Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study

BACKGROUND: Zinc supplementation was hypothesized to have therapeutic potential against prostate cancer, but its influence on prostate cancer incidence especially at high doses is controversial. METHODS: A total of 47,240 men from the Health Professionals Follow-up Study were followed from 1986 to 2016. Men reported their zinc supplement use at baseline and biennially thereafter. Clinical features of prostate cancer included stage, grade, lethal and aggressive (T4 or N1 or M1 or Gleason 8–10) outcome. Multivariable Cox proportional hazards models were used to evaluate the association between zinc supplement use and incidence of prostate cancer. RESULTS: During a median follow-up of 28.3 years, we documented 6,980 incident prostate cancer cases including 1,053 lethal and 1,143 aggressive. Zinc supplement use was not associated with overall, localized, low- and intermediate-grade prostate cancer. However, compared to never-users, men who used supplement zinc more than 75 mg/day were at higher risk for lethal (HR: 1.76, 95% CI: 1.16–2.66, P(trend) = 0.001) and aggressive prostate cancer (HR: 1.80, 95% CI: 1.19–2.73, P(trend) = 0.006). Similarly, men who took supplemental zinc for 15 or more years had a higher risk for lethal (HR: 1.91, 95% CI: 1.28–2.85, P(trend) <0.001) and aggressive prostate cancer (HR: 1.55, 95% CI: 1.03–2.33, P(trend) = 0.004). CONCLUSION: Zinc supplementation of more than 75 mg per day or over 15 years may substantially increase risk of lethal and aggressive prostate cancer. Caution is warranted regarding excessive usage of zinc supplements among adult men. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00922-0.