Copper is Essential for Health

Introduction

Copper is a trace element, is required for our bodies to function, and is crucial for optimal health.  In fairly recent years, experts were worried that everyone was getting too much copper, and too much is toxic to our bodies. I'm convinced that many people have low levels of copper.

Copper plays a role in some diseases, including Alzheimer’s disease, Huntington disease, Menkes disease, Parkinson disease, prion disease, and Wilson’s disease. (R)

 

The Many Functions of Copper (not a complete list) (R, R, R)

  • Cellular respiration
  • Neurotransmitter biosynthesis
  • Pigment formation
  • Connective tissue strengths
  • Cofactor for many enzymes (tyrosinase, peptidylclyce alpha-amidating mono-oxydase, copper/zinc superoxide dismutase (SOD), ceruloplasmin, hephaestin, dopamine beta-hydroxylase, and cytochrome c oxidase)
  • Iron metabolism
  • Blood coagulation
  • Blood pressure
  • Cross-linking of connective tissues
  • Defense again oxidative stress
  • Energy, Aerobic respiration (cytochrome c oxidase)
  • Myelination of brain and spinal cord
  • Reproduction
  • Hormone synthesis
  • Strength of skin and blood vessels
  • Production of thyroxine (thyroid hormone)
  • Tyrosinase (contains copper and converts tyrosine to melanin)
  • Part of dopamine B-hydroxylase (converting dopamine to norephinephrine)
  • Superoxide dismutase
  • Component of lysyl oxidase (synthesis of collagen and elastin)
  • Promotes skin regeneration and improves wound healing

 

Copper Deficiency

Many people don’t consume enough copper, but copper deficiency is rare. (R)

Risk Factors for Copper Deficiency (R)

  • Inadequate dietary intake
  • Chronic diarrhea
  • Celiac disease
  • Inflammatory Bowel Disease (Crohn’s disease, ulcerative colitis)
  • Gastrointestinal surgery
  • Antacids
  • Liver disease, decreased bile excretion

 

Copper deficiency leads to a ton of issues, such as problems metabolizing cholesterol and glucose, bone disorders (osteoporosis), increased susceptibility to infection, blood pressure control, heart function, and many others. (R)

You can look at the list of functions that copper plays a role in above, and assume that all of those would be inhibited.

 

Ceruloplasmin

You can’t talk about copper without talking about ceruloplasmin. Ceruloplasmin is the main protein that carries copper in the body, and about 90-95% of the plasma copper is contained in ceruloplasmin. (R)

Ceruloplasmin oxidizes iron, which is necessary for iron to bind to transferrin.  This is why copper deficiency can lead to iron deficiency anemia. (R)

Ceruloplasmin is an antioxidant because it binds to free copper ions and prevents them from catalyzing oxidative damage. (R)

Ceruloplasmin deficiency causes more copper to roam freely, leading to excess free copper, as well as copper and iron accumulation in tissues. (R)

Ceruloplasmin is an acute phase plasma protein, meaning, concentrations of ceruloplasmin increase when inflammation increases. (R)

Pregnancy and estrogen supplementation also increase ceruloplasmin levels. (R)

Ceruloplasmin is mainly produced in the liver, and persons with active liver disease often have lower levels of it. (R)

Vitamin A (retinoic acid) increases ceruloplasmin levels in rats. If you have low ceruloplasmin levels, be sure you’re getting enough vitamin A (as well as all of the other vitamins and minerals).  If copper deficient though, vitamin A does not increase ceruloplasmin unless copper is also consumed. (R)

 

Superoxide Dismutase

Superoxide radicals are generated from natural metabolic processes and white blood cells destroying bacteria and viruses. Superoxides damage cell membranes, which is why they need to be converted to something that doesn’t harm our bodies, via superoxide dismutase. Insufficient copper decreases superoxide dismutase activity, which increases the amount of superoxides, and thus cell membrane damage. (R)

 

Zinc and Copper Balance

Copper and zinc compete for absorption in the small intestine. (R)

50 mg/day of supplemental zinc may cause copper deficiency, because it increases metallothionein levels. Metallothioein has a higher affinity for copper than zinc (it likes to bind to copper more than zinc), which reduces intestinal absorption. (R)

Estrogen and oral contraceptives increase copper absorption and its half-life, which decreases the absorption of zinc. (R)

