Is Depression a Disease—or a Symptom of Inflammation?


The idea that depression and other mental health conditions are caused by an imbalance of chemicals (particularly serotonin and norepinephrine) in the brain is so deeply ingrained in our collective psyche that it seems almost sacrilegious to question it. 

Of course Big Pharma has played a role in perpetuating this idea. Antidepressant drugs, which are based on the chemical imbalance theory, represent a $10 billion dollar market in the U.S. alone. According to the CDC, 11 percent of Americans over 12 years old take antidepressants, and they are the second-most prescribed medications (after cholesterol-lowering drugs). Doctors wrote a staggering 254 million prescriptions for antidepressants in 2010. (1)

New research suggests that depression may be primarily caused by inflammation.

Yet as popular as this theory has become, it is riddled with problems. For example: 

  • Reducing levels of norepinephrine, serotonin and dopamine does not produce depression in humans, even though it appears to do so in animals.
  • Although some depressed patients have low levels of serotonin and norepinephrine, the majority do not. Several studies indicate that only 25 percent of depressed patients have low levels of these neurotransmitters.
  • Some depressed patients have abnormally high levels of serotonin and norepinephrine, and some patients with no history of depression have low levels of them. (2)

What if depression isn’t caused by a “chemical imbalance” after all? More specifically, what if depression itself is not a disease, but a symptom of an underlying problem? 

That is exactly what the most recent research on depression is telling us. A new theory called the “Immune Cytokine Model of Depression” holds that depression is not a disease itself, but instead a “multifaceted sign of chronic immune system activation.” (3)

To put it plainly: depression may be a symptom of chronic inflammation.

The connection between depression and inflammation

A large body of research now suggests that depression is associated with a low-grade, chronic inflammatory response and is accompanied by increased oxidative stress. 

In an excellent review paper by Berk et al, the authors presented several lines of evidence supporting the connection between depression and inflammation: (4)

  • Depression is often present in acute, inflammatory illnesses. (5)
  • Higher levels of inflammation increase the risk of developing depression. (6)
  • Administering endotoxins that provoke inflammation to healthy people triggers classic depressive symptoms. (7)
  • One-quarter of patients who take interferon, a medication used to treat hepatitis C that causes significant inflammation, develop major depression. (8)
  • Remission of clinical depression is often associated with a normalization of inflammatory markers. (9)

During an inflammatory reaction, chemicals called “cytokines” are produced. These include tumor necrosis factor (TNF)α, interleukin (IL)-1, interferon (IFN)ɣ, and interleukin (IL)-10, among others. Researchers discovered in the early 1980s that inflammatory cytokines produce a wide variety of psychiatric and neurological symptoms which perfectly mirror the defining characteristics of depression. (10)

Interestingly enough, antidepressants (particularly SSRIs) have been shown to reduce the production of pro-inflammatory cytokines like TNF-α, IL-1, interferon IFN-ɣ and increase the production of anti-inflammatory cytokines like IL-10. (11, 12) They also change the gene expression of some immune cells that are involved in inflammatory processes. This suggests that SSRIs are anti-inflammatory, which would explain their mechanism of action if inflammation is a primary driver of depression.

The research on this topic is robust, and the connection between depression and inflammation is now well-established. But if depression is primarily caused by inflammation, the obvious question that arises is, “what is causing the inflammation?”

Common causes of inflammation and depression

If you’ve been following my blog for any length of time, you know that inflammation is at the root of nearly all modern disease, including diabetes, Alzheimer’s, cardiovascular disease, autoimmune disease, allergies, asthma, and arthritis. So perhaps it shouldn’t come as much of a surprise that depression is also caused by inflammation. 

The downside of this connection is that our modern diet and lifestyle are full of factors that provoke inflammation—and thus cause disease. The upside is that if we address these factors and reduce inflammation, we can prevent and even reverse the chronic, inflammatory diseases that have become such a fixture of industrial civilization.

According to the authors of the Berk et al review paper I referenced above, the following are the most common causes of inflammation that are associated with depression. 


There are several problems with the modern diet. It is high in foods that provoke inflammation, such as refined flour, excess sugar, oxidized (rancid) fats, trans fats, and a wide range of chemicals and preservatives. And it is low in foods that reduce inflammation, like long-chain omega-3 fats, fermented foods, and fermentable fiber. Numerous studies have associated the Western diet with major depressive disorder. (13)


One of the most harmful consequences of the modern diet has been the dramatic increase in obesity. Obesity is an inflammatory state. Studies have shown higher levels of inflammatory cytokines in obese people, and weight loss is associated with a decrease in those cytokines. (14) Obesity is closely linked with depression, and while that relationship is likely multi-factorial and complex, inflammation appears to play a significant role. (15)

Gut health

Disruptions in the gut microbiome and leaky gut (i.e. intestinal permeability) have both been shown to contribute to inflammation and correlate with depression. For example, a leaky gut permits endotoxins called lipopolysaccharide (LPS) to escape the gut and enter the bloodstream, where they provoke the release of inflammatory cytokines such as TNF-α, IL-1 and COX-2. (16) And numerous studies have linked unfavorable changes to the bacteria inhabiting our gut with major depressive disorder. (17


Stress may be one of the most obvious causes of depression, but the link between stress and inflammation is less well-known. Research has shown that psychosocial stress stimulates the pro-inflammatory cytokine network, including increases in TNF-α and IL-1. (18) These increases in inflammatory cytokines are in turn closely related to depressive symptoms, as described above. 

Physical activity

There’s a huge amount of evidence indicating that exercise is an effective treatment for depression—in many cases as effective or more so than antidepressant drugs. It has also been shown to prevent depression in healthy people with no pre-existing symptoms. (19) Interestingly enough, while exercise initially produces the same inflammatory cytokines that are associated with depression, that is quickly followed by induction of anti-inflammatory substances. (20) This is known as a hormetic effect, where an initial stressor provokes a compensatory response in the body that has positive, long-term consequences. 

Sleep deprivation

Chronic sleep loss has been shown to increase inflammatory markers even in people that are otherwise healthy. (21) And although temporary sleep deprivation has been used to therapeutically improve depression, chronic sleep loss is a well-known contributing factor to developing depression in the first place. (22

Chronic infection

Chronic infections produce ongoing inflammation, so it’s no surprise to see that depression is associated with Toxoplasma gondii, West Nile virus, Clostridium difficile, and other pathogens. (23, 24, 25

Dental caries and periodontal disease

Dental caries and periodontal disease are another source of chronic inflammation, and thus a potential cause of depression. According to one large study of over 80,000 adults, researchers found that people with depression were more likely to have tooth loss even after controlling for several demographic and health factors. (26

Vitamin D deficiency

Low levels of vitamin D are common in Western populations, and there is growing evidence linking vitamin D deficiency to depression. Vitamin D modulates immune responses to infection, including reducing inflammatory markers like TNF-α and IL-1 that are associated with depression. (27) Supplementation with vitamin D to normalize serum 25D levels has been shown to to reduce inflammatory markers in some, but not all cases. (28)

Final thoughts and recommendations

The early 1980s discovery that inflammatory cytokines produce all of the characteristic signs and symptoms of depression should have made a big splash. For the first time ever, scientists had discovered a class of molecules that were tightly and consistently associated with depression, and, when administered to healthy volunteers, produced all of the symptoms necessary for the diagnosis of depression. 

Unfortunately, the “chemical imbalance” theory continues to be the dominant paradigm for understanding depression nearly 30 years after this profound discovery, despite the weak correlation between serotonin, norepinephrine, and dopamine and depressive symptoms. There are probably several reasons for this—and you’d be correct if you guessed that some of them are financial—but I’ll leave that discussion for another time.

The significance of this finding is huge—both for patients and clinicians. It shifts our focus from viewing depression as being a disease caused by a chemical imbalance, which often requires medication to correct, to being a symptom of a deeper, underlying problem. It also leads to entirely new avenues of treatment—many of them more effective and safer than antidepressant drugs.

Understanding the physical roots of depression can have a profound effect on people who are suffering from it. Although the stigma surrounding depression has decreased in recent years, many who are depressed still carry the burden of thinking that there’s something wrong with them, and the depression they experience is “their fault”. When my patients with depression learn that there’s an underlying physiological cause of their symptoms, they often feel a tremendous sense of relief and empowerment. What’s more, when we address this underlying cause, their mood improves dramatically and they quickly realize that the self-judgment and shame they felt about being depressed was misplaced and unwarranted.  

I don’t mean to suggest that emotional and psychological factors don’t play an important role in depression. In many cases they do, and I’ve written on that topic before. However, the assumption in mainstream medicine that depression is exclusively caused by those factors is obviously not true, and too often these other potential underlying causes go unexplored. The doctor prescribes an antidepressant, the patient takes it, and that’s the end of the discussion.

With this in mind, what can you do if you’re suffering from depression? Follow these two steps:

  1. Adopt an anti-inflammatory diet and lifestyle. This means eating a nutrient-dense, whole foods diet, getting enough sleep, managing stress, engaging in appropriate (not too little or too much) physical activity, and nourishing your gut. For more on how to do this, see my book Your Personal Paleo Code (published in paperback as The Paleo Cure in December 2014).
  2. Investigate other underlying causes of inflammation. On your own or with the help of a good functional medicine practitioner, explore other possible causes of inflammation that could be contributing to depression. These include gut issues (SIBO, leaky gut, dysbiosis, infections, etc.), chronic infections (viral, bacterial, fungal), low vitamin D levels, dental caries and periodontal disease, exposure to heavy metals and mold or other biotoxins, obstructive sleep apnea, and more.

Now I’d like to hear from you. Were you aware of the link between depression and inflammation? If not, how has learning about it changed your view of depression? Have you experienced an improvement in depressive symptoms after implementing an anti-inflammatory diet and lifestyle? Let us know in the comments section.

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Comments Join the Conversation

  1. YV says

    Ok, so far I’ve heard words. Are there any references to scientific studies available to support this Inflammation Theory of Depression. Why does the author of this article did not provide any?

    • Chris Kresser says

      There are 28 scientific references in the article. The numbers in parentheses after sentences are links to the studies.

      • Mo says

        I’d like to know what you think of the mood cure by Julie Ross. Using a primal diet and amino acid supplements for anxiety depression etc. It seems to tackle the inflammation and prov ides natural medications to improve moods and behaviors.

  2. Gina K. says

    Prolonged exposure to external stress from 2010 when job loss, declining jobs/low pay and at age 62 caused spiraling anxiety and depression. Living on social security income, inflationary cost of living makes it impossible to afford the fresh/organic nutrient rich and toxin free diet that I need to have a strong immune system and minimal inflammatory response. What specialist might be helpful?

  3. MT says

    I’m curious with how this theory fits in with commonly suggested supplements for treating depression? My nutritionist recently suggested 5-htp for my depression, because of it being a precursor to serotonin. I have also seen L-tryptophan suggested by other Paleo writers. Would either of these be a wise choice, or pointless if serotonin isn’t the actual problem of depression?

    I suffer a lot of bloating, constipation, fatigue, hair loss and anxiety as well – soon to be tested for SIBO. Any advice on the usefulness (or not) of supplements would be much appreciated.

  4. ann jary says

    i am very depressed with taking medication some pills can make you this way so i try do without i suffer with inflammation ibs arthritis back problems knee problems and believe you me i have tried everything and nothing works from coconut oil garlic pills primrose oil and stuff off internet

  5. N.G. says

    Everyone look up Dr. John Sarno, 20/20 interview; Howard Stern Dr. Sarno interview; as well as other interviews relating to his work. He has helped so many with the same issues you are all talking about without all the meds and their side effects.

    • Mary D. Reynolds says

      It’s funny that you mention Dr. Sarno because it was one of the first things I thought about when reading the article. I started believing in his anger theory after it cured my chronic back pain for about 90% in 2011. I definitely recommend anyone with a depression to look up some videos on Dr. Sarno.

      I must say that it also worked for my depression but not completely. If you deal with your emotional issues but still decide to eat unhealthy or live an unhealthy lifestyle it’s kinda counterproductive. I think most of us agree that the mind and body are somewhat intertwined. That if one is out of balance, the other is as well.

      After reading an review on I decided to start a depression self-help program. A lot of the program dealt with exposure therapy and CBT and it worked wonders for my depression, in addition to starting a paleo diet with a lot of fermented foods.

      I still have my moments from day to day but it’s in no way comparable to the constant burden of a heavy depression. At the moment I dealt with the depression all hope was lost. So I can relate to anyone suffering and I hope this helps somebody suffering from it. It’s not as overcomable as it feels :)

  6. says

    I haven’t heard much discussion about the use of amino acids to rebuild neurotransmitter function. Sometimes depleted NTs really are the cause of the issue, and rebuilding them using precursors works within minutes! Feeding the brain before tweaking the brain!!! And sometimes we still need to tweak by using antidepressants and other meds. In response to a previous post, liposomal curcumin (from turmuric) is a good brain anti-inflammatory. But start with a low dose. Also, keeping blood sugar absolutely stable by eating protein every 3-4 hours is crucial. Christina

    • doug gerard says

      Always get your amino-acids from foods, not tablets. An over abundance of one amino-acid can disrupt the bodies protein balance.

    • Louis says

      I have to agree with Doug.

      Your attitude to food will change your life, and if your attitude changes, then you might become closer to finally rid yourself of depression.

      Anyone had experience with mediterreanean diet? I have found a website, that mentions a Destroy Depression System book which has information about this kind of diet. Apparently, it works and helps you live your life better.

      Does it really work?

  7. Kelley says

    This article clarified for me why I seem to respond so poorly to exercise. I’ve suffered from depression on and off since my osteoarthritis became and issue about 15 years or so ago, and I’ve been diagnosed with fibromyalgia and IBS (symptoms of IBS eliminated with the Paleo diet). My depression and body aches have been really bad this past week since I renewed my commitment to exercise. Understanding how this response works will help me plan for it and see it through.

    • Alice says

      I used to have diagnosed Osteoarthritis and Deputry’s Contractures but I looked up the involved cytokines Like Cox 2, LOX 5, IL-1b, IL-6, IL-8, TNF-alpha and started taking Boswellin ( a frankinsence product) nettle tea, chinese scullcap( can take tea or pills-made my own) turmeric with a little black pepper, safflower petals and a few raisins soaked in Gin with juniper berries added and evaporated to remove the alcohol. The pain, in joints all over, stopped , the contractures disappeared, I could flex my hands without getting stuck, the shiny finger-joint lumps almost completely disappeared and I can flatten my left hand and almost flatten my right hand. Glad that is done. But I still got a diagnosis of bi-polar which greatly improved eliminating gluten. Off psych meds, no more fog or forgetfulness or flat personality. Working on my Hashimoto’s, might get to take Lugol’s to address that. Cooking/draining my goitrogenic foods. Good health to you!

  8. Janet says

    Thanks Chris. Your work has been life changing for me. Went gluten free 3 years ago and most of my issues went away. Eliminating gluten, adopting an anti-inflammatory and paleo diet , getting enough sleep and eliminating stress factors plus making my own food have yielded results beyond any reasonable expectations. I am so thankful for all you have done and for freely sharing your knowledge.

