Low histamine food list

Histamine isa tissue amine and chemical molecule that gets biosynthesized by the decarboxylation of the amino acid, histidine. The biosynthesis of histamine is catalyzed by the presence of L-histidine decarboxylase and the co-factor pyridoxal 5’-phosphate or the active form of B6 (the chemical reaction is presented in figure 1 below). Of all biogenic amines observed in foods, the excessive levels of histamine and tyramine are considered highly toxic and produce unwanted effects in the human body.

In 1910, the pioneer researchers in the biogenic amines, Dale and Laidlaw, clarified the physiological and pathophysiological functions of histamine in our bodies. Biosynthesized histamine is stored in basophils, mast cells, gastric enterochromaffin cells, lymph nodes and thymus.

Histamine is involved in several physiological functions such as stimulation of gastric acid secretion and nociceptive nerve fibers, alteration of blood pressure, inflammation, increased vascular permeability, cytokine production, smooth muscle contraction and vasodilatation. Histamine is also synthesized in the brain, specifically in the neurons present in the posterior region of the hypothalamus. As a neurotransmitter, it maintains wakefulness and carries impulses like pain and itching sensations. Of all G-protein-coupled receptors, H1, H2, H3 and H4 interact with histamine and activate the signal transduction pathways, thereby initiating the biological mechanisms.

Also, histamine actively participates in local immune response, immunomodulation, hematopoiesis, day-night rhythm, wound healing effects and regulation of histamine- and polyamine-induced cell proliferation and angiogenesis in various tumor models and intestinal blood supply. As per the concentration of histamine present in the plasma, different activities are exhibited as mentioned in the below table 1 (Adapted from Mainz et al., Am. J. Clin. Nutr. 2007).

There are two important pathways in the histamine metabolism, namely diamine oxidase (DAO)-dependent and histamine N-methyl transferase (HNMT)-mediated metabolic pathways. DAO facilitates the oxidative deamination of the primary amine group of histamine. Conversely, in the second pathway, the enzyme HNMT converts histamine into 1-methylhistamine through methylation of the secondary amine “N” of the imidazole heterocyclic ring.

In a nutshell, based on the need for physiological processes in the human body, the deamination and methylation reactions are catalyzed by the enzymes, DAO and HNMT respectively. DAO converts histamine into imidazole 2-acetaldehyde, followed by imidazole acetic acid and finally, imidazole acetic acid riboside is formed. Conversely, Histamine is metabolized in the presence of HNMT to obtain methylimidazole acetic acid through the production of intermediate methylimidazole acetaldehyde. It is worth noting that the conversion of histamine into different by-products is the protective role of DAO and HNMT against excess histamine, either from ingested foods or produced by the intestinal microbiota. Therefore, both enzymes DAO and HNMT help balance and maintain optimum levels of histamine in the human body.

The deficiency and single-nucleotide polymorphisms (SNPs) of enzymes including L-histidine decarboxylase, DAO and HNMT may be suggested an influential role in histamine intolerance. Research studies have revealed that more than 50 SNPs in the DAO-encoding gene have been detected to date. Some of key SNPs (namely rs10156191, rs1049742, rs2268999 and rs1049793) discovered in Caucasian people could produce a protein with impaired activity. Individuals of Asian and African decent may be more affected by SNPs rs45558339 and rs35070995 which have also been reported to show DAO enzyme deficiency. On the another hand, the main SNP related to HNMT (rs11558538) has been associated with reduced HNMT activity. Overall, these SNPs lead to reduced or deficient enzyme activity, which increases the levels of histamine in the plasma and is then typically followed by a histamine intolerance reaction (particularly in these individuals with DAO and HNMT SNPs – or genetic mutations).

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Histamine and other biogenic amines such as tyramine, putrescine and cadaverine are present in varying concentrations in different foods, which increases as they age. The following determines the formation of biogenic amines in food:

1. availability of free amino acids
2. presence of decarboxylase-positive microorganisms 
3. ideal conditions for bacterial growth and
4. decarboxylase activity

Either food that we consume or proteolysis reactions during food processing and storage may yield free amino acids. Plenty of bacterias and a few yeast types demonstrate high L-histidine decarboxylase activity (assisting the conversion of histidine into histamine) as a result, this increases histamine production. It’s worth noting that high levels of histamine and other biogenic amines are typically found in products of microbial fermentation which include processed meats, aged cheeses, sauerkraut and wine, also in microbially spoiled food. So, the presence of histamine, tyramine, putrescine and cadaverine are all considered as indicators of food quality. Other biogenic amines can combine with histamine and cause intolerance or adverse effects. Besides histamine-rich food, several foods such as citrus fruits, a few types of fish and licorice actually contain less histamine; however, they can stimulate a histamine release from mast cells. The mechanism behind this stimulation of endogenous histamine from these particular foods has not yet been discovered. The concentration of histamine in various food categories is presented in Table 2.

Table 2. Histamine content in various types of food categories (Adapted from Bover-Cid et al., 2014).

