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Omega-3s vs. Depression: Do they Really Help?
Headlines distorted study findings: More studies needed, but evidence to date is promising 11/11/2015 By Craig Weatherby
Once again, news headlines distorted the actual results of a new study.
The study's authors analyzed the evidence from 26 placebo-controlled clinical trials involving people diagnosed with major depression.
In brief, the authors found insufficient evidence to determine whether omega-3 fish oil can substantially ease the symptoms of major depression.
Their analysis did not find omega-3 fish oils ineffective for treating depression.
Instead, the authors simply couldn't find enough high-quality evidence to conclude that omega-3 fish oil can alleviate major depression.
They didn't examine whether omega-3s can help alleviate mild-to-moderate depression ... a hypothesis backed by substantial clinical evidence.
Before we delve into the new evidence review, let's look at what's known about depression and omega-3s.
Omega-3s versus depression: The evidence so far
Nine years ago, the American Psychiatric Association concluded that people who consume higher amounts of the omega-3s (EPA and DHA) from fish oil are less likely to suffer depression or related mood disorders (see Top Psych Panel Says Omega-3s Deter Depression, Bipolar Disorder).
The evidence to date suggests (but does not prove) that omega-3s can alleviate mild-to-moderate depression ... and help people with major depression who don't respond to standard antidepressant drugs and other treatments.
About half of major depression patients don't respond to standard antidepressants like Prozac: a condition called "atypical” depression.
Last year, Dutch researchers reported that the patients suffering from atypical depression who ate the most fish responded the best to antidepressant drugs.
Specifically, those who ate fatty fish (i.e., fish rich in omega-3s) at least once a week had a 75 percent chance of responding to antidepressants, while those who never ate fatty fish had only a 23 percent chance of success (see Fish Boosts Anti-Depressant Drugs).
(You'll find these and many other reports concerning the effects of omega-3s on mood and mental performance in the Omega-3s & Brain Health section of our news archive.)
One of the world's leading experts – NIH clinical psychiatrist and biochemist Joseph R. Hibbeln, M.D. – summarized the available evidence in a video titled "Depression: How Does Omega-3 Fatty Acid Intake Affect This?”.
New review sees mixed evidence and calls for more, better trials
The new analysis was conducted using the rigorous criteria of the highly regarded Cochrane Collaboration (Appleton KM et al. 2014).
The authors came from several different British universities and gathered data from 26 randomized, controlled clinical trials involving a total of 1,458 participants.
All but one of the trials compared omega-3 fish oil supplements to placebo (inactive) capsules, while the remaining trial compared omega-3 fish oil to a standard anti-depressant drug.
The authors of the British evidence review found that while people who were given omega-3 capsules reported lower symptom scores than people who took placebo capsules, the effect was small and weaknesses in the studies undermined confidence in the results.
As lead author Katherine Appleton put it, "We found a small-to-modest positive effect of omega-3 fatty acids compared to placebo, but the size of this effect is unlikely to be meaningful to people with depression, and we considered the evidence to be of low or very low quality.” 
She added, "At present, we just don't have enough high quality evidence to determine the effects of omega-3 fatty acids as a treatment for major depressive disorder." 
As you can see, news headlines that characterized the results of the evidence review as proving that "omega-3s don't work for depression” were very misleading.
The British team's evidence review affirmed the results of a review published nine years ago by the same group:
"The current meta-analysis provides evidence that EPA may be more efficacious than DHA in treating depressionlarger, well-designed, randomized controlled trials of sufficient duration are needed to confirm these findings. (Appleton KM et al. 2006)
The conclusions of both British evidence reviews were echoed in a similar review published last year by Brazilian scientists:
"Several studies have demonstrated beneficial effects of omega-3 in the prevention and treatment of major depression. However, not all the results have shown significant statistical benefits. More studies are necessary ...” (Mello AH et al. 2014)
Although we lack conclusive proof, the evidence to date strongly suggests that omega-3s from seafood – especially EPA – support healthy mood, and may enhance the benefits of conventional drug treatments.
What is depression?
Depression is generally defined as a lack of pleasure in activities that were previously enjoyable.
