MikronährstoffCoach®: Mikronährstoffe / mikronaehrstoffcoach.com

Sources and physiological effects

Dietary sources
Copper is a trace element contained in numerous foods in different concentrations. Offal such as liver or kidneys are considered rich in copper,fish and crustaceans also contain higher amounts of copper. For vegetarians and vegans, it is more difficult to cover copper requirements. Wholemeal products, nuts, chocolate, cocoa and pulses are considered valuable plan sources of copper. Newly laid water pipes should also not be neglected as a source of copper, especially when water has low pH values.
Physiological effects
Iron metabolism	Co-Factor in the conversion of stored iron (ferritin) into transport iron (transferritin)
Antioxidant	Decomposition of oxygen radicals as a co-factor of antioxidative superoxide dismutase
Melanin production	Co-factor of tyrosinase, an enzyme for skin and hair pigmentation
Synthesis of collagen	Contributes to the cross-linking of collagen and elastin
Energy metabolism	Co-factor of the mitochondrial respiratory chain

EFSA Health Claims

Health Claims		EFSA Opinion
Copper	Contributes to the maintenance of normal connective tissue Contributes to hair pigmentation Contributes to a normal transport of iron in the body Contributes to normal skin pigmentation Helps protect cells from oxidative stress Contributes to a normal energy metabolism Contributes to a normal function of the nervous system

Recommended intake

D-A-CH reference values for copper intake (Reference values EFSA and NHI )
	Age	Copper (mg/d)
Infants (months)
	0-4	0.2 - 0.6
	4-12	0.6 - 0.7
Children (years)
	1-4	0.5 - 1.0
	4-7	0.5 - .1.0
	7-10	1.0 - 1.5
	10-13	1.0 - 1.5
	13-15	1.0 - 1.5
Youth/adults (years)		Women	Men
	15-19	1.0 - 1.5	1.0 - 1.5
	19-25	1.0 - 1.5	1.0 - 1.5
	25-51	1.0 - 1.5	1.0 - 1.5
	51-65	1.0 - 1.5	1.0 - 1.5
	> 65	1.0 - 1.5	1.0 - 1.5
Pregnancy	N/A
Breastfeeding	N/A
Increased requirements	Sport (loss of copper due to perspiration) high zinc intake, chronic diarrhea, celiac disease, short bowel syndrome

Recommended intake according to food labelling regulations
(=100 % Daily Value)		1 mg
Nutrient safety
UL	Long-term daily intake, for which no negative effects on health are to be expected	10 mg/d (according to NIH)
NOAEL	Maximum intake, with no observed adverse effect	N/A
Safety	EFSA has been working on the safety of copper.

Detailed information

Copper – Co-factor in blood formation and pigmentation of skin and hair

Copper is an integral component of a number of enzymes and is therefore involved in many redox reactions. Its main functions include participation in hematopoiesis, electron transport in the respiratory chain and antioxidative defense. In hematopoiesis, copper catalyzes iron oxidation and therefore the incorporation of iron into the transport protein transferrin. This is the only way iron is available for blood formation (1). Due to the close connection with iron metabolism, a copper deficiency can be responsible for the development of hypochromic microcytic anemia (1). At the same time, the copper transport protein ceruloplasmin also functions as an antioxidant that prevents iron-induced lipid peroxidation (2).
Copper is a co-factor responsible for the pigmentation of skin and hair. The activity of the enzyme tyrosinase depends on the binding of two copper atoms. Copper deficiency can limit the function of tyrosinase and thus lead to pigment disorders of skin and hair (3)

Copper and rheumatoid diseases

Copper is also a co-factor in cartilage mineralization, elastin formation, collagen (4) and trabecular bone (5)(6). A study of chondrocytes in osteoarthritis patients suggests that copper can stimulate collagen formation (7). Studies in patients with osteoarthritis demonstrate increased copper content in the synovial fluid (6). In patients with rheumatoid arthritis there is increased copper levels in plasma and hair (8). This is attributed to the activity of copper-dependent immunomodulating cytokines and the increased secretion of ceruloplasmin, which is responsible for the transport of copper from the liver into the bloodstream (9).

Copper and cardiovascular diseases

Copper could also play a therapeutic role in cardiovascular diseases.
Copper-containing lysyl oxidase is essential for the formation and cross-linking of collagen and elastin, which is why a copper deficiency can lead to elastin degradation in the vessels and to macroangiopathies (10). Copper deficiency could also be involved in the development of aneurysms. Changes in the copper level of aneurysm patients suggest a correlation of pathogenesis with oxidative stress (11) and impaired collagen and elastin formation (12).
In animal experiments, targeted copper supplementation also had positive effects on the lipid profile in serum. This is attributed to the increased antioxidant activity and the resulting reduction in oxidative stress (13). A study in young women showed significantly increased erythrocyte superoxide dismutase activity and improved fibrinolytic capacity. An increased copper intake of 3 – 6 mg/day could therefore reduce the risk of cardiovascular disease (14).

