Zinc Toxicity in the Management of Macular Degeneration

James Meschino DC, MS, ROHP

In 2001, the Age-Related Eye Disease Study, a multi-center, intervention trial involving 4,757 patients between the ages of 55 and 80 years old, showed that supplementation with antioxidants and zinc slowed the progression of macular degeneration. More specifically, in this study, conducted by the National Eye Institute (NEI), patients who were at high risk of developing more advanced stages of age-related macular degeneration (AMD) reduced their risk by approximately 25% when treated with a high-dose combination of Vitamin C, Vitamin E, Beta-carotene, and zinc. According to the NEI this was the first effective treatment ever shown to successfully slow the progression of AMD.

Participants in this double-blind, placebo-controlled clinical study, who suffered from varying degrees of AMD, were provided with one of four treatments: zinc alone; antioxidants alone; a combination of antioxidants and zinc; or a placebo. After 6.3 years of treatment the results showed that taking zinc alone (80 mg per day, plus 2mg of copper) or antioxidants alone (Vitamin C–500mg, Vitamin E–400 IU, Beta-carotene–25,000 IU per day) were effective interventions, but the best results occurred in those taking both antioxidant and zinc supplements at the above described doses.

Since this study was published, a number of companies have formulated eye-care supplement products intended to slow the progression of macular degeneration. Many eye doctors recommend these supplements to patients, which can be purchased without a prescription in drug stores and health food stores throughout North America.

Health practitioners should realize that many of these eye-care supplements contain high doses of zinc. As such, you must be aware of the risk of zinc toxicity that may occur from additional zinc from a multiple vitamin (or from other supplements or functional drinks or bars). There is great individual variation with respect to zinc intake that can initiate zinc toxicity. Practitioners should be aware that documented evidence indicates that a total zinc supplementation of 60 mg per day appears to be the lowest threshold level at which some people show signs of zinc toxicity. However, many people can tolerate higher daily dosages. It’s important to realize that many supplements used to treat macular degeneration contain 40 – 70 mg of zinc in the daily dosage.

Thus practitioners must be familiar with signs and symptoms of zinc toxicity, if they are recommending eye-care supplements, or recommending supplements containing zinc that result in a total daily zinc supplementation at or above 60 mg.

Zinc Toxicity
Zinc toxicity can occur in both acute and chronic forms. Acute adverse effects of high zinc intake include nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, and headaches.  One case report cited severe nausea and vomiting within 30 minutes of ingesting 4 g of zinc gluconate (570 mg elemental zinc). This scenario may occur in patients taking zinc lozenges to treat a sore throat.

Intakes of 150–450 mg of zinc per day have been associated with such chronic effects as low copper status, altered iron function, reduced immune function, and reduced levels of high-density lipoproteins.

Reductions in a copper-containing enzyme, a marker of copper status, have been reported with even moderately high zinc intakes of approximately 60 mg/day for up to 10 weeks.

Note that the doses of zinc used in the AREDS study (80 mg per day of zinc in the form of zinc oxide for 6.3 years, on average) have been associated with a significant increase in hospitalizations for genitourinary causes, raising the possibility that chronically high intakes of zinc adversely affect some aspects of urinary physiology.

My suggestion is to encourage patients with macular degeneration to take an eye-care supplement that contains no more than 30 mg of zinc. In addition, I would recommend that the patient take a high potency multiple vitamin and mineral supplement that contains additional 15 mg of zinc and a B-50 complex (as well as 1,000 mg vitamin C, 400 IU vitamin E, 10,000 IU beta-carotene, 100 mcg selenium).  This recommendation is based on the 2009 study (Christen W.G. et al, Archives of Internal Medicine) showing that B-vitamin supplementation reduced risk of macular degeneration by 34% in women with risk factors for heart disease. This effect was likely mediated by the ability of certain B-vitamins (Folic acid, Vitamin B12, Vitamin B6) to lower homocysteine levels, which damages blood vessels, including vessels in and around the retina. This approach helps guard against zinc toxicity (while still supplying ample amounts of zinc therapeutically) and fortifies the eye with specific antioxidants and B-vitamins that are important in preventing and managing macular degeneration, and cataracts.

1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001.
2. Lewis MR, Kokan L. Zinc gluconate: acute ingestion. J Toxicol Clin Toxicol 1998;36:99-101.
3. Hooper PL, Visconti L, Garry PJ, Johnson GE. Zinc lowers high-density lipoprotein-cholesterol levels. J Am Med Assoc 1980;244:1960-1.
4. Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol 2007;177:639-43.
5. W.G. Christen, R.J. Glynn, E.Y. Chew, C.M. Albert, J.E. Manson. Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women: The Women’s Antioxidant and Folic Acid Cardiovascular Study. Archives in Internal Medicine
   2009, Volume 169;4:335-341