Is Depression a Disease—or a Symptom of Inflammation?
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Is Depression a Disease—or a Symptom of Inflammation?

by Chris Kresser

Last updated on

A depressed person
Depression and inflammation are linked. Find out how.

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)

Research suggests that depression may be primarily caused by inflammation. Check out this article to find out more about the depression–inflammation connection. #healthylifestyle #chriskresser #wellness

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?”

Nine 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. 

1. Diet

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)

2. Obesity

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)

3. 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

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4. Stress

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. 

5. Lack of 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. 

6. 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

7. 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

8. 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

9. 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)

The Biggest Problem with the Chemical Imbalance Theory

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 theres an underlying physiological cause of their symptoms, they often feel a tremendous sense of relief and empowerment. Whats 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 thats the end of the discussion.

What to Do If You’re Suffering from Depression

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, The Paleo Cure.

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 me know in the comments section.


Join the conversation

  1. I was reading some articles about this magic truffles and shrooms before engaging my self for the first time. Like this one from .They say that it has a very potent effect on the brain and hallucination. Unlike marijuana does it have any medical use? In one article that I’ve read magic truffles or shrooms compaired to synthetic drugs are very alarming. Also magic mushroom are use on reducing the symptoms of depression, obsessive-compulsive disorder and anxiety. It can also help people to quit smoking and alcohol addiction.

    • It’s interesting to note that a known halucinogen, ketamine, is now being investigated to break therapy resistence in Prof Schoevers research group in Groningen, The Nls. For those who don’t want to part from their AD meds.

  2. Hi All, I just want to ask if anyone ever tried using medical cannabis as an alternative meds? I have read many articles about medical marijuana and how it can help you in terms of chronic pain, bone injuries, eating disorder/anorexia, anxiety disorders and panic attacks, inflammation, even cancer and a lot more. Like this article about a marijuana strain from: . Cbd and thc are also new to me and I don’t even smoke. If this is true I cant find any solid conclusive evidence that speaks to its efficacy. Any personal experience or testimonial would be highly appreciated. Thanks

  3. We have great experience with Solaray’s Special Formula Turmeric and Pharma Nord’s SelenoPrecise. Both are great anti-inflammatory tools. Will help with anything from oxidative stress, arthritis and a number of inflammation-related issues, including overuse injuries and even hypothyroidism (SelenoPrecise).

  4. The difference between depression and inflammation or fatigue is condition of adrenals and levels of cortisol. Depressed patients suffer enlarged adrenals that over-produce cortisol and cause weight gain. Inflamed patients with fatigue suffer shriveled adrenals that produce little or no cortisol. Inflamed, fatigued patients lose weight easily and exhibit signs of all hormoen deficicency: thyroid underfunction, pituitary dysfunction, adrenal deficiency, sleep and metabolism hormone imbalance. Anyone who measures just one set of hormones without blood-testing or ultra-sound testing for all hormones is a charlatan. Should not be treating inflamed, fatigued patients at all. Psychiatry has no place in treating Chronic Fatigue Syndrome.

  5. Another perspective from someone who is daily helping people with depression is that depression is when you turn your anger inward towards yourself. At the same time you cover that with tears. So the task with someone who is depressive is to get to the anger and find healthy ways of expressing it.

    • It’s a little scary you’re helping so many people with depression. Not only is the idea that depression is anger inward ARCHAIC (in use by EARLY psychoanalysts or ones today with little experience) and created by Freud, there has been no convincing evidence for it. As someone who is healing (quite successfully) from depression, you really need experience and properly taught before dealing with depressed people. The last thing anyone, especially depressed people, need is a focus on “expending emotions”. A way, way more healthy, realistic and working approach is to know and understand how thoughts and emotions work in tandem. For anyone dealing with *mental* depression, this article will somewhat apply to you, but you’re much better off looking into Dr. David D Burns work and Martin Seligman. For those with the more physical “depression”, this article will be more applicable to you, and I would suggest also looking at your calorie count and making sure that not only are you eating foods healthy for YOUR body, but also ENOUGH.

  6. My 8-year old daughter recently started having daily stomach aches and a little depression. I believe they are connected and are related to inflammation, as she comes from a long line of inflammatory diseases (including depression and other auto-immune disorders). However, she eats gluten free and breakfast and lunch and paleo at dinner. Takes omega 3, probiotics and vitamins 5-6 days/wk and does not eat a lot of sugar. So I am wondering where to go from here. Obviously breakfast and lunch could be improved, maybe a stronger probiotic, but what else can I do?

  7. Thank you for this!! I first noticed my health was deteriorating iat Christmas 2015, I had already eliminated dairy & gluten in June 2015, I got ill in Africa in 2014 and on returning home my doctor asked why I needed to repeat blood tests and said “I wish I cod close weight like you” I was skeletal, I hadnt eaten in 9 days, ot took me 3days to travel from the Sahara to sebuta the spanish territory where I ended up in hospotal with dehydration, kidney issies and goodness knows what, I was given 9 different drips!! My gut has bee
    n bad since that but I kept eating and dealing with more regular stomach cramps, bloating, I was already diagnosed with IBS years previously by a professor.
    So in Dec I was getting more and more ill, I started working at a school where I would pick up every cough and cold feom the children, I felt like I had no immunity and I was constantly feeling ran down, up until then I was eating well and at a healthy weight. The more the IBS symptoms happened the kore I started eliminating food to find the cause or trigger, but with zero help from the gp I continued to cut foods, my doc tested for allergies and didnt believe Iin IBS and offered me antidepressants. I have worked out most days since I was 15, then 28, I didnt want meds I wanted to find the reasons why! I saw another doc who advised me to take buscapan… she didnt listen or understand why I wanted to eliminate foods that affected me rather than mask the symptoms. I went back to the second gp who by now I had lost a lot of weight.. he said because now I had anxiety towards food and had eliminated a whole range of stuff that he will only presfribe antidepressants to surpress my anxiety to allow me to eat more. I saw a CBT therapist, who worked with the GP who then started telling me at each session I needed antidepressants. . I bought a book on gut health and learnt that you are able to test gut bacteria by the american gut. (Im still waiting for the results) I decided to try on my own, I started eating better and forcing myself to go for a bike ride, a bit scary cause I was so underweight, ive now gone private for a full GI test to find the imbalances and issues caused in my gut and will work with a private nutritionist to work out a protocol of supplements, pre/pro biotics, but I have had to go through deep dark depression and suicidal thoughts due to the lack of support! Private healthcare will cost over £1000 (uk) but at least I will learn where and what the inflamation is

