InteractionsGuide Index Page

 
Case Analysis Toolclose
Enter Each Substance:


Analysis Search Terms:

Copper

Nutrient Name: Copper.
Synonyms: Copper carbonate, copper citrate, copper gluconate, copper glyconate, copper lysinate, copper sebacate, copper sulfate, cupric acetate, cupric oxide; cuprum.
Elemental Symbol: Cu.
Related Substance: Chlorophyllin.

Summary Table
Drug/Class Interaction TypeMechanism and SignificanceManagement
Allopurinol
/
Allopurinol, a potent inhibitor of xanthine oxidase, forms a complex with copper that can reduce cardiac damage, which appears to be due to copper- and ascorbate-mediated DNA breakage, in patients undergoing cardiac bypass surgery. The mechanisms involved are not fully understood, but the resulting complex exhibits low redox activity.Chelation of copper by allopurinol may help protect against cardiac damage during reperfusion of the heart. Avoid copper before bypass surgery.
Antacids

Antacids can inhibit copper absorption and induce intestinal alkaline pH, which can precipitate dietary copper. Copper depletion and deficiency may result from excessive or extended use of antacids, especially with pyloric stenosis. Mechanism reasonable, but clinically significant adverse effects probably infrequent.Coadminister with extended antacid use.
Cimetidine
/
Animal studies indicate cimetidine complexes with Cu(II) [and Fe(III)] ions and may elevate tissue copper concentrations, particularly in the liver. By binding copper (and iron), cimetidine may also act as a free-radical scavenger. Although the proposed mechanisms are plausible, evidence remains preliminary.Coadminister if indicated. Separate intake by at least 2 hours.
Ciprofloxacin

Copper and other minerals can bind to ciprofloxacin and reduce its absorption. Copper evidence preliminary, but parallel phenomenon with iron generally recognized. Drug efficacy could be impaired.Separate intake by at least 2 hours.
Clofibrate fibrates
/ / /
Clofibrate may enhance copper metabolism and elevate hepatic copper levels, and may reduce hypercholesterolemia, particularly with compromised copper status. Research is limited, with mixed findings and conclusions.Coadminister, as appropriate; monitor.
Ethambutol
/ /
Ethambutol forms chelate complexes with copper (and zinc), which may contribute to drug-induced optic neuropathy.Coadminister and monitor visual function. Separate intake by at least 2 hours
Famotidine H2receptor antagonists (H2RAs)

Famotidine and H2RAs interfere with the acidic gastric environment optimal for copper absorption. Such drug-induced changes can inhibit copper absorption and induce alkaline intestinal pH, which can precipitate dietary copper. Subsequent copper depletion and deficiency may result from excessive or extended gastric acid–suppressive therapy. Mechanism reasonable but frequency of clinically significant adverse effects unknown.Coadminister with extended H2RA use. Separate intake by at least 2 hours.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
/
Copper tends to complex with NSAIDs and might enhance their anti-inflammatory effects while reducing their ulcerogenic effects. Evidence preliminary and promising, but mixed; clinical implications likely significant.Consider coadministration.
Oral contraceptives (OCs)
Estrogens/progestins
Hormone replacement therapy (HRT)

Exogenous female hormones, especially progestins, may enhance copper absorption and elevate copper levels. Clinical significance may vary with age, specific medication, and other factors and could contribute to increased adverse drug effects, e.g., cardiovascular risk.Avoid concomitant copper supplementation unless risk of depletion or other prevailing benefits.
Penicillamine, trientine, and tetrathiomolybdate
Chelating agents
/
These chelating agents are designed to bind copper and limit its absorption and accumulation, particularly in treatment of mineral deposition disorders such as Wilson's disease and increasingly in antiangiogenic cancer therapy. Interaction is purposeful, and its clinical significance is generally recognized.Limit dietary and avoid supplemental copper intake. Monitor for adverse drug effects.
Valproic acid
Anticonvulsant medications
/
Valproic acid and related antiepileptics may induce copper deficiency and disrupt copper homeostasis by increasing excretion into bile. Preliminary evidence of depletion pattern; prevalence uncertain. Possible risk of clinical significance primarily with long-term anticonvulsant therapy.Monitor copper (and zinc) status. Copper administrator warranted with deficiency indications or other risk factors.
Zidovudine (AZT)
Reverse-transcriptase inhibitor (nucleoside)
antiretroviral agents
/ / /
Coadministration of zinc with AZT can reduce adverse effects and enhance efficacy but extended therapy requires complement of copper to prevent adverse effects from zinc, thus providing a more comprehensive approach to supporting patients on AZT. Evidence preliminary, clinical significance unconfirmed.Coadminister copper with extended zinc use.
nutrient description

Chemistry and Forms

Copper carbonate, copper citrate, copper gluconate, copper glycinate, copper lysinate, copper sebacate, copper sulfate; copper amino acid chelates; cupric acetate, cupric oxide.

Physiology and Function

Copper is an essential trace mineral that is present in all tissues and acts as a cofactor in several key enzyme systems. The average adult body contains about 80 to 120 milligrams of copper, most of which is stored in the liver. Copper stimulates iron absorption and is an important catalyst in hemoglobin synthesis and function. Copper is necessary to make adenosine triphosphate (ATP) and acts as an essential component of cytochrome oxidase, which is necessary for energy metabolism, cellular respiration, and myelin formation.

Copper is involved in the synthesis and breakdown of several hormones. Copper serves as a cofactor in dopamine–β-hydroxylase, which oxidizes ascorbic acid and synthesizes norepinephrine. It is also involved in the catabolism of estrogenic hormones. Copper may play a role in emotional regulation and cognitive function.

Copper is absorbed in the small intestine, where it is transferred across the gut wall by albumin, and carried on transcuprein and albumin to the liver, where it is incorporated into liver enzymes and secreted into the blood on the protein ceruloplasmin. Copper absorption has been found to be greater in women (71%) than in men (64%), age 20 to 59 years, but did not differ in men and women 60 to 83 years old. Copper elimination is primarily via bile, with small amounts eliminated in urine, sweat, and epidermal shedding.

Copper plays a central role in decreasing inflammation through both ceruloplasmin and the copper-containing form of superoxide dismutase (SOD). Ceruloplasmin is a weak, broad-specificity oxidase whose main functions include copper transport and extracellular scavenging of superoxide and other oxygen radicals. Adequate ceruloplasmin levels also minimize copper toxicity by limiting absorption of copper. Copper, along with zinc, as well as manganese, is found in cytostolic SOD. SOD is a primary quencher of superoxide radical, a prevalent and highly reactive free-radical form of oxygen produced during oxidative phosphorylation, which can be quite destructive if not rapidly quenched. SOD slows age-related deterioration, protects against chemical sensitivities (along with polyphenol oxidase), and enables the normal humoral immune response. There are also copper-containing amino acid chelates that have SOD activity. During inflammatory conditions, such as acute infections, serum copper levels, as ceruloplasmin, generally increase by 20% to 30%, whereas serum iron levels decline. Plasma copper, enzymatic ceruloplasmin, and immunoreactive (RID) ceruloplasmin have been observed to be significantly higher in women than in men, but SOD and in vitro 67 Cu uptake by red blood cells does not appear to differ between the genders.

Histaminase, which breaks down histamine to control allergies and inflammation, is another copper-dependent enzyme involved in regulating inflammatory processes. Tyrosinase, an enzyme that requires copper, plays a role in melanin synthesis, enabling skin pigmentation and hair coloration, as well as keratinization of hair.

Some researchers have proposed that copper deficiency is associated with elevated cholesterol and triglycerides, the development of atherosclerosis, and increased risk of cardiovascular disease.

Copper functions in the synthesis of collagen and repair of connective tissue, providing structural elasticity not only throughout the musculoskeletal system, but also in tissues of the lungs, blood vessels, and skin. Lysil oxidase, a copper-containing enzyme secreted by connective tissue cells, is necessary for the formation of the cross-links of collagen and elastin.

