Copper

Copper/Drug Interactions:

  • AntacidsAntacids: Based on secondary sources, antacids may interfere with copper absorption.
  • AntibioticsAntibiotics: In vitro evidence suggests that copper may have antibacterial effects against Streptococcus mutans (141; 142). The effects with other antibacterial agents are unclear.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on human study, copper deficiency may cause deficiencies of copper-dependent coagulation factors such factor V, factor VIII, and fibrinogen (28; 29; 30; 31).
  • AnticonvulsantsAnticonvulsants: Based human study, anticonvulsants like valproic acid can cause depletion of copper (33; 34; 35). In other human study, chronic administration of anticonvulsants including phenytoin, phenobarbital, carbamazepine, and valproic acid does not produce copper deficiency (143). Based on study in epileptic patients on long-term anticonvulsant therapy, carbamazepine monotherapy induced fewer disturbances in copper metabolism than phenytoin monotherapy (144).
  • Antilipemic agentsAntilipemic agents: Based on clinical study, copper has the potential to increase blood total cholesterol and LDL cholesterol and decrease HDL cholesterol and VLDL (25; 26); however, other study has found no correlation, and clinical significance is unclear (76; 130).
  • Antineoplastic agentsAntineoplastic agents: Based on preliminary study, copper may have antineoplastic effects, although dietary copper reduction did not result in increased survival in patients with glioblastoma multiforme in human study, and clinical significance is unclear (145).
  • Antipsychotic agentsAntipsychotic agents: Higher copper levels have been observed in schizophrenic patients taking depot neuroleptics (146).
  • ContraceptivesContraceptives: Based on studies in women, plasma and serum copper levels may increase in women taking oral contraceptives (11; 12; 13; 14).
  • DiureticsDiuretics: Diuretics, particularly thiazide diuretics, have been found alter copper levels (147).
  • Drugs used for osteoporosisDrugs used for osteoporosis: In clinical study, urinary pyridinoline/creatinine and deoxypyridinoline/creatinine (biomarkers of bone resorption) were significantly increased (by 30% and 25%, respectively) when subjects were switched from a medium- to a low-copper diet and were significantly decreased (by 30% and 22%, respectively) when subjects were switched from low- to high-copper diets (71). When trace minerals, including copper, were added to a calcium-supplemented diet, bone loss was further arrested in older women, compared to a diet supplemented with calcium alone (148). However, various studies have found no effect on various markers of bone metabolism with copper supplementation, including serum osteocalcin (a marker of bone formation), urinary creatinine concentration, the urinary pyridinoline-urinary creatinine ratio (a marker of bone resorption), and the deoxypyridinoline-urinary creatinine excretion ratio (a marker of bone resorption) (70; 73).
  • EstrogenEstrogen: Based on human study, estrogen and oral contraceptives containing estrogen may increase serum and plasma copper levels (149; 11; 12; 13; 14)
  • Ethambutol (Myambutol?)Ethambutol (Myambutol?): Based on in vitro study, ethambutol may chelate copper (150). Copper chelation in the retina may contribute to ethambutol-induced optic neuropathy, but it is unclear whether supplemental copper can prevent this adverse effect.
  • Gastrointestinal agents, miscellaneousGastrointestinal agents, miscellaneous: Based on in vitro and human study, a proposed mechanism of action for copper's gastrointestinal effects is an alteration of tight junction permeability, thereby increasing permeability to sucrose, but not lactulose or mannitol (151), however clinical significance is unclear.
  • Hepatotoxic agentsHepatotoxic agents: Chronic copper supplementation of 30-60mg during three years has reportedly caused severe liver cirrhosis (36). According to a double-blind study, seven subjects had no evidence of liver damage after consuming 10mg of copper gluconate daily for 12 weeks (128). Up to 7mg daily of total copper sulfate intake did not adversely affect liver function in healthy adults (62; 87).
  • ImmunosuppressantsImmunosuppressants: Copper is involved in the development of immune cells and immune function in the body. However, copper supplementation has been shown to cause immunosuppressive effects in clinical study (27).
  • Nephrotoxic agentsNephrotoxic agents: Based on animal study, excess dosing of copper may lead to kidney failure (52; 53; 54; 55; 56; 57; 58).
  • NifedipineNifedipine: Based on human studies, a lower concentration of copper was found in red blood cells after use of 30mg of nifedipine (152).
  • Penicillamine (Cuprimine?, Depen?)Penicillamine (Cuprimine?, Depen?): Penicillamine may dramatically increase the urinary excretion of copper, and individuals taking penicillamine for reasons other than copper overload may have an increased requirement for copper. Based on a study of patients with primary biliary cirrhosis, therapy with D-penicillamine and a low-copper diet may sustain increased urinary copper excretion for up to one year (153).
  • Trientine (Syprine?, Trien?)Trientine (Syprine?, Trien?): Based on secondary sources, trientine may chelate copper and is used in the management of Wilson's disease.
  • Zidovudine (Retrovir?, AZT)Zidovudine (Retrovir?, AZT): Based on human study, levels of copper may be reduced in individuals treated with zidovudine (154). Based on clinical study, a decrease in the copper-zinc ratio may be beneficial in HIV/AIDS patients (46).

