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Treat Elevated Histamine, Naturally

treat elevated histamine naturally

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 will order 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 a reflection of one's methylation status. This is because of the methyl compound that limits the ability for the HMT enzyme to break down histamine. Persons who are "undermethylated" lack, this methyl enzyme and so typically have elevated whole blood histamine levels. When treated with methyl supplying amino acids such as methionine and SAMe, the mood related disorders are often improved. Because HMT is also present in the plasma, histamine levels may be controlled to some extent with methionine and SAMe. But when suffering symptoms of elevated plasma histamine (rash, seasonal allergies, inflammation, itching, hives, conjunctivitis, congestion, etc), the enzyme diamine oxidase, DAO, is more responsible for histamine breakdown and control of these allergy symptoms.

This post below does not discuss the role of whole blood histamine and methylation for the purpose of determining cause managing methylation related mood disorders. 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.  For the record, Walsh providers prefer Whole Blood Histamine values for predicting methylation status vs 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.

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 or the over response by histamine receptors.  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.

Tests for diagnosing Mast Cell Activation Disorder based on the research of Afrin and Co are listed here... 

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.

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

Mast Cell Activation Disorder 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.

Low Dose Naltrexone LDN for Symptoms of Histamine Overload

Very low dosages of the pharmaceutical drug naltrexone is being used for histamine intolerance and other inflammatory conditions with great success. It is more commonly recommended in full strength, as an opiate receptor stimulator/blocker for pain syndromes. Because it is a receptor agonist and antagonist, it has a unique characteristic of treating pain without the risk of narcotic overdose. It is also used for treating heroin and other opiate overdoses its receptor antagonist effect allows it to bind some of the opiate receptors sites and block the effects of opiates. As a overdose treatment, most states allow over the pharmacy counter sales for a single, low dose therapy.

Below is a excerpt from a research publication that describes the mechanism of action and treatment benefits of naltrexone.

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain
Jarred Younger,corresponding author Luke Parkitny, and David McLain

"Naltrexone, given at low dosages (in the range of 3–5 mg), has been demonstrated to reduce symptom severity in a small number of chronic conditions, including fibromyalgia (1), Crohn's disease (23), multiple sclerosis (45), and pruritus associated with systemic sclerosis (6). The use of naltrexone at this dosage range is typically referred to as low‐dose naltrexone (7). As an orally available compound that is structurally similar to naloxone, naltrexone may work to reduce disease severity by attenuating inflammatory processes (8). This antiinflammatory effect is distinct from the better‐known effect of naltrexone in the blockade of neuronal opioid receptors and may instead involve the antagonism of immune cell receptors, including microglia in the central nervous system (910).

Microglia are the resident macrophages of the central nervous system, and the primary form of immune defense in the brain and spinal cord. The cells normally exist in a resting (ramified) state but are activated by a range of triggers, including cell death, peripheral inflammation, and infection (11). Once activated, microglia undergo drastic morphologic changes and produce proinflammatory factors, such as cytokines, excitatory amino acids, and nitric oxide (12). These inflammatory factors can interact with neurons via multiple channels (13) to cause hyperalgesia, fatigue, and other symptoms (14). The behavioral symptoms of activated microglia (classically called sickness behaviors) are very similar to the primary complaints of fibromyalgia, suggesting that activated microglia may underlie the condition. Fibromyalgia may therefore represent a state of hypersensitive microglial activity and heightened inflammation in the central nervous system. Compounds such as naltrexone, which are known to suppress microglial activity, may therefore be helpful in treating fibromyalgia. By antagonizing microioglial activity (likely via action on Toll‐like receptor 4), naltrexone may suppress the release of proinflammatory factors and thereby reduce pain and other symptoms of fibromyalgia."

Most functnal medicine practitioners are familiar with this LDN low dose naltrexone therapy and prescribe it via a compounding pharmacy. Cost ranges from $75-150 for a prescription. To save costs, some will take a single full strength Naloxone tablet of 50mg and dissolve in water and take 1/30th of this volume on a nightly basis.  This is not recommended as stability and consistency are not predictable. It is advisable to contact your physician for a properly prepared prescription.

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 within whole blood cells, 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.

