Copper

What it is

Copper is an essential trace mineral found in some foods and sold as a supplement. It is needed by several enzymes, called cuproenzymes, involved in energy production, iron metabolism and connective tissue.

What the research says

Copper is essential, and deficiency causes anaemia, low white cells and nerve damage that copper can correct. Beyond correcting deficiency, trials do not show benefit: a meta-analysis found no effect on blood lipids, a 12-month trial found no effect on cognition in mild Alzheimer's disease, and small trials found no effect on bone markers. Too much copper damages the liver; a US UL of 10 mg/day applies. A common, avoidable cause of deficiency is excess zinc, including from zinc-containing denture cream.

Evidence grade: Well established.

What goes wrong

In a case series, four denture wearers with neurological disease had low copper and high zinc from very heavy denture-cream use; copper supplementation gave mild neurological improvement in two who stopped the cream. (Source 1)

• Case series, Very low certainty.
• Size: 4 patients.
• Who: adults using large amounts of zinc-containing denture cream.
• How long: chronic use.
• Result: denture creams contained about 17,000 to 34,000 μg/g zinc; mild improvement in 2 patients.
• Funding: not stated.

Copper supplementation resulted in mild neurologic improvement in two patients who stopped using denture cream.

A man given 2 to 8 mg/day copper for acquired copper deficiency developed end-stage liver disease and haemolytic anaemia a decade later, with very high liver copper at transplant. (Source 2)

• Case report, Very low certainty.
• Size: 1 patient.
• Who: middle-aged man with acquired copper deficiency myeloneuropathy.
• How long: about 10 years.
• Result: explant liver copper 5436 mcg/g dry weight.
• Funding: not applicable.

The copper concentration was 5436 mcg/g on dry weight (Fig. 2).

Men consuming 7.8 mg/day copper for 147 days accumulated copper, with some immune and antioxidant indices adversely affected. (Source 3)

• Randomized trial, Low certainty.
• Size: not stated.
• Who: adult men.
• How long: 147 days.
• Result: copper loading; some immune and antioxidant indices worse.
• Funding: not stated.

one study in adult men who consumed 7.8 mg/day of copper for 147 days showed that they loaded excess copper during that time, and some indices of immune function and antioxidant status suggested that these functions were adversely affected by the high intakes of copper

Position, NIH ODS (updated 18 October 2022): chronic high copper exposure can cause liver damage and gastrointestinal symptoms. (Source 4)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: general population.
• How long: chronic.
• Result: not quantified.
• Funding: government.

Chronic exposure to high levels of copper can result in liver damage and gastrointestinal symptoms (e.g., abdominal pain, cramps, nausea, diarrhea, and vomiting).

High-dose zinc supplements (50 mg/day or more for long periods) can deplete copper, an interaction between supplements. (Source 3)

• Official position, Moderate certainty.
• Size: not stated.
• Who: people taking high-dose zinc.
• How long: extended periods.
• Result: not quantified.
• Funding: not stated.

Excess intake of supplemental zinc, at doses of 50 mg/day or more for extended periods of time, may result in copper depletion.

What the evidence supports

Copper deficiency causes an anaemia that does not respond to iron but is corrected by copper, plus neutropenia. (Source 3)

• Official position, Moderate certainty.
• Size: not stated.
• Who: people with copper deficiency.
• How long: not stated.
• Result: not quantified.
• Funding: not stated.

One of the most common clinical signs of copper deficiency is an anemia that is unresponsive to iron therapy but is corrected by copper supplementation.

What the evidence does not support

A meta-analysis of 5 RCTs found copper supplementation did not change total, LDL or HDL cholesterol. (Source 5)

• Meta-analysis, Low certainty.
• Size: 176 participants across 5 RCTs.
• Who: adults.
• How long: not stated in abstract.
• Result: TC SMD -0.05 (95% CI -0.52 to 0.43); LDL-C SMD 0.22 (-0.46 to 0.89); HDL-C SMD 0.18 (-0.14 to 0.49)
• Funding: not stated.

Cu supplementation has not affected blood lipids in the result of meta-analysis.

A 12-month RCT of 8 mg/day copper in mild Alzheimer's disease found no difference from placebo on ADAS-Cog or MMSE; the trial was partly funded by the International Copper Association. (Source 6)

• Randomized trial, Low certainty.
• Size: 68 randomised.
• Who: patients with mild Alzheimer's disease.
• How long: 12 months.
• Result: no significant differences in primary outcomes; well tolerated.
• Funding: industry co-funded (International Copper Association) plus university.

