Copper 101

Overview:

Copper is an essential trace element that is vital to human life. Unfortunately, it is one of the human body’s most misunderstood yet crucial minerals.

Due to developments over the last century (you can read more here), copper has, for many people, become either insufficient in their diet and/or sabotaged by excessive iron and other chemicals introduced to use.

We cannot emphasize enough how copper is essential to the proper function of our cells, especially our energy creation and cleaning of the byproduct, or the exhaust, of our cellular respiration – reactive oxygen species (ROS). When left unchecked by copper, excessive ROS leads to inflammation and metabolic dysfunction. Metabolic dysfunction is the underlying cause of the majority of illnesses we face.

Our body has complex homeostatic mechanisms designed to maintain a balance of copper in our bodies. And while copper can be toxic in certain forms and at certain levels in the body, the fear of it has been greatly exaggerated, and we will address the potential risks below.

Key Benefits of Copper:

  • Essential for a healthy metabolism
  • Essential for managing and mitigating ROS
  • Essential for a healthy immune system
  • Essential for healthy bones
  • Essential for proper growth and development
  • Essential for balancing thyroid activity
  • Essential for healthy hair, skin, eyes
  • Essential for wound healing
  • Stabilizes glucose and cholesterol metabolism.
  • Low levels of copper increase cholesterol in the serum.
  • Low levels decrease glucose tolerance.
  • Low levels increase LDL and triglycerides and decrease HDL.(1)
  • Mitigates DNA damage
  • Mitigates diabetes
  • Mitigates heart and heart vessel damage & dysfunction.
  • Necessary for cell proliferation, differentiation, and cell death.(2)
  • Essential for the normal growth and development of human fetuses, infants, and children.
  • Essential for emotional regulation.
  • Essential to maintaining the brain’s biochemistry.(3)
  • Essential for many enzymatic reactions and neurotransmitter biosynthesis.
  • Normalizes blood pressure
  • Mitigates fatty liver disease
  • Preventing the accrual of iron in tissues and organs.
  • Essential to iron homeostasis.
  • Ceruloplasmin (copper-dependent enzyme) is essential to the normal movement of iron throughout the body.(4)(5)
  • Necessary for hemoglobin synthesis – i.e., making red blood cells.(6)
  • Is involved in the development and maintenance of cardiovascular and skeletal integrity, central nervous system structure and function, and erythropoietic function, including iron metabolism.(7)

Key Risks of Copper:

  • In the wrong form and in excessive amounts, it becomes toxic to the body. However, this toxicity rarely happens by accident. We will elaborate towards the end of the article.
  • Chronic dietary copper toxicity is not typically viewed as a significant human public health concern. The most common risk is due to a mutation or defect in a person’s genes that affect copper pumps. Copper is made bioavailable through its insertion into key enzymes and proteins. The ones that are most important to copper are the copper pumps. ATP7A (Menkes disease) & ATP7B (Wilson disease). Thus, copper is only dangerous in normal use and consumption to a person when a genetic mutation affects a copper pump and its ability to be properly transported, leading to copper build-up and dysregulation.(8)(9)

What you need to know about Copper – Cu:

Humanity has used copper for at least the last 6000 years for health, sterilization, disinfection, and wound treatment. You can read more about the history of copper here below.

Medical Uses of Copper in Antiquity
https://www.copper.org/publications/newsletters/innovations/2000/06/medicine-chest.html

Using Copper to Improve the Well-Being of the Skin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556990/

Interestingly, copper generally does not exist in the body in measurable amounts in ionic form. Instead, all quantifiable amounts of copper in the body exist in tissues as complexes with the organic compounds of proteins and enzymes. One of the most important is Ceruloplasim. We will dive more into this enzyme later. (But let’s just say it is one of the body’s most important and underappreciated enzymes.) Some copper complexes store copper, others transport it, and others play essential roles in cellular, structural, and metabolic processes.

