Histamine toxicity

Histamine is a basic amine that is utilized and stored by the basophils and mast cells. Its primary functions include contraction of smooth muscle, cardiac stimulation, and increase in vascular permeability by acting on H1-receptors and gastric acid secretion by acting on H2-receptors.

Histamine toxicity is a biochemical state of high or sustained border-high blood levels of histamine. Histamine overload is caused by either mastocytosis or excessive mast cell degranulation and affects individuals with a wide range of systemic symptoms.

The baseline levels of blood histamine in individuals affected by chronic mast cell degranulation are not always elevated above the reference range since the condition is a result of a chronic process and not an acute histamine response against an invading allergens. Nevertheless, the significance of the condition is an ongoing and elevated histamine degradation process that utilizes and depletes biochemical resources necessary for other body functions.


There are two types of histamine reactions – one is within the digestive track, causing bloating and distress and the other one is systematic, that affects the immune system and neurological /psychological states. In some individuals, mast cell degranulation does not lead to pronounced skin reactions but affects brain histamine H3 receptors. When you eat a histamine rich nutrient, you may get a gastrointestinal discomfort without a systemic response. However, if you were affected by a stress or ingested a food that caused the mast cells to degranulate increasing the blood concentration of histamine, there will be no gastrointestinal distress, but a systemic disturbance that can be presented as anxiety, insomnia and restlessness. Keeping a diary of foods that you eat and how you sleep afterwords, can help you to avoid the foods that trigger the mast cells degranulation.

Some of the symptoms of excessive mast cell degranulation are

  • When histamine is released, one of the first symptoms many experience is chills
  • Hypercalcemia can be invoked by chronic histamine modulation of H2 receptors via immunoreactive PTH (iPTH) secretion
  • Over-reactive nervous system, anxiety, sleep disorders, palpitations, intolerance to stress, hot flashes, sweating
  • Electrolyte disturbances, mouth dryness
  • Migraines, sensitivity to light, seasonal allergies, itching, frequent colds
  • Systemic inflammation including joints, skin, organs
  • Pathogen overgrowth such as intestinal dysbiosis, SIBO, candida, h.pylori
  • Interstitial cystitis
  • Premature ejaculation in men
  • Implication in chronic fatigue, pain and inflammatory syndromes such as fibromyalgia, asthma, costochondritis, arthritis, Meniere’s disease, liver disorders
  • Decreased bone density and osteoporosis
  • Systemic low grade acidosis
  • Same as implicated in mastocytosis

Digestive issues, protein intolerance, malabsorption causing low amino acid profile and vitamin deficiency issues occur due to pancreatic insufficiency and low stomach acid conditions that could be a result of excessive H2 receptors stimulation.


Some of the reasons for excessive mast cell degranulation are exposure to environmental and dietary allergens, dehydration to electrolyte imbalances, chemicals and drugs, physical factors such as injury, heat, cold, vibration and chronic diseases such as pancreatic insufficiency or adrenal insufficiency. In case of adrenal insufficiency, it is often a symptom of malnutrition invoked by malnutrition caused by pancreatic insufficiency. However, if a body is healthy and the exposure to mast cell degranulation agents is not overly toxic, the reason for histamine build up in the body is its inability to cope with toxins and downgrade the histamine.

The most effective and beneficial long term method of dealing with histamine overload is to treat the underlying the condition that causes nutritional imbalances resulting in build up of toxins in the body. However, if the cause cannot be immediately identified and/or the treatment is complex and does not immediately gain results, managing an excess of histamine systemically is critical to prevent damaging of organs in the body while maintaining a better quality of life.

Reducing the excess and effects of histamine toxicity

There are multiple approaches to manage acute and chronic histamine overload

1. Treatment of the underlying cause(s)
2. Dietary avoidance of histamine rich foods
3. Physical factors
4. Drugs
5. Nutritional supplements

1. Treatment of underlying causes

When histamine build up is apparent looking at the symptoms alone, it is a clear sign that there is an underlying cause that impairs the body’s ability to cope with toxins and their excretion via detoxification pathways and its reduced capacity of eliminating of the excess histamine. One of the implications of pancreatic insufficiency is deficiency of Diamine oxidase (DAO) enzyme that is a major histamine downgrading element within the small intestine. Deficiency of DAO enzyme is the reason behind of intolerance of histamine rich foods.

Chronic electrolyte imbalances may cause increased mast cell degranulation, weakened immune system, kidney and liver disorders that can all contribute to metabolic byproducts and pathogen toxins build up.

