3 contro­ver­sial amino acids in Hist­amine Into­le­rance and MCAS

First, I want to note that a suffi­cient supply of protein and, above all, essen­tial amino acids, which the body cannot produce itself, is critical for good health. Parti­cu­larly in pati­ents who, due to mast cell acti­va­tion syndrome (MCAS) or food into­le­rances, only eat limited amounts of food, it is crucial to ensure a suffi­cient intake of protein and, above all, essen­tial amino acids.

However, some amino acids should only be taken with caution in hist­amine into­le­rance syndrome (HIS) or MCAS. For example, care should be taken with histidine and N‑acetylcysteine (NAC – a stabi­lized form of the amino acid cysteine).

One should also consider that bacte­rial fermen­ta­tion processes can convert the amino acids lysine, orni­t­hine, and tyro­sine into cada­verine, putre­scine, and tyra­mine, which can be proble­matic in biogenic amine into­le­rance. Into­le­rance against other biogenic amine is common in people with hist­amine into­le­rance syndrome.1

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.

Histidine in Hist­amine Into­le­rance and Mast Cell Acti­va­tion Syndrome

Hist­amine is gene­rated in the body from histidine as a meta­bolic product of histidine decar­b­oxylase. Hist­amine is broken down by diamine oxidase (DAO) and hist­amine methyl­trans­ferase (HNMT). In rarer cases and to a smaller extent, monoa­mine oxidase B (MAO) also plays a role in hist­amine degra­dation. I describe these processes in detail in the article regar­ding the causes of hist­amine intolerance.

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

An addi­tional supply of histidine above the average level is thus able to increase the hist­amine level in the body. As a rule of thumb, one does not have to supple­ment this amino acid if one eats suffi­cient quan­ti­ties in their diet.2

How Much Histidine Do You Need per Day?

However, histidine is one of the essen­tial amino acids, and thus, the body cannot produce it. At least 8–12mg/kg histidine per day is needed to stay healthy. With a regular diet, Euro­peans consume between 2.12 and 2.40g per day, and in the US, the average amount consumed is even a bit higher.3

In addi­tion, the amino acid’s break­down product hist­amine also plays an essen­tial role in the body, and too low hist­amine levels also prove to be proble­matic for health.

N‑Acetylcysteine (NAC) in HIS & MCAS: Poten­tial for Side Effects

N‑acetylcysteine is a radical scavenger (anti­oxi­dant) that releases the amino acid cysteine after deace­tyla­tion in the liver. This amino acid is required for the forma­tion of glutathione, another important anti­oxi­dant.4

NAC is used prima­rily as an expec­torant for bron­chitis but has also shown success in animal models in redu­cing lipid peroxi­da­tion, which results in cellular damage from free radi­cals and plays a notable role in athe­ros­cle­rosis.4

N‑acetylcysteine also improved the health status of rheu­ma­toid arthritis pati­ents in a smaller, double-blind, rando­mized study.5

However, N‑Acetylcysteine (NAC) may cause incre­ased hist­amine release from mast cells resul­ting in side effects in sensi­tive people and contra­dic­ting the bene­fi­cial effects from anti-inflamma­tory actions.6

In a study using intra­venous NAC infu­sion in humans incre­ased hist­amine levels were found in just a portion of the subjects. This increase was only present in those who comp­lained of side effects.7

Because of the anti-inflamma­tory and immune-balan­cing proper­ties that N‑acetylcysteine appears to have, it is necessary to consider whether it can be used in mast cell- or hist­amine-mediated dise­ases.8 This evalua­tion should be made with the help of quali­fied medical personnel.

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Lysine in Hist­amine Into­le­rance & MCAS: Likely Safe

Lysine is often used in comple­men­tary medi­cine for the preven­tion of recur­rent herpes infec­tions. It is an essen­tial amino acid and ever­y­body should make sure to take in suffi­cient amounts through food.

In an expe­ri­ment with human mast cells, lysine solu­tion impacted skin mast cells but resulted in no reac­tions from lung, intes­tinal, or other­wise loca­lized mast cells in humans.9,10

Thus, one can assume that this amino acid is very unli­kely to be proble­matic for people with allergic dise­ases: Still, it would be best to have a suffi­cient dietary intake so that no addi­tional supple­men­ta­tion is needed.

