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Copper and zinc are antagonistic nutrients that must remain in balance with each other. These nutrients can be measured via blood samples, and their balance can be assessed using the copper-to-zinc ratio. The copper-to-zinc ratio can be influenced by high and low levels of either nutrient, and some research indicates that the ratio is more important than the individual nutrient levels.
Imbalances in this ratio are implicated in several health conditions and inflammation in general. In fact, the copper-to-zinc ratio has been researched for its use as an inflammation marker in those with sickle cell disease, inflammatory bowel disease, and COVID-19. One study found an association between the copper-to-zinc ratio, oxidative stress, and ectopic pregnancy, and the ratio was determined to be helpful in diagnosing ectopic pregnancies, even more so than individual copper and zinc values.
However, whether inflammation results from or causes an imbalance in the copper-to-zinc ratio is debatable. While excess copper may promote oxidative stress, alterations in micronutrient metabolism in favor of copper have been seen during acute infection. Nonetheless, the importance of the copper-to-zinc ratio has been shown in several conditions.
Notably, the optimal blood copper-to-zinc ratio does not directly translate to dietary requirements as the body requires much more zinc compared to copper, and altering the dietary ratio does not necessarily alter the blood ratio. This is where some confusion exists as it must be specified whether the ratio is referencing blood levels or supplements. The optimal serum or plasma copper-to-zinc ratio is believed to be between 0.7-1.0, but it has been recommended to consume 8-15 mg zinc for every 1 mg copper if using supplements. When considering the health effects of the copper-to-zinc ratio in research, it is the blood ratio being referenced.
The Importance of the Copper-to-Zinc Ratio
Cancer. Disruptions in copper homeostasis may play a role in cancer development in several ways, including its ability to promote tumor growth and stimulate angiogenesis. Proliferating cancer cells have an increased demand for copper, and controlling or depleting copper may be helpful in treatment of different types of cancer. On the other hand, zinc deficiency plays a role in oxidative DNA damage and may impair repair responses. According to a population-based cohort study involving nearly 2,000 patients with breast cancer, the serum copper-to-zinc ratio may be predictive of overall survival after diagnosis. Specifically, results indicate that a higher copper-to-zinc ratio is associated with poor survival, yet no association was seen for either trace mineral alone. Additionally, a systemic review and meta-analysis involving more than 3,500 lung cancer patients found that these patients had a significantly higher copper-to-zinc ratio than the 3,314 healthy controls.
Conversely, a 2024 study involving women with endometrial cancer found that lower serum copper and zinc levels may be associated with an increased risk of cancer occurrence. In contrast, there may be a lower cancer occurrence in those with a specific copper-to-zinc ratio of 1.20-1.46, which is higher than the proposed optimal ratio of 0.7-1.0. A different study on endometrial cancer and trace minerals found a higher copper-to-zinc ratio in patients with endometrial cancer compared to those without, but the difference was not significant. However, the authors did report that menopausal status and body mass index (BMI) influenced copper concentration, adding to the complexity of the relationship between zinc, copper, and endometrial cancer.
Immune Health. Zinc and copper play essential roles in immune health, and zinc deficiency alone is associated with infectious diseases like malaria, HIV, and respiratory infections. Historically, copper was valued for its antimicrobial effects as early as 2600 BC when the Egyptians used it to sanitize water and treat wounds.
Part of the normal immune response depletes plasma zinc, reducing its availability to pathogens. Instead, zinc accumulates in the liver while remaining low in serum. On the other hand, copper accumulates at infection sites as well as in the blood and peripheral tissues during systemic infection, which is the result of acute phase ceruloplasmin overexpression. Within macrophages, or white blood cells, copper acts as a bactericidal agent to kill pathogens. Copper is also being researched for its antiviral and antifungal effects.
The copper-to-zinc ratio may be a biomarker for early-onset infections, as shown in a study linking a higher copper-to-zinc ratio in children and adolescents with increased risk of respiratory tract infection. In newborns, the copper-to-zinc ratio increased during acute infection and is a possible biomarker for identifying early-onset infections. A high copper-to-zinc ratio was reported in children with malaria and male adults with pneumonia.
Neurological and Mental Health. The copper-to-zinc ratio is implicated in conditions such as Alzheimer’s disease, attention-deficit/hyperactivity disorder (ADHD), autism, epilepsy, depression, and bipolar disorder. Iron, zinc, copper, and manganese are “neurometals,” as they exist in the brain and play important roles in brain structure and function. Zinc and copper are the second and third most abundant neurometals, respectively.
One study involving children with ADHD observed decreased levels of magnesium and zinc and an elevated copper-to-zinc ratio. Another study found a higher copper-to-zinc ratio in hair and urine samples in children diagnosed with ADHD compared to controls. Autism spectrum disorder (ASD) is also being researched for its connection to zinc and copper, and a recent cross-sectional study found a significant association between ASD and zinc deficiency as well as copper toxicity in children between the ages of 2-9 years. Authors speculate that copper toxicity plays a role in ASD in several ways, including by dysregulating dopamine, serotonin, and epinephrine; reducing the conversion of glutamate to GABA, two neurotransmitters possibly implicated in ASD; and by causing neuronal excitation, and even impulsive behaviors, by inhibiting GABA-mediated responses.
