Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.

Randomized, multicenter ancillary cognitive study in older adults with age-related macular degeneration at 82 US clinical sites. Participants underwent periodic telephone-based cognitive testing from enrollment in 2006 to follow-up through 2012.

This was a 2x2 factorial oral supplementation comparison within AREDS2. Participants received omega-3 long-chain polyunsaturated fatty acids as DHA 350 mg plus EPA 650 mg daily, lutein 10 mg plus zeaxanthin 2 mg daily, or the corresponding no-supplement comparison conditions. The cognitive ancillary outcomes were followed for about five years.

Omega-3 LCPUFAs and lutein/zeaxanthin did not improve cognitive function. For omega-3 LCPUFAs versus no omega-3 LCPUFAs, the yearly change in composite cognitive score was -0.19 versus -0.18, with a between-group difference of -0.03 (99% CI, -0.20 to 0.13; P = .63); TICS yearly change was -0.10 (99% CI, -0.24 to 0.04; P = .07), and the odds of TICS score <30 was 1.12 (99% CI, 0.91 to 1.39; P = .15). For lutein/zeaxanthin versus no lutein/zeaxanthin, the yearly composite score change was -0.18 versus -0.19, with a difference of 0.03 (99% CI, -0.14 to 0.19; P = .66); TICS yearly change was -0.01 (99% CI, -0.16 to 0.13; P = .80), and the odds of TICS score <30 was 1.08 (99% CI, 0.87 to 1.33; P = .35). No statistically significant interaction was found between omega-3 LCPUFAs and lutein/zeaxanthin.

The analyzable samples were smaller than the randomized active-arm totals, indicating attrition. Participants were predominantly White older adults with age-related macular degeneration, which limits generalizability, and cognitive outcomes were assessed by telephone rather than in person. No adverse event data were provided in the supplied text, and multiple nutrient comparisons raise the possibility of multiplicity-related interpretation issues.