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Omega-3 Fatty Acids and Depression
  by Anthony Kane, MD


Bipolar disorder and unipolar depression are serious debilitating
psychiatric conditions. Bipolar depression is particularly difficult
to treat, since treatment often pushes the patient into a manic
episode. Bipolar depression carries a 19% suicide rate and bipolar
patients have only a 50% chance of returning to normal functioning.

In the past fifty years there has been about a 20 fold increase in a
number of cases of depressive disorders. 5% of people in the United
States will have at least one episode of serious depression this
While most medical research focuses on pharmacological treatment,
there is a growing body of evidence that nutrition in general, and
omega-3 fatty acids in particular may be of great benefit to numerous

Omega-3 Fatty Acids

Omega-3 fatty acids are long-chain, polyunsaturated fatty acids,
which must be obtained through the diet. Long chain omega-3 fatty
acids, like eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)
can be ingested directly from foods such as fish or fish oil.
they can be manufactured in the liver from alpha linolenic acid (ALA),
a shorter omega-3 fatty acid. This conversion is limited. Only
of ALA is ultimately converted. Aging, illness and stress, as well as
amounts of omega-6 rich oils, such as corn, safflower, sunflower, or
cottonseed oil interfere with the conversion.

Fish oil contains high levels of the omega-3 fatty acids EPA and DHA.
Flax seed oil contains high amounts of ALA. The dietary intake of
oils has dramatically declined in Western countries over the last
The ideal dietary ratio of omega-6 to omega-3 fats is approximately
The ratio of omega-6 to omega-3 fats in the average American diet is
about 20:1.

Given that approximately 20% of the dry weight of the brain is made
up of fatty acids it would not be surprising if inadequate intake of
omega-3 fatty acids would have some neuropsychiatric consequences.
There is a lot of research linking low levels of omega-3 fatty acids
numerous psychiatric conditions and many indications that omega-3
fatty acids have therapeutic value.

Omega-3 Status in Psychiatric Patients

Numerous studies connect dietary consumption of omega-3 fatty
acids with depression. Countries with high consumption of seafood,
high in omega-3 fatty acids, have lower rates of bipolar and unipolar
depression, post-partum depression, and seasonal affective disorder.
These studies do not prove that low levels of dietary omega-3 fatty
acids cause depression. There are other differences of life style
may also play a role. However, the evidence is strong enough to
encourage researchers to investigate the role of omega-3 fatty acids
in mental illness.

Studies of the fatty acid status in psychiatric patients have shown
that depressed patients have lower levels of EPA and DHA. This
connection has been demonstrated in mild depression, major
depression, seasonal depression, post-partum depression, and in

Possible Mechanisms of Omega-3 Fatty Acids

We have limited knowledge of how omega-3 fatty acids function in
the brain. There are three major areas in which omega-3 fatty acids
seem to play a role.

Omega-3 fatty acids are essential components in neuronal membranes
and play a critical role in how they function. They allow the nerve
cell to be more receptive to neurotransmitters, enhancing their

Omega-3 fatty acids also may chemically influence major depression.
Certain chemicals in the brain, called cytokines, which play a role
in the inflammation response, also cause feelings of depression.
Omega-3 fatty acids, and EPA in particular, block the action of these
cytokines. It is worth noting that many antidepressants also block
these inflammatory cytokines.

In addition, there is a chemical in the brain called brain derived
neurotrophic factor. This chemical supports the survival and growth
neurons. Levels of brain derived neurotrophic factor are low in
patients with severe depression. Omega-3 fatty acids enhance the
function of brain derived neurotrophic factor, as do antidepressant
medication and exercise. Interestingly, diets high in saturated fat
sugar, as well as stress inhibit its production.

Clinical Evidence

People with depression have lower levels of omega-3 fatty acids. A
number of studies have shown omega-3 fatty acids to be helpful in
treatment of depression.

Several case studies found that flaxseed oil, which is high in alpha
linolenic acid (ALA) the parent compound for all the omega-3 fatty
acids, improved the symptoms of bipolar depression. Another case
showed that a combination of 4 g EPA/2 g DHA per day improved
the depressed symptoms in pregnancy. These improvements took
about four weeks.