Though more research is needed, the copper-to-zinc ratio is also being researched for its validity as a biomarker for epilepsy, as seen in a study involving 100 children with epilepsy who were either responsive or unresponsive to medication. The study found that low zinc and high copper levels were particularly associated with epileptic children who were considered pharmacoresistant.
Another recent study investigated the copper-to-zinc ratio in patients diagnosed with bipolar disorder. Results showed that those with bipolar disorder exhibited higher copper levels and lower zinc levels compared to healthy controls.
Metabolic Health. Copper has a complex relationship with lipids. Copper deficiency is associated with increased serum cholesterol, triglycerides, and diseases like obesity, non-alcoholic fatty liver disease, and cardiovascular disease, whereas copper overload can reduce serum cholesterol levels. One study concluded that higher copper levels may be protective against non-alcoholic fatty liver disease in men, but high serum copper is also associated with obesity.
On the other hand, zinc plays an important role in metabolism, and deficiency is associated with conditions like insulin resistance, dyslipidemia, obesity, and diabetes. As seen in other health conditions, the copper-to-zinc ratio is essential to consider. A recent study using NHANES data of children (ages 8-18 years) found that a high serum copper-to-zinc ratio was associated with a high likelihood of being overweight or obese, or having central obesity.
A higher copper-to-zinc ratio is also associated with an increased risk of type 2 diabetes. One study found that a higher copper-to-zinc ratio was associated with a higher risk of type 2 diabetes in women with a low dietary zinc intake. This study also found that a low copper-to-zinc ratio, especially in obese women and women consuming more than the RDA for zinc (8 mg per day), was associated with a lower risk of type 2 diabetes. In individuals who already have type 2 diabetes, an elevated copper-to-zinc ratio can worsen inflammation and is associated with a high occurrence of diabetic kidney disease.
What to Know About Supplementation
Zinc is a popular supplement as it has a reputation for supporting the immune system and acting as an antioxidant. A 2023 press release estimates that the supplemental zinc market is worth $10.8 billion. The promises of zinc supplements have led many people to supplement, sometimes with high doses. Additionally, those taking several supplements are sometimes unaware that more than one product contains zinc, increasing zinc intake to potentially harmful levels. Zinc is also found in many cough drops and other cold remedies, making it easy to consume large doses.
Because of the potential toxicity of copper, many people stay away from supplemental doses of it. Unfortunately, this situation could contribute to a problematic copper-to-zinc ratio when zinc supplements are consumed at high levels on a regular basis. One case study from 2019 describes long-lasting neurological deficits from an older woman supplementing with zinc, inducing a copper deficiency. In this case, the patient supplemented with 50 mg zinc for 11 months before developing an unsteady gait. On the other hand, copper supplements can lead to unsafe levels in the body, and when taken with vitamin C, systemic oxidative stress via the Fenton reaction can occur.
The harmful effects of zinc and copper supplementation underline the importance of safe supplementation. Those who wish to use zinc or copper supplements should consider the following guidelines under the supervision of their healthcare practitioner.
Test before supplementing with single minerals. It’s best to avoid supplementing with only zinc or copper without knowing serum levels and/or the copper-to-zinc ratio. Zinc and copper status are often determined via blood draw. While zinc and copper levels can also be assessed via hair, it’s suggested that plasma copper is more sensitive to pathologic changes, and plasma zinc is responsive to both supplementation and depletion. Several factors including gender, age, and pregnancy can affect serum copper and zinc results. In hair samples, hair growth rate and use of hair color and toner can affect results. To calculate the copper-to-zinc ratio, simply divide the copper level by the zinc level after ensuring both numbers are in the same units, which is generally µg/dL. An online conversion tool can be helpful in this instance. It’s proposed that an ideal copper-to-zinc ratio ranges from 0.7-1.0.
In those with high copper levels, zinc supplements can reduce the absorption of copper and increase its excretion from the body. However, in severe cases of copper toxicity, chelation therapy may be necessary. It’s important to always work with a healthcare practitioner to address imbalances in zinc and copper, especially to rule out the possibility of an underlying factor, such as infection, influencing a high copper-to-zinc ratio.
Consider all sources of minerals. It is important to consider all sources of zinc and copper beyond food and supplements when assessing risk of an imbalance. For example, a patient using excessive amounts of denture adhesive that contained zinc presented with severe copper deficiency symptoms. Additionally, copper might leach from copper cookware or copper piping, especially if the water is stagnant or the pipes are corroding. Those with privately owned wells should test their water for contaminants, including copper. The Environmental Protection Agency sets standards for safe drinking water, and test kits are available for those who wish to test their home tap water, especially if the home uses copper piping.
Know the risks. High levels of either mineral come with risks. Taking excessive amounts of zinc in supplemental form can lead to side effects, including nausea, vomiting, headaches, and loss of appetite. Using nasal sprays with zinc might also disrupt the sense of smell. Excessive copper can cause digestive issues, including nausea, vomiting, abdominal cramps, and diarrhea. The tolerable upper intake level (TUL) for zinc is 40 mg per day for adults, and the TUL for copper is 10,000 mcg per day for adults. It’s important to check the TUL for other age groups.
Final Remarks
The copper and zinc relationship is just one example of the delicate balance that nutrients have with one another. Recognizing how nutrients interact can help formulate a better plan to maintain optimal health through diet and supplements. As always, consult with a doctor or other healthcare professional who can guide zinc and/or copper supplementation that ensures adequate amounts of both to retain the ideal ratio.
