Caff­eine in Hist­amine Into­le­rance, MCAS & Asthma

Caff­eine is a stimu­la­ting subs­tance, and as such respon­sible for the well-known effects of coffee. Moreover, espe­cially in people not used to drin­king a lot of coffee, it incre­ases alertness and can help over­come tired­ness. Still, some people are more sensi­tive to the effects of caff­eine than others and expe­ri­ence a feeling of fidge­ti­ness or rest­less­ness and, as such, take a some­what skep­tical posi­tion when it comes to this drink.

Many arti­cles about hist­amine into­le­rance only focus on coffee consump­tion and equate caff­eine with coffee, thereby disre­gar­ding all other sources of caff­eine – e. g. black tea. The slightly super­fi­cial result of those arti­cles is often that coffee being a DAO inhi­bitor should be avoided by people suffe­ring from hist­amine into­le­rance: What role does caff­eine play in hist­amine meta­bo­lism in allergic patients?

This article is about a health issue. It is important that you have your symptoms examined and treated by medical profes­sio­nals. This article is not intended to be, and cannot be, a substi­tute for the care and advice of medical profes­sio­nals that may be avail­able to you.

Is Caff­eine a DAO inhi­bitor? Missing Evidence for this Thesis.

Caff­eine is widely consi­dered a DAO inhi­bitor, but I was unable to locate reli­able scien­tific studies that support this theory despite exten­sive efforts. Nevertheless, the internet is full of arti­cles precisely stating this. Just one example is the blog of the late Yasmina Ykel­en­stam (Healing Hist­amine), presen­ting one of the most common argu­ments for the DAO inhi­bi­ting effect of coffee:

According to some blog­gers, the DAO inhi­bi­ting effect of coffee or black tea is based on a simi­la­rity between caff­eine and the suppo­sedly DAO inhi­bi­ting subs­tance theo­phyl­line, as both subs­tances belong to the group of methylxan­thines. 1 However, there is proof that theo­phyl­line does not inhibit the diamine oxidase enzyme (DAO).2

Mean­while, the SIGHI (Swiss Inte­rest Group Hist­amine Into­le­rance) has removed theo­phyl­line from its list of medi­ca­tions that should be avoided. However, other websites still list theo­phyl­line as proble­matic – poten­ti­ally without good cause, as explained above.

Histamine Metabolism & Degradation via DAO & HNMT
Hist­amine Meta­bo­lism & Degra­dation via DAO & HNMT

Caff­eine in Hist­amine Mediated Dise­ases: Pro-Inflamma­tory or Not?

A variety of studies suggests that caff­eine has anti-inflamma­tory effects but there are other studies sugges­ting the exact oppo­site effect. It appears a defi­ni­tive judgment has not been estab­lished and is not expected anytime soon.

Consi­de­ring all avail­able evidence, it appears that coffee has a limited anti-inflamma­tory effect that exceeds the impact attri­buted to the contained caff­eine. One possible explana­tion might be that secon­dary plant-derived subs­tances found in coffee have other anti-inflamma­tory quali­ties.3

A variety of tea blends contain caff­eine in rele­vant amounts as well. According to a table published by the Mayo Clinic, black tea contains 47 mg per 237ml (8 oz.) and, as such, about half the amount of the 96 mg included in the same amount of coffee.4

Despite both drinks contai­ning signi­fi­cant amounts of caff­eine, tea consump­tion is usually seen as less critical than coffee. How can that be? Both bever­ages contain next to caff­eine and a range of other subs­tances, various tannic acids. However, these tannic acids differ between coffee and tea, and so does the indi­vi­dual tole­rance level.

People suffe­ring from hist­amine into­le­rance are frequently very limited in what they can safely eat or drink. Drin­king coffee is not only a matter of achie­ving the necessary amount of fluid intake, but coffee is some­thing to be savored and enjoyed. I, for my part, would not want to abstain from drin­king coffee without good reason. 😉

Coffee background with coffee beans

The Effect of Caff­eine on Neuro­logic & Psychic Symptoms

Has caff­eine a stimu­la­ting effect on the excre­tion of glut­amate and histamine?

A study from 2014 looked at the effect of caff­eine on the frontal part of the hypo­tha­lamus. This part of the brain is involved in the regu­la­tion of our vege­ta­tive nervous system. It controls crucial func­tions in our body by releasing various hormones, inclu­ding body tempe­ra­ture, blood pres­sure, and other invol­un­tary processes. 5

Caff­eine incre­ases neuro­trans­mitter release (messenger subs­tances in our brain) of glut­amate and hist­amine in the hypo­tha­lamus. However, conclu­sions derived from this obser­va­tion and applied to other cells in our body are of minimal vali­dity.5

In people who are very sensi­tive to changes of the messenger mentioned above subs­tances, caff­eine might play a role in displea­sing sensa­tions expe­ri­enced. There is also a possi­bi­lity – and this is a specu­la­tion of mine – that a more potent effect might be seen in people with an inherited defi­ci­ency (e. g., HMNT vari­ants) that results in slow hist­amine metabolization.

