Histamine: Mast Cell Disorder or Methylation Imbalance?

If you think you may suffer from histamine intolerance, a mast cell disorder, mastocytosis, or mast cell activation syndrome (MCAS), and are researching like mad trying to figure out how to overcome it, then this article is for you.

Before I begin, you need to know that mast cell degranulation/histamine intolerance are completely different issues to undermethylation. Where folks get tripped up the most is in thinking they are the same, but they are very different creatures indeed.

Keep in mind there is still much to learn about mast cell degranulation, as there are many different variants of this creature. Research shows different blockages or plugs in the system are leading to different disorders. Methylation is one part of that, and our current understanding of histamine as it relates to epigenetics is helping pave the way.

Special thanks to Dr. William Walsh of the Walsh Research Institute for his time and wisdom so I could write this piece.

Produced by basophils and mast cells, histamine wears many hats:
  • Protects against infection and inflammation allowing white blood cells to engage pathogens in infected tissues.
  • Regulates physiological functions in the gut, especially the release of gastric acid as part of the breakdown of proteins in the digestion of food.
  • Acts as a neurotransmitter affecting sleep cycles and cognitive function.
  • Naturally occurring in food and continues to rise the longer food sits, and during the process of fermentation.
  • Through bacteria using histidine decarboxylase enzymes unrelated to those found in animals.

Once formed, histamine is either stored or rapidly inactivated by its primary degradative enzymes, histamine-N-methyltransferase or diamine oxidase (DAO).

In a healthy individual, if everything is functioning properly, the right amount of DAO will reside in the GI tract where nearly all histamine from food is metabolized (destroyed/eliminated by DAO).

DAO is responsible for controlling histamine levels in blood fluids, not basophils and mast cells. Blood fluids are supposed to be very low in histamine. Mast cells are where most of the histamine in the body should reside.

An individual with DAO weakness may have normal whole blood histamine, but very elevated plasma histamine and depressed DAO levels. Antihistamines and certain antidepressant medications can cripple DAO function and make symptoms worse.

Systems That Control Histamine

Mast cell disorders and methylation imbalances are epigenetic in nature and both are connected to histamine, but there are separate systems for controlling histamine. They are (a) blood basophils and tissue mast cells and (b) blood plasma.

Histamine elevations in plasma cause crippling skin and intestinal problems, while the histamine in basophils and mast cells correlate with mental problems (methylation imbalances).

Very elevated histamine in blood signals blood basophil cells where additional methylation of histamine is needed (this is how we check methylation status). Keep in mind that you can be over, under, or normally methylated, and still have an intolerance to histamine.

Folks that have low DAO activity (again, epigenetic in nature) also tend to have low levels of histamine in serum and plasma, which affects the histamine/mast cell relationships.

The interesting tie that binds the mast cell/methylation relationship together is the undercurrent of severe oxidative stress.

And what’s often behind oxidative stress?

Yep, it’s that pesky metal I frequently write about and see daily in my practice: copper.

This also explains why mast cell disorders most commonly affect women, with the onset of serious symptoms beginning between the ages of 35 and 50 (but can occur much younger than that). The reason we ladies are hit so hard is because of the estrogen copper relationship.

Estrogen Copper Mast Cell Relationship

When estrogen rises, so too does copper and is also affected by the onslaught of hormonal events such as puberty, pregnancy and menopause. Exogenous sources are also a trigger for us including birth control, hormone replacement therapy (synthetic and natural sources), IUD’s, vitamin and mineral supplements, food, and drinking water.

Copper lowers dopamine and increases norepinephrine leading to anxiety, depression and in some cases, psychosis. With copper overload depression, 95% are female.

Postpartum depression is especially interesting because with each successive pregnancy, copper levels continue to rise rather than go back to normal after baby is born.

A classic symptom of histamine intolerance in women is that they feel uncomfortable and miserable throughout life, but during pregnancy feel fabulous. This is because DAO can be at 500 times higher concentration during pregnancy. 1

All of this explains why females make up the highest percentage of mast cell disorders.

Copper Metabolism and Regulation

By metallothionein (MT) (a family of cysteine-rich proteins and a wonderful antioxidant in its own right) in the GI tract where most MT exists. If a person has an excess of copper in the GI tract, more MT is automatically expressed, which then binds to copper and prevents the amount of copper that can make it into the liver and bloodstream.

That’s the primary way copper is regulated or to put it another way, copper elevation is prevented.

When a person has chronic, elevated copper, it means there is a genetic weakness to MT function. When copper gets into the bloodstream, it gets there by binding to proteins such as albumen as it leaves the intestinal membrane, then goes into the liver where most of the copper becomes bound to ceruloplasmin (a copper-binding protein that acts like a chaperone carrying copper throughout the body and delivering it where it’s needed).

What’s also interesting is ceruloplasmin’s ability to destroy histamines (along with the copper-containing enzyme histaminase).

In a normal, healthy individual, copper is regulated throughout the bloodstream and bound to ceruloplasmin. If you wind up with too much copper in the liver, the excess is supposed to bind with ceruloplasmin and MT and go out through the bile duct.

A small percentage of free copper is normal, but if a person has a much higher level – higher than 30% – this is a definite indicator of high oxidative stress.

We currently have two different indicators to check for oxidative stress:
  1. Inordinate amount of copper in the bloodstream that’s not bound to ceruloplasmin.
  2. The copper/zinc relationship itself. Elevated copper is always associated with low zinc, and low zinc is a well-known factor in oxidative stress. In fact, every mast cell client I work with is low in zinc.

Pyrrole disorder (double deficiency of zinc and vitamin B6) is another marker for high oxidative stress and should also be considered. 2

Copper/zinc imbalances are associated with both mast cell disorders and methylation imbalances. Copper/zinc imbalance does not cause MT dysfunction, it’s the other way around, which is directly connected to genetic mutations (epigenetics).

So the cycle goes something like this:
  1. Genetic mutations begin way back in the family tree as a result of nutrient imbalances.
  2. MT dysfunction begins to express itself.
  3. Grandma is affected, then mom, then you.
  4. Copper dysregulation occurs (along with an increase in other heavy metals) with each successive generation, which pushes zinc and other protective nutrients to an all-time low.
  5. Results in greater occurrence of oxidative stress disorders such as mast cell activation syndrome (MCAS), autism (a distinctive feature of autism is undermethylation and very high oxidative stress, many at 50% free copper), Alzheimer’s disease, methylation imbalances, autoimmune diseases (it’s no coincidence that the majority of these disorders occur in women), and increased mental health disorders such as depression, bipolar and panic disorders, schizophrenia, Parkinson’s disease, eating disorders, and AD(H)D.
MT proteins also perform a wide variety of vital functions, including but not limited to:
  • Detoxification of mercury and other toxic heavy metals
  • Development and functioning of the immune system
  • Delivery of zinc to cells throughout the body
  • Prevention of yeast overgrowth
  • Regulation of stomach acid pH
  • Taste discrimination by the tongue
  • Protection of enzymes that break down casein and gluten
  • Enhanced efficiency of the intestinal and blood-brain barriers
  • Reduction of inflammation after injury or illness 3

When it comes to diet, it’s important to make the distinction between cause and effect because most folks believe it’s the food causing the imbalance, but in reality, there is an imbalance of MT.

So the effect of these disorders is that people become intolerant to things like casein, gluten, and high histamine foods. This does not mean that these foods are the cause of the disorder.

It’s the other way around.

Intolerance is an effect of massive oxidative stress and lack of MT function.

And make no mistake, it’s not that many of these foods are not inherently toxic, because we know that they are (and should be avoided for healing to occur), but they are only one slice of the overall epigenetic pie.

Keep in mind that long-term, restricted diets will only provide partial benefits until the system as a whole is brought into balance. Not to mention the toll this takes on your emotional well-being.

More research and intense study is needed, and Dr. Walsh is currently looking at the factors that enhance genetic expression and utilization of DAO once it’s present in the body, which is the same line of research he did with MT.

If you know of someone who struggles with histamine intolerance or a mast cell disorder, please share this post. If you are struggling, please share your experience in the comments below. It is through sharing your story that we create community, eliminate guilt and shame, and bring about healing.

Love,
Sami G

 

 
References:
[1] Oxford Journal. Effects of Histamine and Diamine Oxidase Activities on Pregnancy: A Critical Review.
[2] Mensah Medical. Pyrrole Disorder.
[3] Walsh, William J. (2012). Nutrient Power: Heal Your Biochemistry and Heal Your Brain. (190). New York, NY: Skyhorse.
Additional sources:
Experimental Biology and Medicine. The Histaminase Activity of Ceruloplasmin.
American Journal of Clinical Nutrition. Histamine and Histamine Intolerance.
Pfeiffer, Carl C. (1975). Mental And Elemental Nutrients. New Canaan, CT: Keats Publishing.
Lontie, Rene. (1984). Copper Proteins and Copper Enzymes. Boca Raton, FL: CRC Press.

Comments 247

  1. Working with a “Functional Medicine” doctor right now.
    I have low serotonin, high histamine, all of my sex hormones
    are very high;including DHEAS, Testosterone, progesterone,
    estrogen.
    Symptoms of depression started with postpartum depression,
    with the help of anti-depressants for 12 years, until the last 4 years.
    It stopped working.
    Doctor working on adrenals and detoxing liver to move estrogens
    through.
    If this doesn’t help me, where begin with all of the testing for
    copper overload and methylation?
    Thank you

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      Hi Carrie,
      Based on what you’ve shared, I highly encourage you to look at copper. Keep in mind that adrenal fatigue is just another word for oxidative stress and that adrenal stress index tests are not reliable. When you are ready, you can email us here for more information on working with me.

      1. Hi , in desperation of help , my gp is treating me for under-methylation with high vit B , zinc compounded capsules and cream to detox , also glutathione spray under the tongue to support liver detox , have lost 2 kilos in weight now 41.5 kgs , migraines , anxiety , nausea , profuse sweating and balanc s all over the place , I’m 57 yrs old and have had under-methylation since very young , introverted , anxiety motion sickness since I can remember now I’m being treated I feel worse than I have for a long time , please help with any ideas or suggestions , getting to me and my family for being silly and accepting this treatment , I don’t know what to do , assurance or anything that might help me I’m desperate for help before I get to depressed , thank you

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          1. How do you get these tests done when you have an uncooperative GP? I am on subsidized health plan and can’t afford $thousands. My doctor doesn’t believe in integrative medicine, and refused to do the tests recommended by the IMD I paid for out of pocket ($900 for one consult). I’ve had to figure this whole mess out on my own, and the closest I’ve got to any answer and relief for the vicious asthma and allergies that have wrecked my life is histamine intolerance and low histamine diet. I’d like to think I will someday know what the heck went wrong with me and fix it enough to have a life again, but how when no doctors care enough to dig deeper than the surface, anyone that does is $$$$$ I don’t have, and there is so much more to this problem?!