In another case study, a patient with depression that didn't
to medication was placed on 4 g pure EPA. After one month, the
patient's depression improved and after nine months the patient
was symptom free. Utilizing MRI technology, the researchers
found that after EPA treatment, there were structural changes in
the brain that showed a reversal of some of the brain abnormalities
commonly found in depressed patients.

There was one double blind controlled study that found that 9.6 g
of omega-3 fatty acids (6.2 g EPA/3.4 g DHA) helped bipolar disorder
depression. Another study found that 2 g of pure EPA enhanced the
effectiveness of antidepressant medication. There were no side

Another study found that 1 g of EPA could reduce aggression and
depression in borderline personality disorder patients, again with no
negative side effects.

The antidepressant effect of omega-3 fatty acids seems to be the
result of EPA. When DHA was given alone or in equal amounts with
EPA, researchers did not see these antidepressant effects.

In summary, omega-3 fatty acids have been tested in numerous
psychiatric conditions and found helpful in:

      Bipolar depression
      Unipolar depression
      Depression during pregnancy
      Anorexia nervosa
      Depression associated with borderline personality disorder
      Post-partum depression
      Reduction of suicidal thoughts

In general, treatment took three to four weeks to be effective,
with the exception of anxiety and insomnia, which took six weeks.
Although doses of up to 9.6 g were used, there were no significant
side effects noted.

Other Dietary Considerations

Certain nutrients are known to influence omega-3 status. Deficiencies
in four of these nutrients, zinc, selenium, folic acid and dietary
antioxidants, are common in patients with depression.

Zinc levels are lower among patients with depression. In a recent
study, 25 mg zinc supplementation improved depressive symptoms.
Elsewhere it was shown that two months of zinc supplementation,
25 mg/day significantly increased omega-3 levels.

Depressed patients have lower levels of folic acid. There is also
clinical evidence that folic acid helps treat depression and can
the effectiveness of antidepressant medications.

At least five studies link low levels of selenium to negative mood.
Selenium deficiency can interfere with the normal conversion of ALA
to EPA and DHA, and results in an increase in the omega-6:omega-3
ratio. Selenium also plays a role in the human antioxidant defense

Omega-3 fatty acids are extremely vulnerable to oxidation reactions.
Dietary antioxidants are known to influence the antioxidant defense
system and can influence omega-3 status. Some evidence suggests that
antidepressant medications may reverse the severity of oxidative
damage in depressed patients.

Conclusion and Recommendations

There is plenty of research evidence that omega-3 fatty acids,
particularly EPA, may alleviate depression in many people. Fish oil
supplements are well tolerated, have almost no side effects, and are
inexpensive. So far, we cannot recommend that you use fish oil to
drug therapy, but it would be a good idea to add them to the therapy.
You should see results in about 4 weeks, though the maximum benefit
may not appear until nine months.

Researchers have yet to determine the optimum dosages. Studies have
used between 1-6.4 g of EPA a day. EPA seems to be the omega-3 that
is helping.

Although this is a guess, based upon the current research I would
suggest the following regimen for depression:

     A fish oil supplement of 2 g of EPA daily. 
         This can be taken at once or 1 g twice a day. Alternatively
         flaxseed oil, which is high in ALA, can be used. Normally,
         about 14 g of ALA converts to 2 g of EPA.

     A general multivitamin supplement containing high levels of
        vitamin C, vitamin E, and about 500 mcg of Folic acid.

     A general mineral supplement containing selenium. Alternatively,
         eating two Brazil nuts a day will provide all the selenium
you need.

Again I want to stress, this regimen is not in place of medication.
However, I suspect that many people who take these things will need
much less medication. Some will be able to get off medication
completely. Even if this regiment does not help in depression, it may
help to prevent or alleviate a number of other conditions, not
here. Best of all there are no side effects.

Finally, I want to stress that if you or someone you care about is
suffering from depression, this is something you must try. Though
there is
still very scanty research, the best run studies show the EPA is
effective in
almost 90% of depressed patients. Given that there are no real side
effects to taking fish oil in contrast to the very serious side
antidepressant drugs have, you do not want to wait around for twenty
years until the AMA finally gets around to recommending this

Anthony Kane, MD
ADD ADHD Advances

Anthony Kane, MD is a physician and international lecturer. Get
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