Imbalances or deficiencies in essential fatty acids which are critical brain components can contribute to depression and neurological disorders. A study just published online in the journal Acta Pædiatrica delineates the decisive difference they make in adolescents. The authors set out to…

“…study the relationship between polyunsaturated fatty acids (PUFA) status and depression in adolescents with eating disorders (ED) and weight loss.”

They measured essential fatty acids (FA) in the red blood cell membranes of 217 adolescents with eating disorders. As the clinicians reading this know, erythrocyte fatty acids also reflect the fatty acid status of the brain. The study subjects were also examined for depression by clinical interviews and psychological self-report instruments. A clear-cut picture emerged from the data:

“Adolescents with ED and depression did not differ from those with ED only in terms of age, BMI, weight loss and duration of disease. In their FA profile depressed adolescents had lower proportions of eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), the end products of the ω3 PUFA series. The ratio of long chain (>18 carbons) ω6/ω3 PUFA was therefore higher in depressed adolescents. Indices of desaturase activites did not differ between depressed and not depressed adolescents.”

In other words, the only difference among the factors examined in this study between the adolescents with and without depression  was their essential fatty acid status. Thus the authors conclude:

“Low ω3 status is related to depression in adolescents with ED. This cannot be explained by differences in weight (loss) and duration of disease, nor by differences in PUFA processing by desaturases. Data suggest a lower dietary intake of ω3 PUFA in those with depression. Further investigations should determine whether ω3 PUFA status improves by refeeding only or whether supplementation with PUFA is warranted.”

See also the Parents’ Guide To Brain Health for additional evidence of the role of fatty acids, along with information on the other important aspects.

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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.”

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There are fascinating and profound biological differences between men and women, so it’s not surprising that a study just published in Nutrition, Metabolism and Cardiovascular Diseases proves that there is a gender difference in the blood ‘anti-stickiness’ benefit from omega-3 fatty acids. The authors begin by stating:

“Increased platelet aggregation is a major risk factor for heart attacks, stroke and thrombosis. Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) reduce platelet aggregation…Recent in vitro studies have demonstrated that inhibition of platelet aggregation by LCn-3PUFA is gender specific. We examined the acute effects of dietary supplementation with EPA or DHA rich oils on platelet aggregation in healthy male and females.“

Platelet aggregation is the ‘sticking together’ or clotting of the sub-cellular blood platelets. Blood that is too ‘sticky’ or clots too easily is a risk factor for heart attacks and strokes and a hindrance to the blood perfusion of tissues. The authors dosed males and females with EPA or DHA rich oil and measured the post-supplementation platelet aggregation. What did the data show?

“EPA was significantly the most effective in reducing platelet aggregation in males…whereas DHA was not effective relative to placebo. In contrast, in females, DHA significantly reduced platelet aggregation at 24 h (while EPA was not effective. An inverse relationship between testosterone levels and platelet aggregation following EPA supplementation was observed.”

This paper follows another recent study reporting that cholesterol levels vary with the menstrual cycle. Practitioners must bear in mind these and other gender differences. The authors conclude:

“Interactions between sex hormones and omega-3 fatty acids exist to differentially reduce platelet aggregation. For healthy individuals, males may benefit more from EPA supplementation while females are more responsive to DHA.“

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This study recently published in the American Journal of Clinical Nutrition provides more evidence for the importance of essential fatty acids for brain function. In this case the authors are interested in the effect of docosahexaenoic acid (DHA) supplementation on prefrontal cortex regulation of attention.

“Emerging evidence suggests that docosahexaenoic acid (DHA, 22:6n–3)…positively regulates cortical metabolic function and cognitive development…The objective was to determine the effects of DHA supplementation on functional cortical activity during sustained attention in human subjects.”

After giving the randomly assigned test cohort DHA supplements they compared cortical activation patterns during sustained attention with those given placebo by functional magnetic resonance imaging (fMRI).

What did their data show?

“At 8 wk, erythrocyte [red blood cell] membrane DHA composition increased significantly from baseline in subjects who received low-dose (by 47%) or high-dose (by 70%) DHA but not in those who received placebo (–11%). During sustained attention, both DHA dose groups had significantly greater changes from baseline in activation of the dorsolateral prefrontal cortex than did the placebo group…The erythrocyte DHA composition was positively correlated with dorsolateral prefrontal cortex activation…”

That last phrase is especially important: DHA is not the only fatty acid that is important for neuronal (brain cell) function. EPA, arachadonic acid and others also play important roles. How do we know with certainty whether someone needs supplementation, which fatty acid should it be, and how much? The Essential Fatty Acid Profile measures the red blood cell membrane content of fatty acids (and is equivalent to the neuronal membrane composition) that we use is the lab technology used by these investigators.

