What are the causes of copper deficiency in patients with gastrointestinal disorders, such as celiac disease, Crohn's disease, or ulcerative colitis, and those undergoing treatments like hemodialysis or taking medications such as zinc supplements?

Causes of Copper Deficiency

Copper deficiency develops through four primary mechanisms: malabsorption from gastrointestinal disorders or surgery, excessive zinc intake that competitively inhibits copper absorption, inadequate dietary intake or prolonged parenteral nutrition without adequate supplementation, and increased gastrointestinal losses from fistulae or ostomies. 1

Gastrointestinal Malabsorption

Surgical Causes

• Bariatric surgery, particularly Roux-en-Y gastric bypass, is the most common surgical cause because copper is absorbed primarily in the stomach, duodenum, and jejunum—areas bypassed or altered by these procedures 2, 3, 4
• Gastrectomy and subtotal colectomy with small bowel resections impair copper absorption at critical intestinal sites 2
• Short bowel syndrome from any cause reduces the absorptive surface area available for copper uptake 2, 5

Inflammatory Bowel Disease

• Crohn's disease and ulcerative colitis cause copper deficiency through chronic mucosal inflammation, malabsorption, anatomic changes affecting absorptive capacity, and increased gastrointestinal losses 1
• Patients with enterocutaneous fistulae or enterostomies experience ongoing copper losses that exceed normal dietary intake 1
• Celiac disease causes copper malabsorption even in patients without overt gastrointestinal symptoms, and should be screened for with gliadin and tissue transglutaminase antibodies 6

Zinc-Copper Competition

Zinc supplementation exceeding 30 mg daily is a critical and often overlooked cause of copper deficiency because zinc and copper compete for the same intestinal absorption pathways 1, 7

• The optimal zinc-to-copper ratio is 8:1 to 15:1; ratios exceeding this range precipitate copper deficiency 7
• Chronic zinc toxicity is treated with copper sulfate specifically because of this competitive relationship 1
• Always measure both zinc and copper levels simultaneously before initiating supplementation of either mineral 7

Inadequate Intake or Provision

Parenteral and Enteral Nutrition

• Prolonged total parenteral nutrition without copper supplementation or with inadequate copper content causes deficiency within months 1, 5
• Patients on long-term complete enteral nutrition, particularly those with jejunostomy tubes, develop copper deficiency from inadequate provision 1, 7
• Patients on parenteral nutrition require copper monitoring every 6-12 months 1, 7, 8

Dietary Insufficiency

• Premature infants undergoing rapid growth on copper-poor diets represent a classic nutritional deficiency scenario 5
• Restrictive eating patterns (vegetarianism, veganism, anorexia nervosa) may provide insufficient copper intake 1

Increased Losses

Gastrointestinal Losses

• Patients with enterostomies, enterocutaneous fistulae, or chronic diarrhea lose copper through gastrointestinal secretions at rates exceeding normal dietary replacement 1
• Inflammatory bowel disease with active inflammation increases both mucosal losses and systemic requirements 1

Renal Losses

• Prolonged renal replacement therapy (hemodialysis >2 weeks) removes copper through dialysate 1, 7
• Hypercatabolic states including burns, trauma, and sepsis increase urinary copper losses 1
• Alcoholism and diabetes mellitus increase renal copper excretion 1

Medication-Related Causes

• Sulfasalazine use in inflammatory bowel disease patients creates specific risk for micronutrient deficiencies including copper 1
• Multiple medications increase urinary copper losses, though specific agents are not consistently identified across guidelines 1

High-Risk Populations Requiring Screening

Post-bariatric surgery patients require copper level monitoring every 6-12 months indefinitely because neurological manifestations may be irreversible if treatment is delayed 7, 3, 4

• Patients with inflammatory bowel disease, particularly those with small bowel involvement, fistulae, or ostomies 1
• Patients on long-term parenteral or enteral nutrition 1, 7
• Major burn patients and those on continuous renal replacement therapy exceeding 2 weeks 7
• Patients taking high-dose zinc supplements (>30 mg daily) 7

Critical Clinical Pitfall

Copper deficiency myeloneuropathy mimics vitamin B12 deficiency (subacute combined degeneration) but neurological damage may be permanent if treatment is delayed, whereas hematological abnormalities typically reverse with supplementation 2, 3, 4. This makes early recognition in at-risk populations essential, as routine copper testing is inexpensive compared to the cost of irreversible neurological sequelae 2.