New research could help clear up a longstanding mystery about omega-3s. The essential fatty acids, found primarily in fish and other seafood, are crucial for brain health. And large-scale studies draw links between diets rich in seafood and a lowered risk for Alzheimer’s, as well as other neurodegenerative diseases like dementia (Zhang et al., 2016).

But despite decades of scientific scrutiny, researchers have never been able to definitively prove that omega-3 supplements are an effective treatment for Alzheimer’s.

Now, scientists from the University of Southern California think they have the answer to this apparent contradiction. Omega-3 fatty acids are indeed vital, but may have a hard time crossing into our brains, where their neuroprotective effects are needed.

So, previous studies may have simply used omega-3 supplement doses that were too small to reach the brain in meaningful quantities. Upping the daily intake of omega-3s could make the difference for our brain health, the authors say (Arellanes et al., 2020).

Omega-3s and Alzheimer’s

The study, published in the journal EBioMedicine, looked at 33 people aged 55 and older with no symptoms of cognitive impairment. The researchers divided the participants into two groups. Every day for six months, one of the groups got a little more than two grams of DHA, an omega-3 fatty acid. The other group got a placebo. Crucially, that two-gram omega-3 dose was significantly higher than in most studies, where participants typically received a gram or less. Both groups also took vitamin B supplements, as the nutrient plays a key role in helping our bodies use omega-3s (Arellanes et al., 2020).

In studies done on animals, DHA supplements helped reduce the beta-amyloid plaques that are characteristic of Alzheimer’s and prevented the loss of neurons (Hooijmans et al., 2020). Other research shows DHA also promotes general brain health and reduces oxidative stress in the body (Arellanes et al., 2020).

At the end of this latest study, the researchers tested both groups to see how much DHA was in their blood and cerebrospinal fluid. That meant the researchers had to administer a spinal tap, a painful procedure that involves sticking a needle into a patient’s back.

The patients “were generous with their time, and they were courageous to do the lumbar punctures,” said co-author Hussein Yassine, associate professor of medicine and neurology at USC’s Keck School of Medicine, in a press release.

As expected, those given omega-3 supplements had high levels of DHA in their bloodstreams — around 200 percent more than the placebo group. However, far less DHA actually showed up in their brains. There, they had just 28 percent more DHA than the controls.

The researchers say this suggests omega-3 fatty acids don’t make it into our brains very easily. Therefore, to get the brain-boosting benefits of omega-3s, scientists and doctors may need to consider giving patients higher doses.

Overcoming an Alzheimer’s-Related Gene

There was also intriguing evidence for how a gene implicated in Alzheimer’s disease may cause brain damage. Some of the study participants had the APOE4 gene, which predisposes people to Alzheimer’s. The researchers found connections between the gene and another fatty acid called EPA. People with the APOE4 gene had brain levels of EPA three times lower than those without the gene, they found.

This discovery may mean that APOE4’s relationship with Alzheimer’s has something to do with how the gene influences fatty acids in the brain. It’s still too early to say what that influence might be, however. For example, the gene could make the brain use more omega-3s than normal. Or, it could simply prevent the fatty acid from reaching the brain entirely.

Long-Term Omega-3 Benefits

The researchers are currently putting together a larger study to explore the effects of larger doses of omega-3s on brain health. That study will follow 320 patients with the APOE4 gene as they take high-dose omega-3 supplements over the course of two years. It should help explain how the behavior of fatty acids in the brain is related to Alzheimer’s. It will also explore another hypothesis: that omega-3 supplements might also need to be taken over long periods to have the greatest effect.

Past research has shown that longer-term consumption of omega-3 supplements causes greater increases in fatty acid levels in the brain (Yassine et al., 2016). It’s a sign that, in addition to higher doses, it might also be necessary to keep taking omega-3 supplements for the long term.

If previous studies in animals are any indication, their work might return successful results. A 2016 study summing the results of previous research found that long-term use of fatty acid supplements in animals helped reduce harmful beta-amyloid plaques and prevent neuron loss (Zhang et al 2016).

The same could be true for humans as well, confirming something that scientists and observant seafood proponents have long suspected: Omega-3 fatty acids play an important role in protecting our brains from the degenerative diseases that steal us from ourselves.


Arellanes IC, Choe N, Solomon V, et al. Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial. EBioMedicine. July 2020:102883. doi:10.1016/j.ebiom.2020.102883

Hooijmans CR, Rutters F, Dederen PJ, et al. Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD). Neurobiology of Disease. 2007;28(1):16-29. doi:10.1016/j.nbd.2007.06.0071.

Yassine HN, Rawat V, Mack WJ, et al. The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer’s disease. Alzheimer’s Research & Therapy. 2016;8(1). doi:10.1186/s13195-016-0194-x

Zhang Y, Chen J, Qiu J, Li Y, Wang J, Jiao J. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies 1–3. The American Journal of Clinical Nutrition. 2015;103(2):330-340. doi:10.3945/ajcn.115.124081