Copper - Kresser Institute Membership Site

Marker Name: Copper

REFERENCE RANGES FOR SERUM COPPER CONCENTRATION:

Laboratory reference range: 72–166 µg/dL

Functional reference range: 81–157 µg/dL

DESCRIPTION:

Copper is an essential trace element for metalloenzymes involved in cellular respiration, neurotransmitter synthesis, decomposition of superoxides, collagen cross-linking, bone formation, production of melatonin and melanin, and thrombosis.^1,2 The copper-containing protein ceruloplasmin transports copper from the liver to peripheral tissues, but it also acts as an acute phase reactant.² Copper is present in all tissues but is particularly concentrated in the liver and brain.^3-5

Humans absorb approximately 1 mg of copper in the diet, while secreting and reabsorbing between 4 and 5 mg of copper in the digestive tract, each day.⁶ Copper is absorbed in the stomach and proximal small intestine.⁷ At low levels of copper intake, energy-requiring (i.e., “active”) transporters shuttle copper across the wall of the gastrointestinal tract.^1,7 When copper intake is high, the mineral can passively diffuse into the portal circulation. Once copper is absorbed, it is carried by albumin and amino acids to the liver.^1,8

Once copper enters the liver, it has one of three fates: it is stored in the liver bound to the protein metallothionein, it enters the bloodstream bound mainly to the protein ceruloplasmin, or it is excreted in the bile.⁶ Excretion of copper into the gastrointestinal tract is one of the main ways in which total body copper is regulated.^9,10

An elevated serum copper level (hypercupremia) may be caused by a number of diseases and disorders, most notably Wilson disease, but also hyperthyroidism, hemochromatosis, primary biliary cirrhosis, and primary sclerosing cholangitis.¹¹ Wilson disease is a rare genetic condition in which copper is not effectively incorporated into ceruloplasmin, nor is it properly excreted from the liver into the bile.¹² As an acute phase reactant, copper levels can be transiently elevated subsequent to infection, trauma, infarction, inflammatory arthritis, and certain forms of cancer.^2,13 A mild elevation of copper is normal during pregnancy, and serum copper levels may exceed three times the upper limit of normal in the third trimester.¹³

Conditions that cause decreased absorption of copper such as bariatric surgery or inflammatory bowel disease can also cause copper deficiency. In fact, gastric surgery is the most common cause of acquired copper deficiency.¹⁴ Menkes disease is a rare genetic disease that disrupts the transport proteins that mediate copper uptake from the intestine, thus reducing copper absorption.¹ Excessive consumption of zinc or iron can interfere with copper homeostasis and lower copper levels in the serum.¹⁵ Since copper is bound to proteins in the portal and systemic vasculature, disorders that diminish carrier protein levels will also diminish serum copper levels (e.g., nephrotic syndrome, protein malnutrition, aceruloplasminemia, etc.).^14,16,17

To determine the etiology of abnormal serum copper, it is useful to evaluate related markers such as ceruloplasmin, iron, and zinc.¹ Care should be taken to distinguish between copper and iron deficiency, which may present similarly.¹⁹ Since these nutrients compete for absorption, supplementation with iron could exacerbate copper deficiency, and vice versa.¹

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^{1,11-13,20,21}

Normal pregnancy
Excessive copper intake
Hyperthyroidism
Hemochromatosis
Wilson disease
Ceruloplasmin (acute phase reactant) elevation
- Infarction
- Coronary artery disease
- Infection
- Inflammation
- Neoplastic disease (e.g., leukemia)
- Trauma
- Renal failure
Primary biliary cirrhosis
Primary sclerosing cholangitis
Drugs
- Oral contraceptives
- Estrogens
- Carbamazepine
- Phenobarbital

Low in:^1,15-18,20

Menkes disease
Nutrient imbalances
- Excessive zinc ingestion
- Excessive iron ingestion
Gastrointestinal malabsorption
- Post-gastrectomy
- Post-gastric bypass surgery
- Celiac disease
- Inflammatory bowel disease
- Chronic diarrhea
- Cystic fibrosis
Hypoproteinemia
- Malnutrition
- Nephrotic syndrome
Chronic dialysis (hemodialysis, peritoneal dialysis)
Prolonged total parenteral nutrition
Aceruloplasminemia
Drugs
- Clioquinol
- Tetrathiomolybdate
- Corticosteroids

FUNCTIONAL RANGE INDICATIONS:

High in:

Same as conventional indications

Low in:

Same as conventional indications

References: