When your mom told you to eat your fish because it would make you smarter, she wasn’t just sharing an old wives’ tale. It turns out that today’s science continues to point to new and positive associations between omega-3 and brain health. And while consuming long chain omega-3 EPA and DHA found in fatty fish (and supplements) may not technically make you smarter, the scientific research is digging up brain-related benefits from this nutrient across a variety of brain-related functions.
To sum it up, we’re learning that omega-3 fatty acids EPA and DHA are essential nutrients that, among other benefits, help build your brain’s structure and regulate its ability to perform.
In this week’s blog we’ll review three studies published this summer that focus on omega-3 and the brain. Each study focuses on a different area of brain health: brain aging, Alzheimer’s disease and depression.
Although not providing definitive answers in these areas, the studies leave us and the scientific community wanting more. As science should.
These studies provide us with a greater impetus for better understanding of how omega-3 benefits the brain. And guess what: the science seems to be showing that, once again, mother knows best.
Let’s take a look.
Omega-3 EPA and DHA May Help Counteract the Effects of Air Pollution on the Brain
Air pollution is a growing problem, which environmentalists say is responsible for as many as five million premature global deaths each year.
When one thinks about the ravages of air pollution, demolition of lung function is likely what first comes to mind. But air pollution may also indirectly damage the brain, says a 2019 study in the scientific journal Brain, which found that exposure to tiny air pollutants, particulate matter with diameters generally 2.5 microns and smaller (PM2.5), may increase the risk of Alzheimer’s disease, related dementias and accelerated memory decline.
That’s what makes a new study published this month in Neurology, a journal of the American Academy of Neurology, so relevant for readers of this blog.
The researchers noted that omega-3 fatty acids had previously been shown to fight inflammation and maintain brain structure in aging brains. In addition, other research has found the nutrients reduced neurotoxin-related brain damage from lead and mercury. In this study, the authors specifically looked at whether omega-3 fatty acids could have a protective impact against a different and dangerous type of neurotoxin—PM2.5—found in air pollution.
The prospective cohort study was conducted among a subset of women enrolled in the Women’s Health Initiative Clinical Trials. From this population of 7,000 subjects in the late 1990s, approximately 1400 of those women were included in a subsidiary study known as the Women’s Health Initiative Memory Study-Magnetic Resonance Imaging (WHIMS-MRI) trial. The current study drew from the WHIMS population, using stored blood of 1315 dementia-free women, aged 65-80, who lived in areas with widely varying levels of air pollution levels.
It was designed to examine whether long-chain omega-3 fatty acid blood levels could modify the potential neurotoxic effects of PM2.5 exposure on normal-appearing brain volumes.
An article in nutraingredients-usa.com, based on an interview with OmegaQuant’s Dr. Harris, who is an author of this latest Neurology study, shared that the researchers also sought to correlate the effects of PM2.5 in the study cohort with those subjects’ omega-3 blood levels, as measured by the Omega-3 Index from OmegaQuant.
In the interview, Dr. Harris explained that using data from the original hormone therapy study was a creative way to look at this particular issue. He told the reporter, “I was very surprised to hear about the protective effect of omega-3s in this area” and although it was unclear as to how the nutrients worked protectively, Dr. Harris presumed it might be from some sort of anti-inflammatory effect.
The study authors advised more research should be conducted to determine whether these results could be generalized to the wider population.
New Alzheimer’s Study Finds Using the Proper Dose of Omega-3 is Key to Finding Benefit from the Nutrient
In order for omega-3 fatty acids to benefit the brain, they have to find a way to get into the brain. Another study examined this question in Alzheimer’s disease (AD) patients. AD is a form of dementia and a brain-crippling disease that leaves family and friends of patients to watch helplessly as their loved ones disappear into an fog of severe memory loss, erratic behaviors and isolation. Around 5.7 million Americans have AD, and about 50 million people worldwide have some form of dementia. There is no known cure.
