• Copper is an essential cofactor for oxidation-reduction reactions involving copper-containing oxidases. Copper enzymes regulate various physiologic pathways, such as energy production, iron metabolism, connective tissue maturation, and neurotransmission. (More information)
  • Copper deficiency can result from malnutrition, malabsorption, or excessive zinc intake and can be acquired or inherited. Symptoms include deficiencies in blood cells, bone and connective tissue abnormalities, and neurologic disorders. (More information)
  • Marginal copper imbalance has been linked to impaired immune function, bone demineralization, and increased risk of cardiovascular and neurodegenerative diseases. However, the use of more precise indicators of nutritional copper status needs to be considered for future research. (More information)
  • Organ meats, shellfish, nuts, seeds, wheat-bran cereals, and whole-grain products are good sources of copper. (More information)
  • Copper toxicity is rare and often associated with genetic defects of copper metabolism. (More information)

    Copper (Cu) is an essential trace element for humans and animals. In the body, copper shifts between the cuprous (Cu1+) and cupric (Cu2+) forms, though the majority of the body's copper is in the Cu2+ form. The ability of copper to easily accept and donate electrons explains its important role in oxidation-reduction (redox) reactions and in scavenging free radicals (1). Although Hippocrates is said to have prescribed copper compounds to treat diseases as early as 400 B.C. (2), scientists are still uncovering new information regarding the functions of copper in the human body (3).


Copper is a critical functional component of several essential enzymes known as cuproenzymes (4). Some of the physiologic functions known to be copper-dependent are discussed below. 

Energy production

The copper-dependent enzyme, cytochrome c oxidase, plays a critical role in cellular energy production. By catalyzing the reduction of molecular oxygen (O2) to water (H2O), cytochrome c oxidase generates an electrical gradient used by the mitochondria to create the vital energy-storing molecule, ATP (5).

Connective tissue formation

Another cuproenzyme, lysyl oxidase, is required for the cross-linking of collagen and elastin, which are essential for the formation of strong and flexible connective tissue. The action of lysyl oxidase helps maintain the integrity of connective tissue in the heart and blood vessels and also plays a role in bone formation (2).

Iron metabolism

Four copper-containing enzymes, known as multi-copper oxidases (MCO) or ferroxidases, have the capacity to oxidize ferrous iron (Fe2+) to ferric iron (Fe3+), the form of iron that can be loaded onto the protein transferrin for transport to the site of red blood cell formation. The MCO family comprises the circulating ceruloplasmin (which represents ~90% of plasma copper), the membrane-bound ceruloplasmin (called GPI-ceruloplasmin), and two proteins called Hephaestin and Zyklopen found in the intestine and the placenta, respectively (6). Interestingly, mice that do not express ceruloplasmin (Cp-/-) have normal copper metabolism but abnormal iron accumulation in the liver (7, 8). Similarly, individuals lacking ceruloplasmin display iron overload in selected tissues, including liver, brain, and retina (9). This supports the idea that the ferroxidase activity of ceruloplasmin is essential to the flux of iron in the body. Moreover, the fact that iron mobilization from storage sites is impaired in copper deficiency supports the role of MCO in iron metabolism (10).

Central nervous system

A number of reactions essential to normal function of the brain and nervous system are catalyzed by cuproenzymes.

Neurotransmitter synthesis

Dopamine β-hydroxylase catalyzes the conversion of dopamine to the neurotransmitter, norepinephrine (11).

Formation and maintenance of myelin

The myelin sheath is made of phospholipids whose synthesis depends on cytochrome c oxidase activity (2).

Melanin formation

The cuproenzyme, tyrosinase, is required for the formation of the pigment melanin. Melanin is formed in cells called melanocytes and plays a role in the pigmentation of the hair, skin, and eyes (2).

Antioxidant functions

Superoxide dismutase

Superoxide dismutase (SOD) functions as an antioxidant by catalyzing the conversion of superoxide radicals (free radicals or ROS) to hydrogen peroxide, which can subsequently be reduced to water by other antioxidant enzymes (12). Two forms of SOD contain copper: (1) copper/zinc SOD is found within most cells of the body, including red blood cells; and (2) extracellular SOD is a copper-containing enzyme found at high levels in the lungs and low levels in plasma (2).


Ceruloplasmin may function as an antioxidant in two different ways. Free copper and iron ions are powerful catalysts of free-radical damage. By binding copper, ceruloplasmin prevents free copper ions from catalyzing oxidative damage. The ferroxidase activity of ceruloplasmin (oxidation of ferrous iron) facilitates iron loading onto its transport protein, transferrin, and may prevent free ferrous ions (Fe2+) from participating in harmful free-radical-generating reactions (12).

Regulation of gene expression

Cellular copper levels may affect the synthesis of proteins by enhancing or inhibiting the transcription of specific genes. Copper may regulate the expression of genes by increasing the level of intracellular oxidative stress. A number of signal transduction pathways are activated in response to oxidative stress and can lead to an increase in the expression of genes involved in the detoxification of reactive oxygen species (13).

Nutrient interactions


Adequate copper nutritional status is necessary for normal iron metabolism and red blood cell formation. Anemia is a clinical sign of copper deficiency, and iron has been found to accumulate in the livers of copper-deficient animals, indicating that copper (via the copper-containing ceruloplasmin) is required for iron transport to the bone marrow for red blood cell formation (see Iron metabolism) (2). The connection between copper availability and iron metabolism has also been established in humans; copper deficiency can lead to secondary ceruloplasmin deficiency and hepatic iron overload and/or cirrhosis (10). Oral copper supplementation restored normal ceruloplasmin levels and plasma ferroxidase activity and corrected the iron-metabolism disorder in a copper-deficient subject (14). Moreover, infants fed a high iron formula absorbed less copper than infants fed a low iron formula, suggesting that high iron intakes may interfere with copper absorption in infants (15).