The enzyme Hist­amine-Methyl­trans­ferase (HMNT) is respon­sible for the intracel­lular meta­bo­liz­a­tion of hist­amine. People with specific genetic vari­ants resul­ting in a lower HNMT acti­vity appear to be more affected by allergic symptoms stem­ming from decre­ased hist­amine meta­bo­liz­a­tion. There is also a greater possi­bi­lity of hist­amine-induced symptoms of the central nervous system.6,7 In my article about the causes of hist­amine into­le­rance, you can read up on the effects of diamine oxidase (DAO) and HNMT on histamine’s meta­bo­liz­a­tion and the genetic vari­ants affec­ting it.

Caff­eine can create a well-known stimu­la­ting effect by releasing exci­ta­tory messenger subs­tances in our brain, among others affec­ting the A2A-adeno­sine receptor. Specific muta­tions in genes enco­ding the adeno­sine receptor system are suspected to be related to incre­ased levels of anxiety and even panic following caff­eine uptake in certain indi­vi­duals.8

Some scien­tists even specu­late about the useful­ness of A2A-Adeno­sine receptor inhi­bi­tors like caff­eine in trea­ting depres­sion. These subs­tances might help alle­viate the loss of energy and moti­va­tion frequently seen in pati­ents suffe­ring from depres­sive episodes.9

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Caff­eine in Mast Cell Acti­va­tion syndrome (MCAS) & Allergies

Does caff­eine have an anti-allergic effect?

Caff­eine could cause the release of hist­amine, as explained above, but at the same time, there is evidence that suggests it has anti-allergic charac­te­ris­tics as well.10

Rese­ar­chers caused severe allergic reac­tions in rats and observed that the allergic reac­tions were less severe in a group treated with caff­eine.10 A study from 1997 has shown caff­eine to reduce the release of hist­amine from mast cells of the peri­to­neum.11

Consi­de­ring this it appears that caff­eine can have a posi­tive effect on allergic reac­tions by affec­ting the ability of mast cells to release hist­amine. The other type of cells having a large part in the genesis of allergic symptoms, baso­philic granu­lo­cytes appear to be affected by caff­eine as well. According to a study from 2019, were less likely to release their trans­mitter subs­tances – among those hist­amine – when under the influ­ence of caff­eine.12

Maybe people suffe­ring from mast cell acti­va­tion syndrome or aller­gies who have a good tole­rance for caff­eine could benefit from caff­eine uptake.

However, if into­le­rance to sali­cylic acid is present, coffee and tea might have distinctly adverse effects.

Caff­eine with Into­le­rance to NSAIDs / Sali­cylate Sensitivity

Although caff­eine can help with asthma, pati­ents suffe­ring from Morbus Samter (AERD) or into­le­rance to sali­cylic acid, coffee, or black tea might cause symptoms because of their high sali­cylate content. Espe­cially proble­matic have proven blends contai­ning bergamot (e. g. Earl Grey) or lemon beebalm (Lady Grey) and others because of the very high content of sali­cylic acid.13

Can Caff­eine be of Use in Pati­ents with Asthma?

Some studies report a posi­tive effect of caff­eine on asthma pati­ents. They report a dila­ta­tion of bron­chia (the small tubes through which air flows into the lungs), easing the distress of those patients.

Caff­eine has the poten­tial to falsify the results of pulmo­nary func­tion testing.

The effect observed in these studies was strong enough for rese­ar­chers to consider caff­eine consump­tions before pulmo­nary func­tion tests as poten­ti­ally impac­ting the usabi­lity of the results.14 A critical review of avail­able scien­tific lite­ra­ture published in 2010 goes as far as to suggest that pati­ents comple­tely avoid caff­eine intake prior to lung func­tion tests or at least docu­ment the intake to avoid test results that are not reli­able.15

If asthma is one of the cardinal symptoms of hist­amine into­le­rance, caff­eine might be of benefit to those pati­ents. However, great care should be taken if at the same time an into­le­rance to sali­cylic acid is present.


