May 17, 2022
Written by: Morgan Kindel
Dietary fat has a bad rap these days. Practically the second you walk into a grocery store, you are almost guaranteed to see the words “low-fat” or “fat-free” as a selling point for a food item. But here’s the thing: our brains actually need fat to function. Fat is essential for a wide range of brain functions, from neuronal signaling, to formation of neuronal membranes, to the synthesis of messenger molecules (neurotransmitters) themselves.
But before dousing your next meal in butter in the name of brain health, it’s important to acknowledge that there are different types of dietary fats that differ in the effects they have on your brain.
When we think about dietary fat, what we’re usually considering is a group of molecules called fatty acids (FAs). Despite there being many different types of fatty acids, these molecules all share some common features. One important shared feature is a chain of carbon and hydrogen atoms, called a hydrocarbon chain. If you’ve ever read a nutrition label on the back of a food, you’ve probably seen that fats can be classified as either saturated or unsaturated. This classification is determined by small differences in the structure of the hydrocarbon chain. Interestingly, this small change leads to huge differences in the properties of these fats. Compare butter (a saturated fat) with olive oil (an unsaturated fat) – butter is solid at room temperature, whereas olive oil is liquid. These differences between butter and olive oil can all be boiled down to the absence of just a few hydrogen atoms!
Unsaturated fats can be further classified into either monounsaturated or polyunsaturated, depending on how many hydrogen atoms are missing. And depending on which carbons in the chain are missing a hydrogen, polyunsaturated fatty acids can be even further classified.
One group of polyunsaturated fatty acids, omega 3 fatty acids (FA) is especially noteworthy in the context of brain health and wellbeing.
If you’ve ever heard about the brain-boosting benefits of omega 3 FA’s before, you’ve likely heard about them in the context of cognition. Indeed, there is ample evidence that dietary omega 3 FAs reduce aging-related deficits in memory and learning. However, a lesser known (but equally exciting) effect of omega 3 FAs on the brain is its effects on our mood.
How can a fat molecule, of all things, have the power to alter our mood? This question has been a central driving force for much of the research surrounding omega 3 FAs and mood, and (spoiler alert) we don’t have too many concrete answers just yet. But scientists are starting to uncover some of the ways in which omega 3 FAs act in the brain to alter mood and behavior1.
One of the most effective ways to understand the function of something is to remove it and see what “breaks”. Because animals (including humans) cannot synthesize omega 3 FAs on our own, we are left to rely on dietary sources of omega 3 FA’s. So, removing dietary omega 3 can give scientists a pretty good idea of what omega 3 is normally doing. For example, simply removing omega 3 from the diets of rodents2,3 shows an astounding increase in depressive-like behaviors. Perhaps even more interestingly, the onset of these depressive-like behaviors is associated not just with decreased levels of omega 3 FA’s in the brain, but also decreased levels of the neurotransmitter serotonin4, which plays a role in mood regulation.
In line with this, levels of omega 3 FAs in the brain have also been linked to mood disorders, such as depression and anxiety, in humans. Clinical studies have shown that individuals who consume lower levels of omega-3 have an increased risk of developing a mood disorder5. Additionally, omega 3 FA levels in the prefrontal cortex of postmortem brains of individuals with depression have been shown to be reduced compared to individuals without depression6. However, these are just correlational studies. A correlational study examines whether two things (in this case, omega 3 FA intake and depression) are related – so, lower omega 3 intake is correlated with a higher risk of depression. What this study does not show is that a lower omega 3 intake causes depression; it could also be that depressed individuals prefer eating foods lower in omega 3, or there could be some other factor influencing both omega 3 FA levels and depressive symptoms. However, in combination with results from the previously mentioned experimental studies in rodents, it is plausible that low levels of dietary omega 3 FAs reduce omega 3 FA levels in the brain, which could decrease serotonin levels and explain the increase in depressive-like symptoms.