Copper is an essential element and its level in the body is strictly controlled. Under most conditions, excess copper is excreted in the urine and feces (via the bile). In cases of elevated copper, the adverse effects that develop are often caused less directly by copper toxicity than by its interference with the absorption and distribution of other mineral nutrients, such as iron and zinc.

Copper sulfate, cupric acetate, and alkaline copper carbonate are among the forms of copper best absorbed in the gut. Nevertheless, even though animal studies have demonstrated that it is poorly absorbed in the gut, cupric oxide (CuO) is the form of copper most often used in over-the-counter (OTC) preparations. Chlorophyllin is a relatively new, water-soluble copper complex of chlorophyll.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Copper has been proposed as offering therapeutic benefit in a wide range of conditions. Such therapeutic action has largely been premised on the hypothesis that administration will enhance or restore healthy function in the numerous enzyme systems where copper plays a critical role. Nevertheless, direct evidence confirming copper's efficacy in treating most of the diseases proposed is largely lacking, other than to prevent or treat those directly attributable to, or exacerbated by, copper deficiency or depletion.

Historical/Ethnomedicine Precedent: As the classical metal of Venus, copper was associated with the female reproductive system in ancient times.

Possible Uses

Anemia, aneurysms, atherosclerosis, athletic performance, benign prostatic hyperplasia, burns, cardiac arrhythmia, cardiovascular disease, decubitus ulcers, hypercholesterolemia, hypoglycemia, immune enhancement, Menkes’ syndrome, muscle spasms, osteoporosis, peptic ulcer, peripheral vascular disease, rheumatoid arthritis, skin cancer (prevention), sprains and strains, stomach cancer (prevention), vitiligo, wound healing.

Deficiency Symptoms

Most research into copper deficiency has focused on acute, severe deficiency. Such frank clinical copper deficiency is relatively rare in humans and animals on typical, varied diets. However, marginal, chronic deficiency is not uncommon. Dietary surveys indicate that the average dietary intake of copper in the U.S. population is only half of the recently established recommended dietary allowance (RDA). Most cases of copper deficiency involve premature infants, infants suffering from malnutrition, or children with iron deficiency anemia, severe protein malnutrition, chronic diarrhea, or other malabsorption difficulties. Overt symptoms in adults are rare but may occur with inadequate or unbalanced dietary intake over an extended time or in those who consume zinc supplements chronically without counterbalancing copper. The determination of copper needs and marginal deficiency is obscured because copper deficiency may not manifest as decreased levels of copper-dependent enzymes, but it may still significantly lower their activity.

Because copper is required for a wide range of enzyme systems and metabolic processes, a deficiency can cause a variety of disorders. Laboratory animals fed copper-deficient diets tend to develop anemia, cardiac abnormalities and abnormal electrocardiograms, and elevated levels of serum cholesterol, triglycerides, and glucose. Symptoms of copper deficiency in humans include fatigue, hypotonia, hypothermia, growth retardation, reduced resistance to infection, various nervous system disorders, anemia, neutropenia, degeneration of vasculature, cardiac damage, hemolysis with potential liver and brain damage, various cardiovascular problems, impaired respiration, emphysema, elevated low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol, impaired collagen formation, breakdown of connective tissue, bone demineralization, osteoporosis, depigmentation of skin, and changes in structure and appearance of hair.

Genetic Conditions Relating to Copper

Two primary genetic diseases involve copper metabolism: Menkes’ syndrome and Wilson's disease.

Menkes’ syndrome results from an X-linked mutation of genes encoding Cu-binding P-type adenosinetriphosphatase (ATPase) for the efflux of Cu, ATP7A. Apart from the distinctive kinky or steely hair, this syndrome is also characterized by stunted growth, abnormalities in cardiovascular and skeletal development, progressive cognitive decline, and premature death. This inborn error in metabolism limits absorption of copper in the intestines and uptake in the liver. Copper subsequently accumulates in the intestinal cells and produces symptoms resembling copper deficiency.

Wilson's disease, caused by the mutation of genes encoding Cu-binding ATPase for the efflux of Cu, ATP7B, is characterized by accumulation of copper in the liver, leading to severe hepatic damage; elevated copper levels subsequently affect the brain and result in neurological problems.

Dietary Sources

Oysters are the most abundant food source of copper. Other copper-containing foods include soy, peas, and other dried legumes; dark-green leafy vegetables; whole-grain breads and cereals; seafood, including crab and lobster; lamb, pork, and other meats, especially organ meats such as liver; nuts (almonds, pecans, walnuts); raisins, prunes, and pomegranates; and tea, coffee, and chocolate.

Foods rich in copper are generally also rich in iron.

Nutrient Preparations Available

Copper sulfate, cupric acetate, cupric oxide, and alkaline copper carbonate. As previously noted, CuO is the form most often used in OTC preparations, primarily because of its low cost. Chlorophyllin is a copper complex of chlorophyll.

Copper is usually found in multimineral or multivitamin/multimineral formulations.

Copper is often taken with, although preferably ingested apart from, long-term zinc administration to counteract the tendency to copper depletion associated with zinc intake without copper. Recommended Zn/Cu ratio in formulations is 10:1 to 15:1.

Dosage Forms Available

Capsule, tablet; cupric sulfate: injection (U.S.).

Dosage Range

Adult

Dietary: 1.0 to 1.5 mg/day

Supplemental/Maintenance: 1 to 2 mg/day

Pharmacological/Therapeutic: 2+ mg/day

Pharmacological doses of copper in scientific studies usually range from 2 to 4 mg per day. Copper dose is usually based on zinc intake. Many experts consider the optimal zinc/copper ratio as 10:1. Some practitioners of nutritional therapeutics use zinc at dosages up to 45 mg/day as part of therapeutic protocols. In such cases, LDL and HDL cholesterol levels need to be monitored. Zinc may need to be reduced or copper increased; even so, doses of copper greater than 3 mg/day are usually avoided.

Pediatric (<18 Years)

Supplemental/Maintenance: 0.5 to 1.0 mg/day

Pharmacological/Therapeutic: 1 to 2 mg/day

Laboratory Values

Serum ceruloplasmin concentrations and white blood cell (WBC) levels have been considered the most reliable methods of evaluation but often are insensitive to subtle changes in copper status. Copper-containing enzymes, such as Cu-Zn SOD, cytochrome- c oxidase, and diamine oxidase, may be more reliable, but evidence to date is not conclusive. 1 LDL and HDL cholesterol levels are sometimes used.

Serum, plasma, urinary, or hair copper concentrations are not considered particularly reliable because these monitoring parameters are subject to many variables and may not accurately demonstrate actual copper load; when used, such determinations are recommended monthly.

safety profile

Overview

Copper is generally considered safe when taken at customary dietary or typical supplemental dosage levels. Chronic copper toxicity from intentional intake in adults is rare. Long-term doses of 10 to 35 mg per day are considered safe. The tolerable upper limit (UL) of copper intake established by the U.S. National Institute of Medicine for adults is 10 mg per day, combining dietary and supplemental sources. However, research has suggested that the body cannot eliminate more than 3 mg/day, so in individuals who are copper replete or overloaded, greater than 3 mg/day dietary copper may contribute to further accumulation.

Nutrient Adverse Effects

General Adverse Effects

In adults, 10 mg of copper daily can induce nausea, and 60 mg may cause vomiting. Tissue elevations usually occur only when intake is 300 to 500 times above normal. The adverse effects on zinc metabolism represent the primary adverse effect of excessive copper levels.

Mutagenicity

No human data are available. Results from short-term tests on mutagenicity have been negative or inconclusive.

Adverse Effects Among Specific Populations

Copper intake exerts particular risk for individuals with Wilson's disease, a genetic disorder that causes a toxic accumulation of copper in the liver, kidneys, central nervous system (CNS), and cornea. Maximum safe daily dosages of copper intake for individuals with severe liver or kidney disease are of concern but have not been determined. Copper toxicity has occasionally been reported in individuals living in houses where copper from water pipes has leached into the drinking water.

