Amino Acids in Hist­amine Into­le­rance and Mast Cell Disease (MCAS)

Amino acids are buil­ding blocks of body proteins and there­fore essen­tial for life. Certain amino acids cannot be produced by the body itself; conse­quently, they must be inge­sted through food. It is there­fore important to have a balanced supply of protein in the diet, which is some­times more chal­len­ging in cases of hist­amine into­le­rance and/or food aller­gies and mast cell diseases.

Amino acids that may be useful in hist­amine into­le­rance syndrome (HIS) and mast cell acti­va­tion syndrome (MCAS) include:

  • Crea­tine
  • Glycine
  • Methio­nine (e.g., when abstai­ning from all animal and certain vegan protein sources.)

Histidine should be avoided in cases of hist­amine into­le­rance, as hist­amine is formed from it in the body by means of histidine decarboxylase.

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.

Crea­tine in Hist­amine Into­le­rance and Mast Cell Acti­va­tion Syndrome (MCAS)

Crea­tine is one of the most rese­ar­ched dietary supple­ments. Studies exist on its use from osteo­po­rosis to neuro­de­ge­ne­ra­tive diseases.

These show that crea­tine may be helpful in a variety of meta­bolic processes. The following effects of crea­tine have already been demons­trated in scien­tific studies1–4:

  • Reduc­tion of chole­sterol and triglycerides
  • Reduced fat accu­mu­la­tion in the liver
  • Reduc­tion of homo­cys­teine levels
  • Improved blood sugar control
  • Increase in strength and/or muscle mass
  • Better cogni­tive function
  • Improved bone density (when accom­pa­nied by exercise)
  • Parti­ally forma­tion of an anti­de­pres­sant effect as well as reduc­tion of fatigue

In addi­tion to the “typical” areas of appli­ca­tion in sports, injury manage­ment, and reha­bi­li­ta­tion after trai­ning, crea­tine has posi­tive effects that can benefit people with hist­amine into­le­rance and mast cell dise­ases. Espe­cially since crea­tine-rich foods such as salmon, beef, etc. are often only poorly tole­rated in these conditions.

Crea­tine could possibly help suffe­rers who comp­lain of poor perfor­mance due to “brain fog”. In addi­tion, suffe­rers often have problems main­tai­ning their weight or buil­ding up muscles. Both aspects are crucial to coun­teract subse­quent problems ranging from under­weight to osteoporosis.

Histamine mediated symptoms in mast cell diseases like rashes, nausea, runny nose, sneezing, diarrhea
Hist­amine mediated symptoms in mast cell diseases

Crea­tine Side Effects

It all sounds almost a little too good to be true — doesn’t it? The effects in the studies are not necessa­rily all that great and often more subtle.

Nevertheless, crea­tine is one of the safest supple­ments avail­able. It has been used in doses ranging from 0.3 to 0.8 g/kg of body weight per day in a wide variety of subject groups (elderly, children, and even pregnant women) with no harmful side effects.1

One side effect described is weight gain. On the posi­tive side, crea­tine ingestion does not appear to suppress the body’s amino acid produc­tion. Even high doses up to 30 grams per day were not asso­ciated with an accu­mu­la­tion of kidney disease..1

Crea­tine in the Diet and Dose Recommendations?

Prof. Dr. Theo Walli­mann5 recom­mended as early as 1984 to aim for 3 grams of crea­tine per day for general health. Now the ques­tion arises: Can’t I reach this amount with my diet?

The answer is: probably not — one to two grams of crea­tine are contained in one pound (!) of raw beef. Vege­ta­rians gene­rally tend to have lower levels.

Supple­men­ta­tion: An Easy Way to Increase Crea­tine Levels?

There are diffe­rent approa­ches to taking crea­tine: for example, the so-called “loading phase”, in which a higher amount of crea­tine is taken over five to seven days to reple­nish the stores. After that, the dose is reduced to a main­ten­ance dose.

Another option is a constant supple­men­ta­tion of, for example, 3 grams a day. In addi­tion, care should be taken to ensure that the crea­tine is taken with carbo­hy­drates because it is better absorbed that way.1

Sleepless, woman suffering from insomnia, sleep apnea or stress, headache or migraine

Glycine: Remedy for Insomnia Caused by Histamine?

Glycine is a non-essen­tial amino acid, which means that humans can produce it. It is synthe­sized from choline, threo­nine, and serine. In the produc­tion of glycine from choline, methyl groups are gene­rated. It is also a precursor of creatine.

Glycine protects gastro­in­tes­tinal cells in various cell and animal models and has an anti-inflamma­tory acti­vity, so it would be of great inte­rest to study this in humans. Like­wise, the amino acid hindered the deve­lo­p­ment of gastric ulcers in animal models.6

It also has a hepa­to­pro­tec­tive effect, meaning that it appears to have a posi­tive impact on liver health.6

Another benefit of glycine is that this amino acid improves subjec­tive sleep quality and may help with sleep disor­ders.7 Hist­amine is an exci­ta­tory neuro­trans­mitter that has a stimu­la­ting effect on the central nervous system. Pati­ents with hist­amine into­le­rance syndrome (HIS) or mast cell acti­va­tion syndrome (MCAS) often describe sleep and wake rhythms disturbances.