        2. Did you start the supplements slowly, and GRADUALLY titrate up? Too much too fast can make symptoms worse at first causing agitation, anxiety… Also did he test your copper? You could be decoppering perhaps from the zinc and this can cause horrible symptoms of done too fast…. Not sure where you are located but I have a son who is a severe undermythelator; he has been with Mensah for over 7 years ( he is now 13), I find dr Mensah and Dr bowman to be the authority over everyone… At the very least if you are far away you could be tested via direct healthcare access and then do a phone consult with dr Mensah to see if something is being missed. My guess is that it is. It’s worth the money and time to do this. You should be able to achieve positive results with treating your undermythelation…

        3. hi Robyn,
          what happens when we take supplements is we begin to change our biochemistry. When you feel worse taking them it is because your body is struggling with trying to detox what is being removed. It is important to support your liver during this time. If you are still struggling feel free to contact me

    2. Good day

      I have been diagnosed with adrenal fatigue and Fibromylgia. Years id stomach discomfort, extreme anxiety and heart palps that have landed me .in ER. chest pains
      Painful neck and shoulders. These are my worst stmptoms.
      Seen so many doctors
      Wish I had relief.

      1. Your symptoms sound like mine, which turned out to be actually Lyme disease, a bacterial infection I acquired from a known tick bite in my foot. Antibiotics helped my symptoms, also turmeric takes down the pain. You can discuss at www lymenet org in the Medical Questions section, also get Lyme doctor referrals in the Seeking a Doctor section.

  2. I know I have a problem with histamine and I’ve been taking quercithin I was going to do the sprouted pea shoots or take DAO supplement,Ihave MTHFRmutation plus Lyme so it gets a little complicated. I am also considering something that looks promising ,I will let you know if it works. I am doing a consultation with Dr. Mensa hnext week so I’ll have more information. Thank you

    Warm regards

    Patty

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  3. Amazing how it all fits together. My daughter struggled with histamine and mental health issues until her doctor put all of the pieces together. We are now following Dr. Walsh’s nutrient therapy and she is a happy and healthy kid again. Such a blessing.

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      Hi Abbey,
      I’m so happy your daughter is doing well! Thanks for sharing your story and keep up the great work of being an amazing mom!

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      Author

      Hi Karen,
      Absolutely! Especially since Gilbert’s Syndrome is a byproduct of an inherited gene mutation.

      1. How does the interaction of Gilberts syndrome display. Am trying to see if I’m on the right track with the symptoms that are being displayed. Thanks

        1. I would like to know too as I have Gilbert’s and have just been diagnosed with Gilbert’s possible methylation problems.

  4. So if antihistamines interfere with the dao activity, does that mean H1 and H2 blockers are not good to help with the itch and swelling associated with histamine release? Is it better to treat the hives and angioedema swells with H2 rather than H1 blockers or do they both interfere with dao activity? DAO supplementation alone does NOT control my symptoms I have tried to wein from antihistamines with assistance from DAO and I have not been successful?

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      Hi Lisa,
      Although H1 and H2 blockers work differently, the end result is the same, so yes, both interfere. I recommend testing for copper/zinc and methylation status, along with a low histamine diet that is appropriate for your biotype.

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  5. right now I’m attending the Australasian Mastocytosis Society Annual Conference in Sydney Australia, so this article is of real interest. Dr Theoharides is going to talk about Histamine tomorrow at the conference. Thanks for sharing this article, very informative.

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  6. I am wondering if this article explains my severe insomnia, that I inherited from my mom and she did her mother as well as her siblings. I also have auto-immune issues, gastro-paresis, thyroid disease, auto-immune issues that cause nearly chronic joint pain, brain fog, etc.. just wish I could figure out how to fix it.. been to so many sleep clinics that no one will even take on my case anymore.

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    1. There’s a possibility that you might have Lyme disease, which causes insomnia and other symptoms you’re describing. Check it out in discussions in the Medical Question section at www lymenet org, also Lyme doctor referrals there in the Seeking a Doctor section.

  7. I also have severe reactions to gluten,casein, and so many other foods that never hurt me before, am B6, B12 and Vitamin D deficient, and anemic. 23andme testing helped me with this.. b/c doctors kept testing me for individual vitamins b/c of insomnia, but no matter how much I took, it kept coming up as deficient.. knowing genetically which kinds work for my body has helped this slightly. Insomnia is still terrible though.. w/o medication.. and have tried over 27 of them.. over past ten years, I only get about four hours of sleep every four nights.. the other three in between, nothing. I could keep a job down before and drive, but now the last ditch effort meds are failing and I”m scared!

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      Hi Faith,
      Thank you for sharing your story. I know exactly how you feel. It is scary, but I also know there is hope. I recommend functional testing to check copper/zinc and methylation status. You can email us here for more information.

    2. Faith, I strongly urge you to work directly with Dr. Mensah or Dr. Bowman of Mensah Medical. From my understanding they go beyond the limitations of what 23&Me can show – to get to the root of your issues. I also used to suffer from insomnia (for years) as well as gluten intolerance; candida issues; brain fog; adhd symptoms…
      After testing (order the metabolic panel from Direct Healthcare Access) that showed undermythelation; pyroluria and low zinc – Dr. Mensah wrote an individualized nutrient protocol…every issue that I suffered with has improved greatly – especially my sleep!
      I am aware of other doctors who study methylation and these issues but after a lot of research and a son who has shown HUGE improvement with bipolar/mood/hyperactivity issues after working directly with Dr. Bowman – I would never go anywhere else.
      These two doctors, are the best in the world, in my opinion. And they can be accessed through DHA and a phone consult to begin with, if necessary. Making no excuse not to access their clinic.
      I would not wait, they will help you with your multiple issues.

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        Amen! I couldn’t agree more. I will add that being an actual patient is a very different and more comprehensive experience than just consultation so I always encourage that.

        1. Yes!! Being an actual patient allows the greatest amount of intervention of Dr Mensah and Dr Bowman. For our son at age 7, and he was at rock bottom with a full blown mood disorder – we were at our wits end. We had tried everything and nothing had worked. As a full patient, Dr Bowman worked very carefully with us every step of the way. He is now 12 and in full recovery as a normal, healthy, happy boy! What Mensah Medical does requires extreme targeted precision – Walsh says rifle shot precision- I could not agree more! It’s worth the time, effort and money – it has been a complete miracle for us and honestly, I would go to the ends of the earth for both Dr Mensah and Bowman. They gave us our son back and gave him a brand new healthy life!

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            I’m so very happy for you and your family Michele! Likewise, my life has completely changed for the better as a result of their guidance. They are wonderful human beings and I love them very much.

          2. Thanks for your comment. I suffer the same. I know this is an old thread, so probably no-one will see this. But if there’s any way you can share what type of protocol worked, and what was your status/symptoms that would be so useful! I am on agimarx@gmail.com – or just here 🙂 Thanks

    3. Faith, thanks for your comment. I know this is an old thread, so probably no-one will see this.

      I suffer the same, especially the insomnia and then also severe anxiety. If there’s any way you can share what type of protocol worked, that would be so useful! I am on agimarx@gmail.com – or just here Thanks

  8. This is so fascinating, although difficult to fully understand/comprehend. I stumbled across my compound heterozgous MTHFR status by randomly looking at blood work from 2 yrs. ago. So tired of feeling like garbage every day. I’m getting ready to visit a doctor who specializes in methylation pathways, as it is so confusing to try to sort out myself. Foods and supplements can help or hurt you, and it’s hard to understand what to take and how much, and when to back off. I remember getting a biomeridian scan years ago which showed elevated copper, but you don’t really know what everything means at the time. I also have liver/gallbladder struggles and have been having major histamine reactions (hugely swollen eyes) for the first time in my life. It’s overwhelming to figure it out, and of course I want my 4 children tested to see what their issues would be. Thanks for this article!! Will be sharing it with others.

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      Hi Jodi,
      Thank you for sharing your story, and I’m glad my article was of benefit to you. I do recommend functional testing to check copper/zinc and methylation status. You can email us here for more information.

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      This is dependant on your biochemistry, learned via proper testing. I do not recommend self-diagnosing/self-supplementation. Nutrients are very powerful.

      1. If one has Lyme – it is likely one has not been detoxing mercury well, and so starting at very low levels of zinc supplemetation is advised, like 15 to 30 mg only a few days a week to start, and building up. This is mostly to avoid detoxing mercury too fast. A binder needs to be used as well – like charcoal, clay, chlorella. blue green algae, etc. to avoid bouncing mercury through out the body. Some practitioners, such as Dr Klinghardt are saying with Lyme strive for zinc / copper balance and thus advise taking small amounts of copper with zinc to assist. However Dr Walsh seems to advise to supplement zinc well and high enough levels, especially where HPU (Pyrrole) is involved, which also is often the case with infection.

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          Detoxifying mercury is but once piece of the puzzle when it comes to Lyme. Again, it’s important to look at the the overall oxidative stress component that is unique to the individual before making any kind of nutrient recommendations.

          1. Did not mean to imply to self medicate with vits– I am in total agreement to seek professional support before self treating with any nutrients/vitamins as they are often very potent (as with detoxing mercury with zinc). It is delicate. As a nutritionist in working with Lyme (both w my own family and other patients) – I have seen copper is not the evil we like to make it out to be. It is essential to all electrical impulses as a conductor (nerves). It just needs to be in the right amount in the right place in the body. So self medicating with zinc is indeed not advised. One needs professional guidance.
            In that regard, I highly recommend Dr Albert Mensah (sorry on Alberto, typo) – as he has been very helpful in explaining much of this to me and our family. It is whole blood histamine that is the measurement of methylation status – (available throught Direct labs via a doctor or ND), and this is an important distinction from regular histamine measurements, which your article explains can diverge. What I find fascinating is the fact that the different measures are indicative of different functional areas, as this must be very new research and makes complete sense.
            Thank you again for your time to write this out Sam.
            Angela (Msc)

          2. So right – chronic infections are very complex. I am beginning to look at lyme (bacteria), candida (fungal) and mold (micotoxin) infections as related for some people.

            There is evidence that they exchange DNA, (just as reportedly zika and dengue down here in Brazil. Worrying).

            When the hormones are really off balance and hard metals are occupying the role of minerals because the “bugs” are using minerals to create biofilm (one explanation), what is the order of tasks in your opinion?

            Do you lower the microbial load first and then work on re mineral and methylation support? Or visa versa? Dr Mensah answered this question once in a webmar and said one has to deal with infection first. Do you agree?

            Many thanks, Angela

  9. What are your thoughts on EDS and Chiari malformatoin? My story is long and complex but I have both the above dx and MCAD. Also listed on my multiple dx are POTS, small fiber neuropathy and iron deficiency anemia. Thank you.

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      Hi Cynthia,
      EDS and Chiari malformation are not my areas of expertise, but everything else you’ve listed has a connection to copper.

  10. I found the information so very interesting, as usual I wish I could understand it all but it is the way my brain does NOT work properly anymore. I was diagnosed with RA, but she also mentioned how HIGH my histamine levels were and I must have severe allergies. I have knows for a long time I have lyme disease as I am on a refuge and all my animals have had it, my husband had it and I remember the distinct bulls eye rash but doctor didn’t believe me. I show myco pneumonia and so many other things but always HIGH histamine. how does one get tested for all this?
    thanks for the education, it is a constant battle putting the puzzle together to try and find healing.

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  11. Hello, I am Marjon from Holland and I am a therapist in nutrition and hormone balances. Can you give me more details what kind of dieet these clients shout / must take?