    • Copper/Herb/Supplement Interactions:

  • Amino acidsAmino acids: Based on study in infants, free amino acids as part of a total parenteral nutrition regimen may increase urinary copper excretion (155).
  • AntacidsAntacids: Based on secondary sources, antacids may interfere with copper absorption.
  • AntibacterialsAntibacterials: In vitro evidence suggests that copper may have antibacterial effects against Streptococcus mutans (141; 142). The effects with other antibacterial agents are unclear.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on human study, copper deficiency may cause deficiencies of copper-dependent coagulation factors such factor V, factor VIII, and fibrinogen (28; 29; 30; 31).
  • AnticonvulsantsAnticonvulsants: Based human study, anticonvulsants such as valproic acid can cause depletion of copper (33; 34; 35). In other human study, chronic administration of anticonvulsants, including phenytoin, phenobarbital, carbamazepine, and valproic acid, does not produce copper deficiency (143). Based on study in epileptic patients on long-term anticonvulsant therapy, carbamazepine monotherapy induced fewer disturbances in copper metabolism than phenytoin monotherapy (144).
  • AntilipemicsAntilipemics: Based on clinical study, copper may increase blood total cholesterol and LDL cholesterol and decrease HDL cholesterol and VLDL (25; 26); however, other study has found no correlation, and clinical significance is unclear (76; 130).
  • AntineoplasticsAntineoplastics: Based on preliminary study, copper may have antineoplastic effects, although dietary copper reduction did not result in increased survival in patients with glioblastoma multiforme in human study, and clinical significance is unclear (145).
  • AntipsychoticsAntipsychotics: Higher copper levels have been observed in schizophrenic patients taking depot neuroleptics (146).
  • BoronBoron: Based on secondary sources, boron may increase plasma copper levels and serum ceruloplasmin in humans when coadministered with copper.
  • CadmiumCadmium: Based on animal research, copper may increase the concentration of cadmium in tissues (156); however, cadmium supplementation does not appear to significantly alter copper levels in rats (157).
  • CalciumCalcium: Based on preliminary study, calcium may alter the metabolism of copper (31).
  • ChromiumChromium: Based on human study, supplementation with a combination of copper and chromium may reduce lymphocyte proliferation ex vivo (27).
  • ContraceptivesContraceptives: Based on studies in women, serum and plasma copper levels may increase in women taking oral contraceptives (11; 12; 13; 14).
  • Dehydroepiandrosterone (DHEA)Dehydroepiandrosterone (DHEA): Based on animal studies, low copper levels may result in decreased serum DHEA levels, although it is unclear if increased copper intake increases DHEA levels (158; 159; 160).
  • DiureticsDiuretics: Diuretics, particularly thiazide diuretics, have been found alter copper levels (147).
  • FolateFolate: Based on human study, long-term high-copper intake may result in small but significant decreases in plasma concentrations of folate (24).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Based on in vitro and human study, a proposed mechanism of action for copper's gastrointestinal effects is an alteration of tight junction permeability, thereby increasing permeability to sucrose, but not lactulose or mannitol (151), however clinical significance is unclear.
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: Chronic copper supplementation of 30-60mg during three years has reportedly caused severe liver cirrhosis (36). According to a double-blind study, seven subjects had no evidence of liver damage after consuming 10mg of copper gluconate daily for 12 weeks (128). Up to 7mg daily of total copper sulfate intake did not adversely affect liver function in healthy adults (62; 87).
  • ImmunosuppressantsImmunosuppressants: Copper is involved in the development of immune cells and immune function in the body. However, copper supplementation has been shown to cause immunosuppressive effects in clinical study (27).
