Too much EPA without DHA may cause cognitive deficits, study finds

Omega-3 fatty acids are essential for the human body's functioning, but scientists recently discovered that too much omega-3 fatty acid EPA (eicosapentaenoic acid) alone can damage learning and memory function in mice.

The study, involving adult and prepubescent mice, is published in the journal Nature Communications, Oct. 29.

The research team discovered that, although EPA given alone produced detrimental effects, no damaging effects occurred when given in combination with a specific ratio of another omega-3 fatty acid, DHA (docosahexaenoic acid).

The study also found that the detrimental cognitive effects occurred only when the EPA levels were elevated and did not have a lasting impact once EPA levels became normal.

The results of the study were unexpected. EPA, along with another omega-3 fatty acid, DHA (docosahexaenoic acid), are widely used therapeutically, including for cardiovascular disease prevention and brain disease treatment.

Although fatty acids are well studied in general, the effect of EPA and DHA supplementation on cognitive functioning isn't well known, the study says. Also unknown is the mechanism of how these fatty acids work on the molecular level. This research looked at both the cognitive effect and its possible mechanism.

The researchers used a variety of concentrations of EPA derived from the U.S. Food and Drug Administration (FDA) recommended dosage for humans. The groups of mice with different EPA doses were then put through a series of cognitive tests. These included a water maze, fear conditioning within different contexts and normal object recognition.

The mice treated with EPA performed the cognitive tests poorly, compared to a control group of mice that did not receive EPA. However, despite cognitive and memory deficits, the mice dosed with EPA retained motor and sensory skills.

Notably, as soon as EPA levels in these mice returned to normal, the mice regained former cognitive and memory ability. This was also the case after longer-term EPA doses. The researchers repeated the EPA dosing every day for a month, then tested the mice 24 hours after the last dose. The detrimental effects were not present.

The study results held for both adult and prepubescent mice (assumed to be the equivalent of human 2 to 3-year-olds).

The study determined that elevated EPA in the hippocampus was involved in the affected learning and memory. In addition to testing in vivo, the researchers also looked at the EPA effects on the hippocampus in vitro, in sacrificed mice.

The researchers caution that EPA supplements should always be combined with DHA at a "natural ratio" in order to protect learning and memory functions. They also note that infant formulas contain some EPA, so care should be taken with further supplements of fatty acids.