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Micronutrient Information Center

References: Copper


1.  Linder MC, Hazegh-Azam M. Copper biochemistry and molecular biology. Am J Clin Nutr. 1996;63(5):797S-811S.  (PubMed)

2.  Turnlund JR. Copper. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2006:286-299.

3.  Prohaska JR. Copper. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Ames: Wiley-Blackwell; 2012:540-553.

4.  Prohaska JR. Impact of copper limitation on expression and function of multicopper oxidases (ferroxidases). Adv Nutr. 2011;2(2):89-95.  (PubMed)

5.  Uauy R, Olivares M, Gonzalez M. Essentiality of copper in humans. Am J Clin Nutr. 1998;67(5 Suppl):952S-959S.  (PubMed)

6.  Vashchenko G, MacGillivray RT. Multi-copper oxidases and human iron metabolism. Nutrients. 2013;5(7):2289-2313.  (PubMed)

7.  Meyer LA, Durley AP, Prohaska JR, Harris ZL. Copper transport and metabolism are normal in aceruloplasminemic mice. J Biol Chem. 2001;276(39):36857-36861.  (PubMed)

8.  Harris ZL, Durley AP, Man TK, Gitlin JD. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci U S A. 1999;96(19):10812-10817.  (PubMed)

9.  Kono S. Aceruloplasminemia. Curr Drug Targets. 2012;13(9):1190-1199.  (PubMed)

10.  Thackeray EW, Sanderson SO, Fox JC, Kumar N. Hepatic iron overload or cirrhosis may occur in acquired copper deficiency and is likely mediated by hypoceruloplasminemia. J Clin Gastroenterol. 2011;45(2):153-158.  (PubMed)

11.  Harris ED. Copper. In: O'Dell BL, Sunde RA, eds. Handbook of nutritionally essential minerals. New York: Marcel Dekker, Inc; 1997:231-273.

12.  Johnson MA, Fischer JG, Kays SE. Is copper an antioxidant nutrient? Crit Rev Food Sci Nutr. 1992;32(1):1-31.

13.  Mattie MD, McElwee MK, Freedman JH. Mechanism of copper-activated transcription: activation of AP-1, and the JNK/SAPK and p38 signal transduction pathways. J Mol Biol. 2008;383(5):1008-1018.  (PubMed)

14.  Videt-Gibou D, Belliard S, Bardou-Jacquet E, et al. Iron excess treatable by copper supplementation in acquired aceruloplasminemia: a new form of secondary human iron overload? Blood. 2009;114(11):2360-2361.  (PubMed)

15. Food and Nutrition Board, Institute of Medicine. Copper. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, D.C.: National Academy Press; 2001:224-257. (National Academy Press)

16.  Guo CH, Wang CL. Effects of zinc supplementation on plasma copper/zinc ratios, oxidative stress, and immunological status in hemodialysis patients. Int J Med Sci. 2013;10(1):79-89.  (PubMed)

17.  Milne DB, Omaye ST. Effect of vitamin C on copper and iron metabolism in the guinea pig. Int J Vitam Nutr Res. 1980;50(3):301-308.  (PubMed)

18.  Finley EB, Cerklewski FL. Influence of ascorbic acid supplementation on copper status in young adult men. Am J Clin Nutr. 1983;37(4):553-556.  (PubMed)

19.  Jacob RA, Skala JH, Omaye ST, Turnlund JR. Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. J Nutr. 1987;117(12):2109-2115.  (PubMed)

20.  Harris ZL, Klomp LW, Gitlin JD. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am J Clin Nutr. 1998;67(5 Suppl):972S-977S.  (PubMed)

21.  Bustos RI, Jensen EL, Ruiz LM, et al. Copper deficiency alters cell bioenergetics and induces mitochondrial fusion through up-regulation of MFN2 and OPA1 in erythropoietic cells. Biochem Biophys Res Commun. 2013;437(3):426-432.  (PubMed)

22.  Peled T, Landau E, Prus E, Treves AJ, Nagler A, Fibach E. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood-derived CD34+ cells. Br J Haematol. 2002;116(3):655-661.  (PubMed)

23.  Lazarchick J. Update on anemia and neutropenia in copper deficiency. Curr Opin Hematol. 2012;19(1):58-60.  (PubMed)

24.  Shaw JC. Copper deficiency and non-accidental injury. Arch Dis Child. 1988;63(4):448-455.  (PubMed)

25.  Blackmer AB, Bailey E. Management of copper deficiency in cholestatic infants: review of the literature and a case series. Nutr Clin Pract. 2013;28(1):75-86.  (PubMed)

