High Histamine food list
1. Histamine and its physiological functions
Histamine is a type of biogenic tissue amine – L-histidine decarboxylase (HDC) and the cofactor pyridoxal 5’-phosphate or the active form of vitamin B6 mediate the conversion of histidine into histamine (its chemical reaction is represented in figure 1). The key enzymes such as diamine oxidase (DAO) and histamine N-methyltransferase (HNMT) degrade histamine into different by-products.
Figure1. Biosynthesis of Histamine from L-histidine.
As perthe International Union of Pure and Applied Chemistry (IUPAC)nomenclature, the chemical name of histamine is 2-(1H-imidazol-4-yl)ethanamine.
Essentially, the biogenic amines such as histamine, tyramine, putrescine and cadaverine at low concentrations have been reported to possess hazardous adverse effects on the human body. The storage of histamine is principally in lymph nodes, basophils, mast cells, gastric enterochromaffin cells and thymus. There are four histamine receptors, namely, H1, H2, H3 and H4, distributed in various parts of the human body. Histamine binds with respective receptors and displays the pharmacological effects.
Histamine exhibits many biological processes,
- Alteration of blood pressure
- Stimulation of gastric acid secretion and nociceptive nerve fibers
- Mediating the inflammation process and immunomodulation
- Increased vascular permeability and cytokine production
- Smooth muscle contraction and vasodilatation
- It is considered a neurotransmitter
- Wound healing effects
- Modulates day and night rhythms
- Regulation of histamine- and polyamine-induced cell proliferation and angiogenesis
2. Functions of DAO and HNMT
Enzymes such as diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT) are actively involved in the metabolism of histamine by negating high levels of histamine in the human body.
Other names of DAO are histaminase and amiloride-binding protein that facilitates the oxidative deamination of histamine. The critical role of DAO is to eliminate the excess histamine and regulate the levels of histamine entering the blood circulation from the digestive tract. The expression of DAO is found in a few specific tissues such as the placenta, kidney, small intestine and ascending colon.
The primary function of HNMT controls histamine expression and its biosynthesis by N-methylation of histamine in various organs including kidney, liver, colon, spleen, spinal cord cells, ovaries, bronchi and trachea.HNMT selectively metabolizes histamine in the central nervous system. DAO can metabolize not only histamine, but it also metabolizesother biogenic amines like cadaverine and putrescine.
3. Histamine receptors and its pharmacological functions
Histamine unveils its pharmacological effects through binding to various histamine receptors (H1, H2, H3 and H4), thereby initiating appropriate pharmacological activities.
- H1 histamine receptor – it is ubiquitously present in the peripheral nervous system and smooth muscle. H1 receptor has been known to have an important role in allergic response and its activation on smooth muscle leads to vasoconstriction. Other activities such as increased vessel permeability, blood vessel dilatation, stimulation of sensory nerves in the airways and bronchoconstriction have resulted in the activation of the H1 receptor. Also, its activation further facilitates the chemotaxis of eosinophils, followed by few symptoms including nasal congestion, rhinorrhoea and sneezing. The stimulation of the H1 receptor in the cerebral cortex could interrupt potassium channels in neuronal cell membranes, followed by the depolarization of the neurons and an increase in neuronal excitation. As a neurotransmitter, histamine maintains wakefulness and conducts nociceptive pain impulses.
- H2 histamine receptor – parietal cells in the stomach, heart, immunecells and vascular smooth muscle have an H2 receptor. Activation of the H2 receptor results in vasodilation and gastric acid secretion that is essential for digestion.The binding of histamine with the H2 receptor also causes activation of neutrophils and basophils, a reduction in the chemotaxis, stimulation of suppressor cells, natural killer cell activity and lymphocyte proliferation. The combination of H1 and H2 receptors leads to rhinorrhoea and inflammation of nasal airways.
- H3 histamine receptor – it is referred to as a presynaptic auto receptor, mainly present in nerve cells and broadly distributed in all regions of the central nervous system. However, it is highly expressed in the hippocampus, cortex, caudate nucleus, thalamus, hypothalamus and olfactory tubercle. The availability of H3 receptor throughout the cortex plays a critical role in the modulation of several neurotransmitters such as GABA, acetylcholine, norepinephrine and dopamine in the central and peripheral nervous system.
- H4 histamine receptor – it is found on immune cells and tissues that include the thymus, bone marrow, the spleen and peripheral blood leukocytes. Besides immune cells, the H4 receptor is present in the lung, liver, colon and epicanthus. Activation of the H4 receptor leads to the chemotaxis of eosinophils and the upregulation of adhesion of biomolecules.
