Fatty acids in disorders of neurodevelopment, learning and behavior

The brain is made mostly of fat. The correct balance of fatty acids is necessary for neuronal health, nerve transmission, maintaining a normal threshold of excitability,  and the regulation of inflammation in the brain and elsewhere. A fascinating study published recently in the journal Neuropharmacology reveals the relationship between fatty acids, electrical activity (EEG), and brain function in adolescent boys with ADHD.

"Abnormal fatty acid status has been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Delayed maturation in ADHD may result in raised frontal low frequency (theta) electroencephalographic activity (EEG) and a reduction in posterior high frequency (beta, alpha) activity."

The authors data revealed a compelling picture when they investigated the links between the resting-state EEG and levels of omega-3 fatty acids in the red blood cells in 46 adolescent boys with ADHD symptoms (the same test that we employ):

"Docosahexaenoic acid (DHA) levels were positively associated with fast frequency activity: alpha during eyes-open and beta during eyes-closed conditions. Frontal theta activity during both eyes-open and eyes-closed conditions was...positively associated with eicosapentaenoic acid (EPA) levels. Alpha activity correlated positively with performance on fluency for categories (semantic memory). Theta activity correlated inversely with performance on delayed (25 min) verbal memory (recall + recognition/2). "

Their conclusion contains a valuable clinical 'pearl':

"Results support differential associations for DHA and EPA with fast and slow EEG activity respectively. Results support EEG activity as an objective biomarker of neural function associated with long-chain omega-3 fatty acids in ADHD."

A paper published in the journal Prostaglandins, Leuokotrienes and Essential Fatty Acids adds more evidence for the role of omega-3 fatty acid status in ADHD. The authors begin by observing:

"Lower levels of long-chain polyunsaturated fatty acids, particularly omega-3 fatty acids, in blood have repeatedly been associated with a variety of behavioral disorders including attention-deficit/hyperactivity disorder (ADHD)."

When they analyzed a range of markers for key nutrients, antioxidants, oxidative stress, inflammation and fatty acids (with the appropriate controls) in relation to ADHD, their data offered a useful insight:

"The proportion of omega-3 fatty acids was found to be significantly lower in plasma phospholipids and erythrocytes in the ADHD group versus controls..."

The same journal recently presented a very interesting study on the association between fatty acid status and the brain electrical (EEG) expression of emotional activity in boys with ADHD. The authors state:

"Affective impairment is observed in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Low levels of long-chain polyunsaturated fatty acids (LC-PUFA), specifically omega-3 (ω-3) fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD."

The authors measured lipid fractions in the red blood cells of adolescent boys with ADHD and correlated them with an EEG indicator brain function, event-related potentials (ERP), in response to facial expressions of happiness, sadness and fearfulness. What did the data show?

"The results supported the hypothesis of a positive association between eicosapentaenoic acid (EPA) and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of docosahexaenoic acid (DHA) and the right temporal N170 amplitude in response to covert expressions of fear. The arachidonic (AA)/DHA ratio was negatively associated with the right temporal N170 amplitude also to covert expressions of fear."

Their conclusion summarizes their additional insight into the issue of fatty acids and ADHD:

"These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings in the literature on EFA supplementation in ADHD and depression."

We can also thank the journal of Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) for recent scientific confirmation of something that I have personally found to be often overlooked but of critical importance in a number of cases of pediatric neurological disorders: the necessity of adequate amounts of arachidonic acid in the brain.

"Small individual studies report that people with learning disorders have lower than normal blood concentrations of docosahexaenoic acid and arachidonic acid...relatively little attention has been paid to the significance of the low arachidonic acid concentration."

The authors correlated data on various learning disorders with arachidonic acid (AA) and docosahexaenoic acid (DHA) concentrations. Most clinicians are aware of the pro-inflammatory effect of excessive levels of arachidonic acid, but too few know how important it is that AA not be too low. Their data show that this must not be neglected:

"A meta-analysis...showed that red blood cell arachidonic acid and docosahexanoic acid concentrations were significantly lower than normal...Plasma/serum arachidonic acid and docosahexaenoic acid concentrations were also significantly lower than normal. However, in absolute amounts the arachidonic acid was as severely depressed as docosahexanoic acid within red blood cells."

Even six years ago researchers were reporting in PLEFA on the utility of essential fatty acids in the treatment of impulsivity disorders."Essential fatty acids (EFAs) have been shown to benefit patients with depression, schizophrenia and dementia. More recently, their role in disorders characterised by impulsivity has attracted some attention. The psychiatric conditions of attention-deficit hyperactivity disorder and borderline personality disorder as well as the phenomena of deliberate self-harm and violence have been ameliorated by the supplementation of EFAs in a number of recent clinical trials. This paper summarises the burgeoning clinical and basic research indicating the existence of significant deficits of EFAs in impulsivity disorders and the supplementation studies of EFAs in these diverse conditions..."As for the benefits of appropriate supplementation, a paper published a few months ago in PLEFA offers welcome evidence. The authors observe:

"Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA) are critical for infant and childhood brain development, but levels of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are often low in the Western diet...Arachidonic acid (ARA) is also important for infant growth and development."

They review the science on essential fatty acids as a an important intervention in childhood neurodevelopmental disorders:

"Increasing evidence from both epidemiological and intervention studies, reviewed here, indicates that DHA supplementation, during pregnancy, lactation, or childhood plays an important role in childhood neurodevelopment...Several studies have demonstrated positive associations between blood DHA levels and improvements on tests of cognitive and visual function in healthy children."

Moreover:

"Controlled trials also have shown that supplementation with DHA and EPA may help in the management of childhood psychiatric disorders... In all studies, DHA and EPA supplementation is typically well tolerated."

We can also appreciate an earlier study reporting a very desirable behavioral outcome from an omega-3 fatty acid emulsion:

"Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control. There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale."