Copper (Serum Copper): Understanding Your Blood Test Series

1. Overview: What this test reveals and why it is important

Copper is an essential trace element that serves as a cofactor for numerous enzymes (cuproenzymes) critical for:

· Iron metabolism: Ceruloplasmin (ferroxidase) oxidises ferrous iron to ferric iron, enabling iron binding to transferrin and preventing iron deficiency.

· Neurotransmitter synthesis: Dopamine beta-hydroxylase converts dopamine to norepinephrine.

· Antioxidant defence: Superoxide dismutase (SOD, copper‑zinc dependent) protects cells from oxidative damage.

· Connective tissue formation: Lysyl oxidase cross‑links collagen and elastin.

· Energy production: Cytochrome c oxidase (mitochondrial).

· Melanin synthesis: Tyrosinase.

· Angiogenesis and wound healing.

Serum copper is the most commonly measured marker, but it is not a perfect reflection of total body copper. Approximately 90–95% of serum copper is bound to ceruloplasmin, an acute‑phase protein. Therefore, serum copper levels are influenced by inflammation, pregnancy, and oestrogen status. Measurement of ceruloplasmin and free (non‑ceruloplasmin‑bound) copper (calculated or directly measured) provides additional information, particularly in Wilson's disease.

Clinical utility:

· Diagnosis of Wilson's disease: Low serum copper and ceruloplasmin, with elevated urinary copper and hepatic copper content.

· Diagnosis of Menkes disease: Low serum copper and ceruloplasmin in infants with neurological deterioration and characteristic hair.

· Assessment of copper deficiency: In patients with risk factors (malabsorption, malnutrition, bariatric surgery, prolonged parenteral nutrition, excessive zinc supplementation).

· Assessment of copper toxicity: In Wilson's disease (untreated), chronic cholestasis, or acute ingestion.

· Monitoring treatment: In Wilson's disease (chelation therapy or zinc) and during copper replacement.

Important principle: Serum copper is an acute‑phase reactant. It rises with infection, inflammation, pregnancy, and oestrogen use (including oral contraceptives) due to increased hepatic synthesis of ceruloplasmin. A high level in these settings does not indicate toxicity. Conversely, a low level may be masked by inflammation. Interpretation always requires clinical context and, ideally, concurrent measurement of ceruloplasmin and inflammatory markers (CRP).

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2. What does it measure

a. Units of measurement

· Micrograms per decilitre (mcg/dL) – common in the United States.

· Micromoles per litre (µmol/L) – used in many other countries.

· Conversion: 1 µmol/L = 6.355 mcg/dL.

b. Normal Range

(Reference ranges vary by laboratory, age, sex, and assay; the following are general guidelines.)

Adults:

· Serum copper: 70–140 mcg/dL (11–22 µmol/L)

· Ceruloplasmin: 20–40 mg/dL (200–400 mg/L)

Children:

· Infants (0–6 months): 20–70 mcg/dL (3–11 µmol/L) – physiologically low.

· Children (6 months – 6 years): 70–130 mcg/dL (11–20 µmol/L)

· Older children: Adult range.

Pregnancy:

· Markedly elevated due to oestrogen‑induced ceruloplasmin synthesis.

· Third trimester: 120–200 mcg/dL (19–31 µmol/L) is common.

· Interpret with gestation‑specific reference ranges.

Oral contraceptives / hormone replacement therapy:

· Elevated serum copper (up to 150–180 mcg/dL) due to oestrogen effect.

Interpretation notes:

· Low copper: <70 mcg/dL (<11 µmol/L) suggests deficiency; <50 mcg/dL (<8 µmol/L) is severe.

· High copper: >140 mcg/dL (>22 µmol/L) may indicate Wilson's disease (if free copper elevated) or acute‑phase response.

· Free (non‑ceruloplasmin‑bound) copper:

· Normal: 5–15 mcg/dL (0.8–2.4 µmol/L).

· Calculated: Total copper (mcg/dL) – (3.15 × ceruloplasmin in mg/dL).

· Elevated free copper (>25 mcg/dL) is characteristic of untreated Wilson's disease.