26.  Best K, McCoy K, Gemma S, Disilvestro RA. Copper enzyme activities in cystic fibrosis before and after copper supplementation plus or minus zinc. Metabolism. 2004;53(1):37-41.  (PubMed)

27.  Rowin J, Lewis SL. Copper deficiency myeloneuropathy and pancytopenia secondary to overuse of zinc supplementation. J Neurol Neurosurg Psychiatry. 2005;76(5):750-751.  (PubMed)

28.  Nations SP, Boyer PJ, Love LA, et al. Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease. Neurology. 2008;71(9):639-643.  (PubMed)

29.  Prodan CI, Bottomley SS, Holland NR, Lind SE. Relapsing hypocupraemic myelopathy requiring high-dose oral copper replacement. J Neurol Neurosurg Psychiatry. 2006;77(9):1092-1093.  (PubMed)

30.  Kumar N, Gross JB, Jr. Mutation in the ATP7A gene may not be responsible for hypocupraemia in copper deficiency myelopathy. Postgrad Med J. 2006;82(968):416.  (PubMed)

31.  Tumer Z. An overview and update of ATP7A mutations leading to Menkes disease and occipital horn syndrome. Hum Mutat. 2013;34(3):417-429.  (PubMed)

32.  Kodama H, Fujisawa C, Bhadhprasit W. Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. Curr Drug Metab. 2012;13(3):237-250.  (PubMed)

33.  Fox PL, Mazumder B, Ehrenwald E, Mukhopadhyay CK. Ceruloplasmin and cardiovascular disease. Free Radic Biol Med. 2000;28(12):1735-1744.  (PubMed)

34.  Jones AA, DiSilvestro RA, Coleman M, Wagner TL. Copper supplementation of adult men: effects on blood copper enzyme activities and indicators of cardiovascular disease risk. Metabolism. 1997;46(12):1380-1383.  (PubMed)

35.  Ford ES. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol. 2000;151(12):1182-1188.  (PubMed)

36.  Malek F, Jiresova E, Dohnalova A, Koprivova H, Spacek R. Serum copper as a marker of inflammation in prediction of short term outcome in high risk patients with chronic heart failure. Int J Cardiol. 2006;113(2):e51-53.  (PubMed)

37.  Leone N, Courbon D, Ducimetiere P, Zureik M. Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality. Epidemiology. 2006;17(3):308-314.  (PubMed)

38.  Kosar F, Sahin I, Acikgoz N, Aksoy Y, Kucukbay Z, Cehreli S. Significance of serum trace element status in patients with rheumatic heart disease: a prospective study. Biol Trace Elem Res. 2005;107(1):1-10.  (PubMed)

39.  Bertinato J, Zouzoulas A. Considerations in the development of biomarkers of copper status. J AOAC Int. 2009;92(5):1541-1550.  (PubMed)

40.  Klevay LM. Cardiovascular disease from copper deficiency--a history. J Nutr. 2000;130(2S Suppl):489S-492S.  (PubMed)

41.  Mielcarz G, Howard AN, Mielcarz B, et al. Leucocyte copper, a marker of copper body status is low in coronary artery disease. J Trace Elem Med Biol. 2001;15(1):31-35.  (PubMed)

42.  Kinsman GD, Howard AN, Stone DL, Mullins PA. Studies in copper status and atherosclerosis. Biochem Soc Trans. 1990;18(6):1186-1188.  (PubMed)

43. Wang XL, Adachi T, Sim AS, Wilcken DE. Plasma extracellular superoxide dismutase levels in an Australian population with coronary artery disease. Arterioscler Thromb Vasc Biol. 1998;18(12):1915-1921.  (PubMed)

44.  Klevay LM. Lack of a recommended dietary allowance for copper may be hazardous to your health. J Am Coll Nutr. 1998;17(4):322-326.  (PubMed)

45.  Milne DB, Nielsen FH. Effects of a diet low in copper on copper-status indicators in postmenopausal women. Am J Clin Nutr. 1996;63(3):358-364.  (PubMed)

46.  Medeiros DM, Milton A, Brunett E, Stacy L. Copper supplementation effects on indicators of copper status and serum cholesterol in adult males. Biol Trace Elem Res. 1991;30(1):19-35.  (PubMed)

47.  DiSilvestro RA, Joseph EL, Zhang W, Raimo AE, Kim YM. A randomized trial of copper supplementation effects on blood copper enzyme activities and parameters related to cardiovascular health. Metabolism. 2012;61(9):1242-1246.  (PubMed)

48.  Turley E, McKeown A, Bonham MP, et al. Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project). Free Radic Biol Med. 2000;29(11):1129-1134.  (PubMed)

