In 2001, the National Eye Institute (NEI) published the results of the Age-Related Eye Disease Study (AREDS), a clinical study about the etiology, pathogenesis, and treatment of age-related macular degeneration (AMD) and cataracts. They repeated the study in 2006, publishing in 2013, using new nutrients and new scientific research to see if they could not only slow the progression of advanced AMD, but also stabilize or even improve vision loss.
We interviewed Edward Paul Jr., OD, PhD, an expert in AMD, about the two AREDS formulations, treating age-related macular degeneration, and his thoughts on how dietary supplements, such as TOZAL®, may benefit the eyes.
FOCUS LABORATORIES, INC (FLI): For the second AREDS formulation, researchers tested the effects of omega-3, a reduced amount of zinc, and the replacement of beta-carotene with lutein/zeaxanthin on AMD progression. What drove this additional research?
DR. PAUL: From a foundational standpoint, AREDS1 was published in 2001, and AREDS2 was published in 2013. During the 12-year gap between the studies, the knowledge base surrounding how nutrients may mitigate the impact of macular degeneration had grown exponentially.
Secondly, we realized that the first AREDS formulation only slowed the progression of AMD in 25% of patients and did nothing for the other 75% of patients who were taking the first formulation. In other words, 25% of patients in the first study went blind at a slower rate as compared to those who did nothing. With AREDS2, researchers looked at efficacy rates of the new nutrients that had been introduced since AREDS was initially developed.
FLI: What’s your opinion on the results of the AREDS2?
DR. PAUL: There were a couple of surprises in the 2013 AREDS2 results. The first surprise showed us over 50 studies1 indicating omega-3 does positively impact macular degeneration—either slowing it, stabilizing it, or in some studies, actually improving vision. But that was not seen in AREDS2.
My theory as to why omega-3 did not have an impact on the AREDS2 formula is based on the use of the processed ethyl ester form of omega-3 instead of the more naturally occurring triglyceride form of omega-3. The more “natural” form has been found to be better absorbed by the body, and therefore, could have impacted the results in AREDS22. It all goes back to the quality of the ingredient that’s being used. For this specific reason, the naturally occurring triglyceride form of omega-3 from fish oil is included in the TOZAL® formulation.
Another confounding point is the decision by the National Eye Institute to leave the dosage of zinc at 80 mg in the AREDS2 formula. Typically, you want to use the smallest dose you possibly can of any medication that might be effective. TOZAL® contains only 25 mg of zinc because this amount has been found to be as effective as 80 mg found in the AREDS2 formula5. It’s surprising, that despite this finding, the NEI still included a higher dose of zinc rather than the lowest, most effective dose.
Less surprising is the replacement of beta-carotene with lutein/zeaxanthin. An important component to TOZAL®, lutein/zeaxanthin is so new to the market that the nutrients didn’t even exist during AREDS1. During AREDS2, researchers found that not only is lutein/zeaxanthin as effective as beta-carotene, it’s probably more effective.
The final AREDS2 formula replaced beta-carotene with lutein/zeaxantin, left the zinc at 80 mg, and excluded omega-3. In reality, TOZAL® clearly checks all of the boxes as a dietary supplement for complete ocular health and, while formulating the final product, I took the findings of AREDS2 very seriously. TOZAL® is an AREDS2-based formulation with some improvements – it has the same amount of vitamin C, and vitamin E with an increased amount of Lutein (15 mg) and Zeaxanthin (3 mg). We reduced the amount of Zinc from 80 to 25 mg and changed to the form of Zinc from oxide to piconlinate. TOZAL® also includes other key ingredients, such as vitamin A, vitamin D and B-complex. Each ingredient has specific benefits that they bring to the supplement, such as assisting the retina to process low light.
FLI: We discussed the difference between dry and wet macular degeneration in a previous blog post. Why is it so much more difficult to treat dry vs. wet macular degeneration?
