Histamine intolerance is a disorder in which histamine builds up in the body due to the inability to metabolize or break down histamine. The intake of high levels of histamine through the diet or the environment contributes to the wide range of symptoms associated with histamine intolerance. Although estimates show a small percentage of people with histamine intolerance (1), the relationships between histamine and histamine intolerance are worthy of examination for the sufferers who might benefit from a change in diet. If suffering from the symptoms of histamine intolerance, can following a low histamine diet help? What are the guidelines for the low histamine diet?
What is Histamine?
Histamine is a bioactive organic compound that can act as a hormone or neurotransmitter (chemical messenger in the nervous system). Histamines play a prominent role in the immune system as part of allergic responses and a driver of inflammation. Studies have shown that histamine can regulate immune responses, affect hormones, and impact digestive juices (2). Histamine also stimulates mucus production in the lungs and sinuses and aids in the contraction of smooth muscles in the gastrointestinal tract and airways.
Foods often provide histamines, and several common food items have high histamine levels. However, the body also makes histamine, as it provides numerous functions.
Many different types of cells synthesize histamine, including mast cells, platelets, and some neurons (1). Cells store histamine, releasing it when triggered by specific criteria, and are the driver behind many symptoms. For example, mast cells release histamine when triggered by repeated contact with allergens such as mold or tree pollens. In this case, histamine may cause sneezing, a runny nose, and a headache. Besides responding to allergens, histamine can be released upon experiencing cold temperatures, particular foods, medications, and even trauma (1).
Histamine Intolerance (HIT) – Impaired Ability to Break Down Histamine
The term “histamine intolerance” does not mean that the body resists histamine’s effects. Instead, histamine intolerance (HIT) means an impaired ability to break down histamine. Many researchers believe HIT starts in the gut with the deficiency of an enzyme, diamine oxidase, which breaks down histamine (3). Note that the term “lactose intolerance” is similar, meaning the impaired ability to break down lactose in the gut (4).
Contributors to Histamine Intolerance
Two enzymes can break down histamine for use by the body, diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). If anything interferes with the normal functioning of these enzymes, it can negatively affect the breakdown of histamine. Unfortunately, many factors can disrupt the ability of these enzymes to break down histamine properly, leading to histamine intolerance (1, 2, 5).
1) Overconsumption of histamine in the diet – Many foods and alcoholic beverages contain histamine. Frequent ingestion of these items can lead to such a high volume of histamine that DAO and HMNT enzymes get overwhelmed, resulting in increasing amounts of intact histamine in the system, which causes adverse symptoms.
2) Medications – Certain medications inhibit DAO enzymes, keeping them from properly breaking down histamine. These medications include some antibiotics, analgesics, antihypertensives, and antihistamines (2).
3) Health conditions: Many inflammation-oriented disorders, such as chronic inflammation, allergies, and Mast Cell Activation Syndrome (MCAS), can produce so much histamine that it overwhelms the ability of DAO and HMNT enzymes to break it all down. Other health conditions can result in DAO enzyme deficiency, such as non-celiac gluten sensitivity (NCGS) and malabsorption of carbohydrates. Those with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) are at greater risk of experiencing HIT.
4) Genetic factors: Mutations in DAO or HMNT genes can cause the creation of inactive or only partially active DAO and HMNT enzymes, significantly reducing the ability to break down histamine.
5) Naturally low levels of DAO or HMNT enzymes: There are individual differences in levels of enzymes in people due to differing chemistry and genetics. Some people will produce fewer DAO and HMNT enzymes because that is what is normal for their bodies. Unfortunately, this could lead to a buildup of histamine in those individuals.
Symptoms of Histamine Intolerance
Because histamine has many roles, a wide range of symptoms can occur when it builds up in the body. This expression in multiple body parts makes it extremely difficult to diagnose correctly, and sufferers can go for years with little relief due to misdiagnoses. According to one study which did careful tracking, gastrointestinal-related problems were the most commonly experienced symptoms of HIT. However, there was a long list of symptoms (see below). Close to 97% of HIT patients in that study indicated they had four or more symptoms. Bloating had the highest ranking in the severity category and had a prominent spot in the list of concurrent symptoms. The combination of bloating and postprandial fullness (fullness after a meal) took the top spot in that category. A shocking 45% of HIT sufferers had more than ten symptoms. Interestingly, it is common in women for HIT symptoms to disappear during pregnancy and return after birth. Below is the list of symptoms categorized by where the symptom is experienced in the body (4, 6).
