Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Hohenheim Consensus Workshop: Copper

European Journal of Clinical Nutrition volume 56, pages 469–483 (2002)Cite this article

Abstract

Copper (Cu) is an essential trace element with many physiological functions. Homeostatic mechanisms exist to allow Cu to act as a cofactor in enzymatic processes and to prevent accumulation of Cu to toxic levels. The aim of this commentary is to better understand the role of dietary Cu supply in deficiency and under physiological and pathological conditions. The essentiality of Cu can be attributed to its role as a cofactor in a number of enzymes that are involved in the defence against oxidative stress. Cu, however, has a second face, that of a toxic compound as it is observed with accumulating evidence in hepatic, neurodegenerative and cardiovascular diseases. The destructive potential of Cu can be attributed to inherent physico-chemical properties. The main property is its ability to take part in Fenton-like reactions in which the highly reactive and extremely deleterious hydroxyl radical is formed. Diseases caused by dietary Cu overload could be based on a genetic predisposition. Thus, an assessment of risk-groups, such as infants with impaired mechanisms of Cu homeostasis regarding detoxification, is of special interest, as their Cu intake with resuspended formula milk may be very high. This implies the need for reliable diagnostic markers to determine the Cu status. These topics were introduced at the workshop by the participants followed by extensive group discussion. The consensus statements were agreed on by all members. One of the conclusions is that a re-assessment of published data is necessary and future research is required.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Abdel Mageed AB, Welti R, Oehme FW, Pickrell RA . 1994 Perinatal hypocuprosis affects synthesis and composition of neonatal lung collagen, elastin, and surfactant Am. J. Physiol. 267: L679–L685

    CAS  PubMed  Google Scholar 

  • Aggett PJ . 1999 An overview of the metabolism of copper Eur. J. Med. Res. 4: 214–216

    CAS  PubMed  Google Scholar 

  • Aguzzi A, Brandner S . 1999 The genetics of prions—a contradiction in terms? Lancet 354: (Suppl 1): 122–125

    Google Scholar 

  • Alt ER, Sternlieb I, Goldfischer S . 1990 The cytopathology of metal overload Int. Rev. Exp. Pathol. 31: 165–188

    CAS  PubMed  Google Scholar 

  • American Medical Association. 1979 Guidelines for essential trace element preparations for parenteral use J.A.M.A. 241: 2051–2054

  • Atwood CS, Moir RD, Huang X, Scarpa RC, Bacarra NM, Romano DM, Hartshorn MA, Tanzi RE, Bush AI . 1998 Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis J. Biol. Chem. 273: 12817–12826

    CAS  PubMed  Google Scholar 

  • Baker DH, Ammerman CB . 1995 Copper bioavailability In Bioavailability of Nutrients For Animals ed. DH Baker, CB Ammerman & Lewis AJ San Diego: Academic Press pp 127–156

    Google Scholar 

  • Battersby S, Chandler JA . 1977 Correlation between elemental composition and motility of human spermatozoa Fertil. Steril. 28: 557–561

    CAS  PubMed  Google Scholar 

  • Belch JJF, Chopra M, Hutchinson S, Stannick RD, Forbes CD, Smith WE . 1989 Free radical pathology in chronic arterial disease Free Rad. Biol. Med. 6: 375–378

    CAS  PubMed  Google Scholar 

  • Beshgetoor D, Hambidge M . 1998 Clinical conditions altering copper metabolism in humans Am. J. Clin. Nutr. 67: (Suppl): 1017S–1021S

    CAS  PubMed  Google Scholar 

  • Blasco N, Galindo A, Pérez M . 1999 may Estimated daily intakes and concentrations of essential trace elements in infant formulas, Abstract on behalf of TEMA 10 Evian/France 2–7

  • Borchardt T, Camakaris J, Cappai R, Masters CL, Beyreuther K, Multhaup G . 1999 Copper inhibits ß-amyloid production and stimulates the non-amyloidogenic pathway of amyloid precursor protein (APP) secretion Biochem. J. 344: 461–467

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bremner I . 1987 Involvement of metallothionein in the hepatic metabolism of copper J. Nutr. 117: 19–29

    CAS  PubMed  Google Scholar 

  • Bremner I . 1998 Manifestations of copper excess Am. J. Clin. Nutr. 67: 1069S–1073S

    CAS  PubMed  Google Scholar 

  • Brigelius R, Spottl R, Bors W, Lengfelder E, Saran M, Weser U . 1974 Superoxide dismutase activity of low molecular weight Cu2+ chelates studies by pulse radiolysis F.E.B.S. Lett. 47: 72–74

    CAS  Google Scholar 

  • Brown DR, Quin K, Herms JW, Madlung A, Manson J, Strome R, Fraser PE, Kruck T, von Bohlen A, Schulz-Schaeffer W, Giese A, Westaway D, Kretzschmar H . 1997 The cellular prion protein binds copper in vivo Nature 390: 684–687

    CAS  PubMed  Google Scholar 

  • Brown DR, Schmidt B, Kretzschmar HA . 1998 Effects of copper on survival of prion protein knockout neurons and glia J. Neurochem. 70: 1686–1693

    CAS  PubMed  Google Scholar 

  • Brujin LI, Houseweart MK, Kato S, Anderson KL, Anderson SD, Ohama E, Reaume AG, Scott RW, Cleveland DW . 1998 Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1 Science 281: 1851–1854