Animal models and observational studies of omega-3 EPA and DHA have shown an association between higher levels of these fatty acids and lower incidence of AD and dementia. To date, clinical trials testing the direct effects of omega-3 supplementation on AD have by and large come up with disappointing results. Why?
Now researchers at the Keck School of Medicine at the University of Southern California (USC), in announcing results of a pilot study, think they may understand why. It could be the dose.
Why Does Dose Matter?
Here’s something to consider: The USC study used a daily dose over 2 grams of DHA, a dose which far exceeded what has typically been used in previous clinical trials testing the preventive power of omega-3s, which is typically 1 gram or less daily. And with the higher dose, they saw some positive results.
But let’s not get ahead of ourselves.
Although a previous study tested the effects of high doses of omega-3 on blood and cerebrospinal fluid (CSF, the fluid that bathes the brain) in patients with AD, USC’s clinical trial was the first to examine this question in people without AD.
The study population consisted of 33 participants from Los Angeles—men and women aged 55 and older—who, although not being cognitively impaired themselves, had a family history of the disease. Typically American, they had generally sedentary lifestyles and they ate little to no fatty fish. None had taken omega-3 fatty acid capsules for at least three months prior to the study.
Approximately half of the group (15 people) carried a gene variant known as APOE4, which is linked to inflammation in the brain and is a known factor for increasing AD risk by a factor of four or more. This will become important later on.
Participants were randomly assigned to either the treatment group or the control group. Those in the treatment group were required to take omega-3 supplements containing 2,152 mg of DHA for 6 months and were also provided instruction to otherwise limit their polyunsaturated fatty acid intake. The control group was instructed to take similarly looking placebo capsules which contained corn/soy oil. Both groups were instructed to take daily vitamin B complex supplements which help the body process omega-3s. Compliance was assessed for both groups by pill counting.
All participants were seen three times: at screening, baseline and 6 months (end of study). The researchers were looking for changes in plasma and CSF levels of DHA and EPA and how these correlated with APOE status (E4 or not) and CSF levels of a biomarker of brain amyloid deposition (A-beta-42). Cognitive function tests were also given.
What did they find? They found that using an appropriate dose is crucial.
More About the Results
At the study’s conclusion, the treatment group had a 200 percent increase in their blood plasma DHA levels compared with the placebo group, but the DHA in the CSF went up by only 28 percent. But that 28% increase was better than that previously reported with lower DHA doses.
In both the plasma and CSF measurements, the percentage increase for DHA for those who did not carry a copy of the APOE4 gene (which is the case for about 75% of Americans) tended to be higher than for those who were carriers.
Further, those in the treatment group who did not carry the APOE4 gene variant showed an increase of EPA in their CSF, which was three times greater than that seen in the APOE4 carriers. (Recall that only DHA was supplemented, not EPA. This finding implies that DHA can, to some extent, raise both DHA and EPA levels in the body).
Remember, this study used a dose of over 2 grams of DHA daily versus many previous clinical trials that administered 1 gram or less daily.
Here Are the Key Takeaways
The study authors believe these results hint that omega-3 levels in the blood may not indicate how much EPA and DHA is reaching the brain. That’s to be expected because of the blood-brain barrier, which carefully protects the brain by letting only certain compounds in from the blood), could potential make it harder for some nutrients to reach the brain. Therefore, future research should strongly consider whether a dose of 2 grams daily of omega-3 is enough to find benefit for a disease like AD or whether even higher doses should be administered
This may be especially true for those who have known risk factors for AD… like carrying the APOE4 gene variant. It appears that these people may be less able to transfer DHA from the blood to the brain than those who don’t carry the gene. This further highlights the need for researchers to consider studies with higher doses of omega-3s.
These study results also reinforce the unique relationship of nutrients to an individual—how much of a nutrient one needs, in this case omega-3 fatty acids, is related to your lifestyle, dietary patterns, genetics, ability to absorb nutrients, and more.
