What causes low copper and low zinc levels, particularly in individuals with gastrointestinal disorders or restrictive diets, such as vegetarians or vegans?

Causes of Concurrent Low Copper and Low Zinc Levels

The most common cause of simultaneous low copper and low zinc is gastrointestinal malabsorption from conditions like inflammatory bowel disease, short bowel syndrome, or bariatric surgery, which impair absorption of both minerals through chronic mucosal inflammation and reduced absorptive capacity. 1, 2

Primary Gastrointestinal Causes

Malabsorptive disorders are the leading etiology when both minerals are deficient simultaneously:

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) causes deficiency through chronic mucosal inflammation, anatomic changes affecting absorptive capacity, and increased gastrointestinal losses in patients with enterocutaneous fistulae or enterostomies 1, 2
• Short bowel syndrome and bariatric surgery dramatically reduce absorptive surface area, leading to deficiency of both minerals that requires monitoring every 6-12 months indefinitely 1, 2
• Chronic pancreatitis and cystic fibrosis impair mineral absorption through pancreatic insufficiency 1
• Celiac disease damages intestinal villi, reducing absorption of both trace elements 3

Patients with enterostomies or enterocutaneous fistulae experience ongoing losses of both copper and zinc that exceed normal dietary intake, making this a critical risk factor to identify 1, 2

Inadequate Intake or Provision

Nutritional support deficiencies represent a preventable but common cause:

• Prolonged parenteral nutrition without adequate supplementation causes deficiency within months and requires monitoring every 6-12 months 1, 2
• Long-term complete enteral nutrition, particularly through jejunostomy tubes, leads to deficiency from inadequate provision 1, 2
• Restrictive diets including vegetarianism and veganism increase risk due to reliance on foods with poorly absorbable zinc (high phytate content) and potentially inadequate copper intake 1, 4
• Eating disorders (anorexia nervosa, bulimia) cause deficiency through severely restricted intake 1

Phytate-rich diets (cereals, corn, rice) strongly inhibit zinc absorption, and this effect is most pronounced with inositol hexaphosphates and pentaphosphates 4

Increased Losses

Hypercatabolic and pathologic states increase losses of both minerals:

• Major burns (>20% BSA), trauma, and sepsis increase urinary losses of both copper and zinc through hypercatabolic mechanisms 1, 2
• Prolonged renal replacement therapy (>2 weeks) removes both minerals through dialysate 1, 2
• Alcoholism increases renal excretion of both copper and zinc while also causing inadequate dietary intake 1, 2, 5
• Diabetes mellitus increases renal copper and zinc excretion 1
• Chronic diarrhea from any cause results in excessive gastrointestinal losses 1

Medication-Related Causes

• Sulfasalazine in inflammatory bowel disease patients creates specific risk for micronutrient deficiencies including both copper and zinc 2
• Multiple medications increase urinary losses of both minerals, though specific agents vary 1

High-Risk Populations Requiring Immediate Screening

Post-bariatric surgery patients are at particularly high risk and require copper and zinc monitoring every 6-12 months indefinitely because neurological manifestations may be irreversible if treatment is delayed 2, 6

Patients on long-term parenteral or enteral nutrition require monitoring every 6-12 months 2, 6

Patients with inflammatory bowel disease, particularly those with small bowel involvement, fistulae, or ostomies, need regular assessment 2

Critical Diagnostic Considerations

Always measure both zinc AND copper levels simultaneously before initiating replacement therapy, as these minerals compete for intestinal absorption and treatment of one can worsen deficiency of the other 2, 6

Check C-reactive protein (CRP) alongside copper levels to differentiate true deficiency from inflammatory conditions that can falsely lower ceruloplasmin (the copper-carrying protein) 6

Plasma zinc decreases significantly when CRP exceeds 20 mg/L, complicating interpretation and potentially masking true zinc status 1

Common Pitfall to Avoid

The most critical error is treating zinc deficiency without checking copper status first, as zinc supplementation exceeding 30 mg daily can precipitate or worsen copper deficiency through competitive inhibition of intestinal absorption 2, 6, 7, 8. This competitive relationship is so strong that chronic zinc toxicity is specifically treated with copper sulfate 1.