    Google Scholar 

  • Buamak PH, Russell M, Milford-Ward A, Taylor P, Roberts DF . 1984 Serum copper concentration significantly less in abnormal pregnancies Clin. Chem. 30: 1667–1670

    Google Scholar 

  • Bueler H, Fischer M, Lang Y, Bluethmann H, Lipp HP, DeArmond SJ, Prusiner SB, Aguet M, Weissmann C . 1992 Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein Nature 356: 577–582

    CAS  PubMed  Google Scholar 

  • Bull PC, Thomas GR, Rommenes JM, Forbes JR, Cox DW . 1993 The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene Nature Genet. 5: 327–337

    CAS  PubMed  Google Scholar 

  • Castillo-Duran C, Uauy R . 1988 Copper deficiency impairing growth of infants recovering from malnutrition Am. J. Clin. Nutr. 47: 710–714

    CAS  PubMed  Google Scholar 

  • Castillo-Duran C, Vial P, Uauy R . 1988 Trace element balance during acute diarrhea in infants J. Pediatr. 113: 452–457

    CAS  PubMed  Google Scholar 

  • Castillo-Duran C, Vial P, Uauy R . 1990 Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants Am. J. Clin. Nutr. 51: 1088–1092

    CAS  PubMed  Google Scholar 

  • Chelly J, Monaco AP . 1993 Cloning the Wilson disease gene Nature Genet. 5: 317–318

    CAS  PubMed  Google Scholar 

  • Cherny RA, Legg JT, McLean CA, Fairlie DP, Huang X, Atwood CS, Beyreuther K, Tanzi RE, Masters CL, Bush AI . 1999 Aqueous dissolution of Alzheimer's disease abeta amyloid deposits by biometal depletion J. Biol. Chem. 274: 23223–23228

    CAS  PubMed  Google Scholar 

  • Cordano A . 1998 Clinical manifestation of nutritional copper deficiency in infants and children Am. J. Clin. Nutr. 67: (Suppl): 1012S–1016S

    CAS  PubMed  Google Scholar 

  • Cordano A, Graham GG . 1966 Copper deficiency complicating severe chronic intestinal malabsorption Pediatrics 38: 506–604

    Google Scholar 

  • Crampton RF, Matthews DM, Poisner R . 1965 Observations on the mechanism of absorption of copper by small intestine J. Physiol. 178: 111–126

    CAS  PubMed  PubMed Central  Google Scholar 

  • Danks DM . 1991 Copper and liver disease Eur. J. Pediatr. 50: 142–148

    Google Scholar 

  • Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt B, Roos RP, Warner C, Deng G, Soriano E, Smyth C, Parge HE, Ahmed A, Roses AD, Hallewell RA, Pericak-Vance MA, Siddique T . 1993 Amylotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase Science 261: 1047–1051

    CAS  PubMed  Google Scholar 

  • Deutsche Gesellschaft für Ernährung (DGE). 2000 Referenzwerte für die Nährstoffzufuhr Frankfurt: Umschau

  • Dieter HH . 1995 Risikoquantifizierung: Abschätzungen, Unsicherheiten und Gefahrenbezug Bundesgesundh. bl. 38: 250–257

    Google Scholar 

  • Dieter HH, Schimmelpfennig W, Meyer E, Tabert M . 1999 Early Childhood Cirrhosis (ECC) in Germany between 1982 and 1994 with Special Consideration of Copper Etiology Eur. J. Med. Res. 4: 233–242

    CAS  PubMed  Google Scholar 

  • Dijkstra M, Vonk RJ, Kuipers F . 1996 How does copper get into bile? New insights into the mechanism(s) of hepatobiliary copper transport J. Hepatol. 24: 109–120

    CAS  PubMed  Google Scholar 

  • Dörner K, Dziadzka S, Hohn A . 1989 Longitudinal manganese and copper balances in young infants and preterm infants fed on breastmilk and adapted cow's milk formulas Br. J. Nutr. 61: 559–572

    PubMed  Google Scholar 

  • Dubick MA, Zidenberg-Cherr S, Rucker RB, Keen CL . 1988 Superoxide dismutase activity in lung from copper and manganese-deficient mice exposed to ozone Toxicol. Lett. 42: 149–154

    CAS  PubMed  Google Scholar 

  • Ehrenkranz RA, Gettner PA, Nelli CM . 1989 Zinc and copper nutritional studies in very low birth weight infants: comparison of stable isotopic extrinsic tag and chemical balance methods Pediatr. Res. 26: 298–307

    CAS  PubMed  Google Scholar 

  • Elmadfa I, Burger P, Derndorfer E, Kiefer I, Kunze M, König J, Leimüller G, Manafi M, Mecl M, Papathanasiou V, Rust P . 1999 Österreichischer Ernährungsbericht 1998 Wien: Bundesministerium für Gesundheit, Arbeit und Soziales und Bundesministerium für Frauenangelegenheiten und Verbraucherschutz

    Google Scholar 

  • Epstein O . 1983 Liver copper in health and disease Postgrad. Med. J. 59: (Suppl): 88–94