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      1. Do you have the name of a doctor in Orange County, CA that can help with Histamine Intolerance and the MTHFR Heterozygous gene mutations for both 1298 and 677?

  12. Do you know if there is a specific test available in NZ for methylation problems and to check copper/zinc status?

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      We have 1 practitioner in NZ: Dr. Kate Armstrong, Colville Community Health Centre, 2299 Colville Rd, RD4, Coromandel, 3506, Phone: 07 866 6618. I can also work with you via Skype.

  13. Daughter has pyroluria and 61% unbound copper. Whole blood histamine indicates overmethylator. She’s homozygous DAO RS3741775. She takes antihistamines daily or else has extreme itching. I don’t understand the correlation as she is overmethylator. Should she be avoiding all antihistamines? She has taken Zyrtec daily for 3+ years at advice of family physician. Appt scheduled with Mensah in June but thinking there is something I can do in meantime.

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      Hi Karen,
      I recommend waiting until you see Drs. Mensah and Bowman. Keep in mind you can be over, under, or normally methylated and still have an intolerance to histamine. They are completely different creatures. After you see them, I’ll be able to assist you with the dietary portion of your protocol.

  14. Wow. This is very helpful. I have been thinking for a while now that my daughter’s autism was due to a methylation imbalance (other articles I’ve read point out other symptoms related to this such as depression, alcoholism – both of which run rampant in my mother’s family predominantly). I don’t even know where to begin to help my daughter. Blood tests? Any advice, however brief would be most welcome.

    Thank you for your research and sharing this information!
    C

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  15. Just letting you know that if anybody wants Australian doctors trained by Dr Walsh our website has the full list – http://www.biobalance.org.au and that includes New Zealand doctors as well as some Asian doctors who have done the training.

    Great to get this information out there.

    Kind Regards,

    Judy Nicol

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  16. Thanks for the really informative article summarizing a lot of research.

    Maybe I missed it, but how exactly do you asses your methylation status? What are symptoms of a methylation problem?

    Thank you.

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      Hi Carol,
      You’re welcome, I’m glad it was beneficial to you. I use a whole blood histamine and/or SAM/SAH ratio test to check for methylation status. You can read more about methylation here.

  17. Hi Sami
    since 2007 I suffer from chronic urticarial and angioedema, skin itching. I tried many doctors of allergy, and chronic taker of H1 and H2 anti histamine, ketotifien tab., anti stress supplements, probiotics, as well as diet of low histamine food. I have a little improvement but not much.
    I am living between Amman-Jordan and Paris.
    can you advice me what do you recommend me to do?

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  18. Lyme effects mast cells and I wonder where Pyrrole Disorder and so much stems from a messed up intestinal and digestive function — such as “leaky gut” (is that the abbarent attachment to albumin of copper ??) — I guess that much is related to a combination of environmental insults. Not some new discovery of our genes . Indeed I wonder if could be related to agricultural use of combinations of herbicide/pesticide/incectisides. (Note that only single use are tested as humanly safe by government regulatory bodies like FDA, not combined use). Add mold in our homes and environment due to global waming and weird weather as well as our bad house construction and then wifi (thank you Apple) and electric magnetic force that grow mold in our homes and bodies – — I think you see where I am going with this. I wonder if it is not just methylation support that can get anyone who is very sick (with Lyme and mold and co infections) better? Methylation support is instrumental for all these steps needed for healing – (immune modulation, protection of cells, detox) — but lowering microbial/micotoxins and parasite/protozoa loads and addressing pathogens will also be needed. Even if we just assume they are there, never give them a name, but apply gentle means of coaxing them out of the body and winning that war through support to proper immunity and protection of cells and organs.
    I am so pleased to see this summary though. You have done a heroic job.
    Angela B. Koch (MSc, Nutrition) and mother of four teenage kids suffering from Lyme and co infections.

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      Hi Angela,
      You bring up some great points and yes, they are all connected. Keep in mind that addressing GI oxidative stress is part and parcel of our methylation treatment approach.

  19. I just realized one thing. I think you may have a mistake in the article. As far as I understand it is whole blood histamine that is the measure related to methylation. The non whole blood does not give you this reading. I think you make have reversed this. I would ask Dr Walsh or Alberto mensah MD to clarify this. But pretty sure it is whole blood histamine that gives the sense of being either under or over methylated.
    Regards, Angela

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      There is no mistake in my article. Reread my post. I clearly stated that “very elevated histamine in blood signals blood basophil cells where additional methylation of histamine is needed (this is how we check methylation status)… Mast cell disorders and methylation imbalances are epigenetic in nature and both are connected to histamine, but there are separate systems for controlling histamine. They are (a) blood basophils and tissue mast cells and (b) blood plasma.” And Dr. Mensah’s name is Albert, not Alberto.

  20. I was directed to your site by a FB post and I have to say that I just came to the conclusion that methylation and probably copper is a problem for me 2 days ago! I’ve been trying to figure it out myself through googling for all of the Walsh information that I could find online over the past months.

    I started having intense itching and swelling last summer and thought it had to do with histamine intolerance. I can’t tolerate any of the gut healing paleo recommendations (bone broth, gelatin, L-glutamine, etc), as they bring on instant migraines for me. I started on AIP Paleo 14 months ago after 17 years of being a vegetarian.

    I get 4-6 migraines a month, which is an improvement on chronic daily headache that went for 3 months with in 2009. Prescribed protryptaline is the only thing that got those to stop, which I’m still taking. Diet alone hasn’t fixed the headaches. I did get to 14 days at a time without any on a ketogenic AIP paleo diet, but I could only handle that for 2 months in the winter. The headaches have gone back up to 4-6 a month on AIP with some reintroductions and have been reconsidering the ketogenic version of my diet, but it’s so hard to do! How can I best move forward with a Walsh nutrient plan so that I have help and am not trying to fix myself?

  21. Dear Sami G.

    I have read this page with great interest. Though I struggle with the medical english so I don’t get all of what you are saying. I am new to this. I had a blood sample analyzed last december showing a bit low diamine oxidas. Not extremely low (60) so at first I didn’t pay notice. But after the holidays I started to face this. I did start with histamine-low diet and it worked for me. I though get backlaches fequently. It is difficult to avoid food that I must avoid. Being a vegetarian since 12 year I see that that might be a drawback.
    My problems increased after two treatments with Aldara for actinic ceratosis. I don’t know if there is a connection but I suspect that.
    You are writing that almost everyone with this problem are women, and the last time I check I noticed i am not a woman. So how come I have this?
    I am also unsure of what to do. My house doctor know about this now after me informing him (on my cost). How can I inform him of all your work and knowledge?
    I live in Norway but I had to go to Sweden (I am swedish but lives in Norway since very long) to get the blood sample. Norway is a high cost country so the same blood sample would have cost me $1000. In Sweden I did pay 1/4 of that.
    So how can my doctor inform me of how to treat this copper/zink inblance when I probably knows more of this than he does?
    I get a bit scared when you list all issues/diseases I should expect in the future.

    Do you know any scandinavian that can be of some help for me?
    Do you know Ulf Bengtsson working at Sahlgrenska hospital in Gothenburg?

    Best wishes
    Lars

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    2. I had the same problem after using aldara, I wish I could contact you. I’ve been suffering with horrible histamine issues ever since applying it, you’re the first person I found who has the same issue as myself. I’ve been to tons of doctors and no one has helped.

      1. I have Ehlers Danlos syndrome and also have had horrific longterm side effects from Aldara. All it took was two applications and it triggered some kind of autoimmune reaction (It’s been almost three years now)
        .

  22. Wow!… I can’t tell you how excited I am to have read your incredibly informative and captivating articles!!… I was recently told I had a tumor in my duodenum, from diagnostics of blood work and ct scan ..likely malignant… Imagine the stress that caused us all… Only upon the biopsies did they discover they were not cancer cells but I’ve developed a rare blood disorder, Eosinophilic Gastroenteritis…. Since the medical world are largely funded by the large drug companies, even though many health practitioners are well meaning and good hearted, the only solutions they offer are steroids and elimination diet. Since it’s rare there’s not a complete understanding of it, but they say it has allergic components…my eyes were at full attention when I saw your article about histamine, which I’ve just digested like a ravenous lion! hehe I’ve already started down the path of natural understanding and healing in fact it was my new found lovely natropath that recommended articles about methylation in our bodies who helped me find your articles… I guess I want to say a big THANK YOU to you for the wonderful way you are touching lives… It’s so exciting to have hope, true our complete future healing of our bodies and planet and social system is in the hands of God, and this brings the greatest hope of all… Still in the meantime we have to live and love and do all we can to help others around us…and your research and efforts are going a long way!!! Warm Christian love from N.Z. Xxxxxx

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      Hi Betty,
      Thank you for sharing your story and your sweet comments. I am so happy my articles have helped you. Indeed, love is a powerful healer. Best to you in your healing journey!

  23. Ps. Additional to previous comment… interestingly the elimination diet has done nothing, in fact my levels have risen!…giving credit to your findings and my suspicion it’s toxins or heavy metals …but to understand more completey WHY my body may not be detoxifying efficiently and how that will have a base in my nutritional healing of my gut, is fantastically empowering and I may yet still work with you too… I completely relate to these issues you understand so well… And I can’t wait to recommend you to others! Xxx

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      Thank you Jay. Coffee drives adrenaline so I don’t recommend it for folks with methylation/copper issues. Personally, I can tolerate coffee once in a while now that my copper and undermethylation issues are fixed, whereas before I couldn’t tolerate it at all. Coffee usage and consumption is really dependent on biochemistry, and I always recommend organic options.

  24. Hello,

    I believe I am an under methylated from my histamine results being 68, copper 99, and zinc 96.

    Anyhow, can you please tell me if it is wise to avoid fermented beverages and foods like kombucha and fermented veggies? Will this make symptoms worse?

    Thanks so much!

    Sue

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      Hi Sue,
      Regardless of lab values, every undermethylator is different so it really depends. Generally though I recommend avoiding them, especially in the early stages of treatment.

  25. Hi Sami,

    Great Article.! on the advice of a friend Ive read Nutrient Power and had bloodwork done, because Iv suffered from some intractable emotional/ psychiatric issues. The results were pretty strange in that the typical imbalance of a copper/zinc wasnt there, instead i had very low copper, very low zinc and very low ceruloplasmin (above the level of Wilsons disease, but just a few points above) . I also tested positive for double mthfr snps and blood histamine levels in the higher degree of the range.

    I cant figure out what might be going on , might I have a sub clinical form of Wilsons disease? Any advice appreciated!!!

    Chanah

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      Hi Chana,
      Thank you, I’m glad you enjoyed it. I definitely have patients that are low in copper, but it’s difficult to provide guidance without a proper assessment. You can email my assistant here for further information.

  26. Is there a doctor in Florida you recommend that can run these tests? This article has set off a light bulb in my mind so many things make sense now. I have MCAD, POTs, EDS and MTHFR.

    Thank you!
    Mari

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      Hi Mari,
      I can assist you with testing or you can wait to attend our outreach clinic in Fort Launderdale in January.