  9. says

    Mental health is not less important than the physical!
    Do not forget about psychosomatic illnesses and other dangerous effects of depression.
    I had been suffering because of depression for a long time after divorce and one day I realized how close to suicide I was…
    But then I reversed my behaviour with an anti-depression system (I wrote my full story in here, hope this help), and now I am a happy woman always in a good mood =)

  10. pauline says

    is there a drug that is effective for treating inflammation on my brain even if it is drug that is already used for something else in the body. I had said for year that my depression is about inflammation. Please let me know if you know names or have experience”
    Thank you


  11. E. Watts says

    I am 61 and am finally convinced that chocolate is THE direct link to my depression. When I eat it, I feel like I am being drug into a very deep pit that I cannot get out of. When I abstain, I am more energetic and have hope.

  12. Jennifer says

    I totally agree that diet is very important in treating depression. And the best example in this case is the Mediterranean diet. Eating primarily plant-based foods, such as fruits and vegetables, whole grains, legumes and nuts, replacing butter with healthy fats, such as olive oil, using herbs and spices instead of salt to flavor foods, limiting red meat to no more than a few times a month, eating fish and poultry at least twice a week help you to be more physically active and also have a healthy life. I suggest you to look at the destroy depression system which is a plan that teaches you the Mediterranean way of life and how to eat your way to a happy, healthy life.

  13. says

    I contribute to the dialogue here from two points of view: one is as a lifelong sufferer of major depression, and the other is from the perspective of a practicing psychotherapist.
    Firstly, in my personal health, I have found that I have had a general inflammatory condition for about 15 years since a bout of pneumonia; this progressed within the last 4 years to an MS type of illness (depression, parasthesia, loss of balance, double vision etc.) – my research led me to conclude that this was caused by a very small and recently discovered bateria Chlamydia Pneumoniae, and 8 months after starting antibiotic treatment my symptoms and disability and depression are almost copletely resolved (check out
    As a practicing psychotherapist, I notice distinct grouping of people who are treated for depression (in particular). One group have a horrific trauma history which corresponds to their depressive symptoms, and the other group have a depression far exceeding the severity of adversity in life. I am in the latter group.

    • Alex says

      Thank you. Your post gives me hope. Had sudden onset adult anxiety that started a year ago. My wife and I are just now starting to see the connection to inflamation and chronic infection. A sinus infection preceeded my bout….

      I have hope for the first time in a year.

  14. Brad says

    Hi Chris,

    I really liked the article and judging by the 242 comments and 22k+ Facebook shares (at this point), it struck a chord with a ton of other people!

    You mentioned chronic infections like Toxoplasma Gondii as being a cause of inflammation which can affect someone’s mental state. About 6 months ago, I found out that my IgG antibody levels to T. Gondii are very, very high. I have done a lot of research of chronic toxoplasmosis, but will spare you most of the details as the main point is that I can’t seem to find anything (drug, herbal medicine) that is known to work against the “latent”/chronic, cyst stage (bradyzoites) of the parasite in humans.

    Have you come across any treatments that I could look into further? My best leads at this point are artemisinin and ginger, but the research behind both of those seems to be surprisingly undeveloped at this point.


  15. Christina says

    Hi Chris,
    I worked this one out the hard way. I was exposed to mold in a rental house for 3 months and then hammered by fertiliser dust when i stayed at a motel, towards the end of that time – they were unloading it from the dock nearby. I was floored. A month later my hair started falling out. It took me a long time and a lot of stress to realise it was inflammation causing the fall. Now I am in a healthy environment but my immune system is still weak, 5 months later. I also have a multinodular thyroid and tend to hyperthyroid if I eat seaweed or other iodine rich foods, or herbs, or certain supplements. I’m sure this is linked to the inflammation and the hair fall too, but the hair fall never happened until the exposure to mold and fertiliser. I got on top of the condition around 6 weeks ago after going onto certain things – natural progesterone cream (raises cortisol/ lowers estrogen’s inflammatory action?); magnesium and serotonin boosting herbs – st john’s wort. Every time i take something that loowers my cortisol however it starts again. Recently I took pine bark extract – apparently exacerbates hyperthyroid, I found out. The proanthrocyanadins are the porblem. The hair started again. I’ve also been working in a job where i feel qute stressed lately. I started getting depressed just before the hair fall started again. Now I’m trying hard to manage my inflammation by managing my anxiety with passion flower, passifying my thyroid, and getting happy. The problem is that I seem to need to raise my cortisol all the time to do this. My palms are literally orange and I believe that it’s a sign of high cortisol. With me I’m guessing that managing my thyroid is one of the key things I need to do, as well as my anxiety. I eat healthfully. Do you know of any anti-inflammatories that don’t upset the thyroid and don’t lower cortisol? I’d like my cortisol to drop of its own accord, when it no longer needs to be raised. I’m down to magnesium and fish oil, but the symptoms continue. Also, do you think that neurotransmitters themselves have an inflammatory/anti-inflammatory role? I felt a lot better wih less symptoms on 5-htp and then st john’s until recently. Is it both ways?

    • Alice says

      I’d try gluten free, dropping goitrogenic foods you are able to and cooking foods like kale or cabbage for eight minutes as one person suggested with draining the water.

  16. Daniela says

    Hi, Chris, My 17 year old daughter has Crohn’s and has struggled with anxiety/depression for almost a decade (since she was put on a huge dose of prednisone for 9 months to put her Crohn’s in remission).. She missed all last year of school and is also not going to school this year (all due to anx/dep). Any advice? we are broken-hearted. We live fairly close to Berkeley. Should we bring her in? Help, please :'(

    • eve says

      Prednisone will definitely mess you up but it’s an anti-inflammatory drug and I was given 60 mg for 2 days in a row for asthma and for about 2.5 weeks I felt SO GOOD. No depression, had plenty of energy, my stomach wasn’t hurting and I slept really good. I’ve had depression for 15 years or so and that 2.5 weeks was the best feeling of my entire life. I wonder if it was the prednisone. (but taking it over a long period of time will def mess you up)

  17. Nick C. says

    Amen to this one. Those drugs are DEADLY. Wish I would’ve known this BEFORE trusting a doctor that a pill was the solution. I am far, far sicker now than I was prior to taking the prescribed drugs. And that is almost always the outcome.

    I am in my fourth year of severe, barbaric and inhumane withdrawal from psych meds that I was given for “work-related stress”. It has ruined my life and health and that of thousands and thousands of others. We’re all online together in little underground communities (since no one believes us that the drugs destroyed us, including the medical “professionals”) trying to get off this stuff and reclaim health, but it can take years and years of suffering to get there, especially if you come off the drugs improperly or too quickly

    There’s help getting off (DO NOT STOP THE DRUGS COLD–they MUST be tapered sloooooowly)

    There’s also tons of facebook groups filled with support and people getting off these meds as well if you search for them.

    • Dixie Chick says

      Very true. The financial gain and greed for recognition in the medical community by psychiatrists and big pharma has caused a nation of people to suffer catastrophic mental illness from antidepressants. I am one such casualty.

      I was never so sick as I am right now trying to come off the effexor nightmare. I was a long term ingesting subscriber to paxil (aka the devil) and tried numerous times with the help of med professionals to come off these toxins. I never wanted to die more than when I was taking full doses of these poisons.

      A big FY goes out to the medical community for not believing the crime that has been and continued to be committed against those of us who lived to tell the truth.

  18. says

    Depression is a common and serious issue in majority of the people. It badly affects mental health of a person. Self-treatment, concealing and medication are the treatment for Depression. I have chosen medication to treat my Depression. I have been on Trainqulene for 3 months and it relived my anxiety. For proper information you can read Trainqulene review here

  19. Laura Smith says

    If you are suffering from depression, I highly suggest getting the destroy depression system.
    Written by a former sufferer of depression, it teaches a simple 7-step process to eliminate depression from your life once and for all.

  20. Lori Batchelor says

    I was diagnosed with Multiple Sclerosis in 1990 and definitely suffered from depression. Prescribed Prozac in 1996 and took it for 15 years until weaned off one month after venous angioplasty for chronic cerebrospinal venous insufficiency (CCSVI) in March, 2014. Incredible symptom improvement and no longer deprived of oxygen in the brain means no more depression for me!

    • Alice says

      Dr Mercola on the internet has an article of a diet plan used to overcome MS in about nine months if you are interested.

  21. says

    Hi Chris, Excellent article! I am delighted to have found your website. I actually teach a year long on-line certification course, (starting again in a couple of weeks), sponsored by The Alliance for Addiction Solutions, which teaches clinicians and anyone else, how to apply these principles to mental health and addiction recovery. It’s exciting to watch more and more clinicians getting trained in this approach, and seeing so many people get well after being sick for so long. I personally had been depressed from day one and it turned out to be a combination of trauma and developmental deficits (I am a psychotherapist along with being a mental health nutritionist), along with deficiencies in both the Omega 3 fatty acids and GLA, (inflammation was part of this); dopamine deficiency, helped by L-Tyrosine; premenstrual hypoglycemia; severe gluten intolerance (I had actually been diagnosed with Celiac disease when I was 2, but the diagnosis got lost!), and IgG reactions to corn and eggs. At its worst, any corn at all would make me acutely suicidal. My depression has now been in complete remission for almost 20 years. I had to explore a lot of layers, but it really is possible to get and stay emotionally well.

  22. Stephanie says

    I have been suffering from depression, pmdd, and a long list of symptoms relating to inflammation. I recently stopped eating gluten and foods that cause inflammation by eating the autoimmune Palio diet and all of my symptoms slowly started disappearing. I feel like the gluten and leaky gut were my biggest problem. I have since started eating poorly again and the symptoms have all returned. It is hard to change your eating habits after so many years if eating wrong but if eating clean and healthy means not putting chemicals in my body then it is we’ll worth it!!

  23. says

    Makes perfect sense. I have gluten intolerance and it caused inflammation for me for years. Went GF when my hands and feet swelled up.

  24. Laura says

    Dear Chris,

    I find this article very interesting indeed. As a patient who has suffered with major depression for over 15 years, this topic is near and dear to my heart. In spite of years of therapy, spiritual practices, and what I consider emotional healing, depression is still a daily struggle and I do not function at all without the SSRI. This concerns me, and I’d love to get to the root of the problem, but it’s tricky because I need to be able to function and don’t have much room for experimentation! I initially found your website by searching, “long term effects of SSRI use.” Thank you so much for your research on this topic.
    What I find most interesting is the connection made between inflammation and depression. From early childhood, I experienced extreme allergies–both anaphylactic and skin allergies–from grass, dyes, certain foods, most antibiotics, to asthma. I also struggled with strange stomach symptoms from the age of about 14. In my 20’s, I began to take an SSRI, and saw a decrease in reaction to some of those allergies. I have never made the connection before, but now it seems pretty clear. I now believe that stress (family dysfunction) and poor nutrition (lots of sugar and processed food) did and does play a large role in my allergies, asthma, digestion and depression. I hope to follow your guidelines for reducing inflammation to tackle these issues. Thanks again for what you do!

  25. Juie Hutchinson says

    I’ve been aware of the link between stress and depression for quite a while although I don’t think stress is the absolute cause of depression.
    In my experience depression is brought on by the inability to rectify the stressful situation – being powerless. Realizing the strength in my personal choices helps to prevent the stress turning into depression. Making small decisions I have power over and carrying them out.

    • prioris says

      STRESS is a waste basket reason for something. It’s a catch all name for – we really don’t know the real reason.

      They have tried to attach depression to cortisol levels and even that has fizzled.

    • Sue says

      I agree that being unable to control or change a stressful situation or event can lead to depression. My adult son (he doesn’t live with me) has schizophrenia and suffers from very low moods and melancoly. I try very hard to find solutions or help for him but most of the time he refuses to try them. This drains me emotionally and for the last few years I have been depressed at times. However, I dislike my depression so much that I actively try to be in the company of good and kind people, be with nature or animals and read as many uplifting books and websites as I can. My husband is my rock and listens to my problems and anxieties without complaint. My GP cannot prescribe anti-depressents for me because I have suffered from hypo-mania in the past and this can be a side effect of the anti-depressants. I would be grateful for anyone elses tips on beating depression. Many thanks.

      • Alice says

        As I think already mentioned, lots of vigorous exercise and sunshine help a lot-and keep the sugars/carbs low too!

      • ann jary says

        when i get depressed with pain i do a jigsaw and it takes my mind off the pain because i am concentrating on something and not the pain

  26. says

    While healthy eating is absolutely critical, don’t overlook the mind-body connection that can be optimized through chiropractic care. In the same way the flow of water is impacted by parking a car on the hose, the healing instructions from your brain can be disrupted by a misalignment in the spine. Your experienced local chiropractor should be an integral part of your health optimization team.

  27. Jamie says

    I’ve tried Betaine HCL (I’ve used 100% Betaine HCL with no fillers as well) and this makes gets me really inflamed. I retain a lot of water and its makes me feel really depressed.

    I’d be really interested if anyone else has experienced this when using Betaine HCL?

    • prioris says

      Do you really need it ? The way to tell if you need HCL Betaine is take it with a meal. If you feel heart burn then you don’t need it. Some people produce enough acid. Other people don’t. I produce enough stomach acid.

  28. D Anderson says

    I had severe depression from 1980 – 2008. In 2008 I threw out all the drugs they had me on. I improved a lot but what really made a difference was when I went on the Virgin Diet in 2012 and gave up the 8 common allergens and then tested them each individually by adding them back. I also had myositis that was cured by giving up gluten and dairy. I have been gluten free and dairy free for 2 years and feel great at age 65. Now I want to go completely Paleo (I still eat rice) and lose my excess weight. I KNOW for sure that a Paleo diet cures depression and inflammation and I will never go back to the SAD diet.

  29. Irv says

    Chris, so well articulated, thank you. I really feel someone needs to do a documentary solely related to mental health and the role diet, epigenetics, and orthomolecular medicine has to play in this all. Andrew Saul sort of took this role on in Food Matters with his (and Dr. Hoffer’s research on niacin).

    As a sufferer of depression, panic, and anxiety for at least 20 years, I decided to change my diet to gluten free, wean off SSRIs (which weren’t working anyway), and star juicing and eating healthier. I have MTHFR (the worst kind) along with other SNPs that don’t allow my methylation cycles to work. I tried so many natural vitamins/amino acids/supplements with no consistent relief of symptoms.

    Until just very recently. I started a regimen of Lithium Orotate and feel as though a huge cloud has been lifted. The constant feel of fight or flight has now dissipated. I’ve read LO does a great job of fighting glutamate toxicity and wondering where cytokines and inflammation relate to glutamine and other excitotoxins?

    Thanks so much for all the great info you provide!

  30. Pender says

    Chris help!!!
    I have severe chronic depression, chronic pain, anger. I’m really tired living has become very difficult, I’m on 2 antidepressants, 2 mood stabilizers, 1 being lithium, sleeping pill so on. I’ve seen a few integrated Dr. and see no difference, I feel myself spiraling again, I have no energy or motivation anymore! If I could I would come and see you Chris but I’m all tapped out from seeing Dr., buying supplements, and having a lot of tests.
    I feel very stuck! Maybe this is it!

