Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males

Abstract

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.

No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status

“…This is in agreement with the ®ndings of several studies which have shown a lack of response of circulating Cp protein levels to daily supplementation with 2 ± 6 mg Cu (Medeiros et al, 1991;Eaton-Evans et al, 1996;Baker et al, 1999b). However, it has been suggested that the speci®c enzymatic activity of Cp, de®ned as the ratio of enzyme activity to the immunoreactive protein, is a better indicator of Cu status than either the enzymatic activity or immunoreactive protein alone (Milne et al, 1988;Milne, 1994).…”

“…The increase in erythrocyte SOD activity in the present study after daily supplementation of the usual diet with 3 or 6 mg Cu for 4 weeks may indicate that the Cu status in the subjects was improved by supplementation. This is in contrast with the ®ndings of other Cu intervention studies, which showed that supplementation of the usual diet with additional Cu (in the range 3 ± 6 mgaday) had no effect on erythrocyte SOD (Medeiros et al, 1991;Eaton-Evans et al, 1996;Baker et al, 1999b). For example, we have recently shown in another double-blind, placebo-controlled crossover trial that Cu supplementation with 3 or 6 mg elemental Cuaday for 6 weeks had no effect on erythrocyte SOD or serum Cp protein concentration in healthy adults (12 males and 12 females, aged 22 ± 46 y; Baker et al, 1999b).…”

“…This is in contrast with the ®ndings of other Cu intervention studies, which showed that supplementation of the usual diet with additional Cu (in the range 3 ± 6 mgaday) had no effect on erythrocyte SOD (Medeiros et al, 1991;Eaton-Evans et al, 1996;Baker et al, 1999b). For example, we have recently shown in another double-blind, placebo-controlled crossover trial that Cu supplementation with 3 or 6 mg elemental Cuaday for 6 weeks had no effect on erythrocyte SOD or serum Cp protein concentration in healthy adults (12 males and 12 females, aged 22 ± 46 y; Baker et al, 1999b). On the other hand, in depletion ± repletion type studies of women, in which SOD activity declined during Cu deprivation, recoveries of SOD activity were documented when either 3 mg (Reiser et al, 1985) or 4.3 ± 6.4 mg Cuaday were fed for more than 30 days (Kelvay et al, 1984;Miline et al, 1990), but not when less than 2.6 mg Cuaday was fed for periods of up to 42 day (Milne et al, 1988;Milne & Nielsen, 1996).…”

“…High rates of bone turnover are also associated with a disruption of the trabecular network leading to a loss of connectivity which is not necessarily re¯ected in a decrease in bone mass (Par®tt, 1984). Importantly, in that study, the increased urinary pyridinium crosslinks excretion observed in healthy adult males at the end of a 6 week period of Cu depletion (0.7 mg Cuaday), was reversed during a subsequent 6 week period of dietary Cu repletion (ie 6.0 mg Cuaday; Baker et al, 1999a), suggesting that the elevated rate of bone resorption was quickly normalised by increasing Cu intake.…”

“…For example, we have recently shown that a low dietary Cu intake (0.7 mgaday) for 6 weeks signi®-cantly increased the rate of bone resorption, as assessed by the urinary excretion of pyridinium crosslinks (sensitive and speci®c biochemical markers of bone resorption; Eyre, 1992;Robins & New, 1997), in healthy adult males aged between 20 and 59 y (Baker et al, 1999a). An increased rate of bone resorption is considered an early indicator of increased bone turnover (Eyre, 1992) and furthermore, an increased rate of bone turnover in adults may be a risk factor for fracture (Riggs et al, 1996), because it exacerbates bone loss (Hansen et al, 1991).…”