Copper deficiency, toxicity and supplementation in children 

Copper is a mineral found in all body tissues and most secretions. It serves as a cofactor for enzymes involved in energy production, iron metabolism, and neurotransmitter synthesis.¹ Additionally, copper is a cofactor for superoxide dismutase, an important part of the body’s antioxidant defense against oxidative stress. Copper is necessary for the synthesis of connective tissues like collagen and elastin, has a hand in blood clotting, immune function, and the activation of several hormones.² Copper is also involved in the development of new blood vessels, regulation of gene expression, and brain development.¹ 

Food sources of copper 

Copper can be found in a wide variety of foods. Some of the best sources of copper are meat, especially organ meats and shellfish. Other sources of copper are cashews, nuts and seeds, legumes, dried figs, potatoes, whole grains, tofu and cocoa2. 

Recommended Dietary Allowance (RDA) for copper 

The RDA for copper is as follows: 

The recommended intake for infants from birth to 12 months is equivalent to the average intake of copper in healthy, breastfed babies.¹ 

Signs of copper deficiency: 

Copper deficiency is rare due to its presence in a wide variety of foods. A deficiency may result in hypochromic, microcytic anemia, indicating a reduction in red blood cell count and hemoglobin content.² Consider copper deficiency in a patient with microcytic anemia with no response to iron supplementation, or with normal ferritin level, especially in patients supplementing zinc (see below).

Signs and symptoms of a copper deficiency include hypopigmentation or depigmentation of skin and hair, impaired immune function, altered cholesterol metabolism, cardiovascular and pulmonary dysfunction, and abnormalities in blood vessels, connective tissue, and bones.² 

Aside from poor dietary intake, copper deficiency may be caused by an overconsumption of zinc, malabsorption from conditions like celiac disease or IBD, and regular use of proton pump inhibitors. Individuals with celiac disease are at a greater risk of copper deficiency as a result of intestinal malabsorption. 

Excessive zinc intake can interfere with the body’s ability to absorb copper, resulting in a deficiency. Copper and zinc share a transporter in the body and if there’s too much of one mineral, the other can’t be transported, absorbed or utilized. Typically, this isn’t an issue when zinc is obtained from whole food sources (oysters, meat, poultry), but can become problematic in those taking high dose zinc supplements. Typically copper deficiency only occurs when a patient is taking > 50 mg of zinc without additional copper for a long period of time (at least > 6 months, but symptoms usually occur at 1+ years). Patients who require long-term zinc supplementation should take additional copper to prevent deficiency. Typically 1-2 mg per 50 mg of zinc is appropriate.

Signs of copper toxicity: 

Copper toxicity is also quite rare but can occur in the United States due to water contamination or accidental ingestion. The Tolerable Upper Limit is 10 mg/day, although 5 mg/day has been known to cause GI discomfort. Acute toxicity may result in gastrointestinal discomfort, nausea, vomiting, diarrhea, weakness, lethargy, and/or anorexia.² Chronic toxicity can cause liver and kidney damage, resulting in blood in the urine, jaundice, and in extreme cases, a lack of urine output altogether.² 

Another cause of copper toxicity is the genetic disorder Wilson’s disease. In Wilson’s disease, a mutation to the ATP7B gene causes a disruption in the excretion of copper into bile, resulting in copper accumulation in the liver. The excess copper leaks out of the liver and is deposited in the joints and organs like the brain, kidneys, heart, and eyes. Common symptoms of Wilson’s disease are greenish brown rings around the eyes known as Kayser Fleisher rings, cirrhosis, inflammation of the liver and kidneys, osteoarthritis, seizures, movement disorders, and psychiatric problems.² Fortunately, Wilson’s disease can be treated with chelation medications that bind and excrete the excess copper. 

Copper Supplementation and side effects: 

Copper sulfate is the most common form of copper found in mineral fortified food products and supplements. Usually copper is taken in a multimineral, rather than on its own. Large doses of copper do not appear to impact zinc absorption in the same way that large doses of zinc can interfere with copper absorption. Early signs of copper toxicity are abdominal cramps, nausea, diarrhea, and vomiting. Only begin a new supplement under the care of your primary care provider. 

