Zinc and Cancer
This fact sheet is a review of study data about the relationship between zinc supplementation and cancer incidence and outcomes.
Zinc is an essential mineral important for growth and development, immune function, protein synthesis, DNA synthesis, cell division, and wound healing.1
Supplementation with zinc has been studied primarily as a component of a multivitamin for chemoprevention against several different cancer types. Zinc supplementation alone has also been evaluated as a preventative for radiotherapy-induced side effects among patients with head and neck cancer (HNC). This fact sheet is a review of study data about the relationship between zinc supplementation and cancer incidence and outcomes.
The double-blind Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) study evaluated the effect of a multivitamin on health outcomes, including the risk of developing skin cancer or prostate cancer.2
The study randomly assigned 13,017 participants aged 35 to 60 to an antioxidant supplement comprised of zinc (20 mg), selenium, β-carotene, and vitamins C and E, or placebo once daily for a median follow-up of 7.5 years.
The study demonstrated a significant decrease in total cancer incidence and total mortality among men, but not women, with antioxidant supplementation compared with placebo.3 This benefit was, however, no longer evident 5 years after supplement discontinuation.
In the SU.VI.MAX study, the incidence of any type of skin cancer was significantly higher with antioxidant supplementation compared with placebo among women (1.3% vs 0.7%; P = .02), which was driven by a higher number of melanomas (0.3% vs 0.08%; P = .01), whereas the number of nonmelanoma skin cancers was similar between groups (0.8% vs 0.5%; P = .15).2
Among men, there was no significant difference in incidence of any type of skin cancer between the antioxidant and placebo arms.
The SU.VI.MAX study demonstrated a nonsignificant decrease in prostate cancer incidence among men who received the antioxidant supplement compared with placebo (hazard ratio [HR], 0.88; 95% CI, 0.60-1.29), which was particularly evident among men with a normal prostate-specific antigen (PSA) at baseline (HR, 0.52; 95% CI, 0.29-0.92).4 The benefit was not observed among men with an elevated PSA at baseline (HR, 1.54; 95% CI, 0.87-2.72). This finding is in contrast with a systematic review and meta-analysis that included 3 different studies, which demonstrated no associated benefit with prostate cancer and zinc supplementation (odds ratio [OR], 1.18; 95% CI, 0.71-1.96).5
Other Cohort Studies
A pooled analysis of the INHANCE consortium, which included 12 case-control studies with 7002 cases of HNC and 8383 controls, evaluated self-reported use of supplements and risk of HNC.6 There was no association between ever using a zinc supplement and the development of HNC after adjustment for multiple potential confounders including other vitamin use, smoking, age, alcohol use, and fruit/vegetable intake.
An analysis of the prospective NIH-AARP Diet and Health Study included 490,593 subjects aged 50 to 71 with no history of cancer and evaluated the risk of upper gastrointestinal cancers with multivitamin and single supplements with 11 years of follow-up.7 Zinc supplementation was not associated with esophageal squamous cell carcinoma, esophageal adenocarcinoma, or gastric cardia adenocarcinoma, but was associated with an increased risk of gastric noncardia adenocarcinoma (HR, 1.28; 95% CI, 1.01-1.63).
A double-blind trial randomly assigned 411 patients who underwent polypectomy for large bowel adenomas to receive antioxidant supplementation with selenium, zinc (30 mg), and vitamins A, C, and E, or placebo once daily for 5 years.8 Antioxidant supplementation resulted in a significant decrease in adenoma recurrence, with a 15-year cumulative rate of 48.3% compared with 64.5% with placebo (HR, 0.59; P = .009). The risk reduction with antioxidant supplementation was similar for small tubular and advanced adenomas.