Histamine
Histamine is a natural chemical present in our bodies and in certain foods. Histamine intolerance is when there is too much histamine in the body and can be caused by exposure to an allergen, consuming high histamine foods, or an inability to produce the enzyme needed to break down histamine in the body.
Quick Facts
Histamine is a natural chemical present in our bodies and in certain foods. It is present in our skin, gastrointestinal tract, heart, lungs and brain. Histamine acts as a neurotransmitter (chemical messenger) in the central nervous system. It is also involved in the secretion of stomach acid. Histamine is produced by mast cells during immune responses to allergens.
When histamine creates an allergic response, a person may experience typical allergy symptoms like congestion or runny nose, watery eyes, itchy skin rashes, sneezing, swelling and inflammation or headaches.
Histamine is present in certain foods that are fermented, aged or smoked.
Histamine becomes problematic for some people when there is too much histamine in the body. This is called histamine intolerance. This excess histamine is caused by exposure to an allergen, consuming high histamine foods, or an inability to produce the enzyme needed to break down histamine in the body. [13, 14]
SIGNS/SYMPTOMS of Histamine Intolerance
Histamine intolerance can manifest in a variety of ways including [15]:
Stomach cramping
Headaches
Facial swelling
Skin rashes
Asthma
Dizziness
Blood pressure changes
Fast/irregular heartbeat
Foods containing Histamine
Fermented or pickled foods like vinegar, yogurt, kombucha, kefir, sauerkraut, pickles, soy sauce, Worcestershire sauce
Alcohol, especially red wine
Leftover meat, fish, and seafood
Smoked, cured, and aged meats
Aged cheeses
Canned foods
Dried fruits and overripe fruits (like bananas)
Certain vegetables like olives, eggplant, spinach, and tomatoes
Histamine alternatives
Low histamine foods include:
Fresh meat and fish that is not leftover or thawed slowly
Fresh dairy products like milk, butter or soft cheeses like mozzarella, ricotta
Gluten-free grains
All fresh or frozen vegetables except those listed above
Vegetable oils or animal fats
Fresh or dried herbs
Herbal teas
Non-dairy milks like almond or coconut
Most fresh or frozen fruits (some fruits don’t contain histamine but are limited on a low histamine diet. For a more complete list of foods for those following a low histamine diet, visit here.
Chemical reactions
The body can respond to foods and/or chemicals in many different ways including allergies and sensitivities. If you suspect a chemical reaction, you can either choose to avoid the chemical or additional testing.
Histamine & Autism in the Research
Histamine & the Brain
Interfering with histamine receptors reduces symptoms and specific behaviors in ASD patients. The histaminergic system also brings about neuroinflammation. The histaminergic system may also be altered in ASD. [1]
Numerous brain neurotransmitters, including histamine, appear to be implicated in the pathophysiology of ASD, since disruption of genes encoding different proteins leads to features of ASD. [2]
Simultaneous targeting of brain histaminergic and cholinergic neurotransmissions is crucial for palliation of ASD-like features. [8]
Several molecular signaling pathways have been identified that link immune activation to ASD traits. [6]
Children with ASD respond disproportionally to stress and present with food and skin allergies that involve mast cells. When stressed, the hypothalamus releases corticotropin-releasing hormone and neurotensin, which stimulates brain mast cells and leads to inflammation, neurotoxicity and disrupts the blood-brain barrier. These brain mast cells may be involved in the pathogenesis of ASD. Furthermore, corticotropin-releasing factor and neurotensin are significantly increased in serum of children with ASD. [7, 10]
Histamine, Allergies and ASD
Most ASD patients also have food intolerances and other allergic symptomatology indicative of mast cell activation. Allergic, infectious, neuroimmune and environmental triggers may activate mast cells to release vasoactive, inflammatory and neurotoxic molecules. These could disrupt the gut-blood-brain-barriers, and/or activate susceptibility genes, thus contributing to brain inflammation and ASD. [3]
Food allergies and sensitivities are significantly associated with ASD and may be more common in children with ASD. These issues may correlate with other behaviors. [4, 9]
Allergies and autoimmune diseases were diagnosed significantly more often among children with autism than among controls. [5]
Mast Cells and Autism
Prenatal stress has been associated with a higher risk for offspring developing ASD. Stress and environmental stimuli trigger mast cells, which could then trigger immune cells in the brain/central nervous system. This may lead to dysfunctional neuronal connectivity. Preventing stimulation of mast cells and/or immune cells could greatly benefit ASD patients. [11]
ASD children may present with "allergic-like" problems in the absence of elevated serum IgE and hives, which suggest non-allergic mast cell activation, probably in response to environmental and stress triggers that could contribute to inflammation. [12]
References
[1] Wright C, Shin JH, Rajpurohit A, et al. Altered expression of histamine signaling genes in autism spectrum disorder. Transl Psychiatry. 2017;7(5):e1126.
[2] Eissa N, Al-Houqani M, Sadeq A, Ojha SK, Sasse A, Sadek B. Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder. Front Neurosci. 2018;12:304.
[3] Theoharides TC. Autism spectrum disorders and mastocytosis. Int J Immunopathol Pharmacol. 2009;22(4):859-65.
[4] Lyall K, Van de Water J, Ashwood P, Hertz-Picciotto I. Asthma and Allergies in Children With Autism Spectrum Disorders: Results From the CHARGE Study. Autism Res. 2015;8(5):567-74.
[5] Zerbo O, Leong A, Barcellos L, Bernal P, Fireman B, Croen LA. Immune mediated conditions in autism spectrum disorders. Brain Behav Immun. 2015;46:232-6.
[6] Estes ML, McAllister AK. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat Rev Neurosci. 2015;16(8):469-86.
[7] Theoharides TC, Stewart JM, Panagiotidou S, Melamed I. Mast cells, brain inflammation and autism. Eur J Pharmacol. 2016;778:96-102.
[8] Eissa N, Jayaprakash P, Stark H, Łażewska D, Kieć-Kononowicz K, Sadek B. Simultaneous Blockade of Histamine H3 Receptors and Inhibition of Acetylcholine Esterase Alleviate Autistic-Like Behaviors in BTBR T+ tf/J Mouse Model of Autism. Biomolecules. 2020;10(9):E1251.
[9] Xu G, Snetselaar LG, Jing J, Liu B, Strathearn L, Bao W. Association of Food Allergy and Other Allergic Conditions With Autism Spectrum Disorder in Children. JAMA Netw Open. 2018;1(2):e180279.
[10] Theoharides TC. Is a subtype of autism an allergy of the brain. Clin Ther. 2013;35(5):584-91.
[11] Theoharides TC, Kavalioti M, Tsilioni I. Mast Cells, Stress, Fear and Autism Spectrum Disorder. Int J Mol Sci. 2019;20(15):E3611.
[12] Theoharides TC, Angelidou A, Alysandratos KD, et al. Mast cell activation and autism. Biochim Biophys Acta. 2012;1822(1):34-41.
[13] Gagic M, Jamroz E, Krizkova S, Milosavljevic V, Kopel P, Adam V. Current Trends in Detection of Histamine in Food and Beverages. J Agric Food Chem. 2019;67(3):773-83.
[14] Kovacova-Hanuskova E, Buday T, Gavliakova S, Plevkova J. Histamine, histamine intoxication and intolerance. Allergol Immunopathol (Madr). 2015;43(5):498-506.
[15] Symptoms. Org.uk. Published November 28, 2011. Accessed May 17, 2021. https://www.histamineintolerance.org.uk/about/symptoms/
Authors
Brittyn Coleman, MS, RDN/LD, CLT
