Fish oil supplements have long been linked with a variety of brain benefits, but new research suggests that one of the omega-3 fatty acids these supplements contain could interfere with the brain's repair processes.
A study of mice affected by mild traumatic head injuries showed that animals fed with diets containing the omega-3 fatty acid EPA (eicosapentaenoic acid) performed worse on spatial memory and learning tasks after the injuries.
Rather than omega-3s aiding recovery as previous research has suggested, it seems EPA might actually get in the way of blood vessel repair, as it reprograms their metabolic activity.
However, not all omega-3 fatty acids behave the same way.
DHA (docosahexaenoic acid), an omega-3 fatty acid known to be important for building and maintaining brain cells, didn't interfere with repair processes in the researchers' follow-up experiments, which used human-derived brain microvascular endothelial cells – the cells that make up the blood-brain barrier.
"Fish oil supplements are everywhere, and people take them for a range of reasons, often without a clear understanding of their long-term effects," says neuroscientist Onder Albayram, from Medical University of South Carolina (MUSC).
"But in terms of neuroscience, we still don't know whether the brain has resilience or resistance to this supplement. That's why ours is the first such study in the field."
The researchers call the observed effects a "context-dependent metabolic vulnerability", a shift in how cells use energy that potentially takes away some of the focus from brain repair under certain circumstances.
The harmful effects of EPA appeared only in injured mouse brains in repair mode, and it's unclear how those effects might play out in living human tissues.
One of the most significant findings from the study is that EPA, and not DHA, accumulated in the brains of mice fed these supplements. This fits with what we know about DHA being more readily built into brain cell membranes than EPA.
What's more, the researchers found that in mice, the destabilizing effects of EPA on blood vessels led to the build-up of toxic tau proteins linked to brain degeneration.
A further analysis of human brain tissue from individuals affected by chronic traumatic encephalopathy (CTE), associated with the repeated head injuries like those tested in the mice, showed a similar kind of metabolic disruption and blood vessel damage.
The researchers speculate that fish oil supplements containing EPA may increase the risk of CTE if, by impairing cellular recovery, it exacerbates the effects of mild concussions that can easily go unchecked.
But those ideas need further testing; the bulk of the evidence we're looking at here is from animal and cell experiments that only flag associations worth exploring further.
These ideas haven't come out of nowhere, though. While omega-3's are touted for their neuroprotective effects, some past research suggests EPA might be causing learning and memory impairments, which DHA helps balance out.
It's becoming clear that omega-3 fatty acids like EPA and DHA can be beneficial, but with caveats. There are no rules that apply equally to all brains.
"This idea of fish oil being a one-size-fits-all benefit doesn't work once you start investigating interactions," says neuroscientist Onur Eskiocak, from Cold Spring Harbor Laboratory.
"But that doesn't mean it's bad for you."
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The researchers are keen to expand their studies of EPA and DHA, looking at their effects on different types of brain cells and across a variety of brain regions, with clinical trials a potential option further down the line.
"This paper is a starting point, but it is an important one," says Albayram.
"It opens a new conversation about precision nutrition in neuroscience, and it gives the field a framework to ask better, more testable questions."
The research has been published in Cell Reports.