Histamine is a natural compound produced in the body that can have various effects. While histamine itself is not harmful, an imbalance between the body's total histamine load and its ability to process it can lead to what is known as histamine intolerance. Despite its name, histamine intolerance is not an allergy to histamine; however, the symptoms it causes can appear similar to allergic reactions due to histamine's role in the body. Because of this, identifying histamine intolerance can be challenging. This article will explore a functional approach to understanding histamine intolerance and its potential causes. It will also outline considerations for managing histamine intolerance. (3, 4)
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What is Histamine Intolerance?
Histamine is a chemical that plays a role in brain function, digestion, and immune responses. As a neurotransmitter, it acts on receptors in the brain to increase wakefulness. It stimulates parietal cells in the stomach to secrete gastric acid required for digestion. Histamine's most well-known role in the body is its ability to trigger immune responses. (2)
Much of histamine is made in the body by granules in specific types of immune cells: mast cells and basophils. After exposure to foreign substances, these cells release histamine at mucosal surfaces to induce an immune response. Typically, histamine is then broken down by specific enzymes. If, however, you cannot break down histamine efficiently, it may build up in the body, potentially leading to histamine intolerance. Histamine intolerance results from an imbalance between accumulated histamine and the body's capacity to process and eliminate it. (1, 2)
Histamine Intolerance Signs & Symptoms
The symptoms of histamine intolerance are linked to the physiological functions of histamine in the body. Typically, histamine intolerance symptoms present after ingesting a high-histamine food or exposure to a substance that triggers a histamine-mediated response. Symptoms strongly resemble allergy symptoms, sometimes making identification difficult. Common symptoms include (1):
- Gastrointestinal symptoms
- Sneezing
- Nasal congestion and runny nose
- Headache
- Flushing
- Hives
- Itching
- Fatigue
More severe cases of histamine intolerance can present with abnormal and painful menstrual cycles, insomnia, irregular heart rate, asthma, anxiety, difficulty regulating body temperature and blood pressure, and dizziness. (3)
What Causes Histamine Intolerance?
Histamine intolerance may result from factors that lead to excess histamine production and deficiencies in the enzymes that break it down.
Reasons for Enzyme Deficiencies
Two main enzymes break down histamine in the body: diamine oxidase (DAO) is primarily responsible for processing histamine in the gut, and histamine-N-methyltransferase (HNMT) is responsible for the conversion of histamine within cells. (4)
Impaired enzymatic function and reduced levels of enzymes are two main reasons why a person may not have sufficient enzyme activity to process histamine from the body. Genetic variations and certain medications can cause decreased enzymatic function or block the enzyme from doing its job. Medications that may affect DAO's activity include (3, 5):
- Antiarrhythmics
- Antibiotics
- Antidepressants
- Antihypertensives
- Muscle relaxants
- Narcotics
- Non-steroidal anti-inflammatory drugs (NSAIDs)
Because DAO is synthesized in the gut, gastrointestinal disorders, including leaky gut, IBS, SIBO, and IBD, can also contribute to enzyme deficiency.
Reasons for Histamine Overproduction
Dietary histamine from histamine-rich foods or foods that may trigger histamine release in the body can contribute to the overproduction of histamine. (3)
Exposure to environmental and dietary allergens can cause immune reactions and histamine release from immune cells. Some people have mast cell disorders, resulting in mast cell overactivation and increased production of chemicals, including histamine.
Mold exposure, leaky gut, SIBO, or other intestinal dysbiosis can contribute to immune dysregulation, potentially leading to increased histamine production.
Estrogen may promote the release of histamine and other chemicals from mast cells and basophils. States of estrogen excess or dominance can increase histamine levels and worsen related symptoms.
Functional Medicine Labs to Test for Root Cause of Histamine Intolerance
Functional medicine labs can help practitioners personalize options for their patients. Below are some of the most common labs ordered for patients experiencing histamine intolerance.
Gut Health Assessment
A comprehensive gut assessment may include a comprehensive stool analysis, a SIBO breath test, and a leaky gut panel.
A comprehensive stool analysis measures biomarkers in stool that provide insight into digestion and malabsorption, intestinal inflammation, and the makeup of the large intestinal microbiome.
A SIBO breath test is performed at home by the patient. It measures gas levels exhaled through the breath that can indicate the overgrowth of bacteria within the small intestine and archaeal overgrowth in the small or large intestines.
The advanced intestinal barrier assessment (IBA) measures direct markers of leaky gut: zonulin, DAO, and LPS. Histamine is also measured to determine the histamine-to-DAO ratio.
Genetic Testing
Genetic variations of the DAO and HNMT genes can be identified with a genetic panel. Additional variations identified can also guide recommendations, like the best form of vitamins to use and additional support.
Female Hormone Panel
A female hormone panel measures sex hormones essential to women's health, primarily estrogen, progesterone, and testosterone. When evaluating a women's hormonal balance, it is important to look at each form of estrogen and the estrogen-to-progesterone ratio.
Mycotoxins
The most accurate way to screen for and identify mold exposure is to measure mycotoxins in the urine.