  27. Could it be? Ater my gastric bypass I can’t eat tomatoes, spinach, oranges and chocolate anymore because of the pain and the diarrea. I have astma, chronic rhinittis (for both I use corticosteroids) since 2009 and now I am wondering. Could it be? Do you have any thoughts on that? I really would like to hear them if you have.

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      Hi Caat,
      Histamine is released every time we consume food and is a big part of the digestive process so yes, gastric bypass surgery can definitely create a histamine intolerance issue.

      1. How much does what we eat before a wbh test affect the results? I would like an accurate methylation result. I know there are snps upreg and downreg. But wbh I have no idea. I know certain things make me react more and if I avoid them will it not be better for the bigger picture?

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          Hi April,
          Antihistamines will skew results. Avoiding trigger foods is important, but until the body’s master antioxidants (glutathione and metallothionine) are restored via balancing methylation cycles, an elimination diet will only provide partial benefits.

          1. Thanks. I’m piecing together a lot. I appreciate the input. I have thought of seeing Mensah, but I don’t know if I could tolerate the supps. I tolerate no methyls so far. There’s a lot going on and I react to so much. Obvious issues but what to do??! Most things I need I can’t take because of something else. I will test the few you listed. I’ve been life long needle phobic but I’m healing. Hopeful!!

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            You are most welcome April. I can help you with testing when you are ready. Generally in highly sensitive individuals we start with a very low dose until more can be tolerated. It’s never our intention to create more trauma than what you’ve already endured. You can heal, please remember this.

  28. Hi Sami,

    I recently discovered from a hair element analysis that I have high copper (out of range). Reading up on copper toxicity has led me down several different rabbit holes, and I am feeling a bit confused. I am having a hard time sorting out all of this information on methylation status and the possible connection to elevated copper. From my reading, I would guess that I am an overmethylator (creative type, hypersensitive, chronic insomnia, anxiety/depression, food intolerance, severe fatigue, intolerance to SAMe and SSRI medication). There may be some element of family predisposition, I suspect my grandmother was high copper/or an overmethylator – she had bipolar with psychotic features.

    I see that MTHFR testing has a lot of buzz right now, but would that help to identify overmethylation? It seems like most of the discussion surrounding this testing concerns undermethylation.

    Can you recommended any sources for further reading that may help to clarify this confusion? Is there any kind of testing that can clearly reveal what my methylation status is?

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      Hi Vanessa,
      Thank you for sharing your story. Current genetic testing such as MTHFR has no way of telling you have much methyl is in your body (over or under) and whether those specific SNPs are expressing or not. I highly recommend a proper assessment and functional testing to determine methylation status (whole blood histamine and/or SAM/SAH ratio is how levels are determined), which I would be happy to assist you with. You can also check out Dr. Walsh’s book, Nutrient Power: Heal Your Biochemistry and Heal Your Brain.

      1. Hi Sami,
        Thanks for the suggestion, I will get a copy of the book a.s.a.p. I am interested in working with you, can you still order all the labwork if I am residing in Canada?

        I was inspired to read your story (bio), I can really relate to a lot of the things you experienced. I am glad to read a success story with treating copper overload, and to know that I don’t necessarily need to invest in expensive chelation therapies to get better. Looking forward to learning more, getting my methylation status checked, and getting started on a program.

        I have one more question for you: do you find that people with copper overload tend to have chronic insomnia? Does this go away once the copper levels are balanced?

        Big Thanks!

  29. Thank you so much. This is the single best lay persons explanation of my condition that I’ve seen, and I’ve been searching for a long time!

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      Hi Amy,
      The short answer is yes, but I don’t recommend zinc supplementation without a proper assessment and testing. You really need to know what your levels are first before diving into nutrient therapy. Too much too soon can create painful results.

  30. Which genes are tied to MT? Are there tests for that or DAO function? I do have ++ DAO, lots of others, and pyroluria. HTMA looked ok for zinc unless it was false med high and copper was one of the only balanced things. Lots of issues, avoiding tons of things and keeping issues at bay by avoiding. Thanks. Good read.

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      Hi Apri,
      This is currently being researched. Keep in mind that mast cell degranulation is extremely idiosyncratic with so many variables and layers. The most important thing right now is that you get properly tested. HTMA alone is not enough. It must be used in conjunction with other testing methods.

  31. Has a link been examined between histamine and/or copper with connective tissue disorder, more specifically causing a spontaneous spinal fluid leak in the dura of the spine? Lots of sufferers looking for an answer in this area.

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      Hi Sara,
      I am not aware of any research in this area, but this is something I see that may be connected to copper/zinc imbalances that might affect histamine tolerance.

  32. I WANT this theory to work for me but Im opposite to everything you say and Im confirmed systemic mastocytosis. No PGDFA or MTHFR mutation. Do have CKIT and CD2. Im deathly allergic to the pregnancy hormone beta HCG, and same with estrogen. I AM on progesterone hormone therapy and am in induced menopause with improved symptoms. The hormone therapy of course made my estrogen flare at first amd I was very sick and in hospital etc. but once it kicked in amd my ovaries shut down, I felt so much better. I just keep seeing this article and want it to work for me but its totally opposite lol….

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      Hi Liz,
      Thanks for your comment. The fact that you are estrogen intolerant points to a copper/zinc imbalance (especially considering your reaction to progesterone therapy), which is directly connected to the various histamine relationships. Keep in mind that we all respond differently, and I encourage you to get properly tested.

  33. I have been diagnosed with idiopathic anaphylaxis since I turned 45. I eat well (mostly vegetarian) and continue to gain weight, feel fatigued and have joint pain. When I ate the Paleo for awhile I actually felt great.

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      Hi Ingrid,
      Thanks for sharing your story. Vegetarian diets are high copper/folate diets and can create the symptoms you are experiencing depending on your biochemistry. This is one of the many reasons protein is so important. I’m glad you found relief from adding it to your diet.

    2. The mold toxicity if exposed can cause rapid weight gain so maybe, besides what Sam recommends you want to check out Richie Shoemaker site?

  34. Does an elevated ADMA ratio indicate oxidative stress? I believe my doctor said it does – he was concerned about the oxidative stress and I had a Spectracell lab test run which showed I was low in B5, D3 and K2. Interestingly, looking at the results (now many months later), it appears that I have high calcium and my copper levels seem higher than my zinc levels. Of course, the Spectracell test was only concerned with nutrient deficiencies. I called them today to see if they would have flagged a report if I was too high in certain minerals and they said they are only looking for deficiencies.

    I am also double homozygous MTHFR C677T. When I am “eating badly”, I get itchy skin at night, especially in between my fingers and on my palms. I also seem to have a constant low level of post-nasal drip. Gets much worse with drinking red wine.

    Will be reading and researching more. Do you know of any doctors in the central FL area that you would recommend? Thank you so much.

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      Hi Jennifer,
      I don’t use Spectracell so cannot advise on that, but yes, that would be indicative of oxidative stress. I use blood, urine and hair tissue mineral testing to determine deficiencies and overloads that comprise oxidative stress. I don’t know of anyone in your particular area, but I do work with clients remotely and testing is very easy to complete. We also have an outreach clinic in Fort Lauderdale in January – http://mensahmedical.com/mainclinicoutreachclinics.html.

  35. Sami, this article is fantastic on so many levels, I am blown away. I just want to say thank you for writing it!!! It has explained some things for me that I have wondered about for a long time. You rock!

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  36. Hi there, can you recommend anyone in Sydney, Australia who specializes in this? Although I am feeling better than I was, it is a constant battle just to maintain any kind of balance. I am being treated for Pyroluria, carry MTHFR gene, and struggle with what appears to be histamine excess/intolerance (genetic testing also support this). However being so extremely sensitive makes it difficult for me to maintain any kind of routine in supplement taking. I was formerly diagnosed with CFS, fibromyalgia, Leaky gut, food intolerances, environmental sensitivities, PTSD, anxiety disorder (10 years ago), but am now focusing on getting to the root of my issues. I find it all rather confusing, as science was never my strong point. I have had testing through 23&me, and whilst I have a great nat/path, feel I need somebody who specialises more in these fields. Your work & knowledge is remarkable thank you, I hope you are able to recommend someone.

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  37. Thank you for writing this as it hits home for me with all of the issues I’ve had in the last year. I have low levels of copper and ceruloplasmin and symptoms of either a histamine intolerance or MCAD. Can you tell me the link between these and what I should be doing or looking for? No doctors I’ve seen have made this connection for me.

  38. I have Lyme and almost all mt pathways are blocked. I don’t sleep and am in a lot of pain. Had a heavy metal test I have high levels of copper. My Lyme doc has me on a special b complex and am suppose to avoid histamine foods. Not noticing any difference. What else can I do

    1. An ND who works with Lyme could be best start as lowering microbes ( including mold mycotoxins) is first step and modulation immune system ( cytokines) and inflammation as well addressing biofilm a with enzymes – is advised prior to addressing hormonal and methylation issues. An experienced ND could steer you to supporting detox with diet ( including low histamine diet) and with liver etc support, crucial for tolerating any treatments including addressing methylation or genetic glitches or ” killing bugs” which put enormous stress on detox channels.
      Super interested in Sami ideas on addressing mast cell issues in Lyme.
      Best,
      Angela

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    1. Hello, thank you so much for writing this article it gives me hope. I’m 47 yr old female and I suffer from chronic sinus headaches caused by allergies/inflammation . I started having this issue after the birth of my second child at age 24. I’m allergic to tress, grass, and weeds; living is Southern California I struggle with this year round. I know the sinus headaches are from inflammation in the sinus passages but can figure out how to prevent it. Ive had sinus surgery and received allergy injections with no relief. When I see the doctor they give me an antibiotic and basically tell me to suffer with the debilitating Pain – and that’s it nothing else they can do. I take an antihistamine every single day, a decongestant when a storm front moves in (I guess I’m sensitive to pressure Change from weather change), Motrin for pain when needed. I know the pain is caused by inflammation but can’t figure out how to prevent it. I also feel tired most of the time ( doesn’t matter how much sleep I get), dry skin, itchy skin, and my skin takes forever to heal, and I have some depression but not too concerned with that because I think it’s just part of not feeling well. These headaches can last for days, are very frequent, and are debilitating. I don’t know what else I can do and I was wondering after reading this article if I should get tested? Please advise. Thank you so much

  39. Hello, thank you for writing this article it has given me hope. I suffer from allergies (trees and grass) and constantly have terrible sinus headaches because of swelling. I’ve tried medication, allergy shots & sinus surgery and nothing has helped me with prevention. I see the doctor and given antibiotics and basically told to suffer with the pain and that is it, nothing else they can do. I started having allergies after the birth of my second child around age 24. I also have dry skin, my skin inches often, and takes forever to heal. I feel tired a lot of the time (doesn’t matter how much sleep I get). I have some depression issues but consider this to pretty normal and am not too concerned about that. I take an antihistamine every single day year round,Motrin for pain, when needed, & a decongestant before a storm come which sometimes helps prevent those types of headache ( I guess I’m sensitive to pressure change related to weather). I know my pain is from inflammation this is very obvious to me. This affects my quality of life and I’m desperate for relief. Do you think I should get tested?