Clinical uses of copper or considerations of copper in naturopathic medicine

Autism Spectrum Disorder 

Several studies have indicated a relationship between copper, zinc, and Autism Spectrum Disorders (ASD). Children who have ASD are more likely to have zinc deficiency, copper excess, and a low zinc to copper ratio compared to neurotypical children.³ A zinc deficiency may result in neuropsychological changes, similar to those seen in ASD, like “emotional instability, irritability, and depression”.³ Zinc deficiency may also interfere with cognitive performance and block NMDA receptors.³ On the other hand, copper toxicity may have neurotoxic effects, causing depression, irritability, fear, nervousness, learning and behavioral disorders.³ Another study found that zinc therapy in children with ASD significantly improved hyperactivity and stimming in children who have ASD and GI disease.⁴ However, these results were not seen in children who did not have GI disease.⁴ 

Here are a few reasons why copper might be associated with psychiatric changes in children with ASD:

1. Impaired copper metabolism: Some individuals with ASD may have impaired copper metabolism, leading to either copper deficiency or excess copper accumulation. Abnormal copper levels can impact neurotransmitter balance and function, which in turn can influence brain activity and contribute to psychiatric symptoms.
2. Oxidative stress: Copper is involved in the production of reactive oxygen species (ROS) during normal physiological processes. Excessive copper or imbalances in copper-related enzymes can lead to increased oxidative stress, which is associated with neuroinflammation and neuronal damage. Oxidative stress has been implicated in the development of psychiatric symptoms in ASD.
3. Neurotransmitter imbalances: Copper is involved in the synthesis and metabolism of several neurotransmitters, including dopamine and norepinephrine. Disruptions in copper levels or copper-related enzymes can affect neurotransmitter balance, potentially contributing to psychiatric changes observed in children with ASD.
4. Genetic factors: Genetic variations in copper-related genes, such as ATP7A and ATP7B, have been associated with both ASD and copper metabolism disorders. These genetic factors may contribute to altered copper handling and potentially influence the risk of psychiatric symptoms in individuals with ASD.

It’s important to note that while there is some evidence linking copper dysregulation to psychiatric changes in children with ASD, the exact mechanisms and the role of copper in ASD are still being researched. Additionally, copper abnormalities are not universally observed in all individuals with ASD, and the relationship between copper and psychiatric symptoms in ASD is complex and multifactorial.

ADHD

A similar association has been made between copper concentration and ADHD, although the results are inconclusive.⁵ Like with ASD, most of the evidence points towards the copper to zinc ratio, rather than the individual mineral concentrations.⁵ However, it appears that low copper intake and concentration levels are associated with a predisposition for ADHD, while elevated levels are more likely to be associated with ASD.⁵ One study found that elevated copper to zinc ratio may contribute to the risk and/or severity of ADHD. Clinical copper supplementation studies have not been conducted and thus a causative relationship cannot be determined. 

Celiac disease

Individuals with Celiac disease (CD) often struggle with malabsorption due to damage to their intestinal lining. GI malabsorption increases the risk of developing numerous micronutrient deficiencies, including copper. The actual incidence of copper deficiency in CD is unknown, but it should be investigated on an individual basis, especially in the presence of limb weakness indicating anemia.⁶ A high quality gluten free diet with copper supplementation will likely resolve the patients symptoms completely.⁶ 

Testing copper levels (serum copper vs. ceruloplasmin)

To test copper levels in the body, healthcare professionals typically use blood tests. Here are two common blood tests used to assess copper status:

1. Serum Copper: This test measures the amount of copper circulating in the blood. It provides an overall indication of copper levels but may not always reflect the body’s copper status accurately. Serum copper levels can be influenced by factors such as recent dietary intake or acute illness.
2. Ceruloplasmin: Ceruloplasmin is a protein that carries the majority of copper in the blood. Measuring ceruloplasmin levels can provide a more reliable assessment of copper status. Low levels of ceruloplasmin may indicate copper deficiency, while high levels can be associated with copper overload.

