The histamine (mast cell) depression link

histamine mast cells and depression

While you could say it’s pretty normal to be down in the dumps over having been sick for most of your life, I’ve often found it interesting that an impressive number of us with histamine intolerance, mast cell activation disorders and mastocytosis appear to suffer from crushing depression.

So convinced was I of the link, that I never really bothered to look it up for myself, until it dropped into my lap, as it did a few months ago when I shared the news that researchers in Finland had successfully treated schizophrenia with antihistamines, rather than anti-psychotics (read my post here). This wasn’t news to me given that I had previously experienced almost ALL the schizophrenia symptoms during high histamine episodes/attacks. Yes, even hallucinations.

I know, what more could a gal ask for?

An increase in the number of emails I get about a possible depression link finally lit a fire under my butt and I instinctively knew that NIH funded mast cell/histamine researcher Dr Theoharides [1] was the man to approach on this. His groundbreaking research has linked mast cells/histamine to: multiple sclerosis, autism, cancer, parkinson’s, alzheimers, depression, schizophrenia and more [2].

(Disclosure – I am a huge fan of his work).

He’s a busy guy, but sent over a bucket load of research (most of it too complicated for the layperson – myself included) and this line: Mast cells are definitely associated with depression due to release of cytokines that affect brain function.”

His research clearly shows why those of us with mast cell activation/histamine intolerance disorders are more likely to suffer from depression and other psych conditions – the kind that are likely to get us a psych (mis)diagnosis, rather than a mast cell histamine one. As I did, starting with simple anxiety diagnosis for the shaking I was experiencing, progressing to depression after I was prescribed downers (xanax), then into bipolar as the SSRI drove me into complete manic episodes and then down, down, down the rabbit hole for 8 years before I finally re-claimed my sanity through diet.

According to a growing body of research, by Dr Theoharides and others, shows that pro-inflammatory brain cytokines are implicated in depression  [3]. In English: mast cells cause inflammation in the brain, which causes depression. For all of you histamine intolerance folks: there’s histamine in the body already, stored in mast cells, until we need it for healing and other important body functions, and there’s the histamine we get from foods. More on that later…

Dr Theoharides notes that the role of inflammation in neuropsychiatric diseases was long suspected, but new findings report decreased mitochondrial function in as many as 60% of autism patients, “a neuropsychiatric developmental disorder showing many similarities with schizophrenia…[4]”

In short, neuroinflammation, involving mast cells, can manifest in many different ways. In some people it can cause disorders involving a loss of speech (autism) or psych disorders (schizophrenia, bipolar, major depression), or demyelination disorders like Multiple Sclerosis. Please understand, I’m not saying that autism is a psychiatric disorder.

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Dr Theoharides chart

Dr T concludes, in an editorial for the Journal for Clinical Psychopharmacology, that: “there is no doubt that available evidence indicates brain mitochondrial dysfunction and heightened immune response in neuropsychiatric diseases. However, it is still hard to understand how in certain cases these changes affect mostly behaviour, whereas in others they lead to loss of speech (autism) or demyelination and mostly neurological problems (MS).[5]”

In my interview with her, pioneering mast cell doctor Marianna Castells shared her discovery (along with her teacher) of mixed organic brain syndrome:

“The cognitive changes consisted of diminished attention and memory, and the affective changes of anger, irritability, and, to a lesser extent, depression. These manifestations fluctuated with the level of disease activity, and appeared in some cases to respond to histamine antagonists and disodium cromoglycate, medications used to control the excessive mast cell activity. It is important for psychiatrists to be aware that mental status changes can represent psychiatric manifestations of mastocytosis, a readily treatable medical disorder. [6]”

The psychological manifestations of mast cell/histamine disorder can be so extreme, as to be heartbreaking. In our interview Dr Castells relayed the story of a woman committed to an institution by her family. She exhibited bipolar type tendencies and clouded thinking. By chance the woman fell over (not from a great height) and broke her collarbone. Someone was smart enough to wonder why such a young woman would break bones so easily (the majority of mast cell peeps have bone density issues due to disrupted calcium absorption), and so Castells was called in to consult. A quick round of testing revealed that her tryptase was elevated, in addition to her prostaglandins, which according to Castells are one of the reasons for brain fog, or “mixed brain syndrome” as she and her predecessor dubbed the condition 20 years ago. After a short treatment with mast cell meds and antihistamines, the woman was “cured” of her psych issues and released to her family.