· Serum copper alone is insufficient for Wilson's diagnosis – must be combined with ceruloplasmin, 24‑hour urinary copper, and slit‑lamp examination for Kayser‑Fleischer rings.

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3. Other factors connected to this

a. Direct correlation (factors that directly lower or raise serum copper)

Factors that lower serum copper (deficiency states):

· Inadequate intake:

· Malnutrition, prolonged parenteral nutrition without copper.

· Excessive zinc supplementation – zinc induces intestinal metallothionein, which binds copper and prevents its absorption. This is the basis for zinc therapy in Wilson's disease.

· High‑dose iron supplements – may compete with copper for absorption.

· Malabsorption:

· Coeliac disease, inflammatory bowel disease (Crohn, ulcerative colitis), short bowel syndrome, cystic fibrosis, chronic pancreatitis.

· Bariatric surgery (especially gastric bypass).

· Increased losses:

· Nephrotic syndrome (ceruloplasmin lost in urine).

· Burns, exfoliative dermatitis.

· Genetic disorders:

· Menkes disease (kinky hair disease): X‑linked recessive defect in ATP7A, a copper transporter. Copper cannot be absorbed from gut or distributed to tissues. Presents in infancy with:

· Progressive neurological deterioration.

· Characteristic hair: Sparse, kinky, brittle (pili torti).

· Hypothermia, hypotonia, connective tissue laxity.

· Death in early childhood.

· Occipital horn syndrome: Milder ATP7A mutation; connective tissue abnormalities.

· Other:

· Myelopathy / neuropathy due to copper deficiency (mimics subacute combined degeneration of B12 deficiency).

· Anaemia (microcytic or normocytic) and neutropenia – copper is required for haematopoiesis.

· Hypoalbuminaemia – ceruloplasmin is an acute‑phase protein; low albumin may be associated with low copper.

Factors that raise serum copper (elevated states):

· Wilson's disease (untreated):

· Low total serum copper (due to low ceruloplasmin) but elevated free copper.

· Paradox: Total copper is low, but free copper is high and toxic.

· Acute‑phase response:

· Infection, inflammation, tissue injury, surgery, malignancy – IL‑6 stimulates hepatic ceruloplasmin synthesis.

· Serum copper rises within 24–48 hours and may remain elevated for weeks.

· Pregnancy:

· Oestrogen stimulates ceruloplasmin synthesis; levels double by third trimester.

· Oestrogen therapy:

· Oral contraceptives, hormone replacement therapy.

· Cholestatic liver disease:

· Primary biliary cholangitis, primary sclerosing cholangitis – copper accumulates in liver and serum due to impaired biliary excretion.

· Acute copper toxicity:

· Ingestion of copper salts (suicidal or accidental) – severe gastrointestinal symptoms, haemolysis, hepatic necrosis, acute renal failure.

· Industrial exposure (rare).

· Haemochromatosis / iron overload: May be associated with elevated copper.

b. Indirect correlation (factors that influence copper interpretation or cause artefactual changes)

· Timing of test: Fasting samples are preferred to minimise postprandial variation.

· Infection / inflammation: Serum copper rises; measure CRP concurrently. A normal copper with elevated CRP may indicate true deficiency masked by inflammation.

· Pregnancy / oestrogen use: Always interpret with these factors in mind.

· Sample handling: Avoid haemolysis (copper is released from red cells, falsely elevating levels). Use trace element‑free tubes (royal blue‑top).

· Albumin levels: Ceruloplasmin is an acute‑phase protein; low albumin may be associated with low ceruloplasmin and low total copper.

· Age: Neonates have physiologically low copper and ceruloplasmin; adult levels by 6 months.

· Circadian rhythm: Minor; not clinically significant.

· Medications:

· Penicillamine, trientine, tetrathiomolybdate – copper chelators used in Wilson's; lower serum copper.

· Zinc – lowers copper absorption.

· Iron supplements – may compete with copper.

· Antacids, PPIs – may reduce copper absorption (weak evidence).

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4. Disorders related to abnormal values

a. When copper is low (deficiency – clinically significant)

Wilson's disease (untreated):

· Paradoxical presentation: Low total serum copper and low ceruloplasmin, but elevated free copper.

· Hepatic: Steatosis, hepatitis, cirrhosis, fulminant liver failure.