Too much copper and low zinc are associated with hyperactivity, attention deficit disorders, behavior disorders, and depression. Increased levels of copper have been found in those with autism and paranoid schizophrenia. Persons with autism have also been found to have lower ceruloplasmin levels. (R)

Zinc and copper should be consumed in a ratio of roughly 10 mg zinc: 1 mg copper. (R)

 

 

Iron and Copper Balance

red blood cells.jpg

Ceruloplasmin is important for both iron and copper transport. Hephaestin is also important for copper transport. If copper levels are low and/or ceruloplasmin and hephaestin are low, then iron will not be transported adequately, leading to anemia. (R)

Simply put, adequate copper is needed for healthy iron metabolism and red blood cell formation. (R)

 

Vitamin C (Ascorbic Acid) and Copper Balance

1,500 mg/day of supplemental vitamin C (ascorbic acid) significantly reduces ceruloplasmin activity. (R)

Be mindful of vitamin C supplements.  Whole food vitamin C is likely better.

 

Alzheimer’s Disease

Some patients with Alzheimer’s disease have been found to have normal plasma copper levels, but higher levels of copper in cerebrospinal fluid, which may contribute to the disease itself through oxidative stress. (R)

Another study found that persons with Alzheimer’s disease have also been found to have decreased copper zinc superoxide dismutase activity, and this found significantly lower levels of plasma copper, as well as magnesium zinc, iron, and selenium. (R)

 

Huntington Disease

Persons with Huntington disease have elevated levels of copper in the brain, which causes oxidative stress and neurodegeneration.  (R)

 

Mutations in ATP7A and ATP7B

Small intestinal cells contain a transporter protein called copper membrane transporter 1 (CMT1), which carries dietary copper inside cells.  Inside the intestinal cells, some copper is bound to metallothioneins, and some is bound to copper transport protein ATOX1, which carries copper to the trans-Golgi network. When copper concentrations rise, the enzyme ATP7A releases copper into the portal vein, which travels to the liver.  In the liver, ATP7B helps bind copper to ceruloplasmin, releases it to the bloodstream, and secretes it into bile so excess copper can be excreted. (R)

Mutations in ATP7A leads to Menkes disease, while mutations in ATP7B leads to Wilson’s disease. (R)

 

Menkes Disease

helix.jpg

Menkes disease is a genetic disorder cause by a mutation in the ATP7A gene, leading to decreased copper transport across cell membranes, and causes low levels of both copper and ceruloplasmin. This causes dysfunctional copper transport and decreased copper-dependent enzyme activities, leading to brain damage and hyperactive tendon reflexes. (R)

Symptoms of Menkes Disease (R)

  • Weak muscle tone
  • Sagging face
  • Seizures
  • Mental retardation
  • Developmental delay
  • Kinky, colorless hair
  • Brain disorders
  • Osteoporosis
  • Early childhood death

 

Wilson’s Disease

Wilson’s disease is a genetic disorder cause by mutations in the ATP7B gene. Persons with Wilson’s disease have a decreased ability to excrete copper into the bile, as well as decreased incorporation of copper into ceruloplasmin. (R)

Increased levels of free copper lead to copper overload in the liver, eyes, brain, and other tissues. Kayser-Fleischer rings in the eyes are a sign of copper accumulation.

Serum ceruloplasmin <20 mg/dL could indicate Wilson’s disease. Levels <5 mg/dL are strongly suggestive, but low levels are also found in persons with copper deficiency. Further testing is needed if Wilson’s disease is suspected. A 24-hour urine test is usually the next step. 24-hour copper >100 μg is usually considered a diagnosis of Wilson’s disease. Patients with autoimmune hepatitis or chronic cholestasis may also have levels this high, so more testing could be needed. (R)

Treatment of Wilson’s disease includes reducing copper overload and restoring copper levels to normal using chelation therapy. Zinc supplementation can be used as well, but mostly for maintenance treatment. Zinc increases metallothioneins, which decreases copper absorption in the gut. (R)

75 - 150 mg/day of zinc divided in three doses is recommended, depending on age. It takes about 3 weeks for intestinal metalloproteins to increase to therapeutic levels. Fortunately, zinc supplementation has very few side effects.