Pregnancy and Nursing

Maximum safe daily dosages of copper intake for pregnant or nursing women have not been determined. There are no reports in the literature reviewed of teratogenicity or embryotoxicity in humans induced by excess copper intake. However, animal studies indicate that a deficiency or excess of copper in the body can cause significant harm to developing embryos.

Infants and Children

Maximum safe daily dosages of copper intake for infants and young children have not been determined. Copper can exert a lethal dose in children at levels as low as 3.5 g. The copper (and zinc) status of epileptic children taking valproate derivatives should be monitored.

Toxicity Signs and Symptoms

Symptoms of moderate copper toxicity include weakness, dizziness, fainting, headache (severe or continuing), burning sensation in the throat, gastrointestinal disturbances, loss of appetite, vomiting, excess salivation, metallic taste in mouth, dyspepsia, epigastric pain, painful urination, and low back pain. Severe cases can result in hemolytic anemia, hypertension, liver damage, jaundice, hemochromatosis, hemoglobinuria, hematuria, kidney failure, coma, and death. O’Donohue et al. 2 reported a case of adult chronic copper self-intoxication, after daily doses of 30 to 60 mg for 3 years, which resulted in severe liver cirrhosis necessitating orthotopic liver transplantation.

Contraindications

Biliary disease, cancer, heart bypass patients, liver disease, migraines, Wilson's disease. Copper is also contraindicated during the course of anticopper therapies. Some individuals may have a total body excess of copper resulting from a lifetime of drinking water from copper plumbing, and copper supplementation may not be desirable in such people.

Precautions and Warnings

Some individuals may become sensitized to copper sulfate and develop allergic contact dermatitis.

interactions review

Strategic Considerations

Many medications may deplete copper or interfere with its metabolic functions, sometimes incidentally, but often intentionally. Copper supplementation may be appropriate to correct drug-induced depletion patterns. In certain cases, however, such action is central to the therapeutic strategy, and supplementation is contraindicated, except in response to specific episodes of adverse effects of excessive copper deficiency caused by depletion. Conversely, in some situations, drugs such as allopurinol may provide benefit by reducing copper levels.

