High Dose Zinc Increases Hospital Admissions Due to Genitourinary Complications

Purpose

Zinc is a common dietary supplement that is widely believed to have beneficial health effects. To assess the impact of high dose supplemental zinc on genitourinary diseases we analyzed a recent randomized trial comparing zinc, antioxidants and their combination to placebo for complications related to the genitourinary tract.

Materials and Methods

In a further analysis of the recent Age-related Eye Disease Study we examined the data pool for primary International Classification of Diseases, 9th revision codes given for hospital admissions related to urological problems. The Age-Related Eye Disease Study randomized 3,640 patients with age related macular degeneration to 1 of 4 study arms, including placebo, antioxidants (500 mg vitamin C, 400 IU vitamin E and 15 mg β-carotene), 80 mg zinc and antioxidant plus zinc. Statistical analyses using Fisher’s exact test were performed.

Results

We found a significant increase in hospital admissions due to genitourinary causes in patients on zinc vs nonzinc formulations (11.1% vs 7.6%, p = 0.0003). The risk was greatest in male patients (RR 1.26, 95% CI 1.07–1.50, p = 0.008). In the study group of 343 patients requiring hospital admission the most common primary International Classification of Diseases, 9th revision codes included benign prostatic hyperplasia/urinary retention (benign prostatic hyperplasia), urinary tract infection, urinary lithiasis and renal failure. When comparing zinc to placebo, significant increases in urinary tract infections were found (p = 0.004), especially in females (2.3% vs 0.4%, RR 5.77, 95% CI 1.30–25.66, p = 0.013). Admissions for urinary lithiasis approached significance in men on zinc compared to placebo (2.0% vs 0.5%, RR = 4.08, 95% CI 0.87–19.10). There was no increase in prostate or other cancers with zinc supplementation. A significant decrease in prostate cancer diagnoses was seen in patients receiving antioxidants vs placebo (RR = 0.6, 95% CI 0.49–0.86, p = 0.049). Subgroup analysis revealed that this finding was significant in men who smoked but not in nonsmokers.

Conclusions

Zinc supplementation at high levels results in increased hospitalizations for urinary complications compared to placebo. These data support the hypothesis that high dose zinc supplementation has a negative effect on select aspects of urinary physiology.

Key Words: prostate, prostatic neoplasms, zinc, prostatic hyperplasia, complications

Abbreviations and Acronyms: AREDS, Age-Related Eye Disease Study, ARMD, age related macular degeneration, BPH, benign prostatic hyperplasia, GU, genitourinary, ICD-9, International Classification of Diseases, 9th revision, UTI, urinary tract infection