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Can Tylenol Cure Depression?

To the detriment of our own health, we have siloed mental and physical health as separate things. Despite a plethora of research showing how the two are interwoven and impact one other, we still have professionals who treat only the body and those who treat only the mind.


Let me give you one salient example. In 2019 a systematic review was published by the Journal of Neurology, Neurosurgery and Psychiatry showing that several over the counter anti-inflammatory medications (such as ibuprofen) and omega 3 fatty acids – both anti-inflammatories – produced significant improvement in depressive symptoms (PMID: 31658959).


Long before this review, evidence was emerging that showed people who went on anti-inflammatories for autoimmune conditions (like arthritis) experienced a “side-effect” of improvement in their depression symptoms.

 

In fact, some studies suggest the way that serotonin reuptake inhibitors (e.g. Prozac) works is not directing by increasing serotonin in the brain, but by their secondary mechanism of reducing inflammation in the brain.

 

As a result, there is now a plethora of research correlating inflammation in the brain with the clinical manifestation of depression.

 


So, why isn’t every psychiatrist (and every primary care doctor who prescribes psychiatric meds) working on reducing a patient’s inflammation?? Because it takes time and effort, and it's much easier to write a prescription. And - they may just not know how.

 

With our current disease-care model, you have to take your health into your own hands.


How do you know if you are inflammed? There are some tale-tale signs and symptoms of inflammation in the body in addition to depression. And of course you should always test when able.


Brain fog, chronic fatigue, bloating, unexplained weight gain or inability to lose weight, poor concentration, and poor sleep are all signs you may be inflamed.


Good blood tests (but not perfect) are: hsCRP, Vitamin D, homocysteine, omega 3 index, HbA1c, fasting glucose and fasting insulin.


Why test blood sugar? Becuase metabolic health and inflammation often go hand-in-hand.

 

Now might be a good time to mention that I am in no way suggesting you should take Tylenol daily for depression. These studies on NSAIDs are less about treatment and more about pathophysiology, that is, they give us insight into the biologic cause of depression.


There are many ways to reduce inflammation in the body besides taking over-the-counter NSAIDs (or antidepressants) which have harmful side effects which make long term use unsustainable.

 

Here are some natural ways to reduce inflammation: 

 

1.     Work on gut health. The gut microbiome is key to reducing inflammation. Gut health impacts inflammation through the composition and balance of gut microbiota, the integrity of the gut barrier, and the interaction of gut-derived metabolites with the immune system.

2.     Eliminate highly processed foods. As a general rule of thumb, if it comes in a bag or has more than three ingredients, it’s probably processed. I recommend everyone try a modified elimination diet to see what works best for you. Highly processed would include cooking oils used incorrectly. Each oil has a smoking point and you should be aware of which oil is safe to use and when. Here is a good article covering the most commonly used cooking oils.

3.     Focus on good fats. This includes avoiding fried foods, easily the most inflammatory of all food groups. While I don’t demonize all seed oils, I have seen in my own practice that people who avoid foods with sunflower, safflower, peanut, soybean and canola oil tend to have lower levels of inflammation. We want to preferentially select foods with high quality omega 3 fats in our diet because these fatty acids are broken down into anti-inflammatory cytokines. Read more about omega 3 and 6 fats below.

4.     Move. Your. Body. Exercise is beneficial for so many reasons. In the case of inflammation, movement works by increasing blood and lymph flow which helps the body get rid of waste. It also increases BDNF, brain derived neurotrophic factor, a growth factor released when we do vigorous exercise which encourages new growth and connections between brain cells. Many studies have shown that a depressed brain is a disconnected brain. The nerve cells no longer talk to one another - they are isolated (what a metaphor for depression, right?). Side note, BDNF is also produced when nerve cells are exposed to ketamine.