· Neurological: Dysarthria, dystonia, tremor, parkinsonism, ataxia.

· Psychiatric: Depression, personality changes, psychosis.

· Ophthalmic: Kayser‑Fleischer rings (copper deposition in Descemet's membrane of cornea).

· Renal: Fanconi syndrome, renal tubular acidosis.

· Haematological: Haemolytic anaemia (from acute copper release).

Menkes disease:

· Infants: Low serum copper and ceruloplasmin.

· Neurological: Seizures, hypotonia, developmental regression.

· Hair: Sparse, kinky, depigmented (pili torti).

· Connective tissue: Loose skin, joint laxity, bladder diverticula.

· Vascular: Tortuous arteries, aneurysms.

Acquired copper deficiency (common causes):

Cause Mechanism

Excessive zinc supplementation Most common cause in clinical practice. Zinc induces metallothionein, which binds copper in enterocytes and prevents absorption.

Malabsorption (coeliac, Crohn, bariatric surgery) Impaired intestinal absorption.

Prolonged parenteral nutrition without copper Iatrogenic.

Nephrotic syndrome Urinary loss of ceruloplasmin.

Enteropathies Protein‑losing enteropathy.

Gastric surgery Reduced gastric acid impairs copper release from food.

High‑dose iron supplements Competition for absorption.

Malnutrition Inadequate intake.

Clinical manifestations of copper deficiency:

System Manifestations

Haematological Microcytic or normocytic anaemia (unresponsive to iron), neutropenia (often severe), thrombocytopenia (less common).

Neurological Myelopathy (spastic gait, sensory ataxia, dorsal column dysfunction) – mimics subacute combined degeneration of B12 deficiency. Peripheral neuropathy. Optic neuropathy.

Bone Osteoporosis, fractures (in children).

Skin / hair Depigmentation, kinky hair (in Menkes).

Immune Recurrent infections (due to neutropenia).

Cardiovascular Cardiac arrhythmias, aneurysms (in Menkes).

b. When copper is high (elevated – clinically significant)

Wilson's disease (untreated) – free copper:

· High free copper is diagnostic and correlates with disease activity.

Acute copper toxicity:

· Ingestion: Metallic taste, nausea, vomiting, epigastric pain, diarrhoea (often green‑blue). Severe cases: haemolysis, jaundice, hepatic necrosis, acute renal failure, shock.

· Chronic toxicity (rare):

· Industrial exposure (vineyard workers, fungicide exposure).

· Haemodialysis using copper tubing (historic).

· Indian childhood cirrhosis (genetic susceptibility + excess copper intake from brass utensils).

Cholestatic liver disease:

· Primary biliary cholangitis, primary sclerosing cholangitis – copper accumulates due to impaired biliary excretion.

· Serum copper may be elevated, but free copper is usually normal; hepatic copper is high.

Acute‑phase response:

· Transient elevation; not pathological.

Pregnancy / oestrogen use:

· Physiological; not pathological.

Haemochromatosis / iron overload:

· Modest elevation; not clinically significant.

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5. Best way to address aberrant levels

Important principle: Copper levels are not treated in isolation. The underlying disease – Wilson's, Menkes, deficiency due to malabsorption or zinc excess – is treated.

a. Quick ways or using Medications

For Wilson's disease:

· Lifelong treatment is mandatory.

· Two main approaches: Chelation (removes copper) or zinc (blocks absorption).

· Chelating agents:

· Penicillamine:

· First‑line for decades, but side effects common.

· Dose: 750–1500 mg/day in divided doses, on an empty stomach.

· Monitor: Urinary copper, neurological status, complete blood count, urinalysis.

· Side effects: Fever, rash, lymphadenopathy, proteinuria, lupus‑like syndrome, bone marrow suppression, worsening of neurological symptoms (in 10–20%).

· Trientine:

· Preferred chelator (better tolerated than penicillamine).

· Dose: 750–1500 mg/day in divided doses, on an empty stomach.

· Monitor: As for penicillamine.

· Side effects: Less frequent; sideroblastic anaemia (rare).

· Tetrathiomolybdate (investigational): Blocks copper absorption and binds copper in serum; used in acute neurological Wilson's.