  31. Silke says

    Thanks Chris,
    this post motivated me even more to find the reason for my chronic intestine problems and see if my depression will improve after being cured…

  32. Theresa Sheehan says

    So happy for this. I have made the same discovery through personal research. Try to tell Doctor’s and ‘professionals’ to no-avail, like talking a different language. which makes me think they are incompetent and not fit to be in charge of such things. It is shambolic.

  33. Ladylene says

    A very interesting article which I have been researching for months now. I have suffered chronic depression for 7 years, along with celiac, fibromyalgia and chronic fatigue. It has cost me everything including recently, my husband. I have been eating Paleo for more than 6 months now, and started AIP (autoimmune Protocol) 2 months ago. I take Vit D, C, B, probiotics (tablets, fermented foods and kefir grains). I have no change in my symptoms and I’m very frustrated. I’m beginning to wonder if its worth fighting any more .. there is not much left in my life to lose. Please .. what am I missing? I am positive that all of these symptoms are due to inflamation .. I have the most incredible pain down my spine, but xrays, tests, scans show nothing. For the first time in this I feel like I have come to the end of my learning and therefore the end of hope. Any suggestions on where to go from here?

    • Alice says

      Two people on different sites said that limiting (or removing) oxalate containing foods from their diets greatly improved their fibromyalgia. Maybe you will have the same results.

  34. says

    This would explain why my husband, a 100% service-connected disabled veteran, cannot take anti-depressants or anything like them. He was diagnosed almost 12 years ago after his medical retirement from the Marine Corps. The VA put him on several medications (anti-depressants, pain pills, etc.) which did not have the intended effect and he had to check himself into the VA hospital for treatment. He has not taken any of those pills for 10 1/2 years.

    This correlation between inflammation and depression makes so much sense to me because of what we have gone through. I do see his symptoms fluctuate with inflammation.

    Thank you for your insightful article! I’m going to continue to research this and incorporate more changes in diet and exercise.

    • ernie toews says

      Research Dr Abram Hoffer, psychiatrist, orthomolecular medicine, helped thousands recover from ” mental illness ” after years of pharmaceuticals. His book ( Niacin The True Story) Inflammation makes sense. He explains that depression is NOT chemical imbalance, but nutrient deficiency, or dependency.

      ( Niacin can cure depression, anxiety, schizophrenia, bipolar, alcoholism, borderline,)
      (Depression is NOT a chemical imbalance…. Here’s proof)

  35. says

    I am very pleased to find this article. Very well written, a couple of things are left out (such as mentioning that excessive alcohol intake also adds to raging inflammation – alcohol is processed in the body as sugar and having excess of that “one glass”….very inflammatory);

    I read so many who don’t quite get it accurate, they leave out the Vitamin D3 + K2 connection (NOTE IT SHOULD BE D3 with K2 for maximum absorption and assimilation)

    Regardless – I am signing up to watch this Blog. Very well written. Thank you.

    Carole B Starr AS BS MBA Health and Happiness Fitness Coach

  36. Allison Jones says

    In my case, gut dysbiosis and food sensitivities correlate strongly with depression.

    I’ve been dealing with streptococcus gut overgrowth for a few years now – earlier this year, the strep had grown back after treatment, but I didn’t realise it until I had stool testing done. Anyway, I was eating high amounts of dairy and had the most awful muscle aches, fatigue and depression. It was when I read about casein intolerance due to strep overgrowth (as it blocks the DPP-IV enzyme to digest casein) that I realised what was happening and promptly stopped eating dairy.

    Other factors for me are pyroluria (high copper states are believed to contribute to oxidative stress), being homozygous for MTHFR C677T and low DHEA levels. Low DHEA-s is suggested to play a role in chronic inflammation:

  37. robert clowes says

    Thank you so much for all the great work you are doing. Started the Paleo diet one yr, ago and its worked miracles. Enjoy all your articles and pass them on as much as I can. Thanks

  38. Craig says

    I 100% agree with you that in general, Western medicine takes the wrong approach to identifying and treating the causes of depression. I also believe in the correlation between diet, exercise, and mental health, find this to be true in my own personal experience. But an interesting thing about inflammation related to mental states, is another common occurrence I experience from time to time. When I am extremely anxious or stressed for extended periods of time (a week or more, usually brought on my identifiable life events), I almost always develop muscle inflammation and pain in my back. No matter how much I heat and ice or massage it, it persists almost debilitatingly until my mental state is resolved. I think this is related to the topics you are discussing here, but it is essentially the opposite effect. I begin with an unhealthy mental state, which in turn brings on the muscle inflammation. I do believe they are highly related, but I feel the root cause may still lie yet deeper. Not solely on physical grounds, but hidden within the psyche as well. There is so much we don’t know about brain processes and chemistry, and thought for that matter. Yet the brain is (as far as we know) our consciousness and our center for controlling the whole body. It would make sense that the mental links directly to the physical in a multitude of ways, including many we cannot currently correlate or even imagine.

  39. Sophie says

    Hi Chris great article, finally someone mainstream and highly regarded getting the word out..I am a nutrition scientist and specialise in the role of inflammation in illness – particularly mental health. One of the most effective things people can do for inflammatory health, and specifically depression, is take 1g pure EPA Omega-3. I have had mind-blowing results with Igennus ( Pharmepa Step 1 in people with long term clinical depression, so much so, that within weeks of starting it they report huge noticeable differences! Quote from one 55 year old male with 10 years+ MDD ‘I feel like someone has flipped a switch’! For those of you who need science here’s a few studies showing the significant benefits of EPA (there’s plenty more):
    I’m happy to email papers and answer questions. Happy health all :-)

    • prioris says

      Thanks for the info Sophie
      Several recent clinical studies, especially those focusing on the benefits of omega-3 in inflammatory conditions, have investigated the actions of pure-EPA oils (fish oil that is concentrated to contain only EPA, with no DHA). EPA plays two vital roles in protecting against excess inflammation in the body:

      1) By displacing the omega-6 AA content of cell membranes, EPA can directly reduce the amount of inflammatory products produced from AA

      2) EPA also reduces the activity of the enzyme responsible for the release of AA from cell membranes into circulation, again preventing its conversion into inflammatory products.

      Since EPA also produces its own anti-inflammatory products, increased EPA levels in the blood and cell membranes effectively regulates inflammatory pathways and reduces total inflammatory ‘load’. Supplementing the diet with pure EPA (without DHA present) therefore maximises the beneficial actions of this important nutrient for inflammatory conditions, as it is unopposed by the competing actions of DHA for uptake and processing.

      • John Es says

        Pretty interesting stuff.

        Is there a protocol for loading up on EPA?

        I guess I’m willing to give it a go. I’m inclined to *further* reduce omega-6. And reduce my DHA intake to my weekly pound of sockeye.

        I’d give it 60 days of 2-3 grams of EPA a day, and see how I feel, splitting the dose over 2 or 3 meals. I always eat sat. fat at meals.

        Any other tips?

        (I’m also inclined to load up on Theracurmin)

        • prioris says

          That would be good if you experiment with it and report back the results. The OmegaVia EPA 500 looks like the most economical brand to get to try it out.

          You will have to pioneer the loading. You could try some high doses for 3 or 4 days to see what happens. Split the dose during those days. Make sure you take it with fats. I have read that it is better to take the triglyceride and ester type in split dose but I’d do what is most convenient. Over those months it will eventually reach your cells.

          • John Es says

            I don’t expect to feel any effects in 3-4 days.

            I picked up some Nordic Naturals EPA Elite at Vitamin Shoppe. One capsule has 800mg EPA with 30 mg “other Omega-3″. I’m going to start out taking 3 per day. One at each meal. I always eat fat with meals, and I also have some ice cubes of coconut oil / ghee / macadamia nut butter to take with the supplement. I figure the cost of this supplement is a little over $2 per day.

            • says

              Our doc says that EPA also act on mm9 which is the main cause of Multiple sclerosis and as stated on some studies NCBI that they may also act on depression. We had been using Vision Group Corp Omega-3 supplement as an alternative anti depressant and anti inflammatory ever since. Though the effect may vary from individuals we don’t have to worry of any drug to drug interaction and another less worry of any long term side effect…

    • prioris says

      this is one problem i have with fish oil (triglyceride or esther) … absorb-ability

      there is a 2 to 1 ratio of EPA to DHA in krill oil

      i’d like to see them make a pure EPA in phospholipid form

      i may buy it anyway to try it out
      Studies show that krill oil is absorbed 10-15 times as well as fish oil.

      About 80-85 percent of fish oil is never absorbed from the intestine, which causes about half of those who take it to have “burp back,” which is unpleasant enough, and many end up discontinuing it.

      When you consume fish oil, your liver has to attach it to phosphatidyl choline in order for it to be utilized by your body.

      But krill oil ALREADY contains phosphatidyl choline!

  40. Randi Hager says

    I have suffered from depression on and off for about 10 years. The whole time researching different avenues. I have read through all the comments and tried most if not all of them and the only thing that has ever worked for me was SSRI’s. Like night and day difference. Are there people that really DO have the chemical imbalance?

    • Gary says

      Stick with what works.
      Obviously diet and exercise can and do sometimes help but as you know, the pills work.

    • Dawn says

      I’ve suffered from lifelong depression. Diet and exercise do tend to improve the situation, but only a little. I, too, have tried pretty much everything on this thread. In my mid 30s I decided that enough was enough. Zoloft was the third antidepressant my doctor tried, and it has changed my life. It is worth whatever side effects I may have in store for me to not live like that anymore.

  41. Jan says

    Thanks for the article Chris. What is your view on the research showing that PUFA (including omega 3) slow down cellular metabolism and efficiency ?

  42. Sandra Schofield says

    Have you ever or do you have bipolar two (manic-depression)…if not you cannot imagine what life is like and it is wonderful to see people trying to make an good excuse as to why we get depressed and that it is curable if we just do this or that….it is very painful..R.I.P. Robin Williams but sorry I know how he felt and it is a disorder of the brain and no one would wish this upon themselves…and your theory just sits aside with a million others. People don’t need to find a cure because there is none The best cure is speaking up if you are depressed without thinking the world will think you are with the stigma that has caused so many to die by suicide…Robin Williams has opened double doors on this disorder and in his death he is still helping so many because finally we are talking about this and depressed people are coming out shall we say…no diet change, no uninflammitory pill or likewise is going to help because it is a disorder and needs to be looked at in this way only not all the crazy things that could be causing it!!

  43. joeyjoejoe says

    All this talk of inflammation and no mention of aspirin? Aspirin has been shown in clinical trials to work as well as SSRIs against depression.

  44. prioris says

    from my experience, one thing that has helped my depression is krill oil. It is not quick. You really have to take it for probably 6 months. It is important to take astaxanthin to protect against brain aging etc caused by fish oil.

  45. Debra Nisbet says

    I can fully understand now that all these things are connected. I have been on Aropax for about 15 years and have always had gut problems, balance problems and energy and sleep problems. I have been so committed to trying to lose weight thinking it would ease the stess issues, that I have neglected my healthy eating. I am feeling so much better by following Paleo and adding back the fruits I have been craving. It has been a vicious cycle of yo-yoing weight issues, depression etc so now I am finally on the right track for me that I have started to once again decrease my Aropax. Having lots of support helps immensley as well. I am getting out of bed now feeling like starting a new day and not having the off-balanced brain fogs. I am finally starting to lose some of the muscle and joint pain I’ve had for many years…..:)) :)) :))

  46. says

    Worth mentioning, for people who suffer from IBS:

    Ribose (monosaccharide) can cause surprising, long-lasting constipation–>depression. Look into avoiding FODMAP foods.

    Not just “magnesium”, but Magnesium -oxide & citric acid, can be a life-saver for quickly overcoming the constipating effects of eating something that ignites your IBS syomptoms.

  47. says

    Great article. Robin William’s suicide and link to depression points out how medication is not the answer. We need to replenish our good gut bugs with whole and fermented foods as well as eliminate processed food. Almost every ailment goes back to the gut, so no wonder there is an increase in so many diseases as fast food overwhelms our lives.

  48. George Ingram says

    Having by some miracle reached the age of 80, and having picked up all the intelligence on diet, vitamins, and exercise and so on, I find myself increasingly achy and with increased difficulty following my exercise routine. I suppose I must expect ageing to have effects that can’t be circumvented, but it is still discouraging to find my CRP to be constantly elevated (4 or 5), and fasting glucose nudging 100 even with fasting insulin at a low 2 to 4. I have no symptoms of diabetes or metabolic syndrome (except for blood pressure), but I’m afraid to present this to my GP for fear she will want to give me the usual destructive drugs, which I’m striving hard to keep to a minimum.

  49. CBG says

    Yes, I have read many articles about inflammation in the body and how it leads to so many problems, like diabetes. I knew it was also linked to Alzheimer’s disease. These findings regarding inflammation and depression come as no surprise to me. This article is important for all to see, and I am sharing it on my FB page.

  50. Wenchypoo says

    I’m going to suggest that not only may a Vitamin D deficiency be involved, but a B-vitamin and Omega-3 deficiency as well. Since most mental disorders (schizophrenia, hallucinations, etc.) usually boil down to either or both of these two deficiencies, why not depression too?

    • Chris Kresser says

      I would agree. There are many other possible causes of inflammation that weren’t mentioned in this article, though I did mention long-chain omega-3 in the diet section.

  51. Claire says

    I can’t figure out what is causing my inflammation. Currently CRP is 12. My health was improving over a few years while I changed my eating habits to WAPF, then a bit of GAPS, then PHD. My energy levels went up, I had fewer colds…2 years ago my CRP was 0 and TSH great but today both are high. It all started a year ago with a bout of ‘food poisoning’ that ‘reoccurred’ occasionally throughout the year (mild lower left tummy pain and usually associated with a short bout of diarrhoea). I’m not experiencing symptoms currently but my CRP is 12.
    I’ve had a private comprehensive digestive stool analysis. No pathogens found, just perfect digestion and normal low levels of inflammation in gut. I still feel that I do have some sort of chronic infection that got hold of me 1 year ago. I am now pregnant. What can I do since this inflammation (for which I can’t find the cause) is affecting my thyroid? I’m already doing an anti inflammatory diet, I’m working hard on circadian rythm entrainment and trying to get some exercise daily. My Vitamin D levels are very good at 80+ (my Vit D was too low in the days where my CRP was 0!)

    • Chris Kresser says

      Stool test is only one way of testing gut function. Also SIBO breath test, urine organic acids, and urine amino acids. I would also investigate heavy metal toxicity, mold/biotoxins, food intolerances, chronic infections, especially given your history.

      • Claire says

        Thanks Chris. What are the best tests/labs for chronic infections, is it just via stool that chronic infections can be found? Or are there other ways.
        My stool test by Genova Diagnostics (joined with Metametrix I believe) did not find any infections.

      • Claire says

        Also, I am wondering if it’s worth taking serrapeptase, even though I am pregnant. I can’t find any contraindications. Have you had any experience with it?

  52. Summer says

    Thank you very much. I had suspected as much with my own Major Depression because when i managed my inflammation through the lifestyle choices you mentioned my depression simultaneously lifted every time. It is challenging to keep making wise choices but well worth it. I believe this inflammation depression link wholeheartedly. Thanks again

  53. salley says

    I’ve suffered with depression most of my life. I finally collapsed and thanks to a naturopath she got me on track. Yes i had leaky gut among many other things. I’ve been on a strict anti inflammatory diet for many years now, as well as avoiding allergy good such as gluten, dairy, soy and eggs. She says I have no inflammation yet the depression is back. I stayed free from depression for 3 years. She says my tests are better than ever so is now thinking it’s just my chemistry. Another Dr. thinks I’m bipolar II.

