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Histamine is often overlooked as a cause of chronic health problems yet the fix for this issue can be quite straightforward. In this article, I cover the details of histamine and how to follow a low histamine diet.
Histamine intolerance (HIT) affects approximately 1% of the population. Approximately 80% of those affected are middle-aged.1 Histamine intolerance occurs when an individual has more histamine in their system than they can breakdown. Excess systemic concentrations of histamine can result from overproduction, overconsumption, and/or having a reduced ability to clear out histamine from the body. For those with HIT, eating a diet that results in increased histamine can contribute to chronic inflammation due to the ongoing exposure to histamine. This excess histamine often accumulates as a result of decreased diamine oxidase (DAO) activity.2, 3 The resulting excess histamine contributes to the physical symptoms associated with HIT. Following a low-histamine diet along with supplemental DAO is often recommended to decrease the symptoms associated with HIT. Eating a low-histamine diet involves more than simply eliminating foods that are high in histamine. This article will help to explain the challenges with following a low histamine diet and will highlight the many ways excess histamine can occur in food and in the body.
Histamine Synthesis and Degradation
Excess histamine concentrations may be exogenously released from food or endogenously produced. Histamine is synthesized by a variety of cells in the body including mast cells, basophils, platelets, histaminergic neurons, and enterochromaffin cells. Endogenous histamine is released in response to a variety of immune and inflammatory related stimuli as well as certain foods, alcohol, or drugs which can activate release.1 Endogenous histamine supplies are also controlled by genes that code for the enzymes that synthesize and degrade histamine. Genetic polymorphisms in histamine receptors and DAO can decrease the rate of DAO activity, reducing the rate of clearance and increasing systemic histamine concentrations.3 Exogenous sources of histamine mainly comes from ingested foods. Several factors in food processing and storage can increase the histamine content of certain foods as well.
Histamine is normally metabolized by amine oxidases in healthy individuals. These amine oxidases include monoamine oxidase (MAO), DAO, and histamine N-methyltransferase (HNMT), with DAO being the primary enzymes for metabolism of histamine.5 It is thought that low gastrointestinal levels of DAO contributes to an individual being unable to break down histamine in the intestines, resulting in the increased sensitivity to histamine found in common foods. As excess levels accumulate, intolerance symptoms develop.1, 2, 6, 7
Symptoms Associated with Histamine Intolerance
There is great heterogeneity in the presentation of symptoms in those with HIT, making it difficult to define a clear clinical picture. Histamine intolerance is generally suspected when symptoms appear after the ingestion of histamine containing food.3 Symptoms may develop immediately or can be delayed as much as three hours following ingestion.5 Histamine receptors are found ubiquitously throughout the body, making different organ systems susceptible to adverse reactions due to excess histamine concentrations. This results in a wide variety of symptoms that may be exhibited by an individual, contributing to the difficulty in diagnosis.
These symptoms include gastrointestinal issues such as abdominal pain, bloating, diarrhea, and constipation. Extraintestinal complaints may affect neurological, respiratory, dermatological, and/or hemodynamic systems.2 Histamine has vasoactive properties that may result in flushing, headaches, and/or hypertension.5 Other common symptoms related to HIT include brain fog, fatigue, dizziness, itching, and difficulty swallowing, low blood pressure, nasal congestion, sneezing, and menstrual cramps.2, 3
Low-Histamine Diet and DAO Supplementation
Following a low-histamine diet along with DAO enzyme supplementation is currently the recommended strategy to prevent the symptoms associated with HIT. Sanchez-Perez et al. (2021) reported a >70% efficacy rate among the clinical studies examined in their review of low-histamine diets. They also found that only 32% of the excluded foods in a low histamine diet contained histamine. Foods containing other biogenic amines (BAs), like putrescine, were thought to be responsible for the increased symptoms related to HIT. They state that it is possible that certain foods, while containing no or low levels of histamine, may act as histamine liberators resulting in excess accumulation of histamine.2 There is also great heterogeneity in the foods recommended for a low-histamine diet. Fermented food products and beverages were consistently recognized as a primary food group to be avoided.