· Zinc (zinc acetate, zinc sulphate):

· Mechanism: Induces intestinal metallothionein, which binds dietary copper and prevents its absorption.

· Indications:

· First‑line for presymptomatic patients.

· First‑line for maintenance after initial chelation.

· Pregnancy (zinc is safer than chelators).

· Dose: 50 mg elemental zinc three times daily (adults), separated from food by at least 1 hour.

· Monitor: 24‑hour urinary copper, neurological status, zinc levels (to avoid toxicity), copper deficiency.

· Side effects: Gastric irritation (take with protein, not with food that binds zinc).

· Dietary copper restriction:

· Avoid high‑copper foods (liver, shellfish, nuts, chocolate, mushrooms, dried legumes, avocados) – but this is secondary to pharmacotherapy, not primary treatment.

· Monitoring:

· 24‑hour urinary copper: Goal <100 mcg/day on zinc; >200–500 mcg/day on chelation (reflects drug effect).

· Serum free copper: Goal <15 mcg/dL.

· Liver function tests, neurological examination, slit‑lamp exam annually.

For Menkes disease:

· Early treatment is critical.

· Copper histidinate: Subcutaneous injections (not oral, as absorption is defective).

· Dose: 250–500 mcg/kg/day initially, then adjusted.

· Outcome: May improve survival and neurological outcome if started very early (preferably neonatal). Established neurological damage is irreversible.

For acquired copper deficiency:

· Identify and treat the underlying cause:

· Stop excessive zinc supplementation.

· Treat malabsorption: Gluten‑free diet for coeliac disease, immunosuppression for IBD, pancreatic enzymes for chronic pancreatitis.

· Adjust medications: If possible, reduce high‑dose iron, PPIs, antacids.

· Copper replacement:

· Oral copper (mild‑moderate deficiency):

· Copper gluconate, copper sulphate, copper chloride – available as supplements.

· Dose: 2–4 mg elemental copper/day (typically 2 mg daily).

· Duration: Until neurological and haematological improvement and normalisation of serum copper (usually 4–12 weeks).

· Monitor: Serum copper, complete blood count, neurological exam at 4–8 weeks.

· Intravenous copper (severe deficiency, malabsorption, neurological symptoms):

· Copper chloride added to parenteral nutrition or given as separate infusion.

· Dose: 0.5–1.5 mg/day (maintenance) to 2–4 mg/day (repletion).

· Must be managed by clinical nutrition team.

· Monitoring:

· Serum copper and ceruloplasmin: Recheck at 4–8 weeks after starting therapy.

· Complete blood count: Anaemia and neutropenia improve within 2–4 weeks.

· Neurological symptoms: Myelopathy may improve slowly over months; full recovery is variable.

For acute copper toxicity:

· Emergency management:

· Supportive care: IV fluids, anti‑emetics, pain control.

· Gastric decontamination if large, recent ingestion.

· Chelation therapy: Dimercaprol (BAL), penicillamine, or trientine – under specialist guidance.

· Haemodialysis for renal failure; does not remove copper efficiently.

· Monitor: Hepatic and renal function, haematological status.

Do not self‑prescribe copper or zinc supplements – both can cause serious toxicity. All therapy must be supervised.

b. Using Supplements or Holistic medicine

Copper is itself a supplement. The principles above cover therapeutic use.

For supporting copper status and overall health:

· Avoid excessive zinc: The most common cause of acquired copper deficiency. Do not take >30 mg elemental zinc/day without medical supervision.

· Vitamin C: May enhance copper absorption; also supports immune function.

· Probiotics / prebiotics: Support gut health and may improve absorption in malabsorptive conditions.

· Avoid:

· High‑dose iron supplements taken simultaneously – separate by 2 hours.

· Calcium supplements – may compete with copper; separate by 2 hours.

Supplements to AVOID in copper deficiency:

· Zinc (high‑dose) – as above.

· Iron (high‑dose) – if not indicated.

· Synthetic folic acid – no direct interaction, but use methylfolate.

· Cyanocobalamin – no direct interaction, but use methylcobalamin.

