Review identifies potential modes of action for omega-3s and anxiety

By Hank Schultz contact

- Last updated on GMT

Review identifies potential modes of action for omega-3s and anxiety
A review conducted by researchers in New York uncovered six potential modes of action for how omega-3s might alleviate symptoms of anxiety. But the researchers found lots of nits to pick with the research, too, and made recommendations for future studies in this area.

The research was published online last week in the journal Nutritional Neuroscience​. The team of researchers from the City College of New York combed through 197 papers that examined the role of omega-3s supplementation in connection with cognitive outcomes like depression.

Authors left with small sample

Only six papers met the criteria for inclusion, covering a total of 496 participants. This was primarily because anxiety as an outcome cropped up fairly infrequently, but also because some of the research had questionable methodology, said lead author Ashley Polokowski, who is a PhD candidate at CUNY. 

“When reviewing the papers for inclusion, we knew that there was not going to be a significant amount of papers that fit into our criteria given that much of the omega-3 research in psychology has focused on depression and not anxiety; however, I do not think we were expecting only six in our final review. I think that conducting research early on in this field, it was difficult to rigorously test given the nature of researching nutrition. There are many variables at play and initial studies have to test different methods and interventions in order to see what is successful and make improvements as we move forward,”​ Polokowski told NutraIngredients-USA.

Polokowski and her co-authors found four potential modes of action for omega-3s in connection to anxiety. Those are inflammatory response, brain-derived neurotrophic factor (BDNF), cortisol, and cardiovascular activity.

Higher inflammation states have been associated with anxiety, and omega-3s have been shown to be helpful in this regard. BDNF is a protein that regulates nervous system functions by encouraging neuronal survival. Omega-3s are associated with higher levels of this protein. Cortisol is a stress-related cytokine, and omega-3s are associated with modulation of this factor. 

And in the cardiovascular activity mode of action, omega-3s have been associated with a modulation of heart rate variability. Lower variability (the time between heart beats) is associated with higher levels of anxiety.

Heterogenous research

Polokowski noted the research on omega-3s in this area is highly heterogenous, which greatly complicates the task of deriving an overall signal from the studies. Dosages were all over the map, with some studies using higher dosages of DHA than EPA or vice versa. Dosages ranged from a high of 2800 mg overall of omega-3s down to about 1500 mg of EPA and DHA, and one study administered 255 mg of ALA and LA (linolenic acid) in a 4:1 ratio.

The authors had these recommendations for future studies:

  • Standardization of dosage and duration of omega-3s supplementation
  • More rigorous measurement of variables
  • Effective blinding of participants
  • Designing experiments that test mediation
  • Increasing sample diversity. 

More rigor needed in studies

Harry Rice, PhD, chief science officer of the Global Organization of EPA and DHA Omega-3s (GOED), said it’s clear that the heterogeneity of omega-3s research is one of the things that clouds the message about the category.

“In general, I agree with the authors' recommendations for designing future studies investigating the mechanism(s) associated with EPA/DHA's ability to reduce anxiety. What the authors are recommending is rigor and that's table stakes when you're conducting research. The way I look at it is that it's more expensive in the long run to cut corners and draw the incorrect conclusions. I can't begin to tell you the number of publications concluding no benefit of omega-3s and when you get into the details, it appears the outcome(s) may have been different if the dose had been larger or the duration of treatment longer,” ​Rice said.

“While the experimental design of studies has improved slowly over time, some investigators still overlook some basics when designing their experiments. Not measuring pre- and post-treatment omega-3 levels, as well as not providing a high enough dose of omega-3s are two of my biggest criticisms when it comes to the design of RCTs, in general, but particularly in trials investigating an outcome measurement like anxiety, which is more prevalent in individuals with low omega-3 levels and seems to require multiple grams of omega-3s,”​ he added.

Source: Nutritional Neuroscience
Published online 28. Sept. doi.org/10.1080/1028415X.2018.1525092
“Omega-3 fatty acids and anxiety: A systematic review of the possible mechanisms at play”
Authors: Polokowski A, et al.

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