  • IronIron: Adequate copper nutritional status appears to be necessary for normal iron metabolism, transport, and red blood cell formation. High iron intake may interfere with copper absorption. However, results from limited available human study suggest there was no inhibition of intestinal copper absorption by iron supplementation (161).
  • MagnesiumMagnesium: Based on clinical study, serum copper levels may affect serum magnesium levels, and serum magnesium levels may affect serum copper levels (79). In individuals given low levels of magnesium, red blood cell magnesium was lower when dietary copper was low than when it was high. When dietary magnesium was low, serum copper was lower in the women fed marginal copper than in those fed adequate copper. When dietary magnesium was high, there was no effect of low dietary copper on serum copper levels.
  • MolybdenumMolybdenum: Based on animal studies, molybdenum may reduce copper levels (162; 163; 164; 165; 166), possibly through an interaction in the intestines (167; 168; 169; 170).
  • Nephrotoxic agentsNephrotoxic agents: Based on animal study, excess dosing of copper may lead to kidney failure (52; 53; 54; 55; 56; 57; 58).
  • Osteoporosis herbs and supplementsOsteoporosis herbs and supplements: In clinical study, urinary pyridinoline/creatinine and deoxypyridinoline/creatinine (biomarkers of bone resorption) were significantly increased (by 30% and 25%, respectively) when subjects were switched from a medium- to a low-copper diet, and were significantly decreased (by 30% and 22%, respectively) when subjects were switched from low- to high-copper diets (71). When trace minerals, including copper, were added to a calcium-supplemented diet, bone loss was further arrested in older women, compared to a diet supplemented with calcium alone (148). However, various studies have found no effect on various markers of bone metabolism with copper supplementation, including serum osteocalcin (a marker of bone formation), urinary creatinine concentration, the urinary pyridinoline-urinary creatinine ratio (a marker of bone resorption), and the deoxypyridinoline-urinary creatinine excretion ratio (a marker of bone resorption) (70; 73).
  • PhytoestrogensPhytoestrogens: Based on human study, estrogen and oral contraceptives containing estrogen may increase serum and plasma copper levels (149; 11; 12; 13; 14).
  • Rapeseed oilRapeseed oil: Based on animal study, coadministration of rapeseed oilmeal with copper may result in altered metabolism (171; 172).
  • SeleniumSelenium: Based on animal studies, copper may reduce serum selenium levels (22; 23).
  • TaurineTaurine: Based on animal studies, supplementation with taurine may reduce toxic effects of copper when given in combination (58).
  • Vitamin CVitamin C: Based on a study in low-birthweight infants fed cow's milk formula, vitamin C supplementation does not alter copper balance, absorption, or retention (140). However, based on animal studies, vitamin C supplements may cause copper deficiency (173; 174; 175).
  • ZincZinc: Based on human and animal studies, high levels of supplemental zinc intake over extended periods of time may result in decreased copper absorption in the intestines or in copper deficiency (176; 177; 178; 179; 28; 180; 181; 182; 183; 184; 75; 185; 186), possibly due to increased synthesis of the intestinal cell protein metallothionein, which binds some metals (56; 57; 187). However, some studies in humans suggest that high dietary zinc may not interfere with tissue or plasma concentrations of copper (188; 189; 190; 191; 192). On the other hand, a significant interference by copper supplementation on zinc absorption was noted in infants (32; 137), although another human study found copper supplementation had no significant effect on zinc absorption (193). Based on a liver histologic study of Wilson's disease patients, copper concentration was reduced by treatment with zinc, suggesting that oral zinc was able not only to prevent further accumulation of copper but also to promote, at least in part, the depletion of its stores (45). Based on human study, a decrease in the copper-zinc ratio may be beneficial in HIV/AIDS patients (46).