According to the research presented in the below referenced article, there are known compounds that inhibit this conversion intracellularly and to some extent extracellularly. Not all of these compounds are readily available and others, such as methionine or its more potent version SAMe should not be taken without the whole blood histamine test and confirmation of methylation status based on these results by a qualified practitioner.

Effects of various compounds on histidine decarboxylase activity: Active site mapping
Yoshiteru Sakamoto, Takehiko Watanabe, Hideyuki Hayashi, Yoshitaka Taguchi, and Hiroshi Wada

"DOPA, homocysteine, cysteine, methionine and urocanic acid were the best inhibitors; β-phenyllactic acid, phenylpyruvic acid and carnosine were less strong inhibitors; valine, oxaloacetic acid andNτ-methylimidazole acetic acid were weak inhibitors." 

Other Inhibitors of HDC are:
·    Catechins – found in green tea, chocolate, kola nut, peaches, acai, apricots, apples, blackberries, raspberries, plums with skin and broad beans
·    NAC N-acetyl cysteine
·    Test and treat any underlying infection of SIBO (Small Intestinal Bacterial Overgrowth) H Pylori (very common with gastritis)

Histamine and Probiotics

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/migraines
  • Painful menstrual periods
  • Gastrointestinal symptoms
  • Intolerance to fermented foods and alcohol
  • Mucous in sinuses
  • Asthma

Supplements, dietary and OTC medicines that increase DAO levels include:

Effect of dietary fatty acid and micronutrient intake/energy ratio on serum diamine oxidase activity in healthy women
MakotoMiyoshiM.T., Ph.D.,et.al


"Serum DAO activity in both phases was positively correlated with intake of long-chain fatty acidssaturated fatty acids, and monounsaturated fatty acids (P < 0.05). Intake of phosphoruscalciumzinc, magnesium, iron, and vitamin B12..." was found to be beneficial to women during the luteal phase of the menstrual cycle. This suggests a role for lipids and micronutrients in DAO levels. 

Another relevant article from the Canadian Journal of Gastroenterology and Hepatology found that malabsorption of carbohydrates was associated with low levels of DAO  

Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption

The aim of this retrospective study was to analyze the concomitant prevalence rates for lactose malabsorption (LM), fructose malabsorption (FM), and histamine intolerance (HI) in patients with so far unexplained gastrointestinal (GI) symptoms. 

Other supplements that either contain DAO or improve levels of DAO:

  • White Pea
  • Kidney, Placenta and Liver Glandular Extracts
  • 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 professional with proper 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.

Probiotics that lower histamine:

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 reduce histamine and mast cell expression:

  • Methionine and SAMe supplements (do not take if experiencing depression, schizophrenia or other mood disorders without proper methylation status assessment and professional advise.)
  • Increase proteins high in methionine
  • DAO diamine oxidase from natural sources (kidney glandular, placenta and White Pea are sources of naturally occuring DAO)
  • Probiotics B infantis, B longum, L plantarum
  • Vitamin C 
  • B6 (can also increase histamine carboxylase)
  • Avoid lectin in diet – potatoes and tomatoes
  • Avoid fermented foods
  • Cromolyn sodium– OTC mast cell stabilizer
  • Benadryl (but it lowers DAO and may ultimately cause increased histamine receptor levels)
  • Bromelain and Quercitin
  • Chocamine  – mast cell stabilizer
  • Improve adrenals with herbal and glandular supplements
  • Curcumin (also decreases DAO)
  • NAC N-acetyl cysteine
  • Catechins (green tea etc)
  • Fatty Acids (long chain and 
  • Micronutrients- Calcium, Iron, Magnesium Zinc, Phosphorus, B12, B6, Vitamin C, 
  • Various glandulars
  • Various herbs
  • White Pea
  • Reishi Mushrooms

Biotype Nutrients is a source for purchasing supplements to manage elevated histamine and MAST Cell disorder. The site offers many top name brands and quality sources. DISCLAIMER - This is a site developed and owned by Second Opinion Physician for the benefit of persons treating elevated histamine and related conditions.

Histamine and Depression

Per the research of William Walsh PhD and Carl Pfeiffer, MD, whole blood histamine levels are used to determine ones methylation status for treating 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

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.