Allergies
IgE-mediated allergies (environmental and dietary) should be ruled out as histamine intolerance mimics and potential triggers of increased histamine production in the body.
Functional Medicine Considerations for Histamine Intolerance
Addressing the potential causes of histamine intolerance is important for managing symptoms. This article will not discuss this in depth due to the complexity of the many possible causes. Lab findings should guide this aspect of the approach, often including addressing gut health, balancing hormones, reducing mold exposure, and managing allergies. You can check out the Rupa Health Magazine for articles about these issues.
Diet and Nutrition Considerations for Histamine Intolerance
Implementing a low-histamine diet may be helpful in managing histamine intolerance. Foods with high histamine content and those that may stimulate the release of histamine should be considered for reduction or limitation in the diet. Studies show that improvements in gastrointestinal and dermatological symptoms can be observed in 33-100% of patients as soon as four weeks after implementing dietary modifications. (4)
High Histamine Foods to Consider Limiting
- Hard and semi-hard cheeses
- Fermented foods: pickled vegetables, sauerkraut, kimchi, yogurt, kombucha
- Shellfish
- Processed or smoked meats
- Soy: tempeh, tofu, miso, soy sauce
- Mushrooms
- Avocado
- Olives
- Dried fruits
- Canned food
- Chocolate
- Vinegar
- Alcohol
- Leftovers
Histamine-Releasing Foods to Consider Limiting
- Spinach
- Eggplant
- Tomato
- Bananas
- Plums
- Pineapple
- Citrus fruits
- Strawberries
Low-Histamine Foods to Consider Including
- Freshly caught and cooked fish, meat, and poultry
- Cooked eggs
- All vegetables except those listed above
- Fruits: apple, cantaloupe, figs, honeydew, mango, watermelon
- Unbleached and unprocessed grains and flours
- Coconut
- Dairy alternatives: coconut milk, rice milk, hemp milk, almond milk, macadamia milk
Supplement Considerations for Histamine Intolerance
Supplements may be considered in a histamine intolerance protocol to support histamine processing pathways, stabilize mast cells, and help manage symptoms as needed.
DAO
Supplemental DAO taken before meals may help support the breakdown of dietary histamines in the digestive tract, potentially alleviating digestive symptoms related to meals.
Enzyme Cofactors
Nutrient cofactors are required to support the enzymes involved in histamine's processing pathways. Individuals with histamine intolerance can be sensitive to supplements; dosing can vary between individuals depending on their tolerance. Cofactors to consider supplementing in individuals with histamine intolerance include:
- Vitamin B1: 500-1000 mg daily
- Vitamin B2: 400 mg daily
- Vitamin B5 (Pantothenic Acid): 2-3 g daily
- Vitamin B6 (P-5-P): 70-200 mg in the evening
- Vitamin B12: 1000-5000 mcg daily
- Vitamin C: 1000-5000 mg daily in divided doses; decrease the dose if loose stool develops
- Magnesium: start at 200 mg in the evening and increase to bowel tolerance; decrease the dose if loose stool develops
- Copper: 1-3 mg daily
Mast Cell Stabilizers and Antihistamines
Quercetin - found naturally in foods including garlic, onions, apple, and parsley - is known for its antioxidant activity and potential to support histamine management. It is often dosed at 400 mg three times daily.
Stinging nettle leaf is also traditionally used in managing allergies, supported by research showing its potential to reduce symptoms in individuals with allergic rhinitis. Nettle leaf is commonly dosed at 400-600 mg three times daily.
Curcumin is the active component of turmeric and has properties that may support inflammation management. It has been studied and is often considered for individuals with mast cell concerns. It is typically dosed at 1 gram 2-3 times daily.
Omega-3 Fatty Acids
Omega-3 fatty acids (EPA and DHA) are known for their potential to support immune function and help manage inflammation. Using 3-5 grams of combined EPA and DHA daily may help manage symptoms associated with histamine overload.
Probiotics
Supporting a healthy gut microbiome is important for individuals with histamine intolerance to help manage intestinal inflammation and promote a healthy balance between histamine-producing and degrading bacteria. Certain strains of bacteria, like Lactobacillus casei, produce histamine. Probiotics that exclude histamine-producing and include histamine-scavenging bacterial strains may help manage the body's histamine levels. Seeking Health's Probiota HistaminX, dosed one capsule daily, is a popular option in managing histamine intolerance.
When to Retest Labs
The amount of time it takes to restore a healthy balance of histamine levels in the body varies from person to person, depending on the chronicity of symptoms, underlying factors, and ability to comply with management strategies. Many doctors and patients will opt to gauge the plan's efficacy by monitoring symptoms, which can begin to improve anywhere from one week to a few months. If labs are being repeated, waiting 1-3 months from baseline is generally recommended to assess the response to strategies accurately.
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Summary
Histamine intolerance can cause uncomfortable symptoms. If you suspect that you experience histamine intolerance, work with a healthcare provider who can order the appropriate labs to rule out other conditions that can cause similar symptoms and identify the underlying contributors to histamine imbalance. By considering dietary modifications and exploring supplement options, while addressing potential causes, it is possible to experience relief from histamine-related symptoms over time.
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