The Nutritional Relationships of Copper David L. Watts, D.C., Ph.D., F.A.C.E.P.1 Introduction
milligrams percent. When sampled properly,
The mineral copper was shown to be an TMA can provide a good index of nutritional
essential nutrient for hemoglobin synthesis in copper status13 14 and relationship to other animals in 1928.1 The therapeutic use of copper synergistic and antagonistic trace elements. and its requirements in humans was later reported by Mills and others.2 3 Copper has since been Conditions Associated with Copper Imbalance found to be a constituent of many important
One of the earliest conditions found to be
enzymes including cytochrome c oxidase, associated with copper deficiency is iron superoxide
(cytoplasm), deficiency anemia, which could only be corrected
Ceruloplasmin, dopamine B-hydroxylase, lysyl with copper supplementation. Copper deficiency oxidase, tyrosinase, and monoamine oxidase.
impairs iron absorption, reduces heme synthesis,
The copper content of a healthy adult has been and increases iron accumulation in storage
reported to be approximately eighty milligrams.4
tissues. These processes are dependent upon
The highest level of copper is found in the liver copper through the effects of the copper enzyme and brain, followed by the heart, kidney, Ceruloplasmin.15 A chronic copper deficiency pancreas, spleen, lungs, bone, and muscle.
can result in hemosiderosis, a condition characterized by an increase in iron accumulation
Copper Evaluation Through Tissue Mineral
in body tissues due to an impairment in the
Analysis (TMA) of Human Hair
reutilization of hemoglobin iron. Hemosiderosis
TMA of hair has proven to be a good method is known to occur in malignancies, inflammatory
for assessing nutritional copper status. Recently disorders, and rheumatoid arthritis.16 Medeiros5 reported positive correlations of TMA copper levels in animals based upon three levels Arthritis and Copper of dietary copper intake. This study supports the
Iron accumulation in the joints due to copper
feasibility for the use of TMA in detecting deficiency can be a major contributor to changes in the diet of copper and other minerals. rheumatoid arthritis.17 Studies reported by Medeiros' study also confirms the findings of Kishore et al illustrated the relationship of copper earlier investigators, which also support the deficiency and arthritis in animal studies. validity of using TMA in assessing copper Adjuvant arthritis was more severe in animals on status.6 7 8 9 Ikeda, et al10 found that the hair a copper deficient diet, and the tissue iron levels concentration of copper correlates with blood were found to be over four hundred percent of hemoglobin levels in children. Hair copper normal.18 It has been stated that rheumatoid concentrations have been found to reflect liver arthritis has become prevalent within the past copper concentration.11 A study reporting the century due to industrialization, i.e. the increased mineral content of maternal and neonate hair production and use of copper antagonists such as revealed an excellent correlation of metals cadmium, zinc, lead, etc. Rainsford hypothesized including copper and establishes a basis for the that the low incidence of rheumatoid arthritis in use of TMA in monitoring the nutritional mineral Europe during pre-industrial times may have status of both the mother and fetus.12
been due to the protection by copper commonly
The ideal TMA level of copper established by used in cooking and eating utensils of the
period.19TMA studies of patients with rheuma-
Trace Elements, Inc., P.O. Box 514, Addison, Texas 75001.
Journal of Orthomolecular Medicine Vol. 4, No. 2, 1989
toid arthritis almost always reveal a low tissue while elevated tissue copper is found with copper level. The more chronic cases show high chronic viral infections. Presently it is not clear iron/copper ratios. An elevated tissue iron/copper whether infectious conditions cause the TMA ratio can also indicate a chronic bacterial copper abnormalities, but it is strongly suspected infection. Rheumatoid arthritis can be secondary that copper status can predispose an individual to to and sometimes caused by an infectious agent either a viral or bacterial infection. The indication resulting in copper depletion or a disturbance in that copper can be a causative factor in the copper balance. It is also well known that incidence of viral or bacterial infections is spontaneous remission of rheumatoid arthritis reflected in studies by Luster and co-workers. occurs in conditions associated with increased They report that estrogen has an enhancing or copper retention such as pregnancy and biliary suppressing effect upon the immune system.28obstruction.20 An Australian study (Walker, et al) Thus the relationship between copper and demonstrated improvement of symptoms of estrogen cannot be overlooked. It has also been rheumatoid arthritis by absorption of copper reported that women have an increased through the skin from the wearing of copper susceptibility to viral infections prior to bracelets.
menstruation (at which time estrogen and copper
TMA studies clearly show that individuals levels are high) and an increased tendency toward
with some forms of rheumatoid arthritis, have bacterial
increased copper requirements. However, TMA menstruation (at which time estrogen and copper studies have revealed that tissue copper levels are levels fall). Generally speaking, we find that above normal in patients with osteoarthritis. This copper deficiency causes a disturbance in cellular can be explained by the calcium-copper-vitamin immunity, while copper excess causes a D relationship discussed later.