    • I can relate Kayleigh! Long ago, I came back from Puerto Vallarta, Mexico with intestinal cramping and pains. This was back in 1989. I had no idea I had a parasite in the colon..this created the IBS and candida overgrowth…plus eventually a bacterial overgrowth.
      I have struggled most of my life with anxiety and depression all due to not being breast fed and given numerous broad spectrum antibiotics and never told to take probiotics.
      You have a bacterial overgrowth, so I hope that you can get this diagnosed by a Gastroenterologist first, then you need to take antibiotics to kill off the bad bacteria, then you need to implement the good guys (bacteria) back into the digestive tract. Otherwise, you’ll end up with heartburn or barrett’s esophagus from bad bacteria relocating from the colon into the small intestines. You will need a Functional/Integrative Medicine MD that specializes in Gastroenterology that can help to get back onto the road of life.
      Unfortunately, for me, I have mold that spread from the digestive tract into my tissues, because the candida and bacterial overgrowth weren’t treated properly and timely, so I am suffering with mold in my arms, legs, back, kidneys, liver, bladder. It loves fats and metals…it has been quite a journey for me. Please get help right away….I wish that someone could have helped me along the way long ago. Can’t go back!
      Good Luck to you…you have quite a support network here.

      • Ann, So sorry re what you have been through. Just wanted to mention that I breast fed my older son for 6 mos., but he has struggled w/ depression for years. (I do agree that breast feeding is important for many reasons). He wasn’t on antibiotics very often as a child, but I did know to put him on probiotics during & after antibiotics. My point is that depression is complex & not necessarily caused by what we may think. Best anti-depressive results for everyone in my family have been by adopting an Ancestral (Paleo) diet and exercise. C. Kresser has also written more recently about the most common micronutrient…deficiencies Including magnesium) that can contribute to depression. My favorite new book is ‘Paleo Principles’ (late 2017) by Sarah Ballantyne, PhD. It is the most comprehensive Paleo book written that also provides the Science that supports the paleo diet & lifestyle. (It isn’t a book about depression, though it is addressed under mental health: 1-2 grams daily of omega 3’s help depression in multiple studies. Also, low levels of the following are linked to depression: Vitamin D, B6, B9, B12, Zinc, & certain amino acids. These can all be corrected. Of course, many studies show exercise helps. Dr. Ballantyne states exercising outdoors w/ exposure to sunlight may be more beneficial to mental health than exercising indoors. (Brisk 20 min. walk outside w/ increased light exposure, 5 days per week). Yes, you can definitely move forward!

    • Well done love n you keep going, no doubt you will get much better as you heal your gut. Including bone broth in your diet everyday will help with the gut healing, from clean grassfed or free range animals of course, cheap and wonderful. I use a pressure cooker to make mine and double or triple cook the bones replacing and saving the broth after the first cook and i get a very “jelly” broth from it and enough to last a week.
      God bless you!

  8. Thank you for this enlightening article! I was diagnosed with bipoloar disorder 20 years ago and hospitalised 5 times during this period, vowing every time that this would never happen again. Recently, I have started looking at techniques such as mindfulness and visualization, as well as a whole foods diet to support my continued well-being and to try ways other than medication (which I still do of course take, although in reduced form – Lithium is essential, at least for the time being.. and I am working closely with my psychiatrist on types of medication and dosage needed) and what you say in this article is a real eye-opener for me. Having read a lot of books on mental health and related topics, I have yet never come across the link with inflammation. I will pursue this avenue further and already feel like there could be much good coming from it. My nutritionist recommended your site, so thank you both for this information and your dedication to this approach to healing! Natalie

    • Hey Natalie, you might want to take a look at the thyroid secret as well…in episode 2 they discuss the link between brain disorders (bipolar included) and thyroid disease. Just Google the thyroid secret and go from there, it’s been very enlightening for me so hopefully for you as well?

  9. I have celiacs, hashimotos, mthfr, mao gene, IBS and multiple chemical sensitivities. I know also my anxiety, depression, and paranoia were due to inflammation. I currently can not eat eggs, gluten, dairy, lugumes or soy. I am doing yoga outside. I take supplements and magnesium. I am currently trying L glutamine but so far it is had to sleep and I have nightmares. Maybe I am taking to much. It really makes me feel weird ? I guess I will back off. It made my joints and fatigue feel better. My joints pain, fibromyalgia and celiac rash only come back when I have cross contamination. Sometimes bad gut problems. I usually take activated charcoal and it helps.

    • Have you looked into the possibility that you have Mold illness? Candida or a bacterial overgrowth as well?
      Something to consider…
      Lyme can also affect you as well.
      Hopefully, you can find an Integrative/Functional Medicine MD. to help on your journey to correcting your health.
      Have you had a breath hydrogen test to determine you have a bacterial overgrowth in the gut by a Gastroenterologist?
      Eating a nutrient dense diet is helpful. Also, taking some glutathione will help with detoxification. I apply glutathione cream to my skin each day that helps. Its a special prescription done by a compounding pharmacy. You could be very toxic and your system has an imbalance. Not sure if eating bone broth could help to heal your gut…I would talk to the experts.

    • i would look at the autoimmune protocol as presented by sarah ballantyne to rebuild your immune system. i have similar intolerances/allergies. the only cavest i would add is to slowly increase the more fibrous allowed starches so as to not overwhelm a healing gut.

  10. Many forms of depression are triggered by the air we breath and low exposure to sunlight in the winter months.
    Our modern living patterns have drastically changed our responses to nature’s cues. Many of us are spending our working day in air-conditioned offices lit by banks of electrical lighting tubes.
    Our circadian clock is regulated by light. It is constantly setting and resetting our hormonal requirements depending on the season of the year. An imbalance of hormones can lead to Seasonal Affective Disorder or SAD. A common cause of depression. SAD light therapy can often help this type of depression.
    Lack of negative ions in the air we breath can also cause mild depression. Our modern lifestyle effectively strips the desirable negative ions out of the air and replaces them with positive ion molecules. Result tiredness and depression. Negative ion generators are available for home use to purify and revitalise the air we breath.
    Hope this helps someone too.