    • Copper/Food Interactions:

  • Amino acidsAmino acids: Based on study in infants, free amino acids as part of a total parenteral nutrition regimen may increase urinary copper excretion (155).
  • Dietary fiberDietary fiber: Based on human study, hemicellulose, cellulose, or pectin in the diet may increase fecal copper loss (194), and diets high in fiber from fruits and vegetables may reduce mean daily balances of copper (195).
  • FructoseFructose: Based on human study, dietary fructose may enhance copper balance in diets low in copper (196). However, rat study indicates that a diet high in fructose may increase copper deficiency (197).
  • LactoseLactose: Based on review study, lactose may interfere with copper metabolism (198).
  • Rapeseed oilmealRapeseed oilmeal: Based on animal study, coadministration of rapeseed oilmeal with copper may result in altered metabolism (171; 172).
  • SucroseSucrose: Based on human study, a copper solution (10mg/L) significantly increased gastric permeability to sucrose (151).
  • Vegetarian dietVegetarian diet: In one human study, copper was less efficiently absorbed from a vegetarian diet than from a nonvegetarian diet (199); however, in another human study, total apparent copper absorption was greater from the lacto-ovo vegetarian diet due to a greater copper content (200).

    • Copper/Lab Interactions:

  • Blood pressureBlood pressure: Based on secondary sources, hypertension may be associated with copper toxicity.
  • Ceruloplasmin (Cp)Ceruloplasmin (Cp): Ceruloplasmin is an indicator of copper status. The response to copper exposure depends on Cp values and on gender, such that women with higher Cp values and men with lower Cp values exhibit the greatest response (67). In human and animal copper supplementation studies, increased ceruloplasmin levels have been noted in some (26), but not all studies (70; 71; 73).
  • Coagulation panelCoagulation panel: Based on human study, copper deficiency may cause deficiencies of copper-dependent coagulation factors such factor V, factor VIII, and fibrinogen (28; 29; 30; 31).
  • Complete blood countComplete blood count: Copper T intrauterine contraceptive devices (IUDs) have been linked to the development of anemia in some users (6; 5; 7; 8; 15; 16; 17; 18; 19; 20; 21).
  • FolatelevelsFolatelevels: Based on human study, long-term high-copper intake may slightly decrease plasma concentrations of folate (24).
  • HemoglobinHemoglobin: Based on human study, hemoglobin may decrease during Nova T intrauterine contraceptive device use (8), but increase with copper supplementation (26). Based on secondary sources, copper toxicity may be associated with hemoglobinuria.
  • HomocysteineHomocysteine: Based on human study, long-term high-copper intake may result in small but significant decreases in plasma concentrations of total homocysteine (24).
  • IronIron: Adequate copper nutritional status appears to be necessary for normal iron metabolism, transport, and red blood cell formation. High iron intake may interfere with copper absorption. However, results from limited available human study suggest there was no inhibition of intestinal copper absorption by iron supplementation (161).
  • Lipid profileLipid profile: Based on human studies, copper supplementation may increase blood total cholesterol and LDL cholesterol and decrease HDL cholesterol and VLDL (25; 26); however, other studies have found no correlation (76; 130).
  • Plasminogen activator inhibitor type I (PAI-I)Plasminogen activator inhibitor type I (PAI-I): Based on human study, copper may reduce levels of PAI-I (48).
  • Serum copperSerum copper: Based on clinical study, copper supplementation may increase levels of serum copper (48), however, some studies have found no change in serum copper (26).
  • Serum diamine oxidaseSerum diamine oxidase: Based on human study, copper supplementation may increase serum diamine oxidase activity (77).