A clinical trial involving 365 older adults found that high-dose omega-3 supplements reached the brain but offered no measurable cognitive benefits or protection against hippocampal shrinkage.
Millions of people take fish oil supplements hoping to preserve their memory and protect themselves against Alzheimer’s disease as they age. However, a two-year clinical trial has found that even high doses of omega-3 fatty acids may not deliver the brain-health benefits many users expect.
Researchers at the University of Southern California’s Keck Medicine found that fish oil supplements increased levels of docosahexaenoic acid (DHA) in participants’ central nervous systems but did not significantly improve memory or other cognitive abilities, or prevent shrinkage of a brain region critical to memory.
The findings, published in the journal eBioMedicine, came from a study of 365 adults aged 55 to 80 who were considered at increased risk of developing Alzheimer’s disease.
Participants were randomly assigned to receive either a daily supplement containing 2,000 mg of DHA or a placebo. All participants rarely ate fish, a major dietary source of omega-3 fatty acids, and 47% carried the APOE4 genetic variant, which is associated with an increased risk of Alzheimer’s disease. The trial was double-blind, meaning neither participants nor researchers knew who was receiving the active supplement.
The researchers first examined whether the supplements were reaching the brain. Measurements of DHA in cerebrospinal fluid showed an average increase of 17% after six months among participants taking the supplement, indicating that the fatty acid had reached the central nervous system.
However, the increase did not translate into measurable improvements in brain function. After two years, cognitive tests showed no significant advantage among those taking fish oil compared with participants who received the placebo, ScienceDaily reported.
Brain scans also found no evidence that the supplements prevented shrinkage of the hippocampus, a region involved in forming and organising memories that is particularly vulnerable to changes associated with ageing and Alzheimer’s disease.
“We all wish there was a silver bullet for preventing Alzheimer’s, but our findings showed that fish oil supplements do not appear to protect brain health,” said Hussein Naji Yassine, the study’s lead investigator and director of the USC Center for Personalized Brain Health.
Why diet may matter more than supplements
The results raise questions about why increasing the amount of an essential fatty acid in the brain does not necessarily improve cognitive health.
DHA is a major component of brain cell membranes and supports communication between nerve cells. The researchers are investigating whether the brain’s ability to absorb and use omega-3 fatty acids varies according to age, genetic risk, overall health and dietary habits.
One possibility is that omega-3s may work differently when consumed as part of a balanced diet rather than in isolation. A Mediterranean-style eating pattern, which includes fish, vegetables, fruit, whole grains, legumes, nuts and olive oil, provides a range of nutrients and has been associated with a lower risk of Alzheimer’s disease.
The researchers cautioned that the findings do not mean omega-3 fatty acids are unnecessary or that eating fish offers no health benefits. Rather, the trial did not find measurable cognitive protection from high-dose DHA supplements in the group studied.
Healthy habits remain important
The researchers emphasised that brain health depends on a broader range of factors, including regular physical activity, sufficient sleep and a balanced diet. These lifestyle measures were not directly tested in the trial, but remain important components of overall health.
“Staying healthy throughout life remains the most powerful tool we have for reducing Alzheimer’s risk, including regular exercise, quality sleep and a balanced diet,” Yassine said.
The study was supported by the US National Institutes of Health and the Alzheimer’s Drug Discovery Foundation. Its findings suggest that taking fish oil alone should not be viewed as a proven strategy for preventing Alzheimer’s disease or age-related cognitive decline.