High supplemental zinc intakes of 50 mg/day or more for extended periods of time may result in copper deficiency. High dietary zinc intakes increase the synthesis of an intestinal cell protein called metallothionein, which binds certain metals and prevents their absorption by trapping them in intestinal cells. Metallothionein has a stronger affinity for copper than zinc, so high levels of metallothionein induced by excess zinc cause a decrease in copper absorption. In contrast, high copper intakes have not been found to affect zinc nutritional status (2, 15). Zinc supplementation (10 mg/day for eight weeks) was able to restore normal plasma copper/zinc ratios in 65 subjects on long-term hemodialysis who initially exhibited low zinc levels and elevated copper levels. Whether improving zinc and copper status of hemodialysis patients can impact their clinical outcomes needs to be assessed (16).


High fructose diets have exacerbated copper deficiency in rats but not in pigs whose gastrointestinal systems are more like those of humans. Very high levels of dietary fructose (20% of total calories) did not result in copper depletion in humans, suggesting that fructose intake does not result in copper depletion at levels relevant to normal diets (2, 15).

Vitamin C

Although vitamin C supplements have produced copper deficiency in guinea pigs (17), the effect of vitamin C supplements on copper nutritional status in humans is less clear. Two small studies in healthy, young adult men indicate that the oxidase activity of ceruloplasmin may be impaired by relatively high doses of supplemental vitamin C. In one study, vitamin C supplementation of 1,500 mg/day for two months resulted in a significant decline in ceruloplasmin oxidase activity (18). In the other study, supplements of 605 mg/day of vitamin C for three weeks resulted in decreased ceruloplasmin oxidase activity, although copper absorption did not decline (19). Neither of these studies found vitamin C supplementation to adversely affect copper nutritional status.


Clinically evident or frank dietary copper deficiency is relatively uncommon. Serum copper and ceruloplasmin levels may fall to 30% of normal in cases of severe copper deficiency. Hypocupremia (low copper content in blood) is also observed in genetic disorders of copper metabolism, such as aceruloplasminemia and, paradoxically, in Wilson's disease, which are not linked to dietary copper deficiency. One of the most common clinical signs of copper deficiency is an anemia that is unresponsive to iron therapy but corrected by copper supplementation. Although the anemia is thought to result from defective iron mobilization due to decreased ceruloplasmin activity, the absence of ceruloplasmin in individuals with inherited aceruloplasminemia is not always associated with overt anemia (20). Copper deficiency may also lead to abnormally low numbers of white blood cells known as neutrophils (neutropenia), a condition that may be accompanied by increased susceptibility to infection. Copper depletion studies have suggested that reduced copper availability might affect erythroid and myeloid cell lineage, supporting a role for copper in the regulation of blood cell renewal (21, 22). More research is clearly needed to uncover the mechanisms underlying copper deficiency-induced anemia and neutropenia (4, 23). Osteoporosis and other abnormalities of bone development related to copper deficiency are most common in copper-deficient, low-birth-weight infants and young children. Less common features of copper deficiency may include loss of pigmentation, neurological symptoms, and impaired growth (2, 5).

Individuals at risk of deficiency

Cow's milk is relatively low in copper, and cases of copper deficiency have been reported in high-risk infants and children fed only cow's milk formula (24). High-risk individuals include premature infants (especially low-birth-weight infants); infants with prolonged diarrhea; infants and children recovering from malnutrition; and individuals with malabsorption syndromes, including celiac disease, sprue, and short bowel syndrome due to surgical removal of large portions of the intestine. Individuals receiving intravenous total parenteral nutrition lacking copper or other restricted diets may also require supplementation with copper and other trace elements (2, 5). Copper deficiency in infants with cholestasis (reduced biliary excretion of copper) has been linked to long-term parenteral nutrition lacking copper (25). Case reports indicate that cystic fibrosis patients may also be at increased risk of copper insufficiency (26). Finally, excessive zinc intake has led to secondary copper deficiency in individuals using zinc supplements or zinc-enriched dental creams (27, 28).

Acquired copper deficiency

A neurologic syndrome has been described in adults with acquired copper deficiency (29). The symptoms include central nervous system demyelination, polyneuropathy, myelopathy, and inflammation of the optic nerve. The etiology is unknown in absence of prominent risk factors (see Individuals at risk of deficiency); case reports describe increased intestinal copper content suggesting a malabsorption syndrome like Menkes disease, but mutations in ATP7A gene were not linked to the condition (30) (see Inherited copper deficiency). Oral copper replacement (2 mg/day of elemental copper) normalizes serum copper and ceruloplasmin concentrations, stabilizes the condition, and significantly improves the quality of life of affected subjects. However, the duration of copper supplementation has not yet been established, and dosing increments might be required in cases of relapse (29).

Inherited copper deficiency

Copper trafficking within most cells except hepatocytes (liver cells) is facilitated by a Cu1+-transporting ATPase called ATP7A. Mutations in the ATP7A gene impair the transport of intracellular copper, which accumulates in the cytosol of enterocytes and vascular endothelial cells (31). This results in systemic copper deficiency and decreased cuproenzyme activity. Copper transport into the brain is also affected, leading to copper accumulation in the blood-brain barrier and reduced cuproenzyme activity in neurons. Affected individuals are diagnosed with Menkes disease (MD) or with a milder form of the disease called occipital horn syndrome (OHS). The clinical features of MD include intractable seizures, connective tissue disorders, subdural hemorrhage, and hair abnormalities ("kinky hair"). OHS patients exhibit muscular hypotonia and connective tissue abnormalities, including exostosis on occipital bones. Subcutaneous injections of copper-histidine are used to bypass the defective intestinal absorption and improve copper metabolic function in patients. However, copper entry into the brain remains limited (reviewed in 32).

The Recommended Dietary Allowance (RDA)

A variety of indicators were used to establish the RDA for copper, including plasma copper concentration, serum ceruloplasmin activity, superoxide dismutase activity in red blood cells, and platelet copper concentration (15). The RDA for copper reflects the results of depletion-repletion studies and is based on the prevention of deficiency (Table 1).