There were however no significant differences in primary outcome measures (Alzheimer's Disease Assessment Scale, Cognitive subscale, Mini Mental Status Examination) between the verum [Cu-(II)-orotate-dihydrate; 8 mg Cu daily] and the placebo group.

Two small trials in healthy adult men and women giving 3 to 6 mg/day copper for six weeks found no effect on bone turnover markers. (Source 3)

• Randomized trial, Low certainty.
• Size: 2 studies (sizes not stated)
• Who: adults.
• How long: 6 weeks.
• Result: no effect on markers of bone resorption or formation.
• Funding: not stated.

supplementation of 3 to 6 mg/day of copper for six weeks had no effect on biochemical markers of bone resorption or bone formation in two studies of healthy adult men and women.

Position, NIH ODS (2022): evidence is insufficient to link copper levels with cardiovascular risk, or to say whether copper supplements affect cardiovascular disease. (Source 4)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: general population.
• How long: not applicable.
• Result: not applicable.
• Funding: government.

Overall, the evidence to date is insufficient to support any conclusions about the association between copper concentrations and CVD risk or the impact of copper supplementation on CVD.

How much

• Reference intake: US Food and Nutrition Board RDA for adults: 900 µg/day. US survey mean intakes (NHANES) are 1.1 mg/day in women and 1.3 mg/day in men, per the Linus Pauling Institute. (Source 3)
• Upper limit: US Food and Nutrition Board UL for adults: 10 mg/day from food and supplements, based on liver damage. (Source 3)
• Studied: 8 mg/day copper (as copper orotate) for 12 months in mild Alzheimer's disease. (Source 6)
• Studied: 3 to 6 mg/day copper for six weeks in bone-marker trials. (Source 3)

A common belief, and what the research shows

The belief: Extra copper protects the heart or brain.

What the research shows: A meta-analysis found 'Cu supplementation has not affected blood lipids in the result of meta-analysis.', and an 8 mg/day trial in Alzheimer's disease found 'oral Cu intake has neither a detrimental nor a promoting effect on the progression of AD.'

Questions and answers

What is it?

Copper is an essential trace mineral found in some foods and available as a supplement. (Source 4)

What does it do in the body?

Copper is needed by several enzymes, called cuproenzymes, involved in energy production, iron handling, connective tissue and brain chemistry. (Source 3)

Is it good or bad for you?

Copper is essential, but too much harms the liver. Supplements beyond correcting deficiency have not shown benefit in trials for cholesterol or Alzheimer's disease. (Source 4)

How do you get more of it?

Copper comes mainly from foods such as organ meats, shellfish, nuts and seeds. Copper supplementation is used to treat diagnosed deficiency, as in the denture-cream cases. (Source 1)

If it is harmful, what reduces it?

Copper overload is seen in Wilson disease, an inherited condition, and from long-term excess intake. In Wilson disease, the drug penicillamine binds copper to increase its removal. (Source 4)

Why might someone be low in it or missing it?

Common causes are long-term high-dose zinc (including from zinc-containing denture cream), gastric bypass surgery and malabsorption, and the inherited Menkes disease. (Source 3)

Which whole foods contain it or feed it?

Copper is in many foods and is most plentiful in organ meats such as liver, shellfish such as oysters, nuts and seeds; wheat-bran cereals and whole grains are also good sources. (Source 3)

What happens if you do not have it?

Deficiency causes anaemia that does not respond to iron, low white cells with more infections, and a nerve and spinal cord disorder that can be lasting. (Source 3)

How can you test for it?

Serum copper and ceruloplasmin can be measured and are low in severe deficiency, but pregnancy, inflammation and infection distort them, and no reliable biomarker of copper status exists. (Source 3)

References

1. Neurology. Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease. 2008. DOI 10.1212/01.wnl.0000312375.79881.94. Read the source
2. BMC Gastroenterology. Exogenous copper exposure causing clinical wilson disease in a patient with copper deficiency. 2021. PMID 34238237, DOI 10.1186/s12876-021-01859-6. Read the source
3. Linus Pauling Institute Micronutrient Information Center, Oregon State University. Copper. n.d.. Read the source
4. NIH Office of Dietary Supplements. Copper: Fact Sheet for Health Professionals (updated October 18, 2022). 2022. Read the source
5. Biological Trace Element Research. Effects of Copper Supplementation on Blood Lipid Level: a Systematic Review and a Meta-Analysis on Randomized Clinical Trials. 2020. PMID 33030656, DOI 10.1007/s12011-020-02423-1. Read the source
6. Journal of Neural Transmission. Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial. 2008. DOI 10.1007/s00702-008-0080-1. Read the source