This information indicates that any factor that
Infections — Bacterial
antagonizes copper retention can be considered as
Infections are known to affect mineral having anti-viral properties. Those that are
requirements.21 During a synergistic such as vitamin D, B1, B12, and B10,
bacterial infection iron is sequestered into storage which enhance copper retention, can be consi-tissue
(reticuloendothelial-bone-spleen-liver). dered as having anti-bacterial properties (see
This is a normal response since bacteria require figure 1 and 2). As an example, vitamin A, which iron in order to proliferate; therefore, the body is considered to be an anti-infectious vitamin, can removes this nutrient source from the serum.22 23 specifically be categorized as anti-viral. This is Secondarily, serum copper rises due to its also true of vitamin C and zinc. However, zinc, removal from storage tissues thereby improving vitamin C, and vitamin A are mutually the capability to mount an attack and overcome antagonistic to copper; if taken in excessively the invading organism. The opposite is seen in high dosages by individuals with a copper the tissue mineral concentrations. In chronic deficiency, they can actually promote infectious infectious states, the tissue iron increases while processes — especially those of bacterial origin. the tissue copper decreases. This tissue mineral
pattern (elevated iron/copper ratio), is strongly candidiasis is frequently associated with copper indicative of a chronic infection. The most excess. Therefore, minerals and vitamins common source of chronic infections have been antagonistic to copper can be considered to have dental abscesses often present for years without anti-fungal and anti-yeast properties (see figure 1 the patient's knowledge. Infections — Viral Malignancies and Copper
Viral infections produce an anabolic response,
Low TMA copper levels are also frequently
while bacterial infections produce a catabolic found in some types of malignancies,response. Tissue copper deficiency is commonly seen with chronic bacterial infections,24 25 26 27
The Nutritional Relationships of Copper
most of which are of the catabolic or highly infarcts. Klevay has reported that a relative metastatic type. High tissue iron/ copper may or copper deficiency may contribute to ischemic may not be present depending upon the type of heart disease.36 A deficiency of copper relative malignancy. There have been reports that tissue to zinc produces a decrease in HDL (high iron accumulation is found in tissues and lymph density lipoproteins) and an increase in LDL nodes with Hodgkins disease.29 TMA research is (low density lipoproteins).37revealing the increased requirements for copper in
some malignancy conditions. The necessity for cardiovascular
copper is obvious due to its role in respiratory lesterolemia, which is associated with hy- enzyme systems and its participation in superoxide pothyroidism. Copper in excess has adverse dismutase activity, which helps protect the cell effects upon thyroid activity and zinc status. from damage from oxygen toxicity. Cytochrome c oxidase, the terminal oxidase in the electron Orthopedic Disturbances and Copper transport chain, is copper dependent. A reduction Imbalance in cytochrome c oxidase activity results in the
As mentioned previously, adequate copper is
mitochondria becoming enlarged and deformed required for the normal production and integrity with advanced copper deficiency. Animal studies of elastin and collagen, which are components have confirmed the effects of some copper of ligaments and the nucleus pulposus of the compounds as an anti-neoplastic agent. The intervertebral disc. Other minerals and vitamins addition of copper decreased tumor growth, are also involved in collagen and elastin decreased metastasis, and increased survival of synthesis. As an example, vitamin C is required animals with certain types of neoplasms.30 Several for the hydroxylation of proline to hydroxy-reports indicate that serum copper levels rise with proline, which forms chains of tropollo-gen. the severity of some malignancies and return to Vitamin C, iron, and manganese are all normal with remission.31 32
involved in the conversion of lysine to hydroxylysine. Manganese is required for the
One of the early signs of copper deficiency is glucosyltransferase, and zinc is involved in
osteoporosis.33 34 A number of enzymes involved in protein synthesis. Each of these nutrients is collagen synthesis and cross-linking of the organic affected by copper (see figure 1 and 2). matrix of bone require copper. Bone changes in
Davies38 reported studies of lathyrism, which
copper deficiency include a loss of trabecular apparently produces copper deficiency resulting formation with thinning of the cortex. It is common in structural skeletal abnormalities including to find low tissue levels of calcium in conjunction scoliosis, spondylosis, and kyphoscoliosis. with low tissue levels of copper on TMA studies.