    PubMed  Google Scholar 

  • Evans PJ, Bomford A, Halliwell B . 1998 Non-coeruloplasmin copper in human serum, does it exist? Abstract on behalf of the 5th Meeting of the European Copper Research Group Kinsale, Ireland 28–29 April

  • Ferrante RJ, Browne SE, Shinobu LA, Bowling AC, Baik MJ, MacGarvey U, Kowall NW, Brown RH Jr Beal MF . 1997 Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis J. Neurochem. 69: 2064–2074

    CAS  PubMed  Google Scholar 

  • Fleming CR . 1989 Trace element metabolism in adult patients requiring total parenteral nutrition Am. J. Clin. Nutr. 49: 573–579

    CAS  PubMed  Google Scholar 

  • Fransson G-B, Lönnerdal B . 1983 Distribution of trace elements and minerals in human and cow's milk Pediatr. Res. 17: 912–915

    CAS  PubMed  Google Scholar 

  • Freedman JH, Ciriolo MR, Peisach J . 1989 The role of glutathione in copper metabolism and toxicity J. Biol. Chem. 264: 5598–5605

    CAS  PubMed  Google Scholar 

  • Gittlin JD . 1998 Review: aceruloplasminemia Pediat. Res. 44: 271–276

    Google Scholar 

  • Goldstein S, Czapsky G . 1986 The role and mechanism of metal ions and their complexes in enhancing damage in biological systems or in protecting these systems from the toxicity of O2 J. Free Radic. Biol. Med. 2: 3–11

    CAS  PubMed  Google Scholar 

  • Goldfischer S, Sternlieb I . 1968 Changes in the distribution of hepatic copper in relation to the progression of Wilson's disease (hepatolenticular degeneration) Am. J. Pathol. 53: 883–901

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goyers P, Brasseur D, Cadranel S . 1985 Copper deficiency in infants with active celiac disease J. Pediatr. Gastroenterol. Nutr. 4: 677–680

    Google Scholar 

  • Gutteridge JM . 1980 Iron–oxygen reactions and their use in clinical chemistry Med. Lab. Sci. 37: 267–273

    CAS  PubMed  Google Scholar 

  • Gutteridge JM . 1994 Hydroxyl radicals, iron, oxidative stress, and neurodegeneration Ann. N.Y. Acad. Sci. 738: 201–213

    CAS  PubMed  Google Scholar 

  • Gutteridge JMC . 1984 Copper-phentroline induced site specific oxygen radical damage to DNA. Detection of loosely bound trace copper in biological fluids Biochem. J. 218: 983–985

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hadorn HB . 1999 Copper-associated liver diseases in children. Proceedings of the 4th Emma-Thaler-Symposium (Introduction) Eur. J. Med. Res. 4: 212–213

    CAS  PubMed  Google Scholar 

  • Hall AC, Young BW, Bremner I . 1979 Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat J. Inorg. Biochem. 11: 57–66

    CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JM . 1985 The importance of free radicals and catalytic metal ions in human diseases Mol. Asp. Med. 8: 89–193

    CAS  Google Scholar 

  • Halliwell B, Gutteridge JM . 1990 Role of free radicals and catalytic metal ions in human disease: an overview Meth. Enzymol. 186: 1–85

    CAS  PubMed  Google Scholar 

  • Harris ED . 1991 Copper transport: an overview Proc. Soc. Exp. Biol. Med. 196: 130–140

    CAS  PubMed  Google Scholar 

  • He J, Tell GS, Tang Y-C, Mo P-S, He G-Q . 1992 Relation of serum zinc and copper to lipids and lipoproteins: the Yi people study J. Am. Coll. Nutr. 11: 74–78

    CAS  PubMed  Google Scholar 

  • Hesse L, Beher D, Masters CL, Multhaup G . 1994 The beta A4 amyloid precursor protein binding to copper F.E.B.S. Lett. 349: 109–116

    CAS  Google Scholar 

  • Hillman LS . 1981 Serial serum copper concentrations in premature and SGA infants during the first three month of life J. Pediatr. 98: 305–308

    CAS  PubMed  Google Scholar 

  • Hornshaw MP, McDermott JR, Candy JM, Lakey JH . 1995 Copper binding to the N-terminal tandem repeate region of mammalian and avian prion protein: structural studies using synthetic peptides Biochem. Biophys. Res. Commun. 214: 993–999

    CAS  PubMed  Google Scholar 

  • Hurley LS, Keen CL . 1979 Teratogenic effects of copper In Copper in the Environment. Part II: Health Effects ed. JO Nriagu 33–56 New York: John Wiley

    Google Scholar 

  • Johnson PE, Milne DB, Lykken GI . 1992 Effects of age and sex on copper absorption, biological half-life, and status in humans Am. J. Clin. Nutr. 56: 917–925

    CAS  PubMed  Google Scholar 

  • Joo S-J, Betts NM . 1996 Copper intakes and consumption patterns of chocolate foods as sources of copper for individuals in the 1987–88 nationwide food consumption survey Nutr. Res. 16: 41–52

    CAS  Google Scholar 

  • Kardos J, Kovacs I, Hajos F, Kalman M, Simonyi M . 1989 Nerve endings from rat brain tissue release copper upon depolarization. A possible role in regulation neuronal excitability Neurosci. Lett. 103: 139–144

