Who Found the Role of Copper, and How an Anemia Study Led to a Trace Mineral

The history of copper starts with a 1928 rat study on hemoglobin, moves through two rare inherited disorders, and ends at an upper limit that now sets the ceiling for copper intake. Zinc and copper can work against each other on the same label.

The history of copper starts with a rat study, not with a mineral label. In 1928, Hart, Steenbock, Waddell and Elvehjem reported on copper as a supplement to iron for building hemoglobin in the rat. The story then runs through two rare inherited disorders, ceruloplasmin (a copper enzyme that carries most of the copper in plasma), and an upper limit that now sets the ceiling for copper intake. Copper matters in both directions. A shortage can show up as anemia, among other effects, and an excess can harm the liver ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). That is why the amount printed on a supplement label matters as much as the form. ## In this article - A 1928 rat study tied copper to hemoglobin - Menkes and Wilson showed copper's two sides - How zinc can crowd copper out of absorption - The upper limit and the forms on labels - Bottom line ## A 1928 rat study tied copper to hemoglobin According to PubMed, the record for the 1928 paper carries a 2002 publication date and appears in the Journal of Biological Chemistry. PubMed classifies it as a seminal and historical article and has no abstract for it, so this page relies on the title, which says copper worked as a supplement to iron for hemoglobin building in the rat ([PubMed](https://pubmed.ncbi.nlm.nih.gov/12243126/)). For the iron side of the same story, read the [iron supplements history](/blog/history/history-of-iron-supplements-and-the-ferritin-test). Anemia is one of the effects the NIH lists for copper deficiency in animals and humans, along with hypopigmentation and increased risk of infection. The NIH also says copper deficiency is uncommon in humans, and typical US diets meet or exceed the copper RDA ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). Copper works mainly through enzymes. The NIH describes it as a cofactor for several enzymes, called cuproenzymes, involved in energy production, iron metabolism, neuropeptide activation, connective tissue synthesis and neurotransmitter synthesis. Ceruloplasmin carries more than 95 percent of the total copper in healthy human plasma, and defense against oxidative damage depends mainly on copper-containing superoxide dismutases ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). For the energy side of that picture, see our [mitochondrial health guide](/health/mitochondrial-health-complete-guide). ## Menkes and Wilson showed copper's two sides Two rare inherited disorders show what goes wrong with copper in each direction. In 1962, Menkes and four colleagues published a report in *Pediatrics* titled "A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration" ([PubMed](https://pubmed.ncbi.nlm.nih.gov/14472668/)). The NIH describes Menkes disease as a rare, X-linked, recessive disorder of copper homeostasis caused by mutations in *ATP7A*, which encodes a copper-transporting ATPase. Intestinal absorption of dietary copper drops sharply in these individuals. Typical signs include failure to thrive, impaired cognitive development and unusually kinky hair. Most individuals die by age 3 if untreated, but subcutaneous copper injections started in the first few weeks after birth can reduce mortality risk and improve development ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). Wilson disease is the other side. The NIH describes it as a rare, autosomal recessive disease caused by mutations in *ATP7B*, which leads to abnormally high tissue levels of copper. Its neurologic and liver damage can result in cirrhosis. Lifelong copper chelation therapy or high doses of zinc can prevent permanent organ damage in these patients ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). ## How zinc can crowd copper out of absorption The zinc link matters for anyone taking both minerals. High dietary zinc can interfere with copper absorption, and excessive zinc supplements can lead to copper deficiency. Reductions in erythrocyte copper-zinc superoxide dismutase, a marker of copper status, have been reported with zinc intakes of about 60 mg a day for up to 10 weeks. The NIH cites this interaction as one reason the adult upper limit for zinc is 40 mg a day ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). For the zinc side, see our [zinc ingredient page](/ingredients/zinc). ## The upper limit and the forms on labels The RDA for adults 19 and older is 900 mcg a day. For the same group, the tolerable upper intake level is 10,000 mcg, or 10 mg a day, according to the NIH. Chronic exposure to high levels can cause liver damage and gastrointestinal symptoms such as abdominal pain, cramps, nausea, diarrhea and vomiting. The upper limits do not apply to people receiving supplemental copper under medical supervision ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). Toxicity