Copper Deficiency

What Is Copper Deficiency?

[dropcap]C[/dropcap]opper is an essential trace element that is required for a number of enzymes which are necessary for normal metabolic function.

In the body almost all the copper is present as a component of copper proteins which are produced and controlled by the liver.

Q: How does the liver control copper?

A: The liver maintains proper copper balance by binding free copper to proteins and by excreting excess copper as part of bile that is then emptied into the intestinal tract and excreted in stool.

Metabolic balance studies have demonstrated that daily copper losses are approximately 1.3 mg/day.¹

Among its specific functions listed below, copper is essential for energy production, blood and nerve functions, blood components, immunity, and collagen tissue. 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.

Animal studies suggest that adequate copper levels during pregnancy are critical to development of higher brain function in the offspring.²

What Is Copper Deficiency In Celiac Disease and/or Gluten Sensitivity?

• Definition. Copper deficiency results when the level within cells is too low to meet metabolic needs of the body for this mineral. Deficiency of copper was found both in typical as well as in atypical cases of celiac disease.³
• Signs. Deficiency is characterized by these features:

• Impaired energy production and antioxidant protection;
• Faulty blood cell formation and instability of blood cell membranes ;
• Faulty elastin formation and poor collagen and connective tissue strength;
• Loss of proprioception causing ataxia;
• Loss of pigmentation of hair and skin;
• Impaired thyroid and adrenalin production.

• Outcome. Brain degeneration and failure to make normal blood cells can result in death.
• Low absorption. A study investigating copper uptake from an oral test dose of copper sulphate solution close to the recommended daily dietary intake demonstrated significantly reduced uptake in patients with celiac disease. Copper deficiency and proximal intestinal disease should be suspected in patients with otherwise unexplained anemia, especially neutropenia.⁴
• Diagnosis. Unfortunately, current laboratory techniques do not seem to be adequate for the diagnosis of marginal copper deficiency, although gross deficiencies are readily detected. Plasma copper concentrations may not drop significantly unless body stores are severely depleted.⁵
• Testing. Romberg’s test for sensory ataxia (loss of proprioception) resulting from copper deficiency is an easy self test: feet together and eyes closed with hands at sides for one minute. Positive if swaying and unsteady.

How Prevalent Is Copper Deficiency In Celiac Disease and/or Gluten Sensitivity?

Copper deficiency has increased frequency of in persons with untreated celiac disease.⁶ Conversely, in genetically normal people, acquired, environmental, or dietary abnormalities rarely cause clinically significant copper deficiency.⁷

Copper deficiency was found in three patients out of 22 at diagnosis of celiac disease who presented with blood abnormalities.²

What Are The Symptoms Of Copper Deficiency?

Copper deficiency is marked by these symptoms:

• Apathy.
• General Weakness.
• Muscle weakness.
• Blood Abnormalities that include iron deficiency anemia (fatigue, paleness, shortness of breath), leukopenia or low white blood cell count (reduced resistance to infection), neutropenia, and thrombocytopenia or low platelet count (poor blood clotting).
• Collagen tissue abnormalities: weak blood vessels, joint and tendon problems, hemorrhoids, weak spinal discs, premature graying of hair, decreased skin pigment (loss of color).
• Diarrhea.
• Ataxia (loss of coordination).
• Impaired respiratory function.
• Impaired healing.
• Increased triglyceride levels.
• Impaired thyroid hormone production.
• Impaired adrenalin production.
• Contributes to osteoporosis.

How Does The Body Get Copper?

• Copper must be obtained from the diet since it cannot be made by the body. Like all minerals, copper must be ionized (receives an electric charge) in stomach acid during digestion, otherwise it cannot be absorbed into the body.
• Copper absorption occurs through the upper small intestinal lining. Entry of copper ions at the mucosal surface is by facilitated diffusion. Exit of copper ions at the basolateral membrane of the lining is primarily by active transport by intestinal copper-binding protein that is also involved with zinc absorption.⁸
• About 30% of dietary copper is normally absorbed. However, because of shared transport with zinc, high zinc supplements (150 mg/day) were found to dramatically decrease the amount of protein available to bind copper.
• In the bloodstream, copper is bound to and carried by proteins, particularly ceruloplasmin.