Although histamine is involved in a copious number of physiological mechanisms in our bodies, the ingestion of foods containing high levels of histamine causes damaging effects on the body. The balance of histamine is reliant on the body’s histamine degradation systems functioning properly; this is required for the body to appropriately regulate the excess levels of histamine.

Histamine intoxication is also a type of food poisoning that can happen after the consumption of foods with high histamine levels (higher than 500 mg/kg) which actually subjugates the degradation mechanisms. In 2018, a meta-analysis was performed to identify the foods, which typically cause histamine intoxication. The study covers research data between 1959 and 2013 that focus on several studies of histamine intoxication and revealed that the causative food in 98% of the cases accounted for was fish and the remaining cases were due to cheese.

Histamine intoxication is essentially characterized by a short incubation period with low to moderate severity and subsiding in a few hours. The symptoms of histamine intoxication affect the skin, gastrointestinal tract, hemodynamic and neurological functions.

Histamine intolerance is an impaired ability to metabolize ingested histamine and is referred to as enteral histominosis, a condition caused by a sensitivity to dietary histamine. It is a disorder which originates from a decreased histamine degradation capacity in the intestine due to diminished DAO activity. This lower DAO activity results in the accumulation of histamine in plasma and creates adverse effects.

Because of the ubiquitous presence of four histamine receptors in different parts of the human body, especially abundant in the gastrointestinal tract and its surrounding regions, histamine intolerance mainly triggers gastrointestinal and extra-intestinal related clinical symptoms such as allergic response, nasal congestion, rhinorrhoea, the dilation of blood vessels and inflammation of airways. In an attempt to better understand the extent ofgastrointestinal issues as they relate to histamine intolerance, a study was conductedin 133 patients with histamine intolerance and the symptoms were evaluated. Of all clinical manifestations, 92% of patients had issues pertaining to the gastrointestinal system such as abdominal distention as the most common and serious symptom.

Other symptoms including diarrhea, abdominal pain, constipation and post-meal fullness were observed in 55-73% of patients. The appearance of more than three symptoms involving different organs shows the complex nature of histamine tolerance and the abundant existence of histamine receptors in different systems, having a mean of 11 clinical manifestations per patient. Secondary to the gastrointestinal tract, malfunction in the cardiovascular, nervous, respiratory and dermatological systems were detected in the patients; the detailed symptoms from the study are listed below.

Numerous studies have showed that the prevalence of the symptoms related to histamine intolerance is connected with the deficiency of DAO in the individuals. The study revealed that more than 80% of 316 patients showing a range of clinical symptoms associated with histamine intolerance and remarkably lower plasma DAO activity as compared to the control group.

The retrospective study demonstrated that gastrointestinal and dermatological symptoms along with headaches were observed in 14 patients with the diagnosis of histamine intolerance and significantly reduced DAO activity.

In another study with 27 patients, with regard to headache symptoms, the deficiency of DAO was reported in 23 patients. Further, the study claimed that 85% of individuals might show histamine intolerance due to the DAO deficit. In the same study, researchers found that patients with a low histamine diet for four weeks had revealed a notable increase in DAO activity and 90% of patients showed the reduction or remission in the frequency of headaches.

A low-histamine diet and avoidance of high histamine food and histamine releasing foods would be primarily advisable to reduce the clinical manifestations of histamine intolerance. Also, the supplementation of DAO (encapsulated porcine kidney DAO) has recently been regarded as a complementary therapeutic approach to increase dietary histamine degradation in people who have a deficiency or impairment of the DAO enzyme in the intestine.

The following things can help determine if you have histamine intolerance.

• Crosslink between food consumption and histamine-elicited symptoms
• Identification of the list of foods that trigger the symptoms
• Determine the histamine content for the foods which causes symptoms
• Exclusion of other causes including allergic, metabolic and toxic concerns
• Analysis of DAOSNPs (or genetic mutations)
  o rs45558339
  o rs35070995
  o rs10156191
  o rs1049742
  o rs2268999
  o rs1049793 
• Analysis of HNMTSNPs (or genetic mutations)
  o rs11558538
  o rs1050891
  o rs758252808
  o rs745756308 
• Determine the DAO and HNMT content in the plasma using ELISA-type immunoassay and radioimmunoassay tests as well as what their activity levels are in the intestinal mucosa.
• Design a double-blind, placebo-controlled clinical trial of oral histamine provocation in combination with the determination of serum histamine levels and the characteristic physical parameters such as erythema, blood pressure and heart rate.

A specific dietary recommendation for a low-histamine diet is not readily available; however, the below list of foods could be very useful if you wish to lessen the symptoms of histamine intolerance.