GI tract:
abdominal pain and/or cramping
belching
bloating
chronic constipation
diarrhea
dysmenorrhea (painful cramps during menstruation)
emesis (vomiting)
flatulence
intestinal colic (painful spasms in the intestines)
nausea
postprandial fullness (fullness after a meal)
Skin:
acne
flush
hives
pruritus (itching)
rash, eczema
swollen, reddened eyelids
Cardiovascular system:
cardiac arrhythmia
circulatory collapse
dizziness
headaches
hypotonia (weak muscle tone)
low blood pressure
palpitation (pounding or racing heart)
Respiratory system:
asthma
dyspnea (shortness of breath)
nose congestion
rhinorrhea (runny nose)
sneezing
Additional Symptoms:
chills, shivers
extreme tiredness
sleep disorder
sudden changes in mood or concentration
swelling around the eyes, lips, and throat
weepy eyes
Testing for Histamine Intolerance (HIT)
There is no one standard test for diagnosing HIT. Testing blood or urine for histamine or utilizing a skin prick test can help positively identify HIT. However, these tests have to be considered along with reported symptoms, patient history, and eliminating the presence of other illnesses because any single finding may not be enough to diagnose HIT. Conditions with the same symptoms must be ruled out. High levels of histamine may not be due to HIT as allergies, infections, and DAO-blocking medications can also cause high histamine levels.
It may be helpful to test for IgE immune reactions. Total IgE may be helpful, as well as IgE reactions to specific inhalants (such as tree and grass pollens) and mold, to see if the patient is experiencing allergies. While IgE tests for inhalants are not diagnostic tests for HIT, they can indicate if the immune system is responding to allergens that can also trigger the release of histamine.
The Low Histamine Diet as Diagnostic Indicator
One of the most valuable tests for diagnosing and treating HIT is to implement the low histamine diet. If removing high-histamine food items relieves symptoms, then it is a powerful indicator that histamine intolerance is involved. This indicator is so strong that some doctors eschew the lab tests and request that the sufferer remove high histamine foods and drinks for a time to see what happens. If removing high histamine foods gives relief, it becomes a strategy for managing symptoms.
The Low Histamine Diet Explained
The idea behind the LHD is to avoid foods that are either high in histamine naturally or that cause the release of histamine when eaten. The LHD can significantly reduce symptoms when dietary histamines are drastically reduced. The time it takes for symptoms to decrease due to implementing the LHD may vary. Steinbrecher et al. discovered increased DAO enzyme activity in patients after four weeks of the LHD, with 90% of these participants reporting fewer headaches (2). After refraining from particular foods and reducing symptoms, previously avoided foods can be sampled one at a time to determine if they can be added back into the diet without provoking symptoms again.
It is difficult to tell if a food or drink is high in histamines just by looking at it. Preserved, processed, aged, and fermented products likely have high histamine levels (2). Research has produced lists of food and drinks that are high in histamines and should be removed from the diet for a while (7). Unfortunately, researchers argue for different thresholds of high and low histamine levels. Also, some foods do not contain histamine but do cause it to be released (8) or block the DAO enzyme.
There is no norm or standard for foods to avoid on the LHD (9), so many lists exist. One group of researchers cleverly side-stepped that issue by reviewing multiple studies and counting which foods were excluded most often (9). The following list is a subset from that paper, with the most frequently excluded foods listed first.
Foods to Avoid:
Dry-fermented sausages
Cured, semi-cured, and grated cheese
Beer
Wine
Fish and fish derivatives
Tomato
Spinach
Sauerkraut
Citrus fruits
Strawberries
Chocolate
Eggs
Soy-fermented products
Pineapple
Banana
Yogurt
Eggplant
Avocado
Seafood
*Note that many of these foods have excellent health benefits for a majority of the population. It is important to work with a knowledgeable practitioner to diagnose your symptoms and create a healthy eating plan tailored to your specific needs rather than just eliminating foods unnecessarily.