    CAS  PubMed  Google Scholar 

  • Keen CL, Uriu-Hare JY, Hawk SN, Jankowski MA, Daston GP, Kwik-Uribe CL, Rucker RB . 1998 Effect of copper deficiency on prenatal development and pregnancy outcome Am. J. Clin. Nutr. 67: (Suppl): 1003S–1011S

    CAS  PubMed  Google Scholar 

  • Kehoe CA, Turley E, Bonham MP, O'Connor JM, McKeown A, Faughnan MS, Coulter JS, Gilmore WS, Howard AN, Strain JJ . 2000 Response of putative indices of copper status to copper supplementation in human subjects Br. J. Nutr. 84: 151–156

    CAS  PubMed  Google Scholar 

  • Kelley DS, Daudu PA, Taylor PC, Mackey BE, Turnlund JR . 1995 Effects of low-copper diets on human immune response Am. J. Clin. Nutr. 62: 412–416

    CAS  PubMed  Google Scholar 

  • Kimberlin RH, Millson GC, Bountiff L, Collis SC . 1974 A comparison of the biochemical changes induced in mouse brain cuprizone toxicity and by scrapie infection J. Comp. Pathol. 84: 263–270

    CAS  PubMed  Google Scholar 

  • Klein D, Lichtmannegger J, Heinzmann U, Müller-Höcker J, Michaelsen S, Summer KH . 1998 Association of copper to metallothionein in hepatic lysosomes of Long-Evans cinnamon (LEC) rats during the development of hepatitis Eur. J. Clin. Invest. 28: 302–310

    CAS  PubMed  Google Scholar 

  • Klevay LM . 1975 Coronary heart disease: the zinc/copper hypo-thesis Am. J. Clin. Nutr. 28: 764–774

    CAS  PubMed  Google Scholar 

  • Klevay LM . 1980 Interactions of copper and zinc in cardiovascular disease Ann. N.Y. Acad. Sci. 355: 140–151

    CAS  PubMed  Google Scholar 

  • Klevay LM . 1985 Atrial thrombosis, abnormal electrocardiograms and sudden death in mice due to copper deficiency Atherosclerosis 54: 213–224

    CAS  PubMed  Google Scholar 

  • Klevay LM . 1993 Ischaemic heart disease: nutrition or pharmacotherapy J. Trace Elem. Electr. Health Dis. 7: 63–69

    CAS  Google Scholar 

  • Klevay LM, Inman I, Johnson LK, Lawler M, Milne DB, Lukaski HC, Bolonchuk W, Sandstead HH . 1984 Increased cholesterol in plasma in a young man during experimental copper depletion Metabolism 33: 1112–1118

    CAS  PubMed  Google Scholar 

  • Kok FJ, Duijn CMV, Hofman A, Voet GBVD, Wolff FAD, Paays CHC, Valkenburg HA . 1988 Serum copper and zinc and the risk of death from cancer and cardiovascular disease Am. J. Epidemiol. 128: 352–359

    CAS  PubMed  Google Scholar 

  • König JS, Elmadfa I . 1993 Copper status in Austrian school and Kindergarten children at the age of 4–19 years. In Proceedings of the Eighth International Symposium on Trace Elements in Man and Animals—TEMA-8, ed. M Anke, 896–897 Dresden

  • Lai CC, Huang WH, Klevay L, Gunning WT III Chiu TH . 1996 Antioxidant enzyme gene transcription in copper-deficient rat liver Free Rad. Biol. Med. 21: 233–240

    CAS  PubMed  Google Scholar 

  • Lee SH, Lancey R, Montaser A, Madani N, Linder MC . 1993 Ceruloplasmin and copper transport during the latter part of gestation in the rat Proc. Soc. Exp. Biol. Med. 203: 428–439

    CAS  PubMed  Google Scholar 

  • Lin SJ, Culotta VC . 1995 The ATX1 gene of Saccharomyces cervesiae encodes a small homeostatic factor that protects cells against reactive oxygen toxicity Proc. Natl. Acad. Sci. USA 92: 3784–3788

    CAS  PubMed  Google Scholar 

  • Linder MC . 1991 The Biochemistry of Copper New York: Plenum Press

    Google Scholar 

  • Linder MC, Hazegh-Azam M . 1996 Copper biochemistry and molecular biology Am. J. Clin. Nutr. 63: 797S–811S

    CAS  PubMed  Google Scholar 

  • Liu R, Althaus JS, Ellerbrock BR, Becker DA, Gurney ME . 1998 Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis Ann. Neurol. 44: 763–770

    CAS  PubMed  Google Scholar 

  • Liu Y, Liu J, Iszard MB, Andrews GK, Palmiter RD, Klaassen CD . 1995 Transgenic mice that over-express metallothionein-1 are protected from cadmium lethality and toxicity Toxicol. Appl. Pharmac. 135: 222–228

    CAS  Google Scholar 

  • Lönnerdal B . 1998 Copper nutrition during infancy and childhood Am. J. Clin. Nutr. 67: (Suppl): 1046S–1053S

    PubMed  Google Scholar 

  • Lönnerdal B, Bell JG, Keen CL . 1985 Copper absorption from human milk, cow's milk and infant formulas using a suckling rat model Am. J. Clin. Nutr. 42: 836–844