    I need help. Where do I go from here?

  54. Stuart says

    I found this article quite interesting because it seems to be drawing connections between a number of conditions which i have accepted to be connected for some time due to my own experiences. For about 6 years i suffered chronic pain in my back, neck, shoulders, arms, chest and even my leg. In parallel i suffered gastrointestinal issues, eczema, asthma, allergies and even depression. I tried everything that modern medicine could trow at me with varying degrees of success and always with temporary gains no matter how consistent and strict i was. I have been extremely good with my diet/nutrition for over 10 years and know about as much as you need to know to lead a healthy lifestyle – however this never really made a difference to me and certainly didn’t stop me getting these conditions.

    Late last year i came to understand the true nature of my condition and haven’t suffered from any of the above since! I was lucky enough to stumble across the answer and after applying the right principles i was amazed to find that it didn’t take long at all to overcome the chronic pain and the other conditions seemed go at the same time!

    Basically, the answer is something that is even more “radical” than what you are suggesting. All of the above conditions, including chronic pain syndromes, gastro-intestinal syndromes, allergies, asthma, headaches, migraines, depression and anxiety are all just symptoms. They are not symptoms caused by inflammation but actually this inflammation (where it actually exists) has got a common cause. The cause of all of these conditions is actually something which is common in nearly everyone you know in some form or another and could be thought of as the human condition. It is the result of the nature of our evolution and a battle between old and new parts of our brain. These conditions are actually a defense mechanism created to protect you from the consequences (as trivial as they may seem) of extreme unconscious emotion becoming conscious. This is based upon concepts first developed by Freud (for those who are interested it is about the id, ego and super-ego or in more modern parlance the child, adult and parent parts of the mind). The theory, originally known as TMS (Tension Myositis Syndrome) is slowly being more readily accepted in the psycho-analysis world as PPD (Psychophysiologic disorders) and I urge any of you that suffer from any of these to take this theory seriously and to read more about it.

    I would recommend the two books i have read that helped me:
    The Mindbody Prescription and
    The Divided Mind, both by Dr. John E Sarno.

    I realise this is a step change in all of your thinking and i haven’t really got the space or time to go into much detail about it but if you knew me before and now you would not hesitate in reading these books. They’re fairly cheap so there’s no good reason to not give them a try. If you can read them with an open mind i promise the future will become a very different place for you.

    I wish you all well and will be overjoyed if even one of you takes the plunge to read the books and come to the same realisation as me.


  55. Doris Hasslocher says

    Chris, have you seen William Walsh’s work at Biobalance? He sees deficiencies in key nutrients plus genetic/epigenetic defects in neurotransmitter synthesis/removal as responsible for several mental health issues including depression. Many psychiatrists are adopting his methods (very targeted supplementation) with great results. I would love to hear your take on this. Thanks for another great article.

  56. Chris says

    I have dealt withSAD for many years. Sisters and brother are on depression meds. I have been against medicating and just suffer through. I found a paleo diet to help my brothers immune disease and tried it for myself. It was awesome! Brain function, gut health, depression symptoms, even my skin feels healthy. unfortunately the western diet makes it too easy to be unhealthy and difficult and confusing to set up an ongoing healthy diet.

  57. Cassandra Cassandra says

    The problem with articles like this is that he sites the central premise as a fact when it is not a fact at all. I am sure BigPharma do make a big deal out of anti-depressants being the ultimate cure, but obviously they are bias. As far as I’m aware the Psychological community has NEVER said depression was caused by chemical imbalance. Depression is a complex interaction between cognitive, social, behavioural and physical factors, which is best treated by a combination of cognitive, behaviour, social and physical interventions. Anti-depressants were designed to ease the therapy process, not to be a stand-alone treatment. Chemical imbalance is a common symptom, which perpetuates the other symptoms, but it is almost always triggered by an external factor- sometimes disease, but more commonly extreme or prolonged pressure or trauma.

    So while I think that having a healthy diet and lifestyle is wonderful, especially if it helps you to take control over your symptoms, I think it is wholy damaging to compound negative stereotypes of depression to make your argument, and to attribute these stereotypes falsely to those individuals who are trying to further the cause of correct treatment for people suffering depression.

    • Chris Kresser says

      Hi Hellen,

      The problem is the lag time between what researchers have discovered and what the general public still believes. Most doctors and people still believe the “chemical imbalance” theory because Big Pharma did such an excellent job of spreading that meme. Similarly, most people believe eating dietary cholesterol raises your blood cholesterol levels despite the fact that this has been completely disproven in the scientific literature (for 70% of the population, at least). It takes a long time to change a paradigm.

  58. says


    If following a Paleo diet and supplementing with fish oil is not enough to break through inflammation, which seems to be the case for me, what would you recommend? After years of trying to address the inflammation issue I believe there is a hump I’m not able to get over, similar to how an allergic reaction sometimes needs to be stopped with an acute steroid injection. I’ve followed all the rules and I’m not seeing improvement, so how can I bring out the big guns?

    Thank you. I love your work.

    • Chris Kresser says

      Hi Justin,

      I would explore all of the potential causes of inflammation I mentioned in the article, as well as things like mold/biotoxins, heavy metals, chronic infection, etc.

  59. Libby says

    Years ago started having panic attacks out of no where, which started doctor visits, medication for anti-depressant & anti-anxiety crippling terror at the young age of 28, I was a young mother with 3 small kids and wanted to died. This was in 1988 thank God my sister worked for a Chiroprator that turned me onto a book called “the yeast syndrome” and candida overgrowth. I basically followed the book, my doctor was not receptive to the concept of nutrition affecting health. I quit taking the meds which also included Ativan to take the edge off lol and slowly got off the meds ate meat, veggies, eggs & yogurt. The book is still in print was published in 1985 these Doctors that wrote book were way ahead of the times. Anyway it is basically paleo diet with nutritional support of herbs and vitamins. After that experience I am very skeptical of better living though modern medicine!

  60. says

    We dispense LDN and a few male customers are reporting improvement in their BPH (Benign Prostatic Hyperplasia) symptoms, especially the ones related to numerous bathroom visits. The more we look the more it seems systemic inflammation may be at the root of numerous immune diseases; MS, arthritis, IBS, and so on. Of course, there will always be the recommendation to reduce or eliminate environmental inflammation triggers (sugars, processed foods, grains, and so on). Please note that I am not suggesting that there is any empirical data to support these comments regarding BPH.

  61. Nate says

    This is a great article. I did a 60 day Paleo diet and noticed a drastic change in my attitude, energy level, confidence and the almost disappearance of my leaky gut syndrome. However, one day I caved in and ate all inflammatory items on a Paleo do not eat list. Within a week, I was stressed out, sluggish, dazed, confused and had mood swings and depression swings out of nowhere. After reading this article, I can attest that depression is a symptom of inflammation.

  62. Debbie says

    I think depression is even more complex than inflammation. The mind is more than inflammation. Depression can be intertwined with someone’s personality to the point where it’s not unlike eye or hair color. Most studies show anti-depressants don’t work, and I’m not sure alleviating inflammation would work either. Maybe in some cases – where people become ill and the depression is a result of that. But I think the majority of depressives are that way for deeper reasons having to do with our modern society and not knowing how to live in it.

  63. Lynn says

    Amazing article, thank you for sharing. As someone who has suffered depression most of my life and currently also other inflammatory issues this is very helpful information to have. Does not surprise me at all. I always wondered why some people could just have a short bout of depression treated with med’s if the underlying cause was an imbalance?

  64. says

    The universe is funny. I have been experiencing horrible depression all week and was trying to figure out what i was going to do because 5htp..etc nothing was working and boom …in my inbox was your article. You continue to amaze me with your boldness and I sincerely pray our healthcare will improve in this country so people do not have to suffer. Thanks Chris

  65. says

    Someone close to me suffered from serious depression his whole life. After a health crisis, he removed Gluten from his diet. Six weeks later the rash he’d had on his feet for as long as he could remember, and he started feeling good. A couple of months later (still gluten-free) he told me that he felt that his depression had lifted. Now gluten-free for about six months, he feels that he has found his cure for depression and finally (in his mid 50’s) he feels like he got his life back!

  66. says

    Yes, I agree 100%. It took me 19 years to study, experiment and find a way to move from a toxic lifestyle, toxic relationships, and a world of liars, to live holistically while my adoptive parents forced and threatened me since age 16 to take toxic psychiatric drugs. I now know they used their expensive “expert psychiatrists” to validate their story and to hide their abuses of their myself and the other 2 children they adopted. They “parented” their children by drugging them, suppressing any potential healthy connection to our own bodies, and lives.

    I am so grateful for your speaking to the root causes, the true power we have to take steps to feel good, to release the lies that are being perpetuated in every mainstream propaganda machine from grocery stores, conventional agriculture, medicine without morals, and Big Pharma being the machine that keeps the toxic food coming, and the medical bills growing.

    I am free of all this, thanks to health food stores, a weekly farm box delivered to my door (for $35. – all organic and diverse) and people like you who have the courage and heart to share what is actually true. Thank you, Chris!…

    and my thanks forever to Dr. Hyla Cass, MD, Dr. Peter Breggin, and Donna Gates/Body Ecology Diet author – they made me aware of wonderful choices, and The Truth about my body and mind, so I could heal. Also, Dr. Rev. Michael Bernard Beckwith & Rickie Byars Beckwith of Agape Int’l Spiritual Center were instrumental and I think it is worth mentioning my heroes. They are beautiful examples that the Truth is alive and well. They help me and I hope they help you keep it tuned in and turned on. I’m doing my best here co-creating a 260-acre regenerative design community on Maui. Love, Aloha, Claire

  67. says

    I know that I have never felt better, and my depression and anxiety is so much better and easier to manage since I have changed my diet. I have been eating Paleo for the last several months and I know cutting out gluten has helped me tremendously. Also I am type 2 diabetic and my blood sugar levels have dropped from being in the high 300’s to the low to mid 100’s now. I am so happy!

  68. Jamie says

    As someone who is at the extreme end suffering from major depression I agree with what you say. However I would add to that by saying that childhood trauma, such as emotional, physical or sexual abuse in childhood has a major impact on depression in later life.

    In my own experience I was emotionally and physically abused by my parents as a child and this has left a long lasting impact which has been a key factor on my depression. After reading up on this seems to be via negative neural wiring in my brain. I also volunteer with people suffering from mental health issues such as depression and when I ask them if they have suffered trauma in their childhood, without fail they always describe some sort of abuse or trauma.

    As well as the steps you have mentioned to overcome depression I would mention techniques to help rewire your brain via neuroplasticity in a positive way by doing such things as meditation practise and mindfulness based cognitive behavioral therapy. I’ve been eating a paleo diet and lifestyle for 4 years now, and by far the most important step for me has been positively re-wiring my brain which I have only just been doing very recently.

    With that said, I can see how having your brain wired wrongly produces inflammation and by re-wiring it in a positive manner reduces inflammation. My personal thoughts are that this seems an under-researched area in the paleo scene due to the massive effects it can have on health, especially depression (and other mental illnesses).

      • Jamie says

        The brain can re-wire itself throughout the life course through neuroplasticity where it literally changes the neural networks in the brain and this changes how the brain functions. For example depressed people can have a smaller hippocampus which is a key part of the limbic system and is involved in memory and recollection and the amygdala is often over-active. The amygdala is activated when a person recalls emotionally charged memories such as anger, fear and depressive thoughts. They often work together in a negative feedback loop causing depressive thoughts and a depressive mood. Mediation can help to quite down the amygdala and help the hippocampus physically grow as well as thickening the grey matter of the brain, especially in the pre-frontal cortex, the part that really make’s us human and is involved in personality.

        Other ways I have personally used to help re-wire my brain is through mindfulness based C.B.T, essentially positive thoughts and actions (which I understand is very hard to do at first when depressed but it worked for me). Socialisation has really helped me too so I volunteer, got involved in some groups to meet new people and cut out all the bad ones I didn’t want in my life.

        Whilst we have a brain that can biologically control human behaviour, thoughts and emotions, it does not control all of human behaviour. We have a mind that is not separate to the brain and the mind can be used through the power of will to help re-wire the brain.

        A couple of fantastic books to read are The Mind and the Brain: Neuroplasticity and the Power of Mental Force by Jeffrey M. Schwartz which is one of my favourite books of all time or The Mindful Brain: Reflection and Attunement in the Cultivation of Well-Being by Daniel J. Siegel

        • Jamie says

          With that said I can only talk about personal experience and with my own personal experience I can say that eating an inflammatory diet and so forth makes me feel depressed. I react to corn and oats in the way someone with coeliac disease reacts to gluten and that makes me feel severely depressed like nothing else. Doing all I can to limit inflammation via diet, sleep etc. is the pre-requisite to combat depression. I just find it fascinating the interplay between my emotional and physical health and the effects this has on my inflammation and depression.

  69. Karen says

    My experience of depression occurred in connection with severe hypothyroidism and I am wondering if this ties into the inflammation question. My thyroid had been malfunctioning for years without my knowledge and I finally ended down the black hole. Luckily I was diagnosed with thyroid lymphoma fifteen years ago, at 52, and recovered with the aid of surg/chemo/radiation. I was given synthroid, which kept me balanced for ten years, no depression.

    Two years ago I switched to a desiccated thyroid product and felt even better. However through a misunderstanding on my next prescription, which was for a year because we were sailing to Central America, I ended up taking too low of a dose for 4 months, I should have been taking 180mg and was only getting 150. On the lower dose I gradually went down again, until my husband finally realized what had probably happened and suggested I take more of the thyroid. I took the extra 30mg daily, which was now up to the exchange rate of the synthroid I had been taking, and within two weeks the depression was gone.

    Then three months ago, when I got a new prescription but for a different size pill, I again took the wrong dosage, and became very stressed and then depressed. Again my husband, after believing I had gone completely nuts, realized what was going on and suggested I take an extra dose for a few days. I did the math on my new pills and realized the mistake. Again the depression lifted once the dosage was right. There is no doubt in my mind that the depression was caused by low thyroid.

    Is having a low amount of thyroid associated with inflammation? Are there ways to build the system so that the low intake of thyroid does not cause this depression and, possibly, inflammation? I still have half my thyroid but was told it’s not functioning, or at least not much. I suddenly realized that if I was out somewhere and lost the pills, well, the thyroid keeps us alive, right? Until that moment I never realized I was so dependent on these little pills. Without them, which would come first, mental collapse, suicide, or does the system finally just give out, is that what happened to people before they had these pills? How long did they last?!

    Do you think that the depression is caused by inflammation caused by low thyroid, is that how this works? I would really love to know if there is anything else that would build up the system. I keep picturing this end-of-the-world scenario where there is no manufacture of thyroid pills. Or we’re marooned on a desert island. What would I do?

    Thanks so much for any ideas.

  70. Jennifer S. says

    Inflammation! This makes so much sense. The depression I lived with for 30+ years lifted when I changed my diet. I notice that when I eat things I shouldn’t, those old feelings come back pretty quickly. I’ve always wondered what exactly was causing it.

