AREDS is a Landmark Research Project that Evaluated
the Natural History of AMD and Cataract
It featured a controlled, randomized clinical trial that evaluated the effect of pharmacological doses of nutritional supplements on the rate of progression to advanced AMD.1
The researchers evaluated the protective effects of zinc and/or a formulation that consisted of nutrients with antioxidant properties, including vitamin C, vitamin E and beta-carotene. The researchers concluded that a combination of these antioxidants with zinc led to an overall 25% risk reduction in disease progression in individuals who had a moderate risk of AMD development.1 The overall risk of moderate vision loss was reduced by 19% at five years.1
However, like many other groundbreaking studies, the original AREDS researchers generated numerous unanswered questions and suggestions for areas of further study. Many of these items have already been or will be addressed by AREDS2. The enrollment for AREDS2 concluded in June 2008, and participants will be followed for five to six years. The first official reports from AREDS2 are anticipated in 2013.2
The primary objective of AREDS2 is to evaluate the effect of dietary carotenoids—including lutein and zeaxanthin—and/or omega-3 fatty acids—including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—on the progression to advanced AMD.3
In an ideal world of healthy living, these dietary compounds would be best obtained through a balanced diet. In reality, however, our food intake is severely deficient of these important nutrients.
The average western diets contain 1.3mg to 3mg of lutein and zeaxanthin, with a ratio of lutein to zeaxanthin of 7:1.4,5 The highest natural concentrations of lutein are found in dark green leafy vegetables, such as spinach, kale and collard greens, whereas zeaxanthin is the major carotenoid found in corn, orange peppers and oranges.
Additionally, both lutein and zeaxanthin are found in a high-mole percentage in egg yolk.6 It is important to note that approximately 78% of dietary lutein and zeaxanthin is sourced from vegetables.6
Of the numerous carotenoids found in nature, just lutein, zeaxanthin and meso-zeaxanthin are present in human macular pigment.8 Because these carotenoids are likely to play a part in the maintenance of normal cell physiology, the absence or reduced bioavailability of either one may account for the development of the structural changes that occur in patients with AMD.
Both lutein and zeaxanthin were considered for study in AREDS; however, neither carotenoid was commercially available for manufacturing in a research formulation.3 However, AREDS2 researchers are studying their efficacy in preventing the progression of macular degeneration in subjects who present with intermediate drusen.
AMD is a major cause of blindness among individuals with European ancestry and accounts for more than 50% of all blinding conditions.10
The Eye Disease Prevalence Research Group estimates that 1.2 million U.S. residents are living with neovascular AMD and 970,000 have geographic atrophy; these numbers expected to rise 50% by the year 2024.10
There are three major purported risk factors for AMD: age, positive family history and smoking. In fact, smoking is the only consistently proven risk factor for AMD.11-14 As with other age-related diseases, the free radical theory of aging has been proposed as an underlying cause of AMD. This theory proposes that oxidative stress occurs in the retina because levels of reactive oxidative intermediates (ROIs) increase to a level that exceeds the detoxifying capacity of antioxidants.
We have now learned that diets rich in lutein and zeaxanthin have been shown to protect against the development of AMD.21-24 Oral supplementation of lutein or lutein/zeaxanthin combinations in individuals at risk for AMD development and control subjects increased mean serum levels of the carotenoid metabolites that constitute the macular pigment. These effects are not always uniform in all individuals.25-29
Omega-3 Long Chain Polyunsaturated Fatty Acids
One important question being addressed by AREDS2 is whether high supplemental doses of omega-3 fatty acids will inhibit the development of advanced AMD. Researchers have previously determined that DHA and EPA may serve as cytoprotective agents against several retinal diseases as well as cataracts.30 DHA is a major component of retinal photoreceptor outer segment membranes, and an insufficiency of this essential fatty acid can result in altered retinal function.31-35
Overall, epidemiological studies have shown a higher prevalence of AMD in individuals with diets high in total fat intake (exempting diets that are specifically high in omega-3 fatty acids).36-43
Another important supplement investigated in AREDS was zinc. The tolerable upper level of daily zinc intake is 40mg; however, AREDS researchers supplemented patients with 80mg of zinc per day.44,45 AREDS2 investigators are examining the effects of both 80mg and 40mg dosages of zinc per day to determine whether a lower dose could still prevent the development or progression of AMD.
AREDS2 will also investigate the effect of eliminating beta-carotene from the original AREDS formulation. This is of particular interest because high doses of beta carotene alone, or in combination with vitamin E, are associated with a statistically significant risk of developing lung cancer in smokers.48,49 Therefore, it is not recommended to place any patients who smoke or recently quit smoking on beta carotene supplementation.
The Million-dollar Question
Have we now officially determined that dietary and lifestyle changes at an early age can reduce the risk for AMD development and progression?
The answer is quite clear: Yes.
Results from AREDS and other nutritional studies strongly indicated that the earlier an individual begins to make lifestyle alterations and take nutritional supplements, the less risk he or she has for degenerative eye disease. And, for older patients who may already be at an increased risk for AMD, it is better late than never when it comes to the use of nutraceuticals.
In the very near future, the results from AREDS2 will shed more light on the most effective management options for AMD as well as address which specific nutritional supplements are most useful in disease prevention and treatment
EyeScience Macular Health Formula was designed to take the best of both AREDS and AREDS 2. Together with additional clinically proven nutrients, our formula is the most complete ocular supplement designed for those with and without AMD.