Further­more, glycine causes body tempe­ra­ture to drop at night. Rese­ar­chers believe this drop may also improve sleep.8 In addi­tion, REM sleep was prolonged in one study.9

Side Effects. Glycine is Consi­dered Harm­less Even in High doses

Glycine is consi­dered very safe even in high doses, both in humans and animals. In rats, high doses over four weeks of 2g/kg were not toxic.10 In some cases, doses of up to 30 (!) grams per day were used in human studies. In one case, nausea with vomi­ting occurred, which caused the discon­ti­nua­tion of treat­ment in this indi­vi­dual..11℗

MAP Amino Acids for Hist­amine Intolerance

MAP stands for Master Amino Acid Pattern. According to Prof. Dr. Lucà-Moretti, it repres­ents the optimal ratio of the eight essen­tial amino acids for humans so that as little nitrogen waste and ammonia as possible is produced. MAP® supple­ments are used to correct protein defi­ci­en­cies. Supple­men­ta­tion with MAP® is compa­ra­tively expensive.

To ensure adequate protein intake in cases of hist­amine into­le­rance, one should watch their protein supply to provide a balanced amino acid profile, so no further supple­ments like MAP® are needed. For example, one can mix pea and rice protein in a 30% to 70% ratio for an opti­mized amino acid profile.

Rice protein does not contain enough lysine but more methio­nine. It, there­fore, makes sense to alter­nate and rotate protein sources to ensure optimal supply.

In the case of severe kidney or liver disease, it may be advi­s­able to reduce the nitrogen and ammonia drop through protein intake — but this must decide the atten­ding medical professional.

Methio­nine or S‑Ade­nosyl-Methio­nine in Hist­amine Into­le­rance, Aller­gies or MCAS

Methio­nine is a sulfur-contai­ning amino acid found prima­rily in animal protein sources such as salmon, chicken, and non-animal proteins like soybeans, chick­peas, and millet. As a rule, people consume enough of this amino acid in their diet.

S‑ade­nosyl-methio­nine, or S‑ade­nosyl-L-methio­nine (SAMe), is the active form of methio­nine, but it is rela­tively unstable in some supple­ment forms. SAMe is a methyl group donor in the body and plays an essen­tial role in methyla­tion processes in the human body.

One of the degra­dation pathways of hist­amine is via hist­amine methyl trans­ferase (HNMT for short) and is also based on a methyla­tion reac­tion, which is why there is repeated specu­la­tion as to whether taking methio­nine could help allergy suffe­rers.12 However, studies in humans are still lacking.

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

Since a suffi­cient amount of methio­nine, espe­cially S‑ade­nosyl-methio­nine, is asso­ciated with reduced oxida­tive stress in animal models of asthma, one should make sure to ingest enough methio­nine in the diet.13.13

In addi­tion, methio­nine is used in Germany to prevent recur­rent urinary tract infec­tions by provi­ding this amino acid to acidify the urine.

n a retro­spec­tive study with pati­ents after kidney trans­plan­ta­tion, methio­nine was able to provide an almost half reduc­tion in the occur­rence of urinary tract infec­tions, but the effect was some­what weaker compared to the intake of cran­berry juice.14

Side Effects: Increase Homo­cys­teine Levels and Gastro­in­tes­tinal Complaints

Exces­sive intake of methio­nine can increase homo­cys­teine levels, which is consi­dered a risk marker for athe­ros­cle­rosis, among other things.15 This is parti­cu­larly the case when there is no adequate intake of folic acid, vitamin B6, and B12.

Gastro­in­tes­tinal comp­laints may also occur.16 There­fore, it is best to see if one can meet one’s needs through diet or work speci­fi­cally with thera­pists to address this.

Excur­sion: Methyla­tion is not yet fully unders­tood: It influ­ences epige­netic processes to a high degree. Epige­ne­tics is respon­sible for control­ling whether specific genes are “swit­ched on or off”. There­fore, I would be very cautious about taking high doses of methio­nine or SAMe, for example, or like­wise methylated folic acid (methyl folate or 5‑MTHF) without proven defi­ci­en­cies or thera­peutic guidance.

