122 The nutrition handbook for food processors for enzyme function. Symptoms usually appear within the first months of life, and can result in death in early childhood. In clinical copper deficiency, the most common defects are: cardiovascular and haematological disorders including iron-resistant anaemia, neutropenia and thrombocytopenia; bone abnormalities including osteoporosis and fractures; and alterations to skin and hair texture and pigmentation.Immunological changes have also been indicated. 9.32These changes may be accompanied by depressed serum copper and blood cupro- enzymes, with caeruloplasmin concentrations observed at 30% of normal.6 It has been clearly demonstrated that very many of the changes induced by severe copper deficiency are also risk factors for ischaemic heart disease in humans. Human copper depletion studies have produced impaired glucose clearance, blood pressure changes, electrocardiographic irregularities and significantly increased LDL cholesterol with decreased HDL cholesterol. In copper-deficient animals, cardiovascular disorders observed include lesion and rupture of blood vessels, cardiac enlargement, myocardial degeneration and infarction(MI). It has been argued that copper deficiency is the only nutritional deficit known to affect adversely so many risk factors for ischaemic heart disease. The proposed link between copper deficiency and cardiovascular disease is supported by data gathered from studies of cardiovascular patients Post-mortem measurement of tissue copper has revealed lower-than-normal opper concentrations in ischaemic hearts, in the liver and heart of individuals with severe atherosclerosis, and in leucocytes of patients with highly occluded coronary arteries A variety of mechanisms may contribute to the cardiovascular effects of copper deficiency. There is evidence for alterations in the activity of copper- dependent enzymes, increased oxidative stress and damage to biomolecules, and interference with the maintenance of blood pressure. An interaction of these three mechanisms of damage has been proposed to have even further potential for harm.36 which need not be limited to cardiovascular defects. The adverse effects elicited by copper deficiency are numerous and as varied as the roles of copper in health. In the light of this, it has been proposed that long-term sub-clinical opper deficiency may contribute to the pathogenesis of a number of degenera- tive and inflammatory conditions. 37 5.6 Copper toxicity Copper toxicity is rare because levels in food and water are generally low and because increased dietary intake results in decreased absorption and increased excretion. Cases of both acute and chronic poisoning have, however, been reported. Acute toxicity has been known to result from accidental or deliberate consumption of copper salts and, more commonly, from contamination of drinks by copper containers. A 1957 report of contamination of cocktails stored for just two hours in a metal cocktail shaker was used in 1988 by US Environmental Pro- tection Agency(EPA)Office of Drinking Water to derive drinking water regulafor enzyme function. Symptoms usually appear within the first months of life, and can result in death in early childhood.31 In clinical copper deficiency, the most common defects are: cardiovascular and haematological disorders including iron-resistant anaemia, neutropenia and thrombocytopenia; bone abnormalities including osteoporosis and fractures; and alterations to skin and hair texture and pigmentation.23 Immunological changes have also been indicated.19,32 These changes may be accompanied by depressed serum copper and blood cupro￾enzymes, with caeruloplasmin concentrations observed at 30% of normal.6 It has been clearly demonstrated that very many of the changes induced by severe copper deficiency are also risk factors for ischaemic heart disease in humans. Human copper depletion studies have produced impaired glucose clearance,33 blood pressure changes,34 electrocardiographic irregularities and significantly increased LDL cholesterol with decreased HDL cholesterol.21 In copper-deficient animals, cardiovascular disorders observed include lesion and rupture of blood vessels, cardiac enlargement, myocardial degeneration and infarction (MI).33 It has been argued that copper deficiency is the only nutritional deficit known to affect adversely so many risk factors for ischaemic heart disease.35 The proposed link between copper deficiency and cardiovascular disease is supported by data gathered from studies of cardiovascular patients. Post-mortem measurement of tissue copper has revealed lower-than-normal copper concentrations in ischaemic hearts, in the liver and heart of individuals with severe atherosclerosis, and in leucocytes of patients with highly occluded coronary arteries.33 A variety of mechanisms may contribute to the cardiovascular effects of copper deficiency. There is evidence for alterations in the activity of copper￾dependent enzymes, increased oxidative stress and damage to biomolecules, and interference with the maintenance of blood pressure. An interaction of these three mechanisms of damage has been proposed to have even further potential for harm,36 which need not be limited to cardiovascular defects. The adverse effects elicited by copper deficiency are numerous and as varied as the roles of copper in health. In the light of this, it has been proposed that long-term sub-clinical copper deficiency may contribute to the pathogenesis of a number of degenera￾tive and inflammatory conditions.37 5.6 Copper toxicity Copper toxicity is rare because levels in food and water are generally low and because increased dietary intake results in decreased absorption and increased excretion.38 Cases of both acute and chronic poisoning have, however, been reported. Acute toxicity has been known to result from accidental or deliberate consumption of copper salts and, more commonly, from contamination of drinks by copper containers.6 A 1957 report of contamination of cocktails stored for just two hours in a metal cocktail shaker was used in 1988 by US Environmental Pro￾tection Agency (EPA) Office of Drinking Water to derive drinking water regula- 122 The nutrition handbook for food processors