5.     Eliminate problematic foods specific to your genetics. I have one gene coding for Celiac’s disease. While it takes two mutated genes to be diagnosed with full-blown Celiac's, I have found that having one gene is enough to develop sensitivities to gluten significant enough to cause a rise in inflammatory markers on blood tests. In my opinion, there are currently no good tests for food sensitivities. The best way to find your personal sensitives is with an elimination diet coupled with testing to confirm what's working.

6.     Adds herbs and spices to your diet. Turmeric, saffron and rosemary and are particular good anti-inflammatory foods to add into your diet. Eliminate vegetable oils and cook with avocado, ghee or olive oil (be sure to understand the smoke point of each kind of oil and choose accordingly).

7.     Supplement when needed. If you’re not a culinary daredevil, you can take anti-inflammatory compounds in supplement form. Highest bang for your buck? A high quality fish oil (get at least 1 gram per day), curcumin (the active in tumeric), Vitamin D (if deficient) and probiotics.

 


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Deep Dive on Omega Fats:

Omega-3 and omega-6 fatty acids are both essential polyunsaturated fatty acids (PUFAs) that play critical roles in the body, but they have different effects on inflammation due to the distinct types of eicosanoids they produce.




Omega-3 Fatty Acids

  1. Sources and Types:

  • Major sources include fatty fish (like salmon, mackerel, and sardines), flaxseeds, chia seeds, and walnuts.

  • The primary omega-3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

  1. Mechanism of Action:

  • Anti-Inflammatory Eicosanoids: Omega-3 fatty acids, particularly EPA and DHA, are metabolized into eicosanoids, such as prostaglandins and leukotrienes, which are less inflammatory compared to those derived from omega-6 fatty acids.

  • Resolvins and Protectins: EPA and DHA are also precursors to specialized pro-resolving lipid mediators (SPMs) like resolvins and protectins. These compounds actively resolve inflammation and promote healing.

  • Gene Expression: Omega-3 fatty acids influence gene expression related to inflammation. They can inhibit the activity of NF-κB, a protein complex that controls the transcription of pro-inflammatory genes.

Omega-6 Fatty Acids

  1. Sources and Types:

  • Major sources include vegetable oils (such as corn oil, soybean oil, and sunflower oil), poultry, eggs, and nuts.

  • The primary omega-6 fatty acid is linoleic acid (LA), which is converted in the body to arachidonic acid (AA).

  1. Mechanism of Action:

  • Pro-Inflammatory Eicosanoids: Arachidonic acid (AA), derived from omega-6 fatty acids, is metabolized into eicosanoids such as prostaglandins, thromboxanes, and leukotrienes, which tend to be more pro-inflammatory.

  • Balance and Competition: Omega-6 and omega-3 fatty acids compete for the same enzymes (cyclooxygenase and lipoxygenase) for conversion into their respective eicosanoids. A higher intake of omega-6 can lead to a higher production of pro-inflammatory eicosanoids.

  • Role in Inflammation: While omega-6 fatty acids are necessary for immune function and inflammation (a vital part of the body's defense mechanism), excessive amounts can promote chronic inflammation, contributing to diseases like cardiovascular disease, arthritis, and asthma.


Balance and Ratio

The balance between omega-3 and omega-6 fatty acids is crucial for maintaining health. Historically, human diets had a ratio of omega-6 to omega-3 ranging from 1:1 to 4:1. However, modern diets, particularly in Western countries, often have a ratio as high as 20:1 or more, skewed heavily towards omega-6. This imbalance can promote inflammation and increase the risk of inflammatory diseases.

Summary

  • Omega-3 fatty acids are anti-inflammatory due to their conversion into less inflammatory eicosanoids and their role in producing resolvins and protectins that resolve inflammation.

  • Omega-6 fatty acids are considered pro-inflammatory primarily because they are converted into eicosanoids that promote inflammation, which is necessary in moderation but can be harmful in excess.

  • The key to minimizing chronic inflammation is maintaining a balanced ratio of omega-3 to omega-6 fatty acids in the diet.

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