Decreasing the amount of histamine in the diet has been shown to decrease symptoms related to HIT. Following a low histamine diet can be confusing as there is a lack of consensus as to which foods should be included versus excluded. It can also be difficult for individuals to monitor the intake of histamine from the diet as there are no labeling requirements on foods for histamine.2 The daily intake of histamine, on average, is 1000mg/kg. Healthy individuals should be able to metabolize this amount without any problems.5 The recommended range for those undertaking a low-histamine diet is between 5-50 mg/kg. Some experts suggests that even lower levels are necessary and recommend an intake of foods with histamine levels below 1 mg/kg.2 Supplementation with DAO may also prove beneficial in reducing symptoms. Manzotti et al. (2016) demonstrated that individuals with DAO activity <3U/mL were highly likely to have HIT and those with DAO activity <10 U/mL were likely to be intolerant. Histamine intolerance was not expected in individuals with DAO activity >10U/mL.8
Biogenic Amines and a Low-Histamine Diet
Fermented foods (cured cheese, sausages, fish, fermented foods, certain vegetables) and fermented beverages (wine and beer) contain biogenic amines (BAs). These BAs are produced when amino acids undergo decarboxylation by substrate specific decarboxylase enzymes.5 The BA, histamine, is formed from the amino acid histidine. Other common BAs in foods include tyramine, putrescine, phenylethylamine, spermine, spermidine, cadaverine, and agmatine.5, 9 High amounts of histamine have been found in semi-cured and grated cheeses—particularly parmesan and bleu cheese, fermented foods such as fish paste and fish sauce, sauerkraut, fermented soy products, and cured sausages.2
The BA tyramine is found in some aged cheeses and can be related to increased symptoms such as increased blood pressure and migraines in HIT individuals.3 Other substances and foods may affect histamine levels. Foods high in putrescine (citrus fruits, bananas, and fermented foods—sausages, soy products, and cabbage) may interfere with DAO activity in the intestines.2 Food sources of putrescine may also enhance the toxic effects of histamine.5 Foods high in any of these BAs should be avoided on a low-histamine diet as they may affect the metabolism and degradation of histamine.3
Alcohol and Nutritional Deficiencies May Affect Histamine Levels
Alcohol and certain medications may elicit a release of histamine or inhibit MAO and DAO.5, 1 Consumption of alcohol can also increase the toxic effects of histamine. This results in competitive inhibition as the acetaldehyde produced in the breakdown of alcohol competes with histamine for the enzyme aldehyde dehydrogenase, resulting in increased histamine.2 It is worth noting that a deficiency in any of the cofactors needed by the enzymes used in the metabolism of histamine may impair its biotransformation and elimination, resulting in increased systemic levels of histamine as well. Therefore, nutrient deficiencies may need to be addressed for those that do not get sufficient relief solely from dietary avoidance of histamine-rich foods. For example, cofactors used by DAO include copper, vitamin C and Vitamin B6. A deficiency in any of these would affect DAO synthesis.3
Factors Affecting Histamine Levels in Foods—Length of Storage, Temperature, Vacuum Packing, and Additives
It is impossible to completely eliminate histamine from the diet. There are many factors that determine the content of BA and histamine including freshness, pH, food source, salt content, content of proteins, processing and storage. There are several factors involved during the manufacturing process that affect the BA concentration in foods. Increased storage times increases the amount of BAs formed by the microorganisms present in food during storage. For those with HIT it is important to choose fresh foods sourced with a minimal amount of contamination prior to and during processing. Choosing foods as fresh as possible helps decrease the histamine content, providing less time for the creation of histamine from the increased bacterial decarboxylase activity seen during storage.2 Foods with a shorter period of fermentation may also have lower BA levels. Several bacterial groups have been shown to have decarboxylase activity and can thereby increase BAs and histamine specifically. These include yeasts found in cheeses and some bacteria species found in seafood, wine, fermented soy products, and yogurt.2, 5
An increase in BAs is also noted as storage temperatures increase. It is therefore a good idea to keep histamine-rich foods chilled during storage. Storing and processing fish at or below temperatures of 39.9 degrees Fahrenheit has been shown to decrease the amount of histamine that is formed.5
Choosing foods that have been vacuum packed may also decrease the amount of BAs that develop during storage, though some studies show no benefit to this type of storage. Other processes during manufacturing that may decrease the rate of BA formation include the addition of substances such as ascorbic acid, malic acid, and citric acid, pasteurization, smoking, and irradiation. Cooking does not appear to alter the content of BAs.5
Miscellaneous Tidbits
Premenopausal women with HIT may find that they tolerate histamine containing foods better during the luteal phase of their cycle and less so during the follicular phase as DAO activity has been found to be higher during the luteal phase. 10 This could explain one of the causes of increased gastrointestinal symptoms experienced by some women during menstruation.
