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AREDS2 continues to provide useful guidance on nutritional supplements
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The long-awaited results of the AREDS2 were reported at the Association for Research in Vision and Ophthalmology meeting. Some of the findings were as expected, and one in particular was a surprise. A few thoughts on the outcomes and my personal interpretation.
This is a meaningful and valid study with 82 centers, 6,916 eyes of 4,205 patients between the ages of 50 years and 85 years, and 6 years’ duration. The patients studied were high-risk patients with bilateral large drusen or large drusen and severe vision loss from age-related macular degeneration in the fellow eye. The control group received the AREDS1 formula, not placebo, because AREDS1 has been shown to benefit these high-risk patients and it was considered unethical to use placebo.
The first expected finding was that inclusion of 15 mg of beta carotene increased the risk of lung cancer to 2% from 0.9%. Second, inclusion of 10 mg of lutein and 2 mg of zeaxanthin as a replacement for beta carotene was equally to slightly more effective. So, it makes sense to eliminate beta carotene and replace it with 10 mg of lutein and 2 mg of zeaxanthin. Reducing the zinc concentration resulted in no measurable benefit in regards to mitigating side effects, and when accompanied by 2 mg of copper, it seems safe, with decades of use and hundreds of thousands of doses of the AREDS1 formulation. Conclusion: Zinc can be retained at 80 mg along with 2 mg of copper. The 500 mg of vitamin C and 400 IU of vitamin E were retained in both formulations and also make sense for inclusion.
On the unexpected side, omega-3 supplementation at 1,000 mg per day showed no benefit. One potential explanation is that only 1,000 mg of the less well-absorbed ester form of omega-3 was administered. Many experts in the field prefer the re-esterified triglyceride form of omega-3 because it is better absorbed and potentially more potent. In addition, many recommend 2,000 mg a day, and that is the dose that I have found to be the minimum for efficacy when treating meibomian gland dysfunction (MGD) and associated evaporative dry eye. Omega-3s will not be part of the official AREDS2 formulation. Still, for me, they will remain a recommendation for those with progressing AMD and the commonly associated MGD with dry eye symptoms. I will encourage patients to use the re-esterified triglyceride form of omega-3 at a minimum dose of 2,000 mg per day.
Finally, somewhat disappointing to me, none of the formulations showed a measurable benefit in retarding the development or progression of cataract. Years ago, when studying the early ICAPS formulation (Alcon) in a multicenter study, a group of investigators and I found some retardation of cataract as measured using a densitometer, which was more sensitive than Snellen visual acuity measurements. Again, the literature is mixed on the effect of antioxidant vitamins and omega-3s on cataractogenesis, but there is no evidence in any study that either accelerate the development of any form of cataract.
Many, including me, offer nutritional supplements to our patients at an earlier stage of AMD than studied in AREDS, AREDS2 or other studies. There is increasing evidence that antioxidant vitamins and omega-3s have a positive impact in regard to our patients’ general health and may reduce the risk of cardiovascular diseases such as stroke and heart attack and some cancers. In addition, omega-3s help many patients with ocular surface disease and can enhance skin and joint health. I personally remain comfortable recommending a formulation like the one affirmed in the AREDS2 at the earliest stages of AMD and even in patients with a positive family history of significant vision loss from AMD. I am also comfortable recommending 2,000 mg per day of the triglyceride form of omega-3 when MGD and early AMD coincide in the same patient. There are some patients who cannot tolerate omega-3s, and their use in the face of anticoagulation needs to be cautious, with an informed primary care doctor and patient. In addition, some patients cannot swallow the large capsules. In these cases, they can be broken up and added to food. Liquid or chewable versions with similar contents are available at many pharmacies and health foods stores.
Nutritional supplements are a critical component of ophthalmology practice, and AREDS1 and AREDS2 have provided useful guidance for clinicians. Still, we must interpret them in the light of other published findings and use our best clinical judgment when advising each individual patient. As in other areas of treatment, some of us will be more aggressive in our recommendations for nutritional supplements and others more conservative. Considering the high safety profile and potential systemic benefits, I personally lean toward the aggressive side, allowing an informed patient to make the final decision.