

Copper Status in Celiac Disease

Current evidence regarding copper deficiency in celiac disease shows:

• According to the 2024 guidelines for monitoring established celiac disease, there are no significant differences in copper levels between celiac patients and the general population 1
• A study analyzing the National Health and Nutrition Examination Survey (2009-2014) found that copper levels in people with celiac disease were similar to those without celiac disease, despite reduced caloric intake 1
• However, case reports have documented copper deficiency in some celiac patients, which can contribute to anemia and neutropenia 4, 5

When to Consider Copper Deficiency

Consider copper deficiency in celiac patients with:

• Persistent anemia despite adherence to a gluten-free diet and iron supplementation 2
• Concurrent neutropenia 5
• Neurological symptoms alongside hematologic abnormalities 4
• Severe malabsorption or extensive small bowel involvement 1

Diagnostic Approach for Anemia in Celiac Disease

1. First-line testing:

   • Complete blood count
   • Iron studies (ferritin, transferrin saturation) 1
   • Folate and vitamin B12 levels 3
   • Inflammatory markers (ESR, CRP) 3

2. Second-line testing (if anemia persists):

   • Copper levels (serum copper <12 μmol/L with elevated CRP suggests deficiency) 1
   • Evaluate gluten-free diet adherence through antibody testing 1
   • Consider follow-up duodenal biopsy to assess mucosal healing 1

Management Algorithm

1. Initial approach:

   • Strict gluten-free diet (primary treatment) 1
   • Iron supplementation for iron deficiency anemia 1

2. For persistent anemia:

   • Verify strict gluten-free diet adherence 1
   • Consider IV iron if oral iron is ineffective (especially with severe villous atrophy) 1
   • Test for copper deficiency if anemia persists despite above measures 4

3. If copper deficiency confirmed (levels <8 μmol/L):

   • Provide copper supplementation (4-8 mg/day) 1
   • Monitor response after 2-3 months 5

Important Clinical Considerations

• Up to 20% of celiac patients remain iron deficient despite strict gluten-free diet adherence 1
• Copper deficiency can cause irreversible myeloneuropathy if not detected and treated appropriately 4
• Children with celiac disease may be at higher risk for zinc deficiency than adults, which can interact with copper metabolism 6
• Anemia in celiac disease is often multifactorial - consider both nutritional deficiencies and inflammation 3

Monitoring Recommendations

• Monitor hemoglobin and ferritin during follow-up, particularly in premenopausal women 1
• Consider copper testing in patients with persistent anemia and neurological symptoms 4
• Reassess nutritional status after at least 12-24 months on a gluten-free diet to allow for intestinal healing 7