The brain is protected from toxins and other insults by the blood-brain barrier. It’s an important line of defense against damage and infection. But with aging it becomes “leaky,” leaving the brain susceptible.

If only there was a way of preventing this. Well, actually, there is. And best of all, you don’t need another vitamin pill or even a medication. All you need is food…

Since a leaky blood-brain barrier can exert very damaging effects on memory and language and is one of the first events to occur in Alzheimer’s disease, researchers from England investigated whether a little-known food molecule called TMAO (trimethylamine N-oxide) had any impact on the blood brain barrier and whether it would improve cognition.

Many Reasons To Be Hopeful 

The researchers were interested in TMAO for several reasons.

Precursors to TMAO such as choline and L-carnitine have been shown to improve cognitive function, and there’s evidence that patients with Parkinson’s disease have lower circulating TMAO.

A previous study found gut microbe-derived short-chain fatty acids, formed from bacterial fermentation of dietary fiber, promote blood-brain barrier integrity, and protect the brain’s blood vessels. There are many other classes of gut microbe-derived metabolites of which TMAO is one. Would that too support the integrity of the blood-brain barrier?

Protective roles for TMAO have also been reported in animal models for high blood pressure, heart disease, and unstable blood sugar, all of which have negative effects on the brain.

For these reasons the researchers had high hopes TMAO would prove to be good news for brain health.

Improves Recognition Memory 

After conducting an extensive series of cellular and animal experiments researchers found TMAO supports the integrity of the blood-brain barrier following an acute inflammatory assault.

When TMAO is ingested in food it’s broken down by bacteria in the gut. It’s then transported to the liver and rapidly converted back to TMAO which then enters the circulation and finds its way to the blood-brain-barrier. This was the first demonstration of a direct interaction of a microbe-derived metabolite with the blood-brain barrier.

This food molecule also had protective effects on the brain’s blood vessels, the brain’s astrocytes – cells that help control blood-brain barrier permeability – and microglia, the brain’s immune cells.

In addition, not only did TMAO make the blood-brain barrier less leaky in mice, but cognition was improved, and the rodents had a better memory for previously encountered situations.

Not only does this study demonstrate the value of TMAO but adds to previous findings showing the importance of gut microbes and the metabolites they produce.

Opens Up Exciting Dietary Possibilities 

First author and microbiologist at Nottingham Trent University, Professor Lesley Hoyles, explains more about how TMAO, which is found in high quantities in fish and seafood, interacts directly with the blood-brain barrier to keep it intact and protect the brain’s blood vessels.

“This work is a big step forward in better understanding how our diet could positively influence cognitive function and healthy aging.

“Microbiota-produced metabolites come from gut bacteria and have numerous effects on our bodies. We have demonstrated that TMAO – a bacterial metabolite associated with the human gut microbiome and found in high quantities in fish and seafood – has a direct and beneficial interaction with the blood-brain barrier and influences cognitive function.

“This opens up a range of new work exploring dietary interventions that connect the gut and brain.”

Lead author Dr. Simon McArthur at Queen Mary University of London added: “We know that damage to the brain’s blood vessels is a feature of many neurological diseases, including stroke and dementia. By identifying the gut bacteria as able to modify brain blood vessel integrity, our findings open up exciting new avenues for protective intervention by manipulating the diet.

“We have long known that eating fish is good for your brain – now we can add the gut bacteria as a fresh aspect to this old adage.”

My Takeaway 

The big question I have is what about taking fish oil? Does this help increase TMAO levels? While these researchers didn’t weigh in on the topic, another study found that, yes, it does.

Research in China found that fish oil increased choline circulation levels in blood plasma while raising the concentration of TMAO.

The studies suggest that regularly eating fish and/or consuming fish oil supplements can help you protect your brain and strengthen your memory and cognitive function. The studies also confirm the importance of a healthy gut in the production of TMAO—so keeping your digestive system in healthy balance with a probiotic supplement is important.


  1. https://www.qmul.ac.uk/media/news/2021/smd/molecule-found-in-seafood-plays-role-in-
    protecting-and-improving-cognitive-function-researchers-find.html
  2. https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01181-z 
  3. https://pubs.rsc.org/en/journals/journalissues/ra#!issues