Excessive tissue copper is also associated
Through TMA studies, osteoporosis has been with structural skeletal defects. Pratt and linked with both copper deficiency and copper Phippen reported findings in which elevated excess and has been categorized as type I or type II hair copper occurred with idiopathic scoliosis.39osteoporosis respectively.35
synergistically in contributing to scoliosis.
The structure and integrity of the vascular produce relaxation of the pelvic ligaments at the
system is intimately related to copper. An adequate sacroiliac joints and symphysis pubis40 in amount of copper is required for the production of preparation for the birthing process. The the enzyme lysyl oxidase, which is involved in the resulting elasticity allows less resistance for the quality and quantity of elastin formation and fetus when passing through the birth canal. The collagen
copper effect of estrogen is, of course, not confined
deficiency is related to vascular defects such as only to the pelvis. By antagonizing or aneurysms, heart enlargement, heart failure, and producing
Journal of Orthomolecular Medicine Vol. 4, No. 2, 1989
deficiencies of other nutrients (see figure 1 and conditions commonly seen with low tissue copper 2),
ligamentous laxity throughout the skeletal antibiotic
structure. Therefore, any factor that contributes to hyperglycemia, emotional disturbances (manic increased copper retention such as, oral disorders), type I insomnia, and increased contraceptive
pregnancy, sympathetic neuroendocrine activity.
cholestasis, etc., can result in structural skeletal instability and ligamentous laxity. Factors Contributing to Copper Deficiency Neurological Minerals
Copper deficiency is known to affect the
central nervous system. Reports of animal studies antagonistic to copper.49 50 Prolonged high intake have shown defects in myelination with copper of these elements, singularly or in combination, deficiency.41 Observation of TMA studies has can produce a copper deficiency, especially if the shown low tissue copper levels in multiple nutritional or tissue copper status is marginal. The sclerosis patients. Douglas, et al, confirmed this nutritional minerals shown in figure 1 can be used finding in their report, in which they found in the treatment of copper toxicity. Copper significant differences in hair copper levels in supplementation, however, can aid in decreasing forty multiple sclerosis patients compared to the toxic effects of some heavy metals as well as forty-two controls.42 Similar observations have inhibiting their absorption. A report by Fields, et been seen on TMA patterns of patients with al, revealed that copper is adversely affected by Parkinson's disease. Information from animal the consumption of fructose. Copper deficiency studies strongly suggests that copper deficiency was exacerbated in animals fed fructose, and can be a factor in Parkinson's disease in humans, contributed to fatty degeneration of the liver. since dopamine levels were found low in both copper deficient animals and patients with Vitamins Parkinson's.43
Vitamins that are considered antagonistic to
Menkes disease, also known as Steely Hair copper are shown in figure 2. Excessive intake of
disease is an inherited inborn error of copper any one or combination of these vitamins can metabolism in infants. Infants with this condition contribute to or exacerbate an existing copper manifest most of the conditions described with deficiency. The opposite may also occur: excess copper deficiency. This condition is usually fatal copper intake or retention may produce a defi-with a life expectancy of about two years. ciency of any one or combination of these Diagnosis is difficult since these children appear vitamins or increase their requirements. relatively normal after birth and may not manifest
It is interesting to note a similarity of copper
severe symptoms for several weeks or months.44
deficiency to vitamin C deficiency. Many
This condition emphasizes the need for changes as a result of copper deficiency can be nutritional monitoring of the fetus through the described
mother. Baumslag has stated the practicality of symptoms of copper and vitamin C deficiency are using
Copper similar and can be difficult to distinguish. High
supplementation of the mother should provide vitamin C intake should be approached with cau-this nutrient to the fetus since copper easily tion until copper status is evaluated since vitamin crosses the placenta.45
C is known to affect copper antagonistically,51 5253
Other conditions reported to be related to
and/or enzymes that require copper. The
copper deficiency include suppression of immune biochemical defects of copper deficiency can be response46 (cellular), celiac disease, cystic described as a copper deficient scurvy (CDS). fibrosis
of Although the mechanisms of the biochemical
The Nutritional Relationships of Copper Figure 2.