  11. Interessting. But how come depressed people sith low serotonin often feels so much better taking 5 htp? And people woth dopamine-deficiency caused depression, are so easily addicted? The neurotransmitters must play some key roles in depression as well? But maybe inflammation is the root cause of the imbalance in neurotransmitters to begin with.

    Maybe it doesnt have to do with the acual levels of neurotransmitters, but being less sensitive to the levels we have..?

  12. I have celiac but this post is not about me. When I was diagnosed and learned about the symptoms that gluten causes, I recognized so many of those symptoms in my husband. He suffered from anxiety and depression his entire life, even through childhood. He used to lie on the floor in agony after eating carb-heavy meals like cereal and bagels. So many other little things. He gave up gluten with me (this was several years ago) and overall he has done so much better. By the way, he was tested for celiac and was negative.

    His GI issues are gone. His mental health is better on most days, but here is the problem. He has severe reactions as often as once a week where he gets extremely anxious and severely depressed. These reactions are much stronger than they used to be when they were low-level constantly with him, but they also pass within hours, although usually he will remain in a moderate state of anxiety and depression for a few days before he feels better. Sometimes he will have other mild inflammatory markers with these episodes, such as sore gums and mild GI distress, but not always. Afterwards he will feel fine for a stretch of time, until the next time this happens.

    Needless to say the stress and anxiety is overwhelming both of us. We can’t figure out if he’s reacting to gluten or some other food intolerance, or if something else non-food related might be going on. The house is completely gluten and soy free, and we eat a processed-free diet of fresh organic fruits, vegetables, and wild/pasture-raised meat and eggs. We don’t eat out at restaurants, although he, not very often, goes out with friends or for work and his luck there runs about 50/50, careful as he tries to be notifying servers of allergies. I’m a great gluten litmus since I’m very sensitive, but he eats a few products that I don’t, such as yogurt (plain Stoneyfield), coffee (he grinds it himself), peanut butter (Teddies – gluten free) and Lundberg rice. We haven’t a noticed a pattern directly related to these products but he eats them pretty much every day so who knows?

    He’s allergic to potatoes and soy (no known contact with either) and lately we’ve been suspecting a corn intolerance, so he’s even on baking soda for toothpaste until we suss this out. We’re not sure what else we can do. He only takes one supplement. It’s for vit D since he was severely deficient and it’s free of everything – his levels are great now. Coffee is a life-line for him – I hate to see him on wild goose chases and giving things up to no effect, but would that be the next most reasonable thing to try? He’s gone stretches of time without all the other products I mentioned above, but coffee would be very, very difficult for him to eliminate.

    Are we barking up the wrong tree by continuing to pursue potentially unnecessary food restrictions? We don’t know what medical specialist he can go to – his PCP just wants to send him to a mental care professional. He’s had basic vit/thyroid/cortisol tests and all were normal. As a final option, he’s considering going on anti-depressants, but we’re trying our hardest to find the root cause of the problem before going that route. Does the extreme on/off nature of his symptoms even make sense if it’s not being caused by sudden allergic reactions? It just screams REACTION, and is so consistent with when he really does get glutened.


    • You can get a panel from a brilliant company called Cyrex labs that looks at gluten cross reactive foods. When one has a gluten intolerance, there are several other foods that the body can perceive in the same way as gluten due to their molecular structure, thus the reaction will be the same. The good news is that after identifying them, and taking them out for a period, then the body heals from those ‘cross reactive’ reactions and you can re introduce them one by one. But not gluten obviously. A Dunwoody food panel may also be of help as it shows foods that the body has developed immune complexes around. These tests should calm the symptoms down well as diet will be anti-inflammatory again. Then you can look at root causes and healing those. Whether they be infection, stress, toxic burden etc. I hope this helps!

    • Might be worth considering thyroid even though the tests and back fine. Also is your water fluoridated as this can be an underlying cause. You could also consider meditation and mindfulness.

    • You should check out Dr. Tom O’Bryan, the gut doctor. He’s amazing and understands what you’re going through.
      Go to
      You can test negative for celiac that traditional way, but there are many different gluten proteins, I think they’re called, that the one test won’t test for.
      Talk to his practice, Michelle Ross, or someone they can recommend in your area.

    • Sounds like a terrible leaky gut from eating wheat and gluten which damages the gut lining.
      Go to Dr. Tom O’Bryans office can help!
      You need to heal the gut but you also need to get a food sensitivity test.
      Traditional allergists can do their food allergy testing for major foods.
      So hopefully you have had some help by now.

    • Perhaps eliminating rice, yogurt, and peanuts might help, because both rice and dairy turn into sugar and this article says “Peanuts are one of the most common food allergens. There are naturally occurring molds found on peanuts. Even if you don’t have an anaphylactic response to peanuts, your body may recognize them as foreign invaders and create an inflammatory response.” Also I have a friend who swears by this food elimination diet: Best wishes.

  13. I was diagnosed on 10/27/16 with Chronic Inflammatory Response Syndrome (CIRS) due to four years of being exposed to toxic mold in my office. Levels of .81 trichothecene (stach) and 9.25 gliotoxin (asp/pen) in my mitochondria.

    Some days are better than others but mainly bad. Due to brain and body inflammation (CRP level high), the depression is the hardest thing to overcome. Going from a high-functioning, always full of energy person to someone who just wants to stay in bed all the time has been very difficult (as many of you can understand). I also experience severe itching on my upper arms and shoulders especially at night. It drives me mad and I am awake many nights because of it.

    Been to a transitional doctor because regular docs just want to give you prescriptions and these could make my situation worse. Taking fish oil, magnesium ascorbate, vitamin c, lysine, multivitamin…was taking cholestyramine as a binding agent to remove toxins but made me very, very nauseous so had to quit. Trying chlorella powder now. Think it has even messed up my hormone levels.

    Anyone out there experiencing the similar symptoms?