A lot of misunderstanding has arisen around the fact that copper in the form of ceruloplasmin is found elevated in the serum responding to physiological, disease, or injury stress.  Copper is used widely in different chemical forms as treatment for chronic and acute inflammation. Thus the rise in total serum copper measured in situations with increased inflammation are because copper is part of the body’s natural anti-inflammatory response.(10)

Research has found that copper complexes such as copper aspirinate and copper tryptophanate markedly increase the healing rate of ulcers and wounds. It is not that copper levels rise, leading to physiological, disease, or injury stress. Instead, these events trigger the body’s response of increasing the amount of copper via ceruloplasmin to protect and heal the body.

Copper is intimately involved in the immune system to fight infections, repair injured tissues, and promote healing. Copper also helps to neutralize “free radicals,” which can cause severe damage to cells.
Copper is involved in all four stages of wound healing. Thus depleted copper levels likely result in delayed wound healing.(11)

Interestingly, there is a theory that cancer occurs when a cell is damaged and, in response, reverts to an ancestral operation of a single cell organism. We will dive more into this in future blog posts, but as early as 1912, scientists discovered that copper complexes did not kill cancer cells but caused them to revert to normal cells. Once again, pointing to the theory that copper is part of the body’s routine healing, homeostatic, and repair systems.

As early as 1984, further evidence showed that copper metallo-organic complexes provided radiation protection and radiation recovery activities.

So now, you can see that severe deregulation occurs when copper is deficient in the body. As a result, iron gets trapped in tissues and organs, and oxidative damage runs rampant. Thus, copper protects the body from oxidative stress, infection, and most non-genetic diseases.

Not only is it protective, but copper is essential for the healthy growth and development of human fetuses, infants, and children. The human fetus accumulates copper rapidly in its liver during the third trimester of pregnancy. Further, another download of copper occurs right after birth through the umbilical cord. As a result, a healthy infant has four times the concentration of copper at birth than a full-grown adult. However, this cannot happen if the mother does not have adequate copper in her body.(12)

Copper’s Antimicrobial & Protective Aspects :

Despite the demonstrated benefits, interest in copper diminished in modern times due to the limited understanding of the mechanisms of antimicrobial action and the basis of the promotion of wound healing. Also, it was likely superseded by the discovery of antibiotics and the business associated with them.

Nonetheless, copper is the only hard surface material that has been approved by the U.S. Environmental Protection Agency (EPA). Registered public health claims are as follows: antimicrobial copper alloys continuously reduce bacterial contamination, antimicrobial copper is able to kill >99.9% of bacteria within two hours of contact, antimicrobial copper remains effective in killing >99.9% of bacteria after repeated recolonization, and antimicrobial copper inhibits bacterial growth between routine cleaning activities. The EPA registered almost 300 different copper surfaces as antimicrobial in 2008.(13)

The mechanism by which copper kills microorganisms is multifaceted and not yet fully understood. Literature suggests that copper interacts with microorganisms on different cellular levels, resulting in cell death, including cell membrane permeabilization, membrane lipid peroxidation, protein alteration, and denaturation of nucleic acids.

To further validate the benefits of copper on surfaces and its efficacy, it is believed that bacteria are incapable of developing resistance to copper because: (i) plasmid DNA is completely degraded after cell death by contact killing, preventing the transfer of resistance determinants between organisms, (ii) contact killing is very rapid, and cells are not dividing on copper surfaces, precluding the acquisition of resistance, and (iii) copper and copper alloys have been used by humans for thousands of years, yet no bacteria fully resistant to contact killing have been discovered.(14)(15)(16)

How we absorb and regulate copper in the body:

While we know that we absorb most of our copper in the stomach and small intestine, the site of maximal copper absorption is not known for humans, the amount of copper absorbed ranges from 15 to 97%, depending on copper content, the form of the copper, and composition of the diet.

Various factors influence copper absorption. For example, copper absorption is enhanced by ingesting animal protein, citrate, and phosphate. In addition, copper salts, including copper gluconate, copper acetate, or copper sulfate, are more easily absorbed than copper oxides. Conversely, elevated levels of dietary zinc, cadmium, high intakes of phytate, and simple sugars (fructose, sucrose) inhibit the dietary absorption of copper.

