Copper is an essential cofactor for oxidase enzymes that catalyze oxidation-reduction reactions in various metabolic pathways. These copper-dependent enzymes, or cuproenzymes, participate in, for example, energy (ATP) production, iron metabolism, connective tissue formation, and neurotransmission.

  • Dietary copper insufficiency in humans has been infrequently described; however, copper depletion may occur due to intestinal defects, high supplemental zinc intake, or genetic conditions such as Menkes disease. Intestinal copper absorption is severely impaired in Menkes disease, leading to systemic copper deficiency. Symptoms of low body copper include anemia, bone and connective tissue abnormalities, and neurological dysfunction.
  • Assessing copper status in humans is challenging since no definitive biomarkers exist to detect moderate or subclinical copper deficiency. The development of more precise and sensitive biomarkers of copper nutritional status is thus a critical area for future research.
  • Copper imbalance in humans increases risks of bone demineralization and osteoporosis, fatty liver disease, liver disease mortality, and cardiovascular and neurodegenerative diseases. In certain pathological states, dysregulation of copper homeostasis may not be a primary outcome but could rather be secondary to some aspect of disease pathogenesis.
  • Accurately assessing dietary copper intake is difficult since the copper content of many foods has not been firmly established. However, organ meats, shellfish, nuts, seeds, wheat-bran cereals, and whole-grain products are recognized as good sources of dietary copper.
  • Copper toxicity is rare, being most frequently associated with Wilson disease, a rare inborn error of metabolism that causes copper overload initially in the liver and then subsequently in other tissues, particularly the brain. Toxic effects of copper overload in Wilson disease include disruption of lipid metabolism, as well as damage to mitochondria.
  • Gastrointestinal side effects such as nausea, vomiting, or constipation have been observed in some people taking 3 mg/day of supplemental copper. With copper doses greater than 2 mg/day, gastrointestinal side effects may be reduced by splitting the daily dose.

Drug interactions

  • Administration of hydralazine to hypertensive patients increased urinary copper excretion by 100%. It is possible that long-term treatment with hydralazine would lead to low copper status.
  • Treatment with penicillamine increased urinary copper excretion and decreased serum copper levels in patients with rheumatoid arthritis.

Nutrient interactions

  • Zinc interferes with copper absorption. There are a number of case reports in which supplementation with large doses of zinc for long periods (such as 100–400 mg/day for 2 years or longer) resulted in severe copper deficiency, manifesting as anemia, neutropenia, myelopathy, impaired immune function, or serum lipid abnormalities.
  • Vitamin C. In animals, high intake of vitamin C (such as 1% of the diet) inhibited copper absorption and decreased tissue copper levels

In humans, supplementation with 500–600 mg/day of vitamin C had no clear effect on indices of copper status. However, based on the results of animal studies, it would seem reasonable to administer a copper supplement (such as 2 mg/day) to individuals taking larger doses of vitamin C for long periods.

  • Iron appears to compete with copper for intestinal absorption. In formula-fed infants, increasing the iron content of the formula 4-fold resulted in a 51% decrease in copper absorption. In pregnant women given 0, 18, or 65 mg/day of iron for 16 weeks, serum copper levels were inversely proportional to the iron dose. However, administration of 30 mg/day of iron to 1-year-old infants for 3 months did not affect copper status (see chapter 30 for references).
  • Copper forms an insoluble complex with molybdenum in the digestive tract. Ingestion of large amounts of either of these minerals might lead to a deficiency of the other, particularly if its intake is already marginal. When supplementing with large amounts of copper or molybdenum, it would seem prudent to supplement with other nutrients as well.
  • Alpha-lipoic acid. Alpha-lipoic acid has been reported to chelate copper and to increase urinary copper excretion in patients with Wilson’s disease. For patients who do not have copper overload, it might be worthwhile to supplement with copper (perhaps 1–2 mg/day) when alpha-lipoic acid is being used for long periods.


  • A number of different copper preparations are available, including copper gluconate, copper amino acid chelate, copper sebacate, copper citrate, copper picolinate, and cupric oxide.
  • Cupric oxide should not be used as a copper supplement, because animal studies have shown that its bioavailability “is not significantly different from zero.”

Dosage and administration

The usual dosage range for copper supplementation is 1–4 mg/day for adults.

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