Clinical trial showed that seafood-source omega-3s enhanced circulation
The notion that our brains and spirits benefit from fish habits dates back centuries.
In fact, the origins of fish-veneration date back at least 7,000 years, to the Sumerian civilization: possibly the first in history.
Twelve years ago, leading omega-3 and brain researcher Joe Hibbeln, M.D. — a clinical psychiatrist at NIH — co-wrote a scientific paper on fish as a worldwide cultural symbol.
As Dr. Hibbeln and his co-author wrote, “… fish have been culturally labeled as symbols of emotional well-being and social healing in religious and medical practices among independent cultures, for at least six millennia.”
They reported that fish is a sacred symbol in ancient Egyptian theology — the key goddess Isis is often shown with a fish on her head — as well as in the texts and traditions of Judaism, Christianity, Hinduism, Buddhism, Shintoism (Japan), and Islam.
Likewise, China’s ancient yin-yang icon represents two simplified fish figures swimming in a circle — signifying the dual nature of the universe and its endless cycles.
Dr. Hibbeln and his co-author noted that this history fits with the fact that, as they said, “Consumption of long-chain omega-3 fatty acids, [which are only] rich in seafood, reduces depression, aggression and anger while improving mental well-being.” (Reis LC, Hibbeln JR 2006)
And while it’s not scientific evidence, the case of a 115-year-old Dutch woman — whose brain-autopsy revealed its amazingly youthful status — echoes myth and folklore linking fish to wisdom: see Oldest Woman was Still Sharp: Did Daily Herring Habit Help?.
Before we get to the encouraging results of a recent clinical trial, let’s review previous findings about the effects of “fishy”, seafood-source omega-3s on brain structure and functions.
The brain effects of fishy omega-3 fats
Growing evidence links higher fish intakes or blood levels of seafood-source omega-3 fatty acids (DHA and EPA) to sharper thinking and memory — even in middle-aged and younger people — and to delayed onset of dementia and/or milder symptoms.
So perhaps it shouldn’t be a surprise that MRI and other brain scans reveal that diets rich in fishy omega-3s enhance people’s brain size, structures, and networks.
For more on that topic, see these past reports: Omega-3s May Slow Brain Shrinkage, Omega-3s May Expand, Sharpen Brains, Brain Benefits of Fish Bolstered by MRI Study, and Fish Oil Aided Size and Health of Aging Brains.
And a 2017 report from a team led by prominent brain specialist Daniel Amen M.D. found that fishy omega-3s enhanced blood flow in areas of the brain critical to key functions.
As we reported then, Dr. Amen’s team divided 166 people into two groups, based on their blood levels of omega-3 DHA and EPA, and subjected them to a type of brain scan called single photon emission computed tomography or SPECT.
When the participants' brain images were compared to their omega-3 levels, the results linked higher omega-3 levels to better blood flow in brain regions important for learning, memory, depression, and dementia.
The results also showed statistically significant links between higher omega-3 levels and better performance on neurocognitive (thinking, memory, and mood) tests.
Overall, the study linked higher omega-3 EPA+DHA blood levels to fuller blood flow in key regions, and to improved brain performance.
Dr. Amen summarized the meaning of their findings: “This is very important research because it shows a correlation between lower omega-3 fatty acid levels and reduced brain blood flow to regions important for learning, memory, depression and dementia.”
For more details, see Big, Brainy Omega-3 News, in which we reported the results of three related studies, including Dr. Amen's.
The results of a more recent clinical trial support those findings and may help explain why fishy omega-3s appear to enhance brain volume, structure, networks, and performance.
British-Australian clinical study finds that omega-3s boost blood flow
The new clinical trial was performed by scientists from Britain’s University of Newcastle and Australia’s University of Southern Queensland (Howe PRC et al. 2018).
Previous studies by this same team showed that dietary supplementation with resveratrol (an antioxidant found in grapes), wild green oat extract (high in antioxidants) and (more surprisingly) peanuts can improve both brain blood flow and cognitive (thinking/memory) performance.
They wondered whether fishy omega-3s (DHA and EPA) would produce similar effects, so they conducted a small, randomized, placebo-controlled “pilot” clinical trial designed to test that possibility.
And they chose to test a particularly DHA-rich fish oil, which made sense for three reasons:
- DHA is the most abundant fatty acid in the human brain.
- DHA plays key roles in the structure, growth, and functions of brain cells.
- The body can easily convert dietary DHA into EPA — also important to brain and psychological health — but not vice versa.
The British-Australian team recruited 38 qualifying participants who had borderline hypertension, were between the ages of 40 and 85, and had low habitual intakes of omega-3s from fish and/or supplements.
Average seafood consumption (most commonly salmon and tuna) among the participants was 125 grams (4.4 ounces) per week, and only five of the 38 participants were taking ﬁsh oil supplements.
