There is a good deal of confusion regarding the role histamine plays in the body and what are factors that cause the release of histamine, increase the receptor sensitivity to histamine and the impact of histamine disorder, Mast Cell Activation Disorder.

Whole Blood Histamine as a means of measuring methylation status:

When treating mood disorders utilizing the Walsh Protocol, doctors utilize a lab test that measures whole blood histamine. Histamine in blood cells is regulated primarily by an enzyme called histamine N-methyl transferase, HMT. The levels of whole blood histamine are postulated to be regulated by one's methylation status. This is a different approach to predicting methylation status by genetic testing such as MTHFR and COMT genetic mutations. Walsh trained practitioners are taught that whole blood histamine is a better measure of methylation status and so is used to determine whether the causes of mood disorders such as depression are due to increased or decreased levels of serotonin and dopamine activity. This article does not discuss the role of whole blood histamine and methylation. To understand the use of whole blood histamine as a test for determine one's methylation status and serotonin and dopamine levels, please see this article.

Plasma Histamine and Tryptase Test as a measure of Mast Cell Activation Disorder 

While there are many persons with elevated histamine who suffer from mood disorders, Mast Cell Activation Disorder itself if a diagnosis made from symptoms and blood tests associated with the accumulation or over expression of Mast Cells.  This blog post is intended to clarify the role of mast cells and histamine as an immune reaction to antigens, foods and microbes and the symptoms plus labs used in establishing diagnosis.

What are Histamines?

Histamines are inflammatory mediators released by a variety of cells following exposure to certain antigens or irritants.

They are produced within  mast cells, neurons and basophils. and when released when activated. They

Histamine binds to target receptors in the nose, lung, skin, gastrointestinal tract, brain and near blood vessels via specific histamine receptors, especially H1 receptors.

They are capable of activating 4 receptors: H1, H2, H3 and H4.

The result is typically chemotaxis or a localized inflammatory response, much like what is seen when a red mark appears on the arm when scratched.

Once activated by an antigen, histamine causes a series of events leading to increased vascular permeability and dilation, nerve activation, and inflammatory cascades that are collectively produce symptoms of hypersensitivity including itching, sneezing, increased mucus secretion (i.e. rhinorrhea, etc.), bronchospasm and, if enough vascular tissue is involved, low blood pressure.

With the advent of selective antagonists or antihistamines, histamine binding to receptors are blocked and symptoms are supressed. It appears this is done by interacting with basophils, monocytes, macrophages, eosinophils and T Cells.

Learn more about mast cells, histamines, basophils and receptors.

Histamines are released form mast cells following exposure to allergens, food and bacteria

Histamines are inflammatory mediators released by a variety of cells following exposure to certain antigens or irritants.

They are produced within  mast cells, neurons and basophils. and when released when activated. They

Histamine binds to target receptors in the nose, lung, skin, gastrointestinal tract, brain and near blood vessels via specific histamine receptors, especially H1 receptors.

They are capable of activating 4 receptors: H1, H2, H3 and H4.

The result is typically chemotaxis or a localized inflammatory response, much like what is seen when a red mark appears on the arm when scratched.

Once activated by an antigen, histamine causes a series of events leading to increased vascular permeability and dilation, nerve activation, and inflammatory cascades that are collectively produce symptoms of hypersensitivity including itching, sneezing, increased mucus secretion (i.e. rhinorrhea, etc.), bronchospasm and, if enough vascular tissue is involved, low blood pressure.

With the advent of selective antagonists or antihistamines, histamine binding to receptors are blocked and symptoms are supressed. It appears this is done by interacting with basophils, monocytes, macrophages, eosinophils and T Cells.

Learn more on mast cells, histamines, basophils and receptors.

A condition of excessive histamine release or senstivity with associated symptoms is referred to as Mast Cell Activation Disorder, MCAD

Mast Cell Activation Diorder is a diagnosis based on a wide range of symptoms and lab tests that indicate there is a significant immune reactivity taking place in response to various allergens, foods, microbes and other triggers.

Histamine is released from mast cells that are present in bone marrow, in circulating blood cells such as basophils and eosinophils. They accumulate along the lining of the intestines, the respiratory and sinus tract and in the vascular system. It is here where they respond to irritating or threatening triggers and lead to a cascade of immune reactive conditions that either contain the insulting element or cause harm to the body, or both.