    • Hi Shelly. Yes, you are not alone. I too suffer from CIRS and my body is having a difficult time detoxing due to gene mutations. I suffer from awful depression and cognitive issues, brain fog, really bad motivation. Tried all classes of antidepressants, TMS therapy ketamine infusions, nothing worked. I can’t feel positive emotions and lost all passion for life. I’m very saddened and I’m a mother of a two yr old. I also stay in bed most of the days. I’m barely functional and I was also very active before being diagnosed. I’m only 26 and I feel like my life is over. The depression from the brain inflammation is by far the worst of all the symptoms that I suffer from. I feel numb to the world. The only way to heal is to be in a mold free environment. I have to leave my house and all its belongings, but you do what needs to be done in order to get better. As hard as it may be, try to stay positive and know that you do have a chance of healing. I find that near impossible to believe myself but but it’s what is keeping me alive.

    • Shelley,
      Where did you get the mold test done? I have had mold sensitivity tests done, and my immune system reacts to the toxic molds, like you have mentioned. You may also not be able to eliminate mold from your system as I am.. Ritchie Shoemaker has a protocol.
      Thank you for any help.

    • I have CIRS and am recovering. I work with Dr Andrew Heyman in Aldie VA (I’m not based there) I get local support and we have phone appts.

    • Shelly,
      Can you tell me how and where you were tested for the mold? My doctor’s are clueless.
      I need your help.
      My doctor doesn’t want to give me the Wellchol to eliminate mold from my system because my liver enzymes have been chronically elevated due to having a candida overgrowth that wasn’t treated and became pathogenic.
      Could you please help?

  14. Thank you for this eye opening article! I have been “walking wounded” (what a college professor called depression) for almost 50 years, have been on meds for at least half of those years which definitely helped, and have benefited from talk therapies, consistent exercise (walking, yoga, meditation), too. But, still felt like there was more to do. Chronic inflammation? I have seen articles in the past, but never really given them the time of day. So thankful to you for sharing and to me for reading it ?. I WILL BE reading more about this theory! THANKS AGAIN!

  15. I was not aware of the connection between inflammation and depression. However, I have experienced this myself. After 30 years on an SSRI I have been able to stop it. After 1.5 years of improved nutrition, no sugar, no flour in my diet. I am so excited to be off of the medication. I had tried to get off multiple times before now and my mood always tanked!!

  16. I suffer from Seasonal Affective Disorder (SAD) during the months November to early April. This is alleviated by Light Therapy and yes taking Prozac during these months.

    From April through October I am fine with no problems.

  17. I’ve struggled off and on with depression for years. Also digestive issues. More recently, bacterial and viral infections. Bodily inflammation (like in my joints). Panic attacks and lack of emmotion or feeling or care. A long list of physical and mental/emmotional symptoms. Been treated for Candida overgrowth and yersinia infection in my gut. Being treated for Lyme and virus now.

  18. I have tried everything to help with my depression and anxiety. More recently I’ve been eating mostly AIP. My symptoms have been okay but not where I’d like them to be. I haven’t had a panic attack in a long time, I’m working again, and I’m no longer depressed. All of these things are great — but I still feel very detached from reality and my memory is off. I guess it could be described as pretty moderate to severe “brain fog.” I’m just not myself yet. Today I went to the dentist for the first time in years (we haven’t been able to afford it) and found out I have periodontal disease! I’m wondering if this could be behind some of my issues since it’s inflammation in my body. So now I’ll go in for aggressive treatment for that in two weeks and I’ll definitely be on top of it from now on. I keep searching for the “cure” for what’s going on with me. I’m going to join a new gym opening up in our area next month (we don’t have one where we live yet) and I’m hoping that getting regular cardiovascular exercise will push me in the right direction even more. I know it’s very important to fight inflammation and now there’s a new study showing a correlation between cardiovascular exercise and gut bacteria diversity. I want to beat this!

    • walk around your neighborhood with a couple of bottles of water for weights, do arm exercises with the water & when your thirsty from all your activity drink.
      Start with a short walk say 5 minutes away from the house and then increase it.
      Who needs a gym? But if you need that for accountabiltiy do it.
      Keep trying girl; & good luck & best wishes.
      I used Joe Cross juicing & mostly veg for 3 months then progressed to paleo diet.
      I Feel great – depression free for about 18 months after 25 years of depression.

    • Some studies have shown that depression physically damages the brain. So your body may just need some time to repair itself. It sounds like you’re doing all the right things! Hang in there!

  19. I agree. Based on my experience, the inflammation symptoms precede my anxiety or depression. I get on periodic bases bloating, rumbling and lower pain in my abdomen and a high acid in my stomach. I have Helico Pylori which was under control for more than 10 years and i abused with some alcohol and smoking and the stomach symptoms have returned and so my anxiety. The toxins are causing my neurological problems

    • You more than likely have a small intestinal bacterial overgrowth plus a candida overgrowth. You also may have a leaky gut…which can lead to autoimmune disease.
      Alcohol causes leaky gut when you drink more than the normal amount for a woman or man.
      Get to a functional medicine md for help with this. Getting a stool test to confirm the bacterial gut imbalances will be beneficial. When your gut is upset it will affect your moods. Going Paleo and getting a more healthy nutrient dense diet will help you to eliminate toxins. Alcohol depletes glutathione levels so you need to build up your glutathione stores. Get some multivitamins and mineral supplements and take them daily. Make sure there’s methyltetrahydrofolate and methylcobalamin in them. Drinking alcohol depletes all vitamins and minerals so that the body can’t detoxify itself. It all nutrient dense organically locally raised produce and meats. I drank alcohol due to having anxiety and depression and the professionals long ago just did talk therapy but didn’t address the underlying cause….gluten sensitivities and genetic polymorphisms in my liver (missing the glutathione gene and I don’t detox well through the liver). I am suffering quite a bit. Not sure if I will make it…thanks to western medicine and not finding the answers to my chronic health issues over time.

  20. One strong possible cause of inflammation you left out of this article is GRAIN intolerance and sensitivity/allergy (not JUST wheat and/or gluten, but the entire range of known & unknown grain-related toxic proteins).