Table 1. Recommended Dietary Allowance (RDA) for Copper
Life Stage Age Males (μg/day) Females (μg/day)
Infants  0-6 months 200 (AI) 200 (AI)
Infants  7-12 months  220 (AI) 220 (AI)
Children  1-3 years  340 340
Children  4-8 years  440 440
Children  9-13 years  700 700
Adolescents  14-18 years  890 890
Adults  19 years and older 900 900
Pregnancy  all ages   - 1,000
Breast-feeding  all ages   -  1,300

Disease Prevention

Cardiovascular disease

While it is clear that severe copper deficiency results in heart abnormalities and damage (cardiomyopathy) in some animal species, the pathology differs from atherosclerotic cardiovascular disease that is prevalent in humans (15). Studies in humans have produced inconsistent results, and their interpretation is hindered by the lack of a reliable marker of copper nutritional status. Outside the body, free copper is known to be a pro-oxidant and is frequently used to produce oxidation of low-density lipoprotein (LDL) in the test tube. The copper-containing protein ceruloplasmin has been found to stimulate LDL oxidation in the test tube (33), leading some scientists to propose that increased copper levels could increase the risk of atherosclerosis by promoting the oxidation of LDL. However, there is little evidence that copper or ceruloplasmin promotes LDL oxidation in the human body. Additionally, the cuproenzymes, superoxide dismutase and ceruloplasmin, are known to have antioxidant properties, leading some experts to propose that copper deficiency rather than excess copper increases the risk of cardiovascular disease (34).

Epidemiological studies

Several epidemiological studies have found increased serum copper levels to be associated with increased risk of cardiovascular disease. A prospective cohort study in the US examined serum copper levels in more than 4,500 men and women 30 years of age and older (35). During the following 16 years, 151 participants died from coronary heart disease (CHD). After adjusting for other risk factors of heart disease, those with serum copper levels in the two highest quartiles had a significantly greater risk of dying from CHD. Three other case-control studies conducted in Europe had similar findings. One small study in 60 patients with chronic heart failure or ischemic heart disease reported that serum copper was a predictor of short-term outcome (36). Another prospective cohort study in 4,035 middle-aged men reported that high serum copper levels were significantly related to a 50% increase in all-cause mortality; however, serum copper was not significantly associated with cardiovascular mortality in this study (37). Additionally, serum copper has been found to be elevated in patients with rheumatic heart disease (38).

It is important to note that serum copper largely reflects serum ceruloplasmin and is not a sensitive indicator of copper nutritional status (39). Serum ceruloplasmin levels are known to increase by 50% or more under certain conditions of physical stress, such as trauma, inflammation, or disease. Because over 90% of serum copper is carried in ceruloplasmin, which is increased in many inflammatory conditions, elevated serum copper may simply be a marker of inflammation that accompanies atherosclerosis. In contrast to the epidemiological findings linking increased serum copper levels to heart disease, two autopsy studies found copper levels in heart muscle were actually lower in patients who died of CHD than those who died of other causes (40). Additionally, the copper content of white blood cells has been positively correlated with the degree of patency of coronary arteries in CHD patients (41, 42). Further, patients with a history of myocardial infarction (MI) had lower concentrations of extracellular superoxide dismutase (SOD) than those without a history of MI (43). Thus, due to a lack of a reliable biomarker of copper nutritional status, it is not clear whether copper is related to cardiovascular disease.

Intervention studies

While studies in very small numbers of adults fed experimental diets low in copper have demonstrated adverse changes in blood cholesterol levels, including increased total and LDL-cholesterol levels and decreased HDL-cholesterol levels (44), other studies have not confirmed those results (45). Copper supplementation of 2-3 mg/day for four to eight weeks did not result in clinically significant changes in cholesterol levels (34, 46, 47). Further, research has failed to find evidence that increased copper intake increases oxidative stress. In a multi-center, placebo-controlled trial, copper supplementation of 3 or 6 mg/day for six weeks did not result in increased susceptibility of LDL to oxidation induced outside the body (ex vivo) by copper or peroxynitrite (a reactive nitrogen species) (48). Moreover, supplementation with 3 or 6 mg/day of copper decreased the in vitro oxidizability of red blood cells (49), indicating that relatively high intakes of copper do not increase the susceptibility of LDL or red blood cells to oxidation.


Although free copper and ceruloplasmin can promote LDL oxidation in the test tube, there is little evidence that increased dietary copper increases oxidative stress in the human body. Increased serum copper levels have been associated with increased cardiovascular disease risk, but the significance of these findings is unclear due to the association between serum ceruloplasmin levels and inflammatory conditions. Clarification of the relationships between copper nutritional status, ceruloplasmin levels, and cardiovascular disease risk requires further research.

Notably, it was suggested that elevated plasma copper concentrations could be linked to high homocysteine levels in individuals with vascular diseases (50, 51). Increased levels of homocysteine are associated with arterial wall lesions and increased risk of cardiovascular disease (52). The interaction between homocysteine and copper was linked to impaired vascular endothelial function in animal models (53, 54). However, although copper restriction in animals has shown some beneficial effects on homocysteine levels and atherogenic lesions (55, 56), it is not known whether copper imbalance contributes to the atherogenic effect of homocysteine in humans.

Immune system function

Copper is known to play an important role in the development and maintenance of immune system function, but the exact mechanism of its action is not yet known. Neutropenia (abnormally low numbers of white blood cells called neutrophils) is a clinical sign of copper deficiency in humans. Adverse effects of insufficient copper on immune function appear most pronounced in infants. Infants with Menkes disease, a genetic disorder that results in severe copper deficiency, suffer from frequent and severe infections (57, 58). In a study of 11 malnourished infants with evidence of copper deficiency, the ability of certain white blood cells to engulf pathogens increased significantly after one month of copper supplementation (59). Moreover, 11 men on a low-copper diet (0.66 mg copper/day for 24 days and 0.38 mg/day for another 40 days) showed a decreased proliferation response when white blood cells, called monocytes, were isolated from their blood and presented with an immune challenge in cell culture (60). Recent mechanistic studies support a role for copper in innate immune response against bacterial infections (reviewed in 61). While severe copper deficiency has adverse effects on immune function, the effects of marginal copper insufficiency in humans are not yet clear.