of CDS are different from those caused by vitamin deficiency, include vitamin D, B1, B12, C, and C deficient scurvy, CDS can be produced by folic acid (B10). Supplementation of synergistic excessive vitamin C intake. Conversely, vitamin C vitamins can aid in reducing the effects of copper requirements are increased by excessive copper deficiency and in restoring copper balance. As an intake or tissue accumulation.
production decreases copper retention56 as well
as antagonizes vitamin D metabolism.57 Vitamin
Copper is normally excreted by the liver via D can antagonize the effect of excessive
adrenal stimulation. It has been demonstrated that corticosteroid production, thereby improving copper
the copper retention. This concept can be applied in
administration of adrenal steroids.54 55 Increased helping to reduce the side effects of steroid activity of the sympathetic endocrines tend to therapy. increase the elimination of copper or increase its
The synergistic minerals to copper include
requirements due to increased metabolic demands. calcium, cobalt, selenium, sodium, and iron. The The sympathetic endocrines include the thyroid, rickettsial bone changes that occur with copper adrenal cortex (glucocorticoids), adrenal medulla, deficiency are probably related to the copper-and anterior pituitary.
Nutrients Synergistic to Copper
synergistic and antagonistic. This is due to their
Rarely does a single nutrient deficiency develop co- relationship with copper in metabolic
exclusively. Other nutritional deficiencies and functions such as the requirement for adequate
excess are always involved. Referring to figure 1 amounts of iron and copper for hemoglobin
and 2, we can see the potential of vitamin and production. But excessive iron intake antagonizes
mineral toxicity that can develop in the presence copper absorption on an intestinal level.
of copper deficiency. As an example, the need for vitamin A, C, B6, B3, and B5 is reduced in a Copper Toxicity copper-deficient
vitaminosis of most of these vitamins can be States. TMA studies show that a large percent of reduced by supplying adequate amounts of copper. the population has excessive tissue copper levels. We can see particularly that the adverse effects of This varies geographically due to high copper or hyper-vitaminosis A can be decreased by copper low zinc soils and hard or soft water regions. The supplementation. Synergistic vitamins, those use of copper water pipes and dental prosthesis whose requirements are increased by copper
Journal of Orthomolecular Medicine Vol. 4, No. 2, 1989
have contributed greatly to increased copper
synergistic vitamins and minerals previously
intake. Copper also enters the food chain through
discussed can also contribute to copper toxicity.
the addition of copper to animal feeds and use of
These factors should be explored in relation to
copper in spraying vegetables and grains for the
Wilson's disease, an inborn error of metabolism
prevention of fungus and algae growth.58 Reports
have shown that copper intake in the United
accumulation in the liver due to a lack of
States is approximately three to five milligrams
Ceruloplasmin. Elevated hair copper levels do
per day. The copper intake in India is higher,
not occur with Wilson's disease, but copper accu-
averaging almost six milligrams per day and in
mulation in tissues and organs other than the liver
some areas as much as thirteen milligrams.59
eventually develops. Excessive copper retention
We have learned that metabolic differences
will often develop in the eye, producing the
Kayser-Fleischer rings in the cornea which is a
individuals than others, even with the same
diagnostic sign of this disease. Increased copper
accumulation has also been noted in individuals
studies that vegetarians appear to have a greater
tendency to retain copper than non-vegetarians.
A reduction or blockage in biliary excretion
Henkin60 reported that patients with adrenal
can increase copper accumulation, even if copper
insufficiency had higher serum copper levels,
intake is not excessive. This type of copper
which improved with hormonal therapy. An
increase in parasympathetic neuroendocrine
periods involving several years. Excess estrogens
activity would predispose an individual to an
are known to contribute to gall bladder stasis as
increased copper burden due to a decrease in
well as cholesterol and calcium stone formation.