49.  Rock E, Mazur A, O'Connor J M, Bonham MP, Rayssiguier Y, Strain JJ. The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers. Free Radic Biol Med. 2000;28(3):324-329.  (PubMed)

50.  Mansoor MA, Bergmark C, Haswell SJ, et al. Correlation between plasma total homocysteine and copper in patients with peripheral vascular disease. Clin Chem. 2000;46(3):385-391.  (PubMed)

51.  Celik C, Bastu E, Abali R, et al. The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome. Gynecol Endocrinol. 2013;29(5):488-491.  (PubMed)

52.  Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol. 1999;10(5):417-428.  (PubMed)

53.  Emsley AM, Jeremy JY, Gomes GN, Angelini GD, Plane F. Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta. Br J Pharmacol. 1999;126(4):1034-1040.  (PubMed)

54.  Shukla N, Angelini GD, Jeremy JY. Interactive effects of homocysteine and copper on angiogenesis in porcine isolated saphenous vein. Ann Thorac Surg. 2007;84(1):43-49.  (PubMed)

55.  Uthus EO, Reeves PG, Saari JT. Copper deficiency decreases plasma homocysteine in rats. J Nutr. 2007;137(6):1370-1374.  (PubMed)

56.  Wei H, Zhang WJ, McMillen TS, Leboeuf RC, Frei B. Copper chelation by tetrathiomolybdate inhibits vascular inflammation and atherosclerotic lesion development in apolipoprotein E-deficient mice. Atherosclerosis. 2012;223(2):306-313.  (PubMed)

57.  Failla ML, Hopkins RG. Is low copper status immunosuppressive? Nutr Rev. 1998;56(1 Pt 2):S59-64.

58.  Percival SS. Copper and immunity. Am J Clin Nutr. 1998;67(5 Suppl):1064S-1068S.  (PubMed)

59.  Heresi G, Castillo-Duran C, Munoz C, Arevalo M, Schlesinger L. Phagocytosis and immunoglobulin levels in hypocupremic children. Nutr Res. 1985;5:1327-1334.

60.  Kelley DS, Daudu PA, Taylor PC, Mackey BE, Turnlund JR. Effects of low-copper diets on human immune response. Am J Clin Nutr. 1995;62(2):412-416.  (PubMed)

61.  Hodgkinson V, Petris MJ. Copper homeostasis at the host-pathogen interface. J Biol Chem. 2012;287(17):13549-13555.  (PubMed)

62.  Looker AC, Melton LJ, 3rd, Harris TB, Borrud LG, Shepherd JA. Prevalence and trends in low femur bone density among older US adults: NHANES 2005-2006 compared with NHANES III. J Bone Miner Res. 2010;25(1):64-71.  (PubMed)

63.  Tiidus PM, Lowe DA, Brown M. Estrogen replacement and skeletal muscle: mechanisms and population health. J Appl Physiol. 2013;115(5):569-578.  (PubMed)

64.  Cauley JA. Public Health Impact of Osteoporosis. J Gerontol A Biol Sci Med Sci. 2013;68(10):1243-1251.  (PubMed)

65.  Kanumakala S, Boneh A, Zacharin M. Pamidronate treatment improves bone mineral density in children with Menkes disease. J Inherit Metab Dis. 2002;25(5):391-398.  (PubMed)

66.  Marquardt ML, Done SL, Sandrock M, Berdon WE, Feldman KW. Copper deficiency presenting as metabolic bone disease in extremely low birth weight, short-gut infants. Pediatrics. 2012;130(3):e695-698.  (PubMed)

67.  Baker A, Harvey L, Majask-Newman G, Fairweather-Tait S, Flynn A, Cashman K. Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males. Eur J Clin Nutr. 1999;53(5):408-412.  (PubMed)

68.  Baker A, Turley E, Bonham MP, et al. No effect of copper supplementation on biochemical markers of bone metabolism in healthy adults. Br J Nutr. 1999;82(4):283-290.  (PubMed)

69.  Cashman KD, Baker A, Ginty F, et al. No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status. Eur J Clin Nutr. 2001;55(7):525-531.  (PubMed)

70.  Conlan D, Korula R, Tallentire D. Serum copper levels in elderly patients with femoral-neck fractures. Age Ageing. 1990;19(3):212-214.  (PubMed)

71.  Mutlu M, Argun M, Kilic E, Saraymen R, Yazar S. Magnesium, zinc and copper status in osteoporotic, osteopenic and normal post-menopausal women. J Int Med Res. 2007;35(5):692-695.  (PubMed)

72.  Eaton-Evans J, Mellwrath EM, Jackson WE, McCartney H, Strain JJ. Copper supplementation and the maintenance of bone mineral density in middle-aged women. J Trace Elem Exp Med. 1996;9:87-94.

