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The Histamine Connection: Food and Environmental Allergies


nutrition articles

July 2014

The Histamine Connection: Food and Environmental Allergies

Written by Millie Lytle ND, MPH, CNS

What is Histamine?

Histamine is a nitrogenous compound produced by the body that regulates physiological function in the digestive system, acts as a neurotransmitter, mediates immune responses and is directly involved in the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by white blood cells in nearby connective tissues. Histamine allows white blood cells and proteins to pass through blood capillaries to allow them to target pathogens in infected tissues. It is released into the cells, extracellular body fluid, skin and mucous membranes with any allergic reaction. It produces wheal and flare reactions; typical symptoms like heat, redness, swelling and itching. Histamine is released in high amounts into the tissues within mast cells and blood stream in basophils, when an allergic trigger is introduced repeatedly over a course of 10 days or so.

Histamine-1 (H1) receptors are located in the upper respiratory tract - sinuses, eyes, ears and throat. Histamine-2 (H2) receptors are located in your gut. H2 receptors are triggered when you eat fo m ods that cause acid reflux, indigestion, nausea, gas, bloating and diarrhea. When histamine is low or high for a short period of time, there is no problem. Your body remembers what it’s allergic to, so each time, you have repeated exposure to an agent (food, environmental, pet) that your body has previously deemed “dangerous” it will repeat a cascade of symptoms. Each time histamine is released it allows more proteins to enter tissues. Over time, this reaction can cause hyper-permeability of proteins, where your blood becomes exposed to allergens and you react to more and more foods. Side effects can become even worse if the body is not breaking down histamine at a faster rate than it's being released.

The Histamine Connection could be the reason why you have the following -

  • chronic indigestion, bloating, GERD or ulcers.
  • chronic sinusitis, hay-fever or pet allergies.
  • allergies were worse than ever this year.
  • eczema.
  • leaky gut syndrome.
  • candida.
  • an autoimmune disease.

How Histamine Works

Each time your body reacts to an allergen it releases histamine. If your body is consistently producing histamine, it needs more histamine-breakdown enzymes to neutralize it. This is the reason why allergies can all of a sudden appear, even at 25, 45 or 75 years of age; Your histamine load has been building. Growing clinical evidence is showing that individuals who develop food and environmental sensitivities to otherwise healthy foods have high histamine counts and may not break down histamine as fast as they produce it, causing a massive allergy burden.

Histamine accumulation comes by way of being exposed to too many allergens (exposures to environmental allergens, eating a diet high in histamine or histidine containing or releasing foods and alcohol) combined with a problem in breaking down histamine. For instance, a few studies have shown an overlap in people experiencing allergies to grass pollens with carbohydrate sensitivity to cereal grains and peanuts.1

Problems with histamine degradation comes from one-of-two enzyme deficiencies: histamine N-methyl transferase (HMT in most cells and intercellular fluid) and Diamine Oxidase (DAO in the intestinal mucosa and kidney), allowing histamine to build up. Deficiency in the DAO enzyme system, found in the intestinal mucosa, has been suggested as the most probable cause of histamine intolerance. Diamine Oxidase (DO) is an enzyme that breaks down histamines through oxidation. Some foods and medications prevent your body from releasing DO or prevent DO from doing its job. DAO is expressed mainly in intestinal and kidney epithelial cells where the enzyme is stored in secretory vesicles at the basolateral plasma membrane and released into the extracellular space upon stimulation. Apparently, DAO is released locally to inactivate the excess of extracellular histamine to terminate its action. Besides taking care of endogenously released histamine, DAO in the gut is also responsible for catabolizing dietary histamine present in considerable amounts in certain food to prevent its uptake into the circulation.

HMT is present in most tissues of mammals but the enzyme is absent from body fluids. HMT is responsible for the inactivation of intracellular histamine that is either synthesized in the cell or taken up from the extracellular space, likely after binding to one of its receptors present on the cell surface.2 The fact that HMT is ubiquitously expressed indicates that many cells have to deal with histamine, emphasizing the wide-spread role of this mediator.3 It achieves its goal through the biochemical process of methylation.

Histamine levels and Nutrition

  • Eliminate Foods High in Histamine: Red wine, tomatoes, eggplant, and spinach, Ketchup, Sauerkraut, Sour cream, Yogurt/Kefir, Ripened cheeses (brie, camembert, gorgonzola, stilton), raw and cooked ground beef stored in refrigerator for 12 days, dry sausages such as salami, pepperoni, and chorizo, dry fermented sausages, smoked and dried fish.4
  • Eliminate any foods you are allergic to or that give symptoms (sneezing, congestion, tingling, itching, heartburn, hives). These might be some of the foods covered in other points.
  • Reduce Foods High in other “amines”: ie, Histidine, Tyramine
  • Reduces Foods that Trigger Histamine Release: citrus fruits (oranges and grapefruits), fish, shell fish, MSG and other food additives, papaya, strawberries, pork, pineapple, egg white, nuts (pecans, cashews, walnuts, pistachios, brazil nuts), peanuts, tomatoes, spinach, chocolate
  • Reduce DAO – blocking foods: Mainly wine and spirits.

Ethanol alcohol destructively attacks DAO, so even with a normal level of DAO, histamine saturation in blood will occur.5

  • Increase DAO promoting foods and Supplements4: Instead of an over the counter anti-histamine, go for the natural anti-histamines. Herbs and nutrients such as German Chamomile7, B6 and copper have anti-histamine effect. Here are some of the most promising nutraceuticals to alleviate histamine intolerance.

