Older adults with certain genetic mutations associated with Alzheimer’s disease may actually be protecting their brain health by eating a meat-rich diet. Recent research published in JAMA network open suggest that personalized dietary recommendations based on genetics could help prevent cognitive decline in large parts of the world’s population.
All people have a gene called APOE that provides instructions for making proteins that help transport fat and cholesterol through the bloodstream. There are three main versions of this gene, known as variants, named e2, e3, and e4. People inherit one mutation from each parent, creating different combinations of genes. Apolipoproteins are a family of fat-binding proteins that play a major role in cholesterol metabolism in the liver and brain.
The APOE e4 variant is the oldest form of the gene in human evolutionary history. It first appeared millions of years ago, when our early ancestors transitioned to hunting and began consuming large amounts of meat. Some anthropologists argue that there was a time, millions of years ago, when our ancestors consumed a diet consisting almost entirely of meat. This timeline directly coincides with the emergence of the APOE e4 variant.
Newer subspecies, e3 and e2, appeared much later in human history. Humans eventually transitioned to agriculture and began eating more plant-based foods. The e3 subspecies is thought to have emerged around 200,000 years ago, reflecting an adaptation to an omnivorous diet. Currently, the e3 variant is the most common form among people around the world.
In modern times, the APOE e4 variant is the strongest known genetic risk factor for late-onset Alzheimer’s disease. People who inherit a copy of this variant are much more likely to develop dementia than people with other combinations. In Northern Europe and North America, people with e3/e4 or e4/e4 combinations account for almost 70% of all Alzheimer’s disease cases.
Researchers at Sweden’s Karolinska Institutet wanted to understand how diet interacts with these genetic risks over time. Lead author Jakob Norgren, a researcher in the institute’s Department of Neurobiology, Care Sciences and Society, suspected that there might be clues in human evolutionary history. He and his colleagues hypothesized that the old APOE e4 mutant may be particularly adapted to a meat-rich diet.
If this idea were true, people with older genetic mutations might process animal nutrients differently than people with newer genetic mutations. “This study tested the hypothesis that people with APOE 3/4 and 4/4 would have a lower risk of cognitive decline and dementia with increased meat intake, based on the fact that APOE4 is the evolutionarily oldest variant of the APOE gene and may have arisen at a time when our evolutionary ancestors ate a more animal-based diet,” says Norgren.
To investigate this potential link, the research team analyzed data from an ongoing project called the Swedish National Study on Aging and Care. They focused on a specific group of 2,157 older adults living in urban Stockholm. All participants were at least 60 years old and had not been diagnosed with dementia at the start of the study.
Volunteers provided detailed information about their dietary habits through a validated questionnaire. These forms included 98 food items and captured participants’ eating habits over the previous year. The researchers divided the volunteers into groups based on their total daily intake of meat, unprocessed red meat, poultry, and processed meats such as sausage and bacon. They also took blood samples to determine each participant’s APOE gene combination.
Researchers tracked the volunteers’ cognitive health for up to 15 years. Participants were evaluated every 6 years until they reached age 78 and every 3 years thereafter. At each visit, doctors assessed memory, language skills, and mental processing speed. Two independent doctors examine medical data to diagnose cases of dementia, with a senior neurologist intervening in case of disagreement.
The researchers divided the data into two main groups based on genetics. One group included people with e3/e4 and e4/e4 combinations that put them at high risk for Alzheimer’s disease. The second group consisted of people with all other gene combinations. They compared both groups’ cognitive trajectories with self-reported meat intake.
A clear pattern emerged for individuals with high-risk e3/e4 and e4/e4 genes. In this group, eating more meat was found to slow cognitive decline and better preserve memory. Protective groups were strongest among people in the top 20 percent of meat consumers.
These high-end consumers eat an average of about 870 grams of meat per week, normalizing this measurement to a typical daily calorie intake of 2,000 calories. In this high consumption group, the expected genetic vulnerability completely disappeared. Their rate of cognitive decline mirrored that of people without high-risk gene mutations.
The research team did not observe similar benefits from meat consumption in people with newer genetic mutations. In fact, those with a combination of high-risk genes who ate the least amount of meat had more than twice the risk of developing dementia compared to those without these genetic variants. This suggests that a diet low in meat may cause genetic vulnerabilities associated with old genetic variations.
“There is a lack of research on diet related to brain health, and our findings suggest that traditional dietary advice may be disadvantageous for genetically defined subgroups of the population,” Norgren says. “For those who identify themselves as belonging to this genetic risk group, this finding offers hope; the risk may be modifiable by making lifestyle changes.”
The type of meat consumed played a decisive role in the health effects. Unprocessed meat was associated with improved brain health and lower mortality in high-risk genetic groups. However, processed meat did not have these protective effects.
“Regardless of APOE genotype, a lower proportion of processed meat consumption in total meat consumption was associated with a lower risk of dementia,” said Sara García Ptacek, assistant professor at Karolinska Institutet and senior author of the study. Eating processed foods appears to have a negative impact on cognitive health across all genetic backgrounds.
The researchers also investigated possible biological mechanisms to explain their observations. They measured blood levels of certain vitamins and found that people with the e4 gene mutation seemed to absorb vitamin B12 from meat better than people with other mutations. This suggests that ancient genetic profiles may be uniquely tailored to extract nutrients from animal foods.
This study has several limitations that need to be considered. This was an observational study, meaning the researchers tracked natural habits rather than prescribing a specific diet, making it impossible to prove cause and effect. Participants also self-reported their dietary intake, but this method sometimes introduces memory errors into the data.
Additionally, the study population was primarily of Northern European descent. Because the APOE gene behaves differently in different ethnic groups, these associations may not apply globally. For example, the increased risk of Alzheimer’s disease associated with the e4 variant is known to be weaker in Hispanic and black populations compared to white populations.
Future research should address these gaps through controlled clinical trials. Scientists need to directly test whether increasing their intake of unprocessed meat can actively prevent dementia in people with certain high-risk gene combinations. “Clinical trials are currently needed to develop dietary recommendations tailored to APOE genotypes,” says Norgren.
Such trials could ultimately lead to personalized nutritional plans that protect the aging brain based on an individual’s evolutionary genetic makeup. “As the prevalence of APOE4 is approximately twice as high in Nordic countries as in Mediterranean countries, we are particularly well suited to conduct research on dietary recommendations tailored to this risk group,” continues Norgren.
The results of this study highlight the growing importance of precision nutrition in cognitive aging research. The study, “Meat Consumption and Cognitive Health by APOE Genotype,” was authored by Jakob Norgren, Adrián Carballo-Casla, Giulia Grande, Anne Börjesson-Hanson, Hong Xu, Maria Eriksdotter, Erika J. Laukka, and Sara Garcia-Ptacek.