Until recently, the only condition that was attributed to abnormal levels of mast cells and histamine was referred to as mastocytosis. This is a rare condition that required a bone bioposy to determine the degree of mast cell accumulation. Today, MCAD or Mast Cell Activation Disorder is used to describe the condition of overreaction by the mast cells and excessive release of and reactivity to compounds including histamine, tryptase, heparin and even serotonin.

More on the Signs and Symptoms of Mast Cell Activation Disorder

treat elevated histamine naturally
Biochemical activity of mast cells, initiated by antigen stimulation, ends with release of inflammatory elements including histamine, tyrptase and heparin. Serotonin is also released.

Foods and Antigens that Typically Raise Histamine

Histamine rich foods: Foods that are associated with high histamine levels include fermented foods such as sauerkraut, kombucha, pickles, wine, yogurt, mature cheeses and fermented soy products. It also includes cured, smoked and fermented meats such as salami and sausage, etc. Tomato paste, spinach and canned fish products also have high histamine levels. Citrus foods are histamine liberators which increase histamine release and so should also be avoided.

Histamine is chemically known as a "biogenic amine". Fermented foods have high levels of these biogenic amines. These are foods that are exposed to microbial decomposition as part of the fermentation or in storage. Lactic acid bacteria are the most problematic biogenic amine producers in fermentation. These bacteria break down amino acids into amine-containing compounds. Biogenic amines are commonly found in wines, cider, dairy, meat, fish, beer, spinach, tomatoes and yeast. Biogenic amines in the form of histamine are the product of bacteria breaking down amino acids. Control biogenic amines to treat elevated histamine

Histamine and Lectins
Foods such as potatoes are high in lectins. Lectins can bind the lining of the intestinal wall and cause leaky gut syndrome. Undigested lectins then enter the blood system and lead to antibody formation and which releases histamine. Foods high in lectins include:

·    White potatoes and unmodified potato starch
·    Tomatoes
·    Soy
·    Gluten containing grains
·    Legumes

Histamine and Probiotics
Probiotics in the digestive tract are responsible for producing many compounds in the body. There are bacterial strains that increase histamine as well as intestinal microbes that reduce histamine.

  • Probiotics that increases histamine
    • Lactobacillus casei
    • Lactobacillus reuteri
    • Lactobacillus bulgaricus

 

Foods, Supplements and Antigens that Lower Histamine

Histamine and Mast Cells
Histamine is released from “mast cells”. Mast cells are immune cells that line the mucous membranes of the sinuses, digestive tract, the skin, lungs, eyelids, and tissues surrounding blood vessels and nerves. Activation of mast cells plays a key role in asthma, rhinitis, eczema, itching, pain, autoimmunity and hives. Elevated mast cells are associated with female infertility and decreased sperm motility. Stabilize mast cells to treat elevated histamine.

Histidine Decarboxylase HDC
The conversion of the amino acid histidine into histamine takes place with the help of HDC enzyme. It is possible to slow the conversion of histidine to histamine by inhibitors of HDC. Histidine is taken up by histaminergic neurons through the l-amino acid transporter and is decarboxylated via the specific histidine decarboxylase to form histamine. Histamine is carried by the vesicular monoamine transporter VMAT-2 into vesicles, from which it can be released upon arrival of action potentials. Inactivation in the extracellular space is achieved by methylation via histamine methyltransferase. For this reason, whole blood histamine blood test serves as an important tool for determining methylation status.

Diamine Oxidase DAO
This is an important enzyme that naturally lowers histamine levels in the body. DAO can be provided as a supplement to lower histamine levels. Symptoms of low DAO includes:

  • Skin irritations - hives, itching, rashes, eczema, psoriasis, and acne
  • Headaches
  • Painful menstrual periods
  • Gastrointestinal symptoms
  • Intolerance to fermented foods and alcohol
  • Mucous in sinuses
  • Asthma

Supplements and OTC medicines that increase DAO levels include:

  • Vitamin C
  • Vitamin B6
  • Pancreatic enzymes
  • Benadryl (works only temporarily, more histamine receptors will likely develop, potentially worsening condition.)