    PubMed  Google Scholar 

  • Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR . 1998 Copper, iron and zinc in Alzheimer's disease senile plaques J. Neurol. Sci. 158: 47–52

    CAS  PubMed  Google Scholar 

  • Ma J, Betts NM . 2000 Zinc and copper intakes and their food sources for older adults in the 1994–96 continuing survey of food intakes by individuals (CSFII) J. Nutr. 130: 2838–2843

    CAS  PubMed  Google Scholar 

  • Mc Ardle HJ . 1995 The metabolism of copper during pregnancy—a review Food Chem. 54: 79–84

    CAS  Google Scholar 

  • McKenzie D, Bartz J, Mirwald J, Olander D, Marsh R, Aiken J . 1998 Reversibility of scrapie inactivation is enhanced by copper J. Biol. Chem. 273: 25545–25547

    CAS  PubMed  Google Scholar 

  • Manthey J, Stoeppler M, Morgenstern W, Nussel E, Opherk D, Weintraut A, Wesch H, Kubler W . 1981 Magnesium and trace metals: risk factors for coronary heart disease? Associations between blood levels and angiographic findings Circulation 64: 722–729

    CAS  PubMed  Google Scholar 

  • Markesbery WR, Carney JM . 1999 Oxidative alterations in Alzheimer's disease Brain Pathol. 9: 133–146

    CAS  PubMed  Google Scholar 

  • Mason R, Bakka A, Samarawickrama GP, Webb M . 1981 Metabolism of zinc and copper in the neonate: accumulation and function of (Zn-Cu)-metallothionein in the liver of the newborn rat Br. J. Nutr. 45: 375–389

    CAS  PubMed  Google Scholar 

  • Masuoka J, Hegenauer J, Van Dyke BR, Saltman P . 1993 Intrinsic stoichometric equilibrium constants for the binding of zinc (II) and copper (II) to the high affinity site of serum albumin J. Biol. Chem. 268: 21533–21537

    CAS  PubMed  Google Scholar 

  • Matzuk MM, Dionne L, Guo Q, Kumar TR, Lebovitz RM . 1998 Ovarian function in superoxide dismutase 1 and 2 knockout mice Endocrinology 139: 4008–4011

    CAS  PubMed  Google Scholar 

  • Merz PA, Somerville RA, Wisniewski HM, Iqbal K . 1981 Abnormal fibrills from scrapie-infected brain Acta Neuropathol. 54: 63–74

    CAS  PubMed  Google Scholar 

  • Mills CF, Williams RB . 1962 Copper concentrations and cytochrome-oxidase and ribonuclease activities in the brains of copper deficient lambs Biochem. J. 85: 629–632

    CAS  PubMed  PubMed Central  Google Scholar 

  • Milne DB . 1994 Assessment of copper nutritional status Clin. Chem. 40: 1479–1484

    CAS  PubMed  Google Scholar 

  • Milne DB, Johnson PE . 1993 Assessment of copper status: effect of age and gender on reference ranges in healthy adults Clin. Chem. 39: 883–887

    CAS  PubMed  Google Scholar 

  • Milne DB, Nielsen FH . 1996 Effects of a diet low in copper on copper-status indicators in postmenopausal women Am. J. Clin. Nutr. 63: 358–364

    CAS  PubMed  Google Scholar 

  • Miura T, Horii A, Takeuchi H . 1996 Metal-dependent alpha-helix formation promoted by the glycine-rich octapeptide region of prion protein F.E.B.S. Lett. 396: 248–252

    CAS  Google Scholar 

  • Morris ER, Ellis R, Steele P, Moser PB . 1988 Mineral balance of adult men consuming whole or dephytinized wheat bran Nutr. Res. 8: 445–458

    Google Scholar 

  • Morton MS, Elwood PC, Abermethy M . 1976 Trace elements in water and congenital malformation of the central nervous system in South Wales Br. J. Prev. Soc. Med. 30: 36–39

    CAS  PubMed  PubMed Central  Google Scholar 

  • Multhaup G . 1997 Amyloid precursor protein, copper and Alzheimer's disease Biomed. Pharmacother. 51: 105–111

    CAS  PubMed  Google Scholar 

  • Multhaup G, Schlicksupp A, Hesse L, Beher D, Ruppert T, Masters CL, Beyreuther K . 1996 The amyloid precursor protein of Alzheimer's disease in the reduction of copper (II) to copper (I) Science 271: 1406–1409

    CAS  PubMed  Google Scholar 

  • Multhaup G, Ruppert T, Schlicksupp A, Hesse L, Beher D, Masters CL, Beyreuther K . 1997 Reactive oxygen species and Alzheimer's disease Biochem. Pharmac. 54: 533–539

    CAS  Google Scholar 

  • Multhaup G, Ruppert T, Schlicksupp A, Hesse L, Bill E, Pipkorn R, Masters CL, Bayreuther K . 1998 Copper-binding amyloid precursor protein undergoes a site-specific fragmentation in the reduction of hydrogen peroxide Biochemistry 37: 7224–7230

    CAS  PubMed  Google Scholar 

  • Multhaup G, Hesse L, Borchardt T, Ruppert T, Cappai R, Masters CL, Beyreuther K . 1999 Autoxidation of amyloid precursor protein and formation of reactive oxygen species Adv. Exp. Med. Biol. 448: 183–192