  21. I 100% agree with this.. based on my own trials and research. I’ve spent years trying to control depressive symptoms and anxiety. Started with allergy shots, four years of them.. did seem to help quite a bit, but at that time didn’t know why it helped.. inflammation triggered by allergies was why. Found myself back in the dr office shortly after, first round of antidepressant Paxil… sent me off in psychosis-land.. also tried Celexa and finally Prozac which was a whole other kind of nightmare. Gave the antidepressants a rest and went the beta blocker route… lost a lot of friends in that period because it turned me into a very hostile aggressive person.. got into a few fights before getting off of those.. then I tried good ol’ Sam-e.. almost died from this and I only took a quarter of a tablet. Major psychosis apparently I was trying to overdose on old unsed antidepressants… Skipped taking anything for a long time except magnesium supplements which quickly caused problems as well and I still don’t know why… Then one day while working, I tore a tendon in my forearm and was promptly prescribed Naproxen… finally for the FIRST TIME in my life, I could actually relax… I cried people… This was a miracle to me… Gone was the heavy burdened feeling, the mental fog, the irritability, the anxiety… all of it gone. Took some time but eventually adjusted my diet and have experienced major relief however I do still take aleve on days when the inflammation is high causing pin- pupils.. myopia?, strained sound in my voice, basically stress and tension coming on. Anyway, it works and I’ve told others including my doc at that time and they just give me that weird kind of look like uh huh.. yeah. And I, I just smile because now I can 🙂

    • Wow …thank you for sharing . I too have high levels of inflammation, CRP , esr , ANA ,PTH levels and have been physically unwell and depressed as well and feel numb and blunted and no doctor can actually pinpoint what I have .. Positive genetic markers for celiac but gluten test was normal . One dr says lupus maybe , another one thyroid , maybe parathyroid . 3 yrs of hell and thousands of dollars wasted and no one can tell me what’s wrong . In not living just existing and in pain 24/7 … Worth trying what Chris says which I do already but need to be 100% and try naproxen . I take Valium for muscle pain twice a week

      • Hi Carmen,
        I’m sorry for you’re physical and mental suffering. I too have been extremely ill and so sick I’ve been home bound for approx 17+ yrs 1rst bedridden 21 yrs ago. Like u I do not live at all I just waste away on the couch. Watching tv to try and distract me from my debilitating symptoms is mostly all I do and can do except sometimes read and research my health. Even before this I spent many yrs with severe chronic major depression. I’ve been learning a lot lately because I can’t bare another day literally in the worst hell ever for most of my life. I believe inflammation is cause for a lot as well as digestion and digestive problems like I said and leaky gut syndrome. Toxins are a big problem allergies including food allergies and malnourishment from poor digestion. U may have some of these but one seems to cause the other and then the other so they can be intertwined quite a. It as well as viruses bacteria candida and parasites etc. look into all or some of that as for me I think it’s where I’ll find my answers and root causes of my fibromyalgia and Cfs possible lupus and also near to repair my adrenals and thyroid and possible balance hormones and my blood sugar which has been severe hypoglycemia for yrs and then I have about 100 symptoms. It the debilitating fatigue is the worst pain is horrific as is the insomnia and sleep issues and of course unbearable depression and around the clock anxiety. I just bought several books on these subjects but u might want to check out ” the ultra simple diet” by mark hyman who deals with a lot of these topics and online and maybe in book outlines how to get rid of its if u think u have it but he really addresses inflammation and toxins, being toxic through his 7 day diet, or food plan which is really about health not weight loss, resorting health but if u need to lose weight u probably will. Anyway allergies can result including food and it seems that tests are really unreliable for food allergies. My suggestion is to do the food elimination diet where u eliminate the most common allergen foods and for u I’d definitely take out wheat/ gluten and then in two 3 weeks or longer u introduce 1 at a time and see how u feel. U can also take them out one at a time. It’s seems to be the only truly reliable way to know maybe because there are allergies and there are sensitivities, etc. which don’t show up on tests. It’s worth a shot but all of these things I. mentioned are interrelated so u may want to learn about all and how one causes the other or research what your instincts tell u or just read and see if any of it sounds applicable. I’m just at the very beginning with this and heard inflammation causes many diseases just never heard it causing depression but have heard about diet in connection to depression. I just looked back to childhood at my first symptoms that were with my stomach and digestion so started investigating there and any of my next symptoms and if anyone tied in digestion to fibromyalgia or Cfs. Good luck I hope u find healing answers and great health and get to live life again. No life with debilitating symptoms is as bad as it gets hopefully you’ll get better now and not spend most of your life home bound like me. Best of luck

        • Hi Shannon , thank you so much . I’ve been paleo for a while with the occasional slip up and gluten free . I’ve done an organic acid test which I’m not sure if it was a complete was of money . It’s distressing feeling awful but we plod along and try and survive . I have had to give up my career as the fatigue and pain was getting worse and I sadly after 14 yrs just couldn’t push myself . Next month I’m going to start vitamin C infusions and see if I need counselling to
          With the sadness and stress that this fatigue and fogginess and detachment that this has caused . Pain is one thing but emotional
          Flatness is another and is awful . ?i hope you are feeling better now or an improvement hopefully . I tried LDN but when I titrated up to 3.0 mg I got hit with the worst depression, extra fatigue on top of my bad fatigue ( who knew that was even possible) and teariness and nausea etc xx

          • You may have gut dysbiosis and methylation issues…please get to a Functional Medicine Doctor and see if staying away from gluten and other inflammatory foods can help…they irritate the gut lining which affects the mind. Perhaps you have candida overgrowth too which affects the gut lining which affects the mood. Perhaps you’re deficient in many vitamins and minerals due to a malabsorption issue in the gut. Magnesium is a mineral we all are deficient in as well. Get some Magnesium oil by Ancient minerals on amazon if you think this will help. Go to their website and read the symptoms of a magnesium deficiency as well. Hope this helps. website will help you to find a FM MD.

      • I don’t know if your male or female but I can tell you that I have learned many many women are sick and can’t find answers and the culprit turns out to be breast implants. Many of us are or become hypersensitive to the silicone and some have ruptured implants, as a result, biotoxins have run amok! Most doctors do not recognize bii which is breast implant illness. There’s a site, actually there are many on Facebook but one in particular has about 6,000 women who are very very sick from Bii. This site is called “implant illness by Nicole” I hope this information will help you get to the bottom of your inflammation and in lieu of that will help with your depression.

