Cleo Libonati, RN, BSN

Understanding Copper Deficiency in Celiac Disease

by Cleo Libonati, RN, BSN on July 28th, 2010


 

Copper usually receives little coverage, but this unpretentious nutrient deserves center stage.  It is time for a serious role review.

Here are two reasons: First, deficiency of this trace mineral can debilitate and threaten our lives, and second, deficiency develops with increased frequency in those of us with celiac disease, unlike the general population.

Copper plays a critical role in the formation of a variety of proteins and enzymes involved in functions that keep us alive. Consequently, many disorders caused by copper deficiency stem from failure to adequately produce or release copper proteins and enzymes.

Copper is required for hemoglobin production in red blood cells, production and function of white blood cells, the absorption, transport and use of iron, energy metabolism, the development, growth and maintenance of bone and connective tissue, the formation and maintenance of myelin sheath (outer surface of nerve fibers), adrenal hormone production, thyroid hormone production, muscle tone, immunity, reproduction, tissue repair, pigmentation of hair and skin, and proper growth and development of infants and children.

Copper is so essential for the proper growth and development of infants and children that before birth, babies pull large amounts from their mother’s bloodstream to store it in their liver.  This is nature’s way of absolutely providing for the rapid growth of tissues, particularly blood cells, connective tissue, brain and nervous tissue that occurs after birth and before the baby can obtain copper from food.

Copper is absorbed into our bloodstream from the upper small intestine. It is able to enter the lining unassisted, however, to get through the intestinal wall into the bloodstream, it must attach to a binding protein. In celiac disease, inflammation of the lining hampers copper’s ability to pass into the lining and inadequate availability of proteins limits its ability to transport from the lining into the bloodstream.

Copper deficiency is characterized by fatigue, anemia, neutropenia (low level of neutrophils, the most common type of white blood cell that protect against infection), leukopenia (abnormal decrease of leukocytes or white blood cells), bone and joint abnormalities, skin abnormalities, impairment of nerve and muscle function, impairment of adrenal and thyroid gland function, reproductive difficulties and loss of hair and skin color. In children, neutropenia and leukopenia are the best early indications of copper deficiency. Changes that are due to defective connective tissue formation include bleeding into the covering of bones, bleeding from aneurysms and bleeding from hemorrhoids. Death may result from brain degeneration, failure to make blood cells and hemorhage.

Here are details:

1.   Role of copper in metabolism of iron and formation of hemoglobin.

Iron metabolism. Copper is required for the proper use of iron. As a normal part of blood, 90% of copper in our body is attached to a protein called ceruloplasmin. Ceruloplasmin speeds the oxidation of iron. This chemical conversion of iron is required for its binding to proteins that are involved in hemoglobin production and the transport and absorption of iron. Iron is the essential part of the hemoglobin molecule in red blood cells that carries oxygen through the bloodstream.

Hemoglobin formation. Copper is required in the production of hemoglobin, the vital component of red blood cells that picks up oxygen from the lungs and expressly carries it to cells of the body that require it. Consider that each red blood cell contains 200 million molecules of hemoglobin. Each molecule of hemoglobin is made up of an iron-containing part called hematin and a protein part called globin, hence the name hemoglobin. There are about 35 trillion red blood cells in an average person’s bloodstream. Think about how much hemoglobin that is!

When we consider that a red blood cell dies after 120 days, meaning our red bone marrow must produce 2,400,000 cells per second to maintain normal blood levels, we can better appreciate the impact of copper deficiency in hemoglobin production.2

How does copper deficiency impact iron metabolism and hemoglobin production?

Development of anemia. Copper deficiency causes an anemia that appears identical to anemia caused by iron deficiency. Copper deficiency anemia develops from poor iron utilization stemming from inadequate ceruloplasmin production. That is, inferior blood cells are small and lack adequate hemoglobin. The telltale difference is that blood levels of ferritin, an iron-containing protein, are normal in copper deficiency while they are low in iron deficiency.

Symptoms of copper deficiency anemia. Symptoms include irritability, fatigue, weakness, low energy, loss of appetite, dizziness, faintness, diminished mental alertness and function, and shortness of breath. Anemia, due to copper deficiency, can only be corrected with copper supplementation.

2.   Role of copper in energy metabolism and production.

Copper has a key role in energy metabolism due to the redox ability of copper ions (charged molecules), meaning copper ions rapidly give and take oxygen in chemical reactions.

Within minute powerhouse structures of cells called mitochondria, the copper dependent enzyme, cytochrome c oxidase, provides for the creation of high energy molecules called ATP (adenosine triphosphate) by the mitochondria. ATP is the main source of energy for cell use.

How does copper deficiency impact energy levels?

Low energy and easy fatigue result from inability to deliver adequate oxygen and energy to cells, thereby lessening their normal activities.