The progressive loss of bone mineral density (BMD) leading to osteopenia (pre-osteoporosis) and osteoporosis is commonly observed in the elderly population. Women are more often affected by osteoporosis than men, (e.g., prevalence ratio is 5:1 in non-Hispanic whites) (62), primarily due to the postmenopausal reduction in estrogen production that is essential for maintaining strength of muscle, bone, and connective tissue (63). Osteoporosis is associated with an increased risk of falls, bone fracture, and mortality in individuals over 65 years of age (64). Osteoporosis has also been reported in infants with severe copper deficiency (65, 66), but it is not clear whether marginal copper deficiency during adulthood contributes to osteoporosis. While an increase in bone resorption (breakdown) was observed in 11 healthy adult males with a marginal copper intake of 0.7 mg/day for six weeks (67), the 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 (68, 69). However, it is possible that a reduction in copper intake and absorption in older people reduces the activity of the copper-dependent enzyme, lysyl oxidase, which is required for the maturation (cross-linking) of collagen—a key element in the organic matrix of bone.

Overall, research regarding the role of copper nutritional status in age-related osteoporosis is limited. An early study found that serum copper levels in 46 elderly patients with hip fractures were significantly lower than those of matched controls (70). However, another study found no differences in serum copper levels among postmenopausal women with normal BMD (N=40), osteopenia (N=40), or osteoporosis (N=40) (71). A small study in perimenopausal women, who consumed an average of 1 mg of dietary copper daily, reported decreased loss of BMD from the lumbar spine after copper supplementation of 3 mg/day for two years (72). Additionally, a two-year double-blind, placebo-controlled trial in 59 postmenopausal women found that a combination of supplemental calcium and trace minerals, including 2.5 mg of copper daily, resulted in maintenance of spinal bone density, whereas supplemental calcium or trace minerals, alone, were not effective in preventing loss of bone density (73). However, a more recent randomized, double-blind, placebo-controlled study, which initially enrolled 224 healthy, postmenopausal women aged 51 to 80 years, found daily supplementation with 600 mg of calcium, 2 mg of copper, and 12 mg of zinc for two years decreased whole-body BMD compared to supplemental calcium alone. Moreover, although BMD was clearly reduced in subjects with dietary copper intakes below the RDA (0.9 mg/day), supplemental copper did not prevent the progressive loss of BMD as well as the calcium regimen alone (74). Finally, several studies have suggested that tooth loss might be related to poor systemic BMD (75, 76). When compared with 20 healthy-matched controls, 50 patients (mean age 47.5 years) with low spinal BMD and advanced tooth wear were found with significantly lower copper content in tooth enamel. However, despite evidence suggesting bone demineralization, the serum copper levels in this population were similar to those of the healthy group (77). More research is required to draw conclusions regarding the effects of marginal copper deficiency and copper supplementation on bone metabolism and age-related osteoporosis.

Neurodegenerative diseases

Alzheimer's disease

Cognitive deterioration in individuals with Alzheimer's disease (AD) is linked to the presence of β-amyloid plaques and abnormal Tau protein-forming aggregates. The possibility that copper imbalance is involved in the onset of AD is currently investigated. First, it appears that the fraction of 'free' copper (not bound to ceruloplasmin) is augmented in copper homeostasis disorders, as well as in AD individuals (78, 79). Moreover, AD patients appear to have higher levels of serum copper compared to healthy controls (80). Among the many hypotheses supporting a role for copper in AD onset or progression, it is suggested that copper could be involved in the formation of senile plaques through hypermetallation of the β-amyloid peptides, possibly leading to zinc depletion, enhanced oxidative stress, and even brain damage (81, 82). Recent research has also identified genetic variations (polymorphisms) in the ATP7B gene that may modify the risk of developing AD (83). The protein, ATP7B, is responsible for the excretion of hepatic copper into the biliary tract, and its impairment in Wilson's disease results in increased 'free' copper level in blood and copper accumulation in liver and brain.

More research is needed to investigate whether genetic variants could influence the susceptibility of environmental exposure to high levels of copper. The addition of copper to drinking water has been associated with enhanced pathologic features in animal models of AD (84, 85). One study in a rabbit model reported that combining a high-cholesterol diet and copper (0.12 mg/L in drinking water) could impair cognition (84). A prospective cohort study in 3,718 elderly participants of the Chicago Health and Aging Project, followed for 5.5 years, evaluated the impact of fat and copper intakes using food frequency questionnaires and various cognitive assessments. For individuals with high intakes of saturated and trans fat, cognitive decline was greater for those in the highest quintile of total copper intake compared to the lowest quintile (median intake of 2.75 vs. 0.88 mg/day) (86).

Although a dysfunctional copper metabolism is suggested as a risk factor for AD, it could also be symptomatic of the disease. Moreover, it is still unclear whether copper supplementation or restriction could delay the progression of AD. A small, double-blind, placebo-controlled trial in 68 individuals with mild AD found that supplementation of 8 mg/day of copper for one year delayed the decrease of the β-amyloid peptide Aβ42 in cerebrospinal fluid; a decrease in Aβ42 has been linked to cognitive deterioration (87). However, this delay was not associated with improved cognitive performance (88). Based on the utilization of copper-chelating agents in Wilson's disease, the recent use of slow-release zinc acetate (150 mg/day for six months) in a randomized, placebo-controlled study of 60 patients with mild to moderate AD resulted in a decrease in serum 'free' copper and stabilization of cognition deficits (81). Additional human studies are needed to clarify the role of copper in AD onset and progression, and to evaluate whether dietary copper might help prevent AD in high-risk individuals or manage the disease in AD patients.