      • Have you ever been tested for poor methylation (detoxification)? Could be that you don’t detoxify well through the liver. Just a thought!

  22. Had emergency antiobiotic treatment 4 weeks ago and the digestive system was completed left in havoc. Created massive inflammation, food sensitivities and bowel irritation. Started massive probiotic treatment along with taking 100 mcg selenoprecise daily, and now 3 weeks later the symptoms are only half as bad. It requires patience and time.
    Good read on the overlooked selenium:

  23. I have severe depression atm. Bought on by a loss in the family. I have been diagnosed with over 30 medical conditions. Many mentioned….. including allergies, sleep apnea, oral lichen playnus, ahernia, reynards phenomenon, continuous gut bleeding, obisity, arthritis, fibromyalgia, pollymyalgia, and many more including major inflammation throughout my body. Out of all my medical conditions, depression is the worst

  24. look up MTHFR. It explains a lot and is where my research is heading to and because it is not pharmaceutical driven, they will hate it. look it up

  25. I was happy to stumble across your article via FB. Very late to the conversation I see! However, I feel like I have lived my life as a guinea pig when it comes to depression. I became clinically depressed at age 28, but suffered from chronic depression since age 12ish. I am now 64. When I was first treated with anti-depressants – Norpramin – I believed it to be a wonder drug. It did what therapy could not do. These are the only 2 alternatives at that time and even they were new to most. I was told at the time that I only needed to take them for awhile and that the meds would jump start my brain and then I’d be good to go. Of course, that was not reality. I have been on and off them ever since – hand in hand with therapy. I’ve spent a fortune over the years trying to stay out of the mud and misery of depression. Five years ago after a serious car accident I developed PTSD. The medical profession is so far behind in all of this as to be laughable — although it’s not a bit funny to the person suffering. The only thing my doctor offered me was more drugs for the anxiety. I was given Klonopin. The best thing I ever did was reach out to a Naturopath. She told me I had PTSD. She told me about chronic inflammation. She gave me the tools of meditation, deep breathing, EFT and guided imagery. She put me on herbal supplements and helped me change my diet. My PTSD is gone, my digestion is more regulated, my depression has lifted. I am not yet to the point of being resilient — When I have a period of illness or stress overload I crash hard, but now I know how to get back up again and I am hopeful that I will one day be able to relinquish my anti-depressants. As it is I have cut them in half. My blood pressure has dropped from 140 to 120, my weight has dropped without dieting, my brain has cleared. I agree 110% that it is the power and force of the drug industry and doctors who because of insurance limit visits to one topic and 15 mins. Their solution is ALWAYS more tests or drugs. Never anything else. The medical community and the wholistic health community must get together! And get big business out of the middle of our health and well-being!

    • I would argue that business needs to get out of the way of health. Or, one should consider the ramifications of paying someone else to feed you and tell you what’s wrong with you and sitting back to enjoy the show.

      Life never worked that way for humans for millennia before the industrial revolution and doesn’t now. The difference is that we know better now. We know that inflammation is a sign of brain distress. How many of you are distracted by the symptoms of your brain distress (depression, anxiety (any “behavioral problem”), gut problems, fertility problems, skin problems, hair problems, energy level problems, immune system problems…

      The only thing these things have in common is (diagnostically speaking), is your head. It’s great you’re aware you get inflamed and when and the factors that worsen it…but how many of you have taken to the time to ask “why is my brain so pissed off all the time?”

      Only you will find your true answers, but I’ll give you some clues. A real “first world” problem is to not address root causes and to casually overlook injuries that are not casual. For example, the human skull is approx 6.5 mm thick. It’s also comprised of many bones with some that are meant to articulate (most) with each movement of the face/mandible. Others are more fixed (as adults, top of the head, coincidentally some of the strongest bones in the skull are up top). In other words, the human skull moves, naturally, and easily-which means that forces enacted against it will cause damage. Always. For every action, there is an equal reaction.

      This means that almost all of us are walking around with unaddressed skull deformities/brain injuries unaddressed for lifetimes (hence why our populations are dying younger, getting sicker in their 30’s and up despite “advances”).

      Forces that commonly cause skull deformities/brain injuries:

      Birth (natural and c-section)-lots of brain/pituitary problems because of nose/mid face structure compression.

      Injury such as falls as children, bicycles, ladders, vehicles, motor vehicle accidents, fights, wars, sports, etc

      These are all violent acts to the human body requiring gentleness to let go and recover from.

      We are great at adapting, hence why we still walk the planet. But if you care about living the ways humans are meant to, then start living like they used to. Eat whole foods grown how those foods evolved to grow (ice cream!!). Exercise regularly-gentle and easy walking is all that is necessary to be healthy-mixed with real manual work of course. Be outside more. Keep your inflammation in check. Go see a cranial sacral therapist about your head, acupuncture for inflammation and speedy healing, atlas orthogonal chiro for your spine. Naturopath for your nutrient deficiencies. Massage, sauna, other blood stimulating activities are encouraged as well. Quit neglecting hydration-of your inside and out! Magnesium in all forms is your friends while on your healing journey.

      Leave big pharma back where they came from and trust that only you know your body, not someone who is practicing at what used to be (and still is if you look for it) healing arts vs. medicine. You choose.

      Make a difference. Change your life, then pass on the word.

      • I should add that ice cream doesn’t grow-but it’s hot here as I type this and it’s can be a whole fatty delicious food, so you could see why I typed it.


        • Two last thoughts (my apologies!)

          1. Learn to stretch. Move your body in all the ways it can and should, but gently. This will make you stronger.

          2. We now know trauma can be passed on genetically. Thus, by not addressing these injuries we’ve created a host of fun new symptoms (aka diseases) and humans with behavioral/physical dysfunction, throw in some environmental physical stress and learned/made-up physical and mental stress…that sounds like a kitchen and recipe for gun powder.

          Sound familiar?

    • I believe it. These are some of the interventions Bessel Vander Kolk, a leading voice on the treatment of PTSD recommends – NOT meds.

  26. I found out my depression, anxiety and my ruddy mood swings were a direct result to being subjected to a moldy environment.

