Zinc Supplements Associated With Improved Survival

Laurie Barclay, MD

May 10, 2004

May 10, 2004 — Zinc supplements are associated with improved survival in patients with ocular disorders, according to the results of a randomized trial published in the May issue of the Archives of Ophthalmology.

"Various ocular disorders (eg, visual impairment and cataract and those in persons with diabetes mellitus, severe retinopathy, or visual impairment) have been reported to be significant predictors of a decreased life span, often even after extensive adjustment for potential confounders," write Traci E. Clemons, PhD, from EMMES Corp. in Rockville, Maryland, and colleagues from the Age-Related Eye Disease Study (AREDS) Research Group. "Ocular disorders, in particular cataract, may be markers of systemic processes that are associated with accelerated physiologic aging and earlier death. For example, generalized oxidative damage might play a role in the development of cataract and the aging process."

Using baseline fundus and lens photographs, the investigators graded the macular and lens status of AREDS subjects, who were then randomized to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Median follow-up was 6.5 years.

Of 4,753 AREDS participants, 534 (11%) died during follow-up. Compared with subjects with few or no drusen, those with advanced age-related macular degeneration (AMD) had a 41% increase in mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08 - 1.86). Advanced AMD was also associated with cardiovascular deaths.

Compared with subjects with good bilateral visual acuity, those with visual acuity worse than 20/40 in one eye had increased mortality (RR, 1.36; 95% CI, 1.12 - 1.65). All-cause mortality was increased in subjects with nuclear opacity (RR, 1.40; 95% CI, 1.12 - 1.75) or cataract surgery (RR, 1.55; 95% CI, 1.18 - 2.05), and cancer deaths were also more frequent in these groups.

Compared with subjects not taking zinc, those randomized to receive any zinc (zinc alone or with antioxidants) had 27% lower mortality (RR, 0.73; 95% CI, 0.61 - 0.89).

The major study limitation was the potential for bias, especially selection bias, inherent in all clinic-based studies.

"The decreased survival of AREDS participants with AMD and cataract suggest that these conditions may reflect systemic rather than only local processes," the authors write. "This is the first large randomized trial to report a potential benefit of the use of high doses of zinc on survival. Other randomized studies of zinc supplementation and mortality are needed to confirm these findings."

The National Eye Institute, the National Institutes of Health, the Department of Health and Human Services, and Bausch & Lomb Inc., supported this study. The authors report no relevant financial interest in this article.

Arch Ophthalmol. 2004;122:716-726

Reviewed by Gary D. Vogin, MD

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