Higher omega-3 blood levels linked to reduced early-onset dementia risk despite genetics

A new analysis on more than 217,000 adults reveals a potential link between higher omega-3 fatty acids in the blood and a 35–40% lower risk of developing early-onset dementia, regardless of genetic predispositions for the disease. Moreover, the full spectrum of omega-3s proved even more beneficial than docosahexaenoic acid (DHA) alone.

The study tracked adults from the UK Biobank aged 40 to 64 for an average of 8.3 years, identifying 325 cases of early-onset dementia — a diagnosis before age 65.

Omega-3’s protective association was not only associated with DHA — the most abundant omega-3 fatty acid in the brain — but was even stronger for non-DHA omega-3 fatty acids.

Nutrition Insight speaks to co-author William Harris, Ph.D., founder and president of the Fatty Acid Research Institute and founder of OmegaQuant, to learn more.

“The non-DHA omega-3 contains three fatty acids in unknown ratios: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and DPA,” he tells us.

“We don’t know which of these was most responsible for the favorable outcomes, but it’s likely to be EPA, which suggests a possible more anti-inflammation-based mechanism versus a DHA-induced change in brain cell membrane fatty acid patterns.”

Building up a case for dietary supplements

The study published in Clinical Nutrition found that the participants consuming the highest rates of omega-3s experienced approximately a 35–40% lower risk of dementia, even after adjusting for genetic risk (APOE-ε4), lifestyle factors, and cardiometabolic health variables.

Findings of the study also reinforce the value of using blood biomarkers rather than self-reported diet when studying nutrition and brain health. Omega-3 blood levels representing the greatest risk reduction corresponded to an Omega-3 Index of approximately 8%.

Omega-3’s protective association was not only associated with DHA — the most abundant omega-3 fatty acid in the brain — but was even stronger for non-DHA omega-3 fatty acids.

This test, co-invented by Harris, is a measure of the amount of EPA and DHA in the blood, specifically red blood cell membranes. It compares the composition of omega-3 fatty acids.

For example, Omega Quant notes that someone with 64 fatty acids in a cell membrane of which three are EPA and DHA has an Omega-3 Index of 4.6%. While most consumers have a 6% rate, in the US, most people score 4% or lower.

The study authors note that meeting this benchmark is achievable through regular consumption of fatty fish and/or omega-3 supplements.

Harris notes it is not difficult to reach this benchmark. “It does require a departure from typical US eating patterns. To go from a 5% to an 8% Omega-3 Index requires roughly an additional 1,400 mg of EPA+DHA per day above current intakes.”

“This can be done with a couple of capsules containing 700 mg each, or by eating a 4 oz serving of salmon or sardines daily. Not impossible, but unlikely to capture the imagination of most Americans,” he notes.

Important considerations

The researchers are unsure why the protective benefit associated with omega-3 status is stronger in early-onset dementia than it is in older populations. “Perhaps the older population was having competing fatal events that the younger group was not. That’s just a guess though,” says Harris.

Acknowledging the constraints of observational research, he emphasizes that the evidence could be meaningfully strengthened by looking beyond the UK population. “If we are excluding long-term randomized controlled trials, then observing the same relationship in other cohorts outside of the UK would help strengthen the findings.”

Harris further explains how plasma biomarkers can fill in the gaps often overlooked by standard dietary data. “We did not try to compare diet versus plasma omega-3 as a predictor of early-onset dementia since we don’t have data on dietary omega-3 intake.”

“In general, we have seen plasma levels perform better than, say, fish oil supplement use, as a predictor because the latter does not specify dose, form, compliance, etc. Biomarkers of omega-3 are almost always better indicators of long-term dietary habits than estimates from food frequency questionnaires,” he highlights.

The study authors also note that randomized trials examining dementia incidence are unlikely to be feasible due to the rarity of early-onset dementia and the long follow-up required.

“When a safe, accessible lifestyle factor is consistently associated with lower disease risk, it deserves serious consideration as part of a broader prevention strategy,” comments study lead author Aleix Sala‑Vila, Ph.D.,.

“This is the first large-scale study to show that objectively measured omega-3 status is linked to lower risk of dementia diagnosed before age 65,” she notes. “Most prior research has focused on older populations.”

“Our findings strongly suggest that omega-3 intake earlier in midlife may play a meaningful role in brain health decades before dementia typically appears.”

Last month, scientists found that 76% of the global population is not consuming the recommended levels of omega-3s. Their review flags common confusion surrounding omega-3 recommendations, noting that guidelines typically differ by country.