nutrient-drug interactions
Allopurinol
Antacids
Cimetidine
Ciprofloxacin
Clofibrate and Related Fibrates
ESTROGENS, PROGESTINS, AND ESTROGEN-PROGESTIN COMBINATIONS:
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)
Hormone Replacement Therapy (HRT): Estrogen-Containing and Synthetic Estrogen and Progesterone Analog Medications
Ethambutol
Famotidine and Related Histamine (H 2 ) Receptor Antagonists
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Penicillamine and Related Chelating Agents
Valproic Acid and Related Anticonvulsant Medications (AEDs)
Zidovudine (AZT) and Related Reverse-Transcriptase Inhibitor (Nucleoside) Antiretroviral Agents
nutrient-nutrient interactions
Iron
Molybdenum
Vitamin C
Zinc
Citations and Reference Literature
  • 1.Bonham M, O’Connor JM, Hannigan BM, Strain JJ. The immune system as a physiological indicator of marginal copper status? Br J Nutr 2002;87:393-403.
  • 2.O’Donohue J, Reid M, Varghese A et al. A case of adult chronic copper self-intoxication resulting in cirrhosis. Eur J Med Res 1999;4:252.
  • 3.Malkiel S, Har-el R, Schwalb H et al. Interaction between allopurinol and copper: possible role in myocardial protection. Free Radic Res Commun 1993;18:7-15.
  • 4.Lapenna D, de Gioia S, Ciofani G, Cuccurullo F. Antioxidant activity of allopurinol on copper-catalysed human lipoprotein oxidation. FEBS Lett 1997;409:265-268.View Abstract
  • 5.Tompsett SL. Factors influencing the absorption of iron and copper from the alimentary tract. Biochem J 1940;34:961-969.View Abstract
  • 6.Roe DA. Diet and Drug Interactions. New York: Van Nostrand Reinhold; 1989.
  • 7.Van Kalmthout PM, Engels LG, Bakker HH, Burghouts JT. Severe copper deficiency due to excessive use of an antacid combined with pyloric stenosis. Dig Dis Sci 1982;27:859-861.
  • 8.Conditioned copper deficiency due to antacids. Nutr Rev 1984;42:319-321.
  • 9.Solecki TJ, Aviv A, Bogden JD. Effect of a chelating drug on balance and tissue distribution of four essential metals. Toxicology 1984;31:207-216.View Abstract
  • 10.Naveh Y, Weis P, Chung HR, Bogden JD. Effect of cimetidine on tissue distribution of some trace elements and minerals in the rat. J Nutr 1987;117:1576-1587.View Abstract
  • 11.Lambat Z, Limson JL, Daya S. Cimetidine: antioxidant and metal-binding properties. J Pharm Pharmacol 2002;54:1681-1686.View Abstract
  • 12.Kara M, Hasinoff BB, McKay DW, Campbell NR. Clinical and chemical interactions between iron preparations and ciprofloxacin. Br J Clin Pharmacol 1991;31:257-261.
  • 13.Wallis SC, Gahan LR, Charles BG et al. Copper(II) complexes of the fluoroquinolone antimicrobial ciprofloxacin: synthesis, X-ray structural characterization, and potentiometric study. J Inorg Biochem 1996;62:1-16.
  • 14.Rizk M, Belal F, Ibrahim F et al. Derivative spectrophotometric analysis of 4-quinolone antibacterials in formulations and spiked biological fluids by their Cu(II) complexes. J AOAC Int 2001;84:368-375.View Abstract
  • 15.Powanda MC, Blackburn BS, Bostian KA et al. Clofibrate-induced alterations in zinc, iron and copper metabolism. Biochem Pharmacol 1978;27:125-127.
  • 16.Klevay LM. Clofibrate hypocholesterolemia associated with increased hepatic copper. Drug Nutr Interact 1983;2:131-137.View Abstract
  • 17.Fields M, Lewis CG, Lure MD. Copper deficiency in rats: the effect of clofibrate. J Am Coll Nutr 1992;11:399-404.View Abstract
  • 18.Eagon PK, Teepe AG, Elm MS et al. Hepatic hyperplasia and cancer in rats: alterations in copper metabolism. Carcinogenesis 1999;20:1091-1096.View Abstract
  • 19.Horwitt MK, Harvey CC, Dahm CH Jr. Relationship between levels of blood lipids, vitamins C, A, and E, serum copper compounds, and urinary excretions of tryptophan metabolites in women taking oral contraceptive therapy. Am J Clin Nutr 1975;28:403-412.
  • 20.Dorea JG, Ferraz E, Queiroz EF. [Effects of anovulatory steroids on serum levels of zinc and copper]. Arch Latinoam Nutr 1982;32:101-110.View Abstract
  • 21.Mehta SW, Eikum R. Effect of estrogen on serum and tissue levels of copper and zinc. Adv Exp Med Biol 1989;258:155-162.View Abstract
  • 22.Newhouse IJ, Clement DB, Lai C. Effects of iron supplementation and discontinuation on serum copper, zinc, calcium, and magnesium levels in women. Med Sci Sports Exerc 1993;25:562-571.
  • 23.Liukko P, Erkkola R, Pakarinen P et al. Trace elements during 2 years’ oral contraception with low-estrogen preparations. Gynecol Obstet Invest 1988;25:113-117.
  • 24.Johnson PE, Milne DB, Lykken GI. Effects of age and sex on copper absorption, biological half-life, and status in humans. Am J Clin Nutr 1992;56:917-925.View Abstract
  • 25.Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. Eur J Clin Nutr 1998;52:711-715.View Abstract
  • 26.Bureau I, Anderson RA, Arnaud J et al. Trace mineral status in post menopausal women: impact of hormonal replacement therapy. J Trace Elem Med Biol 2002;16:9-13.View Abstract
  • 27.Salonen JT, Salonen R, Korpela H et al. Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland. Am J Epidemiol 1991;134:268-276.View Abstract
  • 28.Reunanen A, Knekt P, Marniemi J et al. Serum calcium, magnesium, copper and zinc and risk of cardiovascular death. Eur J Clin Nutr 1996;50:431-437.
  • 29.Cole A, May PM, Williams DR. Metal binding by pharmaceuticals. Part 1. Copper(II) and zinc(II) interactions following ethambutol administration. Agents Actions 1981;11:296-305.View Abstract
  • 30.Kozak SF, Inderlied CB, Hsu HY et al. The role of copper on ethambutol’s antimicrobial action and implications for ethambutol-induced optic neuropathy. Diagn Microbiol Infect Dis 1998;30:83-87.View Abstract
  • 31.Kaimbo WK, Bifuko ZA, Longo MB et al. Color vision in 42 Congolese patients with tuberculosis receiving ethambutol treatment. Bull Soc Belge Ophtalmol 2002:57-61.View Abstract
  • 32.Kozlowski H, Kowalik-Jankowska T, Anouar A et al. Famotidine, the new antiulcero-genic agent, a potent ligand for metal ions. J Inorg Biochem 1992;48:233-240.View Abstract
  • 33.Sorenson JR. Copper chelates as possible active forms of the antiarthritic agents. J Med Chem 1976;19:135-148.View Abstract
  • 34.Brumas V, Brumas B, Berthon G. Copper(II) interactions with nonsteroidal antiinflammatory agents. I. Salicylic acid and acetylsalicylic acid. J Inorg Biochem 1995;57:191-207.View Abstract
  • 35.Miche H, Brumas V, Berthon G. Copper(II) interactions with nonsteroidal antiinflammatory agents. II. Anthranilic acid as a potential OH-inactivating ligand. J Inorg Biochem 1997;68:27-38.View Abstract
  • 36.Gaubert S, Bouchaut M, Brumas V, Berthon G. Copper-ligand interactions and the physiological free radical processes. Part 3. Influence of histidine, salicylic acid and anthranilic acid on copper-driven Fenton chemistry in vitro. Free Radic Res 2000;32:451-461.
  • 37.Kishore V. Effects of copper aspirinate and aspirin on tissue copper, zinc, and iron concentrations following chronic oral treatment in the adjuvant arthritic rat. Biol Trace Elem Res 1990;25:123-135.View Abstract
  • 38.Schilsky ML. Wilson disease: genetic basis of copper toxicity and natural history. Semin Liver Dis 1996;16:83-95.
  • 39.Subramanian I, Vanek ZF, Bronstein JM. Diagnosis and treatment of Wilson’s disease. Curr Neurol Neurosci Rep 2002;2:317-323.
  • 40.Brewer GJ. Copper control as an antiangiogenic anticancer therapy: lessons from treating Wilson’s disease. Exp Biol Med (Maywood) 2001;226:665-673.
  • 41.Cox C, Teknos TN, Barrios M et al. The role of copper suppression as an antiangiogenic strategy in head and neck squamous cell carcinoma. Laryngoscope 2001;111:696-701.View Abstract
  • 42.Kodama H, Murata Y, Iitsuka T, Abe T. Metabolism of administered triethylene tetramine dihydrochloride in humans. Life Sci 1997;61:899-907.
  • 43.Klein D, Lichtmannegger J, Heinzmann U, Summer KH. Dissolution of copper-rich granules in hepatic lysosomes by D-penicillamine prevents the development of fulminant hepatitis in Long-Evans cinnamon rats. J Hepatol 2000;32:193-201.