Bromelain was shown to reduce allergic sensitization and the generation of Allergic Airway Disease upon antigen challenge5,6. These results provide additional insight into Bromelain’s anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena.

Mangosteen (Garcinia mangostana L), when compared to Rubus suavissimus extract, inhibited the formation of a proinflammatory prostaglandin called E2 with relatively lower concentrations than the histamine release. These results suggest that the 40% ethanol extract of mangosteen has potent inhibitory activities of both histamine release and prostaglandin E2 synthesis8.

Quercetin, one of the citrus bioflavonoids and a cousin to vitamin C, inhibits cytoplasmic calcium level and NF-kappa B activation. Quercetin is also effective prophylactically, to prevent an allergy attack before the allergy trigger is present. In two pilot, open-label, clinical trials, Quercetin significantly decreased contact dermatitis and photosensitivity, two skin conditions that do not respond to conventional treatment. The researchers determined that Quercetin is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, when taken in sufficient doses orally.9

Chrysin, an extract from the plant passion flower (Passiflora incarnata) reduced histamine release from mast cells. The study showed that ability of chrysin to inhibit histamine was mediated by the modulation of intracellular calcium. In addition, chrysin decreased gene expression of pro-inflammatory cytokines such as, tumor necrosis factor-α, IL (interleukin)-1β, IL-4, and IL-6 in mast cells. Allergies can run in the family, so Chrysin may alter genetic susceptibility. The inhibitory effect of chrysin on the pro-inflammatory cytokine was nuclear factor-κB and caspase-1 dependent. Our findings provide evidence that chrysin lowers allergic inflammatory reactions by blocking histamine release and pro-inflammatory cytokine expression10.

Black Seed and one of its active constituents, thymoquinone, were separately used to treat stomach lesions in 40 male rats. The black seed treatment significantly decreased the number of mast cells and reduced the area of gastric erosions. Thymoquinone treatment was also able to reduce the number of mast cells and the severity of gastric mucosal lesions, but to lesser extent compared to the whole seed. Gastric tissue histamine levels found to be increased in rats with stomach ulcers and the Black Seed as well as the thymoquinone reversed these histamine increases. Black seed was therefore concluded as having anti-peroxidative, antioxidant and antihistaminic effects, which allow it to protect the stomach and digestive tract from alcohol and other carcinogens11.

Several strains of Probiotics native to the small and large intestines have been shown to positively prevent and treat sensitive skin11,12. Therefore probiotics may be effective as a prevention and treatment for reducing allergic rashes, itching and hives.


  1. Martens MSchnoor HJMalling HJPoulsen LK. Sensitization to cereals and peanut evidenced by skin prick test and specific IgE in food-tolerant, grass pollen allergic patients. Clin Transl Allergy. 2011 Dec 9;1(1):15. doi: 10.1186/2045-7022-1-15.
  2. Hubert G. Schwelberger sourced from
  3. Yamauchi KSekizawa KSuzuki HNakazawa HOhkawara YKatayose DOhtsu HTamura GShibahara STakemura M, et al.Structure and function of human histamine N-methyltransferase: critical enzyme in histamine metabolism in airway. Am J Physiol. 1994 Sep;267(3 Pt 1):L342-9.
  4. Maintz LNovak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007 May;85(5):1185-96.
  5. Secor ER JrShah SJGuernsey LASchramm CMThrall RS. Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma. Altern Ther Health Med. 2012 Sep-Oct;18(5):9-17.
  6. Secor ER JrSzczepanek SMCastater CAAdami AJMatson APRafti ET, et al. Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells. Evid Based Complement Alternat Med. 2013;2013:702196.
  7. Kobayashi Y, Takahashi R, Ogino F.Antipruritic effect of the single oral administration of German chamomile flower extract and its combined effect with antiallergic agents in ddY mice. J Ethnopharmacol. 2005 Oct 3;101(1-3):308-12.
  8. Nakatani KAtsumi MArakawa TOosawa KShimura SNakahata NOhizumi Y.Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a Thai medicinal plant. Biol Pharm Bull. 2002 Sep;25(9):1137-41.
  9. Weng ZZhang BAsadi SSismanopoulos NButcher AFu XKatsarou-Katsari AAntoniou CTheoharides 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.
  10. Bae YLee SKim SH. Chrysin suppresses mast cell-mediated allergic inflammation: involvement of calcium, caspase-1 and nuclear factor-κB. Toxicol Appl Pharmacol. 2011 Jul 1;254(1):56-64. doi: 10.1016/j.taap.2011.04.008. Epub 2011 Apr 16.
  11. Kanter M, Coskun O, Uysal H. The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol. 2006 Apr;80(4):217-24.
  12. Guéniche A1, Bastien P, Ovigne JM, Kermici M, Courchay G, Chevalier V, Breton L, Castiel-Higounenc I. Bifidobacterium longum lysate, a new ingredient for reactive skin. Exp Dermatol. 2010 Aug;19(8):e1-8.
  13. Levkovich T, Poutahidis T, Smillie C, Varian BJ, Ibrahim YM, Lakritz, Alm EJ, Erdman SE. Probiotic Bacteria Induce a ‘Glow of Health’. PLoS One. 2013; 8(1): e53867.


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