What Does Copper Do In The Body?

1. Essential for the formation of hemoglobin and red blood cell production, thereby enabling the efficient transport of oxygen throughout the body.
2. Works in balance with vitamin C and zinc to manufacture elastin (a blood vessel protein), collagen (a skin protein), and other structural proteins in bone, cartilage and tendons.
3. Stimulates the absorption of iron through the copper transport protein ceruloplasmin.
4. Needed for hair and skin coloring (production of melanin).
5. Aids in the metabolism of fatty acids and energy production.
6. Essential cofactor to the antioxidant, superoxide dismutase, which prevents oxidative damage to cell membranes.
7. Needed for proper insulation (myelination) of nerve cells.
8. Serves as a cofactor for the synthesis of the neurotransmitter (nerve chemical) norepinephrine.
9. Involved in immunity and the healing process.
10. Needed for taste sensitivity.
11. Required for thyroid hormone secretion.
12. Required for adrenalin production.

How Does Copper Deficiency Develop In Celiac Disease and/or Gluten Sensitivity?

Copper deficiency results from these mechanisms:

• Deficiency results primarily from malabsorption of this mineral due to inflammation of intestinal lining as an immune response to gluten that results in inadequate absorbing surface area.
• Malabsorption can occur as a consequence of low stomach acid. Sufficient acid is required to ionize copper (receives a positive charge) which is required for absorption later in the small intestine.
• Malabsorption can occur as a consequence of insufficient carrier proteins needed to transport ionized into the bloodstream from the absorbing cells of the small intestine.
• Gastrointestinal loss through diarrhea, if present. Chronic diarrhea in children is associated with lower levels of copper, especially when accompanied by malabsorption. Blood copper concentrations were 30% lower and hair copper content decreased three to fourfold in the chronic diarrhea group relative to the control groups. Low copper intakes during recovery from diarrhea may further limit return to adequate copper level.⁹
• Urine loss especially in females.
• Abnormal bile loss (copper is excreted primarily in the bile) through diseases of the liver and gall bladder that can develop from celiac disease.

Does Copper Deficiency Respond To A Gluten Free Diet?

Yes. Copper deficiency responds to a gluten free diet that contains adequate copper and protein.

Please  note: Ingestion of excessive levels of zinc, vitamin C or fructose sugar can interfere with copper absorption which may inhibit return to normal copper in the body.

6 Steps To Correct Copper Deficiency:

• [dropcap]1[/dropcap]Meet, or Exceed the RDA (Recommended Dietary Allowances) for Copper in milligrams (mg) per day:

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1 mg per day for adult males and non-pregnant females;

0.8 mg per day for pregnant and lactating females 14-18 years old;

1 mg per day for pregnant and lactating females 19 years and older. [/box]

• [dropcap]2[/dropcap]Diet – Include Food Sources Richest in Copper:

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Plant Sources:

• Seeds.
• Dark leafy vegetables (turnip greens, spinach, chard, kale).
• Squash.
• Eggplant.
• Asparagus.
• Nuts.
• Legumes.
• Whole grains.
• Chocolate.
• Soybeans.

Animal Sources:

• Liver.
• Oyster.
• Shellfish.

Chef’s Note: Cooking food for a long time in liquid reduces copper content so that the juices should also be consumed to benefit from the food loss, such as using the drippings and juices from meat for gravy and sauces and the liquid from plants in soups.[/box]

 

• [dropcap]3[/dropcap] Diet – Avoid  or Limit These Foods That Deplete or Interfere With Absorption:

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• Refined sugar including table sugar (cane and beet), corn syrup and especially fructose.
• High phytate-containing food like whole bran grains, except when baked with yeast which inactivates phytate (eg. bread).
• Excessive fiber which binds copper, interfering with absorption.