  • 44.Tanabe R. [Disposition behavior and absorption mechanism of trientine, an orphan drug for Wilson’s disease]. Hokkaido Igaku Zasshi 1996;71:217-228.
  • 45.Sorenson JR, Hangarter W. Treatment of rheumatoid and degenerative diseases with copper complexes: a review with emphasis on copper-salicylate. Inflammation 1977;2:217-238.
  • 46.Khan MK, Miller MW, Taylor J et al. Radiotherapy and antiangiogenic TM in lung cancer. Neoplasia 2002;4:164-170.View Abstract
  • 47.Pan Q, Kleer CG, van Golen KL et al. Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Res 2002;62:4854-4859.View Abstract
  • 48.Brewer GJ, Johnson VD, Dick RD et al. Treatment of Wilson’s disease with zinc. XVII: treatment during pregnancy. Hepatology 2000;31:364-370.
  • 49.Hurd RW, Van Rinsvelt HA, Wilder BJ et al. Selenium, zinc, and copper changes with valproic acid: possible relation to drug side effects. Neurology 1984;34:1393-1395.
  • 50.Lerman-Sagie T, Statter M, Szabo G, Lerman P. Effect of valproic acid therapy on zinc metabolism in children with primary epilepsy. Clin Neuropharmacol 1987;10:80-86.
  • 51.Sozuer DT, Barutcu UB, Karakoc Y et al. The effects of antiepileptic drugs on serum zinc and copper levels in children. J Basic Clin Physiol Pharmacol 1995;6:265-269.View Abstract
  • 52.Kurekci AE, Alpay F, Tanindi S et al. Plasma trace element, plasma glutathione peroxidase, and superoxide dismutase levels in epileptic children receiving antiepileptic drug therapy. Epilepsia 1995;36:600-604.View Abstract
  • 53.Verrotti A, Basciani F, Trotta D et al. Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res 2002;48:71-75.
  • 54.Kaji M, Ito M, Okuno T et al. Serum copper and zinc levels in epileptic children with valproate treatment. Epilepsia 1992;33:555-557.
  • 55.Suzuki T, Koizumi J, Moroji T et al. Effects of long-term anticonvulsant therapy on copper, zinc, and magnesium in hair and serum of epileptics. Biol Psychiatry 1992;31:571-581.View Abstract
  • 56.Baum MK, Javier JJ, Mantero-Atienza E et al. Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males. J Acquir Immune Defic Syndr 1991;4:1218-1226.View Abstract
  • 57.Graham NM, Sorensen D, Odaka N et al. Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquir Immune Defic Syndr 1991;4:976-980.View Abstract
  • 58.Allavena C, Dousset B, May T et al. Relationship of trace element, immunological markers, and HIV1 infection progression. Biol Trace Elem Res 1995;47:133-138.
  • 59.Lai H, Lai S, Shor-Posner G et al. Plasma zinc, copper, copper:zinc ratio, and survival in a cohort of HIV-1-infected homosexual men. J Acquir Immune Defic Syndr 2001;27:56-62.View Abstract
  • 60.Jimenez-Exposito MJ, Bullo Bonet M, Alonso-Villaverde C et al. [Micronutrients in HIV infection and the relationship with the inflammatory response]. Med Clin (Barc) 2002;119:765-769.View Abstract
  • 61.Gyorffy EJ, Chan H. Copper deficiency and microcytic anemia resulting from prolonged ingestion of over-the-counter zinc. Am J Gastroenterol 1992;87:1054-1055.View Abstract
  • .[No author listed.] Cuprimine product information (MSD-U.S.). Whitehouse Station, NJ; Merck & Co. Inc; Rec 7/89, Rev 3/89.
  • .[No author listed.] Syprine product information (MSD-U.S.) West Point, PA: Merck & Co, Inc; Rec 11/89, Rev 3/89.
  • .Abdel-Mageed A, Oehme F. A review of biochemical roles, toxicity and interactions of zinc, copper and iron: II: copper. Vet Hum Toxicol 1990;32(3):230-234.
  • .Aggett PJ. An overview of the metabolism of copper. Eur J Med Res 1999;4(6):214-216. (Review)
  • .Aoyogi S, Baker DH. Bioavailability of copper in analytical-grade and feed-grade inorganic copper sources when fed to provide copper at levels below the chicks requirement. Poult Sci 1993;72:1075-1083.
  • .Baker DH, Odle J, Funk MA, et al. Bioavailability of copper in cupric oxide, cuprous oxide and in a copper-lysine complex. Poult Sci 1991;70:177-179.
  • .Baker DH. Cupric oxide should not be used as a copper supplement for either animals or humans. J Nutr 1999;129:2278-2279.
  • .Bedwal RS, Bahuguna A. Zinc, copper and selenium in reproduction. Experientia 1994;50(7):626-640. (Review)
  • .Burkitt MJ. A critical overview of the chemistry of copper-dependent low density lipoprotein oxidation: roles of lipid hydroperoxides, alpha-tocopherol, thiols, and ceruloplasmin. Arch Biochem Biophys 2001;394(1):117-135.
  • .Covington T, ed. Nonprescription drug therapy guiding patient self-care. St Louis: Facts and Comparisons; 1999:467-545.
  • .Cromwell GL, Stahly TS, Moneque HJ. Effects of source and level of copper on performance and liver copper stores in weanling pigs. J Anim Sci 1989;67:2996-3002.
  • .Dunlap W, James W, Hume D. Anemia and neutropenia caused by copper deficiency. Ann Int Med 1974;80:470-476.
  • .Falchuk KH. Disturbances in trace elements. In: Fauci A, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s principles of internal medicine. 14 th ed. New York: McGraw-Hill Companies Health Professional Division; 1998:490-491.
  • .Fields M, Lewis CG, Lure MD. Garlic oil extract ameliorates the severity of copper deficiency. J Am Coll Nutr 1992;11(3):334-339.
  • .Ford ES. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol 2000;151:1182-1188.
  • .George GN, Pickering IJ, Harris HH, et al. Tetrathiomolybdate causes formation of hepatic copper-molybdenum clusters in an animal model of Wilson’s disease. J Am Chem Soc 2003;125(7):1704-1705.
  • .Harris ED. Copper homeostasis: the role of cellular transporters. Nutr Rev 2001;59(9):281-285.
  • .Harvey LJ, Dainty JR, Hollands WJ, et al. Use of mathematical modeling to study copper metabolism in humans. Am J Clin Nutr 2005;81(4):807-813.
  • .Heller RM, Kirchner SG, O’Neill JA Jr, et al. Skeletal changes of copper deficiency in infants receiving prolonged total parenteral nutrition. J Pediatr 1978;92(6):947-949.
  • .Hoffman H, Phyliky R, Fleming C. Zinc-induced copper deficiency. Gastroenterology 1988;94:508-512.
  • .Holt GA. Food and drug interactions. Chicago: Precept Press;1998.
  • .Jaanus SD. Ocular side effects of selected systemic drugs. Optom Clin 1992;2(4):73-96. (Review)
  • .Jacob RA, Skala JH, Omaye ST, et al. Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. J Nutr 1987;117:2109-2115.
  • .Jantsch W, Kulig K, Rumack BH. Massive copper sulfate ingestion resulting in hepatotoxicity. J Toxicol Clin Toxicol 1984-85;22(6):585-588.
  • .Jones AA, DiSilvestro RA, Coleman M, et al. Copper supplementation of adult men: effects on blood copper enzyme activities and indicators of cardiovascular disease risk. Metabolism 1997;46:1380-1383.
  • .Keen CL, Lonnerdal B, Hurley LS. Drug-induced copper deficiency: a model for copper deficiency teratogenicity. Teratology 1983;28(1):155-156.
  • .Kelley DS, Daudu PA, Taylor PC, et al. Effects of low-copper diets on human immune response. Am J Clin Nutr 1995;62(2):412-416.
  • .Klevay LM. Copper in legumes may lower heart disease risk. Arch Intern Med 2002;162(15):1780. (Letter)
  • .Klevay LM, Medeiros DM. Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations about copper. J Nutr 1996;126:2419S-2426S.
  • .Kuzuya T, Amioka K, Nabeshima T. Valproic acid increases biliary copper excretion in the rat. Epilepsy Res 2002;51(3):279-285.
  • .Ledoux DR, Henry PR, Ammerman CB, et al. Estimation of the relative bioavailability of inorganic copper sources for chicks using tissue uptake of copper. J Anim Sci 1991;69:215-222.
  • .Lowe NM, Lowe NM, Fraser WD, et al. Is there a potential therapeutic value of copper and zinc for osteoporosis? Proc Nutr Soc 2002;61(2):181-185. (Review)
  • .Mahabir S, Spitz MR, Barrera SL, et al. Dietary zinc, copper and selenium, and risk of lung cancer. Int J Cancer 2006.Epub ahead of print.
  • .Mason K. A conspectus of research on copper metabolism and requirements of man. J Nutr 1979;109(11):1979-2066.
  • .Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27(3):517-527.