People are diagnosed with "major” depression only when they meet three criteria:
  1. Report suffering from a seriously depressed mood.
  2. The depressed mood has no apparent physical cause, such as chronic pain.
  3. The depressed mood significantly impacts everyday life for at least two weeks.
According to the World Health Organization, major depressive disorders account for three percent of ill health worldwide, and projections for 2030 suggest an increase to six or seven percent.
What are omega-3s?
Omega-3 fatty acids are essential nutrients that come in two basic forms:
  • Short-chain (polyunsaturated) omega-3 ALA from plant foods.
  • Long-chain (highly unsaturated) omega-3s (EPA and DHA) from seafood and fish oil.
The body only requires EPA and DHA, very small amounts of which it can make from plant-source ALA.
Because people can survive if the only omega-3 fatty acid they consume is plant-source ALA, it is the only one officially considered an essential nutrient.
However, that designation is highly misleading.
If your diet lacks seafood source EPA and DHA, your body will convert dietary ALA into small amounts of omega-3 EPA, some of which gets converted into even smaller amounts of omega-3 DHA.
But if you get enough omega-3 EPA and DHA from seafood or supplements, your body will just burn dietary ALA as fuel.
Of the two seafood-source omega-3s, the more important by far is DHA, which is critical to brain and eye functions, and which the body can easily convert into ample amounts of EPA.
Despite the fact that DHA is the most important omega-3 for general brain health, most evidence suggests that EPA is more important for maintaining healthy mood.
Conversely, compared with EPA, omega-3 DHA is far more important for maintaining and optimizing basic mental functions such as thinking and memory, and for baby and child development.
To learn more about the health effects attributed to EPA and DHA, see the section of our Omega-3 Facts & Sources page titled "Long-chain omega-3s: Truly essential to life and health”.
  • Appleton KM, Gunnell D, Peters TJ, Ness AR, Kessler D, Rogers PJ. No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population. Prostaglandins Leukot Essent Fatty Acids. 2008 Jun;78(6):337-42. doi: 10.1016/j.plefa.2008.04.009. Epub 2008 Jun 18.
  • Appleton KM, Hayward RC, Gunnell D, Peters TJ, Rogers PJ, Kessler D, Ness AR. Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Am J Clin Nutr. 2006 Dec;84(6):1308-16. Review.
  • Appleton KM, Peters TJ, Hayward RC, Heatherley SV, McNaughton SA, Rogers PJ, Gunnell D, Ness AR, Kessler D. Depressed mood and n-3 polyunsaturated fatty acid intake from fish: non-linear or confounded association? Soc Psychiatry Psychiatr Epidemiol. 2007 Feb;42(2):100-4. Epub 2006 Dec 11.
  • Appleton KM, Rogers PJ, Ness AR. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2010 Mar;91(3):757-70. doi: 10.3945/ajcn.2009.28313. Epub 2010 Feb 3. Review. 
  • Appleton KM, Sallis HM, Perry R, Ness AR, Churchill R. Omega-3 fatty acids for depression in adults. Cochrane Database of Systematic Reviews 2014, Issue 5 . Art. No.: CD004692. DOI: 10.1002/14651858.CD004692.pub3.
  • Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, Caraci F. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid Med Cell Longev. 2014;2014:313570. doi: 10.1155/2014/313570. Epub 2014 Mar 18. Review.
  • Hibbeln JR, Gow RV. The potential for military diets to reduce depression, suicide, and impulsive aggression: a review of current evidence for omega-3 and omega-6 fatty acids. Mil Med. 2014 Nov;179(11 Suppl):117-28. doi: 10.7205/MILMED-D-14-00153. Accessed at
  • John Wiley & Sons, Inc. (Wiley). Insufficient evidence for the use of omega 3 supplements in treating depression. November 4, 2015. Accessed at
  • Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61.
  • Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct;28(5):525-42. Review.
  • Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnell D, Hayward RC, Heatherley SV, Christian LM, McNaughton SA, Ness AR. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr. 2008 Feb;99(2):421-31. Epub 2007 Oct 24.