Researchers found that eating a low-carbohydrate, high-protein diet can hurt working memory (the ability to remember things for short periods) in mice. However, when mice also received omega-3 supplements—especially a type called DHA found in fish oil—their memory problems improved. The study suggests that if you’re following a low-carb diet, adding omega-3 supplements might help protect your brain’s memory function. This is early research in animals, so more studies in humans are needed before making dietary changes.

The Quick Take

  • What they studied: Whether omega-3 fish oil supplements can prevent memory problems that happen when people eat very low-carb, high-protein diets
  • Who participated: Young, healthy male mice (8 weeks old) divided into six groups receiving different diet and supplement combinations for four weeks
  • Key finding: Mice on low-carb diets showed worse memory performance, but those who also received DHA (a type of omega-3) had their memory problems reversed and showed improved brain cell markers
  • What it means for you: If you follow a low-carb diet, omega-3 supplements might help protect your memory, but this is animal research and human studies are needed to confirm these benefits

The Research Details

Scientists gave mice either a normal diet or a low-carb, high-protein diet. Within each diet group, some mice received no supplement (vehicle), some received EPA (one type of omega-3), and some received DHA (another type of omega-3). All supplements were given by mouth once daily for four weeks. After the treatment period, researchers tested the mice’s memory using a Y-shaped maze test and examined their brain tissue to measure specific genes related to memory and brain cell growth.

The Y-maze test works by letting mice explore a maze with three arms and measuring how often they visit new arms versus ones they’ve already been to—mice with better working memory explore new arms more frequently. Researchers also looked at messenger RNA (mRNA) levels, which are like instruction manuals that tell cells what proteins to make. They focused on genes involved in brain cell growth and a signaling pathway called Wnt, which is important for brain function.

This research approach is important because it allows scientists to understand the exact biological mechanisms happening in the brain. By testing both behavior (the maze test) and brain chemistry (gene expression), researchers can see not just whether omega-3s help memory, but how they might work at the cellular level. This foundation is necessary before testing these ideas in humans.

This is a controlled laboratory study with clear group assignments and standardized testing procedures, which is good for establishing cause-and-effect relationships. However, it’s in mice, not humans, so results may not directly apply to people. The study appears to be well-designed with appropriate controls, but the sample size is relatively small (likely 48 mice total, or 8 per group). Published in a peer-reviewed journal, which means other scientists reviewed the work before publication.

What the Results Show

Mice eating the low-carb, high-protein diet showed significantly worse performance on the memory test compared to mice eating a normal diet. Their working memory declined, as measured by how often they explored new arms of the maze versus familiar ones.

When mice on the low-carb diet also received DHA supplements, their memory performance improved dramatically and returned to nearly normal levels. EPA supplements also helped, but DHA was more effective. Importantly, DHA reversed the low-carb diet’s negative effects on two important brain genes: Lrp6 and Dcx, which are involved in creating new brain cells and supporting memory.

The researchers also found that in mice on the low-carb diet, three brain genes (Lrp6, Wnt5a, and Dcx) showed strong positive correlations with each other, suggesting they work together as a team. This connection was particularly strong in mice receiving omega-3 supplements.

Interestingly, the gene Wnt5 itself wasn’t directly affected by the diet or supplements, but it worked together with other genes in the same signaling pathway. This suggests that omega-3s may work by strengthening connections between genes rather than simply turning individual genes on or off. The study also showed that EPA and DHA, while both helpful, may work through slightly different mechanisms in the brain.

Previous research has shown that omega-3 fatty acids, particularly DHA, are important for brain health and are concentrated in brain cell membranes. This study builds on that knowledge by showing that omega-3s might specifically protect memory function when people eat low-carb diets. The finding that low-carb diets can hurt memory is somewhat surprising and contradicts some popular claims about low-carb diets being universally beneficial for brain function.

This study was conducted only in mice, and mice brains work differently from human brains in important ways. The study only looked at young, healthy male mice, so results might differ in females, older mice, or those with health conditions. The treatment period was only four weeks, which is relatively short. The study doesn’t tell us what happens if people stop taking omega-3 supplements or continue the diet long-term. Finally, we don’t know if these results would apply to all types of low-carb diets or only this specific ratio of nutrients.

The Bottom Line

Based on this animal research, omega-3 supplements (especially DHA) may help protect memory if you follow a low-carb diet. However, this is preliminary evidence from mice, not humans. If you’re considering a low-carb diet and are concerned about memory, discuss omega-3 supplementation with your doctor. Current general recommendations suggest getting omega-3s from fish (like salmon) 2-3 times per week, or taking supplements if you don’t eat fish. Confidence level: Low to Moderate (animal study only, human research needed).

This research is most relevant to people considering or currently following low-carb diets who want to protect their memory and thinking skills. It may be especially important for older adults or anyone concerned about cognitive decline. People with fish allergies or those following vegan diets should discuss alternative omega-3 sources with their healthcare provider. This research is less relevant to people eating balanced diets with adequate carbohydrates.

In the mouse study, benefits appeared after four weeks of supplementation. In humans, omega-3 benefits typically take 4-12 weeks to become noticeable, though some people report improvements sooner. Long-term use (months to years) may provide greater benefits for brain health.

Want to Apply This Research?

  • Track daily omega-3 intake (in grams of EPA+DHA) alongside memory or cognitive performance using simple self-assessments like remembering shopping lists without writing them down or tracking how often you forget why you walked into a room
  • If following a low-carb diet, add one of these daily: a fish oil supplement (1000-2000mg containing EPA and DHA), eat fatty fish like salmon or mackerel, or take an algae-based omega-3 supplement (for vegetarians). Log this in your app alongside your carbohydrate and protein intake to track the relationship
  • Monthly, rate your memory and mental clarity on a scale of 1-10. Track omega-3 supplementation consistency. If following a low-carb diet, monitor whether memory issues improve within 4-8 weeks of starting omega-3s. Share results with your healthcare provider at regular check-ups

This research was conducted in mice and has not been tested in humans. Results may not directly apply to people. This information is for educational purposes only and should not replace professional medical advice. Before starting any new diet or supplement regimen, especially if you have existing health conditions or take medications, consult with your healthcare provider or registered dietitian. Omega-3 supplements can interact with blood-thinning medications. If you are pregnant, nursing, or have a fish allergy, discuss omega-3 supplementation options with your doctor before use.