  • .Medeiros DM, Wildman R. New findings on a unified perspective of copper restriction and cardiomyopathy. Proc Soc Exp Biol Med 1997;215:299-313.
  • .Milne DB. Copper intake and assessment of copper status. Am J Clin Nutr 1998;67(5 Suppl):1041S-1045S. (Review)
  • .Milne DB, Davis CD, Nielsen FH. Low dietary zinc alters indices of copper function and status in postmenopausal women. Nutrition 2001;17(9):701-708.
  • .Milne DB, Johnson PE. Assessment of copper status: effect of age and gender on reference ranges in healthy adults. Clin Chem 1993;39(5):883-887.
  • .National Research Council. Recommended dietary allowances. 10th ed. Washington, DC: National Academy Press; 1989.
  • .Pandit A, Bavdekar A, Bhave S. Wilson’s disease. Indian J Pediatr 2002;69(9):785-791. (Review)
  • .Perry AR, Pagliuca A, Fitzsimons EJ, et al. Acquired sideroblastic anaemia induced by a copper-chelating agent. Int J Hematol 1996;64(1):69-72.
  • .Powanda MC, Blackburn BS, Bostian KA, et al. Clofibrate-induced alterations in zinc, iron and copper metabolism. Biochem Pharmacol 1978;27(1):125-127.
  • .Robinson C, Weigly E. Basic nutrition and diet therapy. New York: MacMillan;1984.
  • .Roe DA. Diet and drug interactions. New York: Van Nostrand Reinhold;1989.
  • .Roe DA. Drug-induced nutritional deficiencies. 2nd ed. Westport, CT: Avi Publishing;1985.
  • .Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and nutrients: the interactive effects. New York: Marcel Decker;1984:505-523.
  • .Rossi L, Marchese E, Lombardo MF, et al. Increased susceptibility of copper-deficient neuroblastoma cells to oxidative stress-mediated apoptosis. Free Radic Biol Med 2001;30(10):1177-1187.
  • .Saltman PD, Strause LG. The role of trace minerals in osteoporosis. J Am Coll Nutr 1993;12(4):384-389.
  • .Sandstead HH. Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am J Clin Nutr 1995;61(Suppl):62S-64S.
  • .Sandstead H. Trace element interactions. J Lab Clin Med 1981;98(4):457-462.
  • .Shepherd RG, Baughn C, Cantrall ML, et al. Structure-activity studies leading to ethambutol, a new type of antituberculous compound. Ann N Y Acad Sci 1966;135(2):686-710.
  • .Squitti R, Lupoi D, Pasqualetti P, et al. Elevation of serum copper levels in Alzheimer’s disease. Neurology 2002;59(8):1153-1161.
  • .Strain JJ. A reassessment of diet and osteoporosis: possible role for copper. Med Hypotheses 1988;27(4):333-338.
  • .Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr 1994;124(7):1060-1064.
  • .Suzuki KT, Ogura Y. [Biological regulation of copper and selective removal of copper: therapy for Wilson disease and its molecular mechanism.] Yakugaku Zasshi 2000;120(10):899-908. [Japanese] (Review)
  • .Suzuki KT, Someya A, Komada Y, et al. Roles of metallothionein in copper homeostasis: responses to Cu-deficient diets in mice. J Inorg Biochem 2002;88(2):173-182.
  • .Threlkeld DS, ed. Miscellaneous products, penicillamine. In: Facts and comparisons drug information. St Louis: Facts and Comparisons;1996.
  • .Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991;44(5):1651-1658. (Review)
  • .Turnland J. Copper nutriture, bioavailability, and the influence of dietary factors. J Am Diet Assoc 1988;88:303-308.
  • .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.
  • .Turnlund JR, Keyes WR, Kim SK, et al. Long-term high copper intake: effects on copper absorption, retention, and homeostasis in men. Am J Clin Nutr 2005;81(4):822-828.
  • .Turnlund JR, Scott KC, Peiffer GL, et al. Copper status of young men consuming a low-copper diet. Am J Clin Nutr 1997;65(1):72-78.
  • .Vanchieri C. Cutting copper curbs angiogenesis, studies show. J Natl Cancer Inst 2000;92(15):1202-1203.
  • .Werbach MR. Foundations of nutritional medicine. Tarzana, CA: Third Line Press;1997. (Review)
  • .Youssef A, Wood B, Baron DN. Serum copper: a marker of disease activity in rheumatoid arthritis. J Clin Pathol 1983;36:14-17.
  • 61.Folkers K, Choe JY, Combs AB. Rescue by coenzyme Q10 from electrocardiographic abnormalities caused by the toxicity of Adriamycin in the rat. Proc Natl Acad Sci U S A 1978;75:5178-5180.View Abstract
  • 62.Choe JY, Combs AB, Saji S, Folkers K. Study of the combined and separate administration of doxorubicin and coenzyme Q10 on mouse cardiac enzymes. Res Commun Chem Pathol Pharmacol 1979;24:595-598.
  • 63.Choe JY, Combs AB, Folkers K. Prevention by coenzyme Q10 of the electrocardiographic changes induced by Adriamycin in rats. Res Commun Chem Pathol Pharmacol 1979;23:199-202.
  • 64.Lubawy WC, Dallam RA, Hurley LH. Protection against anthramycin-induced toxicity in mice by coenzyme Q10. J Natl Cancer Inst 1980;64:105-109.
  • 65.Shaeffer J, El-Mahdi AM, Nichols RK. Coenzyme Q10 and Adriamycin toxicity in mice. Res Commun Chem Pathol Pharmacol 1980;29:309-315.
  • 66.Usui T, Ishikura H, Izumi Y et al. Possible prevention from the progression of cardiotoxicity in Adriamycin-treated rabbits by coenzyme Q10. Toxicol Lett 1982;12:75-82.
  • 67.Shinozawa S, Kawasaki H, Gomita Y. [Effect of biological membrane stabilizing drugs (coenzyme Q10, dextran sulfate and reduced glutathione) on Adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice]. Gan To Kagaku Ryoho 1996;23:93-98.
  • 68.Shinozawa S, Gomita Y, Araki Y. Tissue concentration of doxorubicin (Adriamycin) in mouse pretreated with alpha-tocopherol or coenzyme Q10. Acta Med Okayama 1991;45:195-199.
  • 69.Neri B, Neri GC, Bandinelli M. Differences between carnitine derivatives and coenzyme Q10 in preventing in vitro doxorubicin-related cardiac damages. Oncology 1988;45:242-246.
  • 70.Ronca-Testoni S, Zucchi R, Ronca F, Bertelli A. Effect of carnitine and coenzyme Q10 on the calcium uptake in heart sarcoplasmic reticulum of rats treated with anthracyclines. Drugs Exp Clin Res 1992;18:437-442.
  • 71.Iarussi D, Auricchio U, Agretto A et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med 1994;15 Suppl:s207-s212.
  • 72.Folkers K, Langsjoen P, Willis R et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A 1990;87:8931-8934.
  • 73.Watts GF, Castelluccio C, Rice-Evans C et al. Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin. J Clin Pathol 1993;46:1055-1057.
  • 74.Ghirlanda G, Oradei A, Manto A et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993;33:226-229.
  • 75.De Pinieux G, Chariot P, Ammi-Said M et al. Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol 1996;42:333-337.
  • 76.Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med 1997;18 Suppl:S137-S144.
  • 77.Silver MA, Langsjoen PH, Szabo S et al. Statin cardiomyopathy? A potential role for co-enzyme Q10 therapy for statin-induced changes in diastolic LV performance: description of a clinical protocol. Biofactors 2003;18:125-127.
  • 78.Passi S, Stancato A, Aleo E et al. Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 2003;18:113-124.
  • 79.Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10: a review of animal and human publications. Biofactors 2003;18:101-111.
  • 80.Langsjoen PH, Folkers K, Lyson K et al. Pronounced increase of survival of patients with cardiomyopathy when treated with coenzyme Q10 and conventional therapy. Int J Tissue React 1990;12:163-168.
  • 81.Manzoli U, Rossi E, Littarru GP et al. Coenzyme Q10 in dilated cardiomyopathy. Int J Tissue React 1990;12:173-178.
  • 82.Sinatra ST. Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration. Mol Aspects Med 1997;18 Suppl:S299-S305.
  • 82a.Willis RA, Folkers K, Tucker JL, et al. Lovastatin decreases coenzyme Q levels in rats. Proc Natl Acad Sci USA 1990 Nov;87(22):8928-8930.
  • 83.Ichihara K, Satoh K, Yamamoto A, Hoshi K. [Are all HMG-CoA reductase inhibitors protective against ischemic heart disease?]. Nippon Yakurigaku Zasshi 1999;114 Suppl 1:142P-149P.
  • 84.Rosenfeldt FL, Pepe S, Linnane A et al. Coenzyme Q10 protects the aging heart against stress: studies in rats, human tissues, and patients. Ann NY Acad Sci 2002;959:355-359; discussion 463-355.
