Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression

Alternative Medicine Review, Nov, 2003 by Alan C. Logan

Conclusion

Limited clinical data, combined with rapidly growing support of laboratory and epidemiological studies, suggest omega-3 fatty acids may play a role in the prevention and management of depression. Fish oil supplements are usually well tolerated, with an impressive longterm safety record at doses of 1 g daily. (114,115) EFA supplements rich in omega-3 fatty acids are also generally inexpensive, making them attractive as an adjuvant or alternative to standard pharmacotherapy. At this time, however, there is no established clinically appropriate dose of omega-3 fatty acids for depression. In addition, it is unclear whether the most clinically active component is EPA, DHA, or a combination of the two. (26,116) Supplementation with marine extracts that contain EPA, DHA, and phospholipids is an area warranting further investigation. For now, the bulk of clinical evidence indicates the EPA component of fish oils may be most important in mood stability, and that relatively low levels are required (1 g daily) for successful outcomes.

It should be noted that administration of omega-3 fatty acids, most often via high doses of flaxseed oil, may induce hypomania, mania, or other behavioral changes in a small percentage (less than 3%) of individuals. (104,117)

Further research is necessary before firm conclusions can be drawn regarding the neurobiological influences of omega-3 fatty acids and their clinical value in the treatment of depression. It is anticipated that additional research will shed further light on the neuropsychological aspects of dietary lipids. In the meantime, given the current excess intake of dietary omega-6 fatty acids and the available evidence pertaining to omega-3 fatty acids and brain function, clinicians should ensure adequate intake of omega-3 fatty acids, particularly in patients with mood disorders such as depression.

Table 1. Omega-6 and Omega-3
Content (%) of Dietary Oils

Oil          Omega-6   Omega-3

Safflower      77         0
Sunflower      65         0
Corn           60         0
Cottonseed     50         0
Sesame         45         0
Peanut         32         0
Soybean        51         7
Canola         20         9
Walnut         52        10
Flax           14        57

Table 2. Selected Sources of EPA and DHA

Fish/Seafood      Total EPA/DHA (mg/100 g)

Mackerel                    2500
Herring                     1700
Chinook salmon              1400
Anchovy                     1400
Coho salmon                 800
Rainbow trout               500
Pacific halibut             400
Cod                         300
Shrimp                      300
Catfish                     300
Lobster                     200

Table 3. Consequences of Omega-3 Deficiency in the
Central Nervous System

[??] Dopamine vesicle pool
[??] Dopamine content in frontal cortex
[??] Dopamine content in olfactory bulb
[??] Dopamine content in nucleus accumbens (NA)
[??] Dopamine release from vesicle storage
[??] Normal inhibitory control over NA dopamine
[??] Vesicular monoamine transporter (VMAT2)
[??] Pre/post synaptic dopamine receptor DR2 in frontal cortex
[??] Pre/post synaptic dopamine receptor DR2 in NA
[??] Serotonin receptor (5HT2) density in frontal cortex
     (compensatory response)
[??] Glucose uptake by neurons
[??] Neuronal cytochrome oxidase activity
[??] Blood-brain barrier integrity
[??] Normal cerebral microperfusion
[??] Sodium/potassium ATPase at nerve terminal
[??] Fluidity at surface polar membrane
[??] Phosphatidylserine in cortex, olfactory bulb, and
     mitochondria
[??] Hippocampal CA1 pyramidal neuron cell body size