Supplements that Lower Histamine
The following supplements can help your body metabolize and get rid of histamine:
- Vitamin C
- Quercetin
- Probiotics
- Cordyceps or Reishi mushrooms
- Eleuthero
- N-Acetyl Cysteine
- SAMe
- Potassium bicarbonate
- Sodium bicarbonate
- Nettles
- Luteolin
- Riboflavin
- Niacinamide
- Molybdenum
- Bromelain
- Rutin
- Copper
- B6
Low-Histamine Diet
- Avoid alcohol
- Select all foods as fresh as possible
- Store foods chilled or frozen
- Vacuum wrapped foods may slow down bacterial formation of histamine
- Avoid fermented products— cabbage (kimchi, sauerkraut), pickles, fish, sausages, and soy (tamari, tempeh, tofu, natto, etc.)
- Avoid cured, semi-cured and/or aged cheeses
- Avoid fermented beverages—beer, wine, kombucha
- Avoid fermented dairy and alternative dairy products—yogurt and kefir made from cow, goat, hemp, soy, coconut, etc.
- Avoid canned fish, particularly scombroid species (mackerel, tuna, sardines, and anchovies)
- Avoid cured or fermented meats—sausage, bacon, lunch meats, hot dogs, salami, etc.
- Avoid canned or processed vegetables
- Avoid certain vegetables (tomato, eggplant, and spinach)
- Avoid shellfish and certain fish (oily fish—salmon— is higher than white fish—mahi-mahi)
Avoid foods containing Putrescine and other Biogenic Amines
- Citrus fruits
- Bananas
- Kiwi
- Grapes
- Soybeans
- Olives
- Tea—Black & Green
- Papaya
- Avocado
- Strawberries
- Pumpkin
- Pineapple
- Cherries
- Nuts
- Beer & Wine
- Chocolate
- Fermented/Soured dairy products—yogurt, kefir, sour cream, buttermilk, etc.
Potential Histamine Liberators
- Citrus fruits
- Seafood
- Papaya
- Tomato
- Nuts
- Pineapple
- Spinach
- Chocolate
- Strawberries
- Wheat Germ
- Gluten—Rye, Wheat, Barley
- Some spices—anise, cinnamon, cloves, curry powder, paprika, nutmeg
A low histamine diet can be followed for 1-2 weeks. If there aren’t any noticeable changes in how one feels, then there is no reason to continue and the cause of the health problem is unlikely to be histamine.
References
1. Maintz L, Novak N. Histamine and histamine intolerance. The American Journal of Clinical Nutrition. 2007;85(5):1185-1196. doi:10.1093/ajcn/85.5.1185
2. 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? Nutrients. 2021;13(5):1395. doi:10.3390/nu13051395
3. Hrubisko M, Danis R, Huorka M, Wawruch M. Histamine Intolerance—The More We Know the Less We Know. A Review. Nutrients. 2021;13(7):2228. doi:10.3390/nu13072228
4. Chiu IM, von Hehn CA, Woolf CJ. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci. 2012;15(8):1063-1067. doi:10.1038/nn.3144
5. Doeun D, Davaatseren M, Chung M-S. Biogenic amines in foods. Food Sci Biotechnol. 2017;26(6):1463-1474. doi:10.1007/s10068-017-0239-3
6. Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou M del C. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020;10(8):1181. doi:10.3390/biom10081181
7. Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021;13(4):1262. doi:10.3390/nu13041262
8. Manzotti G, Breda D, Di Gioacchino M, Burastero S. Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol. 2016;29(1):105-111. doi:10.1177/0394632015617170
9. Naila A, Flint S, Fletcher G, Bremer P, Meerdink G. Control of Biogenic Amines in Food—Existing and Emerging Approaches. J Food Sci. 2010;75(7):R139-R150. doi:10.1111/j.1750-3841.2010.01774.x
10. Hamada Y, Shinohara Y, Yano M, et al. Effect of the menstrual cycle on serum diamine oxidase levels in healthy women. Clinical Biochemistry. 2013;46(1):99-102. doi:10.1016/j.clinbiochem.2012.10.013
