Study: Balancing omega-3 and omega-6 impacts cognitive function

By Olivia Haslam

- Last updated on GMT

GettyImages - Brain scan / Andrew Brookes
GettyImages - Brain scan / Andrew Brookes

Related tags Cognitive health Cognitive function Major depressive disorder Brain health omega 3 Omega-6 fatty acid Memory

Reducing omega-6 polyunsaturated fatty acid (PUFA) intake and supplementing with omega-3 may improve neurocognition, a new study focusing on individuals with major depressive disorder (MDD) has concluded.

The authors from New York, USA, suggest: “Findings may inform a therapeutic role for reduced n​-6 PUFA intake and/or n​-3 PUFA supplementation in neurocognitive dysfunction.”

The cross-sectional study examined the relationship between omega-3 and omega-6 plasma phospholipid long-chain polyunsaturated fatty acids (LC-PUFA) levels and neuropsychiatric assessments in individuals with MDD and healthy individuals. 

The authors assessed attentional capacity and executive function, concluding that PUFA imbalance plays a role in attentional functioning and executive performance, however this was not specific to individuals with MDD.


Neurocognitive dysfunction has been linked to neuropsychiatric diseases​, including major depressive disorder (MDD) and suicidal behaviour​. 

Polyunsaturated fatty acids (PUFAs), particularly long-chain PUFAs like arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are known to play a role in brain health​. 

The structural properties of LC-PUFAs are determinants of function, with the omega-3 (n​-3) LC-PUFAs DHA and EPA generally acting in opposition to the omega-6 (n​-6) PUFA, AA. 

Omega-3 PUFAs are neuroprotective, acting through a variety of biological mechanisms including maintenance of membrane fluidity​, regulation of inflammation​, and facilitation of neurogenesis​ and neuronal survival​.

AA, on the other hand, produces eicosanoid (lipid-based signalling molecules) metabolic products that are primarily pro-inflammatory​, therefore the balance of n​-3 to n​-6 LC-PUFAs have been found to affect brain function.

People with MDD often experience memory and processing deficits​, and depression has been found to affect certain types of neuropsychological tasks​.

In the context of depression, research on LC-PUFAs and cognition is limited and inconclusive; some studies​ have found minimal effects on cognitive functions and minor effects on emotional cognition, whereas one previous study​ suggested a link between low n-3 LC-PUFA levels and high hopelessness and suicidality.

The authors note that given that the balance between n​-3 and n​-6 LC-PUFAs plays a critical physiological role in brain health and function​, they aimed to determine whether EPA and DHA levels correlated positively, and AA correlated negatively with attentional and executive functioning, with a particular focus on individuals with MDD at high suicide risk.


The study assessed the correlations between PUFA levels and task performance in three groups of individuals: MDD with a history of suicide attempt (SA, n​ = 20), MDD with no attempts (NA, n​ = 25), and healthy volunteers (HV, n​ = 30). 

They conducted two assessments of attentional capacity, the continuous performance test (CPT) and the colour-word Stroop test, and two assessments of executive function, the object alternation task (OAT) and the Wisconsin Card Sorting Task (WCST). 

The authors assessed performance on tasks of attentional capacity and executive function and its relationship to plasma phospholipid PUFA levels (EPA, DHA, and AA).

Results showed a significant positive correlation of EPA% with continuous performance test scores in the NA group (F​ = 4.883, df​ = 2,72, p​ = 0.01) - a marker of sustained attention.

The AA% correlated negatively with performance on two executive function tasks, object alternation (beta​ = −3.97, z​-score = −2.67, p​ = 0.008) and the WCST (beta​ = 0.80, t​-score = −2.16, df​ = 69, p​ = 0.035), after adjustment for group and age.

There was no detection of any significant associations between DHA% and any neurocognitive outcome measures. 

Results revealed a positive association between EPA levels and sustained attention in individuals with MDD. 

The authors conclude that PUFAs could correct the imbalance in attentional functioning and executive performance; however, no MDD-specific effect was observed. 

The authors suggest that larger, better-powered studies are needed to understand these relationships, noting that the study was limited due to the small sample size, lack of correction for multiple comparisons, and the cross-sectional design that does not establish causality. 

They add: “Ideally, future investigations would utilise fMRI and positron emission tomography with radiotracers such as arachidonic acid​ or docosahexaenoic acid to study the dynamics between peripheral and brain LC-PUFA​ status in relation to neurocognitive function.”



Journal: Nutrients​ 

“Plasma Phospholipid Polyunsaturated Fatty Acid Associations with Neurocognition.”

Authors: Jinjie Ling, John G. Keilp, Hanga C. Galfalvy, Vanessa N. Cardino, Alyina Ahmed, Ainsley K. Burke, Jenifer I. Fenton, J. John Mann, and M. Elizabeth Sublette. 

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