Parkinson's disease

Both neurologically presenting Wilson's disease and inherited aceruloplasminemia are characterized by copper accumulation in the brain, resulting in neurologic symptoms (dystonia and cognitive impairment) that resemble Parkinson's disease (PD) (89). The level of copper is diminished in brain regions of neuronal loss in PD patients (90). However, the recent meta-analysis of studies measuring copper levels in serum, plasma, and cerebrospinal fluid did not find any difference between PD patients and healthy elderly subjects (91).


Food sources

Copper is found in a wide variety of foods and is most plentiful in organ meats, shellfish, nuts, and seeds. Wheat-bran cereals and whole-grain products are also good sources of copper. According to national surveys, the average dietary intake of copper in the US is approximately 1.0 to 1.1 mg (1,000 to 1,100 μg) per day for adult women and 1.2 to 1.6 mg (1,200 to 1,600 μg) per day for adult men (15). The copper content of some foods that are relatively rich in copper is listed in micrograms (μg) in Table 2. For more information on the nutrient content of foods, search USDA's FoodData Central.

Table 2. Some Food Sources of Copper
Food Serving Copper (μg)
Liver (beef), cooked, pan-fried 1 ounce 4,128
Mollusks, oysters, eastern, wild, cooked, moist heat 6 medium oysters 2,397
Crab meat, Alaskan king, cooked 3 ounces 1,005
Crab meat, blue, cooked, moist heat 3 ounces 692
Mollusks, clams, mixed species, cooked, moist heat 3 ounces 585
Cashews nuts, raw 1 ounce 622
Sunflower seed kernels, dry roasted 1 ounce 519
Hazelnuts, dry roasted 1 ounce 496
Almonds 1 ounce 292
Peanut butter, chunk style, without salt 2 tablespoons 185
Lentils, mature seeds, cooked, boiled, without salt 1 cup 497
Mushrooms, white, raw 1 cup (sliced) 223
Shredded wheat cereal 2 biscuits 167
Chocolate (semisweet) 1 ounce 198


Copper supplements are available as cupric oxide, copper gluconate, copper sulfate, and copper amino acid chelates (92).



Copper toxicity is rare in the general population. Acute copper poisoning has occurred through the contamination of beverages by storage in copper-containing containers, as well as from contaminated water supplies (93). Guideline values for copper in drinking water have been set by the US Environmental Protection Agency (1.3 mg/liter) and by the World Health Organization (2 mg/liter) (94). Symptoms of acute copper toxicity include abdominal pain, nausea, vomiting, and diarrhea; such symptoms help prevent additional ingestion and absorption of copper. More serious signs of acute copper toxicity include severe liver damage, kidney failure, coma, and death. Of more concern from a nutritional standpoint is the possibility of liver damage resulting from long-term exposure to lower doses of copper. In generally healthy individuals, doses of up to 10,000 μg (10 mg) daily have not resulted in liver damage. For this reason, the US Food and Nutrition Board set the tolerable upper intake level (UL) for copper at 10 mg/day from food and supplements (15; Table 3). It should be noted that individuals with genetic disorders affecting copper metabolism (e.g., Wilson's disease, Indian childhood cirrhosis, and idiopathic copper toxicosis) may be at risk for adverse effects of chronic copper toxicity at significantly lower intake levels. There is some concern that the UL of 10 mg/day might be too high. In particular, men in a research study consumed 7.8 mg/day of copper for 147 days. They accumulated 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 (95, 96). However, another study did not report any adverse effects in individuals supplemented with 8 mg/day of copper for six months (88).

Table 3. Tolerable Upper Intake Level (UL) for Copper
Age Group UL (μg/day)
Infants 0-12 months Not possible to establish* 
Children 1-3 years 1,000 
Children 4-8 years   3,000 
Children 9-13 years   5,000 
Adolescents 14-18 years 8,000 
Adults 19 years and older 10,000
*Source of intake should be from food and formula only.

Drug interactions

Relatively little is known about the interaction of copper with drugs. Penicillamine is used to bind copper and enhance its elimination in Wilson's disease, a genetic disorder resulting in hepatic copper overload. Because penicillamine dramatically increases the urinary excretion of copper, individuals taking the medication for reasons other than copper overload may have an increased copper requirement.

Linus Pauling Institute Recommendation

The RDA for copper (900 μg/day for adults) is sufficient to prevent deficiency, but the lack of clear indicators of copper nutritional status in humans makes it difficult to determine the level of copper intake most likely to promote optimum health or prevent chronic disease. A varied diet should provide enough copper for most people. For those who are concerned that their diet may not provide adequate copper, a multivitamin/mineral supplement will generally provide at least the RDA for copper.

Older adults (>50 years)

Because aging has not been associated with significant changes in the requirement for copper, our recommendation for older adults is the same as that for adults 50 and younger (97).

Authors and Reviewers

Originally written in 2001 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in April 2003 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in January 2008 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in December 2013 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in January 2014 by:
Joseph R. Prohaska, Ph.D.
Professor of Biochemistry, Emeritus
University of Minnesota Medical School Duluth

Copyright 2001-2023  Linus Pauling Institute


1.  Linder MC, Hazegh-Azam M. Copper biochemistry and molecular biology. Am J Clin Nutr. 1996;63(5):797S-811S.  (PubMed)

2.  Turnlund JR. Copper. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2006:286-299.

3.  Prohaska JR. Copper. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Ames: Wiley-Blackwell; 2012:540-553.

4.  Prohaska JR. Impact of copper limitation on expression and function of multicopper oxidases (ferroxidases). Adv Nutr. 2011;2(2):89-95.  (PubMed)

5.  Uauy R, Olivares M, Gonzalez M. Essentiality of copper in humans. Am J Clin Nutr. 1998;67(5 Suppl):952S-959S.  (PubMed)