DR. PAUL: Let’s start with a simple definition of the two forms. Dry macular degeneration, which accounts for 80-90% of all cases3, is defined as photoreceptor cell death, and in the wet form of macular degeneration, which accounts for 10-20% of cases3, the photoreceptor cell death is specifically due to blood leakage underneath the macula at the center of the retina.
FLI: In other words, the big difference is we don’t really know what causes the photoreceptor cell death in dry macular degeneration, whereas, in the wet form, we know it’s because of the blood vessel leakage?
DR. PAUL: That’s correct. We don’t know a lot about the dry form of macular degeneration other than there is a hereditary component.
FLI: Why do you think dietary supplements and diet are so important when talking about AMD and eye health in general?
DR. PAUL: There are two reasons we’re seeing a boom in macular degeneration today: (1) people are living longer, and (2) the nutrients we get from our food sources are not adequate. About 15 years ago, the American Medical Association (AMA) found that 85% of Americans were deficient in one or more vitamins and nutrients4. Before that, vitamin supplements were considered harmless, but basically useless. The foods we consume—even fruits and vegetables labeled organic—simply do not have the same nutrient value as they did 50 years ago4. For example, the U.S. Department of Agriculture states it would take three apples in 2017 to equal the same nutrient content that one apple had in 1967. They have the same number of calories, but not the same nutrient value. No matter how good you think you’re eating, you’re not getting everything you need in a typical diet.
Dietary supplements, whether for macular degeneration or for general health, are the cheapest insurance policy you’ll ever buy. It takes approximately three small salad bowls of spinach to equal 10 mg of lutein – this amount of lutein can be found in 3 TOZAL® softgels and is the recommended dose in the AREDS2 formulation. Realistically, who’s going to eat three bowls of spinach per day? Technically, you can get all the nutrients provided in a dietary supplement from your diet, but it’s impractical and difficult.
Most of the people who walk through my door are suffering from age-related conditions —whether it’s a 45-year-old man who needs reading glasses or a 75-year-old woman who has AMD. There are lifestyle changes that can slow AMD down or speed it up, but this is a chronic, degenerative, age-related disease. And until we find the fountain of youth or figure out how to stop aging, dietary supplements that are modeled after the AREDS2 research, such as TOZAL®, may be our best way forward.
New treatments have been—and continue to be—developed, which can make the condition more manageable. Regular eye exams, being aware of your risk factors, and early detection can help save your vision. Learn more about AMD in our blog post, “Age-Related Macular Degeneration: 5 Questions, 5 Answers.”
- Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH. Dietary ?-3 Fatty Acid and Fish Intake in the Primary Prevention of Age-Related Macular DegenerationA Systematic Review and Meta-analysis. Arch Ophthalmol. 2008;126(6):826-833. doi:10.1001/archopht.126.6.826 http://jamanetwork.com/journals/jamaophthalmology/fullarticle/420564
- Laidlaw, M., Cockerline, C., & Rowe, W. (2104, April). Comparative bioavailability of omega-3 fatty acids from four different omega-3 supplements. FASEB Journal, 28(1), 272.6. http://www.fasebj.org/content/28/1_Supplement/272.6
- Age-Related macular Degeneration: Facts & Figures. (2016, January 5). Retrieved from Bright Focus Foundation: http://www.brightfocus.org/macular/article/age-related-macular-facts-figures
- Kant AK. Reported Consumption of Low-Nutrient-Density Foods by American Children and Adolescents Nutritional and Health Correlates, NHANES III, 1988 to 1994. Arch Pediatr Adolesc Med. 2003;157(8):789-796. doi:10.1001/archpedi.157.8.789 http://jamanetwork.com/journals/jamapediatrics/fullarticle/481392
- National Institute of Health. (2013, May). For the People: What the AREDS Means for You. Retrieved from the National Eye Institute: https://nei.nih.gov/areds2/PatientFAQ