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  40. Strange I keep ending up at sites saying how this affects women. I have been searching the symptoms that both women and men in our Lyme group have. I keep ending up at histamine intolerance articles. They all speak as if men aren’t prone to it.
    Confuses me, I am not sure if I am going the right direction or not.

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      Hi Lee,
      I understand where you are coming from. Histamine tends to affect women more than men, thus increased research and writing on this topic geared toward women. However, men are also affected. If you’d like to schedule a complimentary session to see how I can help, click here.

      1. Thank you, I was headed in the right direction. I found if we kept a food diary it made it easier to figure out what methylation pathways were blocked. Most of us were javing reactions to foods that inctease gluthione production. Which seems to point towards CBS pathways being blocked.

  41. Hello,

    Thank you so much for your article! Do you recommend any doctors/allergists in the NYC who treat Histamine Intolerance/Mast Cell disease. I have been suffering from itchy skin (with no rashes), psoriasis, awful sleep for many years and cannot find anyone with knowledge/experience on the subject.

    Thank you so much!!!

  42. Hi,
    My daughter was just diagnosed with Mast Cell Activation Syndrome. She’s only 21 and has been suffering for over 10 years. Dr. Miner is treating her for her MCAS but we are having trouble getting any help with controling her symptoms. The doctors keep telling us that they don’t know enough about it so they aren’t willing to do anything to help her. Our only advise is to keep going to the ER for degranulation episodes and pain control. My daughter is now not even able to drink or eat anything. Narcotics are the only pain control that has worked up until now but they don’t even want to give her that now. We has had 4 different kinds of pain blocks, only 1 worked for 3 weeks. But we traveled 1000 miles to Cleveland Clinic to recieve help. I need someone to take over care of my daughters welfare/health. She is going to constant degranulation and system wide pain now. Started in her abdomen and now has spread to her legs and knee joints. She has to use a cane. She suffers 24/7. I’m at my wits end. Please help.

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      1. Can you recommend a Mast Cell doctor in the New York area? I have been searching but cannot find anyone.

        Thanks!

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  43. Hi there,
    Can you help me understand the role of methylation with leaky gut & candida? I have been suffering GI pain for over a year & have now developed thrush along with intolerances to foods high in histamine & salicylates. I have all the classic symptoms-irregular heart beat, prickly heat in my arms, anxiety, insomnia, confusion, & on & on. I am heterozygous MTHFR C677 and was taking Thorne research essential nutrients IV with copper & iron. I just don’t know where to start so I can get better!! Do I stay on the supplement? Treat candida with antifungals? Am I at risk for developing a mast cell disorder?? I can’t seem to find a GI dr or allergist to understand. thanks

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      When the body is not methylating properly, it’s wide open to attack from invaders (pathogens and metals). Until your body’s master antioxidants are restored, it’s difficult to eliminate these types of issues. I’m happy to offer you a complimentary session to see how I can help.

  44. Hello! I’d love if someone can send me some info regarding Lyme, I now have suspected Mcas and possible methylation issues. I’m from Canada and need a good doctor. I just got super sick after a 9 month course of ABX. Thinking I’m toxic or by methylation BC my b12 is super high. Any advice or whom to call please let me know 🙂

    1. Dear Amanda,
      I would recommend contacting two groups (youc an google), the ILAD which is the association for Lyme can help you find a doctor LLMD or LLND referral. The fact that you became so sick on abx may indeed indicate a genetic disorder that can be triggered by infections and ceryain medications etc. and you can contact the Porphyria Association of America who can send you information. However methylation issues I believe often accomany all this due to inate problems of detoxicatoon and getting help from Sam here and the crew working with Dr Mensah would be a wise thing eventually on your road to healing. Best, Angela

    2. Hi – inviting you to come to www lymenet org and discuss in the Medical Questions section, also get Lyme doctor referrals in the Seeking a Doctor section.

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  45. Is there any one in the Phoenix area that you can recommend that understands and can test for these things? My granddaughter has been seen in one of your clinics and is on her way to treatments,but am anxious to see if my reliance upon antidepressants may have a chemical genetic link between us.

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  46. Thank you so much for this article. I am studying nutrition and I am in my late 30ties. I have recently developed an itchy rash (on contact) that comes and goes. It has been going on every day for the last 3 months. I have been researching and histamine or mast cell activation sound like an explanation of what I am going through. Your article makes things clearer and will hopefully help me to address this correctly, through a gut healing protocol.

  47. Thank you so much for writing this. I am in desperate need of help. I have had odd symptoms since I was 16. Migraines, endometriosis, ovarian cysts (that eventually led to a total hysterectomy at 27). Then in my early 20’s I developed reactive airway disease and started having allergic type reactions. I have also been diagnosed with IBS and dermatographia. In 2012 I had a headache/migraine that lasted a year and 1/2. That’s when we started looking a histamine intolerance. I went to one of the top headache clinics in the US with not much help so finally after about a year and 3-4 months I stopped most medication and drastically changes my diet. I started taking DAO supplements and tji ge started turning around. I have continued to be conscious of what I was eating but I did not have to be extremely strict like I did in the beginning. Then about 3 months ago everything crumbled again only this time I had chronic hives on my arms, chest, abdomen and back. I started with severe nausea again with bouts of IBS flare ups. However, the most frightening new symptom was that my tongue and throat would begin to swell. I am also experiencing severe, almost disabling joint and muscle pain in my legs. through the years I have been to several allergist, an rheumatologist/immunologist, and lastly a hematologist. Feb hematologist suspected systemic mastocytosis and started me on several different antihistamines, which of course made my symptoms worse. He did a bone marrow biopsy which ruled out a mast cell disorder. It became very clear the my husband and I know way more about histamine intolerance than any other doctor in the area. I am now hack on the elimination phase of the low histamine diet and taking several probiotics and prebiotics as well as DAO suppelements. My symptoms are slightly better but I am still out of work and don’t really know what to do or where to turn to next. Any and all advice would be appreciated.
    Thanks
    Mandy

    1. Mandy,
      The genetic condition of porphyria can have some of your symptoms, so would advise to check this out. Infection ( often Lyme) can trigger this, plus wrong medications including some supplements, fasting, alcohol, and some foods. The porphyria foundation has kits they can send out to you to share with your doctor. I will let Sam respond to mast cell and methylation concerns.
      My son has both Lyme and porphyria so I am familiar with this.
      Hope you feel better,
      Angela

  48. This is absolutely fascinating to me. I’m 14 years old as of a week before, and it stuns me; the way in which the body is strictly connected. I have suffered from histamine intolerance, and what I think to be a mast cell activation disorder ever since I had been exposed to months of continuous stress. So basically, my question is: if, in some cases, the mast cell disorder is strictly a result of stress which may enhance certain levels of specific elements of the body, then if you heal your body it will go away? I mean – if there is no genetic aspect to the histamine related disease, you can heal yourself?

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  49. Also – I’d like to know how stress can essentially lead to a mast cell disorder, or histamine related disease. Thanks!!

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      Over time stress (emotional and physical) switches on deviant genes (we all have mutations) that can lead to these types of reactions.

  50. Hi Sami,
    I cannot quite wrap my mind around some of what you have written. Could you clarify for me please?
    E.g. You say both “An individual with DAO weakness may have normal whole-blood histamine, but very elevated plasma histamine and depressed DAO levels.” And “Folks that have low DAO activity (again, epigenetic in nature) also tend to have low levels of histamine in serum and plasma”
    I am having trouble marrying these two statements????
    Thanks.

  51. Hi Again,

    Another question. I see that ‘Seasonal Allergies’ are listed under undermethylation symptoms in ‘Nutrient Power’ so does that mean that hayfever is not a histamine intolerance but a mast cell undermethylation issue. My son has seasonal allergies and we have been taking DAO Histamine Digester supplements and cutting out high histamine foods but are we barking up the wrong tree. Is it better addresses by handling undermethylation? Also, will using the DAO Histamine Digester and low histamine diet stuff up a histamine test to ascertain methylation status or will it only affect plasma levels?

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      Seasonal allergies are not typical of mast cell degranulation. DAO and a low histamine diet will not affect any change for your son if he is undermethylated as they are very different creatures. Antihistamines and certain medications can skew whole blood histamine results.

  52. A bit extra on that last question. This study ‘Wollin, Armin, Xiaolin Wang, and Patrick Tso. “Nutrients regulate diamine oxidase release from intestinal mucosa.” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 275.4 (1998): R969-R975.’ says that Oleic acid (unlike other nutrients) helps release DAO into the bloodstream, to degrade free amines and histamine throughout the whole body. Oleic acid dramatically increases the release of DAO into the blood stream by up to 500%. Olive oil is one of the primary sources of oleic acid.
    Since reading this I have been upping the organic olive oil in meals.

  53. I’m suffering from burning mouth syndrome, gastro issues, and having issues with high histamine foods. I don’t have a lot of money and want to spend what I do have wisely. I have compound MTHFR also. What tests should I take for finding out my DAO level and my copper/zinc level?

    1. If you do 23andme and run it through strategene at seeking health they will tell you if you have a DAO mutation which definitively tells you if genetically you have low DAO function. you could be fine genetically and still have low DAO from an infection, medications, diet. But I would start with the genes especially if you know family issue.

  54. “nutritional/nutrient therapy protocol that is appropriate for your biotype is essential” – what does this therapy protocol entail and how do you find hour biotype?

    Im 21 have been sick for years fatigue, IBS, joint pain, rashes, anxiety, depression ect. This February it turned to anaphylaxis for nearly 10 days. I have got symptoms down with food rotation Diet, AIP and Quercetin but am still struggling with my daily face swelling and migraines. Any suggestions to help me find out if it inspected to this article and how to treat it?

    Thank you.

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      Hi Lexi,
      Testing with a thorough assessment is how biotype status is determined. There is never a one-size-fits-all scenario with mast cell degranulation so recommendations will vary from person to person.

  55. Hi, thanks for this article.
    I have a reaction to almost every food , environment, and drugs. At times, it seems that it is getting worse and getting sensitive to more things. I have been working with a functional doctor and his team for the last 1.5 year, after going from doctor to doctor without help or relief. They run tests and found that I have been exposed to mold (high micotoxins in body) as well as high lead levels. Have been treated, levels came down, but not to recommended levels. Taking a lot of supplements, as well as antihistamines (I cannot stop taking them because I automatically get an upper respiratory infection). Allergic to antibiotics and because I was prescribed for so many years, developed clostridium diff.
    I have 2 questions:
    1. How can get a supplement to increase MT?
    2. Do you know any doctor in the Washington DC area (includes Maryland and VA), that specializes in this area?
    Looking forward to your response.

    Again, thank you for caring and sharing such important information.

    Kind regards,
    Adriana

    1. Mensah Medical – Dr Mensah And Dr Bowman come
      To Annapolis, MD in March and also Sept. I would definitely call
      Their main office in Chicago and schedule an appointment. If anyone can figure out your issues, they can. Site is http://www.mensahmedical.com

  56. This is so interesting because I have EoE, a plethora of allergies and now too many mast cells in my gut. Years ago I had a copper wire iud and started to have problems with insomnia, anxiety etc. my doctor kept saying I was full of histamines because I was always flushed and blotchy. We were baffled and could not figure out what the main issue was. It’s taken almost 10 years to iron it out. We do think it’s possible I was having allergic reactions years back and the er doctors just kept trying to pin it as anxiety when I had no reason to have anxiety attacks. We had the iud removed but it took at least a year to feel better. I still have food allergies and gut issues but I now see a mast cell specialist and take h1 and h2 antihistamines. It does make me wonder if I could have a combo issue with DAO and mast cells. I’m sure you are all aware of the Pots, Eds connection with mast cells as well which we think is a problem for me too. Thank you for your research. There is still such little info out there about these issues.

