Should you eat more meat if you have APOE E4?

A new study with interesting findings!

A study came out last week that, quite frankly, surprised me in its findings.

💥💥 The results showed that people with APOE E4 (Alzheimer’s risk allele) who ate the most red meat were at a more than 50% decreased relative risk of Alzheimer’s! What?!? 💥💥

I know that some of you are steak lovers and cheering this finding, while others are shaking their heads, thinking of the studies showing that plant-based diets are best for longevity. And all of you are smartly thinking that there is more to this story.

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First, if you want to know how to check your APOE type from 23andMe raw data, read the Genetic Lifehacks article on APOE. Be sure to carefully think it through before looking at your APOE status. Not everyone wants to know, and that is totally OK.

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Let’s dig into the details of the study, look at the findings, and then check for any weaknesses in the data. If you don’t care about the study details - skip to the end for the interesting part on why APOE E4 may be an ancient adaptation to a time before agriculture and plant-heavy carbohydrates dominated.

First: Who did the study and why…

The study, published in JAMA Network Open, was done by researchers in Sweden at the Karolinska Institute. Of note here - it’s a good journal, peer-reviewed study, and from a world-renowned research institute.

The researchers looked at data from 2157 older adults who had been followed for more than 15 years for the Swedish National Study on Aging and Care–Kungsholmen.

Who was in the study:

The study participants are Swedish, urban, and aged 60+ and dementia-free at the start of the study period. They were followed for 15+ years.

Importantly, the researchers broke out the participants by APOE genotype, with about 25% of the participants carrying an E4 allele.

APOE E3/E4 and E4/E4 individuals are at a significantly increased risk of Alzheimer’s and dementia, compared to people with the typical E3/E3 genotype. So this study was powered to see if there is an effect on dementia risk or on cognitive decline from meat consumption, broken out by APOE type.

Study participants filled out extensive food-frequency questionnaires at multiple time points over the 15+ year period. This gave researchers data on the frequency of foods eaten over the past year.

The researchers also measured global cognition and checked for dementia diagnoses over the time frame.

What did they find?

The meat intake data was broken out into quintiles (top 20% is Q5 and bottom 20% is Q1). In looking at total meat intake and cognitive function, there was a link between the E4 allele, higher meat consumption, and slower cognitive decline.

In APOE E4 carriers (APOE E3/E4 and E4/E4):

• People in the highest meat-intake group (Q5) had slower cognitive decline over 10 years than those in the lowest.

• They also had better episodic memory trajectories.

In non-E4 genotypes (E3/E3 or E3/E2), there was no clear association between higher meat intake and cognitive trajectories.

Not all meat is the same. Importantly, when the researchers divided out processed meat from unprocessed meat consumption, processed meat consumption was associated with worse cognition scores. Higher unprocessed red meat consumption was driving the benefit for APOE E4.

Higher unprocessed meat intake was also linked to lower all-cause mortality in E4 carriers (HR 0.85; 95% CI 0.73–0.99; P = .04).

To me, the all-cause mortality benefit is an important point. There are studies showing that APOE E4 allele carriers who eat a lot of saturated fat are at a higher risk of heart disease. Not all studies show this, but there’s enough of a signal there that I was worried that higher red meat intake may be preventing dementia by causing everyone to die early from heart disease. Not the case here.

But, but… What about…

I know some of you are thinking of a million things that could cause this correlation. Perhaps people who eat more meat are rich with better healthcare, or are better educated?

Covariates, including education, physical activity, smoking, alcohol, multimorbidity, and diet quality, were all adjusted for in the study. It really does seem to be a well-done study, and the Swedish healthcare system is generally good. However, there still could be some residual confounding variables, such as early-life factors or something more nuanced in their lifestyle that isn’t taken into account.

I don’t want to overhype this, though. A social media headline about this study claimed that eating lots of meat completely abolishes the increased risk of Alzheimer’s from the E4 allele. That claim is a bit of a reach, in my opinion.

The dementia association in E4 carriers was calculated to be about half the risk for the top meat consumers compared to the lowest quintile. However, that calculation was based on relatively few dementia events within the E4 groups. It was statistically significant, but a larger cohort and longer study period are needed to truly know the effect size here.

How much meat did they eat?

The meat intake for the lowest quintile (Q1) was about 220g/week, and the middle (Q3) was around 510 g/week. That’s a couple of small servings of meat in a week for Q1. For the upper quintile (Q5), it was around 930g/week - essentially eating meat every day.

The upper quintile consumed quite a bit more meat than the Nordic guidelines for red meat consumption.

Here’s a breakdown of meat consumption (created in Claude using the data from the study):

Why would APOE E4 benefit from meat consumption?

What I found most interesting was the theory of why APOE E4 allele carriers benefited from more unprocessed meat.

APOE is a lipoprotein that carries cholesterol, and it transports lipids in the brain. The APOE E4 type leads to lower plasma APOE levels. In the brain, APOE also helps to regulate the clearance of beta-amyloid.

The E4 allele is thought to be the ancestral human APOE type, with the E3 and E2 alleles being more recent and more adapted to agriculture. Over the course of history, researchers think there was a ‘hypercarnivore’ phase for a long period when <30% of calories came from plants. Then that shifted to swing back to more of a plant-based omnivorous diet.

The lower APOE levels with E4 could then correspond to being adapted to a diet higher in meat and cholesterol and lower in plant sterols.

Here’s how the authors of the study break it down, including different theories and prior assumptions from other studies:

If you want to read more and see the studies on the benefits of APOE E4, check out the Genetic Lifehacks APOE article. The protection against parasites, such as Giardia and Cryptosporidium, would have been a real benefit for our ancestors.

Conclusion:

This study clearly shows a statistical connection between better cognitive function and more meat consumption in people with APOE E4 alleles. Or, to be more precise, in older Swedish adults with APOE E4. The increased risk of Alzheimer’s for E4 allele carriers varies quite a bit by ancestry group, with Asians and European Caucasians being at a much higher increase in relative risk than people with African ancestry.[ref] I would love to see this type of study carried out in people with different ancestry and in different parts of the world.

What do you think? Will this cause you to eat more unprocessed red meat? Let me know in the comments below.