NIH study raises doubt about any benefits omega-3 and dietary supplements like these may have for cognitive decline (credit: Photo courtesy of NEI)
While some research suggests that a diet high in omega-3 fatty acids can protect brain health, a large clinical trial by researchers at the National Institutes of Health found that omega-3 supplements did not slow cognitive decline in older persons.
With 4,000 patients followed over a five-year period, the study is one of the largest and longest of its kind. It was published Tuesday August 25 in the Journal of the American Medical Association.
“Contrary to popular belief, we didn’t see any benefit of omega-3 supplements for stopping cognitive decline,” said Emily Chew, M.D., deputy director of the Division of Epidemiology and Clinical Applications and deputy clinical director at the National Eye Institute (NEI), part of NIH.
Chew leads the Age-Related Eye Disease Study (AREDS), which was designed to investigate a combination of nutritional supplements for slowing age-related macular degeneration (AMD), a major cause of vision loss among older Americans. That study established that daily high doses of certain antioxidants and minerals — called the AREDS formulation — can help slow the progression to advanced AMD.
A later study, called AREDS2, tested the addition of omega-3 fatty acids to the AREDS formula. But the omega-3’s made no difference.
Omega-3 fatty acids are made by marine algae and are concentrated in fish oils; they are believed to be responsible for the health benefits associated with regularly eating fish, such as salmon, tuna, and halibut. Where studies have surveyed people on their dietary habits and health, they’ve found that regular consumption of fish is associated with lower rates of AMD, cardiovascular disease, and possibly dementia. “We’ve seen data that eating foods with omega-3 may have a benefit for eye, brain, and heart health,” Chew explained.
Cognitive function tests
With AREDS2, Dr. Chew and her team saw another opportunity to investigate the possible cognitive benefits of omega-3 supplements, she said. Participants were given cognitive function tests at the beginning of the study to establish a baseline, then at two and four years later.*
The tests, all validated and used in previous cognitive function studies, included eight parts designed to test immediate and delayed recall, attention and memory, and processing speed. The cognition scores of each subgroup decreased to a similar extent over time, indicating that no combination of nutritional supplements made a difference.
“The AREDS2 data add to our efforts to understand the relationship between dietary components and Alzheimer’s disease and cognitive decline,” said Lenore Launer, Ph.D. senior investigator in the Laboratory of Epidemiology and Population Science at the National Institute on Aging. “It may be, for example, that the timing of nutrients, or consuming them in a certain dietary pattern, has an impact. More research would be needed to see if dietary patterns or taking the supplements earlier in the development of diseases like Alzheimer’s would make a difference.”
*All participants had early or intermediate AMD. They were 72 years old on average and 58 percent were female. They were randomly assigned to one of the following groups:
- Placebo (an inert pill)
- Omega-3 [specifically docosahexaenoic acid (DHA, 350 mg) and eicosapentaenoic acid (650 mg)]
- Lutein and zeaxanthin (nutrients found in large amounts in green leafy vegetables)
- Omega-3 and Lutein/zeaxanthin
Because all participants were at risk for worsening of their AMD, they were also offered the original or a modified version of the AREDS formulation (without omega-3 or lutein/zeaxanthin).
Abstract of Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function
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.