Measuring intake of nutrients and their effects: the case of copper 121 toes, tomatoes, bananas and other dried fruits provide sufficient copper in a normal diet to ensure that overt copper deficiency is rare in human populations. Nonethe- less, many Western diets are estimated to supply a level of copper only barely dequate to meet the body's requirements Published estimates of copper intake vary around 1-2mg/d, with few diets containing more than 2 mg/d. 3.1415, 16 17 5.5 Copper deficiency Clinical copper deficiency is seen mainly in malnourished and recovering chil- dren, in premature babies, in patients receiving total parenteral nutrition (TPN) and as a consequence of malabsorption. Copper deficiency also occurs as the result of Menkes syndrome, a rare inherited defect of copper transport. Mal- nourished children are reported to be at particular risk of copper deficiency. A diet consisting exclusively or predominantly of cow's milk, with its poor bioavail- ability of copper, increases the likelihood of copper malabsorption. During nutri tional recovery, growth rate can be 5-10 times the normal rate, increasing copper requirements beyond the dietary intake. Copper deficiency during this period has been shown to impair growth rate and to be associated with increased incidence of respiratory infection. 9 Preterm babies are also at particular risk of copper deficiency, for several reasons. Copper stores are acquired late in foetal development, as metallothionein bound copper accumulates in the foetal hepatocyte nuclei over the last trimester Although neonates appear not to absorb copper well, particularly from highly refined carbohydrate-based diets or cows milk, full-term infants have well leveloped copper stores which can be mobilised during the first six months rapid growth, to supplement dietary intake. Full-term infants are therefore independent of dietary intake for the first weeks of life. Premature babies, especially those with very low birth-weight, do not have such a resource. They also have higher growth rate than full-term babies, with accordingly higher copper requirements. 23 Clinical copper deficiency in adults was unknown until the introduction of TPN, which is now well known to result in elevated urinary copper output and a net depletion of copper status. Although copper is now usually added to TPN infusates, it is often withheld from cholestatic patients since their impaired biliary excretion is expected to result in reduced intestinal losses. The complex interac tions between disease states and copper metabolism, however, make individuals requirements difficult to anticipate, and TPN-related copper deficiency continues to occur intestinal copper losses leading to deficiency. Such conditions include coeliac disease26, cystic fibrosis, shortened intestine following surgery, and chronic or recurrent diarrhoea 29.30 Menkes disease is an X-linked recessive disorder of copper metabolism in which mutations in the mnK gene impair copper transport from cells. The disease is manifest as copper deficiency, because although copper is absorbed by gut cells, very little is transported to the tissues where it is requiredtoes, tomatoes, bananas and other dried fruits provide sufficient copper in a normal diet to ensure that overt copper deficiency is rare in human populations. Nonethe￾less, many Western diets are estimated to supply a level of copper only barely adequate to meet the body’s requirements. Published estimates of copper intake vary around 1–2 mg/d, with few diets containing more than 2 mg/d.13,14,15,16,17 5.5 Copper deficiency Clinical copper deficiency is seen mainly in malnourished and recovering chil￾dren, in premature babies, in patients receiving total parenteral nutrition (TPN) and as a consequence of malabsorption. Copper deficiency also occurs as the result of Menkes syndrome, a rare inherited defect of copper transport. Mal￾nourished children are reported to be at particular risk of copper deficiency. A diet consisting exclusively or predominantly of cow’s milk, with its poor bioavail￾ability of copper, increases the likelihood of copper malabsorption. During nutri￾tional recovery, growth rate can be 5–10 times the normal rate, increasing copper requirements beyond the dietary intake.3 Copper deficiency during this period has been shown to impair growth rate18 and to be associated with increased incidence of respiratory infection.19 Preterm babies are also at particular risk of copper deficiency, for several reasons. Copper stores are acquired late in foetal development, as metallothionein￾bound copper accumulates in the foetal hepatocyte nuclei over the last trimester.11 Although neonates appear not to absorb copper well, particularly from highly￾refined carbohydrate-based diets or cow’s milk20, full-term infants have well￾developed copper stores which can be mobilised during the first six months’ rapid growth, to supplement dietary intake.21 Full-term infants are therefore independent of dietary intake for the first weeks of life.22 Premature babies, especially those with very low birth-weight, do not have such a resource. They also have higher growth rate than full-term babies, with accordingly higher copper requirements.23 Clinical copper deficiency in adults was unknown until the introduction of TPN, which is now well known to result in elevated urinary copper output and a net depletion of copper status.20 Although copper is now usually added to TPN infusates, it is often withheld from cholestatic patients since their impaired biliary excretion is expected to result in reduced intestinal losses. The complex interac￾tions between disease states and copper metabolism, however, make individuals’ requirements difficult to anticipate, and TPN-related copper deficiency continues to occur.24,25 Anumber of malabsorption syndromes have been reported to result in increased intestinal copper losses leading to deficiency. Such conditions include coeliac disease26, cystic fibrosis27, shortened intestine following surgery28, and chronic or recurrent diarrhoea.29,30 Menkes disease is an X-linked recessive disorder of copper metabolism in which mutations in the MNK gene impair copper transport from cells. The disease is manifest as copper deficiency, because although copper is absorbed by gut cells, very little is transported to the tissues where it is required Measuring intake of nutrients and their effects: the case of copper 121