is rare in healthy people without a hereditary copper defect. It has been reported, though, in people whose water carried high copper levels from stagnant water in copper-containing pipes ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). Copper appears on labels in several forms. The NIH lists cupric oxide, cupric sulfate, copper amino acid chelates and copper gluconate, and it says no studies have compared the bioavailability of copper from these and other forms. Copper amounts in supplements typically range from a few micrograms to 15 mg, so read the amount as well as the form ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). ## Bottom line Read the copper and zinc amounts on a multivitamin together, because high zinc can reduce copper absorption. Set the copper amount against the 900 mcg adult RDA and the 10 mg upper limit. If you are considering copper beyond what a multivitamin supplies, check with a clinician first. ## Frequently asked questions ### How did copper enter the story of anemia? Copper entered through a 1928 study of rats, which reported that copper worked as a supplement to iron for building hemoglobin ([PubMed](https://pubmed.ncbi.nlm.nih.gov/12243126/)). The NIH lists anemia among the effects of copper deficiency in animals and humans. It also says copper deficiency is uncommon in humans, and typical US diets meet or exceed the copper RDA. So the anemia link explains how copper entered the research record, but it does not mean most people are short on copper ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). ### What is the Hart effect, and why does it matter? This page could not verify "Hart effect" as a named term in any source it could retrieve, so it does not use the name as fact. The verified anchor is the 1928 paper by Hart, Steenbock, Waddell and Elvehjem. Its title reports copper as a supplement to iron for hemoglobin building in the rat. It matters here because it ties copper to hemoglobin building in a primary source. PubMed has no abstract for the paper, so this page does not state doses or outcome numbers from it ([PubMed](https://pubmed.ncbi.nlm.nih.gov/12243126/)). ### Who first linked copper to blood and iron? This page does not name a first. The earliest source it verified is the 1928 paper by Hart, Steenbock, Waddell and Elvehjem, which ties copper to hemoglobin building alongside iron in rats ([PubMed](https://pubmed.ncbi.nlm.nih.gov/12243126/)). The page did not check every earlier report, so it does not call that paper the first. Treat the 1928 record as the starting point for the copper story here, not as the end of the search for earlier work. ### Why does copper matter in rare genetic disorders? Two rare disorders show copper's two sides. Menkes disease is an X-linked recessive disorder caused by ATP7A mutations, and intestinal absorption of copper drops sharply in it, leading to signs of copper deficiency. Wilson disease is an autosomal recessive disease caused by ATP7B mutations, and it leads to abnormally high tissue copper. A 1962 report on the Menkes disorder appeared in *Pediatrics* ([PubMed](https://pubmed.ncbi.nlm.nih.gov/14472668/)). The NIH places Menkes disease among the groups at risk of copper inadequacy and Wilson disease under health risks from excessive copper ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). ### How does copper relate to zinc in supplements? High dietary zinc can interfere with copper absorption, and excessive zinc supplements can lead to copper deficiency, according to the NIH. Reductions in erythrocyte copper-zinc superoxide dismutase have been reported with zinc intakes of about 60 mg a day for up to 10 weeks. The NIH cites this interaction as one reason the adult upper limit for zinc is 40 mg a day. When a multivitamin or a zinc product is on the shelf, check the copper and zinc amounts on the label together before adding another supplement ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). ### How much copper is too much? For adults 19 and older, the tolerable upper intake level is 10,000 mcg, or 10 mg a day, according to the NIH. Chronic exposure to high levels can cause liver damage and gastrointestinal symptoms. Toxicity is rare in healthy people without a hereditary copper defect, though it has been reported in people whose water carried high copper from stagnant water in copper-containing pipes. The upper limits do not apply to supplemental copper given under medical supervision ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)). ### Which copper forms appear in multivitamins? The NIH says dietary supplements contain many forms of copper, including cupric oxide, cupric sulfate, copper amino acid chelates and copper gluconate. Copper is available in many multivitamin and mineral products, and supplements that contain it range from a few micrograms to 15 mg. The NIH also says no studies have compared the bioavailability of copper from these and other forms, so the form on the label is not a settled guide to absorption ([NIH ODS](https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/)).