  • 85.Laaksonen R, Ojala JP, Tikkanen MJ, Himberg JJ. Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1994;46:313-317.
  • 86.Paloma'ki A, Malminiemi K, Metsa-Ketela T. Enhanced oxidizability of ubiquinol and alpha-tocopherol during lovastatin treatment. FEBS Lett 1997;410:254-258.
  • 87.Paloma'ki A, Malminiemi K, Solakivi T, Malminiemi O. Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo. J Lipid Res 1998;39:1430-1437.
  • 88.Bleske BE, Willis RA, Anthony M et al. The effect of pravastatin and atorvastatin on coenzyme Q10. Am Heart J 2001;142:E2.
  • 89.Rundek T, Naini A, Sacco R et al. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol 2004;61:889-892.
  • 90.Yoshida H, Ishikawa T, Ayaori M et al. Effect of low-dose simvastatin on cholesterol levels, oxidative susceptibility, and antioxidant levels of low-density lipoproteins in patients with hypercholesterolemia: a pilot study. Clin Ther 1995;17:379-389.
  • 91.Baum H. New Scientist 1991:24. {AU: article title?}
  • 92.Bargossi AM, Battino M, Gaddi A et al. Exogenous CoQ10 preserves plasma ubiquinone levels in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Int J Clin Lab Res 1994;24:171-176.
  • 93.Miyake Y, Shouzu A, Nishikawa M et al. Effect of treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung 1999;49:324-329.
  • 94.Pettit FH, Harper RF, Vilaythong J et al. Reversal of statin toxicity to human lymphocytes in tissue culture. Drug Metab Drug Interact 2003;19:151-160.
  • 95.Watts GF, Playford DA, Croft KD et al. Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in type II diabetes mellitus. Diabetologia 2002;45:420-426.
  • 96.Title LM, Cummings PM, Giddens K et al. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758-765.
  • 97.White CM. Pharmacological effects of HMG CoA reductase inhibitors other than lipoprotein modulation. J Clin Pharmacol 1999;39:111-118.
  • 98.Wong B, Lumma WC, Smith AM et al. Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. J Leukoc Biol 2001;69:959-962.
  • 99.Brady AJB, Norrie J, Ford I. Statin prescribing: Is the reality meeting the expectations of primary care. Br J Cardiol 2005;12:397-400.
  • 100.Goldman RE, Parker DR, Eaton CB et al. Patients' perceptions of cholesterol, cardiovascular disease risk, and risk communication strategies. Ann Fam Med 2006;4:205-212.
  • 101.Brown MS. Coenzyme Q10 with HMG-CoA reductase inhibitors. Merck and Co (Rahway, NJ); 1990.
  • 102.Tobert JA. Coenzyme Q10 with HMG-CoA reductase inhibitors. Merck and Co (Rahway, NJ); 1990.
  • 103.Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine: prevention by forms of coenzyme Q of the inhibition by Adriamycin of coenzyme Q10-enzymes in mitochondria of the myocardium. Proc Natl Acad Sci U S A 1976;73:4653-4656.
  • 104.Singh RB, Niaz MA, Rastogi SS et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999;13:203-208.
  • 105.Hodgson JM, Watts GF, Playford DA et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56:1137-1142.
  • 106.Glassman AH, Roose SP. Risks of antidepressants in the elderly: tricyclic antidepressants and arrhythmia-revising risks. Gerontology 1994;40 Suppl 1:15-20.
  • 107.Scahill L, Lynch KA. Tricyclic antidepressants: cardiac effects and clinical implications. J Child Adolesc Psychiatr Nurs 1994;7:37-39.
  • 108.Pinto J, Huang YP, Pelliccione N, Rivlin RS. Cardiac sensitivity to the inhibitory effects of chlorpromazine, imipramine and amitriptyline upon formation of flavins. Biochem Pharmacol 1982;31:3495-3499.
  • 109.Morton RA. Ubiquinones, plastoquinones and vitamins K. Biol Rev Camb Philos Soc 1971;46:47-96.
  • 110.Combs AB, Porter TH, Folkers K. Anticoagulant activity of a naphthoquinone analog of vitamin K and an inhibitor of coenzyme Q10-enzyme systems. Res Commun Chem Pathol Pharmacol 1976;13:109-114.
  • 111.Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;344:1372-1373.
  • 112.Landbo C, Almdal TP. [Interaction between warfarin and coenzyme Q10]. Ugeskr Laeger 1998;160:3226-3227.
  • 113.Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-1227; quiz 1228-1230.
  • 113a.Engelsen J, Nielsen JD, Hansen KF. [Effect of Coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial] Ugeskr Laeger. 2003 Apr 28;165(18):1868-1871. [Danish]
  • 114.Linder MW. Genetic mechanisms for hypersensitivity and resistance to the anticoagulant warfarin. Clin Chim Acta 2001;308:9-15.
  • 115.Aberg F, Appelkvist EL, Broijersen A et al. Gemfibrozil-induced decrease in serum ubiquinone and alpha- and gamma-tocopherol levels in men with combined hyperlipidaemia. Eur J Clin Invest 1998;28:235-242.
  • 116.Kotake C, Ito Y, Yokoyama M, Fukuzaki H. Protective effect of coenzyme Q10 on thyrotoxic heart in rabbits. Heart Vessels 1987;3:84-90.
  • 117.Mancini A, De Marinis L, Calabro F et al. Evaluation of metabolic status in amiodarone-induced thyroid disorders: plasma coenzyme Q10 determination. J Endocrinol Invest 1989;12:511-516.
  • 118.Portakal O, Inal-Erden M. Effects of pentoxifylline and coenzyme Q10 in hepatic ischemia/reperfusion injury. Clin Biochem 1999;32:461-466.
  • 119.Lund EL, Quistorff B, Spang-Thomsen M, Kristjansen PE. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 1998;43:505-506.
  • 120.Rosenfeldt FL, Mijch A, McCrystal G et al. Skeletal myopathy associated with nucleoside reverse transcriptase inhibitor therapy: potential benefit of coenzyme Q10 therapy. Int J STD AIDS 2005;16:827-829.
  • 121.Willis R, Anthony M, Sun L et al. Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status. Biofactors 1999;9:359-363.
  • 122.Kagan VE, Fabisak JP, Tyurina YY. Independent and concerted antioxidant functions of coenzyme Q. In: Kagan VE, Quinn PJ, eds. Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton, Fla: CRC Press; 2001:119-130.
  • 123.Thomas SR, Stocker R. Mechanisms of antioxidant action of ubiquinol-10 for low-density lipoprotein. In: Kagan VE, Quinn PJ, eds. Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton, Fla: CRC Press; 2001:131-150.
  • 61.Folkers K, Choe JY, Combs AB. Rescue by coenzyme Q10 from electrocardiographic abnormalities caused by the toxicity of Adriamycin in the rat. Proc Natl Acad Sci U S A 1978;75:5178-5180.View Abstract
  • 62.Choe JY, Combs AB, Saji S, Folkers K. Study of the combined and separate administration of doxorubicin and coenzyme Q10 on mouse cardiac enzymes. Res Commun Chem Pathol Pharmacol 1979;24:595-598.
  • 63.Choe JY, Combs AB, Folkers K. Prevention by coenzyme Q10 of the electrocardiographic changes induced by Adriamycin in rats. Res Commun Chem Pathol Pharmacol 1979;23:199-202.
  • 64.Lubawy WC, Dallam RA, Hurley LH. Protection against anthramycin-induced toxicity in mice by coenzyme Q10. J Natl Cancer Inst 1980;64:105-109.
  • 65.Shaeffer J, El-Mahdi AM, Nichols RK. Coenzyme Q10 and Adriamycin toxicity in mice. Res Commun Chem Pathol Pharmacol 1980;29:309-315.
  • 66.Usui T, Ishikura H, Izumi Y et al. Possible prevention from the progression of cardiotoxicity in Adriamycin-treated rabbits by coenzyme Q10. Toxicol Lett 1982;12:75-82.
  • 67.Shinozawa S, Kawasaki H, Gomita Y. [Effect of biological membrane stabilizing drugs (coenzyme Q10, dextran sulfate and reduced glutathione) on Adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice]. Gan To Kagaku Ryoho 1996;23:93-98.
  • 68.Shinozawa S, Gomita Y, Araki Y. Tissue concentration of doxorubicin (Adriamycin) in mouse pretreated with alpha-tocopherol or coenzyme Q10. Acta Med Okayama 1991;45:195-199.
  • 69.Neri B, Neri GC, Bandinelli M. Differences between carnitine derivatives and coenzyme Q10 in preventing in vitro doxorubicin-related cardiac damages. Oncology 1988;45:242-246.
  • 70.Ronca-Testoni S, Zucchi R, Ronca F, Bertelli A. Effect of carnitine and coenzyme Q10 on the calcium uptake in heart sarcoplasmic reticulum of rats treated with anthracyclines. Drugs Exp Clin Res 1992;18:437-442.
  • 71.Iarussi D, Auricchio U, Agretto A et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med 1994;15 Suppl:s207-s212.