None of the participants exceeded the exclusion limit for omega-3 supplementation, which was 300 mg per day. And the researchers estimated that the participants’ average EPA + DHA intake at the outset of the trial was about 200mg per day, with no difference between sexes.
In addition, potential participants were excluded if they had signs of dementia, smoked or used nicotine, had neurological, kidney, or liver disease, diabetes, major depression, or impaired vision, and were could not maintain their normal activity levels and diets during the trial.
The qualifying volunteers were randomly divided into two equal groups, and each was assigned to a different daily regimen for the 20-week trial:
- Control group: Placebo capsules containing corn oil.
- Omega-3 group: Fish oil capsules providing 1600mg of DHA + 400mg of EPA.
Blood flow in the middle cerebral artery of each participants’ brains was measured at the outset of the trial and after 20 weeks, using a method called transcranial Doppler ultrasound.
Each participants’ brain blood flow was measured while they were at rest and again while performing a battery of cognitive tests.
The results of those tests are known to reflect — in part — the quality of the connection between neurons (brain cells) and their blood supply, or so-called “neurovascular coupling”.
The primary outcome they measured was greater blood and oxygen flow to the brain in response to excessive levels of carbon dioxide in the blood — called “hypercapnia” — which are typically caused by inadequate uptake of oxygen from the lungs.
And, compared with the placebo group, the fish oil group showed these differences:
- Better blood flow in response to hypercapnia rose by 26% in women, but there was no change in men.
- Neurovascular coupling grew significantly in men only and was linked with rises in the levels of EPA in their red blood cells, rather than rises in DHA levels — even though the fish oil capsules contained substantially more DHA than EPA.
Overall, the fish oil group enjoyed better blood flow responses during a test designed to measure executive function, and better blood flow responses to the overall battery of cognitive tests.
Interestingly, improved blood flow in response to the overall battery of tests was driven largely by positive changes in men.
In fact, every cognitive test appeared to trigger better brain blood flow among men in the fish oil group, compared with those in the placebo group.
Unlike prior trials, few gains in cognition: Why?
As in many other trials, a prior clinical trial from some of the same researchers found that fish oil produced significant cognitive gains, especially from a high-EPA version: see Omega-3 Trial in Seniors Finds Mood & Brain Benefits.
So, they were surprised their new trial didn't detect significant improvements in mood or cognition among participants in the fish oil group.
They speculated that this might have been due to the relatively short duration of the trial, because the doses of omega-3 EPA weren’t high enough, or because the number of participants was too small.
Surprisingly, the blood flow improvements were linked with rises in red blood cell levels of EPA, not DHA, which was at odds with their presumption that DHA would be the primary “active ingredient”, but fits with the results of their earlier clinical trial.
That presumption was based on other studies that have linked DHA rather than EPA to increases in brain blood flow — which seems more in line with the general evidence concerning the roles of DHA and EPA.
They also noted that, despite having mild hypertension, which is a risk factor for cognitive impairment, the blood flow dysfunction seen in the participants may not have been bad enough to compromise their cognitive function.
That possibility fits with the results of an earlier trial from some of the same authors, which detected improvements in verbal ﬂuency among older people with mild cognitive impairment who took supplemental omega-3 DHA.
The authors summarized the overall results this way: “Despite a lack of change in mood or cognition outcomes, the present study adds to a growing number of studies suggesting that omega-3 supplementation can inﬂuence brain functions at least in part by enhancing cerebrovascular function, which may potentially delay future cognitive decline.”
Since it takes years or decades for brain function to decline, it makes sense to ensure ample intakes of both seafood-source omega-3s — DHA and EPA — throughout life, from seafood (especially fatty fish) and/or supplements.
- Amen DG, Harris WS, Kidd PM, Meysami S, Raji CA. Quantitative Erythrocyte Omega-3 EPA Plus DHA Levels are Related to Higher Regional Cerebral Blood Flow on Brain SPECT. J Alzheimers Dis. 2017;58(4):1189-1199. doi: 10.3233/JAD-170281.
- Howe PRC, Evans HM, Kuszewski JC, Wong RHX. Effects of Long Chain Omega-3 Polyunsaturated Fatty Acids on Brain Function in Mildly Hypertensive Older Adults. Nutrients. 2018 Oct 2;10(10). pii: E1413. doi: 10.3390/nu10101413.
- Kuszewski J, Wong R, Howe P. Effects of long-chain omega-3 polyunsaturated fatty acids on endothelial vasodilator function and cognition—Are they interrelated? Nutrients 2017, 9, 487.
- Reis LC, Hibbeln JR. Cultural symbolism of fish and the psychotropic properties of omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):227-36. Epub 2006 Sep 7. Review.
- Sinn N, Howe, PRC. Mental health beneﬁts of omega-3 fatty acids may be mediated by improvements in cerebral vascular function. Biosci. Hypotheses 2008, 1, 103–108.
- 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]