A New Risk with Omega-3?

Is it the fish oil, or the study design?

STUDY: Liao Z-B et al, J Prev Alzheimers Dis 2026;13:100569

STUDY TYPE: Longitudinal cohort study

FUNDING: National Natural Science Foundation of China; Chongqing Municipal Health Commission

Background

Some randomized trials find cognitive benefits with omega-3 fatty acids, but this new observational study suggests they can accelerate decline.

The Study

Researchers used data from older adults in a large database (set up to monitor dementia risk), matching 273 omega-3 users to 546 non-users on age, sex, APOE ε4 status (a risk factor for dementia), and diagnosis. Participants were followed for a median of 5 years. Their cognitive trajectories were tracked with three scales and correlated with biomarkers, including amyloid, tau, structural MRI, and PET scans. In the graph below, higher scores an the ADAS and CDR are worse.

Omega-3 users declined faster on all three cognitive measures compared to matched non-users. These differences weren’t explained by amyloid, tau, or brain atrophy. Instead, FDG hypometabolism (ie, glucose uptake in the brain, a marker of synaptic dysfunction) mediated 20–40% of the problem, suggesting omega-3 may impair synaptic energy metabolism.

But could this be reverse causality? In other words, maybe people are more likely to start omega-3’s when they start to experience cognitive decline. Possibly, but in this study the omega-3 users did not show pre-existing cognitive decline before starting supplementation.

Limitation: Not randomized, so cannot adjust for all other causes; dose and type of omega-3 not known.

Practice Implications

1. How do we make sense of this? The researchers point to a meta-analysis that found cognitive benefits with low dose omega-3, but possible worsening beyond a dose of 1,500 mg a day.
2. To prevent cognitive decline, these trials suggest a dose of 1,000–1,500 mg daily, with a high DHA product (one that is 50–100% DHA and 0–50% EPA). However, trials in dementia are generally negative.
3. The evidence is more robust, however, for psychiatric disorders like depression, borderline personality, schizophrenia, autism, and ADHD, and here the dosing is different, requiring more EPA. This supplement requires care in getting the right dose and formulation. Learn more here.