Clinical trial in people with mild cognitive impairment detected different benefits in older people given omega-3 DHA or omega-3 EPA; Omega-6 fats showed no benefit
by Craig Weatherby
Can omega-3 fatty acids from fish oil help prevent or alleviate depression?
A small but lengthy clinical trial from Australia adds positive evidence to a mixed picture … and it also revealed differences in the brain-mood effects of omega-3 EPA and omega-3 DHA.
Back in 2006, an expert panel of the American Psychiatric Association expressed this positive but qualified opinion of the anti-depression promise of omega-3s from fish: “[Omega-3] EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder …” (Freeman MP et al. 2006).
Omega-3s and mood: The mixed clinical picture
We’ve covered many of the trials testing the effects of omega-3 fish fats on mood, and collected them in the Omega-3s & Brain Health section of our news archive.
Here's a selection:
Since then, several more clinical trials of omega-3s have been conducted, with mixed results, suggesting that the efficacy of fish oil depends on factors such as a person’s degree of depression, genetic profile, overall diet, and the doses and forms of omega-3s (i.e., EPA, DHA, or a combination) he or she consumes.
For example, a person’s intake of omega-6 fatty acids – which, in the U.S. is generally very excessive – appears to affect their vulnerability to depression.
High intakes of omega-6 fats blunt the impact of dietary omega-3s, because omega-6s compete with omega-3s for absorption into cell membranes ... see “'Omega Ratio' Matters to Mood”.
The Aussie study we summarize today was conducted in people 65 or older who’d been diagnosed with mild cognitive impairment (MCI). Evidence suggests that fish-source omega-3s may ease or deter some forms of depression and delay the slide from cognitive decline to dementia as we age.
These twin effects of fish oil may be linked, because depression typically raises the risk that a person with MCI will develop dementia.
Before we look at the new trial, it’ll be helpful to quickly recap the differences between the two omega-3s found in fish oil and human cells.
DHA and EPA: Omega-3s with distinct but complementary characters
Fish oil contains two key omega-3s – DHA and EPA – which serve different but overlapping purposes in the human body.
Generally speaking, DHA is essential to brain and eye functions, while EPA is essential to immune functions, especially inflammation … but there is significant overlap between the two.
Omega-3 DHA and EPA are both essential to ending inflammation after it’s no longer needed to help heal an injury or infection (Calder PC 2009), while omega-3 EPA appears particularly important to mood support and some other aspects of mental health (Martins JG 2009).
Most prior studies have suggested that EPA is the more important fish-source omega-3 in terms of mood support, and this one affirms that idea.
But the outcomes of the new clinical trial suggest that DHA may help keep people verbally fluent as they age.
Trial paints positive but varied picture of omega-3s’ mood potential
The new trial was led by Natalie Sinn, Ph.D., with whom we became familiar as an author of studies regarding omega-3s’ potential for aiding kids with attention deficit disorders (Sinn N et al. 2011).
Dr. Sinn and colleagues from the University of South Australia and the Queensland University of Technology recruited 50 people aged 65 years or older to participate in a small but well-designed (double-blind, randomized, controlled) six-month-long trial.
The trial participants were assigned to one of three groups of roughly equal size, each of which took a different supplement daily for six months:
- Fish oil rich in omega-3 EPA (1.67gm of EPA + 0.16gm of DHA)
- Fish oil rich in omega-3 DHA (1.55gm of DHA + 0.40gm of EPA)
- Vegetable oil rich in omega-6 LA (2.2gm of LA)
Compared with the group receiving omega-6 LA, those who took the EPA-rich fish oil had higher (better) scores on the Geriatric Depression Scale.
In contrast, no mood advantage was detected in the DHA fish oil group.
However, the DHA fish oil group displayed improvements in verbal fluency, compared with the group taking the omega-6 LA supplements.
The Australian team made three key points (Sinn N et al. 2011):
- “DHA-rich and EPA-rich fish oils may be effective for depressive symptoms and health parameters, exerting variable effects on cognitive and physical outcomes.”
- “The present findings suggest that pure EPA supplements employed in some mental health studies may not be the optimal choice.”
- “Future research should further investigate this in larger, clinically depressed samples of people with MCI [mild cognitive impairment] ...”
We couldn’t agree more.
Given the mixed efficacy of anti-depressant drugs, and their adverse side effects, Congress should rapidly fund more research on omega-3s for mood health.
- Calder PC. Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. Biochimie. 2009 Jun;91(6):791-5. Review.
- 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.
- Sinn N, Milte CM, Street SJ, Buckley JD, Coates AM, Petkov J, Howe PR. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br J Nutr. 2011 Sep 20:1-12. [Epub ahead of print]
- van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Hoefnagels WH, Beekman AT, de Groot LC. Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2008 Sep;88(3):706-13.
- van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Olderikkert MG, Beekman AT, de Groot LC. Effect of fish oil supplementation on quality of life in a general population of older Dutch subjects: a randomized, double-blind, placebo-controlled trial. J Am Geriatr Soc. 2009 Aug;57(8):1481-6. Epub 2009 Jun 22.