It is crucial to ensure that protein, and thus often lysine-rich foods, are freshly processed to prevent the break­down of lysine to the protein rot subs­tance cada­verine. Cada­verine (1,5 diami­nopen­tane) is a biogenic amine harmful to health, and it has a very unplea­sant odor.11

It goes without saying that unplea­sant-smel­ling protein products should no longer be consumed but should be disposed of.

Protein rich food

Tyro­sine in HIS & MCAS

The non-essen­tial amino acid L‑tyrosine is derived from the essen­tial amino acid phenyl­ala­nine. Tyro­sine is needed in the human body to produce thyroid hormones (L‑thyroxine) and various brain chemical messen­gers (neuro­trans­mit­ters) such as dopa­mine and norepinephrine.

Tyro­sine by itself does not contain hist­amine, but when bacteria meta­bo­lize it, tyra­mine gets produced. This biogenic amine often causes problems in hist­amine or biogenic amine intolerance.

Since neuro­trans­mit­ters also influ­ence mast cells, one should ensure an adequate supply of proteins and amino acids such as L‑phenylalanine. The body needs this essen­tial amino acid to supply neuro­trans­mit­ters in decent amounts. As a rule of thumb, when consuming enough protein, no addi­tional tyro­sine intake is required in most cases.


1. Biogene Amine — Chemie.de Lexikon. Accessed August 12, 2021. https://www.chemie.de/lexikon/Biogene_Amine.html

2. Gesund­heit­liche Bewer­tung von Amino­säuren — BfR. Accessed August 12, 2021. https://www.bfr.bund.de/de/gesundheitliche_bewertung_von_aminosaeuren-54420.html

3. Moro J, Tomé D, Schmi­dely P, Demersay T‑C, Azzout-Marniche D. Histidine: A Syste­matic Review on Meta­bo­lism and Physio­lo­gical Effects in Human and Diffe­rent Animal Species. Nutri­ents. 2020;12(5). doi:10.3390/nu12051414

4. Gillissen A. N‑Acetylcystein: Neue Erkennt­nisse zu einem bewährten Wirk­stoff. Phar­ma­zeu­ti­sche Zeitung online. Accessed August 16, 2021.

5. Batooei M, Taha­moli-Roudsari A, Basiri Z, et al. Evalua­ting the Effect of Oral N‑acetylcysteine as an Adju­vant Treat­ment on Clinical Outcomes of Pati­ents with Rheu­ma­toid Arthritis: A Rando­mized, Double Blind Clinical Trial. Rev Recent Clin Trials. 2018;13(2):132–138. doi:10.2174/1574887113666180307151937

6. Barrett KE, Minor JR, Metcalfe DD. Hist­amine secre­tion induced by N‑acetyl cysteine. Agents Actions. 1985;16(3–4):144–146. doi:10.1007/BF01983123

7. Waring WS, Bateman D. Hist­amine release is the asso­ciated mecha­nism following acetyl­cys­teine adverse reac­tion in man. Clinical Toxi­co­logy. 2008;46:396.

8. Wang J, Jin Q, Hu Z, Zhou H. The effects of N‑acetylcysteine on the Th1/Th2 ratio in elderly pati­ents with chronic obst­ruc­tive pulmo­nary disease. :6.

9. Lowman MA, Rees PH, Benyon RC, Church MK. Human mast cell hete­ro­gen­eity: Hist­amine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-depen­dent and nonim­mu­noiogic stimuli. Published online 1988:8.

10. Padawer J. The reac­tion of rat mast cells to poly­ly­sine. J Cell Biol. Published online 1970:352.

11. Hirai K. ÜBER DIE BILDUNG VON CADA­VERIN AUS d‑LYSIN DURCH BACILLUS LACTIS AERO­GENES. The Journal of Bioche­mi­stry. 1939;29(3):435–438. doi:10.1093/oxfordjournals.jbchem.a125822

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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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