6.  Vashchenko G, MacGillivray RT. Multi-copper oxidases and human iron metabolism. Nutrients. 2013;5(7):2289-2313.  (PubMed)

7.  Meyer LA, Durley AP, Prohaska JR, Harris ZL. Copper transport and metabolism are normal in aceruloplasminemic mice. J Biol Chem. 2001;276(39):36857-36861.  (PubMed)

8.  Harris ZL, Durley AP, Man TK, Gitlin JD. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci U S A. 1999;96(19):10812-10817.  (PubMed)

9.  Kono S. Aceruloplasminemia. Curr Drug Targets. 2012;13(9):1190-1199.  (PubMed)

10.  Thackeray EW, Sanderson SO, Fox JC, Kumar N. Hepatic iron overload or cirrhosis may occur in acquired copper deficiency and is likely mediated by hypoceruloplasminemia. J Clin Gastroenterol. 2011;45(2):153-158.  (PubMed)

11.  Harris ED. Copper. In: O'Dell BL, Sunde RA, eds. Handbook of nutritionally essential minerals. New York: Marcel Dekker, Inc; 1997:231-273.

12.  Johnson MA, Fischer JG, Kays SE. Is copper an antioxidant nutrient? Crit Rev Food Sci Nutr. 1992;32(1):1-31.

13.  Mattie MD, McElwee MK, Freedman JH. Mechanism of copper-activated transcription: activation of AP-1, and the JNK/SAPK and p38 signal transduction pathways. J Mol Biol. 2008;383(5):1008-1018.  (PubMed)

14.  Videt-Gibou D, Belliard S, Bardou-Jacquet E, et al. Iron excess treatable by copper supplementation in acquired aceruloplasminemia: a new form of secondary human iron overload? Blood. 2009;114(11):2360-2361.  (PubMed)

15. Food and Nutrition Board, Institute of Medicine. Copper. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, D.C.: National Academy Press; 2001:224-257.  (National Academy Press)

16.  Guo CH, Wang CL. Effects of zinc supplementation on plasma copper/zinc ratios, oxidative stress, and immunological status in hemodialysis patients. Int J Med Sci. 2013;10(1):79-89.  (PubMed)

17.  Milne DB, Omaye ST. Effect of vitamin C on copper and iron metabolism in the guinea pig. Int J Vitam Nutr Res. 1980;50(3):301-308.  (PubMed)

18.  Finley EB, Cerklewski FL. Influence of ascorbic acid supplementation on copper status in young adult men. Am J Clin Nutr. 1983;37(4):553-556.  (PubMed)

19.  Jacob RA, Skala JH, Omaye ST, Turnlund JR. Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. J Nutr. 1987;117(12):2109-2115.  (PubMed)

20.  Harris ZL, Klomp LW, Gitlin JD. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am J Clin Nutr. 1998;67(5 Suppl):972S-977S.  (PubMed)

21.  Bustos RI, Jensen EL, Ruiz LM, et al. Copper deficiency alters cell bioenergetics and induces mitochondrial fusion through up-regulation of MFN2 and OPA1 in erythropoietic cells. Biochem Biophys Res Commun. 2013;437(3):426-432.  (PubMed)

22.  Peled T, Landau E, Prus E, Treves AJ, Nagler A, Fibach E. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood-derived CD34+ cells. Br J Haematol. 2002;116(3):655-661.  (PubMed)

23.  Lazarchick J. Update on anemia and neutropenia in copper deficiency. Curr Opin Hematol. 2012;19(1):58-60.  (PubMed)

24.  Shaw JC. Copper deficiency and non-accidental injury. Arch Dis Child. 1988;63(4):448-455.  (PubMed)

25.  Blackmer AB, Bailey E. Management of copper deficiency in cholestatic infants: review of the literature and a case series. Nutr Clin Pract. 2013;28(1):75-86.  (PubMed)

26.  Best K, McCoy K, Gemma S, Disilvestro RA. Copper enzyme activities in cystic fibrosis before and after copper supplementation plus or minus zinc. Metabolism. 2004;53(1):37-41.  (PubMed)

27.  Rowin J, Lewis SL. Copper deficiency myeloneuropathy and pancytopenia secondary to overuse of zinc supplementation. J Neurol Neurosurg Psychiatry. 2005;76(5):750-751.  (PubMed)

28.  Nations SP, Boyer PJ, Love LA, et al. Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease. Neurology. 2008;71(9):639-643.  (PubMed)

29.  Prodan CI, Bottomley SS, Holland NR, Lind SE. Relapsing hypocupraemic myelopathy requiring high-dose oral copper replacement. J Neurol Neurosurg Psychiatry. 2006;77(9):1092-1093.  (PubMed)

30.  Kumar N, Gross JB, Jr. Mutation in the ATP7A gene may not be responsible for hypocupraemia in copper deficiency myelopathy. Postgrad Med J. 2006;82(968):416.  (PubMed)

31.  Tumer Z. An overview and update of ATP7A mutations leading to Menkes disease and occipital horn syndrome. Hum Mutat. 2013;34(3):417-429.  (PubMed)

32.  Kodama H, Fujisawa C, Bhadhprasit W. Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. Curr Drug Metab. 2012;13(3):237-250.  (PubMed)

33.  Fox PL, Mazumder B, Ehrenwald E, Mukhopadhyay CK. Ceruloplasmin and cardiovascular disease. Free Radic Biol Med. 2000;28(12):1735-1744.  (PubMed)

34.  Jones AA, DiSilvestro RA, Coleman M, Wagner TL. Copper supplementation of adult men: effects on blood copper enzyme activities and indicators of cardiovascular disease risk. Metabolism. 1997;46(12):1380-1383.  (PubMed)

35.  Ford ES. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol. 2000;151(12):1182-1188.  (PubMed)

36.  Malek F, Jiresova E, Dohnalova A, Koprivova H, Spacek R. Serum copper as a marker of inflammation in prediction of short term outcome in high risk patients with chronic heart failure. Int J Cardiol. 2006;113(2):e51-53.  (PubMed)