What you need depends on how much you already have. And fortunately, a simple blood test like the Omega-3 Index that measures your blood levels of EPA and DHA can be used in research studies (and by individuals) to determine baseline levels and to monitor improvements with supplementation. The goal is to reach the optimal index of 8-12%. This study reinforces the need for researchers to measure omega-3 levels at baseline and at the conclusion of their studies in order to better understand what Omega-3 Index level is associated with the best outcomes.
Dr. Harris was not an author on this USC study; however, OmegaQuant conducted the fatty acid analysis for this trial. Upon seeing the results, Dr. Harris believes that “the use of approximately 1 gram daily of omega-3 EPA and DHA fatty acids in dementia research may be too low a dose to raise brain DHA levels, especially in people carrying a APOE4 gene variant. We will likely need to see doses of omega-3s even higher than 2 grams daily to reach the full potential benefit of DHA.”
As for the USC researchers, the results of their study were sufficiently intriguing to attract funding for a larger trial for which recruitment is underway. They plan to follow over 300 participants over a two-year period to examine whether high doses of omega-3s can slow cognitive decline in the carriers of the APOE4 gene.
Dr. Hussein Yassine, senior author on the study and associate professor of medicine and neurology at USC’s Keck School of Medicine said, “These pilot studies are so important as a step toward much larger, more complicated studies.”
“Alzheimer’s is a very complex, multi-factorial disease,” advised Dr. Harris. “The results of this study may be a key to research unlocking a preventive measure involving omega-3 EPA and DHA, but consumers should not rush to use that key just yet. The role of omega-3 in helping prevent Alzheimer’s need further exploration. But the good news is we’re now in an era where personalization plays such an important role in health. As a first step for taking omega-3s, it makes sense to find out your Omega-3 Index to determine how much, if any, additional DHA and EPA you need.”
New Meta-Analysis on Perinatal Depression Finds Positive Omega-3 Benefits
Moving from “brain-issues” in older people to those affecting younger women, another recent study—this one a meta-analysis—examined the safety and efficacy of omega-3 fatty acids in a different area of brain health—perinatal depression, which is generally defined as onset of a depression episode, ranging from mild to severe, during pregnancy or postpartum within one year after delivery.
After a thorough literature review, researchers from Peking University, Beijing, and other Chinese-based universities and hospitals and research centers, identified eight randomized controlled trials that met their inclusion criteria. These trials together included 638 participants. The studies were all randomized double blind placebo-controlled trials evaluating the efficacy of omega-3 monotherapy in perinatal depression.
The meta-analysis, published online in Translational Psychiatry on June 17th, found a significant effect of omega-3 EPA and DHA on mild-to-moderate perinatal depression when compared to placebo.
Further, the authors found that these nutrients were well-tolerated with low incidence of side effects. In fact, among the included trials reporting adverse effects, there was no significant difference in incidence of gastrointestinal and neurologic events between the omega-3 and placebo groups, they added.
The researchers noted they also evaluated the effects, separately, in the pre- and post-natal periods and found the effects were significant in both, but were more obvious during postpartum time frame.
In the discussion of their study, the authors gave a nod to the importance of DHA, especially during the perinatal period when DHA is transferred from moms to babies for brain development and retina maturation, either through placenta or breastfeeding.
Therefore, they warned, there are higher risks of omega-3 deficiency for mothers without timely and proper supplementation.
The study had several limitations as pointed out by the authors, including the fact that the sample size and number of studies included were relatively small. In addition, they were unable to suggest an appropriate dosage range at which the benefits were found.
The exact mechanism through which omega-3s improved the depressive symptoms in perinatal women remains unclear.
The authors are calling for more studies, specifically high-quality randomized controlled trials with bigger sample sizes to verify their conclusions.
INFOGRAPHIC: 10 Reasons Every Pregnant Woman Needs to Know Her DHA Level