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• [dropcap]4[/dropcap]Monitor Medications That Deplete or Interfere With Absorption:

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Here are common medications that deplete copper. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

• Zidovudine (Retrovir®) anti-viral agent.
• Antacids/Ulcer Medications  (Pepcid®, Tagamet®, Zantac®).
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®).[/box]

• [dropcap]5[/dropcap]Manage Nutritional Supplements to Obtain Magnesium:

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• A blood level concentration  should be obtained to determine status before supplementing.
• Copper is available as copper sulfate in tablet form and as part of multivitamin/mineral supplements.
• Folic acid helps the body to assimilate copper.

Caution: Ingesting amounts over 10 mg per day regularly can result in nausea, although toxicity will typically only occur at much higher levels (200 times the RDA).[/box]

• [dropcap]6[/dropcap]Other Supplements That Deplete or Interfere With Absorption:

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• Excessive vitamin C supplements and iron supplements inhibit copper absorption. Generally, take 2 hours before or after each other.
• Excessive molybdenum and zinc supplementation can induce secondary copper deficiency.¹⁰Check with your pharmacist.[/box]

What Do Medical Research Studies Tell About Copper Deficiency In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Micronutrient deficiencies in patients with typical and atypical celiac disease.” This study investigating the extent of the digestive/absorptive involvement in atypical presentation of celiac disease in 109 pediatric patients (54 typicalceliac disease, 19 atypical celiac disease, 36 healthy controls) demonstrated that deficiency of copper was found both in typical as well as in atypical cases.¹¹

“Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients.” This study evaluating copper levels in the bloodstream, cerulopasmin protein and 24 hour urine copper levels in celiac disease patients compared to controls showed that copper in the bloodstream was the same as in controls, ceruloplasmin levels were higher in celiacs, and levels of copper in urine was higher (56 +/- 30 micrograms/day) in women and in men (33 +/- 17 micrograms/day. Increased urinary loss may be another cause of copper deficiency in female celiacs besides malabsorption. Increased urinary copper levels in celiac women should not always be regarded as a diagnosis of Wilson’s disease.¹²

“Hematologic manifestation of childhood celiac disease.” This study investigating the blood manifestations of celiac disease (celiac disease) in childhood describes the findings in 22 children with celiac disease in whom the disease remained undiagnosed until they had presented with blood abnormalities, such as anemia, thrombocytopenia, leukopenia or prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Among the various disturbances, two patients were found to have copper and vitamin B(12) deficiency and one patient had combined iron, zinc, and copper deficiency.¹³

“Zinc and copper in hair and plasma of children with chronic diarrhea.” This study compared the copper status of 19 children with chronic diarrhea (8 with celiac disease and 11 without malabsorption) with that of two control groups (19 healthy and 11 malnourished children) and found that chronic diarrhea in children is associated with lower levels of zinc and copper, especially when accompanied by malabsorption. Plasma zinc was depressed in the celiac disease group when compared with the normal children, but was similar to that of the malnourished children. Blood copper concentrations were 30% lower and hair copper content decreased three to fourfold in the chronic diarrhea group relative to the control groups. Low copper intakes during recovery from diarrhea may further limit return to adequate copper level.¹⁴

“Copper malabsorption in celiac disease.” This study investigating copper uptake from an oral test dose of copper sulphate solution close to the recommended daily dietary intake demonstrated significantly reduced uptake in patients with celiac disease. Copper deficiency and proximal intestinal disease should be suspected in patients with otherwise unexplained anemia, especially neutropenia.⁴

“Increased cholesterol in plasma in a young man during experimental copper depletion.” Signs of copper depletion were produced in a healthy man by an amount of dietary copper (0.83 mg/day) similar to that in some contemporary diets. Urinary and fecal loss of copper exceeded intake. Plasma copper, ceruloplasmin, and superoxide dismutase activity in erythrocytes decreased. Cholesterol in plasma increased, and hematologic indices were unchanged. Lipid metabolism may be a more sensitive index of copper nutriture than are changes in hematology. The findings support the hypothesis that inadequate copper nutriture or altered copper metabolism contributes to the occurrence of ischemic heart disease.¹⁵

CASE REPORT SUMMARIES

“Copper deficiency myeloneuropathy due to occult celiac disease.“ This case report describes finding celiac disease in a 69-year-old woman who was evaluated for a 5-year history of progressive gait unsteadiness and weight loss. She had no other gastrointestinal symptoms. Her neurologic examination revealed a sensory ataxia, and electro-diagnostic testing confirmed a myeloneuropathy. She had decreased serum copper levels and markedly elevated gliadin and tissue transglutaminase antibodies. Subsequent duodenal biopsy showed findings consistent with celiac disease.