Supplements and OTC medicines that stabilize mast cells:
·    cromalyn sodium (Nasalcrom)

  • Quercitin
  • Curcumin (also decreases DAO)
  • Reishi mushroom
  • Yohimbine
  • Adrenaline
  • Eleuthero
  • Rutin
  • Theanine
  • Astragalus

 

Cortisol and Corticotropic Releasing Hormone CRH
It is commonly believed that cortisol causes allergies. That’s only part of the picture. The fact is that cortisol itself lowers histamine levels. It is the hormone that stimulates the adrenal release of cortisol that causes histamine release from mast cells. Chronically elevated CRH is associated with stress, as the release of CRH causes cortisol release from the adrenal glands. Under chronic stress, cortisol levels are low as the adrenal glands become exhausted and cannot produce sufficient cortisol. Yet the CRH hormone is likely elevated in chronic stress because the  hypothalamus releases CRH via the HPA axis as the body is trying to induce more cortisol to address the stress perceived by the brain. Chronic stress is thereby a major cause of histamine release from mast cells due to the effect of corticotropic releasing hormone CRH. We can make assumptions about the level of CRH and cortisol by testing salivary cortisol levels. Because they have a circadian rhythm we test four salivary cortisol levels in a day to establish the overall performance and need for supplementation. Treating elevated cortisol or depressed cortisol levels requires a salivary cortisol test and understanding of the underlying condition.

Herbs and cortical extracts are used to down regulate or supplement the adrenal gland performance. This has the effect of lowering CRH and mast cell release of histamine.

 

Inhibitors of HDC are:
·    Cortisol
·    Catechins – found in green tea, chocolate, kola nut, peaches, acai, apricots, apples, blackberries, raspberries, plums with skin and broad beans
·    SAMe
·    NAC N-acetyl cysteine
·    Homocysteine
·    Carnosine
·    Treat any underlying infection of H Pylori (very common with gastritis)

Histamine and Probiotics
Probiotics in the digestive tract are responsible for producing many compounds in the body. There are bacterial strains that increase histamine as well as intestinal microbes that reduce histamine.

  • Decreases histamine
    • Bifidobacterium infantis
    • Bifidobacterium lognum
    • Lactobacillus plantarum

Summary of supplements and recommendations to lower histamine while treating undermethylation:

  • Methionine (500mg-1gm) and SAMe (200mg) supplements
  • DAO diamine oxidase enzymes 2-3 caps (kidney glandular is a good source, as is white pea)
  • Probiotics B infantis, B longum, L plantarum
  • Vitamin C 1000 mg
  • B6 (can also increase histamine carboxylase)
  • Avoid lectin in diet – potatoes and tomatoes
  • Avoid fermented foods
  • Increase proteins high in methionine
  • Use Cromolyn – OTC mast cell stabilizer
  • Bendryl
  • Bromelain and Quercitin
  • Chocamine 1-3 grams – mast cell stabilizer
  • Improve adrenals with herbal and glandular supplements
  • Curcumin (also decreases DAO)
  • NAC N-acetyl cysteine
  • Catechins (green tea etc)
Histamine and Depression

Whole blood histamine levels are tested when determining cause of depression and other mood disorders.

Histamine is reduced or broken down by methyl compounds and so with high histamines the body may become depleted in the methyl groups. Because histamine depletes methyl compounds, it is easy to identify ones methylation status from their histamine levels. Elevated histamine depletes methyl compounds and the resulting undermethylation leads to depression and a host of other mood disorders.

Some common symptoms of undermethylation:
·    OCD obsessive compulsive tendencies
·    SAD Seasonal affective disorder
·    Competitive & perfectionist
·    SSRI medications usually effective
·    Calm exterior with inner tension
·    Strong willed
·    High libido
·    Seasonal allergies

Using the Walsh protocol to treat undermethylation I recommend supplements high in methyl compounds such as the amino acid methionine and SAMe (s-adenosyl methionine).

Diet is also an important factor. Foods that are high in methionine include lean meats, egg whites, poultry, halibut and other fish, soy beans, white beans and brazil nuts. SAMe and methionine help break down histamine by methylating it. Vegetarians and people with high histamine have a hard time getting sufficient methyl compounds in their diets and should be encouraged to take methionine supplements.

 

12 thoughts on “Treat Elevated Histamine, Naturally

  1. Nara says:

    Hi, o have interest of knowing more about the probiotics thay increase and the others crpas that decrease histamine. Do you have the references? Thank you só much!

