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DHA Supports Brain Development and Protects Neurological Function

January 2008

By Russell L. Blaylock, MD

DHA and Neurotransmitters

The beneficial effects of DHA extend beyond promoting optimal neuron function and reducing inflammation. A number of studies have shown that omega-3 oils—especially DHA—can also support healthy levels of neurotransmitters, the chemical messengers between cells. For example, it has been shown that a DHA-supplemented diet can restore neurotransmitter release in the hippocampus and reverse age-related impairment of memory acquisition.51 This may be due, in part, to DHA’s effect on increasing the fluidity of cell membranes, which improves their ability to release neurotransmitters, but it may also involve cell signaling.52,53 Another important effect of DHA is in increasing the density of nerve outgrowths called dendrites, a property that is strongly connected to improved learning in rats as well as humans.54

DHA and Neurotransmitters

In addition, DHA has rather complex effects on a number of neurotransmitters, including serotonin, norepinephrine, acetylcholine, glutamate, and dopamine.46,55,56 Deficiencies in DHA have been shown to lower the level of dopamine and the dopamine receptor D2 in the frontal lobe, which can result in problems with attention and learning.57 This may explain the ability of DHA to promote focused attention and to calm anxiety.

One important effect of DHA-deficient diets was seen in a study using the reward chemical dopamine, which found that long-term omega-3 deficiency raised dopamine levels in a region of the brain closely linked to addiction behavior.58 This, in essence, significantly increases susceptibility to addictive behaviors, whether to foods, sex, or illicit drugs.

Finally, DHA also plays a key role in neurotrans-mitter receptor function. Recent studies have found significant effects of DHA on cell membrane structures called G-protein-coupled receptors, which communicate with the inside of the cell when stimulated by neurotransmitters such as glutamate, serotonin, and acetylcholine.42,59 Since these receptors are inducible, that is, their numbers can be increased on demand or by altering nutrients, dietary changes can significantly affect how the brain functions.

Effect of Omega-3 Oils on Depression and Suicide Risk

Because of the frequent profound effect of EPA, and especially DHA, on cell signaling, membranes, neurotransmitters and receptors, one would expect that omega-3 oils produce equally profound changes in human behavior as well. In fact, a number of studies have found a close correlation between omega-3 oils in the diet and behavior. Of special interest is the effect of omega-3 oils on depression, suicide risk, aggression, anger, and anxiety.

Effect of Omega-3 Oils on Depression and Suicide Risk

Depression has become a major problem, with rates increasing at younger ages than ever before, and the disease occurring even in preteens. Also increasing are rates of anxiety disorders, anger dyscontrol, insomnia, violent suicides, and even homicides. Scientists have proposed a common link between these disorders and chronic brain inflammation. Likewise, a number of medical conditions have been associated with chronic depression, such as cardiovascular disease, cancer, and overall poor health. Until recently, it was assumed that this was because of neuro-endocrine effects or other nonspecific reasons. However, a growing amount of research now indicates these diseases are linked to depression by a common mechanism—a high level of inflam-matory mediators, such as cytokines and inflam-matory prostaglandins.

Unlike acute brain inflammation, as seen with meningitis and encephalitis, subtle, chronic brain inflammation can be silent, except for its behavioral manifestations.60 Chronic brain inflammation can be the result of a number of conditions, such as abdominal obesity, latent viral infections, autoimmune diseases, metabolic syndrome, heavy metal intoxi-cation, and deficiencies in omega-3 oils.

Studies have revealed a close correlation between chronic inflammation and depression.61-65 A recent study even found a strong correlation between inflammatory cytokine levels and the high rates of depression and suicide in anesthesiologists.66 Furthermore, a number of studies suggest that many of the antidepressant medications also act as anti-inflammatory agents and that patients who respond poorly have the highest levels of inflammatory cytokines.67-70

Chronic brain inflammation has also been found in post-traumatic stress disorder and postpartum depression.71,72 It may be that omega-3 oils improve major depression, as well as a number of other neuro-psychiatric disorders, by reducing brain inflammation.