The patient was diagnosed with copper deficiency myeloneuropathy due to celiac disease. Adoption of a gluten-free diet along with copper supplementation resulted in significant clinical improvement, including improvement on electrodiagnostic testing. Celiac disease should be considered in patients found to have copper deficiency, even in patients without gastrointestinal symptoms.¹⁶

Sources:

1. Williams DM. Copper deficiency in humans. Semin Hematol. 1983 Apr; 20(2):118-28. [↩]
2. Fisgin T, Yarali N, Duru F, Usta B, Kara A. Hematologic manifestation of childhood celiac disease. Acta Haematol. 2004;111(4):211-4. [↩] [↩]
3. Botero-López JE, Araya M, Parada A, Méndez MA, Pizarro F, Espinosa N, Canales P, Alarcón T. Micronutrient deficiencies in patients with typical and atypical celiac disease. J Pediatr Gastroenterol Nutr. 2011 Sep;53(3):265-70. [↩]
4. Jameson S, Hellsing K, Magnusson S. Copper malabsorption in celiac disease. Science of the Total Environment. Mar 15, 1985.; 41(1-2):29-36 [↩] [↩]
5. Jackson MJ. Diagnosis and detection of deficiencies of micronutrients: minerals. Br Med Bull. 1999; 55(3):634-42. [↩]
6. Jameson S, Hellsing K, Magnusson S. Copper malabsorption in celiac disease. Science of the Total Environment. Mar 15, 1985.; 41(1-2):29-36 [↩]
7. Mark Beers and Robert Berkow. The Merck Manual, 17th edition. Whitehouse Station, NJ, USA: Merck Research Laboratories, 1999. [↩]
8. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩]
9. Rodríguez A, Soto G, Torres S, Venegas G, Castillo-Durán C. Zinc and copper in hair and plasma of children with chronic diarrhea. Acta Paediatr Scand. 1985 Sep; 74(5):770-4. [↩]
10. http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/absorb_minerals.html [↩]
11. Botero-López JE, Araya M, Parada A, Méndez MA, Pizarro F, Espinosa N, Canales P, Alarcón T. Micronutrient deficiencies in patients with typical and atypical celiac disease. J Pediatr Gastroenterol Nutr. 2011 Sep;53(3):265-70. [↩]
12. Ince AT, Kayadibi H, Soylu A, Ovunç O, Gültepe M, Toros AB, Ya?ar B, Kendir T, Abut E. Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients. Dig Dis Sci. 2008 Jun; 53(6):1564-72. [↩]
13. Fisgin T, Yarali N, Duru F, Usta B, Kara A. Hematologic manifestation of childhood celiac disease. Acta Haematol. 2004; 111(4):211-4. [↩]
14. Rodríguez A, Soto G, Torres S, Venegas G, Castillo-Durán C. Zinc and copper in hair and plasma of children with chronic diarrhea. Acta Paediatr Scand. 1985 Sep; 74(5):770-4. [↩]
15. Klevay LM, Inman L, Johnson LK, Lawler M, Mahalko JR, Milne DB, Lukaski HC, Bolonchuk W, Sandstead HH. Increased cholesterol in plasma in a young man during experimental copper depletion. Metabolism. 1984 Dec;33(12):1112-8. [↩]
16. Goodman BP1, Mistry DH, Pasha SF, Bosch PE. Copper deficiency myeloneuropathy due to occult celiac disease. Neurologist. 2009 Nov;15(6):355-6. doi: 10.1097/NRL.0b013e31819428a8. [↩]