Taking omega-3 daily for memory? Two years of high-dose supplements showed no benefit, study finds

'My memory keeps slipping — should I at least start taking omega-3?'

As people age, many reach for omega-3 supplements first when they worry about memory loss. DHA, the omega-3 fatty acid found in fish oil, is a key building block of the membranes surrounding brain cells. That biological role has long fueled the expectation that taking more of it must be good for the brain.

In South Korea, omega-3 is widely regarded as a memory supplement. The Ministry of Food and Drug Safety recognizes a functional claim that consuming 0.9 to 2 grams of the omega-3 components EPA and DHA combined per day "may help improve memory."

This year, however, conflicting research findings on omega-3 and memory have emerged in rapid succession from the international academic community. Some analyses found that older adults who took omega-3 supplements actually experienced faster cognitive decline, while a clinical trial found no change in memory even after two years of high-dose supplementation.

The controversy was first ignited by a research team from the Third Military Medical University in China. In April, the team published findings in the Journal of Prevention of Alzheimer's Disease (JPAD), based on an analysis of data from participants in the US Alzheimer's Disease Neuroimaging Initiative (ADNI).

When the team compared 273 older adults who reported taking omega-3 supplements with 546 non-users matched for similar baseline conditions, the supplement users showed faster deterioration in cognitive function scores across all three tests examined.

The researchers said a concurrent decline in an imaging marker reflecting how efficiently the brain uses glucose partly explained the difference.

Just four months later, two letters criticizing the Chinese team's analysis appeared in the same journal in August.

One group of researchers noted that an earlier study using the same ADNI data had found the opposite — that omega-3 users had a 64 percent lower risk of Alzheimer's disease. The same dataset, in other words, had yielded diametrically opposite conclusions.

Another group said the ADNI data recorded omega-3 use only as "takes supplements" or "does not take supplements," making it impossible to distinguish between rancid over-the-counter products and pharmaceutical-grade formulations.

In a published response, the Chinese research team clarified that they had never claimed omega-3 supplementation causes cognitive decline. They added, "Our results do not constitute grounds for discontinuing omega-3 supplements or changing clinical guidelines."

As this episode illustrates, observational studies that simply track users and non-users over time cannot establish cause and effect.

A research team at the University of Southern California (USC) recently published results in the journal eBioMedicine from a clinical trial in which 365 adults aged 55 to 80 at risk for dementia were given high-dose DHA for two years. The findings appeared in June.

In fact, the evidence that omega-3 protects memory is less solid than many assume. Observational studies have repeatedly found that people who consume more omega-3 tend to experience less cognitive decline, but clinical trials that actually administered the supplement have produced mixed results.

According to the research team, of 24 randomized clinical trials in which DHA was given to people without dementia, only five — 21 percent — showed improvement in cognitive function.

A large-scale US clinical trial known as VITAL, which gave 4,218 healthy older adults 1 gram of EPA and DHA per day for two to three years, also found no improvement in cognitive function.

Dosage had long been cited as the likely reason for those failures — the thinking being that less than 1 gram a day might not be enough to reach the brain in meaningful amounts. The USC team therefore chose a high dose of 2 grams per day.

Participants were recruited on the basis of eating little to no fish — with daily DHA intake below 200 milligrams — and having at least one cardiovascular or metabolic risk factor, including obesity, high blood pressure, high cholesterol or physical inactivity. The average age was 66, and about half — 47 percent — carried the APOE4 gene variant, which is associated with the greatest increase in Alzheimer's risk.

Half the participants took five DHA capsules daily for two years — three in the morning and two in the evening, each containing 400 milligrams. The other half took identical-looking and identical-tasting placebo capsules made from a blend of corn and soybean oil.

To confirm that DHA was actually reaching the brain, researchers used lumbar punctures. With consent from 181 participants, the team drew cerebrospinal fluid — the fluid that surrounds and flows through the brain and spinal cord — for direct analysis.

The results showed that within six months, DHA levels in the cerebrospinal fluid of supplement users had risen by 17 percent. The omega-3 index — a measure of the proportion of omega-3 in red blood cells — more than doubled, climbing from 4.9 percent to 11.0 percent.

Yet after two years, composite cognitive scores — encompassing memory and other functions — rose by 2.76 points in the DHA group and 2.67 points in the placebo group, in effect identical. The hippocampus, the brain region responsible for memory, shrank slightly in both groups at a rate of less than 1 percent per year, and taking DHA did not slow that shrinkage.

Adverse event rates were similar between the two groups. Adverse events were reported by 40.3 percent of DHA users and 40.9 percent of placebo users, and no serious adverse events were attributed to DHA.

Hussein Yassine, director of USC's Center for Personalized Brain Health and the study's lead researcher, said in a university press release: "We all wish there were a magic bullet to prevent Alzheimer's, but the research suggests that fish oil supplements do not appear to protect brain health."

The team concluded that the findings undercut the argument that previous trials had failed simply because the dose was too low to reach the brain — since this trial had successfully delivered DHA there.

The research team also noted the limitations of relying on a single supplement. Among trial participants, 69 percent did little to no exercise, 39 percent were obese and 52 percent had high blood pressure. The team suggested these underlying health conditions may have blunted the effect of any single nutrient.

The team acknowledged as a limitation that 38 percent of participants dropped out midway, partly due to the COVID-19 pandemic. Those who remained tended to be relatively younger and more highly educated, and their cognitive function and brain health changed so little over the two years that measuring any effect was difficult.

However, the university drew a line, saying the findings should not be interpreted to mean omega-3 is unnecessary or that eating fish provides no health benefit.

DOI: 10.1016/j.tjpad.2026.100569

Liao ZB, Hu ZC, Zeng GH, et al. The association between omega-3 supplementation and cognitive decline in older adults. J Prev Alzheimers Dis. 2026;13(6):100569.

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Yassine HN, Pour SG, Juarez M, et al. CNS target engagement of high-dose DHA supplementation in older adults at risk for dementia: a randomised, double-blind, placebo-controlled trial. EBioMedicine. 2026;129:106316.

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