AREDS 2 Confirms and Refines the Use of Dietary Supplements for Age-related Macular Degeneration
From Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 2013;309(19):2005-2015.
Age-related Macular Degeneration (AMD) is a leading cause of vision loss in the United States. Even though there have been improvements in treating the condition, prevention is a major goal. Improved awareness of the disorder, getting regular eye examinations to determine risk, and decreased tobacco use and ocular sun exposure have help to reduce the incidence of AMD. Researchers for the original 2001 Age-Related Eye Disease Study (AREDS) reported that a nutritional supplement called the AREDS formulation can reduce the risk of developing advanced AMD in patients with intermediate or high risk for the disorder (based on findings during an eye examination). The original AREDS formulation contained vitamin C, vitamin E, beta-carotene, zinc and copper and is sold today as Bausch and Lomb Preservision (AREDS).
In 2006, the same NIH National Eye Institute based research group began a second study called AREDS2 to determine if they could improve or modify the AREDS formulation. Unlike the original study, the participants in AREDS2 all had high risk characteristics for advanced AMD. The vitamin formulation was modified in a variety of ways by:
- Adding the antioxidants lutein and zeaxanthin (note: after the original study, lutein was added and sold as an alternative to Preservision AREDS and is called Preservision with Lutein)
- Adding omega-3 fatty acids
- Removing beta-carotene
- Lowering the dose of zinc
The original AREDS formulation contained:
500 milligrams (mg) of vitamin C
400 international units of vitamin E
15 mg beta-carotene
80 mg zinc as zinc oxide
2 mg copper as cupric oxide
AREDS2 modifications included:
10 mg lutein and 2 mg zeaxanthin
1000 mg of omega-3 fatty acids (350 mg DHA and 650 mg EPA)
25 mg zinc
Results of the AREDS2 Trial
In the 2001 AREDS trial, taking the original formulation reduced the risk of advanced AMD by about 25 percent over a five-year period. These benefits persisted at 10 years as well. By that time, approximately 70% of AREDS1 participants were taking the AREDS formulation. Those who had been assigned to the AREDS formulation in the original trial were 25-30% less likely to develop advanced AMD at 10 years than those who had originally been assigned to the placebo group (no supplemental vitamin).
In the AREDS2 trial:
- Adding omega-3 fatty acids DHA/EPA or lutein/zeaxanthin to the original formulation (containing beta-carotene) had no additional overall effect on the risk of progressing to advanced AMD.
- Participants who took AREDS containing lutein/zeaxanthin and no beta-carotene had a slight reduction in risk of advanced AMD, compared with those who took AREDS with beta-carotene.
- In participants with very low levels of lutein/zeaxanthin in their diet, adding these supplements to the AREDS formulation helped lower their risk of advanced AMD.
- Former smokers who took AREDS with beta-carotene had a higher incidence of lung cancer. (Supplemental beta-carotene has been shown in other studies to increased the risk lung cancer in smokers, which is the main reason lutein was substituted in Preservision. This study further showed that even former smokers were at increased risk of lung cancer with supplemental beta-carotene use).
- The investigators found no significant changes in the effectiveness of the formulation when they removed beta-carotene or lowered zinc.
Final recommended supplement composition based on AREDS2:
Vitamin C (500 mg)
Vitamin E (400 IU)
Zeaxanthin (2 mg)
Zinc (80 mg)
Copper (2 mg)
Further, the study results went on to remark that:
- Most people took a complete multivitamin in addition to the study vitamin, since the study vitamin is not a complete vitamin supplement.
- It would not be possible through diet alone to reach the levels of lutein, zeaxanthin, and zinc found the the AREDS2 supplement.
- There was no increased risk of prostate cancer in men related to the vitamin E component of the AREDS2 supplement.
- There was also some protective effect on progression of cataract in participants who had the lowest levels of dietary lutein/zeaxanthin. When the participants were ranked into five equal-sized groups according to their dietary lutein/zeaxanthin intake, supplementation with lutein/zeaxanthin appeared to make a difference for the group with the lowest dietary levels. Within that group, lutein/zeaxanthin was associated with a 32% reduction in progression to cataract surgery.