Adding lutein, zeaxanthin, and omega-3 polyunsaturated fats to vitamin supplements that are used to help prevent the progression of age-related macular degeneration (AMD) doesn’t improve outcomes, according to a study published online in JAMA. But the study also found that former smokers with macular degeneration who take supplements containing beta carotene have an increased risk of lung cancer and that substituting lutein and zeaxanthin for beta carotene in the existing supplements may reduce this beta carotene–related risk.
With limited options for the treatment of macular degeneration, one of the primary strategies for managing the disease has been to slow its progression. One intervention that appears to help is supplementation with antioxidant vitamins C and E, beta carotene, and zinc. Such treatment has become a common practice after the Age-Related Eye Disease Study (AREDS), a large randomized trial, found that such supplementation reduced progression by 25% at 5 years. In addition, some observational and animal studies have suggested that individuals with diets high in certain other nutrients were also less likely to progress to more advanced forms of macular degeneration.
To probe whether the addition of lutein, zeaxanthin, and omega-3 long-chain polyunsaturated fatty acids to the currently recommended supplement offers benefit, the AREDS team conducted a randomized study of 1608 participants comparing progression of macular degeneration among individuals taking the original supplement plus lutein, zeaxanthin, and omega-3 fatty acids or the original supplement plus placebo. They did not find any additional reductions in progression in the group receiving the add-on supplementation. They did, however, find that former smokers taking the original supplement (current smokers were excluded from groups receiving beta carotene) had an increased rate of lung cancer compared with those taking a revised version of the original supplement that substituted lutein and zeaxanthin for beta carotene.
Emily Y. Chew, MD, of the National Eye Institute (NEI), discussed the findings with news@JAMA:
news@JAMA: Why did you decide to conduct this study?
Dr Chew: More than a decade ago, we showed in the AREDS trial that supplementation with vitamins C and E, beta carotene, and zinc was effective at reducing progression to advanced macular degeneration by 25%. It was surprising at the time that we could reduce progression to the wet form of macular degeneration. With this study, we were hoping to improve on that.
news@JAMA: What led you to believe that adding lutein, zeaxanthin, and omega-3s might help?
Dr Chew: Our AREDS trial was a randomized trial, but we were able to track intakes of dietary nutrients. People who ate green leafy vegetables such as spinach, kale, and collard greens get a lot of lutein and zeaxanthin, and those with diets high in fish get a lot of omega-3s. In the original AREDS trial, we found an almost 40% reduction in the prevalence of macular degeneration in people who had a higher intake of fish or leafy vegetables. Our study found this and other groups found this.
news@JAMA: Do you know what the mechanism for this protective effect might be?
Dr Chew: Lutein and zeaxanthin are present in the eye. Based on observational and basic science studies, these are important constituents of the eye and we were paying attention to that. Lutein and zeaxanthin may protect against oxidative stress and may screen out damaging light effects. Omega-3s may be fighting inflammation. We don’t really know what causes AMD and don’t have good animal models, so it’s tough to research this disorder.
news@JAMA: What did this study tell you about the risks of beta carotene supplementation?
Dr Chew: There were 2 large randomized trials in the 90s that found beta carotene supplementation increased the risk of lung cancer in current smokers. In our current study, we did not offer a supplement containing beta carotene to smokers. But we found that former smokers had a doubling of the risk of lung cancer when they took the beta carotene–containing supplement. This is important because most of the population in AREDS and those with AMD are former smokers, so this is a clinically relevant problem.
news@JAMA: Did you find any benefit to the additional supplementation?
Dr Chew: We can clearly say the omega-3s didn’t add anything. In subgroup analyses of lutein and zeaxanthin supplementation, we saw 10% reduction in progression overall. Among the people with the lowest dietary intake of these nutrients, we saw a 25% reduction in progression.
news@JAMA: Do the data warrant changes to the formulation of the supplements from the AREDS trial?
Dr Chew: Lutein seemed to be better than beta carotene. Based on the totality of evidence, we may have a safer formulation if we remove the beta carotene. The beta carotene is not essential and the lutein is a good substitute.
news@JAMA: Do your findings suggest certain dietary interventions for eye health?
Dr Chew: You are what you eat and people should have good diets. Levels of lutein and zeaxanthin are going down in many individuals’ diets because we aren’t cooking anymore. Sometimes a good diet won’t help you; some people with good diets still get macular degeneration.
The AREDS supplement is at least moderately effective at reducing progression. But only those at risk should take this supplement, and only a eye examination by a professional can tell you if you have macular degeneration. People over the age of 60 years should have their eyes examined by a professional.