  57. Hi Sami, I have the mthfr gene & want to find out if I’m over or under methylating but the pathology ordered the urine whole blood histamine test. Will this test for methylation? Or do I need to do a blood test for this? Thanks Vicki

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      Author

      Hi Vicki,
      We use whole blood histamine and SAM/SAH ratio plasma testing to determine methylation status. Whole blood histamine is a blood test. They are currently the best methods.

      1. Thanks Sami

        The urine whole blood histamine test does this even determine anything for methylation status? My doctor is refusing to do the blood test as they think urine is more accurate but doesn’t know about mthfr or methylation. I’m trying to get the tests done for my naturopath before seeing them. So strange they got me to do urine.

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      Author

      Copper AND zinc are needed to create DAO. Both need to be in balance with one another, but sadly, this is often not the case today.

  58. Hi Sami,

    Thank you for this insightfull article.
    Is there anyone you can recommend in the Netherlands who can help me with this?

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      Author

      Hi Marije,
      I’m glad my post was helpful. Unfortunately, we don’t have anyone in the Netherlands. I can however work with you via Skype. Click here to schedule a complimentary consult.

  59. Hello Sami,

    Thank you so much for such an informative article.

    I’m very glad I came across it. I have just recently seen a functional Doctor in South Africa, as an expat living in Korea where I couldn’t find any doctors to see regarding many issues that were exacerbated when I moved to Korea 2.5 years ago.

    I have been tested for various things and have been found to be a bad methylator, with low vit D, low serotonin and low cortisol (oxidative stress/adrenal fatigue? Is this all the same thing?). I have previously been diagnosed with high levels of free testosterone and also PCOS but all my hormone levels that were tested came back normal.

    I have suffered from allergies to mystery things in food for more than 15 years, and have had sinus problems (like my dad who still suffers from sinus and fatigue and headaches and and and), constantly break out in red rashes for no reason or because of friction on my skin, and the most recent was a rash that developed on my skin that looks like a fungal rash that presents in one place on my upper body, stays for a few months and then disappears only to reappear elsewhere (thought it could be the public baths in Korea). I thought I had gluten sensitivity but test negative, then connected it to possible leaky gut, now think it may be linked to this. The gluten sensitivity seems to come and go.

    I lived in an apartment with mold for over a year in Korea before the landlord simply wallpapered over it (which I doubt fixed the problem). I also gained 20kg’s in 3 months after arriving in Korea (Mold? Stress?).

    My doctor in SA has said it seems I have an overgrowth of gut candida (because of fungal looking rash and gut symptoms and sugar cravings) and I have taken conventional antifungal meds as well as continue to take citricidal plus for it.

    I’ve had homocysteine support prescribed for the under methylation, 5 HTP and l-theanine prescribed for the low serotonin and anxiety I suffer from as well as ashwaganda and omegas, hemp hearts for my deadly painful periods that started 18 months ago, as well as Vit D3 (shouldn’t I also be supplementing with K2 if I take vit D3?)

    I am wondering if this all sounds alright to you or if you think I need more testing to have more conclusive results?

    Also do you know of any doctors in South Korea that could help me as it is going to be difficult to get back to South Africa to be tested again in 6 months.

    Thank you so much for all of the info you have provided so far.

    1. Hello Sami,

      Was just wondering if you think my protocol sounds correct? Also whether I may not be dealing with a histamine sensitivity? I’ve suffered for so long with so many symptoms that doctors can’t seem to figure out. I also recently read that methylation issues are more accurately detected in time or saliva tests, and with so many other factors like copper affecting it, shouldn’t I be tested for things relating to it and not just being placed on natural remedies for trial and error?

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        Author

        Hi Frances,
        Yes, accurate testing and assessment is critical to healing. Other factors are almost always at play such as copper/zinc imbalances, pyroluria, and thyroid issues to name a few. Methylation cannot be determined with a saliva test, and I encourage you to hold off on supplements until you really know your biochemical status. They can make symptoms worse if they are incorrect nutrients for your chemistry.

  60. Hi Samantha,

    great information!

    I have normal to high DAO and am undermethylated. Due to already high levels of serotonine and dopamine (slow versions of MAO and COMT enzzymes) I don’t tolerate methyl donors very well.

    I also ask myself if I am suffering from MCAD.

    Every view days I am suffering from restlessness with severe insomnia (despite exhaustion), diffuse all over the body itching, congested nasal mucosa, constipations. Symptoms last about 20 h before they resolve.

    I already cut out all intolerant foods (did a Igg/4 testing) and all histamin liberators.

    Heat, sleep deprivation, stress, weather changes most often increase symptoms!

    Could it be a mix between MCAD and undermethylation?

    Greetings from Europe
    Manuela

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      Author

      Hi Manuela,
      This is certainly a possibility. Although undermethylation and MCAD are different creatures, they can reside within one person.

  61. I’m in tears! For 6 years I have been to so many natropaths to get an answer on why the heck I have chronic hives that get extra horrible when I’m sick(large red itchy burning patches from head to toe) and are made worse by food allergies, and I keep adding to them. It all started when I was pregnant with my first son at 21. Now after 6 years, 2 more sons, and so much $ spent I still have no answers just more problems! I came out of my last pregnancy with an egg, peanut and almond allergy(on top of gluten and dairy), reactive hypoglycemia, and frequent neasua. over the 6 years I’ve had worsening digestive symptoms, struggled with post pardom depression and anxiety. Where do I start with applying this information and getting help? Im so desperate to feel normal again.

    1. Sarah, I would contact Mensah Medical and be tested. You could have copper
      Toxicity and depressed zinc which is common in post partum and greatly increases oxidative stress which worsens allergies. You also need to be tested for a methylation issue and pyroluria which could also be contributing factors.
      We took one of our sons to about 8-10
      Doctors in desperation to help him. Mensah Medical was able to help him immediately and there testing showed the markers he had; he responded beautifully to treatment and he is so much better.
      Mensah seems
      To find the underlying issues that so many doctors and NP’s just can’t.
      I would not wait, I would call ASAP. They test thru Direct Healthcare Access – I would not hesitate if you want to feel better… We have had 3 boys and also myself tested at Mensah – they are brilliant and will find your issues. I promise you

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          Author

          Hi Sarah,
          In order to become a patient, Dr. Mensah will need to see you in person. We have several outreach clinics all over the US. Click here to view them. I can also get you properly tested with a protocol, and we can work together via phone. Click here to book a complimentary consult to see how I can help.

  62. I look like a classic under-methylator and In the past a doctor prescribed Designs for Health Homocysteine Supreme which contains Folate, Zinc, B-2-6-12, and more. I’m wondering what the test is to determine MT functioning. I’m in a rural area now and am strapped for financial resources, but am looking for a jumping off place.

  63. This article is so very interesting! My 21 yr old daughter has been suffering from severe hormonal issues. Low thyroid (but has never had detectable antibodies), low everything really…cortisol, progesterone, testosterone, DHEA, Vit D. Sensitive to gluten, dairy, citrus, egg, nightshades, caffeine the list goes on. A few months ago in an effort to hear her gut issues,she decided to dive into fermented foods. During the first week she blew up like a balloon (gained 6 lbs in one week) and was utterly exhausted. She stopped all fermented foods/drinks and immediately lost the 6 lbs. Her genetic testing showed issues on her vit D receptor but no other Methylation issues. She is an athlete and trains hard every day but cannot lose the 40 lbs that she has put on the last 5 years. She has never responded to anything (thyroid meds etc). Could all of these things be a result of a histamine intolerance?

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      Author

      It’s certainly possible, but there is no way to know for sure what the root cause is without diagnostic laboratory testing. Her symptoms definitely point to gut dysbiosis, which can cause histamine reactions.

  64. Overgrowth of gut microbes (for we must be talking of all types of microbes: protozoa, bacteria, etc.) is usually indicative of a lack of proper digestion from mouth to stomach to small intestines to large intestines. This may be a co factor of what goes in the mouth (diet) to what the nutrients meet upon arriving inside the body (enzymes in the mouth and down the digestive tract) and how the body reacts to these nutrients (assimilation or rejection). The hostile environment in digestion is not natural. To not assimilate means we must have the wrong (unnatural) foods or the wrong receptive environment (a body fraught with uninvited microbes). Correct the food/nutrients and the microbes (infections) and the gut will heal itself. This is why Sam and Dr Mensah and Dr Walsh are right when giving nutrients to correct the deficiencies. But you must pay attention to lowering the microbial load and to the hormones as well. Sometimes the healing of the lacking deficiencies may work enough to correct the rest. Other times we must delve into the anti-microbial science as well as hormonal balances to help the immune system recover.

  65. HI Sami,
    You are doing a fantastic work! I really apreciated to read this article!
    Being aware, that there are two mechanism to inactivate histamine in the body, I would be interested to find out more about the HNMT, the intracellular way and undermethylation.
    I suffer from MCAS and I am compound heterozygous with MTHFR ( 677+ 1298). This means my methylation Circle is reduced about 70%! Whereas the mastcell activation disease increases a high amount of endogenous Histamine , the MTHFR enzyme deficiency reduces the capability to transforme histamine into histidine and to decrease the intracellular Histamine.
    So it is twice bad!
    I would really appreciate your opinion on this!

    Could you recommend a practicioner in Germany? I can’t find a doctor, who is informed and educated with this subjects.
    Thank you so much!

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      Author
  66. I am confused by something in the article. You write “Folks that have low DAO activity (again, epigenetic in nature) also tend to have low levels of histamine in serum and plasma, which affects the histamine/mast cell relationships.” Wouldn’t low DAO enzyme, allow more L-histidine into circulation which is then converted to histamine by HDC enzyme which does not saturate…leading to higher than normal histamine levels??? Not lower? Too much raw material getting in which is supposed to be rendered inactive but isn’t. In pregnancy the placenta makes somewhere between 500-1000x more DAO than a woman’s body does normally, and it ramps up through about week 16 and then plateaus with some ups and down right at the end of pregnancy. This is why women get so tired during the first trimester until the DAO level becomes stable (even though higher) as the histamine level falls significantly…and just like antihistamines make you sleepy so does a naturally lower histamine level until the body adjusts. And I thought it was this higher basal histamine level with low DAO function which places mast cells at a “hair trigger”, easily provoked to degranulate. typo? Am I wrong? Can you explain? Really trying to figure it out. Working with other migraine patients and CVS patients and IC patients, who all know symptomatically high histamine foods in their low DAO systems lead to high histamine symptoms. Thanks.

  67. Hi Sami,

    My 8 year old son Jeremy is a undermethylator – blood histamine 0.9 umol/L. Mental/emotional issues cleared up on methionine supplementation.
    He has a histamine intolerance, and it would seem a salicylate intolerance. He has been on zinc supplementation which has improved zinc copper levels ratios, but the intolerance persists.
    Could you help?