    CAS  PubMed  Google Scholar 

  • Nagano K, Nakamura K, Urakami KL, Umeyama H, Koiwai K, Hattori S, Yamanato Tmatsuda I, Endo F . 1998 Intracellular distribution of the Wilson's disease gene product (ATPase 7B) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat: an animal model of Wilson's disease Hepatology 27: 799–807

    CAS  PubMed  Google Scholar 

  • Nakamura K, Endo F, Ueno T, Awata H, Tanoue A, Matsuda I . 1995 Excess cooper and ceruloplasmin biosynthesis in long-term cultured hepatocytes from Long-Evans cinnamon (LEC) rat, a model of Wilson disease J. Biol. Chem. 270: 7656–7660

    CAS  PubMed  Google Scholar 

  • National Research Council (NRC). 1989 Recommended Dietary Allowances Washington, DC: National Academy of Sciences

  • O'Donohue JW, Reid MA, Varghese A, Portmann B, Williams R . 1993 Case report: Micronodular cirrhosis and acute liver failure due to chronic copper self-intoxication Eur. J. Gastroenterol. Hepatol. 5: 561–562

    Google Scholar 

  • Okada A . 1994 Copper deficiency with pancytopenia during total parenteral nutrition J. Parenter. Enteral Nutr. 18: 190–192

    Google Scholar 

  • Olivares M, Pizarro F, Speisky H, Lönnerdal B, Uauy R . 1998 Copper in infant nutrition: Safety of World Health Organization Provisional Guideline Value for copper content of drinking water J. Pediat. Gastroenterol. Nutr. 26: 251–257

    CAS  Google Scholar 

  • Pattison IH, Clarke MC, Haig DA, Jebbett JN . 1971 Brain cell cultures from mice affected with scrapie or fed with cuprizone Res. Vet. Sci. 12: 478–480

    CAS  PubMed  Google Scholar 

  • Pauly PC, Harris DA . 1998 Copper stimulates endocytosis of the prion protein J. Biol. Chem. 273: 33107–33110

    CAS  PubMed  Google Scholar 

  • Pedraza-Chaveri J, Torres-Rodriguez GA, Cruz C . 1994 Copper and zinc metabolism in amino nucleoside-induced nephrotic syndrome Nephron. 92: 87–92

    Google Scholar 

  • Pena MM, Lee OJ, Thiele DJ . 1999 A delicate balance: homeostatic control of copper uptake and distribution J. Nutr. 129: 1251–1260

    CAS  PubMed  Google Scholar 

  • Pettersson R, Rasmussen F . 1999 Daily intake of copper from drinking water among young children in Sweden Environ. Health Persp. 107: 441–446

    CAS  Google Scholar 

  • Quinlan GJ, Gutteridge JM . 1988 Oxidative damage to DNA and deoxyribose by beta-lactam antibiotics in the presence of iron and copper salts Free Rad. Res. Commun. 5: 149–158

    CAS  Google Scholar 

  • Raysiguier Y, Gueux E, Bussiere L, Mazur A . 1993 Copper deficiency increases the susceptibility of lipoproteins and tissues to peroxidation in rats J. Nutr. 123: 1343–1348

    Google Scholar 

  • Reaume AG, Elliott JL, Hoffmann EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH Jr, Scott RW, Snider WD . 1996 Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury Nature Genet. 13: 43–47

    CAS  PubMed  Google Scholar 

  • Reiser S, Smith JC Jr., Mertz W, Holbrook JT, Powell AS, Canfield WK, Canary JJ . 1985 Indices of copper status in humans consuming a typical American diet containing either fructose or starch Am. J. Clin. Nutr. 42: 242–251

    CAS  PubMed  Google Scholar 

  • Reiser K, McCormick RJ, Rucker RB . 1992 Enzymatic and nonenzymatic cross-linking of collagen and elastin F.A.S.E.B. J. 6: 2439–2449

    CAS  Google Scholar 

  • Rock E, Gueux E, Mazur A, Motta C, Rayssiguier Y . 1995 Anemia in copper-deficient rats: role of alterations in erythrocyte membrane fluidity and oxidative damage Am. J. Physiol. 269: C1245–C1249

    CAS  PubMed  Google Scholar 

  • Rodriguez A, Soto G, Torres S, Venegas G, Castillo-Duran C . 1985 Zinc and copper in hair and plasma of children with chronic diarrhea Acta Paediatr. Scand. 74: 770–774

    CAS  PubMed  Google Scholar 

  • Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O Regan JP, Deng HX, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, Van den Bergh R, Hung WY, Bird T, Deng G, Mulder DW, Smyth C, Laing NG, Soriano E, Pericak-Vance MA, Haines J, Rouleau GA, Gusella JS, Horovitz HR, Brown RH Jr. 1993 Mutation in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis Nature 362: 59–62

    CAS  PubMed  Google Scholar 

  • Saari JT . 1992 Dietary copper deficiency and endothelium-dependent relaxation of rat aorta Proc. Soc. Exp. Biol. Med. 200: 19–24

    CAS  PubMed  Google Scholar 

  • Sable-Amplis R, Sicart R, Reynier B . 1987 Apparent retention of copper, zinc and iron in hamster. Influence of a fruit-enriched diet Nutr. Rep. Int. 35: 811–818