A proper function of all of the systems in the body starts with digestion. If the digestion is impaired, the nutritional depletion weakens all of the systems responsible with toxin elimination. The most overlooked cause of histamine toxicity is deficiency of pancreatic enzymes, therefore the pancreatic insufficiency should be evaluated first.

2. Dietary avoidance of histamine rich foods

One of the ways to reduce the effects of excess histamine is to avoid consumption of the foods that are rich in histamine and/or trigger histamine release by mast cells. Refer to histamine rich foods list for most common foods that increase systemic histamine toxicity.

Temporarily reduce protein ratio to 15-20% daily.

3. Physical factors that affect mast cell degranulation

Mast cells degranulation can be aggravated by changes in temperatures, intense exercise, physical injuries and/or vibration and sudden altitude changes, sudden scent/odors, sex and emotional stress.

Factors that trigger basophils and mast cells degranulation

  • Overheating
  • Prolonged sun exposure (heat and ultraviolet radiation) induces mast cells to release histamine and inhibits DAO enzyme capacity
  • Emotional stress and sexual climax in individuals with serotonin or estrogen/progesterone imbalances. These trigger release of urocortin (UCN) that stimulates CHR-R (receptors) releasing the corticotrophin-releasing hormone (CRH) which triggers mast cell degranulation [srs].
  • Sexual climax (in those with serotonin or estrogen/progesterone imbalances)
  • Emotional stress
  • Vigorous aerobic exercise dramatically raises histamine levels. Resistance training (weights and yoga) does not raise histamine levels and helps to stabilize histamine response
  • Vibration affecting vertebral stability
  • EMF radiation from Radio or TV broadcasting towers
  • Hypoglycemia (low blood sugar)

Dietary and chemical triggers of mast cell degranulation

  • Histamine rich foods
  • Chemical agents
    • MSG
    • Pesticides
    • Deodorants
    • CT contrast
    • Preservatives
    • Some fragrances
    • Anesthetic agents
    • Artificial sweeteners
    • Antibiotics and antivirals
    • Body washes and liquid soaps
    • Plastic fumes (hot drinks or foods from plastic cups and containers)
    • Fluoride (in tooth pastes and in water used for humidification of air)

Factors that stabilize mast cell activity

  • Balancing foods by arginine to lysine content to avoid chronic herpes family viruses reactivation can help to reduce mast cell degranulation
  • Balancing essential fats in the diet to include all Omega 3, 6 and 9 helps mast cell stabilization.
  • Normalizing the sleep patterns and eliminating insomnia
  • 10-20 minutes of gentle cardio exercise that does not cause significant vasodilation (perspiration) is most beneficial
  • Properly hydrating by slowly sipping water and adding ionic minerals once a day to a glass of water. Drinking fast and in excess can deplete the body of electrolytes.

Factors that help to reduce an ongoing histamine response are 10-20 minute hot baths, warm drinks, 10-15 minute naps, deep breathing, meditation and any other methods that attenuate central nervous system response.

4. Drugs

Using drugs to manage the mast cell degranulation can be helpful but only in extreme cases and should not be used on a regular basis as these chemical compounds produce organ damage if used long tem

  • Antihistamines – blocking H1 and H2 receptors with slow acting antihistamines such as Loratadine and Cetirizine combination
  • Leukotriene antagonists inhibit receptors targeted by leukotrienes released from mast cells.
  • Epinephrine to eliminate the excess of histamine during an anaphylaxis (severe histamine response)
  • Calcium channel blockers reduce mast cell degranulation at the point of trigger
  • Mast cell stabilizers that prevent degranulation such as oral solution of Cromolyn sodium

5. Nutritional supplements

While removing the cause of excessive histamine release by mast cells that is the only way to successfully resolve histamine toxicity and histamine intolerance, natural compounds can be successfully used to address some of the symptoms and conditions that commonly result from excessive histamine levels in the body.

To reduce histamine build up, avoid folic acid, vitamin B12 in excessive amounts as these will build up histamine stores. Also avoid high protein diets and simple carbohydrates.

