Food and Behaviour Research

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Omega-3 for bipolar disorder - Restoring the balance

Date: 2001


This article gives the text of an interview with Dr Andrew Stoll of Harvard University given in September 2001. His pilot study (Stoll et al, Archives of General Psychiatry, 1999) indicated that adding omega-3 fatty acids to conventional treatment could protect against relapse in adults with bipolar disorder. This sparked a series of larger studies to investigate this further, which are still ongoing.

The interview is in 'question and answer' format, and gives very clear explanations in reply to some of the questions most commonly asked about omega-3 fatty acids. It may therefore be of interest to anyone seeking accessible information on the use of omega-3 (and particularly EPA) in the treatment of mental health problems.

Only the introduction to the article is shown here. The full text can be downloaded as a pdf file by using the link below.


In the battle against bipolar disorder, omega-3 fatty acids may be an important ally. At first, the notion seemed too good to be true. Could a natural substance found in fish oils actually play a crucial role in mental health by regulating and enhancing mood? Exploring the scientific literature on possible treatment alternatives for patients with bipolar disorder, Dr. Andrew Stoll, director of the Psychopharmacology Research Laboratory at Harvard Medical School-McLean Hospital, came across study after study suggesting the potential mood-stabilizing benefits of omega-3 fatty acids found primarily in fish oil.

Certainly, the prospect that a naturally occurring substance with fewer side effects than current conventional medicines could be used to treat bipolar disorder created a stir in the psychiatric community. To investigate the theory, Dr. Stoll conducted a landmark study to put omega-3s to the test. Data from the study were compelling, surprising even the researchers themselves. Although many further studies still need to be done, the benefit of omega-3s in balancing the mood swings that occur in people with bipolar disorder and depression, among other mental conditions, looks promising.

The Post recently spoke with Dr. Andrew Stoll to learn more about the therapeutic potential of omega-3 fatty acids in treating bipolar disorder, as well as other psychiatric conditions.

  • Q: Could you tell Post readers about your research into the relationship between fats and mental health, particularly on the use of omega-3 fish oils in bipolar, as well as other, disorders?

A: Several years ago, we were searching for alternatives to mood stabilizers, such as lithium and Depakote, used to treat bipolar. We began investigating what we knew about the chemical mechanisms of lithium and valproate (Depakote) on the brain and discovered that these drugs are not working on the receptors, or re-uptake sites, that Prozac and similar drugs do. They work inside the cell in a process called signal transduction.

In our search, we began looking for compounds that had a similar mechanism in the brain but had never been tested before. Omega-3s, along with other compounds, came up in our search. But omega-3s had a whole list of mechanisms that certainly appeared to have mood effects in people. This discovery was very surprising, because no one had ever looked at using omega-3s in adult psychiatric disorders. Later in our research, we discovered that we are all depleted of these essential fatty acids.

When individuals consume a diet rich in omega3s, their brain cell membranes become more fluid, allowing for smoother flow of chemical messengers, such as serotonin, in the brain.

To test the effect of omega-3 fatty acids on bipolar disorder, we designed a double-blinded, placebo-controlled study in which the active substance was fish oil supplied by the NIH, while the placebo was olive oil.

We conducted a four-month study in 30 patients with manic-depression comparing the two substances. The study was supposed to run nine months, but at the four-month point, we did a planned preliminary data analysis. We looked at the data, and they were extraordinarily different. Two-thirds of the placebo cases in the study had already relapsed, while only two out of the 14 omega-3 subjects relapsed. Because of the results and because the NIH was actually running out of fish oil, we decided to halt the study at the four-month point; then we published the results.

We now have a federal grant to repeat the study on a much larger scale in 120 patients with a more rigorous design. We are 25 percent finished with this study.

In our first study, we found that the magnitude of the effect of omega-3s was comparable to, or stronger than, lithium, valproate, and other conventional medicine. We don't know if the findings will hold up in the later studies.

For several years, I have put hundreds of people on fish oils in my practice, usually as adjuncts to conventional medicines, because these fats are healthy for you, anyway, and there are no side effects.