It is known that a deficiency in omega-3 oils affects serotonergic and dopaminergic neuro-transmission, and that if restored before weaning (discontinuation of nursing), these defects can be repaired in the brain.73,74 Both of these neurotransmitters, as well as inflammation, play a significant role in neuro-psychiatric disorders such as schizophrenia, borderline psychotic personality, suicide, hostility/aggression, bipolar disorder, and major depression.

Shrinkage of the hippocampus of the brain has been described in major depression and in post-traumatic stress disorder.75 This shrinkage (atrophy) is also accompanied by deficiencies in recent memory. Memory deficits may occur before atrophy and neuron loss, and treatment of the depression may help restore hippocampal neurons and connections (neutrites and synapses).76

Low DHA in the Diet Increases Anger and Hostility

While both EPA and DHA have been associated with improvements in major depression, only DHA stimulates neurite outgrowth and synaptic development and repair, that is, brain plasticity.54 Therefore, it may be a better choice in methods to repair the brain damage of chronic depression.

A growing problem in this country is postpartum depression, which is often linked with suicide, homicide, and infanticide. A number of studies have linked low blood levels and red blood cell levels of omega-3 fatty acids with postpartum depression.77-79

For example, a study of 10 pregnant women who developed postpartum depression versus 38 who did not found that the proportion of DHA in the serum phospholipids was consistently lower in the women with postpartum depression.79

Suicide risk has also been linked to low omega-3 levels in the blood and cell membranes.80,81 In one such study, researchers at the Department of Neuroscience at the New York State Psychiatric Institute followed 33 medication-free, depressed patients for two years. Seven of the subjects attempted suicide. Low plasma DHA percentage in serum phospholipids and a high ratio of omega-6 fats to omega-3 fats accurately predicted the suicide attempts.82 Unfortunately, Americans consume far more omega-6 fats than are needed for good health.

With the aforementioned effects of DHA on brain levels of the neurotransmitters serotonin and dopamine, as well as receptor expression and cell signaling in synaptic membranes, one should not be surprised by the dramatic behavioral impact of omega-3 deficiency.

The evidence for the effect of omega-3 oils on another neurotransmitter, glutamate—the most abundant messenger in the brain—is still being debated. There is compelling evidence that a number of neuropsychiatric disorders, including schizophrenia, biopolar disorder, suicide risk, and major depression, are related to abnormalities in glutamate neurotransmission.83-85

Data to indicate that excess glutamate may be responsible for major depression, as well as other psychiatric disorders of mood and impulse control comes from a number of quarters. Firstly, depression and schizophrenia have been linked with a decrease in glutamate transport proteins, which normally carry excess glutamate away from nerve endings. This can greatly increase brain glutamate levels and excitotoxicity,86 and would explain the loss of neurons in the hippocampus seen in schizophrenia and major depression. Secondly, the drug ketamine, which is a powerful glutamate receptor antagonist, also acts like an antidepressant.87 Another drug, riluzole, which prevents the release of glutamate from cells also prevents degeneration of brain cells in depression and raises brain growth factor levels, which are consistently lowered in depression. Finally, careful studies have shown that glutamate receptors in depression are overactivated and glutamate removal systems, which normally protect the brain from glutamate excess, function abnormally. These same studies have found that the gamma-aminobutyric acid (GABA) system, which is essential to protecting the brain against excitotoxicity, also works subnormally.

If indeed, major depression, bipolar disorder, schizophrenia, and suicide risk are related to excitotoxic injury, omega-3 oils may play a significant role in combating these disabling disorders, since several studies have shown that omega-3 oils—especially DHA—significantly reduce excitotoxicity.88,89

Low DHA in the Diet Increases Anger and Hostility

Low omega-3 levels, especially DHA levels, have also been associated with anger and hostility reactions. For example, in the first of a two-part multicenter randomized study, medical students were either given a placebo or fish oils containing 1.5 g per day of DHA for three months.90 In this part of the study, which was done during a high-stress period (during final exams), they found an 8.9% increase in aggression in the placebo group, whereas those taking the DHA experienced no increase in aggressive tendencies.

