High daily doses heightened performance in people with healthy brains 11/21/2019
Today’s report concerns two recent headlines about omega-3s — one positive and one misleadingly negative.
On the positive side, the results of a new clinical trial showed that people who took omega-3 fish oil supplements for 2½ years enjoyed improvements in basic aspects of brain performance.
The misleadingly negative headlines flow from a report by British researchers who reviewed the data from selected clinical trials and asserted that omega-3 fish oil does not help to ease depression or anxiety.
Media headlines about the British team's evidence review are misleading, for two reasons:
- Substantial evidence suggests that omega-3 fish oil and/or diets rich in fish can ease anxiety and depression, and may reduce the risk for those disorders: see Evidence Review Tags Omega-3s as Top Mood Aid and its links to related articles.
- Most of the relatively small amount of clinical evidence is of low scientific quality, which precludes firm conclusions and renders dubious the highly negative assertions made by the British evidence-reviewers.
Let’s first examine the positive brain-performance study, and then scrutinize the British evidence-reviewers' negative conclusions in the context of other recent evidence reviews.
Harvard-led trial sees fish oil boosting healthy brains
There's a good deal of evidence that seafood-source omega-3 fatty acids (DHA and EPA) can help keep people's thinking sharp as they age.
Now, the results of a lengthy clinical trial conducted among heart patients provide significant support for that proposition.
The Harvard-led team behind the new trial noted that while omega-3 fish oil has shown benefit in people suffering from mild cognitive impairment, its effects on healthy brains have been less clear.
Further, as they noted, it hasn’t been clear whether omega-3s could benefit brain function in people with coronary artery disease (CAD), which reduces blood flow to the brain and is a known risk factor for dementia.
To address both questions, a team led by Harvard Medical School researchers conducted a 30-month-long clinical trial, for which they recruited 250 people with coronary artery disease.
The researchers randomly assigned the participants to one of two groups, each containing 125 people:
- Control group: No brain-function drugs or supplements.
- Omega-3 group: Daily fish oil capsules containing 3.36g of omega-3 EPA + DHA
Each participant’s cognitive functions — thinking, reaction times, and memory – was tested at the outset of the trial, again after one year, and at the end of the 30-month study.
In addition, each participant’s blood levels of omega-3s (EPA and DHA) and other fatty acids were measured.
Omega-3s: Not created equal
The body can make very small amounts of EPA and DHA from the omega-3 fatty acid (ALA) that abounds in canola oil, flax oil, and flaxseed. Much smaller amounts of ALA occur in dark leafy greens, avocados, and walnuts.
However, the huge excess of omega-6 fatty acids in the standard American diet — mostly from cheap vegetable oils (i.e., corn, soy, cottonseed, safflower, sunflower) — hinders the body’s ability to convert ALA into EPA and DHA.
Click here to learn more about omega-3s.
Using that blood-test data, the researchers calculated each participant’s “omega-3 index” — which is the percentage of red blood cell fatty acids consisting of omega-3s. (An omega-3 index lower than 4% is linked to substantially higher cardiovascular risks, while an index of 8% or higher is linked to significantly reduced risks.)
And brain tests conducted at the end of the trial showed that — compared with the control group — the volunteers assigned to take omega-3 fish oil displayed better coordination, reaction speed, verbal fluency, and memory.
Specifically, the participants whose omega-3 index measured 4% or higher displayed improvements in visual-motor coordination, verbal fluency, and “psychomotor speed” (i.e., how fast a person detects, and moves in response to, external stimuli).
This is how the researchers expressed their conclusions: “High dose EPA and DHA prevented cognitive decline in cognitively healthy CAD [coronary artery disease] subjects, with younger subjects, non-diabetic subjects, and those achieving an omega-3 fatty acid index [equal to or higher than] 4% having greatest benefit. These findings are especially important for CAD patients as CAD is a risk factor for dementia.”
Study co-author Dr. Francine Welty — a cardiologist at Harvard Medical School — placed their findings in context: “Other researchers have looked at omega-3 fatty acids in people who already have cognitive impairment or dementia. But the people we looked at were cognitively healthy, and we found there may be a benefit from omega-3 fatty acids before cognitive decline begins.”
The results of this new trial make sense, because omega-3 DHA is a key structural and functional component of cell membranes throughout the body — especially the brain — while DHA and EPA are both essential to ending chronic inflammation, which promotes dementia and cardiovascular disease.
“It's really surprising that in 30 months you see that the people who took omega-3 fatty acids did not see a decline in cognitive function and actually saw benefits, compared to those who did not take them," said Dr. Penny Kris-Etherton, a cardiovascular nutrition researcher at Penn State University.
As she went on to say, “This is just one study, and I'd want to see the results reproduced. But it does tell us that at this [dosage] level, omega-3 fatty acids might confer some cognitive benefit.”
Negative finding on omega-3s vs. depression appears unjustified
Media reports on omega-3 fish oil research often make frustrating reading for those aware of the evidence.
The failure of many reporters to challenge studies is probably attributable to time constraints, and the reality that negative and counterintuitive news generates attention and revenue.
Recent, regrettably uncritical coverage of a new evidence review from the University of East Anglia (UEA) is a perfect case in point.