    CAS  Google Scholar 

  • Sachdev HPS, Mittal NK, Yadan HS . 1989 Serum and rectal mucosal copper status in acute and chronic diarrhea J. Pediatr. Gastroenterol. Nutr. 8: 212–216

    CAS  PubMed  Google Scholar 

  • Salmenperä L, Siimes MA, Näntö V, Perheentupa J . 1989 Copper supplementation: failure to increase plasma copper and coeruloplasmin concentrations in healthy infants Am. J. Clin. Nutr. 50: 843–847

    PubMed  Google Scholar 

  • Sann L, Rigal D, Galy G, Benvenu F, Bourgeois J . 1980 Serum copper and zinc concentrations in prematures and small for date infants Pediatr. Res. 14: 1041–1046

    Google Scholar 

  • Schuschke DA . 1997 Dietary copper in the physiology of the microcirculation J. Nutr. 127: 2274–2281

    CAS  PubMed  Google Scholar 

  • Schuschke DA, Reed MWR, Saari JT, Miller FN . 1992 Copper deficiency alters vasodilation in white rat cremaster muscle microcirculation J. Nutr. 122: 1547–1552

    CAS  PubMed  Google Scholar 

  • Scientific Committee on Food (SCF) . 1994 Nährstoff- und Energiezufuhr in der Europäischen Gemeinschaft (Stellungnahme vom 11. Dezember 1992). Ber. wiss. Lebensmittelausschusses, ed. Europäische Kommission, 31. Folge. Amt f. amtl. Veröff. Eur. Gem. Luxemburg

    Google Scholar 

  • Selkoe DJ . 1998 The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease Trends Cell Biol. 8: 447–453

    CAS  PubMed  Google Scholar 

  • Sethi S, Grover S, Khodaskar MB . 1993 Role of copper in Indian childhood cirrhosis Ann. Trop. Pediat. 13: 3–6

    CAS  Google Scholar 

  • Shakespeare PG . 1982 Studies on the serum levels of iron, copper and zinc and urinary excretion of zinc after burn injury Burns Incl. Therm. Inj. 8: 358–364

    CAS  PubMed  Google Scholar 

  • Shaw JCL . 1992 Copper deficiency in term and preterm infants In Nutritional Anemias ed. SJ Fomon & S, Zlotkin New York: Raven Press Nestle Nutrition Workshop Series 30: 105–109

    Google Scholar 

  • Shenkin A, Fraser WD, Mclalland JD, Fell GS, Garden OJ . 1987 Maintainance of vitamin and trace element status in intravenous nutrition using a complete nutritive mixture J. Parenter. Enter. Nutr. 11: 238–242

    CAS  Google Scholar 

  • Shike M . 1984 Copper in parenteral nutrition Bull. N.Y. Acad. Med. 60: 132–143

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shike M, Roulet M, Kurian R, Jeejeebhoy K . 1981 Copper metabolism and requirements in total parenteral nutrition Gastroenterology 81: 290–297

    CAS  PubMed  Google Scholar 

  • Shulman RJ . 1989 Zinc and copper balance studies in infants requiring total parenteral nutrition Am. J. Clin. Nutr. 49: 879–883

    CAS  PubMed  Google Scholar 

  • Simons M, Ikonen E, Tienari PJ, Cidarregui A, Monning U, Beyreu-ther K, Dotti CG . 1995 Intracellular routing of human amyloid protein precursor: axonal delivery followed by transport to the dendrites J. Neurosci. Res. 41: 121–128

    CAS  PubMed  Google Scholar 

  • Simons M, de Strooper B, Multhaup G, Tienari PJ, Dotti CG, Beyreuther K . 1996 Amyloidogenic processing of the human precursor protein in primary cultures of rat hippocampal neurons J. Neurosci. 16: 899–908

    CAS  PubMed  Google Scholar 

  • Spitalny KC, Brondum J, Vogt RL, Sargent HE, Kappel S . 1984 Drinking-water-induced copper intoxication in a Vermont family Pediatrics 74: 1103–1106

    CAS  PubMed  Google Scholar 

  • Stöckel J, Safar J, Wallace AC, Cohen FE, Prusiner SB . 1998 Prion protein selectively binds copper(II) ions Biochemistry. 37: 7185–7193

    PubMed  Google Scholar 

  • Strain JJ . 1994 Newer aspects of micronutrients in chronic disease: copper Proc. Nutr. Soc. 53: 583–598

    CAS  PubMed  Google Scholar 

  • Sukalski KA, LaBerge TP, Johnson WT . 1997 In vivo oxidative modification of erythrocyte membrane proteins in copper deficiency Free Rad. Biol. Med. 22: 835–842

    CAS  PubMed  Google Scholar 

  • Tanner MS . 1998 Role of copper in Indian childhood cirrhosis Am. J. Clin. Nutr. 67: (Suppl): 1074S–1081S

    CAS  PubMed  Google Scholar 

  • Thornalley PJ, Vasak M . 1985 Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals Biochim. Biophys. Acta 827: 36–44

    CAS  PubMed  Google Scholar 

  • Turnlund JR . 1991 Bioavailability of dietary minerals to humans: the stable isotope approach Crit. Rev. Food Sci. Nutr. 30: 387–396

