While the popularity of the anti-inflammatory potential of omega-3 fatty acids and curcumin continues to grow, the clinical utility of these compounds in mitigating inflammation that has been found in depression is still emerging. The focus of this blog will be on the evidence that investigates the role of omega-3s and curcumin on various indices of depression – more specifically, on the inflammatory pathways and cytokines that are currently thought to contribute toward depression’s etiology. 

The most common symptoms of depression include sadness, anxiety, fatigue, anhedonia, decreased motivation, appetite suppression, aggression, feelings of worthlessness, and suicidal ideation. These symptoms can be influenced by the complex interaction between monoamine neurotransmitters and various cytokines. Measuring cytokine levels is not regularly practiced in clinical settings; however, researchers have been measuring blood levels of cytokines in depressed populations for years, and newer evidence suggests that cytokine levels are elevated in depressed populations compared to controls – showcasing a possible clinical treatment option as adjuvant to standards of care. 

The Role of Inflammation in Depression

It is well-known that inflammation is a contributing factor to most of the preventable diseases that we are facing as a society today. Although inflammation is needed for survival in more acute situations like physical injury and infection, chronic inflammation occurring due to modifiable risk factors such as inactivity, nutrient-poor dietary choices, exposure to environmental and industrial toxins, and chronic psychological stress can lead to debilitating conditions that affect millions worldwide. More recently, evidence shows that depressed patients present with significantly higher levels of various inflammatory markers; namely, C-reactive protein (CRP), interleukin (IL)-3, IL-6, IL-12, IL-18, sIL-2R, and tumor necrosis factor-α (TNF-α). 

In the context of depression, one area where there is robust research is the complex interplay between cytokines and monoamines (e.g., serotonin, noradrenaline, dopamine, and glutamate). Briefly, several cytokine-driven pathways are thought to alter how monoamines interact at the synapse level. These alterations can include reduced serotonin availability by upregulating reuptake pumps through the synthesis of inflammatory molecules like reactive oxygen species (ROS), and by blocking production of brain-derived neurotrophic factor (BDNF) through binding of receptors. 

Now that the relationship between inflammation and depression is better understood, what, if any, food-derived compounds positively affect the higher levels of inflammation seen in depressed populations? As the use of alternative interventions for health is becoming increasingly prevalent, it is worthwhile to examine two well-known anti-inflammatory compounds: omega-3 fatty acids and curcumin.  

Evidence Supporting Omega-3 Intake in Depression

Omega-3 fatty acids are essential fats needed for human health. They are essential because humans cannot synthesize them. Omega-3s are found in a wide range of foods, and are especially prevalent in fatty fish including salmon, herring, anchovies, sardines, and mackerel, and in vegetarian food sources like flaxseed, chia seeds, and walnuts. Two omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been extensively studied in the context of depression. 

Investigating the role that any one compound has on a specific disease outcome is challenging in the nutritional epidemiology field as there are multiple compounding factors to consider. However, there are promising data that show clinical utility in a 2023 systematic review and meta-analysis by Kelaiditis and colleagues, which investigated the efficacy of EPA and DHA in improving depression severity. The results showed that in a combined depressed population of 1,426 individuals, intervention with EPA-rich capsules reduced depression severity at concentrations of ≥ 60% of total EPA and DHA and EPA doses between ≥1 and <2 g/day. This data has been confirmed by earlier work. However, these data prove to be equivocal at best. 

The mechanisms describing how EPA and DHA work to reduce inflammation are many, but it is well understood that they exert their anti-inflammatory power by decreasing the expression of several cytokines including IL-1β, IL-2, IL-6, and TNF-α — most of which have been found to be higher in depression. Another potential mechanism of omega-3 efficacy in reducing inflammation in depression is that EPA acts as a competitive inhibitor against arachidonic acid for phospholipase A2, reducing synthesis of the inflammatory eicosanoids. The anti-inflammatory effects of omega-3 fatty acids along with their generally low potential for harm in human subjects make them a compound that should be considered in any comprehensive treatment plan for depression. 

Evidence Supporting Curcumin Intake in Depression

Turmeric (Curcuma longa), a ubiquitous spice, has been used in traditional medicine for centuries due to its anti-inflammatory, antimicrobial, antioxidant, and anti-neoplastic properties. Curcumin is the main curcuminoid found in turmeric and has been studied extensively for its potential as a natural anti-inflammatory. A 2019 meta-analysis of 10 studies (N = 531; n = 285 in curcumin group, n = 246 in comparison group) reported a significant reduction in depressive symptoms for the intervention group as measured by several different scales (Hamilton Depression Rating Scale, full scale and 17-item scale; Montgomery-Åsberg Depression Rating Scale; the Beck Depression Inventory; and others). The authors discussed several mechanisms highlighting curcumin’s efficacy as a powerful antioxidant and anti-inflammatory compound. Most notably, curcumin has been shown to increase brain-derived neurotrophic factor levels and reduce expression of pro-inflammatory transcription factors (nuclear factor kappa B), both of which have been implicated in the pathoetiology of depression. Additionally, CRP, a primary marker of systemic inflammation and found to be elevated in depressed populations, is shown to decrease with curcumin intervention. 

Additional evidence supports the use of curcumin as an anti-inflammatory agent by significantly reducing inflammatory markers found to be elevated in depressed populations; namely, CRP, TNF-α, and IL-6. As mainstream society increasingly embraces natural and alternative interventions, integrating turmeric/curcumin alongside standard care can significantly improve symptoms and reduce inflammation in depressed populations. 

Learn more about omega-3 and curcumin:

Curcumin Supports Antioxidant Status through the Nrf2 Pathway

Do Omega-3 Fatty Acids Help Depression?

Do Omega 3 Fatty Acids Support Mood?

By Bri Mesenbring, MS, CNS, LDN