A UEA team led by Dr. Lee Hooper conducted a meta-analysis — a type of evidence-review — of 31 clinical trials (involving 41,470 people) that had tested the effects of omega-3 fish oil on symptoms of depression and/or anxiety.
In each trial, the participants were randomly assigned to consume more omega-3 fish oil or maintain their usual intake, for at least six months.
The UEA team concluded that fish oil supplements had little or no effect in preventing symptoms of depression or anxiety. As Dr. Hooper said, “The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on depression or anxiety, and they should not be encouraged as a treatment.” (Deane KHO et al. 2019)
However, the review conducted by Dr. Hooper's UEA team excluded some omega-3/depression clinical studies that yielded positive results, such as the unusually large trial whose results we summarized in Fish Oil Rivals Antidepressants in Clinical Trial .
Moreover, the UEA team’s conclusions should be taken with a grain of salt, given the findings of three other recent evidence reviews, including the two described below and the one we summarized just two months ago in Evidence Review Tags Omega-3s as Top Mood Aid.
Other evidence reviews undermine UEA team's conclusions
The findings of two other recent evidence reviews undermine the unjustifiably negative assertions made by Dr. Hooper's UEA team.
One of those evidence reviews, from a Canadian-Chinese team, came to quite positive conclusions — but was ignored in media reports about the UEA team’s new evidence review.
And the other review, conducted by a British team, found insufficient high-quality clinical evidence to enable any firm conclusions.
The trials included in the UEA evidence review covered many more participants (41,470) than these other two evidence reviews, which included 2,160 and 1,438 participants respectively.
But the quality of evidence in a review matters much more than quantity. And it appears that the other two review groups were more selective when they chose the trials to analyze.
Prior review #1: Canadian-Chinese review sees mood benefits
In August of this year, a Canadian-Chinese scientific team published a meta-analysis of 26 clinical trials involving 2,160 participants.
As the authors wrote, “The meta-analysis showed an overall beneficial effect of omega-3 polyunsaturated fatty acids on depression symptoms.” (Liao Y et al. 2019)
Their calculations showed that — compared with placebo capsules — daily omega-3 fish oil produced clinical benefits, but only when it contained substantially more EPA than DHA.
Fortunately, even fairly low EPA doses — under 1 gram per day — eased depression or anxiety symptoms to a clinically significant extent.
Most prior trials have found EPA more effective than DHA for depression, and — in line with that past evidence — the Canadian-Chinese team detected no benefits from fish oils that provided substantially more DHA than EPA.
Prior review #2: British team sees modest potential and calls for more study
Four years ago, a team of British researchers set out to review the best of the generally low-quality clinical evidence and selected the 26 best clinical trials (Appleton KM et al. 2015).
The authors of the review employed the famously rigorous methods of the global Cochrane organization, which is partly funded by the NIH and receives no commercial funds or support.
Unfortunately, as other researchers have noted, most of the available trials are low-quality, making firm conclusions difficult to draw. As the review’s British authors wrote, “… we rated the quality of the evidence for all outcomes as low to very low.”
All but one of the studies — 25 trials involving 1,373 participants — pitted fish oil pills against a placebo, while one small (40-person) trial tested fish oil versus a standard antidepressant drug.
The British team’s analysis found that — compared with placebo pills — omega-3 fish oil may reduce depression symptoms to modest extent, although, as the authors wrote, “… this effect is unlikely to be clinically meaningful.”
And, in line with some prior evidence — see Fish Boosts Anti-Depressant Drugs, and Fish Oil Rivals Antidepressants in Clinical Trial — the review’s authors noted that the “… one study that directly compares omega-3s and antidepressants in our review finds comparable benefit.”
Importantly, the British evidence-reviewers stressed the lack of high-quality evidence, which precludes the kind of sweeping conclusions made by Dr. Hooper's UEA team: “At present, we do not have sufficient high-quality evidence to determine the effects of omega-3s as a treatment for MDD [major depressive disorder].”
For more on this 2015 evidence review, see our original coverage of it in Omega-3s vs. Depression: Do they Really Help?.
- Appleton KM, Sallis HM, Perry R, Ness AR, Churchill R. Omega-3 fatty acids for depression in adults. Cochrane Database Syst Rev. 2015 Nov 5;(11):CD004692. doi: 10.1002/14651858.CD004692.pub4. Review.
- Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS. Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial JAMA. 2009 Oct 21;302(15):1651-7. doi: 10.1001/jama.2009.1487.
- Deane KHO, Jimoh OF, Biswas P, O'Brien A, Hanson S, Abdelhamid AS, Fox C, Hooper L. Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials. Br J Psychiatry. 2019 Oct 24:1-8. doi: 10.1192/bjp.2019.234. [Epub ahead of print]
- Lespérance F, Frasure-Smith N, St-André E, Turecki G, Lespérance P, Wisniewski SR. The efficacy of omega-3 supplementation for major depression: a randomized controlled trial. J Clin Psychiatry. 2011 Aug;72(8):1054-62. doi: 10.4088/JCP.10m05966blu. Epub 2010 Jun 15.
- Liao Y, Xie B, Zhang H, He Q, Guo L, Subramaniapillai M, Fan B, Lu C, Mclntyer RS. Efficacy of omega-3 PUFAs in depression: A meta-analysis. Transl Psychiatry. 2019 Aug 5;9(1):190. doi: 10.1038/s41398-019-0515-5. Review.