4. Effects of the high amount of histamine in plasma
Table 1. Effects of various concentrations of histamine.
|Histamine concentration in plasma (ng/mL)||Pharmacological and clinical effects|
|0-1||Optimal concentration – no histamine intoxication and poisoning|
|1-2||Escalation in heart rate and gastric acid secretion|
|3-5||Tachycardia, headache, pruritus, urticaria and flush|
|6-8||Reduction in arterial pressure|
|~ 100||Cardiac arrest|
5. Histamine intolerance
Histamine intolerance or enteral histaminosis is an imbalance between the histamine degradation system and metabolism of ingested histamine. Basically you’ve eaten more histamine-producing things than your body can get rid of, so you’re dealing with an imbalance. Histamine intolerance is also known as a medical condition that occurs due to reduced diamine oxidase (DAO) activity, which leads to the accumulation of histamine in plasma and creates damaging effects.
Histamine intolerance affects at least 1 percent of the global population. It’s interesting to note that, of those, around 80% are middle-aged women.
With an abundant presence of histamine receptors throughout the human body, histamine intolerance presents most of the clinical manifestationsin various organs such as cardiovascular (tachycardia, palpitations and collapse), gastrointestinal tract (abdominal pain, constipation, diarrhea, emesis, bloating, distention, flatulence, nausea, diarrhea and postprandial fullness), nervous system (dizziness and headache), respiratory system (dyspnea, nasal congestion, rhinorrhea and rhinitis) and skin (eczema, flush, inflammation, pruritus and urticaria).
Histamine intolerance is of two different types,
- Primary histamine intolerance syndrome
- Secondary histamine intolerance syndrome
Primary Histamine Intolerance
Secondary Histamine Intolerance
- Genetic inheritance: genetic variants found in DAO, HNMT, HDC and methyl tetrahydrofolate reductase (MTHFR).
- Medications: few drugs such as Chloroquine, clonidine, isoniazid, diclofenac, cimetidine and verapamil.
- Nutrient deficiencies: some nutrients namely methionine, copper, zinc, vitamins B1, B2, B6, B12 and folate.
- Hormone imbalances: excessive hormone (Oestrogen can induce mast cell degranulation) and insufficient hormone levels (Adrenal fatigue).
- Environment: hazardous environmental conditions like dust mites, mildew, mold and pollens. Environmental estrogenic pollutants can also cause mast cell degranulation.
- Gastrointestinal disorders: Crohn’s disease, Celiac disease, irritable bowel syndrome, small intestinal bacterial overgrowth and ulcerative colitis could lead to inflammation in our bodies and also cause clinical manifestations that are similar tohistamine intolerance. In addition, these diseases even hamper the biosynthesis of DAO and HNMT.
6. Genetic polymorphism of L-histidine decarboxylase, Diamine Oxidase and Histamine N-methyltransferase
Single nucleotide polymorphisms (SNPs) in any gene often create an inactive state of a particular protein. The genes encoding enzymes L-histidine decarboxylase, diamine oxidase and histamine N-methyltransferase have been extensively studied for their SNPs. These SNPs result in the formation of aprotein with altered activity, followed by histamine build up and therefore produce the symptoms of histamine intolerance.
- rs17740607 and rs2073440.
- rs45558339, rs35070995, rs10156191, rs1049742, rs2268999and rs1049793.
- rs1801105, rs11558538, rs1050891, rs758252808, rs2052129 and rs745756308.