I can’t imagine that was a very happy home coming.

All I can say is that I can’t stop thanking my lucky stars that I found my depression cure through diet. Not a low histamine diet, but rather a high nutrient diet rich in anti-inflammatory and antihistamine foods. The kind of diet that helps prevent cancer, alzheimer’s and certainly in my case, lifted the life long depression that inspired doctors to prescribe meds that flushed the best years of my life down the toilet, the depression that caused me, in my darkest days, to harm my body in an effort to feel anything through the numbness, the impenetrable haze of ambivalence towards my precarious non-existence.

Please don’t wait almost a decade, as I did, to examine your mast cells, histamine levels, and really, truly lift a microscope to your diet.

Please don’t forget antihistamine, pain killing foods can still hurt us, so please always check with your doctor before adding new foods to your diet. 

————-REFERENCES————-

[1] www.mastcellmaster.com

[2] www.mastcellmaster.com

[3 + 4] http://www.mastcellmaster.com/documents/brain-health/J-Clin-Psychopharm-2011-Brain-Inflammation.pdf

[5]  http://www.mastcellmaster.com/documents/brain-health/J-Clin-Psychopharm-2011-Brain-Inflammation.pdf

[6] http://www.psychosomaticmedicine.org/content/48/6/437.short

28 responses to “The histamine (mast cell) depression link”

  1. TNVicki Avatar
    TNVicki

    Fascinating. I’m thinking that my problems may have been more histamine related than leaky gut related. I tested positive for 66 food sensitivities, almost all of them are high histamine foods. I’ve been healing from adrenal and thyroid issues and recently healing from panic attacks and brain fog. It’s now making so much sense. Thank you for continuing to share this cutting edge info!

  2. Carole Avatar
    Carole

    This info is so incredible! I’ve just recently been exploring the possible relationship that mast cells might have in my own health problems – diagnosed with MTHFR A1298C last summer along with our oldest daughter, 51, who has had schizophrenia for more than 30 years. Doctors have tried numerous drugs over the years and none have been very successful in dealing with her symptoms. I’ve been studying the 23andme.com tests we did after diagnosis to determine possible additional gene defects and the mast cell possibility has come up in mine so want to explore this further. I’ve recently found a nutritionally-oriented doctor in our area who has taken on our daughter’s case and has done a number of tests (which we don’t yet have the results to) but this is possibly a big factor in her illness also.

  3. Audrey Walker Avatar
    Audrey Walker

    The
    cytokine link is very interesting to me because I benefit greatly from
    Chinese skullcap which is a very potent cytokine reducer. It has to be
    the Chinese skullcap though… very important.. not just regular
    skullcap… which is a great nervine

  4. J Avatar
    J

    Don’t rule out leaky gut (or SIBO) just yet. Leaky gut can (according to some practitioners) cause food sensitivities (due to larger molecules passing through the gut lining causing an immune response).
    If the intestinal mucosal lining is inflamed one’s body will not be able to produce enough DAO enzyme to break down the histamine.
    And of course bacteria/yeast active in the normally sterile small intestine will contribute to mast cell degradation.
    Impaired gut health seems to play an important role in histamine and salicylate intolerance (for many people).

  5. uuliv Avatar
    uuliv

    Thanks for that article. I find it very interesting as it indicates a connection between histamine and autism. I tried the GAPS approach and woke up the very first morning with massive skin issues and swolen eyes. No way for me to try it again. However, GAPS claims that bone broth is a solution for autism and leaky gut, but I found it very toxic due to its high histamine levels. This is a new path to follow now. Thanks a lot for your great work!

  6. Christine Avatar
    Christine

    Have you also looked into Pyrrole Disorder? Goes hand in hand with histamine issues and Mast cell issues and everything inbetween those thigns.