37.  Leone N, Courbon D, Ducimetiere P, Zureik M. Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality. Epidemiology. 2006;17(3):308-314.  (PubMed)

38.  Kosar F, Sahin I, Acikgoz N, Aksoy Y, Kucukbay Z, Cehreli S. Significance of serum trace element status in patients with rheumatic heart disease: a prospective study. Biol Trace Elem Res. 2005;107(1):1-10.  (PubMed)

39.  Bertinato J, Zouzoulas A. Considerations in the development of biomarkers of copper status. J AOAC Int. 2009;92(5):1541-1550.  (PubMed)

40.  Klevay LM. Cardiovascular disease from copper deficiency--a history. J Nutr. 2000;130(2S Suppl):489S-492S.  (PubMed)

41.  Mielcarz G, Howard AN, Mielcarz B, et al. Leucocyte copper, a marker of copper body status is low in coronary artery disease. J Trace Elem Med Biol. 2001;15(1):31-35.  (PubMed)

42.  Kinsman GD, Howard AN, Stone DL, Mullins PA. Studies in copper status and atherosclerosis. Biochem Soc Trans. 1990;18(6):1186-1188.  (PubMed)

43. Wang XL, Adachi T, Sim AS, Wilcken DE. Plasma extracellular superoxide dismutase levels in an Australian population with coronary artery disease. Arterioscler Thromb Vasc Biol. 1998;18(12):1915-1921.  (PubMed)

44.  Klevay LM. Lack of a recommended dietary allowance for copper may be hazardous to your health. J Am Coll Nutr. 1998;17(4):322-326.  (PubMed)

45.  Milne DB, Nielsen FH. Effects of a diet low in copper on copper-status indicators in postmenopausal women. Am J Clin Nutr. 1996;63(3):358-364.  (PubMed)

46.  Medeiros DM, Milton A, Brunett E, Stacy L. Copper supplementation effects on indicators of copper status and serum cholesterol in adult males. Biol Trace Elem Res. 1991;30(1):19-35.  (PubMed)

47.  DiSilvestro RA, Joseph EL, Zhang W, Raimo AE, Kim YM. A randomized trial of copper supplementation effects on blood copper enzyme activities and parameters related to cardiovascular health. Metabolism. 2012;61(9):1242-1246.  (PubMed)

48.  Turley E, McKeown A, Bonham MP, et al. Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project). Free Radic Biol Med. 2000;29(11):1129-1134.  (PubMed)

49.  Rock E, Mazur A, O'Connor J M, Bonham MP, Rayssiguier Y, Strain JJ. The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers. Free Radic Biol Med. 2000;28(3):324-329.  (PubMed)

50.  Mansoor MA, Bergmark C, Haswell SJ, et al. Correlation between plasma total homocysteine and copper in patients with peripheral vascular disease. Clin Chem. 2000;46(3):385-391.  (PubMed)

51.  Celik C, Bastu E, Abali R, et al. The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome. Gynecol Endocrinol. 2013;29(5):488-491.  (PubMed)

52.  Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol. 1999;10(5):417-428.  (PubMed)

53.  Emsley AM, Jeremy JY, Gomes GN, Angelini GD, Plane F. Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta. Br J Pharmacol. 1999;126(4):1034-1040.  (PubMed)

54.  Shukla N, Angelini GD, Jeremy JY. Interactive effects of homocysteine and copper on angiogenesis in porcine isolated saphenous vein. Ann Thorac Surg. 2007;84(1):43-49.  (PubMed)

55.  Uthus EO, Reeves PG, Saari JT. Copper deficiency decreases plasma homocysteine in rats. J Nutr. 2007;137(6):1370-1374.  (PubMed)

56.  Wei H, Zhang WJ, McMillen TS, Leboeuf RC, Frei B. Copper chelation by tetrathiomolybdate inhibits vascular inflammation and atherosclerotic lesion development in apolipoprotein E-deficient mice. Atherosclerosis. 2012;223(2):306-313.  (PubMed)

57.  Failla ML, Hopkins RG. Is low copper status immunosuppressive? Nutr Rev. 1998;56(1 Pt 2):S59-64.

58.  Percival SS. Copper and immunity. Am J Clin Nutr. 1998;67(5 Suppl):1064S-1068S.  (PubMed)

59.  Heresi G, Castillo-Duran C, Munoz C, Arevalo M, Schlesinger L. Phagocytosis and immunoglobulin levels in hypocupremic children. Nutr Res. 1985;5:1327-1334.

60.  Kelley DS, Daudu PA, Taylor PC, Mackey BE, Turnlund JR. Effects of low-copper diets on human immune response. Am J Clin Nutr. 1995;62(2):412-416.  (PubMed)

61.  Hodgkinson V, Petris MJ. Copper homeostasis at the host-pathogen interface. J Biol Chem. 2012;287(17):13549-13555.  (PubMed)

62.  Looker AC, Melton LJ, 3rd, Harris TB, Borrud LG, Shepherd JA. Prevalence and trends in low femur bone density among older US adults: NHANES 2005-2006 compared with NHANES III. J Bone Miner Res. 2010;25(1):64-71.  (PubMed)

63.  Tiidus PM, Lowe DA, Brown M. Estrogen replacement and skeletal muscle: mechanisms and population health. J Appl Physiol. 2013;115(5):569-578.  (PubMed)

64.  Cauley JA. Public Health Impact of Osteoporosis. J Gerontol A Biol Sci Med Sci. 2013;68(10):1243-1251.  (PubMed)

65.  Kanumakala S, Boneh A, Zacharin M. Pamidronate treatment improves bone mineral density in children with Menkes disease. J Inherit Metab Dis. 2002;25(5):391-398.  (PubMed)