  71. says

    Absolutely I relate to this on both a personal and professional level. And just came from a local meeting in Boulder, CO this morning where the Denver Diet Dr. presented as well as a holistic psychiatrist. on this very topic to a group of mental health professionals.

    I’m a classic case e.g. adopted as an infant (gut health), childhood IBS syptoms, anxiety, adolescent alcohol abuse, more depression and anxiety, acid reflux, acne. was finally told to eat gluten free 10 years ago but it didn’t change the bouts with depression and fatigue. Continued sugar addiction. Diagnosed with breast cancer at 41 with co-occurring severe depression. Finally after 4 concerning blood markers of metabolic syndrome/pre-diabetes a cross fit friend handed me Gary Taube’s Why We Get Fat! I emptied my cupboard and within 2 weeks felt improved mood, energy, memory,, focus etc. Body aches went away and eventually lost 20 pounds without even trying.

    Best yet and related to this article the symptoms of depression I’d struggled with my whole life disappeared. As a former psychotherapist and consumer of numerous modalities of psychotherapy and psychotropic drugs I am a full believer.

  72. Bee says

    This spring I thought depression had returned as I had the same symptoms (primarily insomnia) that I had after delivering my son 15 years ago. Diagnosed with postpartum depression and prescribed a boatload of antidepressants back then, I finally got better and began sleeping after losing the baby weight. I had tapered off the antidepressants several years ago.

    Over the 15 years, I gained all the weight back. This time around, I was diagnosed with NASH, low vitamin D, metabolic syndrome, BAV and sleep apnea. It was exactly what I’d felt like postpartum although none of these conditions were considered (and when trying to conceive had been diagnosed with PCOS , which contributes to most of the aforementioned conditions except the BAV).

    This spring I bought the Paleo book and another book on nutrient-rich food and fatty liver, and began eating clean as possible and exercising daily, if only walking for 15 minutes. I’ve lost 30 lbs with about 20 more to go. With that and the cpap, I feel pretty good. It wasn’t a quick recovery but gradual. My liver is back to normal and energy returned. My heart is fine (no one ever investigated the heart murmur during pregnancy) and will be checked every year.

    I feel strongly now I was misdiagnosed with postpartum depression and wrongly treated with antidepressants when I probably had fatty liver and sleep apnea (insomnia was complaint postpartum and I never felt really “depressed” only from lack of sleep).

  73. Cherie says

    I have noticed that the pharmaceutical ads for medications for depression note “body aches” as a symptom of depression.
    Coincidence? My own personal experience has been that body aches are a symptom of inflammation. So if body aches occur with depression, wouldn’t it seem reasonable that depression is a symptom of inflammation, too?

  74. Eileen says

    I heard a news report that the number of children who are “mentally disabled” is at an all time high. Of course, they attributed it to better diagnosis and felt bad because low income people are being “left out” (good for them).

  75. William Giman says

    As a Homeopathic practitioner (retired) when someone came for a consultation for a physical problem, & then mentioned that they had been feeling depressed. Depression is a clinical term, in the old days it was called “sadness” or “melancholy”. It is a mental symptom from their inability to solve or resolve an important life problem, eg family, relationships, etc. This mental symptom can cause physical problems if not resolved in the short/long term. Eg, a person develops Gi problems, because they can’t stomach a personal relationship & can’t figure out how to resolve it

    • says

      I’ve followed this conversation with interest – (and learnt a lot!) hoping to see mention of the value of homeopathic treatment for mood disorders. Homeopathy differs from the other treatments mentioned in that it is ‘energy’ medicine that addresses dis-ease at its fundamental level. It’s safe, non-toxic, compatible with other therapies and extremely potent when correctly used. Don’t buy treatments off the shelf – especially for long-standing problems you need to consult a registered homeopath who will take your case properly and prescribe accordingly. Treatment is always aimed at cure – where cure is possible. So most people shouldn’t need to keep taking a remedy indefinitely. Having said that, I suggest regular followups with an experienced practitioner to keep the mind and body ‘tuned’. If cure is not possible, great benefits may still be achieved and the illness can be managed with the minimum use of drugs, etc. Homeopathy is capable of re-tuning the smallest imbalances and it’s a good idea to seek treatment early, which allows for more rapid results. A rule of thumb: you may expect to need one month of homeopathic treatment for every year of illness.

  76. Jane says

    Just a comment about the article – there is a typo “chronic infections (viral, bacterial, fungal), low vitamin D levels, dental cares and periodontal disease…”

    “Dental cares” should be dental caries, should it not?

    My editor’s eye caught that while I was reading your very informative article :)

  77. R. Hetrick says

    I am on an autoimmune protocol diet for my Hashimotos which developed during a very harrowing time of a cold turkey from a Benzodiazepine and am just finishing up a 3 year taper from Prozac. It has been a long, difficult 4 year journey, fraught with terrible depression and anxiety. The diet has helped somewhat and my body is now allowing me to take some supplements….here is my question…whenever I try to take magnesium, I get very depressed…anyone have any comments on this….very confused…I am low and i need it, but just cannot get it by supplement…

    • Dr. Carrie Carlson says

      Try topical magnesium. If you have kidney disease, watch your kidney blood levels. Topical magnesium works great for leg cramps too. Make sure you’re supporting your liver, with liver support supplements. Go gluten free if you aren’t already. If your gut isn’t happy, could be source of depression. Are you doing Dr. Kharrazians hashimotos protocol?

  78. The Beckster says

    After 30 years of mild to severe depression, multiple drugs, and talk therapy, I saw a meme on Facebook that said, “Before you diagnose yourself with depression or low self-esteem, you actually may be simply surrounded by a$$holes.” A light went off – maybe it wasn’t just me? Maybe the stress of my job, a grumpy husband, and an evil mother was a contributing factor in my depression? I got a new job, encouraged my husband to be more thoughtful, and told my mom to fly a kite. I felt much better!! I added paleo a few months later, and I’m now down to a quarter of the amount of Zoloft I was previously taking. I’m not quite cured, but I’m definitely recovering!

  79. Brian says

    I’ve had chronic depression, anxiety and panic since birth. I’ve been on paleo diet for the last two years with mild effects on my depression and anxiety. I think that low inflammation will help depression but not for those with chronic conditions. Psychopharmcological drugs have helped me and many people immensely. However, if you are on the wrong drug or wrong dosage, you will not see the benefit. You have to actively manage your Psychopharmcological drugs intake. If you don’t you will end up no better off or worse or have too many side effects. If you have chronic depression and anxiety, I’d suggest buying books by Stephen Stahl as they articulate exactly how to utilize psychopharmocological drugs to their benefit. If you do it carelessly, they can have side effects and not be helpful

    It is also too simplified to say that these drugs effect only dopamine, neuroepernephen and serotonin. There are many of neurochemicals in the brain that these drugs act on.

    • Chris Kresser says

      Something I forgot to mention in the article, but will add now, is that there’s evidence that some antidepressants reduce inflammatory cytokine production and that may in part explain why they are helpful in some cases.

      • Chimonger says

        There are apparently [?] minimal blood tests to check for inflammation. This article is spot-on. AND, IMHO, medicine is MISSING inflammatory states too often.
        Q.: What does one do when labs all look “in normal range”, but one’s symptoms all point to inflammatory conditions?
        Q.: Might taking supplements and herbs to decrease inflammation, screw up lab results?
        Q.: Could supplements/herbs require far longer—say, abstaining from them for 2 weeks to one month, to get out of the system, before doing the lab tests to check for inflammatory conditions?
        Q.: Maybe we really need far better tests?
        [Have not been impressed by mechanized lab testing’s prevalence of false results on so many kinds of tests–for at least 30 years now]

      • SKG says

        Are there medicines that you believe are safe and possibly helpful to take? If someone has been struggling with depression most of their life, follow a very healthy diet, supplement with resistant starch, take Prescript Assist, exercise regularly, etc., what do you suggest would be the next step in fighting depression?

        • prioris says

          Research points to EPA without the DHA as treatment for depression. Have you tried that. Have you tried experimenting with high dose EPA.

  80. Susan says

    If inflammatory factors play such a huge role in depression, how is it that many suffer in a cyclical fashion….I would think that unless they know of and are addressing the inflammation,there would not be a cyclical pattern to their experience. My best friend has just come out of a major depression and I need to be able answer questions she may have when I propose that she consider the inflammatory issue. I started personal Paleo Code in May and have seen results in my own life with mood control even though depression has not bee an issue for me…..I’ve also lost ten pounds and am hoping to get my arthritis to decrease… Thanks so much,

    • Chris Kresser says

      Inflammation often also occurs in a cyclical fashion. For example, autoimmune diseases are known to relapse and remit, and vitamin D levels fluctuate throughout the year (which could in part explain seasonal affective disorder).

      That said, as I mentioned in the article, depression is multifactorial and inflammation is not the only contributing factor (though it may be the primary one).

      • TJayne says

        I wonder if histamine and/or methylation issues could also be a cyclical contributing factor? My husband has OCD tendencies (under-methylation) and they really rear their ugly head in the spring and fall (when his seasonal allergies are at their worst = high environmental histamine), thus following a very predictable and cyclical pattern as well. At first I thought it was due to the seasonal change in the amount of daylight and changing vitamin D status… supplementation didn’t change much however. Any thoughts?

      • Debbie says

        Mental illness, including depression is so complex. For myself, life events are a definite trigger – and these can be small events. Life events can also be an up-lifter for me. I am almost always lifted up and fine when around people I like. Sounds simple, right? Hang out with people I like. But, I could never seem to manage that. So – it’s complicated.

    • Allison Jones says

      Cyclical nature may also possibly relate to changes in the microbiome occurring for different reasons and the resulting effect on inflammation.

  81. sara says

    Having dealt with sever obsessive anxiety since 9.. Tracing back to my mom ,grandpa, great grandma and seeing it in one of my sons already (8l ) I would love to just know what the cause is instead of running around in circles wasting time and money trying to heal it. I’m 35 now so I have known no other life. Seeing the strong genetics I can’t help but think genetics play a role in this?

    • TJayne says


      My spouse was diagnosed as having obsessive compulsive disorder long before we met. Although I’ve never witnessed any compulsivity or rituals, he definitely suffers from the obsessive side of it. Our son also has these same tendencies. Both are anxious, highly reactive, and worriers. Tendencies seem to be worse in the Spring and Fall (when allergies are also an issue). While my husband has learned to cope with his OCD quite well, it breaks my heart to see my son not enjoying life as a child should due to anxieties over things he has no control. I have given him low dose 5htp in the past and it worked well (and had the added benefit of greatly reducing his migraines) but can cause upset stomach. More recently I’ve discovered the link of OCD with methylation issues (histamine intolerance). Chris has touched on this subject on this site. Read up on this, as well as the MTHFR mutation and how it affects methylation. Since learning of this, I’ve given my son inositol with great results, but the b vitamins are touchy–certain ones can make OCD worse–depending on whether you are an over- or under-methylator. Read, read, read! Hopefully I’ve offered you something new to research. I hope it leads to some relief for you and your son!

      • Chimonger says

        IMHO, gut Flora and the condition the gut is in, makes a huge difference in many.
        Science is now researching, and gotten some good preliminary results, showing that at least one good flora, L. Rhamnosus [?] has direct effect of remedying depression and anxiety.
        Other Flora do other tasks–that’s why we NEED them so much, and in a broad array.
        Not all fermented foods have the same cultures.
        I look for those listing Rhamnosus–and it indeed seems to help several people I work with.
        When the gut is out-of-balance, inflammation happens–and it’s all downhill from there.

  82. Anne says

    When I stopped eating gluten 11 yrs ago a dark curtain lifted and a depression, I did not even realize I had, disappeared. I did not know I was depressed because that is how I always felt and thought it was “normal”. Even colors got brighter. I never knew how good my brain could feel. If I get the slightest amount of gluten by accident, I become agitated and depressed. I quickly moved to a paleo diet as I realized that I feel my best when highly processed foods are removed too.

    Thanks for another great article Chris.

  83. Kathryn Shimmura says

    Fascinating! Thank you! I tell my psychotherapy clients to make sure to eat healthfully, exercise and get plenty of sleep. Those that do tend to feel better.

    • Chris Kresser says

      There are some very smart psychiatrists using Paleo successfully in their practice, like Emily Deans, Kelly Brogan and Drew Ramsey. In the future I don’t think we’ll have as much of a distinction between disorders which are “psychological” and “physiological”.

      That is one thing I always appreciated about my Chinese medicine training. They view all imbalances as simultaneously emotional, psychological and physical. There’s no way to separate those factors in reality; we just do it arbitrarily with our language.

  84. Gareth says

    Are the same factors at play in anxiety disorders, such that following the recommendations could lead to symptom improvements?

    • Chris Kresser says


      I haven’t seen as much research on inflammation > anxiety, but inflammatory cytokines affect the neurotransmitters that are involved in both depression and anxiety so I think many of the conclusions in this article would hold true for both conditions.

      • Alice says

        I was going through a very stressful period some years back losing three family members over about six weeks, and then having several panic attacks. I started taking a dessicated adrenal gland supplement and craving lots of coffee which i ate as coffee grounds on coffee ice cream to try to calm down.But I had another panic attack any way and was put on psych meds against my assent. Now I have finally been allowed to get off the psych meds and have my mind back! I take regular iron tabs which are supposed to help head off panic attacks. Always low on iron in my former vegetarian diet. Haven’t been able to give blood when on psych meds so haven’t discovered if my iron is still low. Interesting about the Rhamnosus bacteria for anxiety.

  85. JW says

    Great article. So glad you are addressing this issue. I am wondering if you would consider adding alcohol use and abuse to the list of factors associated with the inflammatory process? I work in the mental health field and witness the effects of chronic use and abuse in folks who otherwise are very dedicated to health. Recent research indicates that even light alcohol use is associated with SIBO and an article profiled on NPR this week examined the science behind hangovers suggesting
    inflammation as a probable cause.

  86. Andrea Sapienza says


    Thanks for another amazing piece of work! As usual…

    I inadvertently cured my sub-clinical to clinical depression when I tended to my gliadin antibodies. Now I’m a megaphone for a nutrient dense diet, kick-*** sleep, ultra self-care!


  87. Robert says

    Depression is multifactorial.

    It’s not as simple as eating better and working out for many people. Life events can effect your brain chemistry, relationships, self-talk, nutrition, exercise, chronic stress levels, etc.

    It’s nearly impossible to isolate depression as being caused by _______________ *fill in your favorite thing*

    I think it’s oversimplifying the disorder to state it’s simply a disorder of higher levels of inflammatory cytokines. New research will continue to show some connection between different factors, but the truth is that so many different therapies work for so many different people because there are MANY causes that lead to the phenotype we see as depression.

    With that said, eat well and exercise – sure. But it’s not fair to think we’ve stumbled onto some hidden truth by saying we all just need to be more paleo.

    • Chris Kresser says

      Did you read this paragraph in the article?

      I don’t mean to suggest that emotional and psychological factors don’t play an important role in depression. In many cases they do, and I’ve written on that topic before. However, the assumption in mainstream medicine that depression is exclusively caused by those factors is obviously not true, and too often these other potential underlying causes go unexplored. The doctor prescribes an antidepressant, the patient takes it, and that’s the end of the discussion.