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  68. I have had problems with hives since a toddler. I am 52 yrs old now & for the past 10 years I have had attacks of hives, sweating, chest tightness, vomiting, unconsciousness, fatigue, no energy. Each attack is worse than the one before & I’m always treated for anaphylactic shock……allergic reaction….sent home. Had a severe attack 08/28/16 and have had severe fatigue, energy loss to the point my dr out me on medical leave from work. I broke out in severe blisters in my feet a couple of weeks later that are better, but still not gone, cleared up. I was sent to a hematologist at Stands Hospital in Gainesville, FL. He did a lot of lab work…….histamine plasma level was 45, lymphs were 10.9, RBC low, anion gap low, glucose slightly elevated (135). He said he was no expert in mast cell disorders, but believed this was my problem. I am waiting to see another specialist at shands now. I have been on H1 , H2 antihistamines, steroids & given epipen since first of September, but was also added to cromolyn sodium, iodine/potassium iodide & D3 emulsion drops, which I am waiting to see GI specialist/Nutritionist to do further testing & monitor iodine,d3 emulsion drops. I’ve had another attack, but at onset used an epipen, followed by another & seemed to stop severity of attack. Unfortunately, no one (medically) anywhere near me knows anything about mast cell disorders….closet is Gainesville, FL, 150 miles from me, & I’m finding they don’t know alot. Basically, I’ve been told “mast cell disorder,” but don’t know what…..MCAS, mastocytosis, etc. Does this sound feasible, or should I be checked for something else?
    I am very frustrated, as I have always worked & since severe attack in August, I have had extreme fatigue & no energy and sometimes, spend 3-4 days in bed. I am unable to physically perform at work, and even at home alot. I feel as if I’m “idle, spinning my wheels,” getting no definite answers, just appointments from one specialist to another….but still, no definite answers.
    I have no pattern, no apparent specific triggers, no certain times, days, nothing in sequence regarding attacks.
    I have been told Boston has a mast cell disorder Hospital that only treats with experts of mast cell disorders, but I’m in South GA, and that is a long way to go, especially now that I am out of work, income cut. Any suggestions, advice??
    NEED HELP DESPERATELY!!!
    Thanks,
    BRAD

    1. Brad – I wish I could offer you more advice, my daughter has something going on w mast cells and we recently found out she is homozygous (has two genes) which are associate with mast cell activation. Sounds like you are worse than she is though, she gets migraine, dizziness/BP issues, occasional rash when known allergen consumed. Try histamine block from seeking health (and find out if you have the DAO gene mutation), the enzyme in product will break down histadine in foods and deny your body the raw material it needs to make histamine. Take 2-3 every meal. Google mast cell master and Tufts, professor there has posted a lot of research. He has product called neuroprotekt which is mast cell stabilizer. Have your adrenals tested. Cortisol is immunosuppressive, DHEA is immune stimulative – if your DHEA is elevated it is ginning up your immune reaction.

      1. This is for Brad – have you had copper
        Levels tested? You could also do the brand new SAH test – we ordered this through Mensah Medical- it measures methylation exactly and my son, who was having issues actually showed tendency to OM rather than UM like us; anti histamines were making him worse
        My advice
        Is to call Mensah Medical and explain everything.
        Ask if they can help you…. we took our 10 ur old with similar issues to them after no one else could help.. testing showed high copper; low zinc and OM. He is better now in the nutrients they prescribed. I think you need to be a full patient too. The consult will not be enough.

    2. Dear Brad,
      MCAD is a very new known Disease. Therefore docters don’t know much about it. Mastozytosis is a very rare disease. ( 3 out of a Million!) Get your Tryptase Level tested!
      MCAS is much more Common and it is a very individual disease.
      First step is to find out, what your personal triggers are.
      ( Food, Vibration, Stress, Sports, Medicin, chemicals …. Nearly everything is possible.)
      Writing a diary may help to find out.
      H1 and H2 and Cromoglycin is the Basic Treatment for MCAS. It needs a few weeks until its getting better under medication. DAO is only useful, when Low Diaminoxydase levels are the reason for high Histamine Levels. HNMT can also be disturbed. Than the intracellular breakdown is not functioning. Than you Must be very careful with medicin, which is blocking the HNMT. For example Diphenhydramin . Dimtindenmaleat is said to stabilize the Hystamin-N-Methyltransferase.
      Find out about disturbences in your methylation cycle! Especially MTHFR 677 and 1298.
      If the mastcells express to many messengers like histamine, Zytokine, leukotrienes etc. ( which is the case in Mastcell Activation diseases!) it is very important, that the breakdown through methylation is working well. If this is not the case you are having twice Trouble.
      Unfortunately I can’t give you any advice regarding docters, because I am writing from Europe.
      May have a Look here: http://www.mastzellaktivierung.info
      All the best for you!

      @ Maddy Which polymorphisms are found in your daughter , which arme associated with MCAS?

      1. I think the most common one associated with mast cell activation is CBS A360A. rs1801181. Homozygous for that one. Also for rs2124458, rs2849729. As I understand it CBS mutations are upregulations in the enzyme, the enzyme is too fast and it depletes BH4. We also have some HNMT and MAOb issues so which meds do not interfere??

        1. HI Maddy,
          You are right: CBS defects go along with an upregulation of the CBS Enzyme.
          This depletes BH4, but also it brings up high Levels of taurine and ammonium.
          In some patients it can cause a sulfur – Intolerance.
          Low BH4 level is associated with mood and Neurotransmitter Production.
          MTHFR polymorphism also deplete BH 4, which can cause Mastcell Degranulation. In opposit to the CBS enzyme , the MTHFR enzyme is too slow and therefore not able to spin the Methylation circle properly. This is influencing the Transmission from :
          Folic acid to 5- Tetrahydrofolat ( the active Form),
          Homocystein to Methionin
          BH 2 to BH 4
          Histamine to histidine

          It is not recommended to Support BH4 directly. It is much better to support the Circle and as a secondary effect bring up the BH4 Level.

          It is a very complex subject!
          Good luck !
          Britt

    3. Hi Brad,
      Did you or any doctor every suspect Lyme and/or mold as triggering this? Also did you ever have any screening for porphyria (which can be triggered by infections?). I only ask because mys on has had histamine intolerance as a result of infections and porphyria and suffered attacks similar to what you describe. I am sure Sam has some good ideas to work with your symptoms and can recommend that you work with her to assist, but in terms of underlying causes it might be good to screen for these two issues? Best, Angela

  69. Hi everyone here!
    Sorry for my English in advance 🙂

    This connection of estrogen and copper and mast cells is highly interesting. I just wonder if it is also possible to have normal estrogen and a normal progesterone/estrogen-ratio and still have too much copper after a pregnancy. I mean, is it possible that copper gets high during pregnancy, estrogen falls then after giving birth but copper stays high?

    I was in the situation that I was pregnant with a second child. Unfortunately I had a miscarriage in the 11th week. But after that all my problems startet. I had a lot of symptoms of copper toxicity. Three month after my miscarriage I tested estrogen and progesterone levels and both were in the normal range (estrogen a bit higher but not too much). But my symptoms were extreme. I even went to hospital because I thought I would tripping out. I always said to my husband that it feels like a poisoning from somewhat. But doctors did not check a thing. They said it’s a panic disorder. But it did not feel like panic because I was not anxious about anything. The only thing that I was panicking about was that extreme state I was in. It felt as if I had drunken 20 cups of coffee at once.

    Also I was on a high folic acid supplement for month and a blood test showed that folic acid was much above the normal range. I stopped taking it immediately. Some weeks later I took a B-complex, not knowing that B9 is the same as folic acid. One week later I felt horrible and had severe insomnia. At the same time I took some progesterone (I thought that might calm me). But the opposite happened: I again tripped around like a maniac. What helped almost from the first day was an SSRI. It was like switching of the horror movie. And doctors said: “Well, see, it IS a panic disorder and nothing else!”

    But I think that I am a undermethylater and maybe suffer from copper toxicity.
    Does anyone of you think that could be the case? I know, I have to do testings. I am just waiting for copper/zink/ceruloplasmin/histamine test results.

    Thanks for your help and also thanks to Samantha to share her knowledge with all the people out there!
    Nicca

    1. PS: I forgot to mention the link between all this an histamine. I do not react on histamine foods. But I have a severe reaction from the sunlight. Summer is always horrible for me. It almost feels like an anaphylactic reaction. And also hectic stress, loud noises and emotional situations (also good ones) give me kind of histamine reactions.

      1. It sounds like yes you are an undermythelator AND have high copper and low zinc. It’s very common for certain women to remain with high copper following pregnancy and your symptoms seem consistent with that. Also, as a UM, folic acid and certain other B’s will induce anxiety and panic.. they do for me! It’s horrible!
        I recommmend you contact Mensah Medical http://www.mensahmedical.com
        Personally I feel you would be better suited as a full patient but to get things started right away you can test from Direct Healthcare Access and consider a phone consult. They have outreaches all over the country and while the first appointme t is more; everyone after is less than half. There is a video on the Mensah site also on copper toxicity- watch the entire thing. I would not self treat nor would I see other doctors – I find Mensah to be the best here

        1. Hi Michele and thanks for your answer!
          You know, I spent thousands of Swiss Franks on treatments. Now I have to find solutions myself. If I did reasearch earlier I could afford now a treatment at Sami or Mensah Clinic. But I have spent the money on many doctors and practitioners (and a lot of supps) that were not helpful. But I consider those new treatments you suggest for later. Have to save money first…
          At least I got my lab test back. Zinc is low and copper high but in the normal range. But the ratio is not optimal, I guess. And histamine was very high. So I will take some zinc picolinate and avoid foods with much folic acids.
          The other thinh I adress is my SIBO. That will be a tough project 🙂 So, Christmas without any cookies…

    2. The SSRI can also support the immune response (K cells) and lower inflammation so it may be working in other ways than doctor’s think. I am wondering if you took zinc to lower your copper? Sam will have best advise on all this as its delicate but zinc deficiency can cause some of this as copper is too high. Particularly after a pregnancy. Also I would do some emotional clearance and this type of work if you can as the stress of losing a pregnancy that close to term is very very hard on anyone emotionally. Trauma can be very subtle and can block your system – so that whatever course you take – and I think you would benefit to work with Sam and Dr Mensah to rebalance, the working with ehmotional level to “detox” will be important. Hope you feel better! Angela

    3. The SSRI can also support the immune response (K cells) and lower inflammation so it may be working in other ways than doctor’s think. I am wondering if you took zinc to lower your copper? Sam will have best advise on all this as its delicate but zinc deficiency can cause some of this as copper is too high. Particularly after a pregnancy. Also I would do some emotional clearance and this type of work if you can as the stress of losing a pregnancy that close to term is very very hard on anyone emotionally. Trauma can be very subtle and can block your system – so that whatever course you take – and I think you would benefit to work with Sam and Dr Mensah to rebalance, the working with emotional level to “detox” will be important. Hope you feel better! Angela

      1. Hi Angela!
        Thank you for your answer. I did not know that the SSRI can lower inflammation.
        Because of the emotional part… I’ve had a lot of therapy sessions. I am a practitioner myself (mostly doing Hypnosis and Kinesiology). So I had a lot of support of colleagues who could work with me on the psychological and energy level. But that was not helpful at all in that case.