66.  Marquardt ML, Done SL, Sandrock M, Berdon WE, Feldman KW. Copper deficiency presenting as metabolic bone disease in extremely low birth weight, short-gut infants. Pediatrics. 2012;130(3):e695-698.  (PubMed)

67.  Baker A, Harvey L, Majask-Newman G, Fairweather-Tait S, Flynn A, Cashman K. Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males. Eur J Clin Nutr. 1999;53(5):408-412.  (PubMed)

68.  Baker A, Turley E, Bonham MP, et al. No effect of copper supplementation on biochemical markers of bone metabolism in healthy adults. Br J Nutr. 1999;82(4):283-290.  (PubMed)

69.  Cashman KD, Baker A, Ginty F, et al. No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status. Eur J Clin Nutr. 2001;55(7):525-531.  (PubMed)

70.  Conlan D, Korula R, Tallentire D. Serum copper levels in elderly patients with femoral-neck fractures. Age Ageing. 1990;19(3):212-214.  (PubMed)

71.  Mutlu M, Argun M, Kilic E, Saraymen R, Yazar S. Magnesium, zinc and copper status in osteoporotic, osteopenic and normal post-menopausal women. J Int Med Res. 2007;35(5):692-695.  (PubMed)

72.  Eaton-Evans J, Mellwrath EM, Jackson WE, McCartney H, Strain JJ. Copper supplementation and the maintenance of bone mineral density in middle-aged women. J Trace Elem Exp Med. 1996;9:87-94.

73.  Strause L, Saltman P, Smith KT, Bracker M, Andon MB. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr. 1994;124(7):1060-1064.  (PubMed)

74.  Nielsen FH, Lukaski HC, Johnson LK, Roughead ZK. Reported zinc, but not copper, intakes influence whole-body bone density, mineral content and T score responses to zinc and copper supplementation in healthy postmenopausal women. Br J Nutr. 2011;106(12):1872-1879.  (PubMed)

75.  Sidiropoulou-Chatzigiannis S, Kourtidou M, Tsalikis L. The effect of osteoporosis on periodontal status, alveolar bone and orthodontic tooth movement. A literature review. J Int Acad Periodontol. 2007;9(3):77-84.  (PubMed)

76.  Darcey J, Horner K, Walsh T, Southern H, Marjanovic EJ, Devlin H. Tooth loss and osteoporosis: to assess the association between osteoporosis status and tooth number. Br Dent J. 2013;214(4):E10.  (PubMed)

77.  Sierpinska T, Konstantynowicz J, Orywal K, Golebiewska M, Szmitkowski M. Copper deficit as a potential pathogenic factor of reduced bone mineral density and severe tooth wear. Osteoporos Int. 2013 [Epub ahead of print].  (PubMed)

78.  Squitti R, Barbati G, Rossi L, et al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [β]-amyloid, and h-τ. Neurology. 2006;67(1):76-82.  (PubMed)

79.  Arnal N, Cristalli DO, de Alaniz MJ, Marra CA. Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives. Brain Res. 2010;1319:118-130.  (PubMed)

80.  Ventriglia M, Bucossi S, Panetta V, Squitti R. Copper in Alzheimer's disease: a meta-analysis of serum, plasma, and cerebrospinal fluid studies. J Alzheimers Dis. 2012;30(4):981-984.  (PubMed)

81.  Brewer GJ. Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease. Biofactors. 2012;38(2):107-113.  (PubMed)

82.  Squitti R, Polimanti R. Copper phenotype in Alzheimer's disease: dissecting the pathway. Am J Neurodegener Dis. 2013;2(2):46-56.  (PubMed)

83.  Squitti R, Polimanti R. Copper hypothesis in the missing hereditability of sporadic Alzheimer's disease: ATP7B gene as potential harbor of rare variants. J Alzheimers Dis. 2012;29(3):493-501.  (PubMed)

84.  Sparks DL, Schreurs BG. Trace amounts of copper in water induce β-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2003;100(19):11065-11069.  (PubMed)

85.  Kitazawa M, Cheng D, Laferla FM. Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. J Neurochem. 2009;108(6):1550-1560.  (PubMed)

86.  Morris MC, Evans DA, Tangney CC, et al. Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol. 2006;63(8):1085-1088.  (PubMed)

87.  Kessler H, Pajonk FG, Bach D, et al. Effect of copper intake on CSF parameters in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial. J Neural Transm. 2008;115(12):1651-1659.  (PubMed)

88.  Kessler H, Bayer TA, Bach D, et al. Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial. J Neural Transm. 2008;115(8):1181-1187.  (PubMed)

89.  Skjorringe T, Moller LB, Moos T. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders. Front Pharmacol. 2012;3:169.  (PubMed)

90.  Akatsu H, Hori A, Yamamoto T, et al. Transition metal abnormalities in progressive dementias. Biometals. 2012;25(2):337-350.  (PubMed)

91.  Mariani S, Ventriglia M, Simonelli I, et al. Fe and Cu do not differ in Parkinson's disease: a replication study plus meta-analysis. Neurobiol Aging. 2013;34(2):632-633.  (PubMed)

92.  Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001.

93.  Bremner I. Manifestations of copper excess. Am J Clin Nutr. 1998;67(5 Suppl):1069S-1073S.  (PubMed)

94.  Fitzgerald DJ. Safety guidelines for copper in water. Am J Clin Nutr. 1998;67(5 Suppl):1098S-1102S.  (PubMed)

95.  Turnlund JR, Jacob RA, Keen CL, et al. Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men. Am J Clin Nutr. 2004;79(6):1037-1044.  (PubMed)

96.  Turnlund JR, Keyes WR, Kim SK, Domek JM. Long-term high copper intake: effects on copper absorption, retention, and homeostasis in men. Am J Clin Nutr. 2005;81(4):822-828.  (PubMed)

97.  Wood RJ, Suter PM, Russell RM. Mineral requirements of elderly people. Am J Clin Nutr. 1995;62(3):493-505.  (PubMed)