      I did not suggest that inflammation is the sole cause of depression. Like all chronic, modern conditions, it is multifactorial and the etiology varies from person to person.

      • Catherine says

        Robert’s statement “but the truth is that so many different therapies work for so many different people because there are MANY causes that lead to the phenotype we see as depression” is exactly what your (Chris’s) article is about . . many causes of depression, which are mediated by inflammation, caused by things such as SIBO/dysbiosis, infections, bad diet, etc.

        Chris, have you noticed that addressing the SIBO/dysbiosis of acne patients alleviates depression in those with both? Acne and depression seem to be comorbidities, so I’m interested in whether there are any testimonials for a common cause of SIBO/dysbiosis.

      • Robert says

        Fair enough, Chris. Admittedly, I only read the first 2/3rds or so of the article. I’m a 4th year medical student with a large interest in depression, although I’m not going into psychiatry. I agree that there is too much Rx’ing of random psych drugs to fix symptoms. But this is across ALL of medicine, most often physicians will Rx a drug to fix an issue. Why? Lifestyle changes are VERY difficult and few patients will adapt them. I only found this article because I subscribe to your email and I do enjoy your articles – you research well and I agree that paleo based diets are superior…

        With that said, the title of your article is a bit misleading: “Is Depression a Disease—or a Symptom of Inflammation?”. My criticism (which you addressed in your final words), is that depression IS a disease. Stating that it’s possibly just a symptom of chronic inflammation is minimizing all the other factors that go into making a depressed person depressed. And quite honestly, there are many diseases that are just symptoms from chronic inflammation – e.g. Crohn’s, endless amounts of nervous system diseases, dermatologic disorders, etc.

        I understand your business is to focus on the dietary side that can cause inflammation and I agree, it’s one of the issues for many individuals (especially in America), but as I was stating and you state at the end – there are many issues that cause the disease we call depression – it’s not simply a symptom of inflammation.

        We could test your theory by treating chronic depression with anti-inflammatories. Has anyone every tried a barrage of anti-inflammatories to treat an acute case of depression? A suicidal individual who is on their last wits getting some NSAIDs and steroids? I don’t think we’ve tried that. I’d love to see the study done though.

        I don’t mean to be caustic because I think you’re one of the best sources of nutritional information that I’ve found and I find your work to be great and concise. But as this area is a large interest of mine and I’ve done a bit of reading on it, I balked at the idea that this could be the primary driving force behind depression (as your title makes it sound like).

        Anyway, keep up the good work.

  88. Celida DeFreitas says

    I had never suffered from depression until last winter, when all of the sudden I started to get so sad and uncontrollable crying episodes for no reason, very fearful but didn’t know what I was afraid of. blamed it on the stress of losing so many loved ones in the last 10 years do to terminal illnesses, I felt it was finally hitting me. Intuitively I knew something was wrong, so I got a micronutrient test done by spectracell and other blood work. Found out I was deficient in B12, Inositol, glutathione and coQ10 and some other b vitamins and minerals were borderline. also my D was at 16.
    Started to supplement for what I was deficient in and my sadness started to go away. I was also following a strict paleo diet for 5 years, I knew I was missing something but did not know what. After reading the paleo code I realized I needed more starch so I started eating the starchy tubers such as potatoes and yuca, and green and yellow plantains. What a difference all these changes have made. BTW I found an article about depression being treated with Inositol, go figure. Thanks for all the great info you give us Chris.

  89. Stacey says

    I wish more doctor’s new about diet affecting mental health. I suffered from depression on and off for several years without treatment, but then in my early 40s I had a bout that was definitely not related to any crisis in my environment that needed to be dealt with by talking to someone. I was put on Welbutrin and things perked up considerably, but other health issues started.
    In the end, it was only after realizing that I had a problem with gluten and had cut out all grains for over a year that I realized I was incredibly happy and not stressed. I spoke with my GP about getting off the medication and I haven’t looked back since!

  90. M G says

    Thank you for another excellent piece of information!
    I need a suggestion for the best multi vitamin, pls…used up all my centrum silver and don’t want to buy that again.

    • Nate says

      Just looking at yourself is often revealing. Skin color/disorder, body fat, fatigue, et al. are very telling. Specific to blood tests, the level of C-reactive protein (aka CRP) rises when there is inflammation throughout the body. Erythrocyte sedimentation rate (aka ESR) ferritin, homocysteine and plasma viscosity (aka PV) are other measures. Hope that helps.

  91. Anne says

    Going paleo and getting Vit. D levels up enabled me to get off 3 anti-depressant meds I had been taking for years. It took all of 3 months. Am so a believer in diet dictating your health. The psychiatrist I had been seeing forever never once discussed diet.

  92. Marie-Chantal says

    chronic depression..& no energy for over 20 years all kinds anti-depressants (prozac, effexor, rameron, celexa, ability….etc.)
    omega3, maca, gaba, probiotic, mag/cal, D3, B12, chromium, etc. paleo diet, no extra weight, sleep 9 hours a night (discovered sleep apnea 10 months ago, restmed machine was supposed to change my life!!! DID NOT still no energy) inflammation CRP 0,25 mg/L (very low) high HDL / low LDL ….
    no stress from work (LTD) … no kids….no $ problems….do not smoke nor drink.

    • Dr. Carrie Carlson says

      Have you looked at your heavy metal exposures? Do you have any dental fillings? Environmental exposures like mold, untested well water (arsenic, etc…) have you tested for Genetic SNPs, gene mutations? Like MTHFR? Another thought is kryptopyrole.

    • Catherine says

      My depression seems to stem from low iron due to decreased absorption from some gut dysbiosis, even though my ferritin tests within range, just on the low side. This type of thing can be overlooked by your doctor, but a subset of people experience various symptoms of deficiency when their ferritin falls below 50. It’s something to look into, anyway.

        • Catherine says

          I actually am on lactoferrin, but it doesn’t seem to make a difference, other than reducing acne, which is great too! I keep hoping there’s someone who’s had a similar experience and figured out what the problem was, because right now even my ginormous dose of daily iron is barely making a difference. One month showed only an increase of 2 points in my ferritin.

          • Allison says

            Sorry to hear the lactoferrin hasn’t helped with your iron :( I have had difficulty raising my ferritin levels in the past, so I know how frustrating it is. Hopefully something improves in your digestive system to help you get the ferritin up!

    • Lucy says

      There is some exciting research coming through on the MTHFR gene, someone else here has mentioned it too. You’ll need a holistic type practitioner, get some gene testing (23 and me) and start exploring your Methylation Cycle.

    • says

      Marie, you may be one who needs to examine your spiritual life as well. What is your contentment level? Do you complain a lot, whine, find fault with others or everything? I’m not suggesting that you do; just highlighting that these things in themselves are enough to bring about a chronically negative outlook on life which may lead to depression. Discontentment can also express itself by ‘trying to keep up with the Jones’s,’ or even excessive thrill-seeking. I feel your frustration–I’ve just added you to my prayer list for this week! I believe you can and will feel better! :)

  93. tw says


    What about depression following exercise?

    I have on more than one occasion had depressive symptoms following intensive training on a rowing ergometer and sometimes after a big mtb ride.

    This usually occurs the day following.

    Inflammation as a cause makes sense, but how does one address this assuming the same level of intensity?

  94. Amy says

    This is timely for me, as I experience depression periodically and am in the midst of an “episode”. What I have learned from dealing with this over the past 10+ years: Medication is the ladder to get out of the hole I’ve fallen into – I don’t need it forever, but for at least several months while I ramp up the other strategies. As much as I’d love to use lifestyle interventions to climb back out, once I’m stuck in a deep hole, it’s got to be the ladder.

    All this said, once I’ve climbed out, all these anti-inflammatory activities you’ve identified, help me navigate around future holes and keep me mentally healthy, but they’re not fool-proof. I have made a concerted effort over the past 9 or so months to adopt a lot of these activities – I walk outdoors everyday, do sprints, sail, eat basically primally (dramatically better than a year ago), get vitamin D, go to therapy and actively use my social supports – and I still fell into a very deep hole a couple months ago, likely triggered by the end of a long-term relationship, a major stress event (previous episodes have not always had a clear stress trigger). This is the first time I’ve become depressed while already doing a lot of these healthy lifestyle things, many of which I scaled up anticipating I would need them to get through the impending heartbreak.

    Of course I’m not perfect – I could do better with the probiotics and sleep management – but if the threshold for curing or remaining in remission from depression is doing all of those things consistently, honestly that’s just not realistic. I do think having more knowledge about the link between inflammation and depression is totally worthy, but I hesitate to de-emphasize the value of anti-depressants as they are truly a life line (or ladder, for me).

    • Stacey says

      I suffered from depression on and off for over a decade and only with the last severe round did I get a prescription for Welbutrin. I agree that I would not have been able to get out of the hole without immediate help.
      That said, the Paleo/grain free diet has gone a long way to keeping my mood in the positive. I am no longer on any medication. Currently I am dealing with my dad dying from a very aggressive brain cancer that is incurable. I find myself so overwhelmed with stress that I can’t sleep and feel immobilized on occasion by the physical effects of extreme sadness/depression. This time around I have been able to use GABA and magnesium at night to get sufficient sleep. I wouldn’t say I always get excellent sleep, but it is much better. Going to work and having a routine at home keeps me focused and helps me put things into perspective.
      I think as a society we need to accept that serious problems like a break up with a partner or the death of a loved one should be expected to cause severe sadness and maybe depression – for a while. And that too is natural.

    • Catherine says

      Amy, I agree on using the ladder; sometimes it’s just too much. However, diet is only one possible source of inflammation. After all, there is some pathophysiology here, depression doesn’t just appear out of nowhere. Personally, diet just was not the source of inflammation for my depression, but there are lots of other things to still look into, since there does actually have to be some cause.

      I feel that many people may have missed the point of the article, which is that depression is just a downstream symptom of an inflammatory response to something. The way you worded your comment, for ex: “if the threshold for curing or remaining in remission from depression is doing all of those things consistently” looked to me like you do view depression as a disease, instead of a symptom with a root cause, and I think the outlook is much more hopeful and logical if you consider it from a different perspective.

      I am in the same boat as you, so I know it can get so bad that an antidepressant is needed, but using drugs/herbs/supplements is still merely attempting to treat a symptom without establishing what causes the symptom, or in other words, what the actual disease is. I guess I will use myself as an example . . Depression was actually one of the last symptoms I developed in what I now believe to be some sort of SIBO/dysbiosis. This started in my teens, when I was initially only symptomatic with acne, but by my midteens had progressed to decreased iron absorption, and PCOS. In my 20s the hypothyroid symptoms ramped up and finally the depression. As probably anyone (except my doctor, apparently) can see, there is an underlying disease state (the SIBO/dysbiosis), and depression is just one of multiple downstream symptoms.

      Anyways, because depression can get so bad, I fully support people doing whatever helps, including antidepressants, but I also think finding the root cause is the way to go for a real cure.

      • Amy says

        Wise words, Catherine! Thank you for your response to my comment. It’s so complex and I do think inflammation caused by a variety of things does lead to depression as a symptom. The irony being that to have the mental/emotional/physical stamina to really work on the root causes, I have to pinch out that depression. Oh where to start?!

  95. Pirate says

    I’ve suffered all my life from moodiness and anger. I took Prozac and for the first time ever felt relief…then it stopped working after only 6 mos. It felt just like coming down from a high…boom, over.
    About 4 y ago I changed my diet, eliminating refined sugar, going gluten free, organic…I also had nutritional testing done and take specific supps to address nutrient deficiencies.
    I feel really wonderful now, physically and mentally. I still can get unhappy/angry but its manageable not overwhelming.
    Drugs may have a role but it should be last resort and short term not the first line of defense forever.
    Btw, what about that glutamate and vinegar thing? Would love a f/u post on that. Thanks, bro you do good work!

  96. Ron says

    Chris, do you have any recommendations for people who have been diagnosed with Dementia? Diet suggestions, labs to run, or resources to look at? I think it is such a growing, and nasty disease that a podcast, or blogpost would be great on the subject. Thank you for all you do!

  97. crispy says

    and yet high dose cortisone (profound anti-inflammatory effect)
    can cause severe depression w suicidal tendencies (seen in a friend who used it for ulcerative colitis)

  98. Cindy says

    A while back I read a book called “The Great Influenza” by John Barry. The description of the people who died quickly of the 1918 flu seemed to mimic the symptoms of cytokine storm aka cytokine release syndrome. I’ve often wondered if we actually wnt through a population bottleneck with the people with the strongest immune systems dying before the could have children (WWI was also happening at that time and young soldiers were dying of the flu from being in such close quarters). If the people who survived actually had defective or less responsive immune systems, that could lead to people nowadays having more low level, chronic immune responses leading to some of the diseases we’re seeing more of today. It does seem strange that so many of our problems today can be linked back to inflammation and the immune system……….

    • Geckotreefrog says

      What an interesting comment. I have wondered for a long time about possible causes of the high mortality rate in young, strong people during the 1918 Flu Pandemic. I do think that a contributor to today’s chronic diseases is from compromised ancestral gut biomes. Of course, typical western diet, lack of traditional fermented foods & over use of antibiotics, & even westernized childbirth: “Cleaning out” the birth canal, where newborns would normally receive their Mother’s gut flora, & c- sections, where babies don’t have the opportunity to get exposed. But wait. They could! Some fascinating work is being done by Maria Gloria Dominguez Ph.D; she places sterile bandage material in the vagina of the mother prior to a scheduled c-section to give these babies the benefits of mom’s gut flora. Her work is centered on many facets of restoration of human gut biome, & I first saw her work on a program called ‘Aliens Inside us’, on Smithsonian Channel in 2013. Of course, our departure from Ancestral diets & lifestyles are also big contributors to gut biome problems and chronic illness. There Is a way to have the best of both worlds. & Chris Kresser is one of my main “Go To” sources for even-keeled, evidence based information.

  99. belle says

    I am a herbalist and the association between inflammation and depression is not new, but then we’re used to finding underlying causes!
    Interestingly, St Johns Wort has a few different mechanisms by which it can help people with depression, most well-known is its effect on serotonin levels, but it is also anti-inflammatory, affecting IL-1, IL-6 and TNF-alpha, cortisol and CRH, and also affects GABA.
    Used by herbalists for other inflammatory conditions such as arthritis, gout, gut inflammation and so on…as well as in depression

    • Allison Jones says

      Very interesting! I’m about to start my Naturopathy qualifications, can’t wait to learn a;l about the herbs.

  100. geraldine says

    I have noticed for a long time that when I leave sugar and white flour out of my diet, everything regarding my physical and mental health improves. I drop weight, feel happier, move better and generally enjoy life a lot more. It’s not an exaggeration to say it’s the difference between life and a living death. Regarding depression, I have suffered from in on and off and, now that I think about it, it may be linked to high-sugar eras in my life. This article is life-saving. Thanks so much

  101. Tyrannocaster says

    This is an excellent article. I had been thinking about inflammation as the underlying cause of so many of our problems (I wrote about it here ) but depression was not one of the things that had occurred to me. But what I really wanted to mention is that recently I have been experimenting with pycnogenol, which is supposed to be a pretty good anti-inflammatory (it is derived from the bark of pine trees, BTW) and to my surprise, for once I found that some of the hoopla seems to be justified. I am always a bit at a loss when something like this seems to help as I really don’t believe in magic bullets, but having discovered that magnesium made a HUGE difference in my life I am now on the lookout for other possible supplements that actually work. Most of them that I have tried have made no difference, but I believe that pycnogenol is worth following up on.