For example, animal studies showed that very high doses of methyl folate were asso­ciated with more atopic disease in the offspring. In humans, these study results were incon­clu­sive — some showed this effect and others did not17


1.         Kreider RB, Kalman DS, Antonio J, et al. Inter­na­tional Society of Sports Nutri­tion posi­tion stand: safety and effi­cacy of crea­tine supple­men­ta­tion in exer­cise, sport, and medi­cine. Journal of the Inter­na­tional Society of Sports Nutri­tion. 2017;14(1):18. doi:10.1186/s12970-017‑0173‑z

2.         Stead LM, Au KP, Jacobs RL, Brosnan ME, Brosnan JT. Methyla­tion demand and homo­cys­teine meta­bo­lism: effects of dietary provi­sion of crea­tine and guani­di­noace­tate. Am J Physiol Endocrinol Metab. 2001;281(5):E1095-1100. doi:10.1152/ajpendo.2001.281.5.E1095

3.         Santos RVT, Bassit RA, Cape­ruto EC, Costa Rosa LFBP. The effect of crea­tine supple­men­ta­tion upon inflamma­tory and muscle soreness markers after a 30km race. Life Sci. 2004;75(16):1917–1924. doi:10.1016/j.lfs.2003.11.036

4.         Op ’t Eijnde B, Ursø B, Richter EA, Green­haff PL, Hespel P. Effect of oral crea­tine supple­men­ta­tion on human muscle GLUT4 protein content after immo­bi­liz­a­tion. Diabetes. 2001;50(1):18–23.

5.         ETH Zürich — Theo Walli­mann. Accessed July 29, 2021. https://www.bi.id.ethz.ch/personensuche/personenDetail.view?lang=de&pid=1312E

6.         Razak MA, Begum PS, Viswa­nath B, Raja­gopal S. Multi­fa­rious Bene­fi­cial Effect of Nones­sen­tial Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701. doi:10.1155/2017/1716701

7.         Yama­dera W, Inagawa K, Chiba S, Bannai M, Taka­hashi M, Naka­yama K. Glycine ingestion improves subjec­tive sleep quality in human volun­teers, corre­la­ting with poly­s­om­no­gra­phic changes. Sleep Biol Rhythms. 2007;5(2):126–131. doi:10.1111/j.1479–8425.2007.00262.x

8.         Bannai M, Kawai N. New thera­peutic stra­tegy for amino acid medi­cine: glycine improves the quality of sleep. J Phar­macol Sci. 2012;118(2):145–148. doi:10.1254/jphs.11r04fm

9.         Kawai N, Sakai N, Okuro M, et al. The sleep-promo­ting and hypo­thermic effects of glycine are mediated by NMDA recep­tors in the supra­chi­as­matic nucleus. Neuro­psy­cho­phar­ma­co­logy. 2015;40(6):1405–1416. doi:10.1038/npp.2014.326

10.       Shibui Y, Miwa T, Yama­shita M, Chin K, Kodama T. A 4‑week Repeated Dose Toxi­city Study of Glycine in Rats by Gavage Admi­nis­tra­tion. J Toxicol Pathol. 2013;26(4):405–412. doi:10.1293/tox.2013–0026

11.       Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lich­ten­stein M. Effi­cacy of High-Dose Glycine in the Treat­ment of Endu­ring Nega­tive Symptoms of Schi­zo­phrenia. Arch Gen Psych­iatry. 1999;56(1):29. doi:10.1001/archpsyc.56.1.29

12.       Pacheco Y, Macov­schi O, Biot N, Fonlupt P, Perrin-Fayolle M, Pacheco H. Modu­la­tion by S‑ade­nosyl-methio­nine and S‑ade­nosyl-homo­cys­teine of the human leucocytes hist­amine release. Clin Allergy. 1984;14(1):37–43. doi:10.1111/j.1365–2222.1984.tb02187.x

13.       Yoon S‑Y, Hong GH, Kwon H‑S, et al. S‑adenosylmethionine reduces airway inflamma­tion and fibrosis in a murine model of chronic severe asthma via suppres­sion of oxida­tive stress. Exp Mol Med. 2016;48(6):e236. doi:10.1038/emm.2016.35

14.       Pagonas N, Hörs­trup J, Schmidt D, et al. Prophy­laxis of recur­rent urinary tract infec­tion after renal trans­plan­ta­tion by cran­berry juice and L‑methionine. Trans­plant Proc. 2012;44(10):3017–3021. doi:10.1016/j.transproceed.2012.06.071

15.       Ditscheid B, Fünf­stück R, Busch M, Schu­bert R, Gerth J, Jahreis G. Effect of L‑methionine supple­men­ta­tion on plasma homo­cys­teine and other free amino acids: a placebo-controlled double-blind cross-over study. Euro­pean Journal of Clinical Nutri­tion. 2005;59(6):768–775. doi:10.1038/sj.ejcn.1602138

16.       Phar­ma­Wiki — Methionin. Accessed July 29, 2021. https://www.pharmawiki.ch/wiki/index.php?wiki=Methionin

17.       Sharma S, Litonjua A. Asthma, Allergy, and Responses to Methyl Donor Supple­ments and Nutri­ents. J Allergy Clin Immunol. 2014;133(5):1246–1254. doi:10.1016/j.jaci.2013.10.039



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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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