  7. Bill Avatar
    Bill

    I have been debating taking the HNMT genetic test. Does this discussion point towards more justification for this type of test if you suspect histamine mediated depression or anxiety?

  8. thelowhistaminechef Avatar

    It’s worth exploring HNMT…depression or not.

  9. thelowhistaminechef Avatar

    Have not yet, will do!

  10. thelowhistaminechef Avatar

    Ay! I get sooooooo many emails from people who finally understood it’s a histamine issue right after trying GAPS.

  11. thelowhistaminechef Avatar

    It’s also a mast cell stabiliser and antihistamine!

  12. thelowhistaminechef Avatar

    Hi Carole, I know a few people who have experienced significant relief from schizophrenia through dietary changes. Best of luck with the exploration, please keep us posted on what you find!

  13. thelowhistaminechef Avatar

    Ooooo yes, all sounds very familiar. I had exactly the same.

  14. thelowhistaminechef Avatar

    Leaky gut is basically a mast cell issue according to the latest research. I saw something interesting the other day about quercetin being effective for leaky gut because of the mast cell link. I had SIBO, cleared it up through diet alone and didn’t have any major relief in symptoms.

  15. Unsure Avatar
    Unsure

    I don’t even know where to begin. I believe I have some sort of health issue causing widespread inflammation but have no idea what it is. A year and a half ago I was so sick (showing signs of schizophrenia), my husband and mother considered having me committed. I told my doctor that I believed I had a medical reason for everything that was happening to me. She pretty much laughed at me and said, “Reassure the patient. Reassure the patient!” They did a urinalysis and found I had a UTI. I quit my job and reduced some other stressors in my life. I am much better now but still suffer from inflammation, brain fog, inability to concentrate, bouts of depression, and general malaise. There are so many diets, not to mention terms I don’t understand. Where do I begin? Are there medical tests that will tell me what is wrong with me? Please advise!

  16. Cristian Mihai Avatar
    Cristian Mihai

    Patent US 4725540 describes a method for the preparation of DAO from a DAO-producing microorganism such as Candida krusei or from a lactic acid producing bacterium in a nutrient medium, so that the DAO produced is able to degrade histamine at a pH of between neutral and approximately pH 4. Patent application WO 02/43745 from 2001 describes the systemic use of DAO of vegetable origin for the treatment of diseases mediated by histamine, particularly for the treatment of allergies in general and anaphylactic reactions in particular. Pharmaceutical compositions comprising DAO as an active ingredient have also been described together with the corresponding doses and administration protocols. The DAO used is of plant origin. There has been no mention of the possible use of DAO compositions for the treatment or prevention of attention deficit hyperactivity disorder (ADHD).My question is why it is said that Lactobacilus casei or bulgaricus produce histamine?

  17. Devyn Avatar
    Devyn

    I would recommend looking into Lyme disease. I have all the symptoms you listed, and some others too (including histamine intolerance). Keep in mind there is a strong correlation between Lyme and food sensitivities, especially gluten and casein… check out Dr. Joseph Mercola’s articles on Lyme, and his interviews with Dr. Dietrich Klinghardt.
    Good luck!!

  18. mathis Avatar
    mathis

    Very interesting as I have been led to this path since trying GAPS on my non verbal ASD son (3yo). I don’t blame GAPS however, in fact I thank it for a) opening my eyes to good wholesome, non-processed foods, and b) leading me to the conclusion that it was the histamines my son was reacting to. It’s only been one day since avoiding histamines and I can already see a difference.

  19. Micaela Avatar
    Micaela

    Thank you for all the great information you continuously put out. I am in my final year of a Bachelor Health Sciences in Naturopathy in Australia and have a keen interest in mental health. I am just curious to know if you have also looked at methylation issues (in particular under methylation)? In addition to DAO to breakdown histamine, methylation is also a key component. A lot of people with histamine issues are under methylators.

