It is over 25 years since copper deficiency was first delineated in Menkes Disease. This advanced our understanding of the clinical, biochemical and molecular essentiality of copper (1). This rare genetic disorder is X-linked, manifests from early pregnancy due to failure of copper transport via the placenta and results in steely hair, cutis laxa, atonia, cardiomyopathy, and mental retardation, with death in early childhood.
Safe and adequate adult daily copper intakes were set at 2-3 mg in 1980 (2) however more recent studies analysing duplicate diets suggest actual intakes in the USA may be 1-1.5mg/day. Good dietary sources (>2 microgms/gm ) include seafood, organ meats, legumes and nuts. Refined cereals, sugar, milk and dairy products are low (<2microgms/gm). Often overlooked is the contribution from water through copper pipes and this can vary from 0.1mg/day in hard water to 1mg in extremely acid soft waters. Various factors can influence bioavailability such as protein sources, amino acids, phytates, ascorbic acid, Zinc and Iron cations. Absorption from breast milk is higher than from infant feeds ( 80% have Fe/Cu ratios <20:1 higher than the recommended 10 to 17:1). Copper may be particularily important in premature infants, who are born with low stores (3).
The copper dependent enzymes include Cytochrome oxidase, Dopamine-B mono-oxygenase, lysl oxidase, Petidylglycine alpha-amidating mono-oxygenase( PAM), Superoxide dismutase, ceruloplasmin and amine oxidase. The most promising functional indices of copper status are outlined by Strain (4). These include enzyme activity of PAM and diamine oxidase. Biochemical indicators include urinary pyridinium cross links, immune measures, mitochondrial DNA damage, DNA damage and bone density.
Consequences of copper deficiency
A series of reports in the 1960s highlighted nutritional deficiencies in infants and children recovering from malnutrition in Peru. Cordano (5) recently cited additional cases, including premature infants, in-patients receiving total parenteral nutrition and those on special diets or unmodified cows milk formulae. The most frequent manifestations are anaemia, neutropaenia and bone abnormalities with skeletal fragility and osteoporosis, vascular abnormalities and uncrimpled or steely hair. Neutropaenia was regarded as a sufficiently constant feature to be of diagnostic value (6). However, improvements in assessing status have fueled speculation about the possible effects of mild deficiencies, especially with regard to the cardiovascular effects, which rest largely on the reduced effectiveness of copper dependent enzymes (7,8). Dietary copper deficiency may impair cardiovascular function and contribute to high blood pressure, enhance inflammation, anaemia, reduced blood clotting and arteriosclerosis. The alterations include weakened structural integrity of the heart and blood vessels, impairment of the use of energy by the heart, reduced ability of the heart to contract (cardiomyopathy), altered ability of the blood vessels to control their diameter and to grow, and altered structure and function of circulating blood cells. Further experimental verification will be the aim of future studies and there may be links between these effects and diabetes.
References (1) Kaler SG, ' Diagnosis and therapy of Menkes syndrome, a genetic form of copper deficiency' Am J Clin Nutr, 1998 May, 67:5 Suppl, 1029S-1034S.
(2) ' Trace elements in human nutrition and health ' WHO 1996
(3) Lonnerdal B, ' Copper nutrition during infancy and childhood '
Am J Clin Nutri, 1998 May, 67:5 Suppl, 1046S-1053S. (4) Strain JJ 'Defining optimal copper status in humans '
Proceedings of 10th International Symposium on Trace Elements in Man and Animals. 2000; New York: Plenum Press, in print
(5) Cordano A, 'Clinical manifestations of nutritional copper deficiency in infants and children' Am J Clin Nutri, 1998; May , 67:5 Suppl, 1012S-1016S.
(6) Uauy R et al., 'Essentiality of copper in humans '.
Am J Clin Nutri, 1998 May,67:5 Suppl, 952S-959S.(7) Nath R , ' Copper deficiency and heart disease : molecular basis, recent advances and current concepts.' Int J Biochem Cell Biol, 1997: Nov, 29:11, 1245-54.
(8) Saari JT & Schuschke DA , ' Cardiovascular effects of dietary copper deficiency '. Biofactors, 1999, 10:4, 359-75.