73.  Strause L, Saltman P, Smith KT, Bracker M, Andon MB. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr. 1994;124(7):1060-1064.  (PubMed)

74.  Nielsen FH, Lukaski HC, Johnson LK, Roughead ZK. Reported zinc, but not copper, intakes influence whole-body bone density, mineral content and T score responses to zinc and copper supplementation in healthy postmenopausal women. Br J Nutr. 2011;106(12):1872-1879.  (PubMed)

75.  Sidiropoulou-Chatzigiannis S, Kourtidou M, Tsalikis L. The effect of osteoporosis on periodontal status, alveolar bone and orthodontic tooth movement. A literature review. J Int Acad Periodontol. 2007;9(3):77-84.  (PubMed)

76.  Darcey J, Horner K, Walsh T, Southern H, Marjanovic EJ, Devlin H. Tooth loss and osteoporosis: to assess the association between osteoporosis status and tooth number. Br Dent J. 2013;214(4):E10.  (PubMed)

77.  Sierpinska T, Konstantynowicz J, Orywal K, Golebiewska M, Szmitkowski M. Copper deficit as a potential pathogenic factor of reduced bone mineral density and severe tooth wear. Osteoporos Int. 2013 [Epub ahead of print].  (PubMed)

78.  Squitti R, Barbati G, Rossi L, et al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau. Neurology. 2006;67(1):76-82.  (PubMed)

79.  Arnal N, Cristalli DO, de Alaniz MJ, Marra CA. Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives. Brain Res. 2010;1319:118-130.  (PubMed)

80.  Ventriglia M, Bucossi S, Panetta V, Squitti R. Copper in Alzheimer's disease: a meta-analysis of serum, plasma, and cerebrospinal fluid studies. J Alzheimers Dis. 2012;30(4):981-984.  (PubMed)

81.  Brewer GJ. Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease. Biofactors. 2012;38(2):107-113.  (PubMed)

82.  Squitti R, Polimanti R. Copper phenotype in Alzheimer's disease: dissecting the pathway. Am J Neurodegener Dis. 2013;2(2):46-56.  (PubMed)

83.  Squitti R, Polimanti R. Copper hypothesis in the missing hereditability of sporadic Alzheimer's disease: ATP7B gene as potential harbor of rare variants. J Alzheimers Dis. 2012;29(3):493-501.  (PubMed)

84.  Sparks DL, Schreurs BG. Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2003;100(19):11065-11069.  (PubMed)

85.  Kitazawa M, Cheng D, Laferla FM. Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. J Neurochem. 2009;108(6):1550-1560.  (PubMed)

86.  Morris MC, Evans DA, Tangney CC, et al. Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol. 2006;63(8):1085-1088.  (PubMed)

87.  Kessler H, Pajonk FG, Bach D, et al. Effect of copper intake on CSF parameters in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial. J Neural Transm. 2008;115(12):1651-1659.  (PubMed)

88.  Kessler H, Bayer TA, Bach D, et al. Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial. J Neural Transm. 2008;115(8):1181-1187.  (PubMed)

89.  Skjorringe T, Moller LB, Moos T. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders. Front Pharmacol. 2012;3:169.  (PubMed)

90.  Akatsu H, Hori A, Yamamoto T, et al. Transition metal abnormalities in progressive dementias. Biometals. 2012;25(2):337-350.  (PubMed)

91.  Mariani S, Ventriglia M, Simonelli I, et al. Fe and Cu do not differ in Parkinson's disease: a replication study plus meta-analysis. Neurobiol Aging. 2013;34(2):632-633.  (PubMed)

92.  Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001.

93.  Bremner I. Manifestations of copper excess. Am J Clin Nutr. 1998;67(5 Suppl):1069S-1073S.  (PubMed)

94.  Fitzgerald DJ. Safety guidelines for copper in water. Am J Clin Nutr. 1998;67(5 Suppl):1098S-1102S.  (PubMed)

95.  Turnlund JR, Jacob RA, Keen CL, et al. Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men. Am J Clin Nutr. 2004;79(6):1037-1044.  (PubMed)

96.  Turnlund JR, Keyes WR, Kim SK, Domek JM. Long-term high copper intake: effects on copper absorption, retention, and homeostasis in men. Am J Clin Nutr. 2005;81(4):822-828.  (PubMed)

97.  Wood RJ, Suter PM, Russell RM. Mineral requirements of elderly people. Am J Clin Nutr. 1995;62(3):493-505.  (PubMed)