  20. Micaela Avatar
    Micaela

    Thank you for all the great information you continuously put out. I am in my final year of a Bachelor Health Sciences in Naturopathy in Australia and have a keen interest in mental health. I am just curious to know if you have also looked at methylation issues (in particular under methylation)? In addition to DAO to breakdown histamine, methylation is also a key component. A lot of people with histamine issues are under methylators.

  21. Yvonne Forsman Avatar
    Yvonne Forsman

    Sorry to hear about your problems. I am sure there is a solution, there always is, even if the current doctor doesn’t know, somebody else does! Good luck!

  22. Yvonne Forsman Avatar
    Yvonne Forsman

    Sorry to hear about your problems. I am sure there is a solution, there always is, even if the current doctor doesn’t know, somebody else does! Good luck!

  23. Kelly Avatar
    Kelly

    Wauw you and i thinks the same!
    Ive got also Mast Cell Disorder ( CFS/ME, pyrrol disorder, low thyroid, low adrenals and more).
    Im homozygous mthfr a1298c.
    I do also have depression and histamin problems.

    I did read many medical research with a link that schizofrenia and Autism both are triggerd because of grains ( gluten), and casien ( dairy). When you stops those products youre leaky gut can heal and you can come off from medication.

    B6 works best for autism and schizofrenia! Why? Because it boost neurotransmitters and lowers histamin by stimulating DAO enzym…

    Vitamin B6 works best in P5P form high dose.

    Problem is Celiac persons ( and with other health issues and gut problems), doenst absorp P5P anymore.
    Because of low alkaline phosphatase normal B6 is useless and doesnt work! So you have the need of P5P in high dose to stimulate enzyms lower histamin and produce neurotransmitters.

    I did found a artikel then when consuming grains alkaline phosphatase was low ( so the enzym that makes from b6- p5p). When they put the biopt in a grainfree area the alkaline phosphatase jumpt high ! So than you are able to absorp p5p again when healing the gut.

    So thats the link between P5P – autism- depression- Schizofrenia -low alkaline phosphatase.

    Dr klinghardt recommend high dose p5p with zinc ( zinc and phosphores to boost alkaline phos.) but for absorption you need to heal the gut and choose to go grainfree ( also no corn and rice and topacia etc), best would be paleo and then take high dose p5p.

    Works also with MS, Parkinsons, dementia diabetic thyroid disfuntion and more

    Its starts in the gut but the symptoms from low hormones and high histamin is because of low P5P. Its a shame there is no P5P injections just like methyl b12. That would solve the problem mostly! No pyridoxine injections but really P5P injections! If someone know where to find , please text me 🙂

    But for nog did start with dairy and grainfree dieet ( and LDN to reduce inflamation).

  24. Kelly Avatar
    Kelly

    Wauw you and i thinks the same!
    Ive got also Mast Cell Disorder ( CFS/ME, pyrrol disorder, low thyroid, low adrenals and more).
    Im homozygous mthfr a1298c.
    I do also have depression and histamin problems.

    I did read many medical research with a link that schizofrenia and Autism both are triggerd because of grains ( gluten), and casien ( dairy). When you stops those products youre leaky gut can heal and you can come off from medication.

    B6 works best for autism and schizofrenia! Why? Because it boost neurotransmitters and lowers histamin by stimulating DAO enzym…

    Vitamin B6 works best in P5P form high dose.

    Problem is Celiac persons ( and with other health issues and gut problems), doenst absorp P5P anymore.
    Because of low alkaline phosphatase normal B6 is useless and doesnt work! So you have the need of P5P in high dose to stimulate enzyms lower histamin and produce neurotransmitters.

    I did found a artikel then when consuming grains alkaline phosphatase was low ( so the enzym that makes from b6- p5p). When they put the biopt in a grainfree area the alkaline phosphatase jumpt high ! So than you are able to absorp p5p again when healing the gut.

    So thats the link between P5P – autism- depression- Schizofrenia -low alkaline phosphatase.

    Dr klinghardt recommend high dose p5p with zinc ( zinc and phosphores to boost alkaline phos.) but for absorption you need to heal the gut and choose to go grainfree ( also no corn and rice and topacia etc), best would be paleo and then take high dose p5p.

