Objective: To investigate the effects of changing from a medium (1.6 mg Cuad) to a low (0.7 mg Cuad) or a high (6.0 mgad) Cu intake on biochemical indices of bone turnover in healthy adult males. Design: A longitudinal intervention trial. Setting: The study was conducted at the Institute of Food Research, Norwich, UK. Subjects: Eleven healthy adult males aged 20 ± 59 y were recruited from Norwich Research Park. Intervention: Subjects were given medium (1.6 mgad), low (0.7 mgad) and high (6.0 mgad) intakes of Cu, in that order, over consecutive 8 week periods with a minimum of 4 week washout periods. On the last d of each dietary period fasting ®rst void urine and blood were collected. Results: Serum caeruloplasmin or Cu (indices of Cu status), serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) were unaffected by dietary Cu intake. Urinary PyraCr and DpyraCr (biomarkers of bone resorption) were signi®cantly increased (P`0.05) (by 30% and 25% respectively), when subjects were switched from the medium to the low Cu diet and were signi®cantly decreased (P`0.05) (by 30% and 22% respectively), when subjects were switched from the low to the high Cu diet. Conclusion: The ®ndings of the present study could have implications for bone health in individuals with marginal Cu intakes. Thus, further studies are warranted to better de®ne the relationship of marginal Cu intakes to bone health. Sponsorship: Funding from the European Commission and from the Ministry of Agriculture, Fisheries and Food.

Objective: To investigate the effects of increasing Cu intakes, above the usual dietary intake, on biomarkers of bone metabolism in healthy young adult females (aged 21 ± 28 y) over a 4 week period. Design: A double-blind, placebo-controlled randomised repeat crossover Cu supplementation trial. Setting: The study was conducted at the Royal Veterinary and Agricultural University (RVAU), Copenhagen, Denmark. Subjects: Sixteen healthy young adult females aged 20 ± 28 y were recruited from among students at the RVAU. Intervention: During the 4 week intervention periods in this randomised, crossover trial (3Â4 weeks with a minimum 3 week wash-out period), each subject received, in addition to their usual diet, either 3 or 6 mg elemental Cuaday as CuSO 4 or a matching placebo. On the last 3 days of each dietary period 24 h urines were collected. In addition, blood was collected on the last day of each dietary period. Results: Serum Cu and erythrocyte superoxide dismutase (but not caeruloplasmin protein concentration or activity (putative indices of Cu status)) were signi®cantly increased (P`0.05) after daily Cu supplementation with 3 and 6 mgaday for 4 weeks. Serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline (Pyr)aCr or deoxypyridinoline (Dpyr)aCr excretion, or daily urinary Pyr or Dpyr excretion (biomarkers of bone resorption) were unaffected by Cu supplementation. Conclusion: Copper supplementation of the usual diet in healthy young adult females, while apparently improving Cu status, had no effect on biochemical markers of bone formation or bone resorption over 4 week periods. Sponsorship: Funding from the European Commission.

The influence of Cu supplementation of the usual diet for 6 weeks on biochemical markers of bone turnover and on putative indices of Cu status was investigated in healthy adults (twelve male and twelve female) aged 22-46 years, who participated in a double-blind placebo-controlled repeated crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO 4 , 3 mg Cu-glycine chelate (CuGC), and 6 mg CuGC, each separated by placebo periods of equal length. During baseline and on the last day of each dietary period, fasting morning first-void urine and fasting blood serum, plasma and erythrocytes were collected. The habitual dietary Cu intakes in males and females were approximately 1⋅4 and 1⋅1 mg/d respectively. Females had significantly higher (50 %) plasma caeruloplasmin (Cp) protein concentrations than males at baseline. Cu supplementation had no effect on erythrocyte superoxide dismutase (SOD, EC 1.15.1.1) activity or plasma Cp protein (putative indices of Cu status) in the total group. Similarly, serum osteocalcin (a marker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline : Cr or deoxypyridinoline : Cr excretion (markers of bone resorption) were unaffected in either the total group or in males and females separately, by any Cu supplementation regimen. It is concluded that Cu supplementation of the usual diet in healthy adult males and females had no effect on biochemical markers of bone formation or bone resorption over 6-week periods.

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