But what about on the other end of the spectrum? Can adding omega 3 to your diet boost your mood or protect against the development of mood disorders? Studies in both rodents and humans suggest it can. In one study4, rats given supplemental omega 3 FAs not only showed an increase in omega 3 FA levels in the brain, but also an increase in serotonin! And, although technical limitations prevent us from measuring levels of these molecules in living humans, there is indirect evidence that omega 3 FA supplements may have similar effects in humans.
So, omega 3 FA is important for mood regulation and protective against depression, possibly by modulating levels of neurotransmitters in the brain. But how? It turns out that omega 3 FAs are precursors for another class of neurotransmitters in the brain called endocannabinoids (eCBs). As a result, levels of eCBs in the brain are increased by omega 3 consumption, and eCBs interact with the serotonin system in the brain, to powerfully change how much serotonin is released, and to which neurons in can bind to7. Although this line of research is in its early stage, these findings present the exciting possibility of new approaches to treating symptoms of depression.
In fact, some research even suggests that the magnitude of the effects of increasing dietary omega 3 FAs compares to those of selective serotonin reuptake inhibitors (SSRIs). SSRIs, one of the most common medications prescribed to treat major depressive disorder, work by increasing levels of serotonin the brain. In one study8, individuals diagnosed with major depressive disorder were treated with either EPA (a type of omega 3 FA), the SSRI fluoxetine, or a combination of both for eight weeks. Depressive symptoms of the participants were assessed before, during and after eight weeks of treatment. They found that EPA alone had the same level of effectiveness as fluoxetine on reducing depressive symptoms—symptoms reduced by about 50% in each group. However, when EPA and fluoxetine were taken in combination, the researchers found more than an 80% decrease in depressive symptoms. One limitation of this study was a lack of placebo groups, so it is possible that the placebo effect could have driven at least some of these effects. Despite this, these results are exciting because they suggest that omega 3 FA’s have potent anti-depressive actions that could be complementary to those of SSRIs.
While these findings are promising, it is important to remember that, as is the case with any supplement or nutrient, omega 3 FAs are not simply a “cure all”, in that they cannot and should not replace medications prescribed by medical doctors. That said, it is exciting to consider the possibility that making small dietary changes, such as eating more omega 3 rich foods like fish, walnuts, and flax seeds, or by taking an omega 3 FA supplement, can be a relatively accessible and safe way to boost your mood.
1. Bazinet, R. P. & Layé, S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat. Rev. Neurosci. 15, 771–785 (2014).
2. Bondi, C. O. et al. Adolescent Behavior and Dopamine Availability Are Uniquely Sensitive to Dietary Omega-3 Fatty Acid Deficiency. Biol. Psychiatry 75, 38–46 (2014).
3. DeMar, J. C. et al. One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats. J. Lipid Res. 47, 172–180 (2006).
4. Chalon, S. Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot. Essent. Fatty Acids 75, 259–269 (2006).
5. Lin, P.-Y., Huang, S.-Y. & Su, K.-P. A Meta-Analytic Review of Polyunsaturated Fatty Acid Compositions in Patients with Depression. Biol. Psychiatry 68, 140–147 (2010).
6. McNamara, R. K. et al. Selective Deficits in the Omega-3 Fatty Acid Docosahexaenoic Acid in the Postmortem Orbitofrontal Cortex of Patients with Major Depressive Disorder. Biol. Psychiatry 62, 17–24 (2007).
7. Haj-Dahmane, S. & Shen, R.-Y. Modulation of the Serotonin System by Endocannabinoid Signaling. Neuropharmacology 61, 414–420 (2011).
8. Jazayeri, S. et al. Comparison of Therapeutic Effects of Omega-3 Fatty Acid Eicosapentaenoic Acid and Fluoxetine, Separately and in Combination, in Major Depressive Disorder. Aust. N. Z. J. Psychiatry 42, 192–198 (2008).
Cover Image by by Ulrike Leone (Pixabay)
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