Creating a Balanced Diet
Our team of practitioners and nutritionists will work with you to create a nutritional plan to eliminate certain foods while incorporating those that will be most beneficial for your individual situation.
It’s best if the diet is anti-inflammatory, and it is important to eat a whole-foods diet and drink plenty of water. Below are some foods that we may recommend that you incorporate:
Poultry (chicken, turkey, quail, duck)
Vegetables that are not on the “avoid” list, such as celery, beets, broccoli, cauliflower
Fruits that are not on the “avoid” list
Rice or quinoa
Olive oil or high-heat coconut oil for cooking
Walnuts, chia seeds, flax seeds
Spices: ginger, turmeric, parsley, oregano, cilantro
Benefits of a Low Histamine Diet (LHD)
Given that many of those with HIT suffer from ten or more symptoms that can affect multiple parts of the body, a reduction in symptoms could signify a huge relief. The benefits of the LHD include:
A reduction of symptoms in those with histamine intolerance and other conditions involving the release of histamine.
The reduction of symptoms can aid in diagnoses, separating HIT from allergies and other inflammatory conditions.
A reduction of burden on the body, which may help other health conditions resolve.
Low Histamine Diet (LHD) for Mast Cell Activation Syndrome & Other Conditions
The LHD can be used to address other conditions besides HIT. Mast Cell Activation Syndrome (MCAS), where mast cells release a large volume of chemical mediators such as histamine, can significantly benefit from the LHD. Those with MCAS may reduce dietary intake of histamines to a level that reduces the burden on DAO and HMNT enzymes, allowing the enzymes to focus on breaking down the histamines released due to MCAS. Conditions involving inflammation and association with low DAO in the GI tract, such as Crohn’s, small intestinal bacterial overgrowth (SIBO), and irritable bowel syndrome (10), will also benefit from reduced dietary histamine.
Nutritional Supplements for Countering HIT
Many nutritional supplements can aid in breaking down histamine, inhibiting its release, or providing cofactors necessary for histamine metabolism. Here are just a few that can reduce histamine levels:
Diamine Oxidase (DAO) Enzyme - At the heart of histamine intolerance is an inability to break down histamine efficiently. One reason could be reduced DAO enzyme action due to genetics. Fortunately, DAO enzymes can be derived from pigs, which are very similar to humans in chemistry and physiology. Porcine DAO can be taken in capsules, supplementing naturally occurring DAO enzymes produced by the body. Supplementation of DAO can help break down histamine before it causes painful symptoms from an overabundance (11).
Quercetin – Quercetin is a flavonoid (plant compound) that inhibits histamine release from mast cells (12). Dietary sources include certain fruits (apples), vegetables (asparagus, cabbage, broccoli), and grains (barley, oats, rye), as well as dandelion, nettle, and red clover. However, nutritional supplements contain therapeutic dosages.
Luteolin - Luteolin is also a flavonoid that has strong antioxidant properties. It is in various fruits, vegetables, and medicinal herbs (13). It may be responsible for the yellow-green color in fruits and vegetables, such as the light green of celery. In a study by Kritas et al., luteolin inhibited allergic inflammation that was mast cell-mediated (14). Dietary sources of luteolin are celery, peppermint, and spices such as thyme, rosemary, and oregano. Luteolin is available as a nutritional supplement in therapeutic dosages.
Conclusion
While true histamine intolerance is not very common, those with it can suffer for long periods due to multiple misdiagnoses. An integrative doctor may help reduce the severity and length of suffering by assisting with a low-histamine diet. If you have been chasing symptoms and diagnoses, this diet can be the key to turning your health around and experiencing life without headaches and nagging GI symptoms. If you cannot get a good diagnosis and relief for your symptoms, please schedule an evaluation with one of the functional medicine doctors at TCIM. Helping people overcome health challenges is our mission - and our joy.
