Fats for Thought: How Omega-3 and Olive Oil Impact Depression

Evidence suggests that inflammation plays a crucial role in the pathophysiology of depression. We’ve previously delved into the role of lipopolysaccharides (LPS), which are cell wall components of gut bacteria, in triggering inflammation through the TRL4 cellular signal in immune cells.

LPS in the gut can find its way into the bloodstream via chylomicrons, lipid proteins that facilitate the transportation of dietary fats for metabolism in the liver. When LPS enters the bloodstream, it prompts the activation of immune cells in the blood, leading to systemic inflammation and potentially affecting brain inflammation, thereby impacting mental health. This connection with depression and anxiety is well-established, as evidenced by animal experiments where depression models are often induced in mice through LPS injections.

It’s worth noting that not all dietary fats contribute to elevated LPS levels in the blood, and consequently, their impact on inflammation and mental health varies. There are two specific types of fats that have a positive influence on inflammation and mental well-being.

Fats in the diet that are friendly to mental health

Replacing cooking oil with olive oil may help reduce inflammation and improve depression and anxiety. In a randomized crossover trial conducted in 2015 [1], 28 participants consumed foods with different proportions of palmitic acid (a saturated fat) and oleic acid (a monounsaturated fat) for three consecutive weeks. Animal fats contain more palmitic acid, while olive oil is representative of high oleic acid content. The study showed that consuming foods with higher levels of palmitic acid increased the production of inflammatory cytokines (TNF-a) induced by LPS, leading to inflammation. On the other hand, consuming foods with higher levels of oleic acid reduced inflammatory cytokines. Therefore, consuming olive oil does not increase LPS, while saturated fats increase LPS in the bloodstream.

Including seafood and fish rich in omega-3 fatty acids in your diet is also helpful. Plant oils commonly used for cooking, such as corn oil and soybean oil, are typical representatives of omega-6 fatty acids. Although both omega-3 and omega-6 fatty acids are polyunsaturated fats, their effects on human health are significantly different. Both EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are major types of omega-3 fatty acid.  In a study from 2006 [2], which compared omega-3 fatty acids in 27 social anxiety disorder patients with 22 healthy individuals in a control group, it was found that the anxiety disorder patients had 36% lower EPA and 18% lower DHA levels than the healthy control group.  Aside from the differences in omega-3 fatty acids, there were no significant variations in the values of other fatty acids between the patient group and the healthy group.

In another clinical trial [3], 68 healthy university students were divided into two groups. The omega-3 group consumed 2g of EPA and 0.35g of DHA daily for 12 consecutive weeks. The results showed a 14% reduction in the pro-inflammatory cytokine (IL-6) caused by LPS, along with a 20% reduction in anxiety symptoms. This demonstrates that supplementing with omega-3 can reduce inflammation and alleviate anxiety symptoms.

Supplementing with EPA-Dominant Fish Oil

Fish oil is a fatty acid derived from fish and seafood, rich in omega-3 fatty acids (n-3). However, fish oil is not exclusively composed of omega-3. In regular fish oil, approximately 30% is omega-3, while the remainder consists of other fats, including saturated fats, n-6 fatty acids, and monounsaturated fats. Since the human body cannot synthesize omega-3 fatty acids independently, it must acquire them from dietary sources. Fish oil contains two of the most critical omega-3 fatty acids for human health: EPA and DHA.

In our daily diet, obtaining a sufficient quantity of omega-3 fatty acids can be challenging, which makes using fish oil supplements a more practical approach. A 2014 meta-analysis [4] demonstrated the benefits of fish oil containing omega-3 in the treatment of severe depression patients. Additionally, a 2019 meta-analysis [5] indicated that fish oil with over 60% EPA, at a daily dose of less than 1g, can be a helpful treatment for depression.

A 2012 study [6] highlighted the significant impact of omega-3 fatty acid supplementation in the treatment of depression. This study also classified previous clinical research and determined that those with more than 60% EPA were more successful in treating depression when compared to those with less than 60% EPA. While both EPA and DHA in fish oil are essential for overall health, EPA outperforms DHA in the treatment of depression.

Similarly, a 2014 meta-analysis [7] came to a parallel conclusion after examining 19 clinical studies focused on depression. The consensus was that omega-3 fatty acid supplementation is effective for managing depression, but the EPA content in fish oil significantly influences the results, with EPA proving more effective than DHA in the context of omega-3 fatty acids for depression treatment.

Summary

Dietary fat can transport LPS from the gut to the bloodstream, stimulate the immune system, and lead to the production of inflammatory cytokines, which may result in damage to the blood-brain barrier and the development of brain inflammation.

Omega-3 fatty acids in fats (such as fish oil) are the most beneficial for mental health. They not only do not increase LPS in the blood but can also reduce inflammation.

Omega-6 fatty acids in fats (found in vegetable oils like soybean oil and corn oil) are not friendly. As long-chain fatty acids, omega-6 fatty acids transport LPS into the bloodstream through chylomicron formation, leading to inflammation.

Monounsaturated fats in fats (like olive oil) do not increase LPS in the blood and are considered friendly fats.