    • Epstein says:
    • This is a tough questions. One pub med published study tested varieties of probiotics says can be referenced here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042653/ . Their research indicates probiotic lactobacilli strains Lactobacillus rhamnosus (L. rhamnosus) GG and L. rhamnosus Lc705 were beneficial however, bifidobacterium did not downregulate histamine activity. There are many genetic variations of many many gut flora. Hopefully future research will be able to map out the best probiotics for stabilizing mast cell activation.
  2. Missy Maiorano says:

    I have been suffering from high histamine issues…primarily hives and insomnia…ever since taking a round of Cipro. I’m waiting for my Dutch hormone testing but I already know my estrogen is extremely high and I have almost no progesterone. I’m taking Taurine, GABA, vitamin C, B-6, and zinc. I have a hunch I have low cortisol…I have always lived an extremely fast paced, super-stressed lifestyle. While I wait the 2-3 weeks for my Dutch results, will it hurt to take the taurine and GABA to calm my anxiety? I don’t want to lower my cortisol if it’s already too low…I can’t afford for my Histamine levels to get any worse.

    • Epstein says:

      Thanks for your question, however, it would not be appropriate for me to make medical recommendations via public chat without taking proper history and necessary labs.

  3. Elizabeth Keech says:

    Excellent and helpful article…Can you recommend a physician in Naples,FL who could help treat my adult daughter ? We were recently exposed to significant mold ( that she is allergic to) in our house. We are out of the house until this can be remediated next Wed. Any recommendations would be greatly aporeciated.

  4. Lee says:

    This is a great article but some of the things mentioned are things found to be high in glyphosate and glufonisate which has been found to raise histamines. They use those herbicides to dry beans and grains. Also people may want to avoid GM products because it has been found the body reacts to the BT Toxin in them the same way they would if you had food poisoning.

  5. Karlicia D. Berry says:

    This is excellent! Right on the money when it comes to explanation and advice to help. Thank you so much for publishing this.

  6. Jennifer F Jackson says:

    I find that so many who suffer with histamine problems are also sensitive to salicylates, and it is important to learn about oxalates. The best place to learn about oxalates is “Trying Low Oxalates TLO” facebook group and other groups Susan Owens is the expert. Oxalates cause kidney stones, gout, leaky gut, eye problems, joint pain, lower minerals and sulfur, if this isn’t addressed the other problems persist. Also iodine helps control histamines– and important to note meat must be very fresh (for histamines) so buy fresh and freeze right away. (No leftovers) Iodine info–https://www.youtube.com/watch?v=seymLq1ofXA– also, environmental stress is a trigger to histamine release– heat, cold, mold, … many also fine OMAD (one meal a day helps) and Intermittent fasting– at least 18 hours a day of clean fasting (Plain water only) gives the body a chance to heal — Dr. Jason Fung –“Intermittent fasting … That is the process of autophagy, where sub-cellular organelles are destroyed and new ones are …”

  7. Christine Menaged says:

    Hi
    Thank you for the article. Well done.
    I have a very complex situation. I suffer from gastritis. Had my gallbladder removed do to a pancreatic attack. Everything normalized , but I continue suffering from leaky gut, gastritis, gerd post nasal drip, possible ulcers lots of burning in the gut.
    Recently developed a nagging pain that I believe may be an ulcer. I began taking Carnosine Zinc and I feel it helps my stomach, but I notice when I take carnosine the histidine makes my histamine worse. I also am gluten intolerance and recently also developed a geographical tounge which we think was a fungus infection. I was given several doses is Nystatin and Diflucan which only made it worse. I did take antibiotics a while back. I believe the Zinc carnosine can help me, but I need to balance my micro flora and control my histamine level. When I take Zinc Carnosine I get severe pain in my joints and an ache feeling as if I took gluten. My sinus are also very dry and I am always dehydrated regardless if I drink water. My E&T doctor says I have allergies but I have not suffer ed from any rashes or asthma just very dry sinus and post nasal drip. I also suffer from gerd if the acid gets out of control. Based on your article it appears I was taking the wrong probiotics.
    I would dearly appreciate any suggestion or recommendation you may have.
    Thank you,
    Christine

    • Epstein says:

      Christine, thanks for your comment. It would be difficult to assess your situation from this information alone, and it would not be appropriate for me to do so in this comment section. Suggest that you have a Comprehensive Digestive Stool Analysis x 3 (I use Doctors Data) completed and start with identifying status of your digestive tract flora, parasites, yeast and food digestion. Nasal drip will disrupt the protective gastric mucosa and lead to leaky gut and a worsening of the sinus drainage. You might ask your doctor about chromalyn sodium, aka Nasalchrome. A low carb, low fruit, paleolithic diet along with a broad spectrum probiotic and other digestive support supplements should also give you some relief.

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