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Omega-3 Fatty Acids and Depression

Introduction


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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 year. 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 people.

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. Alternately they can be manufactured in the liver from alpha linolenic acid (ALA), a shorter omega-3 fatty acid. This conversion is limited. Only 5-15% of ALA is ultimately converted. Aging, illness and stress, as well as high 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 these oils has dramatically declined in Western countries over the last century. The ideal dietary ratio of omega-6 to omega-3 fats is approximately 2:1. The ratio of omega-6 to omega-3 fats in the average American diet is about 20:1.

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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 to 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 that 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 suicide.

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 effectiveness.

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 of 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 and 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 respond 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 effects.

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.


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

  • Bipolar depression
  • Unipolar depression
  • Depression during pregnancy
  • Insomnia
  • Anxiety
  • 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 growing clinical evidence that folic acid helps treat depression and can enhance 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 system.

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 replace 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:

  1. 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.
  2. A general multivitamin supplement containing high levels of vitamin C, vitamin E, and about 500 mcg of Folic acid.
  3. 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 discussed 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 effects antidepressant drugs have, you do not want to wait around for twenty years until the AMA finally gets around to recommending this treatment.

Anthony Kane, MD
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