The development of gallstones is found to have a
endocrines include the pancreas, parathyroid, and
higher incidence in women, especially those who
anabolic steroids. Copper is a sedative mineral,
have been pregnant.66 67 Elevation in estrogen
which when in excess, stimulates anabolic
levels during pregnancy68 and oral contraceptive
activity and increases parasympathetic activity.
use have been reported to consistently produce
TMA studies frequently reveal elevated tissue
defects in the excretory functions of the liver.69
copper in women taking oral contraceptive agents
Increased copper retention can develop as a result
which has been confirmed by others,61 62 as well
of viral infections such as mononucleosis and
in women with copper interuterine devices. Since
hepatitis.70 High tissue copper levels are
copper levels are noted to rise especially during
frequently observed in individuals with a history
the last trimester of pregnancy, it is not unusual
of these conditions. Whether excess tissue copper
to find multigravid women with excessive tissue
causes viral manifestation or viral infections
copper accumulation, particularly if their
cause elevated tissue copper accumulation is
pregnancies were not widely spaced. This will
speculative at this time, but one wonders if the
also contribute to inherited copper toxicity in
anti-viral effects of zinc could be due to the
Copper toxicity can occur when there is a
deficiency of the antagonistic nutrients shown in
Medications That May Contribute to Copper Toxicity
and the minerals zinc and iron. The requirements
The main excretory route for the removal of
for these nutrients are known to increase during
copper is through the intestinal tract; therefore,
pregnancy, with oral contraceptive use, and
estrogen therapy.63 Krishnamachari reported that
extrahepatic excretion can potentially contribute
in individuals suffering from pellagra (B
to copper toxicity. There are many medications
deficiency), copper absorption was increased.64
other than estrogens that can contribute to choles-
tasis. These include phenothiazine derivatives,
The Nutritional Relationships of Copper
chlordiazepoxide, desipramine, imi-pramine, and therapy.75 76 77 While a direct effect of copper meprobamate,
in upon insulin has not been confirmed at this time,
psychotropics, sedatives, and tranquilizers. Their it has been confirmed that estrogen does not common trade names are, Thorazine, Stelazine, produce the insulin rise. An indirect effect of Temaril, Norpramin, Tofranil, Librium, and copper can be suspected due to the copper-Miltown; Trade names for chlorothiazide used in calcium-vitamin D synergistic relationship. It is diuretics and anti-hypertensives are Diupres and apparent from TMA studies that copper increases Diuril; tolbutamide and chlorpropamide are used the tissue retention of calcium, and calcium is in anti-diabetic and oral hypoglycemic agents known to mediate the release of insulin.78 79with trade names including Diabenese and Vitamin D metabolites (1, 25(OH)2 D3) enhances Orinase; carbamazepine used for the control of the synthesis of insulin, and insulin enhances the convulsive disorders and severe neuralgias, trade synthesis of vitamin D metabolites.80 Since zinc is name Tegretol; thiouracil and methi-mazole, trade required for the storage of insulin, it is possible name Tapazole, is used as an anti-thyroid that antagonism of zinc by copper could be preparation; indomethacine, trade name Indocin, responsible for the flooding of insulin into the used
contain griseo-fulvin, trade names include excessive tissue copper accumulation via TMA Fulvicin-U/F and Grifulvin. This is only a partial studies include chronic E.B.V. and C.M.V. list of commonly prescribed medications; for fur-
infections, emotional disturbances (depressive
ther information consult the Physicians' Desk disorders), hypoglycemia, fatigue, fibroid tumors, Reference.
low blood pressure, transient high blood pressure, anorexia, PMS, AIDS, dermatosis, endometriosis,
Thyroid Insufficiency and Copper
infertility, hair loss, type II insomnia, and frontal
For several years it has been noted that headaches.
elevated tissue copper is a common finding in
Generally it is often noted that adults who
conjunction with thyroid insufficiency. Copper's show elevated tissue copper accumulation have a effect upon thyroid function involves multiple tendency to be right brain dominant. They are mechanisms. First, by the copper antagonistic usually emotionally oriented and artistically effect upon iron. Dillman and co-workers have inclined. TMA tests of individuals whose reported that iron deficiency results in thyroid occupation or hobby involves creativity such as insufficiency.71
have artists, sculptors, musicians, and actors invariably
concluded that iron status and thyroid function have a tendency toward either a high tissue appears to have a reciprocal relationship in that copper or a low zinc to copper ratio, whereas iron deficiency can impair thyroid function, and individuals with a low tissue copper or high iron stores can be reflective of thyroid function.72
Copper can also affect thyroid function through dominance and often follow intellectual pursuits.