    • Altrubill says

      I suggest Wobenzym N for chronic inflammation. I take 3-4 tablets on waking and don’t eat for at least 45 minutes afterward. I know it works for me because I recently ran out and didn’t take it for a week. My debilitating arthritic hip pain and stiffness returned and I could not walk without looking injured. This resolved within days after re-starting my daily Wobenym N. I’m also taking magnesium carbonate daily and I’ve been eating low carb, high fat for the past 6 months.

  102. Paul says

    I enjoyed the read about depression. I agree with the nutritional approaches to clear the “cloudy view’ of so called depression. Definitely medication is a non -starter and should be eliminated. Once the view is clear a more sensible observation can be engaged in to look a depression. These observation don’t follow the European viewpoint of no psyche to mental depression. Therefore the road out is the road through . Lots of work just to start ahead of us. Keep strong.

    • Chris Kresser says

      Yes, there is some evidence that LDN reduces central nervous system inflammation, which is one reason why it may be effective against depression. It also increases endorphin levels, which could also explain it’s effect.

      • Chelsea says

        There too is evidence that from benefiting from the ‘rebound effect’ by taking LDN which upregulates the body’s own natural supply of met enkephalin (known as OGF) which has demonstrated to be a potent anti inflammatory agent exerting beneficial effects on the immune system ties in nicely with your research and explanation of depression. Thank you!

  103. sophie says

    I wonder if this “research” and the people who then blog about it have ever experienced depression…

    It’s easy to comment from the side-lines…

    • Chris Kresser says

      During my 10-year struggle with chronic illness I experienced severe depression. Healing my illness—which was inflammatory—cured my depression, so I am speaking not only about what the research says, but from personal experience.

      • Rae says

        I too experienced a complete reversal of mild to moderate depression upon discovering (at almost 50) that the underlying cause of a variety of symptoms was celiac disease. I have the blood work correlating, for example, a change in D-25 status from 42 on a more Paleo diet to 26 when travelling and feeling awful, and back to 43 now that I’m finally completely gluten free. My definition of ‘awful’ includes not only digestive but inflammatory symptoms of joint pain, pre-diabetic level blood glucose/A1C readings (despite not being overweight), headaches, etc. My theory has been that the malabsorption (of fat soluble vitamins D, A, K2) caused by the intestinal damage of celiac resulted in inflammation, spiraling into more symptoms. Chris, I wholeheartedly agree with your assessment that depression is a symptom of inflammation which can, in turn, have multiple root causes. Looks like most roads still lead to the gut!

        • Neicee says

          Rae, so true. Known since I was a child something was wrong. Took another 25 yrs. for a doctor to even bring up the subject of celiac. Lost faith in what most of them had to say. Started having heart palps about 3 yrs. ago. Tests showed a high level of blood calcium. Well, the endo scheduled me for hyper-parathyroid surgery. The surgeon insisted on further testing – which seems to be an epidemic where I live. No, it was “only” osteoporosis, everyone seems to be sporting their little throat scars……but wait, they do have very expensive meds available. I read up on them and said NO. Reading for the past 3 yrs. has helped amazingly well. That jerk endo never once recommended D3, magnesium. K-2, nor a slew of others – nor that celiac is known to prevent absorbtion of critical nutruients. Oh, and the magnesium puts me to sleep like a baby and my husband claims that I used to have a hair trigger temper and now I don’t.

      • Amy says

        Thank you for your candor regarding major depressive disorder. I’m 41 and struggle with Endometriosis, Fibromyalgia, interstitial Cystitus and IBS, plus major depression. I was diagnosed with IBS and anxiety at age 7. The other diagnosis followed in my early and mid-20’s. I have a Master’s Degree in Biology and Pathology received in ’99 so the clinical data has changed much over the years – also, as we say “Big Pharma,” has had an enormous impact on what and how information is studied and the results distributed. I’m preaching to the choir I realize. I guess my true question lies with this, I have bought whole-headedly, the Paleo diet/life-style, but still suffer major depression. I’m not on an SSRI or any other type of anti-depressant – having taken them in the past with no positive effect and sometimes extremely negative ones. Behavioral Cog. Therapy also has been of no long-term usefulness – other than the brief time I have a one on one session and am able to verbalize the negativity and severe abuse I endured as a child and in 2 other adult relationships. As I said, even then, the positive results are briefly felt.
        I do have VERY low D3 which I take a daily 5,000 IU dissolvable gel tab for and after many months have not noticed any help – though I need to check on my new D3 baseline on the dose, but the Dr seems to feel that unnecessary. Currently I take an opioid for my anxiety and PTSD and a strong narcotic for pain. I STRONGLY dislike being on any medication like this, but my Dr’s have yet to give me a reasonable alternative except for having a hysterectomy (!) which would be my 16th surgery and which would bring many many other physiological, not to mention neurological implications into play. I used to be a thin active healthy child. I want that back. I have too much life left to live, but I don’t want surgery and going cold-turkey off the opioid and narcotic frightens me and that’s the option my Dr gave me – no weaning schedule!? I guess, even with my own knowledge and the research I try to remain up-to-date on (not via Big Pharm.) I just don’t know where to start and the depression doesn’t help that, neither does having found myself in a position I cannot afford to eat and buy homeopathically. I know I’ve introduced many topics – any suggestions, especially with depression with weight gain appreciated. Also, I really want to explore how genetically predisposed we are to many of these things (knowing already how damaged our environment/ecosystem is) such as premie babies of mother’s who smoked, drank, ate poor diets and where peri-natally depressed themselves – any research you could point me to or any experience with generational illnesses?
        Thank you and thank you for your own tremendous documentation on Paleo/holistic health.

        • prioris says

          As someone has said, you need to take D3 with K2 MK7. they work together with calcium and a little vitamin A.

          15 surgeries is way too many. I could imagine you have been very damaged by the surgeries.

          Usually one can find natural remedies to avoid surgery but doctors stay ignorant of them. you need to exhaust alternative non surgery methods.

          What natural remedies have you tried for IBS, Endometriosis and IC ?

      • Tami O' says

        Thank you Kris, that’s one. Knowledge is good (as evidenced here by all the knowledgeable posts), but WISDOM, is precious.

      • sophie says

        Well it’s still not true for everyone.
        I keep having my body checked for inflammation and I don’t have any (through blood work)
        …and yet I still struggle with clinical depression (dysthymia).

        • John Es says

          I think inflammation is hard to measure. My CRP came in within the reference range, but, I don’t know if that is a very valuable measurement. Mark Sisson seems to think the reference range is too high.

          I was also fairly intrigued by the work of Dr. William Walsh, mentioned in the comments for Chris’ latest podcast on methylation. But, I was also intrigued by Dan Kalish’s work, and have lost my enthusiasm for his “mind mapping” approach. I have no first-hand experience with either approach.

          Here’s a link to The Bulletproof Executive’s interview of Dr. Walsh. I found it interesting, but, not making any recommendations.

          I hope you find a way to feel better, and I think I understand the frustration you might be feeling.

          • prioris says

            there is a supplement that brings CRP level down. One study showed it dropped CRP score by in participants by 50%. The supplement is called Provinal Omega 7 Concentrated Palmitoleic Acid. It seems to have a wide range of positive effect in people. It seems to work pretty quick within one month. Definitely something to look into.

    • Tami O' says

      Amen. Suffering with depression, who has the energy or clarity of mind to even read all this speculation! Just tell us what to do to stop the pain!

  104. Sylvia says

    I found the comment about magnesium and vit D interesting.
    So many people are Vit D deficient and I have always thought that there was more going on than just not getting enough sunshine. Also the magnesium deficiency is not from poor diet. I recently discovered that Aluminium toxicity blocks the absorption of magnesium. Many people have Aluminium toxicity because it is not only in aluminium cans, antiperspirants etc but it is in our water supply. I have bought a water filter to minimise the aluminium as well as many other heavy metals.

    • Geckotreefrog says

      Agreed! A reverse osmosis filtration system (Many under $300) is one of the best health investments you can make. Also removes chlorine & fluoride right at the tap, unlike faucet mount systems. Nobody should be Drinking chlorine, fluoride, aluminum & other junk that is present even in “superior” rated city water supplies.

  105. Peter Jeffries says

    I have Chronic Polymyalgia and Arthritis in many Joints. I’m Diabetic amongst other problems also. I found out I had very low Testosterone. Went on replacement therapy and it had a huge effect on the Polymyalgia and Diabetes and associated decades long intractable depression. I cannot say my problems disappeared but I was able to cope better than before. Testosterone has huge effects in men and women on many aspects of the systems in the body. Lack of it is like a car without fuel. I cannot get up the stairs without it.

  106. says

    Hello Chris

    Very insightful article. I stumbled over the sentence with mold being a a cause of chronic inflammation. Do you have further information about that? Just recently we found out that we had water coming from the apartment above us behind the wooden ceiling in out bathroom. It was full of hidden mold – for an unknown period of time. Now I am a bit concerned about possible long term consequences.
    Any further insight highly appreciated!


    • Chris Kresser says

      Hi Mike,

      I will be writing an article on how mold and other biotoxins can lead to something called “chronic inflammatory response syndrome (CIRS)” soon.

      • John Thomas says

        This is really needed Chris. Although I read estimates that only 2-5% of American homes have toxic mold, the presence of non-toxic mold is much more common, and seems to cause a lot of people (including me) health issues. I assumed it was just an allergic reaction, but I’d like to know more about other effects it might have, and especially any ways you know to deal with the symptoms.

        And thanks for the great article, as always!

  107. Darren says

    I have thought for a long time that dental problems and periodontal disease is a co-symptom of general inflammation not a causal agent. I have no research evidence to back this up, but I haven’t seen research that contradicts that idea either. The gums seem to be the type of tissue that would become easily inflamed/infected during a general low-grade body-wide inflammatory response, similar to the gut and skin.

  108. Edward Hutchinson says

    Excellent article. It’s a pity though there is no mention of MAGNESIUM an anti inflammatory agent most people consuming processed foods fail to meet the current low Magnesium RDA.
    Magnesium enables the Vitamin D form Cholecalcferol convert to calcidiol and then to calcitriol its active hormonal form.
    Correcting magnesium deficiency also impacts of Vitamin d levels and effectiveness.

    • says

      I’m a huge believer in magnesium supplements. After 10 years of constipation and 8 years of heart palpitations and chronic inflammation manifesting as arthritis I found out about magnesium. Within days of starting to take it things began to improve and now, four months later I have a new lease on life. (I had already changed my diet and exercised regularly, am not over weight, don’t smoke etc.)

      • Anne says

        Ardys, How much Magnesium did you take? I , too, suffer from constipation for 5 years or so. I heard advice to take Magnesium (500-1000) day and other source said Magnesium Citrate.

    • Steve Root says

      For me, symptoms of depression (five years ago) abated completely when I quit statin drugs and supplemented with magnesium (drinking mag water, per the affibers’ recipe, plus topical mag oil). My cholesterol levels are sky high, which may make my primary care physician nauseous but is clearly how my brain likes it.

      There is a chance, I suppose, that my self experimentation has had a placebo effect. I embrace it. Anyone with depression should be trying any non-harmful thing they can think of to fix the problem. If something helps, but it is only the placebo effect, fine. As I recall, for the SSRI drug trials the control groups experienced massive improvement in symptoms on a placebo, with the SSRIs only barely beating them (75% improved on SSRIs, 70% improved on placebo).

      I understand that doctors cannot prescribe placebos, which when the alternative is SSRIs seems a shame.

      If you have depressive symptoms, you need to get off of statins (at least as an experiment). Mag water (magnesium bicarbonate) is an outstanding way to supplement magnesium (easy, cheap (20 cents a day) and well absorbed). Mag oil (magnesium chloride (nigari) dissolved in water) applied topically is, in my non-expert opinion, another effective way to get magnesium.

  109. gh says

    In M.E. there is evidence of autoimmune activity against serotonin. Some patients have elevated serotonin, and some have low serotonin. I find a low 50mg dose of 5-HTP helps a bit, but 100mg gives me a headache. So I don’t think I have low serotonin, just that some serotonin is either damaged, or not completing its job because receptor sites aren’t functioning like they should because of inflammation.

    • SC says

      5-HTP 50mg 3x daily has helped me tremendously! I also tried 100mg 1x daily and got nothing more than an upset stomach. I did read somewhere that 5HTP shouldn’t be taken for more than 12 weeks at a time. Does anyone know if this is accurate? No doubt that a healthy diet only brings more benefits.

    • Edward Hutchinson says

      Re Curcumin – anti-inflammatory action.
      Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study used 500 mg twice daily or placebo for 8 weeks and concludes
      “Partial support is provided for the antidepressant effects of curcumin in people with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks after treatment.”
      Other research shows Curcumin works more effectively when taken in conjunction with Vitamin C. Vitamin C also helps resolve depression.
      It also makes sense to ensure natural levels of all anti-inflammatory agents (Omega 3, Vitamin D3, Magnesium and Melatonin) are all restored.

      • Geckotreefrog says

        Totally agree. The only thing to add is that Omega3’s are fragile & easily oxidized when in fish oil capsule form (from some forms of processing, heat in transportation, time sitting on a shelf…). So, Eating foods high in omega 3’s like Wild Caught salmon, mackerel… is best. I bet you know that, Edward, but I’m throwing this in because I only learned about importance of omega 3’s from Food sources in the last half year.

  110. emi11n says

    This is an interesting idea and certainly relates to my experience. I dealt with chronic subclinical depression for over twenty years, sometimes severe enough to reach a clinical level. Lexapro helped a little, birth control pills helped even more, but not enough, and the positive effect faded over time. 1 1/2 years ago i started a paleo diet, and was amazed to find all my mood issues gone without a trace. NO depression at all anymore. I don’t get very stressed out anymore, and events that used to crush me roll right off. I can’t express how wonderful it is to feel NORMAL. I have not had this effect with any other treatment. As to the shame of depression, i really think this is another symptom. I was deeply ashamed, not of being depressed, but of myself and my infinite flaws that I could not stop brooding over. Those things simply don’t bother me much anymore, thanks to my much healthier brain. All thanks to paleo.

  111. Marcia says

    The important thing aboit focusing on inflammation is to solve problems like leaky gut, root canal bacteria, gene problems that cause problems in the body, etc. These are issues for me, and the more I learn about these things, the better my depression gets. The rise in depression among the general population may be linked to all kinds of problems with our diets and health care () and environment. A Paleo diet low in carbs and sugar has helped me, and learning about MTHFR and other gene mutations has helped me, too. There’s a lot to learn. I wish the insurance companies would help with my expenses for supplements.

  112. RBK says

    I never experienced depression until the last year after my relationship with someone who had bipolar II. She was abusive towards me, so the stress was unlike I’ve ever experienced. I’ve managed my Crohn’s very well with GAPS, so I do everything you recommend.