Reference values

Parameter	Substrate	Reference value	Description
Copper in the blood	Serum	0.8 - 1.25 mg/l	60 % of the copper is in serum
	Whole blood	1.0 - 1.3 mg/l	Hematocrit-correlated whole blood analysis enables a correct interpretation of the supply status
Copper in Urine	24-h-urine	10 - 60 µg/24h	24h-collection
Interpretation
Low value		Copper deficiency e.g. due to malnutrition, malabsorption, protein loss via the kidney, Wilson's disease
High value		Chronic infections, liver damage, pancreatic insufficiency, acute episodes of rheumatic disease. Copper poisoning is very rare in adults, as even an oral intake of 1 g of copper leads to nausea and vomiting.
Note on interpretation of results
Increased copper levels can be detected during pregnancy (2nd and 3rd trimesters) and when taking estrogen preparations.

Deficiency symptoms

Impact on	Symptoms
General health	Tiredness, weakness, insomnia
Reproduction	Fertility problems Decreased sperm mobility
Skin and hair	Disorders of skin and hair pigmentation
Immune system	Increased susceptibility to infections
Blood count	Anemia (hypochromic, microcytic)

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	For non-specific and specific symptoms indicating copper deficiency	2 mg/d
	To prevent copper deficiency in high or long-term zinc supplementation	2 - 3 mg/d
	Complementary therapy for inflammatory diseases, in particular osteoarthritis	2 - 3 mg/d

Administration

General mode of administration
When	Copper should be taken between meals (30-60 minutes before) as other micronutrients and food components can interfere with the absorption of copper. Since zinc interferes with copper absorption, copper and zinc should not be taken together, but at different times.
Side effects
Long-term high doses lead to gastrointestinal disorders such as nausea, diarrhea, vomiting.
Contraindications
Wilson's disease (genetic copper storage disease), severe kidney disease

Interactions

Drug interactions
Antiepileptics (phenytoin)	Phenytoin can form complexes with copper and reduce its absorption
Oral contraceptives	May lead to an increase in copper serum levels
Antacids (e.g. Maalox, Cimetidin)	Inhibits copper absorption
Laxatives (e.g. bisacodyl)	Inhibits copper absorption
Gout (Allopurinol)	Can lead to complex formation with copper
Nutrient interactions
Heavy metals and trace elements	Trace elements such as iron, zinc and calcium can reduce the absorption of copper.

Description and related substances

Description

Micronutrient
Symbol: Cu
Ion: Cu²⁺

Related substances

Inorganic compounds such as copper carbonate, copper sulphate and organic compounds such as copper citrate, copper gluconate, copper L-aspartate, copper bisglycinate and copper-lysine complex are permitted.

References

1) Hahn, A. et al. 2005. Ernährung. Physiologische Grundlagen, Prävention, Therapie.
2) Gröber, U. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte. 2002.
3) Ando, H. et al. 2007. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J Invest Dermatol. 127(4):751-61.
4) Tapiero, H. et al. 2003. Trace elements in human physiology and phatology. Copper. Biomed Pharmacother. 57(9):386–398.
5) Kagan, H. M., Li, W. 2003. Properties, specifity, and biological roles inside and outside of the cell. J Cell Biochem. 88(4):660–672.
6) Schumann, K. et al. 2002. Hohenheim Consensus Workshop: Copper. Eur J Clin Nutr. 56:469–483.
7) Yazar, M. et al. 2005. Synovial fluid and plasma selenium, copper, zinc and iron concentrations in patients with rheumatoid arthritis and osteoarthritis. Biol Trace Elem Res. 106(2):123-32.
8) Heraud, F., Savineau, C., Harmand, M. F. 2002. Copper modulation of extracellular matrix synthesis by human articular chondrocytes. Scand J Rheumatol. 31(5):279-84.
9) Strecker, D. et al. 2013. Copper levels in patients with rheumatoid arthritis. Ann Agric Environ Med. 20(2):312-6.
10) Biesalski, H. K. et al. 2002. Vitamine, Spurenelemente und Mineralstoffe. Prävention und Therapie von Mikronährstoffen.
11) Pincemail, J. et al. 2012. On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm. Redox Rep. 17(4):139-44.
12) de Figueiredo Borges, L. et al. 2010. Histopathology of an iliac aneurysm in a case of Menkes disease. Pediatr Dev Pathol. 13(3):247-51.
13) Galhardi, C.M. et al. 2005. Beneficial effects of dietary copper supplementation on serum lipids and antioxidant defenses in rats. Ann Nutr Metab. 49(5):283-8.
14) Bugel, S. et al. 2005. Effect of copper supplementation on indices of copper status and certain CVD risk markers in young healthy women. Br J Nutr. 94(2):231-6.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.