7. Drugs that induce histamine intolerance
- Anaesthetics (Thiopental and prilocaine)
- Analgesics such as (Morphine, pethidine, acetyl salicylic acid, metamizole and diclofenac sodium
- Antibiotics (Isoniazid, amoxicillin, cefuroxime, cefotiam, pentamidine, clavulanic acid, chloroquine and paromomycin)
- Antihypertensives (Verapamil, Dihydralazine and alprenolol)
- Expectorants such as acetylcysteine and ambroxol
- Muscle relaxants (Pancuronium, D-tubocurarine and alcuronium)
- X-ray contrast media
8. High histamine food list
|Vegetables||Eggplant, pumpkin, sauerkraut, spinach, tomato, avocado, olives, pickled and canned vegetables.|
|Fruits||Citrus fruits, banana, pineapple, cherry, cranberry, currant, date, loganberry, nectarine, orange, grapefruit, prunes, plums, raisins, raspberries, strawberries, fruit dishes, jams and fruit juices made with high histamine content ingredients.|
|Meat, poultry and fish||All fish (if they are not freshly caught), shellfish, refrigerated meats, processed, smoked and cured meats.|
|Eggs||Raw egg whites, eggnog, hollandaise sauce and milk shakes.|
|Fats and oils||All fats and oils with preservatives and colorants, prepared gravy, commercially available salad dressings and hydrolyzed lecithin|
|Spices and herbs||Anise, nutmeg, cinnamon, cloves, curry powder, paprika and foods with spices labelling.|
|Nuts and seeds||Walnuts and cashews|
|Legumes||Soy, lentils, beans and peanuts|
|Bread and cereals||Dry dessert mixes, baking mixes, foods cooked in oils consisting of butylated hydroxy anisole, butylated hydroxy toluene and hydrolyzed lecithin|
|Milk and dairy||All cheese, buttermilk and yogurt (except particularly cultured with a low histamine probiotics)|
|Sweeteners||All artificial sweeteners, processed sugars, candies, confectionery, cake decorative consumables, flavoured syrups, prepared dessert fillings, icings and frostings and spreads with histamine-rich ingredients.|
|Beverages||Coffee, carbonated soda and drinks, alcohol when in large amounts, all tea and drinks with flavour or spices.|
|Miscellaneous food items||Chocolate, cocoa, carob, products with artificial flavours, colorants and preservatives, flavoured gelatin, crustaceans, mincemeat, prepared relishes and olives, soy sauce, canned foods, ready meals, pickled and fermented foods, vinegar, yeast and its extracts, wheat germ, benzoates, sulphites, nitrites, glutamates, food dyes and commercial ketchup.|
8.1 Food list that can release endogenous histamine
- Most citrus fruits
- Walnuts and peanuts
- Plums, kiwi, banana, papaya and pineapple
- Wheat germ
- Additives such as benzoate, nitrites, glutamate, food dyes and preservatives
8.2 Foods that can inhibit diamine oxidase
- Black tea and mate tea
- Energy drinks
9. Dietary recommendation for histamine intolerance
- This step is to reduce the symptoms to a large extent
- A mixed diet focusing on vegetables and less biogenic amine containing food intake, nutrient optimization, modification in meal composition and a balanced diet are the key recommendations.
- This phase should be an expansion of food choices under the consideration of individual risk factors such as stress, medications, menstruation and other biological parameters.
- The recommended objectives are the re-introduction of suspected foods and the establishment of individual histamine tolerance patient records and history.
- A balanced supply of nutrients and better quality of life would be considered in this phase and individual nutritional recommendations can be created and implemented.
10. Diagnosis and Diagnostic Parameters in Histamine Intolerance
- What are the expected clinical manifestations and the implementation ofappropriate diagnostic methods for histamine intolerance?
- Any substantial evidence for the pathomechanism of histamine intolerance should be collected, documented and further researched?
- Which are the parameters best utilized in the diagnostic work-up and what is their reliability?
10.1 Presence of DAO in serum:
10.2 Histamine 50-skin-prick test:
10.3 Intestinal enzyme activity assessment:
10.4 Histamine concentration in stool samples:
10.5 Plasma levels of histamine:
10.6 Evaluation of methylhistamine in urine:
11. Connecting dots between MTHFR mutation, methylation and histamine intolerance
- Biosynthesis of carnitine, CoQ10, nitric oxide and metabolism of homocysteine.
- Mainly involved the phase II metabolic pathway thatfacilitates the detoxification of catecholamines, hormones and heavy metals.
- Also, supports the production of glutathione and the sulphation process.
- Assists the bile formation via phosphatidylcholine synthesis.
- Provides the energy in the form of ATP through the biosynthesis of carnitine, CoQ10, creatine, adenosine and NADPH.
- Helps in antigen recognition, cell differentiation and maturation of immune cells.
- Regulates immune responses against antigens and histamine breakdown.
- Controls viral life cycles and tumor growth.
- Involved in the oestrogen metabolism and production of sperm and ova, and maintaining fetal growth.
- Production and breakdown of acetylcholine, adrenaline, dopamine, melatonin, myelin, noradrenaline and serotonin.
12. How methylation or Methylfolate helps in histamine intolerance?
- Eating a low histamine diet
- Cutting out any probiotics or foods (yogurt) which contain lactobacilli strains (consider a spore-based probiotic for optimal effectiveness instead)and
- Supplementing with L-5-Methylfolate to increase your body’s methylation and capacity to metabolize the excess histamine
- Taking a DAO enzyme supplement product to help metabolize the excess histamine