The Origins of AREDS2's High Zinc Dosage
To understand the debate around the zinc content in AREDS2, it is important to first look at the original Age-Related Eye Disease Study (AREDS), conducted by the National Eye Institute (NEI). The initial AREDS trial, published in 2001, established a specific formula of antioxidants and minerals—including a robust 80 mg of zinc—that was found to reduce the risk of advanced AMD progression by approximately 25% over five years in certain high-risk patients. The 80 mg dosage was chosen because it showed the most promising results in the initial testing.
The AREDS formula was revolutionary, but the high zinc content quickly drew scrutiny. The Recommended Dietary Allowance (RDA) for zinc is significantly lower, at 8 mg for adult women and 11 mg for adult men. The 80 mg dose is twice the tolerable upper intake level (UL) of 40 mg per day for healthy adults, the maximum amount recommended to avoid side effects. This raised concerns about potential side effects from long-term, high-dose supplementation.
The AREDS2 Trial: Re-evaluating Zinc Levels
In response to these concerns and new findings about other beneficial nutrients, the NEI conducted the AREDS2 trial, which began in 2006. One of the key objectives was to determine if the amount of zinc could be reduced without compromising the formula's effectiveness. The study compared a modified formula with a lower dose of zinc (25 mg) to the original 80 mg dose.
Key findings from the AREDS2 trial regarding zinc:
- Equivalent Efficacy: The trial found that lowering the zinc dose from 80 mg to 25 mg had no significant effect on slowing the progression of AMD. This demonstrated that a high dose was not superior to a lower one for most participants.
- Uncertainty Remains: Despite this finding, AREDS2 investigators concluded that it is still unclear exactly how much zinc is necessary or optimal to achieve the formula's protective effect.
- Genetic Variation: Subsequent analysis has also suggested that some individuals with specific genetic risk factors (CFH and ARMS2 alleles) may respond differently to zinc supplementation, with some potentially experiencing worse outcomes with the higher dose.
The Risks and Side Effects of High-Dose Zinc
Supplementing with zinc at 80 mg per day, double the UL, carries several known health risks. While copper is included in AREDS formulas to mitigate the risk of deficiency, this is not always enough.
Risks associated with high zinc intake:
- Copper Deficiency: The most common and serious risk is the development of copper deficiency (hypocupremia). Zinc and copper compete for absorption in the gut. Excessive zinc intake can block copper absorption, potentially leading to anemia and neurological problems, such as myelopathy.
- Digestive Issues: High doses of zinc can cause gastrointestinal side effects, including nausea, vomiting, abdominal cramps, and diarrhea. Some participants in the AREDS studies reported stomach upset from the high zinc levels.
- Reduced Immune Function: Long-term excessive zinc intake can interfere with immune system function, potentially making the body more susceptible to infections.
- Genital and Urinary Issues: The original AREDS study found a significant increase in hospitalizations for genitourinary conditions among those taking 80 mg of zinc.
Comparison of AREDS vs. AREDS2 Zinc Doses
| Feature | Original AREDS (Pre-2013) | AREDS2 (Post-2013) |
|---|---|---|
| Zinc Dose | 80 mg (as zinc oxide) | 80 mg (as zinc oxide) or 25 mg options |
| Tolerable Upper Intake Level | Twice the 40 mg UL | Some formulations are twice the UL, others are lower |
| Effectiveness (80 mg vs. 25 mg) | Not compared, 80 mg was the standard | Found no significant difference in effectiveness for most people |
| Side Effects | Increased risk of stomach upset and urinary issues | Lower risk with the 25 mg option |
| Beta-carotene | 15 mg | Replaced with lutein and zeaxanthin |
Is there too much zinc in AREDS2? The Verdict and Alternative Options
For many, especially those experiencing side effects, the 80 mg of zinc found in some AREDS2 supplements may indeed be excessive. The key takeaway from the AREDS2 trial was that a reduced zinc dose (25 mg) provided comparable protection against AMD progression for the overall study population, with fewer reported side effects.
As a result, many supplement manufacturers now offer multiple AREDS2 formulas, including options with lower zinc levels or without zinc entirely. Some ophthalmologists, like Dr. Paul Krawitz, advise a lower-zinc approach, especially for patients with a genetic predisposition to sensitivity.
What to do if you're concerned:
- Consult your doctor: Before making any changes, discuss your concerns with an ophthalmologist. They can assess your individual risk factors and determine the most appropriate course of action for you, potentially including genetic testing.
- Explore low-zinc options: Look for commercially available AREDS2 formulations that explicitly list 25 mg of zinc or less. Several brands adhere to the AREDS2 formula with this reduced amount.
- Prioritize diet: While AREDS2 supplements are effective for specific patients, a diet rich in eye-healthy nutrients (like leafy greens and fish) is the front-line approach for everyone.
Conclusion
The question of whether there is too much zinc in AREDS2 is complex, but the data from the AREDS2 study and subsequent research provide valuable clarity. While the original AREDS trial established 80 mg as an effective dose, AREDS2 demonstrated that 25 mg is just as beneficial for most patients in slowing AMD progression. This finding, combined with the recognized risks of high-dose zinc, suggests that many patients may benefit from choosing a lower-zinc formulation. Discussing your personal risk factors and genetic profile with an eye care professional is the best way to determine the optimal supplement strategy for your needs.
Macular Degeneration Foundation Australia Fact Sheet on AREDS2