    Works also with MS, Parkinsons, dementia diabetic thyroid disfuntion and more

    Its starts in the gut but the symptoms from low hormones and high histamin is because of low P5P. Its a shame there is no P5P injections just like methyl b12. That would solve the problem mostly! No pyridoxine injections but really P5P injections! If someone know where to find , please text me 🙂

    But for nog did start with dairy and grainfree dieet ( and LDN to reduce inflamation).

  25. Kelly Avatar
    Kelly

    Ohh and found also evidence that grains are bad for crohn and CU but even healthy people!

    It was weird because when i stopped eating gluten and dairy i have more mast cell/ histamin issues! But that was normall said a medicall research! I read it from so many celiac patients. so mast cell is also something good! Read the artikels below 🙂
    Hope you write me back!

    Sorry for bad englisch im from the Netherlands!

    http://www.ncbi.nlm.nih.gov/m/pubmed/3744785/?i=2&from=/6826106/related

    http://www.ncbi.nlm.nih.gov/m/pubmed/3728211/

    http://www.ncbi.nlm.nih.gov/m/pubmed/180789/

    http://www.ncbi.nlm.nih.gov/m/pubmed/702197/

    http://www.ncbi.nlm.nih.gov/m/pubmed/19564647/

    https://www.psychologytoday.com/blog/evolutionary-psychiatry/201103/wheat-and-schizophrenia

    http://mthfralliance.com/2014/02/03/why-b6-is-the-queen-b/

    http://www.drkaslow.com/html/alkaline_phosphatase.html

    Those are the best research you will ever find! 🙂

    Hope to hear from you what you think about this 🙂

    Greetings kelly

  26. Kelly Avatar
    Kelly

    Ohh and found also evidence that grains are bad for crohn and CU but even healthy people!

    It was weird because when i stopped eating gluten and dairy i have more mast cell/ histamin issues! But that was normall said a medicall research! I read it from so many celiac patients. so mast cell is also something good! Read the artikels below 🙂
    Hope you write me back!

    Sorry for bad englisch im from the Netherlands!

    http://www.ncbi.nlm.nih.gov/m/pubmed/3744785/?i=2&from=/6826106/related

    http://www.ncbi.nlm.nih.gov/m/pubmed/3728211/

    http://www.ncbi.nlm.nih.gov/m/pubmed/180789/

    http://www.ncbi.nlm.nih.gov/m/pubmed/702197/

    http://www.ncbi.nlm.nih.gov/m/pubmed/19564647/

    https://www.psychologytoday.com/blog/evolutionary-psychiatry/201103/wheat-and-schizophrenia

    http://mthfralliance.com/2014/02/03/why-b6-is-the-queen-b/

    http://www.drkaslow.com/html/alkaline_phosphatase.html

    Those are the best research you will ever find! 🙂

    Hope to hear from you what you think about this 🙂

    Greetings kelly

  27. Kelly Avatar
    Kelly

    http://kellybroganmd.com/article/two-foods-may-sabotage-brain/

    http://www.csaceliacs.org/hows_and_whys.jsp

    The second link is really perfect explanation about glutenfree and higer alkaline phos and why its so important! Really you have to read those links.

    I know you woukd loce them and the puzzle fals in to peaces 🙂

    Have a nice weekend!

  28. Kelly Avatar
    Kelly

    http://kellybroganmd.com/article/two-foods-may-sabotage-brain/

    http://www.csaceliacs.org/hows_and_whys.jsp

    The second link is really perfect explanation about glutenfree and higer alkaline phos and why its so important! Really you have to read those links.

    I know you woukd loce them and the puzzle fals in to peaces 🙂

    Have a nice weekend!

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Yasmina was an award-winning broadcast journalist with a decade of experience covering war zones for CNN and the BBC. She devoted her journalism skills to researching and writing about histamine. Click here to learn about her. Each post is carefully and fully referenced with the latest scientific research. Not sure where to start? Here’s a four week meal plan and overall Histamine Reset.


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