The authors’ conclusion:

“Dietary DHA intake and associated elevations in erythrocyte DHA composition are associated with alterations in functional activity in cortical attention networks during sustained attention in healthy boys.”

For any brain-related disorder we need to objectively answer the questions “What is the brain fatty acid composition? Are there any deficiencies or imbalances? Is supplementation indicated?” When needed, the correct fatty acid supplementation can result in dramatic improvements.

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Neuropathic pain is “pain initiated or caused by a primary lesion or dysfunction in the nervous system”. It includes conditions such as Complex Regional Pain Syndrome (aka Reflex Sympathetic Dystrophy, RSD), and is more common than you might think. There is a neuropathic component to many chronic pain conditions. A paper recently published in The Clinical Journal of Pain reports that omega-3 fatty acids helped people with neuropathic pain.

“Five patients with different underlying diagnoses including cervical radiculopathy, thoracic outlet syndrome, fibromyalgia, carpal tunnel syndrome, burn injury were treated with high oral doses of omega 3 fish oil (varying from 2400-7200 mg/day of EPA-DHA).”

In addition to subjective pain scales objective clinical tools including EMG nerve conduction were used to measure the results:

“These patients had clinically significant pain reduction, improved function as documented with both subjective and objective outcome measures up to as much as 19 months after treatment initiation.”

Omega-3 fatty acids are a well-known natural anti-inflammatory medicine; they are also components of neuronal cell membranes. In my clinical experience  it can be very fruitful in neuropathic and other neurological cases to do an essential fatty acid analysis (blood test) to objectively determine fatty acid deficiencies or imbalances—sometimes the results are unexpected and lead to a clinical breakthrough. You may also enjoy reading an interview with the lead author of the study.

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I hope this never happens to you, but if you or someone you have responsibility for ever sustain a traumatic brain injury (TBI), even a mild one, omega-3 fatty acids are one important part of the solution. This study published in the Journal of Neurotrauma explains how brain injury reduces the activity of a factor important for maintaining brain health called Sir2α (silent information regulator 2 alpha). The authors describe multiple aspects of the protective effect of omega-3 fatty acids and conclude: “Our results suggest that TBI may compromise neuronal protective mechanisms by involving the action of Sir2α. In addition, results show the capacity of omega-3 fatty acids to counteract some of the effects of TBI by normalizing levels of molecular systems associated with energy homeostasis.”

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This paper just published in the Archives of General Psychiatry reports on a randomized, placebo-controlled trial that set out to “determine whether {omega}-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis.” (PUFAs = polyunsaturated fatty acids) The omega-3s (fish oil) reduced progression to psychosis and improved function. The authors conclude: “Long-chain {omega}-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states.” I have found that we can predict who will benefit most from fish oil supplementation for psychiatric and neurological conditions with a fatty acid analysis, a blood test that measures the amounts and ratios of fatty acids in cell membranes.

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This study published recently in the journal Advances in Therapy compared glucosamine sulfate with omega-3 fatty acids (fish oil) to glucosamine sulfate given alone in the treatment of osteoarthritis (degenerative joint disease). Both were effective, but the combination was more effective for higher levels of pain and stiffness.

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This paper, just published in the journal Diabetes, Obesity and Metabolism, documents an improvement in fasting and postprandial (after eating) triglycerides and a reduction in the inflammatory response when fish oil (omega-3 fatty acids) were consumed with the meal. There was also a corresponding reduction in body weight without a reduction in food intake.

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The journal Prostaglandins, Leukotrienes and Essential Fatty Acids published an important paper earlier this year that clarifies why there have been conflicting results in earlier studies on the use of omega-3 fatty acids in the treatment of ADHD. The authors demonstrated that EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) were each associated with a different type of response in different areas of the brain. This is a good example of the importance of the functional medicine approach that investigates the details of underlying causes and customizes treatment for the individual. The authors state “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.” Lapis Light patients already know about the importance of objectively measuring essential fatty acids with the proper blood test for neurodevelopmental and neurodegenerative disorders.

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