Scientists discovered that a brain-healthy nutrient called DHA (found in fish oil) works better when paired with specific partner nutrients. In a mouse study, they found that combining DHA with either EPA or phosphatidylserine (PS) helped the DHA travel to different parts of the brain more effectively. When paired with PS, DHA boosted brain growth and protection. When paired with EPA, it reduced brain inflammation. This suggests that choosing the right combination of nutrients might help us get more brain benefits from fish oil supplements.

The Quick Take

  • What they studied: Whether combining fish oil (DHA) with partner nutrients helps it reach different brain areas more effectively and provide better brain protection
  • Who participated: Laboratory mice (C57BL/6J strain) that received different combinations of dietary supplements over a study period
  • Key finding: DHA paired with PS (phosphatidylserine) preferentially enriched the hippocampus and cortex while boosting brain growth factors, whereas DHA paired with EPA (another fish oil component) enriched the cortex and striatum while reducing inflammation. The choice of partner nutrient determined where DHA went in the brain and what protective benefits it provided.
  • What it means for you: This research suggests that future fish oil supplements might be more effective if formulated with specific partner nutrients based on what brain health goal you’re targeting. However, this is early-stage research in mice, so human studies are needed before changing supplement routines. Talk to your doctor before starting new supplements.

The Research Details

Researchers used laboratory mice to test whether DHA (a nutrient from fish oil) works better when combined with partner nutrients. They gave different groups of mice different supplement combinations: DHA alone, DHA plus EPA (another fish oil component), or DHA plus PS (a nutrient found in cell membranes). They then examined the mice’s brains using advanced techniques to measure where the nutrients ended up and what changes they caused.

The scientists used three main methods to understand what happened: they measured fatty acid levels in different brain regions (lipidomics), they checked protein levels related to brain protection and inflammation (ELISA and western blotting), and they examined which transporters (like special doorways) were activated to help nutrients cross the blood-brain barrier into the brain.

This approach allowed them to see not just whether the supplements worked, but exactly where in the brain they went and what biological changes they triggered.

This research design is important because it goes beyond simply measuring whether a nutrient helps the brain—it reveals the actual mechanism of how it works. By examining specific brain regions separately, the researchers discovered that different nutrient combinations target different areas. This precision approach helps explain why some supplement combinations might work better than others for specific brain health concerns.

This is a well-designed laboratory study using established scientific techniques and a standardized mouse strain commonly used in research. The researchers measured multiple markers of brain health and examined specific brain regions rather than treating the brain as one unit. However, because this is mouse research, results may not directly translate to humans. The study provides mechanistic insights (how things work) rather than proof that humans would benefit. Additional human studies would be needed to confirm these findings apply to people.

What the Results Show

The most striking finding was that the choice of partner nutrient completely changed where DHA ended up in the brain. When DHA was paired with EPA, it accumulated most in the cortex (the brain’s outer thinking layer) and striatum (involved in movement and motivation). When DHA was paired with PS, it preferentially went to the hippocampus (crucial for memory) and cortex.

The researchers discovered the mechanism behind this difference: both combinations increased expression of a special transporter protein called MFSD2A that acts like a doorway helping nutrients cross the blood-brain barrier into the brain. However, each combination appeared to activate this doorway in slightly different ways, leading to different distribution patterns.

Functionally, the two combinations activated different protective programs in the brain. DHA plus PS strongly activated the CREB-BDNF pathway, which is essentially the brain’s growth and repair system—it helps brain cells survive and form new connections. In contrast, DHA plus EPA uniquely suppressed the NF-κB pathway, which is the brain’s inflammatory alarm system. By turning down this alarm, the combination reduced harmful inflammation.

The research revealed that both carrier-DHA combinations enhanced the expression of MFSD2A transporters, suggesting that the choice of carrier influences not just where nutrients go, but also how the brain’s transport systems adapt. This indicates that the brain actively responds to different nutrient combinations by adjusting its delivery mechanisms. The region-specific activation of different protective pathways suggests that tailored combinations could theoretically target specific brain vulnerabilities—for example, using PS+DHA for memory problems or EPA+DHA for inflammatory brain conditions.

Previous research has shown that DHA is important for brain health, but scientists have long struggled with the problem that DHA doesn’t always reach the brain effectively or distribute evenly. This study builds on that knowledge by showing that the solution isn’t just adding more DHA, but rather pairing it with specific partners that act as guides. This represents a shift toward ‘precision nutrition’—tailoring nutrient combinations to specific goals rather than using one-size-fits-all supplements.

This study was conducted in mice, not humans, so we cannot assume the same results would occur in people. Mouse brains are simpler and smaller than human brains, and mice metabolize nutrients differently than humans do. The study doesn’t specify the exact doses used or the duration of supplementation, making it difficult to translate findings to human supplement recommendations. Additionally, the study examined brain tissue after the mice were sacrificed, so we don’t know how long these effects last or whether they translate to actual improvements in brain function or behavior. Finally, this is a single study, so results need to be confirmed by other research teams before drawing firm conclusions.

The Bottom Line

Based on this research, we cannot yet recommend specific supplement changes for humans. This is early-stage research that provides interesting mechanistic insights but requires human studies before practical recommendations can be made. If you’re interested in brain health, current evidence supports eating fatty fish 2-3 times weekly or discussing fish oil supplements with your healthcare provider, but the specific combinations tested here haven’t been proven effective in people yet.

This research is most relevant to: supplement manufacturers developing next-generation formulations, neuroscientists studying brain nutrient delivery, people with neurological concerns who might benefit from targeted brain nutrition in the future, and healthcare providers interested in precision nutrition approaches. People currently taking fish oil supplements don’t need to change their routine based on this single mouse study.

In mice, the changes in brain nutrient distribution and protein expression occurred during the supplementation period, but the exact timeline isn’t specified. If similar effects occur in humans, benefits would likely develop gradually over weeks to months of consistent supplementation. However, this timeline is speculative until human studies are conducted.

Want to Apply This Research?

  • Track daily omega-3 intake (DHA and EPA amounts in milligrams) and note any changes in cognitive function, memory, mood, or inflammation-related symptoms weekly using a simple 1-10 scale. This creates a personal baseline for comparison if you choose to modify your supplement routine.
  • If using a nutrition tracking app, log the specific type of fish oil supplement you take and its ingredient list (noting whether it contains EPA, DHA, PS, or other carriers). This helps you identify which formulations you’re using and allows you to note any patterns in how you feel with different combinations.
  • Maintain a 12-week log of supplement intake and subjective brain health markers (focus, memory, mood, energy). While this won’t prove cause-and-effect, it helps you identify personal patterns. Share this data with your healthcare provider before making supplement changes, especially if you take medications or have existing health conditions.

This research was conducted in laboratory mice and has not been tested in humans. The findings do not constitute medical advice or recommendations to change your supplement routine. DHA and fish oil supplements are generally recognized as safe, but they can interact with certain medications (particularly blood thinners) and may cause side effects in some people. Before starting, stopping, or changing any supplement regimen—especially if you have existing health conditions, take medications, are pregnant or breastfeeding, or have fish allergies—consult with your healthcare provider or registered dietitian. This article summarizes early-stage research and should not replace professional medical guidance.