Fish Oil Supplements and EPA May Disrupt Brain Repair After Head Injury

Fish oil supplements have long been associated with a range of benefits for the brain. However, fresh research indicates that EPA, one of the omega-3 fatty acids found in these products, may disrupt the brain’s ability to repair itself.

EPA and brain repair after head injury

In a study involving mice with mild traumatic head injuries, animals given diets containing the omega-3 fatty acid EPA (eicosapentaenoic acid) performed less well in tests of spatial learning and memory following their injuries.

Earlier research has indicated that omega-3s can support recovery, but EPA may instead hinder blood-vessel repair by altering the way these vessels regulate their metabolic activity.

Not every omega-3 fatty acid appears to act in the same manner.

DHA (docosahexaenoic acid), an omega-3 fatty acid recognised as important for forming and maintaining brain cells, did not disrupt repair mechanisms in the researchers’ follow-up tests. These experiments used human-derived brain microvascular endothelial cells, which form 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 team describes the effects it observed as a "context-dependent metabolic vulnerability": a change in cellular energy use that could, in certain situations, divert some attention away from repairing the brain.

EPA accumulation and blood-vessel damage

The damaging effects of EPA were seen only in injured mouse brains that were attempting to recover, and it remains uncertain how these effects could manifest in living human tissue.

Among the study’s most notable results was the finding that EPA, rather than DHA, accumulated in the brains of mice receiving the supplements. This is consistent with existing knowledge that DHA is incorporated into brain-cell membranes more readily than EPA.

The researchers also established that, in mice, EPA’s blood-vessel destabilising effects resulted in an accumulation of toxic tau proteins associated with brain degeneration.

An additional examination of human brain tissue from people affected by chronic traumatic encephalopathy (CTE) revealed similar metabolic disruption and blood-vessel damage. CTE is linked with repeated head impacts such as the injuries investigated in the mice.

The researchers suggest that fish oil supplements containing EPA could raise the risk of CTE if impaired cellular recovery worsens the effects of mild concussions, which can readily go unnoticed.

Nevertheless, these possibilities require more investigation. Most of the evidence considered here comes from animal and cell studies, which identify associations that warrant further examination.

Fish oil supplements are not one-size-fits-all

The findings are not entirely without precedent. Although omega-3s are promoted for neuroprotective properties, some earlier studies have indicated that EPA may impair learning and memory, effects that DHA helps to counterbalance.

It is increasingly apparent that omega-3 fatty acids such as EPA and DHA may offer benefits, albeit with important qualifications. No single rule applies equally to every brain.

"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."

The researchers intend to broaden their EPA and DHA investigations, examining effects across different brain-cell types and a range of brain regions. Clinical trials may be considered at a later stage.

"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 was published in Cell Reports.