Jonathan Vellinga, MD is an Internal Medicine practitioner with a broad interest in medicine. He graduated Summa cum laude from Weber State University in Clinical Laboratory Sciences and completed his medical degree from the Medical College of Wisconsin.
Upon graduation from medical school, he completed his Internal Medicine residency at the University of Michigan. Dr. Vellinga is board-certified with the American Board of Internal Medicine and a member of the Institute for Functional Medicine.
info@tcimedicine.com
951-383-4333
Sources:
1. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007 May;85(5):1185-96. doi: 10.1093/ajcn/85.5.1185. PMID: 17490952.
2. Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020 Aug 14;10(8):1181. doi: 10.3390/biom10081181. PMID: 32824107; PMCID: PMC7463562.
3. Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021 Apr 12;13(4):1262. doi: 10.3390/nu13041262. PMID: 33921522; PMCID: PMC8069563.
4. Schnedl WJ, Lackner S, Enko D, Schenk M, Holasek SJ, Mangge H. Evaluation of symptoms and symptom combinations in histamine intolerance. Intest Res. 2019 Jul;17(3):427-433. doi: 10.5217/ir.2018.00152. Epub 2019 Mar 7. PMID: 30836736; PMCID: PMC6667364.
5. Kovacova-Hanuskova E, Buday T, Gavliakova S, Plevkova J. Histamine, histamine intoxication and intolerance [Internet]. Allergologia et Immunopathologia. Elsevier; 2015 [cited 2023Jan19]. Available from: https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-histamine-histamine-intoxication-intolerance-S0301054615000932
6. Symptom list [Internet]. Histamine Intolerance. [cited 2023Jan19]. Available from: https://www.histamineintolerance.org.uk/private/symptom-list/
7. Kohn JB. Is there a diet for histamine intolerance? [Internet]. Journal of the Academy of Nutrition and Dietetics. Elsevier; 2014 [cited 2023Jan19]. Available from: https://www.jandonline.org/article/S2212-2672(14)01454-3/fulltext
8. Low histamine diet: Foods to eat and to avoid [Internet]. Medical News Today. MediLexicon International; [cited 2023Jan19]. Available from: https://www.medicalnewstoday.com/articles/low-histamine-diet#foods-to-avoid
9. Sánchez-Pérez S, Comas-Basté O, Veciana-Nogués MT, Latorre-Moratalla ML, Vidal-Carou MC. Low-histamine diets: Is the exclusion of foods justified by their histamine content? [Internet]. MDPI. Multidisciplinary Digital Publishing Institute; 2021 [cited 2023Jan19]. Available from: https://www.mdpi.com/2072-6643/13/5/1395
10. Schnedl WJ, Enko D. Histamine intolerance originates in the gut [Internet]. MDPI. Multidisciplinary Digital Publishing Institute; 2021 [cited 2023Jan19]. Available from: https://www.mdpi.com/2072-6643/13/4/1262
11. Izquierdo-Casas J, Comas-Basté O, Latorre-Moratalla ML, Lorente-Gascón M, Duelo A, Soler-Singla L, Vidal-Carou MC. Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial. Clin Nutr. 2019 Feb;38(1):152-158. doi: 10.1016/j.clnu.2018.01.013. Epub 2018 Feb 15. PMID: 29475774.
12. Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 2012;7(3):e33805. doi: 10.1371/journal.pone.0033805. Epub 2012 Mar 28. PMID: 22470478; PMCID: PMC3314669.
13. Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, et al. Luteolin, a flavonoid, as an anticancer agent: A Review [Internet]. Biomedicine & Pharmacotherapy. Elsevier Masson; 2019 [cited 2023Jan19]. Available from: https://www.sciencedirect.com/science/article/pii/S0753332218367180?via%3Dihub
14. Kritas SK, Saggini A, Varvara G, Murmura G, Caraffa A, Antinolfi P, Toniato E, Pantalone A, Neri G, Frydas S, Rosati M, Tei M, Speziali A, Saggini R, Pandolfi F, Cerulli G, Theoharides TC, Conti P. Luteolin inhibits mast cell-mediated allergic inflammation. J Biol Regul Homeost Agents. 2013 Oct-Dec;27(4):955-9. PMID: 24382176.