Caff­eine might have a posi­tive effect in some pati­ents suffe­ring from allergic reac­tions, espe­cially those with asthma. The tole­rance for caff­eine and the bever­ages that contain it, varies greatly between indi­vi­dual people. There is certainly no reason to demo­nize caff­eine and coffee because both can have posi­tive effects – and be it only to put some lips­tick on the pig of caff­eine addiction. 😉


  1. Ykel­en­stam, Yasmina. Hist­amine & Caff­eine Addic­tion | Healing Hist­amine. Accessed September 13, 2020. https://healinghistamine.com/histamine-caffeine-addiction/
  2. Metaye T, Baudry M, Lale­gerie P. Enhan­ce­ment of mitogen-induced lympho­cyte proli­fe­ra­tion by some inhi­bi­tors of alka­line phos­phatase and diamine oxidase. Inter­na­tional Journal of Immu­no­phar­ma­co­logy. 1989;11(6):629–636. doi:10.1016/0192–0561(89)90148–3
  3. Paiva C, Beserra B, Reis C, Dorea JG, Da Costa T, Amato AA. Consump­tion of coffee or caff­eine and serum concen­tra­tion of inflamma­tory markers: A syste­matic review. Crit Rev Food Sci Nutr. 2019;59(4):652–663. doi:10.1080/10408398.2017.1386159
  4. How much caff­eine is in your cup? Mayo Clinic. Accessed August 18, 2020. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/caffeine/art-20049372
  5. John J, Kodama T, Siegel JM. Caff­eine promotes glut­amate and hist­amine release in the poste­rior hypo­tha­lamus. Am J Physiol Regul Integr Comp Physiol. 2014;307(6):R704-710. doi:10.1152/ajpregu.00114.2014
  6. Maintz L, Novak N. Hist­amine and hist­amine into­le­rance. Am J Clin Nutr. 2007;85(5):1185–1196. doi:10.1093/ajcn/85.5.1185
  7. Hist­amin­in­to­le­ranz: IMD Institut für medi­zi­ni­sche Diagnostik, Labor. Accessed February 17, 2019. https://www.imd-berlin.de/spezielle-kompetenzen/nahrungsmittelunvertraeglichkeiten/histaminintoleranz.html
  8. Alsene K, Deckert J, Sand P, de Wit H. Asso­cia­tion Between A 2a Receptor Gene Poly­mor­phisms and Caff­eine-Induced Anxiety. Neuro­psy­cho­phar­ma­co­logy. 2003;28(9):1694–1702. doi:10.1038/sj.npp.1300232
  9. López-Cruz L, Sala­mone JD, Correa M. Caff­eine and Selec­tive Adeno­sine Receptor Antago­nists as New Thera­peutic Tools for the Moti­va­tional Symptoms of Depres­sion. Front Phar­macol. 2018;9. doi:10.3389/fphar.2018.00526
  10. Shin H‑Y, Lee C‑S, Chae H‑J, et al. Inhi­bi­tory effect of anaphyl­actic shock by caff­eine in rats. Inter­na­tional Journal of Immu­no­phar­ma­co­logy. 2000;22(6):411–418. doi:10.1016/S0192-0561(00)00006–0
  11. Teraoka H, Akiba H, Takai R, Taneike T, Hiraga T, Ohga A. Inhi­bi­tory effects of caff­eine on Ca2+ influx and hist­amine secre­tion inde­pen­dent of cAMP in rat peri­to­neal mast cells. Gen Phar­macol. 1997;28(2):237–243. doi:10.1016/s0306-3623(96)00186–3
  12. Nugrahini AD, Ishida M, Naka­gawa T, Nishi K, Suga­hara T. Anti-degra­nu­la­tion acti­vity of caff­eine: In vitro and in vivo study. Journal of Func­tional Foods. 2019;60:103422. doi:10.1016/j.jff.2019.103422
  13. The RPAH Elimi­na­tion Diet Hand­book with food and shop­ping guide — Allergy Unit — Royal Prince Alfred Hospital. Accessed September 13, 2020. https://www.slhd.nsw.gov.au/rpa/allergy/resources/foodintol/handbook.html
  14. Duffy P, Phil­lips YY. Caff­eine consump­tion decre­ases the response to bron­cho­pro­vo­ca­tion chal­lenge with dry gas hyper­ven­ti­la­tion. Chest. 1991;99(6):1374–1377. doi:10.1378/chest.99.6.1374
  15. Welsh EJ, Bara A, Barley E, Cates CJ. Caff­eine for asthma. Coch­rane Data­base Syst Rev. 2010;(1):CD001112. doi:10.1002/14651858.CD001112.pub2
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Natur­o­path, hypno­the­ra­pist, owner of an immune system gone crazy with various auto­im­mune special effects. She likes reading through medical papers and is an avid learner of all things regar­ding the human immune system. When her joints and body allow it: enthu­si­astic do-it-your­selfer around the house.

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Physi­cian, entre­pre­neur and behind-the-scenes advisor with wide-ranging inte­rests from health manage­ment and public health to photo­graphy and Japa­nese martial arts

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