an insulin effect. Insulin is known to antagonize thyroid function.73 Through observations of TMA Conclusion patterns, it has been noted that elevated tissue
The importance of copper nutriture is obvious
copper is associated with increased insulin due to its requirement in enzyme systems. Often secretion by the pancreas; it is conceivable that the adverse effects of copper toxicity are given copper enhances insulin secretion. Studies that more consideration than copper deficiency. show an association of elevated estrogen with However, copper balance is important particularly elevated insulin support this view. Plasma insulin in relationship to other nutrients. Just as much levels are known to be elevated during pregnancy, consideration should be given to the possibility of being highest in the last trimester.74 The same copper deficiency as to copper toxicity. insulin effect is also observed during estrogen
Journal of Orthomolecular Medicine Vol. 4, No. 2, 1989 References
1. Hart EB et al: Iron In Nutrition. VII. Copper as a
Pertubations, Especially as They Affect Copper
Supplement to Iron for Hemeb-globin Building in
Status, Are a Factor in the Etiology of Arthritic
the Rat. /. Biot. Chem. 77, 1928.
Conditons: An Hypothesis. Inflammatory Diseases
2. Mills ES: Idiopathic Hypochron/emia. Am. J. Med. and Copper. Sorenson, J.R.J., Ed. Humana Press,
3. Daniels AL, Wright OE: Iron and Copper 20. Mason KE: A Conspectus of Research on Copper
Retentions in Young Children. /. Nutr. 8, 1934.
Metabolism and Requirements of Man. J.Nutr.,
4. Cartwright GE, Wintrobe MM: Copper Metabolism
in Normal Subjects. /. Clin. Nutr., 14, 1964.
21. Chandra RH, Newberne AM: Nutrition Immunity and Infection. Mechanism of Interactions. Plenum
Concentration in Rat Hair as Related to Dietary
22. Weinberg ED: Iron and Susceptibility to Infectious
6. Klevay LM: Hair as a Biopsy Material. II
Disease. Bacterial Nutrition. Lichstein H.C., Ed.
Assessment of Copper Nutriture. Am. J. Clin. Nutr.
23. Beisel WR: The Effect of Infection on Host
7. Deeming SB, Weber CW: Hair Analysis of Trace
Nutritional Status. Advances in Human Clinical
Minerals in Human Subjects as Influenced by Age,
Nutrition. Vitale, J.J., Broitman, S.A., Eds. John
Sex and Oral Contraceptive Use. Am. J. Clin. Nutr.,
24. Collie WR et al: Hair in Menkes Disease: A
8. Vir SC et al: Serum and Hair Concentrations of
Comprehensive Review. Hair Trace Elements and
Copper During Pregnancy. Am. J. Clin. Nutr., 34,
Human Illness. Brown, A.C., Crounse, R.G., Eds.
9. Laker M: On Determining Trace Element Levels in 25. Graham GG, Cordano A: John Hopkins Med. J.,
Man; The Uses of Blood and Hair. Lancet, 2, 1982.
10. Ikeda T, et al: Hair Copper and Zinc Concentrations 26 .A1-Rashid RA, Spangler J: N.E.J.M., 285, 1971.
in Handicapped Children with Anticonvulsants. 27. Karpel JT, Peden VH: /. Ped., 80, 1972. Dev. Pharmacol. Ther., 6, 1983.
28. Luster MI et al: Immunological Alterations in Mice
11. Jacob RA et al: Hair as a Biopsy Material v. Hair
Following Acute Exposure to Di-ethylstilbestrol.
Metal as an Index of Hepatic Metal in Rats; Copper
Biological Relevance of Immune Suppression as
and Zinc. Am. J. Clin. Nutr. 31, 1978.
12. Baumslag N, et al: Trace Metal Content of Maternal
Environmental Factors. Dean, J.H., Padarathsingh,
and Neonate Hair. Arch. Environ. Hlth. 29, 1974.
M., Eds. Van Nosstrand Reinhold, Co., N.Y., 1981.
Copper 29. Dumont AE et al: Siderosis of Lymph Nodes in
Concentration with Increasing Distance from the
Patients with Hodgkin's Disease. Cancer, 38, 1976.