Correcting nutritional imbalances responsible for histamine control

Mineral hair analysis is a helpful test to measure the minerals excretion from a body and thus an indicator of mineral content within the tissues. Referring to the test results of a hair mineral analysis, the following minerals are important to have properly balanced

  • Calcium – appears to have a regulatory role, limiting the histamine secretion [srs]. Calcium also helps to mobilize histamine from tissues. If calcium supplements are taken, the total dietary consumption along with calcium supplements should not exceed 1500mg a day. If you have hypercalcemia, calcium supplements are strictly contraindicated.
  • Magnesium – regulates activity of histidine decarboxylase which is responsible in histamine production from histidine. Magnesium is also an important co-factor in DAO enzyme capacity
  • Chromium – stabilizes glucose metabolism, preventing stress and therefore reducing mast cell activity
  • Zinc – inhibits mast cells degranulation. Antagonizes copper. With pancreatic insufficiency may produce anxiety.
  • Manganese – inhibits mast cells degranulation and elevates diamine oxidase activity. Antagonizes copper
  • Copper – required for DAO enzyme capacity responsible for histamine breakdown from foods and in plasmaZinc and Copper generally need to be supplemented in ratio of 8:1 if either one is taken

Reducing toxic levels of histamine

Most of the below supplements (except for herbs) should be taken 30-60 minutes before a meal to increase absorption.

  • Vitamin C (buffered, sustained release) reduces mast cell histamine capacity and increases DAO enzyme activity
    Usage: up to 1000mg daily in morning
  • Methionine (amino acid) – acts as as an anti-folate, adding a methyl group to help histamine mobilization
    Usage: 500mg 3 times daily between meals in divided doses during flare up and 500-1000mg daily in divided doses for maintenance. Take 3-day breaks to keep the body’s ability to process methionine without supplementation.
  • Vitamin B6 – co-factor of DAO enzyme. Inhibits mast cell degranulation [srs]. With pancreatic insufficiency may produce anxiety.
    Usage: 2-10mg daily (If tolerated. May create anxiety). Best taken once in morning with Methionine.
  • Glycine (amino acid) – inhibits histidine. Contraindicated with hypercalcemia.
    Usage: 500-1000mg daily 2 hours after last meal. Produces calming effect, may slow down peristaltic movement and cause constipation.
  • TMG (Trimethylglycine) increases methionine levels and protects the cardiovascular system by neutralizing homocysteine
    Usage: 500-1000mg daily in morning. Can be too stimulating.
  • Quercetin/Bromelain combo & lemon bioflavonoids – limit the histamine release from mast cells. This appears to be the most effective combo to use during an acute histamine release bout.
    Usage: Quercetin and bromelain as a combo in one supplement is more effective. Take for 1-2 weeks then make a 2 week break. Not recommended long term.
  • Pycnogenol (French maritime pine extract, bioflavonoid) – significantly inhibits mast cells degranulation [srs]. May cause hot flashes.
  • Vitamin K2 (Menaquinone-7 /MK-7). Reduces mast cells degranulation by transferring the calcium that facilitates mast cells activation from blood serum into the bones.
    Usage: 100mcg daily
  • N-acetyl-cysteine (NAC) – 200mg in morning to decrease excessive mucous and gently lifts intracellular glutathione for detoxification. NAC can also cause elevated baseline mast cells degranulation. Best taken with vitamin C to limit mast cell histamine capacity.
  • Inositol hexanicotinate (no flush niacin) – increases cell membrane permeability better than regular niacin, helping the nutrients to get into the cells.
  • Essential Fatty Acids (EFA) – in balanced composition of omega 3 and 6 reduces histamine release.
  • Herbs (as additional natural antihistamines)
    • Calming (in evening, binds to H1 & H2 receptors) – rosemary, lemon balm, turmeric, ginkgo biloba, chamomile, skullcap, holy basil leaf, pycnogenol
    • Stimulating (in morning, reduces histamine levels) – garlic, ginger, licorice (100mg max, once a week)
  • Melatonin (sustained release) inhibits mast cell activation.
    Usage: 2-3mg 20 minutes before bed, max 1-2 times per week to avoid hormone dependency.

Reducing mast cell population

  • Lipoic acid, 25mg 3 times daily, in morning and mid afternoon. May cause insomnia if taken late in the day.
  • Vitamin D (only if deficient), 1000-2000UI daily

Improving histamine breakdown within the digestive system

If correcting nutritional imbalances does not produce effective results, using the following can help to further alleviate gastrointestinal issues associated with impaired histamine breakdown. Some of the symptoms of histamine breakdown issues are bloating, burping, stomach pain and indigestion

  • Digestive enzymes (replace pancreas secretion of enzymes, may create dependency)
    • Pancreatin / Pancrelipase
    • Wide spectrum digestive enzymes to address pancreatic insufficiency
    • DAO enzyme supplements such as those found in Histrelief, DAOSin, Histame or a more potent HistoDAO products help to break down the histamine content from histamine rich foods
  • Pancreatic glandular supplements support pancreas function to produce enzymes

Please consult with your doctor before using any of the supplements mentioned on this page.