General caution: Supplements are adjunctive. Copper therapy itself is the primary intervention.

c. Using Diet and Foods (following a plant‑forward, ecologically sustainable approach)

Diet is the foundation of maintaining adequate copper status. A well‑designed plant‑based diet can meet copper requirements through careful food choices.

Core dietary principles – what to emphasise:

· Copper‑rich plant foods (hierarchy adhered):

· Primary plant sources (excellent sources):

· Nuts and seeds: Cashews (highest), sunflower seeds, sesame seeds (tahini), pumpkin seeds, almonds, walnuts. 1 oz (30g) cashews provides ~0.6 mg copper.

· Legumes: Chickpeas, lentils, soybeans (tofu, tempeh, edamame). 1 cup cooked chickpeas provides ~0.6 mg copper.

· Whole grains: Oats, quinoa, barley, millet. 1 cup cooked oats provides ~0.3 mg copper.

· Dark leafy greens: Spinach, kale, Swiss chard. 1 cup cooked spinach provides ~0.3 mg copper.

· Mushrooms: Shiitake, cremini, portobello. 1 cup cooked shiitake provides ~0.5 mg copper.

· Avocado: 1 whole avocado provides ~0.4 mg copper.

· Dark chocolate (≥70% cocoa): 1 oz provides ~0.3 mg copper. Enjoy in moderation.

· Dried fruits: Apricots, prunes, raisins. ¼ cup provides ~0.1–0.2 mg.

· Fungi / algae (encouraged):

· Spirulina, chlorella: 1 tablespoon (10g) provides ~0.1–0.3 mg copper.

· Mushrooms: As above.

· Biotechnology / lab‑grown (acceptable):

· Precision‑fermented proteins (mycoprotein, animal‑free dairy proteins) – may be fortified with copper; emerging area.

· Dairy / eggs (permitted but not emphasised):

· Yoghurt, milk, cheese: 1 cup yoghurt provides ~0.1 mg copper; eggs provide ~0.1 mg each.

· Not necessary for adequate intake.

· Meat, poultry, fish: Deliberately omitted. Effective plant‑based alternatives exist to meet all copper requirements. While organ meats (liver) and shellfish (oysters, crab) are extremely rich in copper, they are not required for optimal nutrition and are ecologically unsustainable. Plant sources are sufficient.

· Enhancing copper absorption from plant foods:

· Vitamin C: May enhance copper absorption; pair copper‑rich foods with vitamin C‑rich foods (citrus, bell peppers, broccoli).

· Adequate protein intake: Copper is often bound to protein.

· Avoid excessive zinc and iron: Do not take high‑dose zinc or iron supplements with copper‑rich meals.

· Foods to avoid / limit in Wilson's disease (if on treatment, dietary restriction is secondary but may be advised):

· Liver, shellfish, nuts, chocolate, mushrooms, dried legumes, avocados, dried fruits, whole grains. However, pharmacotherapy is the mainstay; overly restrictive diets can lead to malnutrition.

Sample copper‑rich plant‑based meals:

· Cashew stir‑fry: Stir‑fried tofu, broccoli, bell peppers, and snap peas with a sauce made from cashew butter, tamari, ginger, and garlic. Serve with brown rice.

· Chickpea and spinach curry: Chickpeas cooked with spinach, tomatoes, onions, coconut milk, and curry spices. Serve with quinoa.

· Mushroom and lentil shepherd's pie: Lentils and mushrooms in a savoury gravy, topped with mashed potatoes.

· Oatmeal with seeds and dark chocolate: Rolled oats cooked with fortified plant milk, topped with pumpkin seeds, sunflower seeds, and a square of dark chocolate.

· Avocado toast: Whole grain sourdough bread topped with mashed avocado, pumpkin seeds, and a squeeze of lemon.

· Trail mix: Homemade mix of cashews, almonds, pumpkin seeds, dark chocolate chips, and dried apricots.

What to avoid or severely limit:

· Ultra‑processed foods, refined carbohydrates – low in copper.

· Excess alcohol – may impair copper metabolism.

· Smoking – not dietary, but cessation improves overall health.

Lifestyle factors with proven benefit:

· Smoking cessation – as above.

· Stress reduction – not directly linked to copper status.

