Eating meat could protect against dementia in people who are predisposed because they carry a common genetic variant, a Swedish study suggests.

The research, in JAMA Network Open, could eventually lead to individually tailored dietary advice for people at risk of cognitive decline due to the presence of the apolipoprotein E ε4 (APOE4) allele.

The study is the first to indicate that meat consumption can maintain the cognitive health of people with APOE ε3/ε4 and ε4/ε4 (APOE34/44) genotypes.

Eating higher than conventionally recommended levels of meat could therefore be beneficial for the quarter of the world’s population who carry these genotypes.

“There is a lack of dietary research into brain health, and our findings suggest that conventional dietary advice may be unfavorable to a genetically defined subgroup of the population,” said lead researcher Jakob Norgren, PhD, from the Karolinska Institute in Sweden.

“For those who are aware that they belong to this genetic risk group, the findings offer hope; the risk may be modifiable through lifestyle changes.”

APOE is the predominant genetic risk modifier for Alzheimer disease, with ε4, ε3, and ε2 alleles combining to create six different genotypes.

APOE4 originated one million to six million years ago and represents the ancestral human form. APOE3 is thought to have emerged approximately 200,000 years ago and being homozygous for this accounts for more than half of all APOE genotypes. The APOE2 genotype arose most recently.

The researchers note there was a general shift toward increased meat consumption 2.5 million years ago, with a hypercarnivorous period that may have coincided with the emergence of APOE4.

Following this, there was a return to more plant-based diets, when APOE3 appeared.

Norgren and team examined how meat consumption was linked with global cognition and the occurrence of dementia among 2157 adults in Stockholm aged 60 years or older who were genotyped for APOE and had no dementia at the start of the study.

They found that eating relatively large amounts of meat was associated with better cognitive trajectories and a lower risk of dementia among people carrying APOE 3/4 and 4/4 genotypes compared with APOE 2/2, 2/3, 2/4, and 3/3.

At lower levels of meat consumption, people with the APOE 3/4 and 4/4 had more than twice the risk of dementia of those who did not carry these genetic variants.

However, this increased risk of cognitive decline and dementia was not seen among the fifth of individuals who ate the most meat, which was estimated at around 870g per week standardized to an energy intake of 2000 calories daily.

Higher unprocessed meat consumption at baseline was significantly associated with reduced mortality among participants with APOE 3/4 and 4/4 genotypes, with a hazard ratio of 0.85.

The trend went in the opposite direction for those without these variants.

Similar trends in terms of APOE interaction were found for outcomes of cholesterol and glycated hemoglobin levels, but not for body mass index or blood pressure levels.

The team used the slope between dietary and circulating levels of vitamin B12 as a possible proxy for nutrient absorption.

They found that absorption was greater with higher meat consumption for participants with APOE 3/4 and 4/4 genotypes while the opposite pattern was true for APOE2 carriers.

Replacement analyses for individual food groups indicated more favorable cognitive associations in APOE 3/4 and 4/4 genotypes when meat replaced cereals, dairy, oils, and legumes, with no associations for the replacement of eggs, fish, or tubers.

For participants with APOE 3/4 and 4/4 genotypes, higher meat consumption aligned with lower blood cholesterol levels and a lower ratio of dietary saturated to polyunsaturated fat, a key dietary factor determining cholesterol levels.

The researchers concluded: “In this cohort study, we found that the APOE34/44 group exhibited the anticipated excess risk of cognitive decline and dementia progression compared with participants with other genotypes when consuming meat at levels consistent with current dietary guideline targets.

“However, this disadvantageous association was absent at higher consumption levels, equivalent to more than twice the target.

Viewed alongside reinterpreted evidence from NHS and UK Biobank focusing on unprocessed meat, these findings point to a consistent gene-diet interaction, with important implications for public health.

“Results reinforce the urgency of investing in precision nutrition research with a focus on APOE, which could ultimately inform future policy development.”