Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality

Background: Experimental data suggest that zinc, copper, and magnesium are involved in carcinogenesis and atherogenesis. Few longitudinal studies have related these minerals to cancer or cardiovascular disease mortality in a population. Methods: Data from the Paris Prospective Study 2, a cohort of 4035 men age 30-60 years at baseline, were used to assess the association between serum zinc, copper, and magnesium and all-cause, cancer, and cardiovascular disease mortality. Serum mineral values measured at baseline were divided into quartiles and classified into low (1st quartile, referent group), medium (2nd-3rd quartiles), and high (4th quartile) values. During 18-year follow up, 339 deaths occurred, 176 as a result of cancer and 56 of cardiovascular origin. Relative risks (RRs) for each element were inferred using Cox's proportional hazard model after controlling for various potential confounders. Results: High copper values (4th quartile) were associated with a 50% increase in RRs for all-cause deaths (RR = 1.5; 95% confidence interval = 1.1-2.1), a 40% increase for cancer mortality (1.4; 0.9-2.2), and a 30% increase for cardiovascular mortality (1.3; 0.6-2.8) compared with low values (1st quartile). High magnesium values were negatively related to mortality with a 40% decrease in RR for all-cause (0.6; 0.4-0.8) and cardiovascular deaths (0.6; 0.2-1.2) and by 50% for cancer deaths (0.5; 0.3-0.8). Additionally, subjects with a combination of low zinc and high copper values had synergistically increased all-cause (2.6; 1.4-5.0) and cancer (2.7; 1.0-7.3) mortality risks. Similarly, combined low zinc and high magnesium values were associated with decreased all-cause (0.2; 0.1-0.5) and cancer (0.2; 0.1-0.8) mortality risks. Conclusions: High serum copper, low serum magnesium, and concomitance of low serum zinc with high serum copper or low serum magnesium contribute to an increased mortality risk in middle-aged men.