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 dismutase (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 15 and brain, followed by the heart, kidney, Ceruloplasmin. 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 Trace Elements, Inc. is 2.5 period.19TMA studies of patients with rheuma- Trace Elements, Inc., P.O. Box 514, Addison, Texas 75001. 99 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.28 obstruction.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 infections directly following 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. disturbance in humoral immunity. 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 21 metabolism and requirements. 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 TMA studies have shown that chronic 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. and 2). 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 27 100 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).37 revealing the increased requirements for copper in Copper excess may also contribute to some malignancy conditions. The necessity for cardiovascular problems from hypercho- 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