Scalp. Am. J. Clin. Nutr., 26,1973.
30. Sorenson RJ et al: Antineoplastic Activities of
14. Hambidge KM: Hair Analysis. Ped. Clin. N. Am.,
Some Copper Salicylates. Trace Substances in Environmental Health XVI. Hemphill, D.D., Ed.
15. Osaki S, et al: The Mobilization of Iron from
Perfused Mamalian Liver by a Serum Copper 31. Dickerson JWT: Nutrition of the Cancer Patient. Enzyme, Ferroxidase I. /. Biol. Chem., 246, 1971.
Advances in Nutritional Research Vo. 5. Draper,
16. Fairbanks VF, et al: Clinical Disorders of Iron Metabolism. 2nd Ed. Grune and Stratum, N.Y., 32. Aspin N, Sass-Kortsak A: Copper. Disorders of 1971.
Mineral Metabolism Vol.1. Trace Minerals.
17. Mowat AG, Hothersall TE: Nature of Anaemia in
Bronner, F., Coburn, J. Eds. Academic Press, N.Y.,
Rheumatoid Arthritis. VII. Iron Content of Synovial
Tissue in Patients with Rheumatoid Arthritis and in 33. Graham GC, Cordano A: Copper Deficiency in Normal Individuals. Ann. Rheum. Dis., 27, 1968.
Human Subjects. Trace Elements in Human Health
18. Kishore V, et al: Effect of Nutritional Copper
and Disease. Prasad, A.S., Ed. Academic Press,
Deficiency on the Development of Adjuvant
Arthritis in the Rat. Trace Substances in 34. Underwood EJ: Trace Elements in Human and Environmental Health XVI. Hemphill,
Animal Nutrition 4th Ed. Academic
The Nutritional Relationships of Copper
53. Hill CH, Starcher B: Effects of Reducing Agents
35. Watts DL: Determining Osteoporotic Tendencies
on Copper Deficiency in the Chick. /. Nutr., 85,
from Tissue Mineral Analysis of Human Hair,
Type I and Type II. Townsend Newsletter For Drs.
54. Evans GW, Cornatzer WE: Biliary Copper
Excretion in the Rat. Proc. Soc. Exp. Biol. Med.
36. Klevay LM: Coronary Heart Disease: The
Zinc/Copper Hypothesis. Am. J. Clin. Nutr., 28,
55. Henkin RI: Trace Element Metabolism in Animals Vol. II. Hoekstra, W.G., et al, Eds. Univ. Park
37. Klevay LM: The Role of Copper and Zinc in
Cholesterol Metabolism. Advances in Nutritional Research. Draper, H.H., Ed. Plenum Pub., N.Y.,
57. Klim RG et al: Intestinal Calcium Absorption in
Exogenous Hypercorticism. Role of 25(OH) D and
38. Davies IJT: The Clinical Significance of the
Corticosteroid Dose. /. Clin. Invest., 60, 1977.
EssentialBioligicalMetals. Charles Thomas, Pub., 58. Scheinberg IH, Sternlieb I: Copper Toxicity and Ill, 1972.
Wilson's Disease. Trace Elements in Human
39. Pratt WB, Phippen WG: Elevated Hair Copper
Health and Disease, Vol. I. Prasad, A.S., Ed.
Level in in Idiopathic Scolosis, Preliminary
59. Aspin N, Sass-Kortsak A: Copper. Disorders of
40. Guy ton AC: Textbook of Medical Physiology, 4th Mineral Metabolism, Vol. I. Bronner, F., Coburn,
Ed. W.B. Saunders, Co., Phil., 1971.
41. Underwood EJ: Trace Elements in Human and
60. Henkin RI: Trace Element Metabolism in Animals Animal Nutrition, 4th Ed. Academic Press, N.Y.,
Vol II. Hoekstra W.G. et al, Eds. Univ. Park Press,
42. Douglas et al: Trace Elements in Scalp-Hair of
61. Underwood EJ: Trace Elements in Human and
Persons with Multiple Sclerosis and of Normal
Animal Nutrition. 4th Ed. Academic Press, N.Y.,
Individuals. Clin. Chem. 24, 1978.