3.   Role of copper in connective tissue.

Connective tissue connects and supports a variety of other tissues. Connective tissue is made up of collagen and elastin proteins. These proteins require copper for synthesis. In addition, copper is a cofactor for the activity of a vital enzyme called lysyl oxidase. This enzyme begins the formation of cross-linkages, which stabilize and provide strength to collagen and elastin.

Elastin is a rubber-like protein that gives strength and flexibility to such organs and tissues as blood vessels, spinal discs, skin, lungs and bronchial tubes, heart, gallbladder, and the digestive tract.

Collagen is a strong, fibrous protein that makes up most of connective tissue. It is a main component of dermis (lower layer of skin) along with soft keratin, tendons, ligaments, deep fascia, bone, cartilage, and teeth (except enamel) forming the matrix of dentin, cementum, and alveolar bone. Collagen fibers also form the periodontal ligament, which attaches the teeth to their bony sockets. It fills out the cornea and lens of the eye.

 

How does copper deficiency impact connective tissue?

 When copper is low, the body diverts copper from activity in connective tissue to more important uses, thereby weakening connective tissue and causing malfunction. Disorders that may develop in organs and tissues composed of connective tissue include:

  • Slipped or herniated spinal discs. Spinal discs are located between vertebra and act like pads to separate and cushion these bones. Discs soften and may shrink due to lack of elastin. The vertebrae then cannot sit properly, causing the spine to get out of alignment, called subluxation. In turn, pressure against nerve roots produce problems in the part of the body served by the affected pinched nerve.
  • Faulty scar development and wound healing. Wounds and scar tissue development require copper for this collagen activity.             
                                            
  • Weakened blood vessels.

1.    Aneurysms. Lack of copper reduces the strength of elastin, a main component of artery walls. Weakening of arterial walls leads to the development of aneurysms or bulging of arteries much like a bubble on a bicycle tire. Rupture of an aneurysm results in hemorrhage that may be fatal, depending on location. For example, a ruptured aortic aneurysm is always fatal because the aorta receives all the blood with each beat of our heart that must go to the body. A ruptured aneurysm in the brain is called a hemorrhagic stroke and is often fatal.

2.   Hemorrhoids. Veins in the anal area weaken and swell from lack of elastin. They may bleed profusely.

3.   Varicose veins. These dilated superficial veins may develop from faulty elastin, thus leading to poor circulation and swelling of the lower legs.

  • Difficulty breathing. Diminished air flow may result from faulty elastin in the walls of bronchial tubes. The main bronchi and smaller bronchioles serve as passageways for air moving in and out of the lungs. In addition, lung tissue may be affected. Emphysema, an abnormal enlargement of air sacs that prevents normal expelling of air during respiration, may develop from lack of or faulty elastin in lung tissues.
  • Premature aging of skin. Depleted collagen and elastin with resulting lack of elasticity and flexibility leads to loose and wrinkling skin.
  • Premature graying. Copper is needed to make melanin, the pigment that colors hair and skin.
  • Bone abnormalities and fractures. The copper enzyme, lysyl oxidase, is involved in the cross-linking of collagen in forming the framework for depositing calcium and other minerals to build and repair bone. Copper is a required cofactor for the activity of lysyl oxidase. Brittle bones, poor healing of bone fractures that occur in weakened bones, especially of the neck, and osteoarthritis may develop.  In preterm infants, osteoporosis, cupping and flaring of the growing portion of long bones and spontaneous fractures develop.
  •  Diverticulosis of the bowel. Limited research points to faulty collagen in the bowel wall that may involve copper deficiency.

Important to note: In addition to copper, vitamin C also plays a vital role in connective tissue. It is a cofactor that is essential for synthesizing collagen. Deficiency of vitamin C results in scurvy, a painful affliction stemming from weakened connective tissue, that can be fatal.

4.  Role of copper in preventing oxidative damage by free radicals.

Copper plays a critical anti-oxidant role in neutralizing certain free radicals that would damage cells. Copper is part of superoxide dismutase, an enzyme that destroys the free radical called superoxide. As the name implies, superoxide is a highly reactive form of oxygen produced during certain normal metabolic reactions. Superoxides must be regulated by conversion to safe molecules through the action of superoxide dismutase to prevent central nervous system and blood vessel damage.

 

How does copper deficiency impact oxidative damage?

Copper, when insufficient to provide for the formation of adequate superoxide dismutase, fails to protect us against the damaging effects of free oxygen radicals.

 

5.  Role of copper in immune system.

Copper, bound in ceruloplasmin, plays an important role in immune responses to infection.

 

How does copper deficiency impact the immune system?

Copper deficiency weakens the immune system, permitting increased vulnerability to infection. Resulting immune malfunctions involve low activity of white blood cells to invading pathogens, poor cell response and low production of hormone by the thymus gland. Neutropenia, or low white blood cell count, is a hallmark of copper deficiency.

