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Lutein/Zeaxanthin Appropriate in AREDS2

Results of a long-term epidemiologic follow-up study of the AREDS2 cohort indicate that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements.1

The beta carotene component of the original AREDS formula was replaced by lutein/zeaxanthin in the revised AREDS supplement because its usage nearly doubled the risk of lung cancer. However, it was unknown whether the increased risk of lung cancer observed in those assigned beta carotene persisted beyond the conclusion of the AREDS2 trial or whether there was a longterm benefit from adding lutein/ zeaxanthin to the original AREDS supplement.

During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs. beta carotene and low vs. high doses of zinc.

During the multicentre study, conducted from 1 December 2012 to 31 December 2018, all participants received AREDS2 supplements with lutein/ zeaxanthin, vitamins C and E, and zinc plus copper. The authors analysed participants with bilateral or unilateral intermediate agerelated macular degeneration (AMD) for five years after the clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analysed from November 2019 to March 2022.

They found that beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.


Chew EY, Clemons TE, Agrón E, Domalpally A, Keenan TDL, Vitale S, Weber C, Smith DC, Christen W; AREDS2 Research Group. Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. JAMA Ophthalmol. 2022 Jun 2:e221640. doi: 10.1001/jamaophthalmol.2022.1640. Epub ahead of print. PMID: 35653117; PMCID: PMC9164119.