Vitamin C and copper interactions in guinea-pigs and a study of collagen cross-links

The purpose of this study was, first to explore metabolic interactions between Cu and ascorbic acid in guinea-pigs, particularly with respect to any possible disadvantages of high ascorbate in the presence of low Cu intakes, and second, to test the hypothesis that variations in ascorbate and/or Cu status might influence collagen cross-linking, either by inducing a change in the crosslinks: hydroxyproline ratio, or by inducing a change in the pyridinoline: deoxypyridinoline crosslinks ratio. Four matched groups, each of eight male weanling Dunkin-Hartley guinea-pigs, were maintained on purified diets containing either no added Cu, or 150 mg Cu/kg diet, and either 0.1 g or 30 g ascorbic acid/kg diet. They were then killed 8 weeks later, and the following indices were measured: body and organ weights; blood haemoglobin; adrenal ascorbate concentrations; Cu concentrations in plasma, liver and femur; superoxide dismutase (EC 1.15.1.1) activity in whole blood and liver; hydroxyproline, pyridinoline and deoxypridinoline in femur and in urine. The principal observations were: Cu intake significantly affected blood and tissue Cu concentrations and superoxide dismutase activity; and ascorbic acid intake significantly affected adrenal ascorbate levels and the deoxypyridinoline: pyridinoline cross-links ratio, especially in bone (femur). There was evidence of a significant interaction between ascorbate and Cu with respect to adrenal and plasma Cu concentrations, blood superoxide dismutase activity and body weights. We conclude that interactions between ascorbate and Cu at the functional level were present but modest, and that a new and potentially powerful functional index of ascorbate status may exist within the deoxypyridinoline:pyridinoline collagen cross-link ratio.