 

6.  Role of copper in thyroid health.

Copper is crucial to production of thyroid hormones.

How does copper deficiency impact thyroid health?

Low copper levels may reduce thyroid function. Limited research suggests that copper status should be investigated in either hyperthyroidism or hypothyroidism, especially if the person does not respond as expected to thyroid medication.

7.   Role of copper in clotting.

Copper is a critical component of coagulation factor V and factor VIII both substances required for proper clotting of blood.

 

How does copper deficiency impact blood clotting?

Copper deficiency increases the activity of factor VIII, increasing susceptibility to development of abnormal blood clots.

8.   Role of copper in the nervous system and brain activity.

Copper is required for various structures of the brain, particularly the formation and maintenance of the myelin sheath. The myelin sheath is a lipid-rich membrane surrounding nerve fibers that acts as an insulator to keep nerve impulses from straying.

Copper-containing enzymes are required in the formation, activity and breaking down of neurotransmitters. Neurotransmitters are essential chemicals needed for proper nervous system activity and include dopamine, epinephrine, norepinephrine, and serotonin.

 

How does copper deficiency impact nervous system health?

Impaired function and decreased size and weight of the brain may result from destruction of neurons that cannot be reversed. Symptoms depend on the affected nerves. There may be peripheral neuropathy, a burning, numbness or tingling in the extremities, weakness or impaired thinking. Hypotonia, or poor muscle tone, may result from low copper. Significant deficiency in infants and young children results in mental retardation.

Impaired activity results from low levels of neurotransmitters. For example, low serotonin results in depression and poor sleep. Low dopamine and norepinephrine results in low mental energy and poor ability to focus.

 

9.   Role of copper in health of infants and small children.

Copper is essential for normal growth and development.

 

How does copper deficiency impact infants and young children ? Copper deficiency first results in anemia and neutropenia, which involve weakness, low energy, irritability and frequent infections like colds and earaches. Other symptoms are poor muscle tone and coordination, persistent infantile diarrhea, impaired growth and weight gain, and bone abnormalities. Significant deficiency in infants and young children results in mental retardation.

 

10.  Role of copper in regulating heartbeats.

An in depth study of postmenopausal women placed on a carefully controlled long-term copper deficient diet has documented the development of ventricular arrythmias.

 

11. Role of copper in cancer.

Colon cancer has been associated with copper deficiency in some research studies. Lysyl oxidase is an enzyme that is involved in tumor suppressor activity. Copper is a cofactor for the activity of lysyl oxidase.

Risk Factors for copper deficiency other than malabsorption

High dose supplements of vitamin C (more than 1,000 mg) may make it harder to absorb copper. There is controversy about the effect of zinc supplements in doses higher than 50 mg. While is has been widely held that high dose zinc supplements interfere with copper absorption, a study published May 2004 did not find interference with copper absorption by zinc in subjects under tightly contolled diets. More research is needed.

Copper storage in the body

Copper is stored in the liver and excess is excreted in bile or by the kidneys.

 

Recommended Daily Allowances

 The Daily Reference Intakes (DRI) for copper are shown in the table below. Please note that amounts of copper listed below are in milligrams (mg) and micrograms (mcg). There are a thousand micrograms in one milligram, that is, I mg equals 1,000 mcg. 

Life Stage            Copper (mcg)

Infants  

 0 – 6 months                   200

 7 – 12 months                 220

Children           

 1 – 3 years                      340

 4 – 8 years                      440

Males  

 9 – 13 years                    700

 14 – 18 years                  890

 19 years and older          900

Females         

 9 – 13 years                    700

 14 – 18 years                  890

 19 years and older          900

Pregnancy                     1,000

Lactation                       1,300

 

Food Sources of Copper

Copper is found widely in animal products, except cow milk, and in foods such as nuts, seeds, whole grains, legumes, and chocolate. However, fruits and vegetables contain little copper. Specific food sources provided by the USDA (US Dept of Agriculture) are listed below.

Food                                   Copper (mg) and (mcg)

Beef liver, 3 oz.                                   2.4        2,400

Oysters, cooked 3.5 oz                        2          2,000

Cashews, dry roasted, 1/4 cup              0.8          800

Pumpkin seeds, roasted, 1/2 cup          0.7          700

Black-eyed peas, cooked, 1/2 cup         0.7          700

Clams, steamed, 3.5 oz                        0.7          700

Sunflower seeds, 1/4 cup                      0.6          600

Molasses, blackstrap, 2 Tbsp.               0.6          600

Unsweetened chocolate, 1 oz                0.6          600

Beans, refried, 1/2 cup                          0.5          500

V-8 juice, 1 cup                                    0.5          500

Tofu, firm, 1/2 cup                                 0.5          500    

Cocoa powder, 2 Tbsp.                         0.4           400

Prunes, dried, 10                                  0.4          400

Salmon, baked, 3 oz.                            0.3          300

 

Storage, Processing, and Cooking

 Processing of whole grains strips them of their germ and bran layer, which contains copper and many other nutrients. The remedy is to buy and consume more whole grains, such as brown rice and buckwheat, and rice and corn bran, that can be added to cereals, baked goods, meat loafs and such. Long-term cooking can substantially reduce the copper in foods such as dried beans. The remedy is to consume the liquid used for cooking rather than pouring it away.  Making soups, stews, pot roasts and casseroles are excellent ways to preserve copper in food preparation.

