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What Are the Health Consequences of a Copper and Zinc Imbalance From a Bioregulatory Perspective?

by James Odell, OMD, ND, LAc

copper and zinc on the periodic chart

The body has an amazing and complex system for managing and regulating the physiological amount of key trace minerals circulating in the blood and stored in cells. Nutrient minerals from our diet are incorporated into the blood and transported into cells. Minerals are excreted if blood and cell levels are sufficient or overloaded. When this system fails to function properly, abnormal levels and ratios of trace minerals can develop. One of the most common trace-mineral (metal) imbalances is expressed in copper-zinc. The ratio of copper (Cu) to zinc (Zn) is clinically more important than the concentration of either of these trace minerals (metals).

Although Hippocrates is said to have prescribed copper compounds to treat diseases as early as 400 B.C. scientists are still uncovering new information regarding the functions of copper in the human body.

Copper is an essential trace mineral necessary for survival. It is essential for enzymes involved with such diverse roles as bone formation, energy metabolism, nerve transmission, elastin synthesis, pigmentation of the skin, normal hair growth, red blood cell production, and cellular immunity. Copper plays an important role in our metabolism, largely because it allows many critical enzymes to function properly.1

Copper can act as both an antioxidant and a pro-oxidant. Free radicals occur naturally in the body and can damage cell walls, interact with genetic material, and contribute to the development of several health problems and diseases. As an antioxidant, Cu scavenges or neutralizes free radicals and may reduce or help prevent some of the damage they cause.2. Under certain imbalanced circumstances, copper can also participate in reactions that result in the production of highly reactive oxygen species (ROS), responsible for lipid peroxidation in membranes, direct oxidation of proteins, and cleavage of DNA and RNA molecules.

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.3

Both copper deficiency and copper excess produce adverse health effects. Thus, maintaining the proper dietary balance of Cu, along with other metal minerals such as zinc, iron, and manganese, is important. Alterations in copper metabolism are associated with genetic and nongenetic diseases, including potential connections to inflammation, cancer, atherosclerosis, and anemia, and the genetic copper deficiency (Menkes syndrome) and copper overload (Wilson disease).

Some symptoms of copper deficiency include anemia, low body temperature, bone fractures, osteoporosis, low white blood cell count, irregular heartbeat, loss of pigment from the skin, and thyroid problems. Some symptoms of copper excess include depression, fatigue, irritability, excitation, and difficulty focusing.

Zinc is involved in numerous aspects of cellular metabolism. It is estimated that about 10% of human proteins potentially bind zinc, in addition to hundreds that transport zinc. It is required for the catalytic activity of more than 200 enzymes 4, 5, and it plays a role in immune function6, wound healing, protein synthesis, DNA synthesis, and cell division.7

Zinc is required for a proper sense of taste and smell.8 It is critical for numerous immunological enzymes9, and supports normal growth and development during pregnancy, childhood, and adolescence10, 11, 12, 13 Zinc, like copper, is shown to possess antioxidant properties, which may protect against accelerated aging and helps speed up the healing process after an injury.

For more information on zinc, review the article titled Think Zinc for Immune Health published in the BRMI E-journal.

Copper Zinc Balance

Several laboratory and human studies have found that high levels of supplemental zinc (50 mg/day or more) taken over extended periods of time may result in decreased copper absorption in the intestine, and copper deficiency with associated hypochromic-microcytic anemia, leukopenia, and neutropenia, as well as other copper deficiency conditions.14, 15, 16, 17, 18

High dietary zinc intake increases 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. This mechanism is exploited therapeutically when using zinc to achieve a negative copper balance in Wilson’s disease. In contrast, high copper intakes have not been found to affect zinc’s nutritional status.19, 20

Supplemental Considerations

When taking zinc at dosages 50 mg or above, it is helpful to also take copper at 1 to 4 mg daily. Thus, typical daily doses of copper are up to 4 mg of elemental copper. Copper deficiency due to high or prolonged supplemental zinc will usually correct itself if zinc is reduced and copper is supplemented.

Copper is also found in a wide variety of foods and is most plentiful in organ meats, shellfish such as lobster and oysters, spirulina, shiitake mushrooms, nuts – particularly almonds, and leafy greens. 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.21

It is also wise to conduct serum copper and zinc levels and caeruloplasmin levels to determine copper-zinc balance and status. Unfortunately, these tests do not always reflect tissue and cellular levels of copper deficiency.


During the recent “Covid-19 years”, many people took zinc at high doses and continue to do so. This zinc regime could potentially cause a zinc-copper imbalance resulting in a copper deficiency. More than the concentration of Zn or Cu in blood serum, it is important to maintain a balance between them. If the balance is changed several organic systems can be affected.


1. Davis CD (2003) Low dietary copper increases fecal free radical production, fecal water alkaline phosphatase activity and cytotoxicity in healthy men. J Nutr 133: 522-527.

2. Adelstein SJ, Vallee BL (1961) Copper metabolism in man. New England Journal of Medicine 265: 892-897.

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

4. Sandstead HH (1994) Understanding zinc: recent observations and interpretations. J Lab Clin Med 124: 322-327.

5. McCarthy TJ, Zeelie JJ, Krause DJ (1992) The antimicrobial action of zinc ion/ antioxidant combinations. Clinical Pharmacology & Therapeutics 17: 5.

6. Solomons NW (1998) Mild human zinc deficiency produces an imbalance between cell-mediated and humoral immunity. Nutr Rev 56: 27-28.

7. Prasad AS (1995) Zinc: an overview. Nutrition 11: 93-99.

8. Heyneman CA (1996) Zinc deficiency and taste disorders. Ann Pharmacother 30: 186-187.

9. Prasad AS, Beck FW, Grabowski SM, Kaplan J, Mathog RH (1997) Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects. Proc Assoc Am Physicians 109: 68-77.

10. Simmer K, Thompson RP (1985) Zinc in the fetus and newborn. Acta Paediatr Scand Suppl 319: 158-163.

11. Fabris N, Mocchegiani E (1995) Zinc, human diseases and aging. Aging 7: 77-93.

12. Maret W, Sandstead HH (2006) Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 20: 3-18.

13.Institute of Medicine, Food and Nutrition Board (2004) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press.

14. Hoffman II, Harry N., Robert L. Phyliky, and C. Richard Fleming. "Zinc-induced copper deficiency." Gastroenterology 94, no. 2 (1988): 508-512.

15. Malavolta, Marco, Francesco Piacenza, Andrea Basso, Robertina Giacconi, Laura Costarelli, and Eugenio Mocchegiani. "Serum copper to zinc ratio: Relationship with aging and health status." Mechanisms of ageing and development 151 (2015): 93-100.

16. Malavolta, Marco, Robertina Giacconi, Francesco Piacenza, Lory Santarelli, Catia Cipriano, Laura Costarelli, Silvia Tesei et al. "Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population." Biogerontology 11 (2010): 309-319.

17. Prasad AS (2004) Zinc deficiency: its characterization and treatment. Met Ions Biol Syst 41: 103-137.

18. Maret, Wolfgang, and Harold H. Sandstead. "Zinc requirements and the risks and benefits of zinc supplementation." Journal of trace elements in medicine and biology 20, no. 1 (2006): 3-18.

19. 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.

20. 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)

21. 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.


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