Leone · Epidemiology (Cambridge, Mass.) 2006 · prospective cohort study · n=4035

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

Cited 271 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective cohort study

PubMed 16570028 · doi:10.1097/01.ede.0000209454.41466.b7 · record verified 2026-08-31

What was done

Serum zinc, copper, and magnesium concentrations were measured at baseline in 4,035 men aged 30-60 years from the Paris Prospective Study 2. Baseline mineral levels were categorized into low (quartile 1, referent), medium (quartiles 2-3), and high (quartile 4). Cox proportional hazards models were used to calculate relative risks (RRs) for all-cause, cancer, and cardiovascular disease mortality over an 18-year follow-up period after adjusting for potential confounders.

What was found

During 18 years of follow-up, 339 deaths occurred (176 cancer, 56 cardiovascular). Compared with low values (quartile 1): - High copper (quartile 4) was associated with higher all-cause mortality (RR = 1.5; 95% CI: 1.1-2.1), cancer mortality (RR = 1.4; 95% CI: 0.9-2.2), and cardiovascular mortality (RR = 1.3; 95% CI: 0.6-2.8). - High magnesium was associated with lower all-cause mortality (RR = 0.6; 95% CI: 0.4-0.8), cancer mortality (RR = 0.5; 95% CI: 0.3-0.8), and cardiovascular mortality (RR = 0.6; 95% CI: 0.2-1.2). - Combined low zinc and high copper was associated with increased all-cause (RR = 2.6; 95% CI: 1.4-5.0) and cancer (RR = 2.7; 95% CI: 1.0-7.3) mortality. - Combined low zinc and high magnesium was associated with decreased all-cause (RR = 0.2; 95% CI: 0.1-0.5) and cancer (RR = 0.2; 95% CI: 0.1-0.8) mortality.

Why it matters

This study provides long-term prospective evidence linking circulating trace minerals—particularly elevated copper, lower magnesium, and specific mineral interactions—with altered risks of all-cause and cancer mortality in middle-aged men.

Limits

The study was conducted entirely in middle-aged men, limiting generalizability to women and other populations. Serum mineral concentrations were measured only once at baseline. Cardiovascular mortality estimates had low precision (wide confidence intervals) due to a small number of events (56 deaths), and residual confounding cannot be ruled out.

Cited by