 

Tests and Treatment

Tests for copper deficiency involve blood analysis of copper and ceruloplasmin levels. At present they are not completely reliable.

Treatment is directed at the cause of the deficiency. In celiac disease, it would be a copper-rich gluten-free diet that may initially require the addition of 2 to 5mg cupric ion daily as oral supplement.

Supplements  can be toxic

While toxicity is not known to occur by consuming food, large dose copper supplements (10-20 mg/day) may contribute to liver damage, abnormalities in red blood cell formation, weakness, and nausea.

Resources 

http://courses.washington.edu/bonephys/ophome.html 

Krause’s Food, Nutrition & Diet Therapy. 10th Ed. W B Saunders Company, 2000.

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Author Information: Cleo Libonati, RN, BSN
Cleo Libonati is president/CEO and co-Founder of Gluten Free Works, Inc. She is the author of Recognizing Celiac Disease
She can be reached by E-mail.


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7 Responses to “Understanding Copper Deficiency in Celiac Disease”

  1. Hi there,

    The title of this article is misleading: it is not about the link between low copper and celiac disease at all but simply a lengthy description of copper deficiency generally. In the entire piece, the word celiac only occurs once where a single point speaks (dubiously it could be argued) to the supposed connection.

    In my clinical practice, I test copper levels fairly often. To date, I’ve not had a low score yet. Most people test high, including celiacs, both kids and adults, with only a rare few normals across all patients. Copper excess is no walk in the park either by the way being linked clearly with issues ranging from mental ill-health to incidence of many cancers. In my experience and that of many others I work alongside, Cu overload is certainly more common than deficiency.

    • Your comment is incorrect. The article is in no way misleading.

      It seems you have conflated two separate issues. The first is “copper deficiency in celiac disease.” The second is “copper excess in your patients.”

      Copper excess is indeed a problem. Do your patients come from a single geographic region? Do they eat similar foods or drink water from the same aquifer? Is copper exposure common to your patients through diet or some other environmental factor? Which assay do you use to test patients? Does testing fairly often equate to one patient per day, one patient in 3, or one patient once every several months?

      For those with undiagnosed copper deficiency, obtaining a proper diagnosis would be difficult should their physicians do not believe in the possibility.

      The article reports increased frequency of copper deficiency in untreated celiac disease and explains the mechanism that leads to it. In addition, the word celiac occurs more than once. See “Jameson S, Hellsing K et al. Copper malabsorption in coeliac disease. Science of the Total Environment.” Also, Copper deficiency in celiac disease. http://www.ncbi.nlm.nih.gov/pubmed/18496230. There are others should you wish to research further. A simple Google search will reveal them.

      The lengthy description will help you understand how copper deficiency arises in celiac disease so you can better treat your patients.

  2. Steph says:

    I just came across this article, and I have to say its very informative, and so true. I’ve suffered many health problems for several years, and by chance a few months ago, I came across an article which said that while people with rhesus positive blood need iron, people with a rhesus negative blood type are more likely to need copper, so I decided to try supplements to see if they’d have any benefit on my health. I’m so glad I did. Over the last 6 months I’ve felt better than I have in years. I have more energy, whereas I’d felt tired all the time, my IBS has improved dramatically, so much so that I can now eat foods I’d had to give up, my low moods have gone, my skin is looking so much better that people are commenting, Im sleeping better, pains from a quite serious degenerative spine condition are far less, i could go on, i havent felt this well in years!

    It’s interesting that you say copper is taken from mothers in large amounts, I’ve had 3 children, and, as much as I love them, it’s since having my children that my problems began and increased.

  3. Julia Foster says:

    Thank you so much for the great information, really thorough and helpful!

  4. […] from this interesting summary: Understanding Copper Deficiency in Celiac Disease July 28th, 2010 by Cleo Libonati, RN, BSN  [I strongly suggest reading this entire […]

  5. Nice Information about Copper. I am working on copper for developing a pharmaceutical copper product to treat copper deficiency. I wish to know more about copper deficiency and its treatments.

  6. Angie Halten says:

    Lots of great information. I had never thought copper deficiency a problem until I read your article. Thanks for this enlightening article. The more we know concerning our health, the better.

    Angie.

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