Restricting high copper foods is not sufficient to treat Wilson’s disease alone. However, it should be a consideration. (R)

Other treatment options for Wilson’s disease include (R)

  • Checking well water and water delivery systems for copper content, and use a purification system if needed. It’s a good idea to filter water anyway.
  • Avoid using copper cooking utensils, pots, and pans.
  • Don’t eat high copper containing foods, including shellfish, nuts, chocolate, mushrooms, and organ meats like liver.
  • Consume more antioxidants, to help offset the oxidative stress associated with free copper.

Testing and Diagnosis for Wilson’s disease (typical findings) (R)

  • Serum ceruloplasmin: <50% of lower normal value
  • 24 h urinary copper: >100 mcg/24 h(adults)   >40 mcg/24h(children)
  • Serum free copper: > 200 mcg/L
  • Hepatic copper: >250 mcg/g dry weight
  • Kayser-Fleischer rings (slit-lamp examination): present

 

Histamine

Copper breaks down histamine, and high levels of copper can lead to low blood histamine. Which is interesting, considering we almost exclusively talk about high levels of histamine these days. Persons with low histamine tend to have racing minds and are hyperactive. (R)

If high copper leads to low histamine, then one would believe that low copper would lead to high histamine.

 

Coppers Role in Ehlers-Danlos Syndrome

Connective tissue formation:  Type IX Ehlers-Danlos syndrome is characterized by abnormal copper metabolism and reduced lysyl oxidase activity.  Lysyl oxidase is a copper dependent enzyme that initiates the crosslinking of collagens and elastin, which is crucial for healthy connective tissue. Persons Ehlers-Danlos syndrome have joint hypermobility and stretchy skin, among other signs and symptoms. (R)

 

Dietary Sources of Copper

55-75% of dietary copper is absorbed, mostly in the upper part of the small intestine. (R)

Recommended Dietary Allowance (RDA) for Copper (R)

Adult men and women: 900 mcg

 

Food Sources of Copper (R)

  • Beef liver, 2.4 oz:  9.7 mg
  • Oysters, 3 oz: 3.7 - 4.8 mg
  • Cocoa powder, 1 Tablespoon: 0.2 mg
  • Soybeans, ¼ cup:  0.77 mg
  • Cashews, ¼ cup:  0.76 mg
  • Mixed nuts, ¼ cup:   0.65 mg
  • Red lentils. ¼ cup dry:  0.63 mg
  • Sunflower seeds, ¼ cup:  0.61 mg
  • Adzuki beans, ¼ cup dry:  0.54 mg
  • Kidney beans, ¼ cup dry:  0.51 mg
  • White beans, ¼ cup dry:  0.50 mg
  • Buckwheat, ¼ cup dry:  0.47 mg
  • Pinto beans, ¼ cup dry:  0.43 mg
  • Black beans, ¼ cup dry:  0.41 mg
  • Green peas, ¼ cup dry:
  • Almonds, ¼ cup:  0.37 mg
  • Chickpeas (garbanzo beans), ¼ cup dry:  0.33 mg
  • Quinoa, ¼ cup dry: 0.25 mg
  • Oats, ¼ cup dry: 0.24 mg
  • Avocado, ¼ cup: 0.18 mg
  • Beef, 3 oz:  0.1-0.2 mg

 

If you can’t get enough copper in your diet due to food restrictions, copper supplementation may be beneficial. You have to be careful though, as too much copper is toxic. It’s a really good idea to get your copper and ceruloplasmin levels tested before supplementing with copper.

 

Copper Toxicity

Copper toxicity has been more concerning than copper deficiency, because water pipes were switched to copper pipes. This increased the amount of copper that drinking water normally contained. (R)

Free copper is very reactive and causes oxidative stress, something we don’t want. Too much free copper is toxic, but this rarely occurs. If too much copper is consumed, the body will not be able to manage the amount of free copper, but again, one would have to consume a lot. The upper tolerable intake level for copper is 10 mg/day.  Most copper supplements are 2 mg.

One study found that individuals who consumed 10 mg of copper gluconate for 12 weeks did not show evidence of liver damage or gastrointestinal distress. (R) Three months isn’t very long, but you shouldn’t be supplementing for very long anyway.

 

Symptoms of Copper Toxicity (R)

  • Nausea
  • Vomiting
  • Abdominal pain
  • Headache
  • Dizziness
  • Weakness
  • Diarrhea
  • Metallic taste