In the second part of the study, using 46 non-stressed students, DHA had no effect on aggression.91 This is because increases in aggression were secondary to stress and DHA appeared to only calm stimulated aggressive urges. This is consistent with the above-cited studies indicating DHA deficiency causes disruption of monoamine neurotransmission (dopamine, norepinephrine, serotonin) as well as acetylcholine and glutamate neurotransmission, all of which are related to impulse and anger control. These effects are also related to the cell-signaling, anti-inflammatory, and membrane fluidity effects of DHA, which are greater than those of EPA (see figure 3 on page 51).

In a later study in 41 university students, researchers compared a high-DHA diet (1.5 g/day) with placebo (soybean oil) over a three-month period to see the effects on hostile responses.92 They found that there was a 27% incidence of hostile answers at baseline, which rose to 92% during final exams. Again, there was no increase in hostility among those taking the high-DHA supplement. They also found that DHA supplementation significantly reduced hostility measures among university staff.

There is even evidence that extra DHA in the diet can reduce aggressive behavior in younger children. For example, in a study examining girls and boys aged 9 to 12 years, adding omega-3-fortified foods (3,600 mg DHA and 840 mg EPA per week) reduced impulsive behavior in both males and females, with stronger results in females.93

One of the effects of higher DHA intake is to reduce plasma norepinephrine levels, which reduces the fight-or-flight response. In one study, DHA’s ability to modulate plasma norepinephrine was quite dramatic, with no effects on cortisol, epinephrine, glucose, or insulin levels.94 DHA could thus be a useful weapon to reduce anxiety and panic attacks.

Supplementing with DHA

Healthy adults should consume 240-1,000 mg of DHA daily to protect their cognitive and neurological health. While many adults already consume omega-3 oil supplements containing both DHA and EPA, DHA standalone products allow those seeking higher DHA/EPA ratios to customize their intake according to their unique health concerns.

Pregnant and lactating women require a minimum of 300 mg DHA daily to promote optimal nervous system development in their children. Parents should ensure that their young children consume at least 150 mg of DHA per day to support health. Omega-3 oils are also available in good-tasting liquid formulations for young children and those who have difficulty swallowing capsules.


From this review we have seen that the omega-3 oils play a major role in brain development, with the highest demand occurring during intrauterine development and the first two years after birth (during the brain growth spurt). Deficiencies during neuro-development in the mother alter not only immediate development, but can set the stage for later disease and brain malfunction.

Because of the high demand for DHA by the developing baby and the preferential extraction from the mother’s supply by the fetus, deficiencies are compounded with succeeding births, should the diet not improve. Likewise, this has a profound effect on the psychological profile of the mother, with severe deficiencies of her DHA resulting in increased rates of postpartum depression, and concomitant increased risk of suicide and homicide.

We have also seen that the effects of DHA and EPA on nervous system cells go beyond structural membrane effects (fluidity), but rather influence cell signaling, neurotransmitters, and receptor expression and function. This also includes gene regulation and expression. The effects of omega-3 oils on inflammation are complex, and go far beyond physically displacing arachidonic acid—the starting material for inflammatory prostaglandins—from the cell membrane. DHA also increases lipoxins, inhibits NF-kb, and produces neuroprotectin-D1 and resolvins.

Because of the complex interaction of omega-3 oils with a multitude of systems, both cellular and via neuronal networks, variations in brain EPA and especially DHA can have profound effects on learning and behavior. Ensuring optimal amounts of these healthful oils is thus essential throughout the healthy life span.

Safety Caution

Individuals who use the medication warfarin (Coumadin®) should consult a physician before supplementing with DHA.95

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.


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