  • 72.Folkers K, Langsjoen P, Willis R et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A 1990;87:8931-8934.
  • 73.Watts GF, Castelluccio C, Rice-Evans C et al. Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin. J Clin Pathol 1993;46:1055-1057.
  • 74.Ghirlanda G, Oradei A, Manto A et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993;33:226-229.
  • 75.De Pinieux G, Chariot P, Ammi-Said M et al. Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol 1996;42:333-337.
  • 76.Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med 1997;18 Suppl:S137-S144.
  • 77.Silver MA, Langsjoen PH, Szabo S et al. Statin cardiomyopathy? A potential role for co-enzyme Q10 therapy for statin-induced changes in diastolic LV performance: description of a clinical protocol. Biofactors 2003;18:125-127.
  • 78.Passi S, Stancato A, Aleo E et al. Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 2003;18:113-124.
  • 79.Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10: a review of animal and human publications. Biofactors 2003;18:101-111.
  • 80.Langsjoen PH, Folkers K, Lyson K et al. Pronounced increase of survival of patients with cardiomyopathy when treated with coenzyme Q10 and conventional therapy. Int J Tissue React 1990;12:163-168.
  • 81.Manzoli U, Rossi E, Littarru GP et al. Coenzyme Q10 in dilated cardiomyopathy. Int J Tissue React 1990;12:173-178.
  • 82.Sinatra ST. Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration. Mol Aspects Med 1997;18 Suppl:S299-S305.
  • 82a.Willis RA, Folkers K, Tucker JL, et al. Lovastatin decreases coenzyme Q levels in rats. Proc Natl Acad Sci USA 1990 Nov;87(22):8928-8930.
  • 83.Ichihara K, Satoh K, Yamamoto A, Hoshi K. [Are all HMG-CoA reductase inhibitors protective against ischemic heart disease?]. Nippon Yakurigaku Zasshi 1999;114 Suppl 1:142P-149P.
  • 84.Rosenfeldt FL, Pepe S, Linnane A et al. Coenzyme Q10 protects the aging heart against stress: studies in rats, human tissues, and patients. Ann NY Acad Sci 2002;959:355-359; discussion 463-355.
  • 85.Laaksonen R, Ojala JP, Tikkanen MJ, Himberg JJ. Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1994;46:313-317.
  • 86.Paloma'ki A, Malminiemi K, Metsa-Ketela T. Enhanced oxidizability of ubiquinol and alpha-tocopherol during lovastatin treatment. FEBS Lett 1997;410:254-258.
  • 87.Paloma'ki A, Malminiemi K, Solakivi T, Malminiemi O. Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo. J Lipid Res 1998;39:1430-1437.
  • 88.Bleske BE, Willis RA, Anthony M et al. The effect of pravastatin and atorvastatin on coenzyme Q10. Am Heart J 2001;142:E2.
  • 89.Rundek T, Naini A, Sacco R et al. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol 2004;61:889-892.
  • 90.Yoshida H, Ishikawa T, Ayaori M et al. Effect of low-dose simvastatin on cholesterol levels, oxidative susceptibility, and antioxidant levels of low-density lipoproteins in patients with hypercholesterolemia: a pilot study. Clin Ther 1995;17:379-389.
  • 91.Baum H. New Scientist 1991:24. {AU: article title?}
  • 92.Bargossi AM, Battino M, Gaddi A et al. Exogenous CoQ10 preserves plasma ubiquinone levels in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Int J Clin Lab Res 1994;24:171-176.
  • 93.Miyake Y, Shouzu A, Nishikawa M et al. Effect of treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung 1999;49:324-329.
  • 94.Pettit FH, Harper RF, Vilaythong J et al. Reversal of statin toxicity to human lymphocytes in tissue culture. Drug Metab Drug Interact 2003;19:151-160.
  • 95.Watts GF, Playford DA, Croft KD et al. Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in type II diabetes mellitus. Diabetologia 2002;45:420-426.
  • 96.Title LM, Cummings PM, Giddens K et al. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758-765.
  • 97.White CM. Pharmacological effects of HMG CoA reductase inhibitors other than lipoprotein modulation. J Clin Pharmacol 1999;39:111-118.
  • 98.Wong B, Lumma WC, Smith AM et al. Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. J Leukoc Biol 2001;69:959-962.
  • 99.Brady AJB, Norrie J, Ford I. Statin prescribing: Is the reality meeting the expectations of primary care. Br J Cardiol 2005;12:397-400.
  • 100.Goldman RE, Parker DR, Eaton CB et al. Patients' perceptions of cholesterol, cardiovascular disease risk, and risk communication strategies. Ann Fam Med 2006;4:205-212.
  • 101.Brown MS. Coenzyme Q10 with HMG-CoA reductase inhibitors. Merck and Co (Rahway, NJ); 1990.
  • 102.Tobert JA. Coenzyme Q10 with HMG-CoA reductase inhibitors. Merck and Co (Rahway, NJ); 1990.
  • 103.Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine: prevention by forms of coenzyme Q of the inhibition by Adriamycin of coenzyme Q10-enzymes in mitochondria of the myocardium. Proc Natl Acad Sci U S A 1976;73:4653-4656.
  • 104.Singh RB, Niaz MA, Rastogi SS et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999;13:203-208.
  • 105.Hodgson JM, Watts GF, Playford DA et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56:1137-1142.
  • 106.Glassman AH, Roose SP. Risks of antidepressants in the elderly: tricyclic antidepressants and arrhythmia-revising risks. Gerontology 1994;40 Suppl 1:15-20.
  • 107.Scahill L, Lynch KA. Tricyclic antidepressants: cardiac effects and clinical implications. J Child Adolesc Psychiatr Nurs 1994;7:37-39.
  • 108.Pinto J, Huang YP, Pelliccione N, Rivlin RS. Cardiac sensitivity to the inhibitory effects of chlorpromazine, imipramine and amitriptyline upon formation of flavins. Biochem Pharmacol 1982;31:3495-3499.
  • 109.Morton RA. Ubiquinones, plastoquinones and vitamins K. Biol Rev Camb Philos Soc 1971;46:47-96.
  • 110.Combs AB, Porter TH, Folkers K. Anticoagulant activity of a naphthoquinone analog of vitamin K and an inhibitor of coenzyme Q10-enzyme systems. Res Commun Chem Pathol Pharmacol 1976;13:109-114.
  • 111.Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;344:1372-1373.
  • 112.Landbo C, Almdal TP. [Interaction between warfarin and coenzyme Q10]. Ugeskr Laeger 1998;160:3226-3227.
  • 113.Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-1227; quiz 1228-1230.
  • 113a.Engelsen J, Nielsen JD, Hansen KF. [Effect of Coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial] Ugeskr Laeger. 2003 Apr 28;165(18):1868-1871. [Danish]
  • 114.Linder MW. Genetic mechanisms for hypersensitivity and resistance to the anticoagulant warfarin. Clin Chim Acta 2001;308:9-15.
  • 115.Aberg F, Appelkvist EL, Broijersen A et al. Gemfibrozil-induced decrease in serum ubiquinone and alpha- and gamma-tocopherol levels in men with combined hyperlipidaemia. Eur J Clin Invest 1998;28:235-242.
  • 116.Kotake C, Ito Y, Yokoyama M, Fukuzaki H. Protective effect of coenzyme Q10 on thyrotoxic heart in rabbits. Heart Vessels 1987;3:84-90.
  • 117.Mancini A, De Marinis L, Calabro F et al. Evaluation of metabolic status in amiodarone-induced thyroid disorders: plasma coenzyme Q10 determination. J Endocrinol Invest 1989;12:511-516.
  • 118.Portakal O, Inal-Erden M. Effects of pentoxifylline and coenzyme Q10 in hepatic ischemia/reperfusion injury. Clin Biochem 1999;32:461-466.
  • 119.Lund EL, Quistorff B, Spang-Thomsen M, Kristjansen PE. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 1998;43:505-506.
  • 120.Rosenfeldt FL, Mijch A, McCrystal G et al. Skeletal myopathy associated with nucleoside reverse transcriptase inhibitor therapy: potential benefit of coenzyme Q10 therapy. Int J STD AIDS 2005;16:827-829.
  • 121.Willis R, Anthony M, Sun L et al. Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status. Biofactors 1999;9:359-363.
  • 122.Kagan VE, Fabisak JP, Tyurina YY. Independent and concerted antioxidant functions of coenzyme Q. In: Kagan VE, Quinn PJ, eds. Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton, Fla: CRC Press; 2001:119-130.
  • 123.Thomas SR, Stocker R. Mechanisms of antioxidant action of ubiquinol-10 for low-density lipoprotein. In: Kagan VE, Quinn PJ, eds. Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton, Fla: CRC Press; 2001:131-150.