43.0'Dell BL: Biochemistry of Copper. The Medical 62. Watts DL: The Effects of Oral Contraceptive
Clinics of North America. 60,1976. W.B. Saunders,
Agents on Nutritional Status. Am. Chiro. Mar.
44. Collie WR: Hair in Menkes Disease: A
63. Altschule MD: Nutritional Factors in General
Comprehensive Review. Hair Trace Elements and Medicine, Effects of Stress and Distorted Diets. Human Illness. Brown, Crounse, Eds. Prager Pub.,
64. Kirshnamachari KAVR: Some Aspects of Copper
45. Scheinberg IH et al: The Concentration of Copper
Metabolism in Pellagra. Am. J. Clin. Nutr., 27,
and Ceruloplasmin in Maternal and Infant Plasma
at Delivery. /. Clin. Invest. 33, 1954.
65. Olatunbosun DA et al: Serum-Copper in Stickle-
46. Prohaska JR, Lukasewycz DA: Copper Deficiency
Suppresses the Immune Response of Mice. Science
66. Bennion LJ et al: Effects of Oral Contraceptives on
the Gallbladder Bile of Normal Women. N.E.J.M.,
47. Mason KE: A Conspectus of Research on Copper
Metabolism and Requirements of Man. /. Nutr.,
67. Ingelfinger FJ: Gallstones and Estrogens. N.E.J.M.,
48. Aspin N, Sass-Kortsak A: Copper. Disorders of
68. Kranitt MJ et al: The Response to Challenge with
Mineral Metabolism, Vol.1. Trace Minerals.
Bronner, F., Coburn, J., Eds. Academic Press,
69. Ockner RK, Davidson CS: Hepatic Effects of Oral
49. Underwood EJ: Trace Elements in Human and
Contraceptives. N.E.J.M., 285,1971.
Animal Nutrition 4th Ed. Academic Press, N.Y.,
70. Altschule MD: Nutritional Factors in General Medicine, Effects of Stress and Distorted Diets.
50. Davies IJT: The Clinical Significance of the Essential Biological Metals. Charles Thomas,
71.Dillman E et al: Hypothermia in Iron Deficiency
Due to Altered Triiodthyronine Metabolism. Am. J.
51.Finley EB, Cerklewski FL: Influences of Ascorbic
Acid Supplementation on Copper Status in Young
72. Tucker DM et al: Neuropsychological Effects of
Adult Men. Am. J. Clin. Nutr., 37, 1983.
Iron Deficiency. Neurobiology of the Trace
52. Carlton WW, Henderson W: Studies in Chickens
Elements, Vol. I. Dreosti, I.E., Smith, R.M., Eds.
Fed a Copper Deficient Diet Supplemented with
Ascorbic Acid, Resperine and Diethylstilbestrol. /.
73. Watts DL, Heise TL: Balancing Body Journal of Orthomolecular Medicine Vol. 4, No. 2, 1989
78. Leclereq-Meyer V et al: Effect of Calcium and
74. Spellacy WN, Goetz FC: Plasma Insulin in
Magnesium on Glucagon Secretion. Endocrinol,
Normal Late Pregnancy. N.E.J.M. 268,1963.
75. Gershberg H et al: Glucose Tolerance in Women
79. Malaisse WJ et al: The Stimulus-Secretion
Receiving an Ovulatory Suppressant. Diabetes
Coupling of Glucose-Induced Insulin Release. /.
76. Javier Z et al: Ovulatory Suppressants, Estrogen,
80. Cross HS, Peterlik M: Hormonal and Ionic
and Carbohydrate Metabolism. Metabolism 17,
Differentiating Enterocyte. Progress in Clinical
77. Flynn A: Estrogen Modulations of Blood Copper
and Biological Research, Vol. 168. Epithelial
and Other Essential Metal Concentrations.
Calcium and Phosphate Transport Molecular and Inflammatory Disease and Copper. Sorenson,
Cellular Aspects. Bonner, F., Peterlik, M., Eds.
R.J., Ed. Humana Press, Clifton, N.J., 1982.
Author: Malte Schütz, MD Quick Reference Guide to Antiretrovirals Regular updates to this publication are posted on the Medscape Web site at http://hiv.medscape.com/updates/quickguide . Please check regularly to ensure you are using the most recent edition. The latest changes are highlighted in blue text. Guide to Antiretroviral Agents Nucleoside Reverse Transcriptase Inhibitor
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