        I did not already take zinc but will soon. At the moment I am struggling with my SIBO treatment. It’s a tough detox with a lot of herx reactions. Maybe I should wait with zinc a month. Otherways my body (and brain) would be too stressed.

        It’s good to read and hear from other people about their stories – like in this conversation here.

        Enjoy your day!

  70. Hi Sami,
    I am a psychiatry registrar, have just come across Dr Walsh in past month, in researching/preparing a presentation on nutrition in psychiatry. I see adolescents with depression, anxiety, panic, migraine etc. Could you advise, in your opinion good first-line, readily available tests (I may not be able to convince the health service to test urine pyrroles or genetics) to try to screen for major metabolic concerns, and whether safe daily limit supplements where vit/mineral clearly low, is advisable? I had a limited understanding of copper/zinc issues, the body biochemistry etc already. I can then recommend Biobalance trained Drs but in psychiatry, very limited here. Also, Mirtazapine (an SNRI alike SSRI) has antihistaminic properties, do I need to withold it to test whole blood histamine? Many thanks, Antonia

    1. Hi Antonia
      I am not an expert on meds. But withhold the meds for the test does not make sense because after one took his last pill the receptors still stay occupied for weeks. Your patients would have to withhold the meds about six weeks. But I guess you don’t want to take that risk.

  71. An excellent presentation, thank you.
    1. Copper toxicity
    I may have missed this point in previous comments, but it seems that there are wise females that wish to avoid artificial hormones in the oral contraceptive pill, or worse, the hormonal contraceptive injection.
    Some decide on the copper intrauterine device (IUD).
    I suspect that this releases copper, potentially to toxic levels, after all, it is local toxicity that produces its contraceptive effect. As you may know the original IUD (back in the 1930s) was made of silver. The point I am making is that such IUDs as the “Copper 7” etc might have been producing toxic effects, including mental disorder since the start of their use. The reason for the choice of copper for these IUD may not bear too much scrutiny.
    2. Gluten Disease and DAO deficiency
    Gluten disease is associated with gut wall thinning and loss of function. It is therefore reasonable to suppose that DAO function is lost (Alongside MAO function etc).

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  72. Hello Samantha

    Thank you for all the info on histamine etc. and I’m hoping you may be able to help me and/or point me in the right direction please.

    I think I have elevated histamine levels in plasma as I have crippling skin problems (at the moment). I never get any digestive symptoms. I’ve always suffered on and off with eczema, but the high histamine levels (I’m guessing is high histamine through lots of research) (this has happened on 6 occasions in my life) are debilitating.
    My upper body is red raw and eyelids can get inflamed. I feel like I’m on fire. The itch at night is unbearable. This started about 6 weeks ago and I’m on a low histamine diet. It has worked to a point and there are now quite a lot of white patches back on my body and the face inflammation is gone. I was never able to tolerate fermented foods. I don’t suffer from depression and never have, although looking
    like a tomato does not help!!

    I’m really looking to get to the root cause of what is happening and wondering can you help at all? When I avoid gluten and dairy
    my skin is perfect, although I’ve tested negative for coeliac, but positive for gluten intolerance. It is difficult to avoid them 100% of the time!

    I have spent way too much money over the years on testing, supplements, foods etc and really can’t afford to do any more without getting a proper answer. Can I ask do you think (or know!) if getting tested for copper/zinc, ceruloplasmin and/or pyrrole disorder would help me to get to the root cause and clear/rid these reactions for good?

    With kindest regards, Maggie

  73. Hi. Looking for some advice! Dtr is going through some stuff. She’s recently diagnosed with mastocytosis. History of asthma, pcos (on bcp), migraines. Taking magnesium & B complex, vitamin C alone, Zyrtec. What should she do to supplement MT? Trying to raise CP. how can she detox copper?

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      Detoxing copper is not a simple process and the nutrients required will vary from person to person so I encourage you to get properly tested.

  74. What do I do – take copper pills? I am desperate. In October 2015, when I was 45, I suddenly got hives every day. In May 2016 I had my first angioedema. By the summer a doctor confirmed it was histamine intolerance. I avoided high histamine foods and I was fine. Then 3 months ago I got hives every day again.
    I slowly figured out it was food high in salicylates. I avoided those and was fine. Yesterday I had my worst angioedema though I had no food high in histamine or salicylates. But I did take ibuprofen 20 minutes before the swelling started. How can I stop this horrible progression? What do I need to do?

  75. I have celiac disease and MTHFR mutation, and I’m VERY low in B12. The doctors keep trying to give me methylcobalamin, but anytime I take it, I break out in cystic acne (zits the size of a nickle), get swollen and bloody lips, and feel like I have the flu. I can’t eat red meat or liver either. Is this something Dr Mensah could help with or is there something you would recommend trying?

  76. How does Dermatographia fit in here? I am considering trying a low-histamine dirt to combat the symptoms and am looking for other options for treatment. I would appreciate any advice you can give me

  77. Hello,

    thank you for your informative Post, which totally goes in my direction and I would appreciate some help.

    I´ve gone through a hard detox via DMPS, without refilling my Minerals, which led me into 3 Years of Horror. Now my Mastcells are going nuts. I´ve made a Bloodserum and Plasma test as well as a Hair Mineral Test. Both have shown a Cooper deficeny (and others). I had lots of stress as well and cooper is necessary for reducing the hormones and it gets ripped out of the body through DMPS. So far so good.

    I´ve taken all the other Minerals, which helped me a lot, but was afraid about the cooper. Now my Bones started too deform and my angles started making horrobale sounds, also my nervs were blank, I couldn´t sleep and think, I didn´t have energy and so on. Searching for a solution, I thought about the cooper and took it. It was like a bomb and my body is working like crazy now. I got very sick after a week with a horror flew, but the other symptoms got better, way better. i can sleep, I have more energy, can think clearly and I am way more stable, but…

    … eversince my mast cell Problem is worse. foods I could tolerate 1-2 weeks ago, are not ok anymore. My liver and my stomach are hurting. I sweet and so on. Now I´m afraid, that the Immunsystem is making my Mast Cell Problem worse. But don´t taking the cooper can´t be the goal either, or? I took Zink and other Minerals that interact with cooper.

    What shall i do? I´m so unsure (and hungry). I feel it has something to do with methylation, because it´s changing over the day.

    Any suggestions? Thank you from germany 🙂

  78. Still trying to get my head around how to differentiate between under methylation and other mast cell disorders. I have been following the Walsh protocol for around 8 months now after high blood histamine results and normal DAO levels but there seems to be very little change. What are the chances I have a mast cell condition rather than under methylation and how do I test for this?

  79. I am 100% new to this so excuse my all questions. I have Ehlers-Danlos syndrome so I have a lot of secondary conditions. Some obvious some not much. My daughter was diagnosed with MCAD after giving birth and having issues after. I have never had an official work up. Seems I fit all the criteria. Recently i have had elevated liver function tests and oddly a high B-12 where i usually am deficient. I had also recently been told that I have diffuse unspecified white brain matter. I feel like there’s an issue/problem with every body system I have and the pieces are to scattered for any one doctor to put together. Any idea where I should start?

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      Author
  80. I have severe MCAS and it simply came from a move to a state that had a lot of trees and foliage. I have always had low zinc but copper is normal. (reg blood work) Does this still apply to me?

  81. Hi, will you contact me? I have many methylation problems…EDS, Gastroparesis, Disphagia, ROE, Mast cell problems..i react to anything and everything..never know what is gonna trigger it and now having symptoms of early anaphylaxis..hormones are making things worse..

  82. I have an appointment March 6th with a functional Dr. I’ve been suffering for 4 months with histamine intolerance symptoms and I’ve suspected methylation is a root cause. I have a MTRR mutation and MAOA on my 23 and me. The 9 Drs I’ve seen have only made it worse including iodine toxicity caused by a dr that I’m still not recovered from. I’m fatigued, lost 25 lbs, flushing, swelling, break out into hives, inflamed throat, swollen gums every day, dehydrated, dry mouth at night possibly from the Allegra 24, I can’t wear makeup or shower, benedryl was giving me terrible rebounds with uncomfortable shaking. I can only tolerate sweet potatoes at the moment after the iodine messed me up. It’s pretty terrifying not knowing what’s going on and only being able to eat one food. I hope to get on a healing path with the next appointment.

    1. Please let me know how your dr appt went and what they said to do and what to try. Please and thank you.

    2. Andrea,
      FYI: I had such horrific dry mouth that I was sent to a rheumatologist to be tested for Sjogren’s Syndrome, an autoimmune disease that can go along with other AI diseases like Celiac Disease and Thyroid Disease, which I have. The Rheumo’s testing, which I’ve been told my my PCP is not always accurate, was negative for SS, but but he informed me that Allegra can cause the same symptoms. I stopped the Allegra and the dry mouth problems went away.

  83. Hello,

    I have had some symptoms over the last few years that make me think it may be a Histamine intolerance. It started as my face getting extremely red if I drink alcohol too fast. Now almost everyday in the afternoon I have some sort of flushing in the face. Also, my skin turns red from very light contact (like backpack straps or briefcase). I am at a loss for how to address. Advice?

    Taylor

  84. It’s not always high copper/low zinc, I have low red cell copper (my red cell zinc is low but copper is much lower), i’m undermethylated, my histamine is high, ceruloplasmin is a little low, serum copper low, hair copper high. Just shows how much misinformation there is floating around, I was told by so many practitioners my copper levels were high but it’s the opposite.

  85. Hi, thank you for the article !
    Is that possible that plasma histamine is high, and whole blood low ?
    Because i have really high plasma and the whole blood test is not available in france. I have a problem with psychotic symptoms (schizophrenia or schizoaffective) and the medication dont work.

  86. What about low copper? Two of my symptoms when I started getting ill were unexplained weight gain (I literally have to eat under 1,400 calories per day or I now gain weight,) and I stopped sweating. I’m asking because I started taking a copper/mineral supplement and noticed within 5 days that I had spontaneously started losing weight, and I started to sweat….and stink! (I haven’t used deodorant/anti-perspirant for 4 years since I didn’t need it anymore.) I take an H2 antihistamine and cromolyn and although it’s helped some with my fatigue, it never touched those 2 symptoms.

    Thank you!

  87. This is one of the most brilliant articles on this subject I have ever read. The fact that histamine has to be methylated to be broken down seems key? And once the gut is effected then it’s all downhill from there. What gut healing strategies, besides you amazing recipes, do you recommend? Thank you for all this!

  88. I don’t know what I have. I have been told that I have sports related hives. I am male and I got my 1st attack in the 1st grade in gym class. I was running and all of a sudden it felt like insects were biting my legs and stomach. I was curled in the fetal position until it passed. There is no rhyme or reason to it. It usually happens on cold days that are very sunny. Or over cast days where the wind is cold but the temperature is warm. It sucks. It kept me from playing football and keeps me from most outdoor activities because most of the time nothing happens but when I get an attack it hurts so bad that I wish I never tried any activity at all

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