In some cases, additional tests may be recommended to evaluate copper metabolism and identify specific conditions related to copper imbalance. These tests can include 24-hour urine copper collection, liver function tests, genetic testing for conditions like Wilson’s disease, or other specialized tests as deemed necessary.

It is important to note that interpreting copper test results should be done in consultation with a healthcare professional. They will consider the individual’s clinical history, symptoms, and other factors to make an accurate assessment of copper status and guide appropriate treatment or intervention if needed.

Ideal zinc:copper ratio

The ideal zinc to copper ratio in bloodwork can vary depending on the reference range used by the laboratory performing the analysis. However, a commonly cited optimal range for the zinc to copper ratio is approximately 0.7 to 1.0.

To calculate the ratio, divide the zinc level (usually measured in milligrams per liter or micrograms per deciliter) by the copper level in the same units. For example, if the zinc level is 10 mg/L and the copper level is 12 mg/L, the ratio would be 10/12, which equals approximately 0.83.

It’s important to note that the reference ranges and interpretation of the zinc to copper ratio can vary among different laboratories and medical professionals. These ratios serve as general guidelines, but individual needs and health conditions should be taken into account when assessing the significance of the ratio. Also remember that serum zinc and copper may not be the best markers of storage of these minerals, and that serum levels (as discussed above) may be influenced by recent dietary intake.

Importance of zinc

For more information on the importance of zinc and the safety of zinc supplementation please read our article: Is zinc supplementation safe for children?

Safety of copper in food and supplement form: 

Copper from whole food sources is generally recognized as safe, except in individuals with Wilson’s disease. Contaminated water sources run the risk of copper toxicity. Copper supplementation should be considered on a case by case basis under the supervision of one’s primary care provider. In most cases patients will not need copper supplementation, and unless there are documented deficiencies the risks of copper supplementation outweigh any potential benefits.

Summary: 

Copper is a mineral found in a wide array of foods, including organ meats, shellfish, legumes, potatoes, whole grains, nuts and seeds. Copper is an important cofactor for many enzymatic processes related to energy production, iron metabolism, neurotransmitter synthesis, connective tissue synthesis and immune function. Excessive zinc supplementation and GI malabsorption may cause copper deficiency, impacting multiple organ systems. Symptoms of copper deficiency include gastrointestinal upset, depigmentation of skin and hair, impaired immune function, cardiovascular and pulmonary dysfunction, and anemia. Copper toxicity is rare, but may be caused by contaminated water or the genetic disorder, Wilson’s disease. Some studies show a correlation between the zinc to copper ratio and Autism and ADHD. More clinical research is required to determine if supplementation is warranted in these conditions. Children with Celiac disease are at risk of numerous mineral deficiencies and should be screened for a copper deficiency before beginning supplementation. 

Resources: 

1. National Institutes of Health. Copper. NIH. 2023.
   
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   Edition. Cengage Learning. 370-388.
   
3. Faber, S., Zinn, G. M., Kern Ii, J. C., & Skip Kingston, H. M. (2009). The plasma
   zinc/serum copper ratio as a biomarker in children with autism spectrum disorders.
   Biomarkers, 14(3), 171-180.
   
4. Russo AJ. Increased Copper in Individuals with Autism Normalizes Post Zinc Therapy
   More Efficiently in Individuals with Concurrent GI Disease. Nutr Metab Insights.
   2011;4:49-54. Published 2011 Sep 29. doi:10.4137/NMI.S6827
   
5. Robberecht H, Verlaet AAJ, Breynaert A, De Bruyne T, Hermans N. Magnesium, Iron,
   Zinc, Copper and Selenium Status in Attention-Deficit/Hyperactivity Disorder (ADHD).
   Molecules. 2020;25(19):4440. Published 2020 Sep 27. doi:10.3390/molecules25194440
   
6. Di Nardo G, Villa MP, Conti L, Ranucci G, Pacchiarotti C, Principessa L, Raucci U,
   Parisi P. Nutritional Deficiencies in Children with Celiac Disease Resulting from a Gluten-Free Diet: A Systematic Review. Nutrients. 2019; 11(7):1588. https://doi.org/10.3390/nu11071588
   

This article was researched by Kayla Martin, CNS and edited by Erika Krumbeck, ND.