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6. How soon can one expect improvement and the ideal time frame to retest

For copper deficiency:

· Oral copper supplementation:

· Haematological response: Anaemia and neutropenia begin to improve within 1–2 weeks; normalisation over 4–8 weeks.

· Neurological response: Myelopathy may improve over weeks to months; recovery may be incomplete if diagnosis delayed.

· Serum copper: Begins to rise within 1–2 weeks; normalisation typically by 4–8 weeks.

· Retesting: at 4–8 weeks.

· IV copper in severe deficiency / malabsorption:

· **Serum copper normalises within 1–2 weeks; monitor weekly initially, then monthly.

For Wilson's disease:

· Chelation therapy:

· 24‑hour urinary copper: Rises within days (mobilisation), then gradually falls as body stores deplete.

· Clinical improvement: Hepatic and neurological improvement may take months; some patients worsen initially (paradoxical worsening).

· Retesting: 24‑hour urinary copper, serum free copper, liver function tests every 3–6 months initially, then annually.

· Zinc therapy:

· 24‑hour urinary copper: Falls to goal (<100 mcg/day) within 2–4 months.

· Retesting: Every 3–6 months initially, then annually.

For Menkes disease:

· Copper histidinate injections:

· Serum copper normalises within days.

· Neurological outcome: Improved if started early; plateau of deterioration may be seen.

For acute copper toxicity:

· **Serum copper normalises within 1–2 weeks after cessation of exposure and chelation.

Retesting interval summary:

· Copper deficiency on treatment: at 4–8 weeks, then 3–6 months, then annually if stable.

· Wilson's disease on treatment: every 3–6 months initially, then annually.

· Menkes disease: as directed by specialist.

· Asymptomatic low copper with normal CRP: repeat in 3–6 months after dietary optimisation.

· During acute illness: do not retest until illness resolved.

Do not retest copper more often than every 2 weeks – meaningful change does not occur faster.

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Conclusion

Copper is the quiet partner of iron, the architect of connective tissue, the guardian of myelin, and the colourist of hair and skin. Its deficiency cripples the bone marrow, mimics B12 myelopathy, and, in infants, devastates the developing brain. Its excess, in Wilson's disease, destroys the liver and etches Kayser‑Fleischer rings on the cornea.

A low serum copper level demands a story: Is it Wilson's disease, with its paradox of high free copper? Is it Menkes, with its kinky hair and progressive neurodegeneration? Or is it the more common tale of excessive zinc, malabsorption, or malnutrition? The answer dictates the therapy: chelation for Wilson's, copper histidinate for Menkes, oral or IV copper for acquired deficiency.

A plant‑based, ecologically responsible diet – rich in nuts, seeds, legumes, whole grains, mushrooms, and dark leafy greens – can provide adequate copper when thoughtfully planned. There is no need for liver, oysters, or other animal products; the cashew, the chickpea, and the shiitake are sufficient. The ecological imperative aligns with the nutritional one: nourish the body without depleting the planet.

Copper is a number – a concentration, a level. The patient is a story of anaemia, neuropathy, liver disease, and resilience. Listen to the patient, not the number – but when the number is low or high, and the story fits, act swiftly, decisively, and with precision.

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Note on dietary recommendations on this site:

For the sake of our environment we adhere to the following dietary preference hierarchy:

1. Plant‑based

2. Fungi / algae / fermented

3. Biotechnology / lab‑grown / cultures

4. Dairy / eggs

5. Meat / fish / poultry (only if no effective alternative exists)

Special notes on copper:

· Copper supplements: Use only under medical supervision. For replacement, choose copper gluconate, sulphate, or chloride. Do not self‑prescribe.

· Plant‑based copper sources: Cashews, sunflower seeds, sesame seeds (tahini), pumpkin seeds, chickpeas, lentils, soybeans (tofu, tempeh), oats, quinoa, mushrooms (shiitake), spinach, dark chocolate.

· Zinc‑copper interaction: High‑dose zinc supplements cause copper deficiency. Do not exceed 30 mg elemental zinc/day without medical supervision.

· Iron‑copper interaction: Separate high‑dose iron supplements from copper‑rich meals or supplements by at least 2 hours.

· Wilson's disease: Treatment is lifelong and must be managed by a specialist. Dietary copper restriction is secondary to pharmacotherapy.

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