After the digestion of foods in the stomach and duodenum, copper is absorbed by cells of the intestinal mucosa, the enterocytes, which are also responsible for releasing copper into the blood plasma. When in excess, the ingested copper will be directly excreted through the feces, but when in lack, cellular mechanisms will be activated to allow greater intestinal uptake.(17)

Copper concentration is tissue-dependent. The body of a 70-kg healthy individual has about 110 mg of copper, 50% of which is found in the bones and muscles, 15% in the skin, 15% in the bone marrow, 10% in the liver and 8% in the brain. Thus, the use of copper is different for each cell, and the effects produced by the imbalances of this metal will be tissue-specific.(18)

Once absorbed, it is taken to the liver. Once in the liver, copper is incorporated into copper-requiring proteins, which are secreted into the blood. Most of the copper (70 – 95%) excreted by the liver is incorporated into ceruloplasmin, the main copper carrier in the blood. The proportion of ceruloplasmin-bound copper can range from 70 to 95% and differs between individuals, depending, for example, on hormonal cycle, season, and copper status. Copper is transported to tissues outside the liver by ceruloplasmin, albumin, and amino acids or excreted into the bile. By regulating copper release, the liver exerts homeostatic control over extrahepatic copper.

Copper Homeostasis:

Copper is absorbed, transported, distributed, stored, and excreted in the body according to complex homeostatic processes, which ensure a constant and sufficient supply of the micronutrient while simultaneously avoiding excess levels. If an insufficient amount of copper is ingested for a short period of time, copper stores in the liver will be depleted. Should this depletion continue, a copper health deficiency condition may develop. If too much copper is ingested, an excess condition can result. Both of these conditions, deficiency, and excess, can lead to tissue injury and disease. However, due to homeostatic regulation, the human body is capable of balancing a wide range of copper intakes for the needs of healthy individuals.

Copper is mainly excreted in the feces. Small amounts can also be eliminated in hair and nails. Bile is the major pathway for the excretion of copper and is vitally important in the control of liver copper levels. Most fecal copper results from biliary excretion; the remainder is derived from unabsorbed copper and copper from desquamated mucosal cells.(19)(20)

Topical Application of Copper:

The exogenous application of copper is considered safe to humans.  Its safety in humans has been demonstrated in various clinical trials. Contrary to microbes, human skin cells can metabolize and utilize copper; consequently, the risk of adverse reactions is negligible. Human cells operate and respond very differently than microorganisms. Microorganisma are exceedingly sensitive to excess concentrations of copper, as they cannot control their extracellular environment to allow for excretion.(21)

Application of ointment preparations, containing up to 20% metallic copper, were found not to cause any adverse reactions or toxicity.(22)

The safety of using copper oxide containing products has been examined in several non-clinical studies and in more than 10 clinical trials. In all the studies, not even one adverse reaction was recorded. The products were found to be non-irritating, non-sensitizing, and safe to use, both when in contact with intact and broken skin. Considering the benefits, minimal downside, “the introduction of copper oxide into ordinary products transforms them into extraordinary products.”(23)

Copper Toxicity & Risks:

There has been a lot of confusion around the risks and toxicity of copper.

Acute fatal poisoning with copper is very rare. Copper as a metal is not poisonous if swallowed. Copper coins are not known to have produced poisoning. However, all copper salts are poisonous. Copper sulphate has been taken in large doses for purposes of suicide (20-70 grams of copper). Copper sulphate has sometimes been swallowed by children attracted by its color.

Acute copper poisoning can result in a progression of symptoms including abdominal pain, headache, nausea, dizziness, vomiting and diarrhea, tachycardia, respiratory difficulty, hemolytic anemia, hematuria, massive gastrointestinal bleeding, and liver and kidney failure, and death.

The long-term toxicity of copper has not been well studied in humans, but it is infrequent in normal populations that do not have a hereditary defect in copper homeostasis.

Chronic cases through time have resulted among the workers who handle copper or its salts. It may result from the continued use of copper vessels for preparing and preserving food, keeping water the whole night, and consuming it tomorrow. In addition, copper worn or touching the body for prolonged periods may result in some copper absorption through the skin.

