Published: May 5, 2013 | Updated: May 6, 2013

By Crystal Phend , Senior Staff Writer, MedPage Today

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Action Points

• Adding lutein, zeaxanthin, and fish oil to daily multivitamin supplements doesn’t boost prevention of age-related macular degeneration (AMD) or cataracts in high-risk individuals.
• Note that none of the additions to the base antioxidant supplements were associated with significant reductions in progression to cataract surgery or significant vision loss over 5 years.

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Adding lutein, zeaxanthin, and fish oil to daily multivitamin supplements doesn’t boost prevention of age-related macular degeneration (AMD) or cataracts in high-risk individuals, two analyses of the Age-Related Eye Disease Study 2 (AREDS2) showed.

None of the additions to the base antioxidant supplements had significant impacts on progression to advanced AMD, Emily Chew, MD, of the National Eye Institute in Bethesda, Md., and colleagues reported in the Journal of the American Medical Association.

Nor were there significant reductions in progression to cataract surgery or significant vision loss over 5 years, the same group reported in JAMA Ophthalmology.

Both papers appeared early online to coincide with presentation at the Association for Research in Vision and Ophthalmology meeting in Seattle.

The only significant findings in either study were:

• A lower risk of cataract surgery with lutein plus zeaxanthin in those with the lowest dietary intake of the supplements (hazard ratio 0.68, P=0.03)
• A lower risk of progression to advanced AMD with lutein plus zeaxanthin in the lowest dietary intake quintile (HR 0.74,P=0.01)
• An elevated risk of lung cancer in a subrandomization to beta carotene versus none in the multivitamin arm (2% versus 1%, P=0.04)

 

The only possible role for lutein and zeaxanthin antioxidants would be for poorly-nourished populations or as a substitute for beta carotene in the AREDS formulation, Chew’s group suggested.

That could be an important finding for smokers and former smokers, who appeared to be the ones mainly affected by the lung cancer risk of beta carotene, commented Douglas Jabs, MD, MBA, chair of ophthalmology at Mount Sinai Hospital in New York City, who was not involved in the study.

The results don’t provide the final word on lutein and zeaxanthin overall, though, he argued in an email to MedPage Today.

“This study enrolled a population of well-nourished people,” he said. “We are unlikely to replicate this study with a similar population, but, as acknowledged by the authors, we do not yet know if there might be benefit of the additional supplementation for patients who are less well-nourished.”

In the original AREDS study, a supplement of high doses of vitamins C and E, beta carotene, and zinc cut progression to advanced AMD and associated vision loss, though not cataracts, in a high-risk group with intermediate AMD or advanced AMD in only one eye.

Because observational studies suggested the other antioxidants might help, too, the AREDS 2 study included a complex randomization to determine which of them might be worth adding to the supplement.

Similar to the initial trial, the sequel included a high-risk population of 4,203 participants, ages 50 to 85, with bilateral large drusen or large drusen in one eye and advanced AMD in the other.

They were randomized to one of the following:

• Lutein (10 mg) plus zeaxanthin (2 mg)
• Omega-3 polyunsaturated fatty acids (350 mg docosahexaenoic acid [DHA] and 650 mg eicosapentaenoic acid [EPA])
• Both of the above
• Placebo

 

“Lutein and zeaxanthin are the main components of the macular pigment,” the group explained. “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, providing biological bases for testing these nutrients.”

All patients were to take the original AREDS formulation or, if they accepted a secondary randomization, a variation without beta carotene, with a lower zinc dose, or with both alterations.

About 30% of patients in each group had advanced AMD over 5 years of follow-up. The hazard ratio wasn’t significantly lower with lutein plus zeaxanthin (0.90,P=0.12), omega-3 fatty acids (0.97, P=0.10), or the combination (0.89, P=0.10).

About a quarter of the group progressed to need cataract surgery over the same span. The hazard ratio with lutein and zeaxanthin was 0.96 (P=0.54) and wasn’t any better with the fish oil supplements.

Risk of three or more lines of vision loss during follow-up came out similar (HR 1.03 with lutein plus zeaxanthin, P=0.61).

None of the nutrients stopped moderate or worse vision loss (a loss of 15 or more letters on the eye chart or treatment for neovascular AMD).

None of the permutations appeared to have an impact on progression to advanced AMD. They weren’t analyzed for impact on cataract surgery.

Limitations may have been competitive absorption of carotenoids that limited the impact of lutein and zeaxanthin in the presence of beta carotene; limited generalizability to less well educated and well nourished populations; and that almost all patients elected to take the other-the-counter supplement Centrum Silver, which contains a small amount of lutein and other carotenes and antioxidants.