So if you think you have a histamine intolerance issue, consider eating these foods:

• Butter, cream cheese and mozzarella
• Cooled/frozen/fresh Chicken
• Egg
• Fresh fruits – except plantains
• Fresh meat (cooled or frozen)
• Fresh pasteurized milk and milk products
• Fresh vegetables –except spinach, eggplant and tomatoes
• Grains and related products such as rice crispbread, rice noodles, white bread, rye bread, oats, puffed rice crackers, millet flour and pasta
• Herbal teas
• Milk substitutes – goat milk and sheep milk
• Most cooking oils – suitability should be checked before use
• Most fruit juices excluding citrus fruits
• Most leafy herbs – suitability should be checked before use
• Specific fresh/frozen fish types – hake, trout and plaice

In addition, the food list that should be excluded from a low-histamine diet in effort to reduce the frequency of histamine intolerance is listed below:

• Milk
• Lentils
• Chickpeas
• Soybeans
• Mushrooms
• Shellfish
• Eggs
• Fermented soy derivatives
• Eggplant
• Banana
• Kiwi
• Pineapple
• Plum
• Nuts
• Chocolate
• Cured and semi-cured cheese
• Grated cheese
• Oily fish
• Canned and semi-preserved oily fish derived products
• Spinach
• Tomatoes
• Fermented cabbage
• Citrus
• Strawberries
• Wine and Beer

Some of the foods, such as strawberries, papaya, pineapples, plums, kiwi, banana, citrus fruits, have been reported for its properties to stimulate the release of histamine endogenously. However, the mechanism responsible for the release of histamine has not yet been discovered. The safety and efficacy of a low histamine diet have been displayed in several clinical studies and significant results derived from clinical studies that showed the improvement or total remission of symptoms connected with DAO deficiency and histamine intolerance.

A prospective study was carried out for four weeks with a low histamine diet in 35 patients with headache and other secondary symptoms such as urticaria, arrhythmia, diarrhea and asthma to evaluate the plasma histamine levels and DAO activity. Interestingly, a 77% reduction in symptoms, a 73% increase in DAO activity, along with no changes in plasma histamine levels were found.

In another prospective study with 36 patients, the low histamine diet was supplemented for 2 weeks and a 33% reduction in atopic dermatitis was reported. One more prospective study comprised of 45 patients was conducted for a low histamine diet over 4 weeks to evaluate chronic headache, dermatological and respiratory symptoms1. It reported that an 82% reduction in dermatological and respiratory symptoms and a 68% reduction in chronic headache was achieved.

The retrospective study on a low histamine diet was performed for 4 weeks in 157 patients to assess chronic idiopathic urticaria (CIU). The results revealed a 46% reduction in CIU. In another retrospective study evaluation of CIU along with gastrointestinal symptoms, an estimation of DAO activity was carried out in 56 patients kept on a low histamine diet for 3 weeks. Notably, the study showed a significant 75% reduction of CIU and gastrointestinal tract symptoms, whereas there were no considerable changes in DAO activity in the plasma of the patients.

Focusing on gastrointestinal symptoms and DAO activity, another study involved 63 patients who were supplemented with a low histamine diet for 7-18 months, of these79% reported a reduction in gastrointestinal symptoms and a 52% rise in DAO activity was noted.

Oral supplementation of DAO has been proposed by several researchers to improve the dietary histamine degradation system. In 2017, the European Commission provided the approval to launch DAO supplements as food for special medical purposes.

According to the literature on DAO enzymes, porcine kidneys are a major source of DAO. A number of studies have proved the ability of porcine kidney derived DAO enzymes to degrade excessive levels of histamine and other biogenic amines in vitro. To date, only a few interventional studies have been reported for the pharmacological efficacy of DAO supplementation inpatients with histamine intolerance.

A randomized, double-blind, placebo-controlled, crossover provocation study, for 39 patients with histamine intolerance symptoms such as headache, gastrointestinal and skin related complaints, was executed using histamine containing and histamine-free tea with DAO capsules or placebo. As compared to placebo controls, a statistically significant reduction of histamine-elicited symptoms was observed in the group taking DAO supplementation. In another randomized double-blind clinical trial, 100 patients with episodic migraine were treated with DAO supplements for one month. The duration of migraine attacks was significantly reduced in the group taking the DAO supplements.

An open-label pilot study proved the efficacy of DAO supplementation for one month of intervention in 28 patients. The study was focused to assess the various symptoms including gastrointestinal, cardiovascular, respiratory and skin issues, together with reduced DAO levels. The study showed a significant improvement in all histamine intolerance symptoms. Concerning DAO plasma levels, 61% of patients revealed a modest increase in DAO levels.

Guidelines of the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Association of Allergologists (AeDA), and the Swiss Society for Allergology and Immunology (SGAI) suggested a phased approach (three-step dietary adjustment; presented in Table 3) which not only allows a person to determine their histamine tolerance but also helps them to avoid the intolerance symptoms.

Table 3. Three-step dietary adjustment (Adapted from Imke Reese et al., 2017).

Histamine intolerance can trigger various uncomfortable symptoms like itchy skin, urticaria, nausea, headaches, digestive problems etc. It has been reported that a histamine-free diet is very helpful in the treatment of chronic spontaneous urticaria. Therefore, a low-histamine diet is highly beneficial for people who develop untoward effects in response to foods containing histamine. Many nutritionists and dieticians suggest that an individualized approach be taken for curbing histamine-induced allergic symptoms. Persons suffering from histamine intolerance must ensure not to miss out on essential nutrients while following a low histamine or histamine-free diet and should seek advice from a dietician or nutritionist.