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

JAMA

Aug 2015

DOI: 10.1001/jama.2015.9677

Citations:164

Influential Citations:4

Interventional (Human) Studies

Enhanced Details

Methods

Double-masked, randomized, placebo-controlled, 2×2 factorial AREDS2 trial across 82 centers in the United States; participants at risk for progression to late AMD; N=4,203; mean age 72.7 years; 57.5% female; AMD criteria: bilateral large drusen or large drusen in one eye with advanced AMD in the fellow eye; ancillary cognitive study enrolled 3,741 (89%), with 3,501 undergoing cognitive testing and 3,073 included in analyses.

Intervention

Omega-3 long-chain polyunsaturated fatty acids (DHA 350 mg + EPA 650 mg) daily (1 g total) by mouth; lutein 10 mg and zeaxanthin 2 mg daily; duration 5 years.

Results

Over 5 years, DHA/EPA and/or lutein/zeaxanthin did not significantly affect cognitive function. Composite score yearly change: -0.19/year with LCPUFAs vs -0.18/year without (p=0.63); TICS change: -0.10 vs -0.10 (p=0.07); lutein/zeaxanthin: -0.18 vs -0.19 (p=0.66); high vs low zinc: -0.20 vs -0.19 (p=0.77); beta-carotene vs no beta-carotene: -0.24 vs -0.18 (p=0.04) but not significant after multiple testing. Conclusion: Among older persons with AMD, oral supplementation with LCPUFAs and lutein/zeaxanthin had no statistically significant effect on cognitive function.

Limitations

Limited generalizability to well-nourished, highly educated older adults with AMD; cognitive testing conducted by telephone; ancillary cognitive study not powered to evaluate all nutrients; participants were older (mean age ~73) and followed for 5 years, which may be insufficient to detect cognitive changes; baseline cognition data not available from the original AREDS; results may not reflect dietary patterns or multi-nutrient interactions.

Abstract

IMPORTANCE Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease. OBJECTIVE To test the effects of oral supplementation with nutrients on cognitive function. DESIGN, SETTING, AND PARTICIPANTS In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study. INTERVENTIONS Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc. MAIN OUTCOMES AND MEASURES The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from -22 to 17, with higher scores representing better function. RESULTS A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was -0.19 (99% CI, -0.25 to -0.13) for participants randomized to receive LCPUFAs vs -0.18 (99% CI, -0.24 to -0.12) for those randomized to no LCPUFAs (difference in yearly change, -0.03 [99% CI, -0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was -0.18 (99% CI, -0.24 to -0.11) for participants randomized to receive lutein/zeaxanthin vs -0.19 (99% CI, -0.25 to -0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, -0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant. CONCLUSIONS AND RELEVANCE Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00345176. show less