It is unclear through studies how much and how long the exposure is required for toxicity. But it has also been found that copper exposure in small amounts has mitigated diseases such as arthritis and improved skin tone and condition.

Chronic copper toxicity through excess consumption has been studied in animal models. These studies examine the consequences of chronic sublethal copper “loading.” Most notably, a study on cebus capucinus monkeys who were fed a high copper diet that increased from an initial 5 mg/kg/day of copper (as copper gluconate) to 7.5 mg/kg/day over two months showed no signs of toxicity. They did show elevated levels of ceruloplasmin. These studies suggest broad copper tolerance and capacity to prevent toxicity in mammals via both adaptive and homeostatic responses.

The key seems to be the type and dosage. Keep in mind that the current RDA is .9mg and is likely being moved to 2.7mg. And it appears that it requires a much higher multiple to become toxic in the short run.

The main concern for the general public regarding copper risk is Wilson Disease. It is the most well-documented disorder of copper toxicity and is an autosomal recessive disorder of copper metabolism with an estimated global frequency of ~1 in 30,000. This rare disease is caused by a mutation in the ATP7B gene that is characterized by excessive copper accumulation, primarily in the liver but also in other tissues, including the brain. Before consuming exogenous copper, you should ensure you do not have this mutation.(24)(25)(26)(27)

References:

  1. Copper chelation and interleukin-6 proinflammatory cytokine effects on expression of different proteins involved in iron metabolism in HepG2 cell line https://pubmed.ncbi.nlm.nih.gov/28118841/
  2. Role of Copper on Mitochondrial Function and Metabolism https://pubmed.ncbi.nlm.nih.gov/34504870/
  3. Copper and iron disorders of the brain https://pubmed.ncbi.nlm.nih.gov/17367269/
  4. Studies on copper metabolism. XIV. Copper, ceruloplasmin, and oxidase activity in sera of normal human subjects, pregnant women, and patients with infection, hepatolenticular degeneration and the nephrotic syndrome https://pubmed.ncbi.nlm.nih.gov/13263429/
  5. The role of ceruloplasmin in iron metabolism https://pubmed.ncbi.nlm.nih.gov/5480864/
  6. Possible correlation between the zinc and copper concentrations involved in the pathogenesis of various forms of anemia https://pubmed.ncbi.nlm.nih.gov/2284564/ 
  7. Biochemistry of copper https://pubmed.ncbi.nlm.nih.gov/5635/
  8. Copper, oxidative stress, and human health https://pubmed.ncbi.nlm.nih.gov/16112185/
  9. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752173/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945467/
  11. https://journals.asm.org/doi/10.1128/CMR.00125-18
  12. Essentiality of copper in humans https://pubmed.ncbi.nlm.nih.gov/9587135/
  13. http://www.epa.gov/pesticides/factsheets/copper-alloy-products.htm
  14. Metallic copper as an Antimicrobial Surface https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067274/
  15. Antimicrobial properties of copper https://en.wikipedia.org/wiki/Antimicrobial_properties_of_copper
  16. https://journals.asm.org/doi/10.1128/CMR.00125-18
  17. Turnlund et al., 1998; Larin et al., 1999
  18. Copper transport https://pubmed.ncbi.nlm.nih.gov/9587137/
  19. Role of Copper on Mitochondrial Function and Metabolism https://pubmed.ncbi.nlm.nih.gov/34504870/
  20. https://en.wikipedia.org/wiki/Copper_in_biology
  21. https://journals.asm.org/doi/10.1128/CMR.00125-18
  22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556990/
  23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556990/
  24. Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease https://pubmed.ncbi.nlm.nih.gov/33804693/
  25. https://en.wikipedia.org/wiki/Copper_in_biology
  26. Copper Toxicity: A Comprehensive Study https://www.researchgate.net/publication/272476283_Copper_Toxicity_A_Comprehensive_Study
  27. Copper sulphate poisoning, which is mostly suicidal https://www.researchgate.net/publication/27791043_Acute_ingestion_of_copper_sulphate_A_review_on_its_clinical_manifestations_and_management/link/0c96051a5578763ce7000000/download

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