Three new studies support the idea that omega-3s enhance mood; only women benefited in one study; omega-3 EPA rivaled Prozac in another clinical trial
by Craig Weatherby

Mood is a matter of more than mere chemistry... but there's ample evidence that nutrition can affect the way we feel.

The results of a new epidemiological study and two new clinical trials support prior findings, most of which link increased intake of omega-3s to reduced risk of depression.

In fact, an expert panel of the American Psychiatric Association concluded in 2007 that adequate intake of omega-3s may help people maintain a good mood. For more on that, see “Top Psych Panel Says Omega-3s Deter Depression, Bipolar Disorder”.

Key Points
  • U.S. epidemiological study finds a 25-34 percent drop in depressive symptoms among women who consume higher levels of omega-3s.
  • Canadian pilot clinical trial finds omega-3 EPA superior to placebo for women with mild depression.
  • Anglo-Iranian pilot clinical trial finds omega-3 EPA as effective as Prozac.
UNC study finds omega-3s lighten women's mood, but not men's
Researchers from Chicago's Feinberg School of Medicine, the University of North Carolina, and the University of California joined to conduct an epidemiological study among 3,317 African-American and Caucasian men and women (Colangelo LA et al. 2009).

The average age of the participants at the start of the study was 35.

The researchers, led by Laura Colangelo, compared the participants' reported dietary intakes of fish and long-chain omega-3s from fish oil (EPA and DHA) to the symptoms of depression measured using a standard test (Center for Epidemiological Studies Depression Scale).

Dr. Colangelo and her team reported that, for the population as a whole, higher intake of EPA, DHA, and EPA plus DHA were associated with a reduced risk of depressive symptoms after ten years.

Women showed more benefit, with those reporting highest intakes of fish reporting 25 percent less depressive symptoms.

Among women, the highest estimated intakes of EPA, DHA, and EPA plus DHA
based on the amounts and kinds of fish they reported eatingwere associated with a 34, 34, and 29 percent reduction in risk, compared to women with the lowest average intakes.

However, the male participants did not report the same benefits. This could be due to differences in how men and women regulate mood. See “Women's Mood-Control System May Differ from Men's”.

The researchers noted that a study with rats suggested that omega-3s may increase dopamine levels, and thereby boost mood, while another mechanism may be linked to inflammation, which omega-3s tend to reduce or moderate.

As they wrote, “Our results are consistent with… other epidemiologic studies that have examined the association of fish intake or dietary omega-3s with depressive disorders or mental disorders. In addition, several small, randomized, double-blind trials found that adjunctive treatment with omega-3s improved depression” (Colangelo LA et al. 2009).

Canadian clinical trial finds mood benefits
Researchers at Quebec's Université Laval conducted a small placebo-controlled clinical trial in menopausal women.

The results, according to a Université Laval press release, “present the first evidence that omega-3 supplements are effective for treating common menopause-related mental health problems,” and show that “Omega-3s ease psychological distress and depressive symptoms often suffered by menopausal and perimenopausal women” (UL 2009).

A team led by Dr. Michael Lucas recruited 120 women age 40 to 55 and divided them into two groups (Lucas M et al. 2008).

Women in the first group took three gel capsules containing a total of one gram of omega-3 EPA from fish oil, every day for eight weeks.

Those in the second group took gel capsules containing sunflower oil without EPA.

Test results before and after the eight-week period indicated that omega-3s significantly improved the condition of women suffering symptoms of psychological distress and mild depression.

However, no positive effect was observed among a small group of women with more severe depressive symptoms.

As Dr. Lucas said, “The differences we observed between the two groups are noteworthy, especially considering that omega-3s have very few side effects and are beneficial to cardiovascular health” (UL 2009).

Many women suffer from depressive symptoms during menopause and perimenopause.

Some take antidepressant drugs such as Prozac for relief even though their effectiveness is controversial (see “Prozac-Type Drugs Proven Little Better than Placebo”).

Mistrust of hormone therapy and antidepressants leads certain women to turn to alternative methods whose effectiveness has not yet been proved.

The study by Université Laval researchers does not prove that omega-3s are effective treatments for mild to moderate depression during menopause and perimenopause, but it adds encouraging preliminary evidence that should be tested in larger trials.

Anglo-Iranian study finds omega-3 EPA equals common anti-depressant
According to clinical findings published last March by a joint Anglo-Iranian team, omega-3 EPA from fish oil cut depression ratings by 50 percent… as much as among participants who took fluoxetine… the generic form of Prozac.

It is not clear what this means, exactly, since fluoxetine/Prozac and omega-3s alike can take longer than the eight week length of this trial to manifest any mood effects.

Also, fluoxetine/Prozac belongs to the leading class of antidepressants, known as selective serotonin reuptake inhibitors (SSRIs), which recent discoveries suggest may be much less effective than advertised (see “Prozac-Type Drugs Proven Little Better than Placebo”).

Putting these caveats aside for the moment, let's take a look at the Anglo-Iranian findings.

Sixty outpatients with a diagnosis of major depressive disorder took one of three regimens daily for eight weeks (Jazayeri S et al. 2008).
  • 1000 mg EPA
  • 20 mg fluoxetine (generic Prozac)
  • 1000 mg EPA + 20 mg fluoxetine (generic Prozac)

The study was double-blind, and the patients were assessed at two-week intervals during  the eight weeks.

And the results were intriguing:

  • The EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone, starting at the fourth week of treatment.
  • Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms.

As the scientists wrote, “In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder… [the] EPA + fluoxetine combination was superior to either of them alone” (Jazayeri S et al. 2008).

Fluoxetine/Prozac is approved for the treatment of major depression, obsessive-compulsive disorder, bulimia, anorexia nervosa, panic disorder, and premenstrual dysphoric disorder (emotional and physical problems linked closely to the menstrual cycle).

More than 22.2 million prescriptions for generic forms of fluoxetine were filled in the United States in 2007, making it the third most prescribed antidepressant.

However, it is not clear how SSRIs work… by maintaining higher serotonin levels, or, as recent evidence suggests, by stimulating connections between neurons.

Interestingly, it appears that the omega-3s from fish also maintain higher serotonin levels. NIH researcher Joe Hibbeln, M.D., reported 10 years ago that low levels of omega-3s correlate closely with low levels of the neurotransmitters dopamine and serotonin: known risk factors for depression and suicide (see “Feel-Good Findings: Omega-3s Boost Mood, Reduce Anger”).

And, like SSRIs, omega-3s stimulate connections between neurons (see “Omega-3s Boost Brain Networks Critical to Memory Capacity”).

These results should not be taken as license to self-treat depression with omega-3s, but they should encourage more research.


  • Colangelo LA, He K, Whooley MA, Daviglus ML, Liu K. Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women. Nutrition. 2009 Feb 3. [Epub ahead of print]
  • Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H, Jalali M, Peet M. Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry. 2008 Mar;42(3):192-8.
  • Lucas M, Asselin G, Mérette C, Poulin MJ, Dodin S. Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr. 2009 Feb;89(2):641-51. Epub 2008 Dec 30.