Scientists discovered that a ketogenic diet (a diet very low in carbs and high in fat) might help protect the brain in people who carry a gene called APOE4, which increases Alzheimer’s disease risk. The study used mice to show that this diet changes the bacteria in the gut in helpful ways, which then improves important brain chemicals. Interestingly, the diet seemed to work better for females than males, and only really helped mice with the risky gene, not those without it. This suggests that eating a ketogenic diet could be a personalized way to reduce Alzheimer’s risk, especially for women who carry this genetic risk factor.

The Quick Take

  • What they studied: Whether a ketogenic diet (very low carb, high fat) could change gut bacteria and improve brain health in mice that carry a gene that increases Alzheimer’s disease risk
  • Who participated: Young male and female mice, some with the APOE4 risk gene and some without it, fed either a normal diet or a ketogenic diet for 16 weeks
  • Key finding: The ketogenic diet increased good bacteria (like Lactobacillus species) and decreased harmful bacteria (like Bacteroides intestinalis), which was linked to improved brain chemicals. Female mice with the risk gene showed the biggest improvements.
  • What it means for you: This suggests that a ketogenic diet might help protect the brain in people who carry the APOE4 gene, especially women. However, this is early research in mice, so more human studies are needed before making major dietary changes. Talk to your doctor before trying this diet.

The Research Details

Researchers used laboratory mice to study how diet affects the gut-brain connection. They divided mice into groups: some had the APOE4 risk gene (like people at higher risk for Alzheimer’s), and others had the APOE3 gene (lower risk). Half of each group ate a normal diet, while the other half ate a ketogenic diet for 16 weeks. The scientists then analyzed the bacteria living in the mice’s guts using advanced genetic testing and measured important brain chemicals.

This type of study is important because it allows researchers to carefully control everything the mice eat and measure exact changes in their bodies. The researchers could also compare males and females separately to see if the diet worked differently for each sex. This kind of controlled experiment in animals helps scientists understand how a diet might work before testing it in humans.

Understanding how diet affects the gut bacteria and brain is crucial because scientists increasingly believe that gut bacteria play a big role in brain health and Alzheimer’s disease risk. By studying this in mice first, researchers can identify which bacteria are helpful and which brain chemicals improve, giving them clues about whether this diet might help people. The fact that the diet worked differently depending on sex and genetics suggests that personalized nutrition approaches could be more effective than one-size-fits-all diets.

This study was published in a respected scientific journal focused on brain chemistry. The researchers used advanced genetic sequencing to identify bacteria and precise measurements of brain chemicals, which are reliable methods. However, this is animal research, so results may not directly apply to humans. The study didn’t specify exactly how many mice were used, which makes it harder to assess the strength of the findings. More research in humans is needed to confirm these results.

What the Results Show

The ketogenic diet produced significant changes in the gut bacteria of mice with the APOE4 risk gene. Specifically, the diet increased beneficial bacteria called Lactobacillus johnsonii and Lactobacillus reuteri while reducing a potentially harmful bacteria called Bacteroides intestinalis. These changes in bacteria were linked to improvements in important brain chemicals involved in energy production, nerve communication, protection against damage, and fat metabolism.

The most striking finding was that female mice with the APOE4 gene showed the greatest benefits. These females experienced restored diversity in their gut bacteria (meaning a healthier variety of different bacterial species) and their brain chemical levels returned to more normal patterns. This suggests the diet was particularly protective for this group.

In contrast, mice with the APOE3 gene (the lower-risk version) showed some changes in their gut bacteria when eating the ketogenic diet, but their brain chemicals didn’t improve as much. This indicates that the diet’s brain-protective effects depend on having the APOE4 risk gene.

The study identified specific relationships between certain bacteria and brain health. Lactobacillus species showed strong connections with improved brain chemicals, suggesting these bacteria may actively help the brain. Bacteroides intestinalis showed the opposite pattern, with higher levels linked to worse brain chemical profiles. These connections suggest that these bacteria could serve as markers to track whether someone’s brain health is improving.

Previous research has shown that people with the APOE4 gene have different gut bacteria and early brain changes even before developing Alzheimer’s symptoms. This study builds on that work by showing that diet can reverse some of these changes. The ketogenic diet has been studied for brain health before, but this is one of the first studies to show how it specifically works through changing gut bacteria in people with genetic risk factors.

This study was conducted in mice, not humans, so the results may not work exactly the same way in people. The study didn’t report the exact number of mice used, making it difficult to assess how reliable the findings are. The mice were young when the diet started, so it’s unclear if the diet would work as well in older people or those already showing Alzheimer’s symptoms. The study only lasted 16 weeks, so we don’t know if the benefits would continue long-term or if people would stick with the diet.

The Bottom Line

Based on this research, a ketogenic diet may help reduce Alzheimer’s risk in people who carry the APOE4 gene, particularly women. However, this is early-stage research in animals. Confidence level: Low to Moderate for humans (more research needed). If you carry the APOE4 gene and are interested in trying a ketogenic diet, consult with your doctor or a registered dietitian first, as this diet isn’t suitable for everyone and can have side effects.

This research is most relevant to people who know they carry the APOE4 gene and want to reduce their Alzheimer’s risk. It may be especially relevant for women with this genetic risk. People without the APOE4 gene may not see the same brain-protective benefits based on this research. Anyone considering a ketogenic diet should talk to their healthcare provider first, especially those with diabetes, heart disease, or other health conditions.

In this mouse study, changes in gut bacteria appeared within 16 weeks, and brain chemical improvements were seen at the same time. In humans, changes might take longer—possibly several weeks to months—before noticeable effects. However, we don’t yet know the realistic timeline for humans, so expectations should be cautious.

Want to Apply This Research?

  • If following a ketogenic diet, track daily macronutrient ratios (percentage of calories from fat, protein, and carbs) to ensure you’re maintaining ketogenic targets (typically 70-75% fat, 20-25% protein, 5-10% carbs). Log this weekly to monitor consistency.
  • Start by gradually reducing carbohydrate intake while increasing healthy fats (nuts, seeds, avocados, olive oil) and moderate protein. Use the app to plan meals that fit ketogenic guidelines and set reminders to track what you eat. Consider adding fermented foods like yogurt or kefir to support beneficial gut bacteria.
  • Track energy levels, digestion, and any changes in mental clarity weekly. If you have genetic testing showing APOE4 status, monitor this diet for at least 8-12 weeks before assessing benefits. Consider periodic check-ins with a healthcare provider to monitor overall health markers and ensure the diet remains appropriate for you.

This research was conducted in mice and has not been tested in humans. The findings suggest potential benefits but do not prove that a ketogenic diet will prevent Alzheimer’s disease in people. A ketogenic diet is not appropriate for everyone and may cause side effects or interact with medications. Before making significant dietary changes, especially if you have existing health conditions, diabetes, heart disease, or take medications, consult with your doctor or a registered dietitian. Genetic testing for APOE4 status should be discussed with a healthcare provider who can explain what results mean for your individual risk. This information is for educational purposes and should not replace professional medical advice.