    In my case, I think its the emotional and psychological factors, and my lack of a support network/friends that contributes to my depression. And the stress of being depressed and not supporting myself financially.

  113. says

    I totally believe the ubtestinal track can have enormous help to leading to other problems. That’s where it starts. I suffer mild depress duo and take Effexor! I also suffer intestinal bloating and colitis. I agree

  114. Marie says

    Would you characterize SAD as a potentially inflammation-driven disorder? I suffer terribly from it.
    My CRP levels have been undetectable, although to be fair I don’t remember whether those were taken in winter, spring or fall (wasn’t summer).
    While light therapy (I bought the little one you recommended) helps and I exercise regularly with benefit for maybe 2 hours after, the most profound effect I’ve experienced has been an SSRI.

        • Geckotreefrog says

          Marie, When possible, it is always better to get your Vit. D3 (really is a hormone) from the sun. Why? because the sun provides other factors that have a synergistic effect. There are also likely additional factors/ benefits provided by sun exposure that haven’t yet been discovered. I am 54, and yes, I still happily wear a bikini. Even if you normally don’t, it is worth getting one (or, something that allows Maximum skin exposure, like a rolled up tank top & shorts) & perhaps you have a back yard to lay out in. I do apply a nontoxic sunscreen to my face, neck & tops of hands to avoid wrinkles. (I like Tropical Sands all natural 30 spf lotion. it is sometimes on Amazon, or order from their website: Really, any brand that uses a physical barrier- Zinc &/ or titanium dioxide- & is biodegradable is safe to use. It’s also reef-safe. There are other good brands like Badger, but they are more expensive. T.S. 30 spf Won’t turn you white; the 50 spf will). Anyway, don’t put sunscreen anywhere unless you are avoiding wrinkles, have a sunburn or need to cover precancerous skin areas. The whole idea is to get maximum skin exposed to the sun on both sides Without getting a sunburn. Try to do this every few days. Even minimal sun exposure is better than none. Your body will store Vitamin D, so “stock up” from the sun during warmer weather & supplement only when it is just too cold to lay outside.

          • Marie says

            Thank you for the suggestion, and I agree entirely. In the summer I have no issues and get as much sun as possible.
            But it’s *seasonal* affective disorder, and the sun simply doesn’t get night enough in the sky, nor would I be able to bring myself to stand exposed in 20 degree weather :) The only option was supplementation.

    • Catherine says

      Marie, I’ve read that there might be a hypothyroid connection with SAD, but I’m not sure if much research was done, or if that connection panned out. It could be something to look into . . my hypo symptoms get much worse in the winter. If it was just the light exposure, I would assume that the light box would alleviate the problem, but since it doesn’t, perhaps the temperature difference is a factor to consider?

      • Marie says

        Yes, I believe the temperature difference is a factor, thank you very much for the suggestion! :) However, I don’t think it’s working through thyroid in my case.
        I’m under constant monitoring for ‘subclinical hypothyroidism,’ (thyroid hormones are just under where they should be) but I tried thyroid medication and all it did was speed up my metabolism enough to lose weight (that I can’t afford to lose). My hypothesis is that the cold triggers a bad nervous system reaction, though I’ve no science to support that that’s even possible.

    • says

      Hi Catherine
      Tryptophan is catabolised through the Kynurenine Pathway in 2 ways, triggered by inflammation and IDO or Indoleamine 2,3, dioxigenase enzyme, which usually produces an agitated depression, due to excessive output of Quinolinic acid, which is an NMDA receptor agonist.
      The second pathway, through the same Kynurenine process, is through TDO or Tryptophan 2,3, Dioxygenase, which results in Kynurenic acid, producing a melancholic depression, due to the antagonistic nature of Kynurenic aci. Severe forms of Tryptophan degradation results in Schizophrenia.
      Hope this helpsw

  115. John McDonel says

    I wish to speculate a little – perhaps these fall into order??? Seeing that most people here have abundant biochemicall knowledge, I hope to provoke ideas: one area of obvious inflammation is injury. Does depression (a chronic state) parallel chronic inflammation in multiple sclerosis due to ‘injury’ (much like varicose veins … of brain vesicles)?
    I found advertising for ‘cleaning arteries’ using EDTA, fascinating. One recent focus was the stagnant brain-blood supply was compromised in folks with multiple sclerosis. Would EDTA help? It is known that people with ms have low D3 [arterial calcium and vitamin K2 levels (M-7 fraction) I do not know. Would the new vitamin D3 patches from help here? They also have the K2 (M-7). Wouldn’t this assist with all nerve-tissue (like excess glucose) alteration (inflammation /depression)?

  116. JT says

    There’s no doubt that inflammation is a major factor in mental health and disease in general but is it possible that inflammation and oxidative stress can inhibit neurotransmitters like dopamine and serotonin thus affecting mood, behaviour and one’s sense of well being?
    In your podcast on the gut-brain connection you talk about how a large percentage of people with IBS have mental health problems and you did a great job at explaining the cyclical nature of disease and how stress impacts the body as a whole. I can’t disagree with you about inflammation and obviously chronic inflammation and chronic stress are a huge problem but i think there’s a variety of factors that create stress and inflammation. Biological, psychological, social, spiritual factors. I think taking steps to address inflammation like you have explained is a big part of the solution but i believe that unfortunately its more complicated then that and there’s many more factors that may be contributing to the problem and that may need to be addressed. Its a challenging problem to assess and solve or identify and prevent in our modern world and with our modern way of living.

    • Chris Kresser says

      Yes, there’s research showing that inflammatory cytokines affect neurotransmitter metabolism. But if that’s the case, the most effective approach will be to reduce cytokine production (i.e. inflammation) rather than focusing on its downstream effects (disrupted neurotransmitter metabolism). This is the primary difference between functional medicine and conventional and even integrative medicine. With a functional approach, we try to identify and then treat the root cause of a problem. With a conventional or integrative approach, it’s often about using drugs or supplements/herbs to suppress/treat symptoms.

      Having said that, depression—like all other modern diseases—is multifactorial and the etiology will differ from person to person. As I mentioned in the article, emotional and psychological factors do play a role and the idea that inflammation is the only cause is overly reductionistic. The point of this article is that inflammation is a major root cause (whether provoked by gut issues, stress, psychosocial problems, sleep deprivation, toxins, etc.) that often goes unexplored.

      • JT says

        That makes a lot of sense and this is why i’m such a big fan of you and your approach! Your trying to bring attention to a very important and very overlooked factor, which is inflammation what causes it.
        It was your articles on stress and practicing pleasure in your 9 steps to perfect health series and your podcast on the gut-brain axis that really opened my eyes to the bigger picture. You pointed me in the direction of people like Gabor Mate and Robert Sapolski, where i became very aware of the sociological and psychological factors of stress, which i think are often overlooked and unexplored as you say. I’m also intrigued by people like Dr Amen and his use of Brain Spect Imaging.
        I look forward to reading more from you on this subject. People need to become more educated on the complexity of modern health problems like add/adhd, mental health problems, addiction, alzheimers/dementia etc.

        • Jean says

          There is no science or credible research behind Dr. Amens claims about SPECT imaging, but he sure is making a lot of money convincing people that there is. I highly doubt that Chris Kresser would give any credibility to him at all. I’m all on board with this depression – inflamation link though since Chris backs it up with solid science.

          • JT says

            I hear what your saying about Dr Amen, and i’m not one to judge the science behind Brain Spect Imaging. Inflammation should definitely be the first thing addressed and as Chris explained with the goal of functional medicine, it makes sense to try identify and address the root cause. But i still think Brain Spect Imaging makes a lot more sense then the current typical approach of using pharmaceuticals based on symptoms or to try and to try and correct “chemical imbalances”.

      • Sue says

        Looking for ways to stop inflammation. Tired all the time, have allergies,fibromyalgia,asthma, others.
        Tired all the time.

        • Faye says

          Stop eating wheat and see if you can manage an organic diet. It helped me tremendously with my myositis (muscle inflamation). My whole body was all inflammation, I got completely cured by wheat-free and organic diet, acupuncture/acupressure and some little excercises everyday. This in less than a year. Regular health care told me there was no cure, only painkillers for the rest of my life……..

          • Yvonne Kotze says

            Diet consisting of a lot of organic fruit and veggies builds the immune system – it’s the building blocks of our bodies – do cure a lot of ailments. When a body is cremated, that is the only real substance left of us – the minerals (building blocks). As soon as you fill up your minerals, which is only present in our soil and in organic fruit and veg, the body is able to take up it’s own function of healing itself. You first detect a deficiency and then you do get symptoms and illnesses. By the time there is an illness, the deficiency is big – but can be reversed. Minerals also work on the psycho-somatic level and are able to reverse depression, Alzheimers, ADHD, etc

        • kimberly says

          Hi Sue – There are so many great herbs available that can help reduce inflammation – Turmeric is one – you can get it at a bulk section at a health food store/coop. One easy and tasty was to take it is to mix 1 tsp-1 tbs of turmeric powder into a cup of warm milk – also add some ground pepper and maybe tsp or so of coconut oil – these will help you body absorb the turmeric. You can sweeten it with honey and even add cocoa powder if you like which is a great antioxidant. Drink this brew 2x/day.
          Also – wondering if you have been tested for Lyme disease or other tick pathogens as these can cause your symptoms and are so frequently undiagnosed. The best lab for these tests is Igenex –
          Good luck!!

        • prioris says

          You likely have infections. You should consider trying a systemic anti fungal first and antibiotic protocol. I’d try the borax protocol also.

          Your asthma would likely be a fungal infection.

          I have come to the conclusion that there are different types of fibromyalgia. When one reads enough symptom reports, the symptoms seem different.

          Costochondritis is reported by around 70% by people with FMS. This is pretty significant but essentially treated as a separate medical condition. The definition of FMS has been corrupted.

          The medical community is just lumping all the cases in a single category. This makes FMS studies invalid and misleading. I think this is by design. There has never been any real effort to address the disease by the government since they want to keep people sick.

          Even worse, the way they diagnose it is very subjective hence not everyone who has it gets diagnosed.

          I think you have to divide FMS into an infectious and non infectious type. Most people likely have the infectious variety.

          I cured my FMS with an antibiotic called minocin pretty quickly after many decades. Most generic minocyclines will not work although a few specific ones will. They have pushed the price of minocin artificially way up. At least some of the FMS will have mycoplasma infection. You should consider an antibiotic protocol and borax protocol.

          One needs to address any fungal infections first. This could solve the problem by making it more difficult for the mycoplasma infection to thrive.

          Another consideration is that the FMS may be just a secondary infection but still resolvable by addressing the secondary infection.

        • Holly says

          All classic symptoms of hypothyroidism and all your issues are 100% curable with the right natural thyroid treatment. This is a must read book, Hypothyroidism the Unsuspected Illness by: Broda O. Barnes, this book is a major eye opener! Orthodox medicine is not taking the right approach to the majority of our health problems. You can also go to the website “stop the thyroid madness” for other information.

        • Jeanne says

          Please get checked for Lyme disease by a Lyme literate doctor. I just found out I have it after suffering for months with fatigue, migraine, muscle aches, neck pain…After seeing eight doctors over the course of 7 months it was my naturopathic dr. that ordered the test. I am on antibiotics now and feeling better. I hope you get the answers you need! :)

        • gibby says

          Look into Mthfr….20 years fatigue headaches Cf Fibra.M allergies soreness depression anxiety……80 percent gone ….methylation restored with a few supplements methylfolate and methylb12 and go grain/gluten free and eliminate as much folic acid from your diet as u can it’s in everything…good luck

        • says

          Have you been thoroughly tested for Lyme Disease through Igenex? I had/have Fibromyalgia and a laundry list of dx’s from over the years. Found out last year that I actually have Chronic Lyme and several very serious tick borne co-infections. This is a MAJOR issue for so many people and it is being kept quiet by the powers that be.

          Check out the free documentary on YouTube called Under Our Skin. I cannot recommend it highly enough to all people.

          That said, a Paleo diet has helped me more than any other type of treatment. My Fibro pains and symptoms virtually disappear when I eat Paleo/Primally. It’s nothing short of a miracle.

          The chronic fatigue/chronic tiredness is likely reactivated Epstein Barr Virus (EBV). Have you been tested for it? I would be willing to bet that you have it, as most Fibro/CFS patients tend to actually have Lyme Disease which reactivates dormant viruses in the body. This will make you feel like you have Mono 24/7. Just unrelenting tiredness. I know because I have the same thing.

          Plus, with these reactivated viruses and other health concerns, the adrenals get run down. Have you thoroughly tested your cortisol levels? You could be dealing with an adrenal issue.

          Please look into Lyme Disease. Information is conflicting – which is why I urge you to watch the film Under Our Skin so that you can understand why the info is so politicized.

          • says

            Also, MTHFR mutations & Mold sickness is extremely common for Lyme patients. I have both issues.

            I struggled with debilitating depression and suicidal thoughts/actions for most of my life up until I finally found out what I’m really dealing with. And with bringing up my B12 levels, eating Paleo, detoxing, changing my hygiene and household products, etc. I have dramatically changed my mental health.

          • prioris says

            EBV has nothing to do with CFS. It is just a secondary infection that only a small number of people with CFS have. Coconut oil works well for EBV.

            Generally Lyme / CFS / Severe MS / FMS / GWS have overlapping symptoms. The powers that be have spent many decades covering up these diseases. Many well known doctors involved with these diseases work covertly for the powers that be along with patient organizations.

            There is no official way to prove what one has because that is the way the powers that be want it. keep things murky. The powers that be already know what causes these diseases but they have made the decision to let people drift in the wind. they do let information out unofficially. Polio disease had the same cover ups.

            They have been coming up with new and improved Lyme tests for decades.

            Separating out MCS from the others is important also.

            I would concentrate on treatments and not focus on what one has. It would be nice to definitively know.

            It’s why I wouldn’t waste my time and risk my health having a colonoscopy etc for anything colon related. It will usually be an infection that needs to be addressed. No matter what tests you have, one is still left with, what does one do for the infection.

            The best way to approach these diseases is the way rheumatoid arthritis is approached.

            This gives a general perspective on how to approach these diseases


            This doesn’t mean everything will get necessarily all cured but if a lot of sickness is removed, it will improve the quality of your life. CFS will have a ciguatoxin involved hence difficult to remove from the body.

            Hayakawa has back tracked from his original ciguatera findings and claimed much of it has mitichondria origins even though he dissected the toxin down to the molecular level in his first studies. His research contracts are with the CDC, NIH, Pentagon etc, the very agencies involved spear heading the cover ups globally. Hence, he needs to talk out of both sides of his mouth. This has resulted in anyone with shellfish poisoning having their tests invalidated also or brought into question.

            You have an infection but can only guess what it is. Now what. The way to circumvent this political game is to take a generic approach to treatment. You might get lucky.

    • JD says

      Yes, it seems facile and contrived for the author to construct this article as an either / or argument of one causative theory against another. There is evidence of complex malfunction in neurotransmitter systems in many cases of depression. There is evidence of abnormally high levels of inflammatory chemicals and stress hormones as well. It is very liky that neither one of these observations can “explain” depression or even preempt one another in a causative chain. They are merely descriptive findings that can help to guide biological interventions for a complex condition.

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