      • There is a test you can have done called a ‘hair-bio profiler’ which can pick up all kinds of things, problematic foods, parasites, deficiencies, radiation, viruses etc. I had it done at a naturopath for two of my sons who had completely unrelated health issues and it was the best money I ever spent. We discovered one of them had a build up of mould which we have since cleared and he is finally symptom free.

  27. I have a history of depression and candida overgrowth. I started taking Prescript Assist in the fall of 2015. I experienced some detox/ die-off symptoms but those dissipated. In February of 2016 I started taking Mercola’s MSM and Lipoic Vitamin C. Again, I experienced severe die-off symptoms so I had to start extra low with the MSM and build up to 2000mg/day. Two months later I feel lighter, I have more energy, and my memory has gotten better! I also supplement with Great Lakes Gelatin and done one month of an anti-inflammatory diet. I’m not any any particular diet now but I have more energy now that I’m 36 than I did in high school! I just started incorporating regular exercise and I feel really great! I really believe now that depression is inflammation of the brain. I recently stopped taking the Prescript Assist and started a lactic based one from Mercola but it spiked my candida so I’m going back onto the SBO probiotic because it manages the candida better.

  28. Speaking of depression, the latest news is about a drug Ketamine, also a street drug known as Special K, being used in suicidal patients with remarkable results. From what I understand Ketamine is a glutamate receptor blocker and there can be bad side effects. But NIH sponsored study in Journal Nature shows that it is a metabolite produced by the breakdown of Ketamine that has the anti-depressant effects without side effects. What do you think of this? Could you explain the Journal Nature research in layman’s terms?

  29. I was suspecting that greatly. I’ve just been healed of anxiety and the like by drinking cold water with turmeric-an anti inflammatory medicine. It was miraculous and a very long time coming. Thank you for your research. I believe you are right.

  30. It must be true about inflamation linked with depression because sometimes just ibuprophen will knock out that bad dark tired feeling

  31. This theory was presented in 1991, so nothing new about it. (Smith RS. The macrophage theory of depression. Medical Hypotheses 35:298-306, 1991.) As far as the chemical imbalances go, cytokines have been shown to produce the various neurotransmitter imbalances. It’s amazing the medical community has been ignoring this plethora of research!

  32. I have Hashimoto’s thyroiditis, with depression and chronic fatigue. I rely heavily on turmeric to help control depression, (along with some other natural products). Turmeric has an anti-inflammatory effect, so I knew that inflammation is a big part of my problem. But I haven’t discovered how to permanently reduce inflammation, despite a multi-pronged effort to address my issues: paleo diet, vitamin/mineral supplementation, high quality probiotics, removing chemicals. Wondering if a long course of antibiotics would remove the inflammation?

    • I’ve had great success with the GAPS (Gut and Psychology Syndrome diet-terribly named I must admit-it’s more aptly named End Inflammation Caused by Poor Diet/Gut problems). I also supplement heavily with Vitamin d, magnesium (a lot and many kinds as there are benefits to absorbing through skin vs gut and only one type passes blood brain barrier), l-glutamine (to aid in gut repair faster), bioavailable zinc (zinc ororate) and bioavailable b complex (to address long term deficiencies-Jarrow’s B-right or Jigsaw’s Bcomplex with SRT are the best I’ve found), and benedryl (to keep immune response in check, I have chronic asthma, allergies and celiac and I want to give the pro system as much of a fighting chance as possible).

      Also, I completely agree with this article and am glad someone took the time to correlate all the research culminated over the last 20 years on facets of this subject. I too, wish the medical community had more incentive to pay attention. Would have saved me lots of time, anguish and money.

    • You might check out the Andy Cutler protocol. Thyroid issues, fatigue, depression and are symptoms of mercury toxicity, which causes inflammation.

      • I have all of these , graves disease ( thyroid ) depression , tired , weak muscles , could inflammation be underlying ?

    • Have you considered that you may have poor methylation (detoxification) in the liver? This will affect the immune system causing toxicity. Maybe some of the things your eating and drinking are inflammatory to your gut? GMO’s and gluten?

  33. 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?

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

      • 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.

    • Being in the medical field consider that it may not be politically & financially beneficial for the pharmaceutical industry to find a rational reason that could improve this huge problem that we the public experience as a result of modified food, pollution, fluoride, etc have created. Think of it as healthfield job security. There are few grants provided to encourage research to support this information. Just a suggestion that you may consider .

  34. 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?

    • Choosing the diet will surely be more cost effective than a specialist now or the many specialists you will be forced to seek out later as chronic problems arise. There are budget friendly options. Some of them include buying the “better” option instead of the “best” but leave the “worse” options behind whenever possible. Your fuel will change your life.

    • It might be beneficial to consider growing your own veggies. Its easy even for inexperienced gardeners.
      It’s astonishing how very little soil can produce so much!

      Wishing you an improved health and wellness!

  35. 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.

  36. 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

  37. 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.

    • 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 🙂

  38. 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

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

    • 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?

  39. 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.

    • 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!

  40. 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.

  41. 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 =)

  42. 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


  43. 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.

    • That may be histamine-induced depression. I’m pretty sure that’s where most of my depression stems from as well. It could also be copper overload, as chocolate has a lot of bioavailable copper.

    • I have the same reaction. It is a result of amines in the chocolate. (histamine/tyramine etc) Aged foods and a number of other things have it too.

  44. 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.

  45. 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.

    • 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.

  46. 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.


  47. 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?

    • 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.

  48. 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 :'(

    • 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)

  49. 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.

    • 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.

      • Oh Effexor that one was by far the worst for me to come down from. My head felt like there were electrodes going of in it. I had to stay home from work. Sorry you are suffering through that one. It took me a few weeks to detox. Best of luck.

        • I was on Effexor for 10 odd yrs about 10 yrs ago. I came off them cold turkey( stopped them without weaning off them) without side effects. I was heavily depressed in thoughts and actions. I sort quite a few ‘helpers’ over this time and did a few courses to help well they worked or rather 1 in particular did. I am a Christian , and no Christians are not immuned to depression , that was the only thing that held firm so I searched for answers and got them.
          I’d tried to come off the pills before this and always had horrible withdrawals.
          My experience showed me that what is today is always attributed to the past. I had no reason to be depressed I had a wonderful husband great kids we were well off a good life so why? My ‘search for life’ exposed my problems that started way back when I was little and continued through my growing years. I addressed these issues and moved forward what release a few months later I did the course again dealt with a few more issues and bingo took the plunge went off the pills and didn’t look back till now.
          I had a stroke at 53 and struggled for a bit before I was put back on Effexor because I wasn’t in control of my emotions.
          If the cause is inflammation I could understand it as a good bleed on the brain must cause swelling plus I have other mRkers there that may lead to MS so I will now look into that cause I hate taking pills.
          A bit off topic but my experience

  50. 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

  51. 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.

