Lutein plus zeaxanthin supplementation may benefit AMD patients with insufficient dietary intakes

According to a new US study, the addition of lutein plus zeaxanthin and omega-3 fatty acids to a supplement that has been proven protective in progression to advanced age-related macular degeneration (AMD) may not significantly further reduce this risk in AMD patients. However, lutein and zeaxanthin may play a role in additionally lowering the risk of AMD progression in patients with low intakes of these carotenoids.

This randomized controlled trial included 4,203 participants, aged 50 to 85, who had age-related macular degeneration (AMD) and were at risk for progression to advanced AMD (1). In addition to the original AREDS formulation (2) – a high-dose daily intake of vitamin C (500 mg), vitamin E (400 IU), beta-carotene (15 mg), zinc (80 mg as zinc oxide), and copper (2 mg as cupric oxide) – participants were asked to take either lutein (10 mg) plus zeaxanthin (2 mg), docosahexaenoic acid (350 mg as DHA) plus eicosapentaenoic acid (650 mg as EPA), both of them, or placebo daily for an average of five years. The study results showed that the AREDS2 formulation did not show an additional reduction of the participants’ risk in progressing to advanced AMD (compared with the effect of disease risk reduction measured for the AREDS formulation before). However, a 26% lower risk of progression to advanced AMD (1) and a 32% lower risk of cataract surgery (3) were shown in participants with the lowest dietary intake of lutein plus zeaxanthin. Also, an elevated risk of lung cancer in the group of former smokers who received a high dose of beta-carotene was observed compared to the group of people who received multivitamins without beta-carotene (a 2% and 1% higher risk, respectively).

The researchers commented that the study enrolled a population of well-nourished people and that there might be benefits of additional supplemented micronutrients for AMD patients who are less well-nourished. For example, in the US, dietary intake of lutein and zeaxanthin is typically less than 1 mg per day. As the number of cases of lung cancer was small and the analyses of mortality risk in the beta-carotene group of former smokers and all other groups showed essentially no change in rates, the results may not be generali-zable, the scientists noted. In 2012, the European Food Safety Authority (EFSA) concluded that exposure to beta-carotene from its use as a food additive and as a food supplement at levels below 15 mg/day should not give rise to concern about adverse health effects in the general population, including heavy smokers (4).

The Age-Related Eye Disease Study (AREDS) demonstrated that daily oral supplementation with antioxidant vitamins and minerals reduced the risk of developing advanced AMD as secondary preventionby 25% five years later (2) and 34% 10 years later (5). In addition, observational studies suggested that higher dietary intake of lutein plus zeaxanthin, omega-3 long-chain polyunsaturated fatty acids (DHA and EPA), or both are associated with a decreased risk of developing advanced AMD (6, 7). Lutein and zeaxanthin are the main components of the macular pigment. DHA is a major structural component of the retina, and EPA may play a role as a precursor to signaling molecules with potential to influence retinal function.

1. The AREDS2 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. Published online May 2013.
   
   2. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001; 119(10):1417-1436.
   
   3. The AREDS2 Research Group. Lutein/Zeaxanthin for the treatment of age-related cataract. JAMA Ophthalmol. Published online May 2013.
   
   4. EFSA Panel on Food Additives and Nutrient Sources added to Food. Statement on the safety of beta-carotene use in heavy smokers. EFSA Journal 2012; 10(12):2953.
   
   5. Chew E. Y. et al. Long-Term Effects of Vitamins C and E, β-Carotene, and Zinc on Age-Related Macular Degeneration: AREDS Report No. 35. Ophthalmology. Published online April 2013.
   
   6. SanGiovanni J. P. et al; Age-Related Eye Disease Study Research Group. Omega-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr. 2009; 90:1601-1607.
   
   7. Augood C. et al. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration. Am J Clin Nutr. 2008; 88(2):398-406.