On the other hand, subgroup analysis comparing lutein and zeaxanthin with the groups given the original AREDS supplement (vitamins C, E, beta-carotene and zinc) revealed a statistically significant reduction in the progression to advanced AMD of 9% for lutein and zeaxanthin in the entire study group, according to data published in the Journal of the American Medical Association.
The findings were also presented yesterday at the Association for Research in Vision and Ophthalmology annual meeting.
In addition, concerns were raised about beta-carotene, with more lung cancers observed in the beta carotene group, compared with the no-beta-carotene group, mostly in former smokers.
“Based on apparent risks of beta carotene and possible benefits that are only evident within exploratory subgroup analyses, lutein + zeaxanthin requires further investigation for potential inclusion in the AREDS supplements,” wrote the authors from the AREDS2 research group.
‘The AREDS2 results reaffirm that lutein and zeaxanthin reduce the risk of AMD’
Jeff Flora, president, human nutrition and health division of Kemin, told NutraIngredients-USA that the company is “very pleased with The National Eye Institute's new recommendation for AREDS2 formulations based on this landmark study.
“NEI's recommendation adds 10 mg lutein and 2 mg zeaxanthin and eliminates beta carotene in the original AREDS supplement.
“Results from AREDS2 report a 18% reduction in progression to advanced AMD in subjects who received 10 mg FloraGLO Lutein and 2 mg Optisharp Zeaxanthin, in addition to an AREDS supplement without beta carotene when compared to the original AREDS supplement with beta carotene.
“This reduction in progression to advanced AMD is even greater (26%) in study subjects with the lowest intake of lutein and zeaxanthin in their diet, which is more representative of the general US population. In the US, the dietary intake of lutein and zeaxanthin is typically less than 1 mg per day. This amount is well below the 10 mg lutein and 2 mg zeaxanthin that the study has proven to be effective,” saidFlora.
“In conclusion, the AREDS2 results reaffirm previous epidemiological data that high dietary intakes of lutein and zeaxanthin reduce the risk of AMD and additionally supports the benefits of substituting 10 mg of lutein and 2 mg of zeaxanthin for beta carotene in AREDS formulations.”
Carotenoids and AMD
An extensive body of science supports the vital role of the carotenoids lutein and zeaxanthin for eye health. Both are found in high levels in the macula, a yellow spot of about five millimeters diameter on the retina.
These compounds are the only carotenoids capable of filtering the harmful blue light than can damage cells in the eye, the rods and the cones.
A thin macular pigment can allow the blue light through and destroy the cells. Maintaining high levels of both carotenoids, and therefore the macular pigment, is a valid approach to maintaining eye health and reducing the risk of diseases, like AMD.
A recent study by researchers in Germany reported that a combination of lutein, zeaxanthin and omega-3 long-chain polyunsaturated fatty acids may boost the pigment in the retina.
The much anticipated AREDS2 study examined whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation might further reduce the risk of progression to advanced AMD. A secondary goal was to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation.
Emily Chew, MD, of the National Eye Institute, National Institutes of Health, Bethesda, MD, and her co-workers recruited 4,203 people aged between 50 and 85 at risk for progression to advanced AMD.
Participants were randomly assigned to receive lutein (10 mg) and zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA + EPA, or placebo. All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both.
A total of 1,608 participants had experienced at least 1 advanced AMD event by the end of the study, said the researchers. Results indicated that the probabilities of progression to advanced AMD by 5 years were 31% for placebo, 29% for lutein + zeaxanthin, 31% for DHA + EPA, and 30% for lutein + zeaxanthin and DHA + EPA.
AREDS2 vs AREDS1
The researchers also performed post-hoc analyses that compared AREDS2 participants randomized to receive lutein + zeaxanthin and AREDS formulation without beta carotene vs those randomized to receive no lutein + zeaxanthin and the original AREDS formulation.
The results of the post-hoc analyses suggested that “lutein and zeaxanthin may play a role for reducing the risk of progression [by 18-26%, depending on initial lutein/zeaxanthin intakes] to advanced AMD when given without beta-carotene,” they wrote. “This hypothesis requires further study.”
Omega-3s: Past research suggests a role for EPA + DHA in decreasing AMD risk
Not everyone was impressed with the study and its conclusions, however. Harry Rice, PhD, VP of regulatory & scientific affairs for the Global Organization for EPA and DHA Omega-3s (GOED), told us: “While results from the present study were highly anticipated, as far as I'm concerned, this study was doomed from the outset given the flawed experimental design; therefore, expectations should have been low.
“There was no true placebo group, rather an active placebo group, making it more difficult to demonstrate a benefit of any of the treatments. More specifically, all subjects assigned to the control group received some variation of the supplement formula used in the original AREDS, which demonstrated that use of high-dose antioxidant and zinc supplements reduced progression of intermediate to late AMD.
“While it may be true that EPA+DHA don't attenuate the progression of intermediate to late AMD, due to a ceiling effect, we cannot conclude with any certainty.
“There are a couple of other important points to keep in mind. This study did not assess primary prevention. While past research suggests a role for EPA+DHA in decreasing the risk of developing AMD, the present research did not address this issue. Rather, it addressed the issue of secondary prevention. With respect to secondary prevention, it's possible that earlier stages of AMD are more responsive to treatment with EPA+DHA,” added Dr Rice.
In an addition report from the AREDS2 research group, the AREDS2 formula was found to have no effect on the incidence of age-related cataracts.
Writing in JAMA Ophthalmology, the researchers concluded: “While observational studies have suggested that higher dietary intake or higher blood levels of lutein and zeaxanthin may have a protective effect on the development of cataract, this randomized, placebo-controlled trial did not find an effect of supplementation with lutein/ zeaxanthin on cataract surgery, cortical or PSC lens opacity progression, or vision loss.
“Whether supplementation would be beneficial for less well-nourished populations requires further study.”
2013, Volume 309, Number 19, Pages 1-11, doi:10.1001/jama.2013.4997
“Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial”
Authors: The Age-Related Eye Disease Study 2 (AREDS2) Research Group
2013, Volume 131, Number 4, Pages 1-7, doi:10.1001/jamaophthalmol.2013.4412
“Lutein/Zeaxanthin for the Treatment of Age-Related Cataract: AREDS2 Randomized Trial Report No. 4”
Authors: The Age-Related Eye Disease Study 2 (AREDS2) Research Group