  52. 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!

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

  53. 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.

  54. 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!!

  55. 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!

  56. 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.

    • 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.

    • 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.

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

      • 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

      • Lithium orotate is available at health food stores and can work wonders, according to John Gray (the Venus/Mars books) and others. Rhodiola tincture and flower essence remedies are great, too. All of these are safe and effective

      • Dear Sue,

        I was diagnosed with bipolar disorder 20 years ago and have been in and out of hospital over the years. Recently, I did an 8-week mindfulness course which changed my outlook on and experience of life in many positive ways. In particular I feel a lot more grateful for the good things in my life, more centered and non-judgmental and therefore no longer so attached to and stressed about wanting and/or expecting certain outcomes to my actions… what also helped me immensely is that I adopted two little kittens last summer who are adorable and like pure therapy, and finally, doing volunteer work, or something “good” on a regular basis is also extremely helpful for maintaining positive mood and feelings of self worth. Hope this can be of some help.

  57. 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.

  58. 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?

    • 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.

  59. 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.

  60. 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!

  61. 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!

  62. 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…

  63. 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.

  64. 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?

    • 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.

    • Ladylene, I hope you are still hanging in there. A very common but seldom diagnosed cause of intractable chronic inflammation is one or more root canalled teeth. If you have ever had a root canal, I strongly suggest that you get a checkup from a holistic dentist a.s.a.p.

      To get started learning more about this, simply do a Google search (without the quotes) for “allintext:root canal inflammation depression hal huggins”. Then follow your nose from there.

      In my case the primary symptom of chronic inflammation, in spite of my eating an overall healthy diet, happened to be endothelial dysfunction leading to a major heart attack, rather than depression. But chronic inflammation can manifest itself in many ways. It was a holistic dentist who finally connected the dots for me, not my cardiologist. He pulled the offending tooth (quite literally the “root cause” of my heart disease), probably saving my life. It is now five years since I almost died on the operating table, and today I am entirely symptom free (as well as medication free) and healthy as a horse.

  65. 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.

    • 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)

  66. 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

  67. 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:

  68. 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

  69. 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.

  70. 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 🙂

    • 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.

      • 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)

        • 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.

          • 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.

            • 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…

    • 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!

  71. 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?

    • 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.

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

  73. 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!!

    • Sandra, you say it is a “disorder” of the brain, but brains are just not inherently disordered…There is a root cause/effect to mental illness. Post traumatic stress disorder can literally change the brain’s neuroplasty, thereby initiating “brain dysfunction”. Poor gut health is also a cause of anxiety, depression, etc. MSG, and other preservatives and artificial dyes can cause behavioral issues. Gluten, for others, may do the same. Speaking up is not something one can always expect a severely compromised brain to do. It sounds good, but many depressed people are incapable of doing so. You say that there is no cure, but have you been to a integrative physician to do batteries of tests for allergies, heavy metal poisoning, etc. Chemicals in the food and environment can definitely reek havoc on brain health. It’s a no one size fits all. Please, and I say this with much respect, reconsider your limited amount of knowledge on the subject and be open minded enough to learn more about Dr. Kresser’s research. I do hope you find peace.

  74. 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.

  75. 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.

  76. 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…..:)) :)) :))

  77. 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.

  78. 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.

  79. 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.

  80. 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.

  81. 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?

    • 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.

  82. 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!)

    • 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.

      • 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.

      • 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?

  83. 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

  84. 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?

  85. Hi
    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.


  86. 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.

  87. 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.

  88. 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.

    • 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.

  89. Chris,

    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.

    • 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.

  90. 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!

  91. 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.

  92. 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.

  93. 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.

  94. 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?

  95. Hi,
    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

  96. 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!

  97. 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

  98. 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!

  99. 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).

      • 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

        • 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.

  100. 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.

  101. 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.

  102. 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.

  103. 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).

  104. 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?

  105. 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).

  106. 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

    • 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.

  107. 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 🙂

  108. 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…

    • 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?

  109. 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!

  110. 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.

    • 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.

      • 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]

      • 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?

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

  111. 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,

    • 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).

      • 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?

      • 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.

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

  112. 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?

    • Sara,

      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!

      • 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.

  113. 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.

  114. 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.

    • 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.

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

    • Gareth,

      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.

      • 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.

  116. 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.

  117. Chris,

    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!


  118. 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.

    • 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.

      • +1
        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.

      • 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.

  119. 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.

  120. 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!

  121. 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.

    • 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.

  122. 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.

  123. 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.

    • 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.

    • 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.

        • 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.

          • 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!

    • 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.

    • 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! 🙂

  124. Chris,

    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?

  125. 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).

    • 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.

    • 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.

      • 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?!

  126. 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!

  127. 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!

  128. 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)

  129. 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……….

    • 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.

  130. 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

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

  131. 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

  132. 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.

    • 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.

  133. 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.

    • 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.

      • 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!

  134. 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…

    • 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.

      • 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!

        • 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.

      • Chris,
        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.

        • 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 ?

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

      • 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).

        • 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.

          • 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.

    • 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!

  135. 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.

    • 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.

  136. Hi
    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.

  137. 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!


    • 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.

      • 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!

  138. 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.

  139. 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.

    • 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.)

      • 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.

    • 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.

  140. 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.

    • 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.

    • 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.

      • 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.

  141. 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.

  142. 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.

  143. 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.

  144. 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

  145. 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.

        • 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.

          • 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.

    • 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?

      • 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.

    • 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

  146. 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)?

  147. 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.

    • 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.

      • 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.

        • 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.

          • 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”.

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

        • 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……..

          • 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

        • 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!!

        • 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.

        • 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.

        • 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! 🙂

        • 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

        • 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.

          • 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.

          • 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.

    • 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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