    CAS  PubMed  Google Scholar 

  • Turnlund JR, King JC, Gong B, Keyes WR, Michel MC . 1985 A stable isotope study of copper absorption in young men: effect of phytate and cellulose Am. J. Clin. Nutr. 42: 18–23

    CAS  PubMed  Google Scholar 

  • Turnlund JR, Keen CL, Smith RG . 1990 Copper status and urinary and salivary copper in young men at three levels of dietary copper Am. J. Clin. Nutr. 51: 658–664

    CAS  PubMed  Google Scholar 

  • Underwood EJ . 1977 Trace Elements in Human and Animal Nutrition 4th edn New York: Academic Press 56–108

    Google Scholar 

  • Varada KR, Harper RG, Wapnir RA . 1993 Development of copper intestinal absorption in the rat Biochem. Med. Metab. Biol. 50: 277–283

    CAS  PubMed  Google Scholar 

  • Vergara JD, Zietz B, Dunkelberg H . 2000 Gesundheitliche Gefährdung ungestillter Säuglinge durch Kupfer in Haushalten mit kupfernen Trinkwasserleitungen. Erste Ergebnisse einer prospektiven Studie Bundesgesundheitsbl. Gesundheitsforsch. Gesundheitsschutz 43: 272–278

    Google Scholar 

  • Wadsworth JD, Jackson GS, Hill AF, Collinge J . 1999 Molecular biology of prion propagation Curr. Opin. Genet. Devl. 9: 338–345

    CAS  Google Scholar 

  • Wang X, Manganaro F, Schipper HM . 1995 A cellular stress model for the sequestration of redox-active glial iron in the ageing and degenerating nervous system J. Neurochem. 64: 1868–1877

    CAS  PubMed  Google Scholar 

  • Wapnir RA . 1991 Copper-sodium linkage during intestinal absorption: inhibition by amyloride Proc. Soc. Exp. Biol. Med. 196: 410–414

    CAS  PubMed  Google Scholar 

  • Wapnir RA, Devas G . 1995 Copper deficiency: interaction with high fructose and high fat diets in rats Am. J. Clin. Nutr. 61: 105–110

    CAS  PubMed  Google Scholar 

  • Weiss KC, Linder MC . 1985 Copper transport in rats involving a new plasma protein Am. J. Physiol. 249: E77–E88

    CAS  PubMed  Google Scholar 

  • White AR, Reyes R, Mercer JFB, Camakaris J, Zheng H, Bush AI, Multhaup G, Beyreuther K, Masters CL, Cappai R . 1999 Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice Brain Res. 842: 439–444

    CAS  PubMed  Google Scholar 

  • WHO. 1993 WHO Guidelines for Drinking Water Quality, 2nd edn, Addendum to Vol 1 (Recommendations) Geneva: WHO 6–7

  • WHO. 1996 Trace Elements in Human Nutrition and Health Geneva: World Health Organization

  • WHO. 1998 Copper. Environmental Health Criteria 2000 Geneva: World Health Organization

  • Widdowson EM, Dancey J, Shaw JLC . 1974 Trace elements in foetal and early postnatal development Proc. Nutr. Soc. 33: 275–284

    CAS  PubMed  Google Scholar 

  • Wiedau-Pazos M, Goto JJ, Rabizadeh S, Gralla EB, Roe JA, Lee MK, Valentine JS, Bredesen DE . 1996 Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis Science 271: 515–518

    CAS  PubMed  Google Scholar 

  • Williams DR . 1983 Historical outline of the biological importance of trace metals J. Inherit. Metab. Dis. 6: (Suppl 1): 1–4

    CAS  PubMed  Google Scholar 

  • Williamson TL, Cleveland DW . 1999 Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons Nature Neurosci. 2: 50–56

    CAS  PubMed  Google Scholar 

  • Yount NY, Mc Namara DJ, Al-Othman AA, Lei KY . 1990 The effect of copper deficiency on rat hepatic 3-hydroxy-3-methylglutaryl co-enzyme A reductase activity J. Nutr. Biochem. 1: 27–33

    Google Scholar 

Download references

Author information

Author notes

  1. K Schümann: Guarantor: S Truswell.

  2. HK Biesalski: Contributors: HK Biesalski.

Authors and Affiliations

  1. Walther-Straub-Institut für Pharmakologie und Toxikologie der LMU, München, Germany

    K Schümann

  2. Institute of Biochemistry and Nutrition, Hohenheim University, Stuttgart, Germany

    HG Classen, J Bernhardt & HK Biesalski

  3. Umweltbundesamt, WABOLU, Berlin, Germany

    HH Dieter

  4. Institut für Ernährunswissenschaft der Universität Wien, Vienna, Austria

    J König

  5. ZMBH-Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany

    G Multhaup

  6. Katharinenhospital, Stuttgart, Germany

    M Rükgauer

  7. GSF, München, Germany

    KH Summer

Authors
  1. K Schümann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. HG Classen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. HH Dieter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J König
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G Multhaup
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Rükgauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. KH Summer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Bernhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. HK Biesalski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to HK Biesalski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schümann, K., Classen, H., Dieter, H. et al. Hohenheim Consensus Workshop: Copper. Eur J Clin Nutr 56, 469–483 (2002). https://doi.org/10.1038/sj.ejcn.1601315

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601315

Keywords

This article is cited by

Search

Advanced search

Quick links