Special Edition: Brain Boosting Ingredients

EPA stands alone as a depression fighter

By Hank Schultz

- Last updated on GMT

Related tags: Omega-3 fatty acid, Epa

EPA stands alone as a depression fighter
Omega 3s have been studied for their effect on cognitive health for decades. The science linking EPA with this health indication is less well developed than that for DHA, but new results are coming to the fore all the time, experts say.

The DHA story in brain health is, at its base, fairly straightforward.  The brain consists of fatty tissue, and a lot of that is DHA itself, said Keri Marshall, ND, chief science officer of Nordic Naturals.

“The brain is 60 percent fat and about 40 percent of that fat should be DHA,”​ Marshall told NutraIngredients-USA.

Although it is certainly an oversimplification, another way to look at it is that DHA’s effects are manifested mostly as a building block of cell membranes, while EPA manifests its effects in the ways cells interaction with one another via the bloodstream.

“DHA is structural and EPA is hormonal,”​ said Chris Speed, a clinical dietician and experienced omega 3s formulator.

One of the most influential studies on EPA and its effect on cognitive indications has to do with depression and to begin with, as for all omega 3s science, the two long chain fatty acids were administered together in the form of fish oil. Studies administering EPA and DHA in this form have show positive outcomes associated with depression.  A 2008 study analyzing the omega 3s data form the National Health and Nutritional Examination Survey  concluded: Any EPA+DHA intake was significantly associated with fewer depressive symptoms.”

Picking the omega 3s apart

Since then, researchers have been trying to parse out which omega 3 does what. “The best data we’ve got is in the area of depression.  It looks that in the studies that tended to be more favorable, the product had more EPA than DHA,”​ said William Harris, PhD, an omega 3s researcher at the University of South Dakota.

In a meta analysis published in 2009 the author analyzed data from 28 studies and concluded that EPA was likely more responsible for positive depression outcomes than EPA. Another meta analysis from 2011 that looked at 15 trials with 916 total participants concluded that omega 3 supplements in which EPA accounted for 60% or more of total omega 3s were the most effective for depression. Supplements with a lower ratio of EPA to DHA were judged to be ineffective. The range of ‘excess’ EPA doses ranged from 200 mg to 2,200 mg.

A recent study featured 81 participants with mild to moderate depression who received 1g/day of either EPA, DHA or a placebo for 12 weeks.  Results were significantly better in the EPA group, and six patients in this group showed a 50% or greater improvement in their scores on the Hamilton Depression Rating Scale, whereas none of the DHA group did. “Overall, these data suggest greater efficacy of EPA compared to DHA or placebo as an adjunctive treatment in mild-to-moderate depression. However, further, randomized controlled trials are needed to support these findings,”​ the authors concluded.

Root cause: inflammation

The other main health indication for which EPA alone has been studied is in lowering high triglyceride levels as a way of reducing cardiovascular disease risk. Unlike EPA for mood support, this area of research has been driving by the development of Amayrin’s prescription drug that consists of a synthetic form of EPA. For Speed, EPA’s positive effect in both areas comes as no surprise, as he sees a root cause underlies both heart disease and depression.  Western diets are saturated (pun intended) with omega 6 fatty acids, a known inflammatory factor.  One of the theories of omega 3 supplementation overall is that high levels of n-3 PUFAs are needed to counteract the high levels of omega 6s;  if Westerners ate less fatty and processed food, less omega 3s would be needed.

“I don’t think there is a big difference between heart disease and mental disease, because we know at the root of what we are dealing with is cellular inflammation.  We have too much arachidonic acid production because of so much omega 6, so we need to block the reactions of arachidonic acid that produce pro inflammatory metabolites, these eicosanoids that as a family turn on inflammation,”​ Speed said.

In the brain inflammation can interfere with the way that nerve cells interact with neurotransmitters like dopamine, neuropenepherine and serotonin that affect the perception of emotions. The mechanisms have yet to be determined, Speed said, but the association is becoming clearer all the time, and EPA works to quell that inflammation.

“The reason why EPA works so well is that it fits into the particular enzymes that reduce those eicosanoids far better better than DHA and prevents arachidonic acid from producing too much eicosanoids,”​ he said.

“It’s really becoming an exciting part of why omega 3s are really important for mental wellness,”​ he said.

Picture still fuzzy

While the picture of EPA’s standalone effects on depression and heart disease are becoming clearer, more pieces of the puzzle are missing than have been filled in, meaning much work remains to be done, Harris said.  Studies driven by an interest in one product or approach (such as all the work that has been done on DHA and its effects on the developing brain), while expanding the overall store of knowledge, can also serve to marginalize other approaches

“You can get the impression that EPA has noting to do with human development, for example.  Well, we don’t know that.  It just hasn’t been studied very much,”​ he said.


“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.”

Martins JG., J Am Coll Nutr.​ 2009 Oct;28(5):525-42.

“Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression.”

Sublette ME​, et al. J Clin Psychiatry.​ 2011 Dec;72(12):1577-84. doi: 10.4088/JCP.10m06634. Epub 2011 Sep 6.

“Associations between omega-3 poly-unsaturated fatty acids from fish consumption and severity of depressive symptoms: an analysis of the 2005-2008 National Health and Nutrition Examination Survey.”

Hoffmire CA, et al. Prostaglandins Leukot Essent Fatty Acids.​ 2012 Apr;86(4-5):155-60. doi: 10.1016/j.plefa.2012.03.003. Epub 2012 Apr 1.

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