A Current Insight into Histamine Intolerance

Abstract

Food intolerance is an abnormal non-immunological response of the organism to certain foods or their components. Histamine intolerance is one of the food intolerances that develops due to the inability to metabolize histamine, leading to symptoms. Diamine oxidase (DAO) and Histamine-N-methyltransferase (HNMT) enzymes are involved in histamine metabolism. It is estimated that a decrease in enzyme production or activation due to various factors results in the accumulation of histamine, leading to the pathogenesis of histamine intolerance. Individual differences exist in symptoms, but abdominal distension and pain, itching, eczema, urticaria, headache, nasal congestion, and rhinitis are common symptoms. Studies show that DAO enzyme activation is decreased, especially in individuals with idiopathic symptoms. The variety of symptoms and lack of differential diagnostic tests make diagnosing histamine intolerance difficult. Additionally, the same dietary histamine source can cause different symptoms in different individuals. In contemporary diagnosis and treatment approaches, histamine-restricted diets are considered the most reliable method. The exclusion of other diseases and positive responses to a histamine-restricted diet support the diagnosis of histamine intolerance. Treatment includes the administration of histamine elimination diets for a specific period, reintroducing histamine sources into the diet, and monitoring symptoms. s. This review includes current data on the dietary sources of histamine, its metabolism, histamine intolerance, and associated health problems. Today, histamine in foods and histamine intolerance are relatively new terms. Therefore, more research is required to determine diagnostic algorithms, treatment options, and the epidemiology of histamine intolerance.

Keywords

• Histamine
• food intolerance
• nutritional therapy

Ethical Statement

Not applicable

Histamin İntoleransına Güncel Bakış

Abstract

Besin intoleransları, bazı besinlere veya bileşenlerine karşı immünolojik olmayan anormal organizma cevabıdır. Histamin intoleransı, histaminin metabolize edilememesi ve semptom yaratması ile gelişen besin intoleranslarından biridir. Diamin oksidaz (DAO) ve Histamin N metil transferaz (HNMT) enzimleri histamin metabolizmasında görev alan iki enzimdir. Çeşitli faktörlerin etkisiyle enzim üretimi veya aktivasyonlarının azalması ve histaminin parçalanamaması sonucu vücutta birikmesi ile histamin intoleransı patogenezinin geliştiği tahmin edilmektedir. Semptomlar arasında bireye göre değişmekle beraber abdominal distansiyon, karın ağrısı, kaşıntı, egzama, ürtiker, baş ağrısı, burun tıkanıklığı, rinit yer almaktadır. Özellikle sebebi bilinmeyen semptomlara sahip bireylerde DAO enzim aktivasyonun azaldığını gösteren çalışmalar mevcuttur. Farklı organları etkileyen semptomlarının olması, ayırıcı bir tanı testinin bulunmaması ve aynı histamin kaynağının farklı bireylerde farklı reaksiyonlara sebep olması histamin intoleransı tanısını zorlaştırmaktadır. Günümüzde tanı ve tedavi yaklaşımlarında histamin kısıtlı diyetler en güvenilir yöntem olarak kabul edilmektedir. Aynı semptomlarla seyredebilecek diğer hastalıkların varlığının dışlanması ve histamin kısıtlı diyete olumlu cevap, histamin intoleransı tanısını desteklemektedir. Tedavi, histamin eliminasyon diyetlerinin belirli bir süre uygulanmasını, histamin kaynaklarına beslenmede yeniden yer verilmesini ve semptomların takibini içerir. Bu derleme çalışmasında mevcut verilerle histaminin diyetsel kaynakları, metabolizması, histamin intoleransı ve ilişkili sağlık sorunları ile histamin eliminasyon diyetlerine yer verilmiştir. Besinlerde histaminin belirlenmesi ve histamin intoleransı, oldukça yeni bir kavram olduğundan, histamin intoleransı epidemiyolojisini belirlemek, tanı algoritmalarını ve olası tedavi seçeneklerini doğrulamak için daha fazla araştırmaya ihtiyaç vardır.

Keywords

• Histamin
• besin intoleransları
• beslenme tedavisi

References

1. 1. Kovacova-Hanuskova E, Buday T, Gavliakova S, Plevkova J. Histamine, histamine intoxication and intolerance. Allergologia et Immunopathologia. 2015;43(5):498–506.
2. 2. Vlieg-Boerstra BJ, van der HS, Oude Elberink JN, Kluin-Nelemans JC, Dubois AE. Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods: what is the evidence? The Netherlands Journal of Medicine. 2005;63:244–249.
3. 3. EFSA Panel on Biological Hazards (BIOHAZ). Scientific opinion on risk based control of biogenic amine formation in fermented foods. EFSA Journal. 2011;9:1–93. doi: 10.2903/j.efsa.2011.2393
4. 4. Comas-Basté O, Luz Latorre-Moratalla M, Sánchez-Pérez S, Teresa Veciana-Nogués M, del Carmen Vidal-Carou M. Histamine and other biogenic amines in food. From scombroid poisoning to histamine intolerance. Biogenic Amines. 2019;1.
5. 5. Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine intolerance: The current state of the art. Biomolecules. 2020;10(8):1–26.
6. 6. Reese I, Ballmer-Weber B, Beyer K, et al. German guideline for the management of adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Association of Allergologists (AeDA),and the Swiss Society for Allergology and Immunology (SGAI). Allergo Journal International. 2017;(26):72–79. doi: 10.1007/s40629-017-0011-5.
7. 7. Gagic M, Jamroz E, Krizkova S, Milosavljevic V, Kopel P, Adam V. Current trends in detection of histamine in food and beverages. Journal of Agricultural and Food Chemistry. 2018;67(3):773-783.
8. 8. Doeun D, Davaatseren M, Chung MS. Biogenic amines in foods. Food Science and Biotechnology. 2017;26:1463–1474.

9. 9. Ladero V, Calles-Enriquez M, Fernandez M, Alvarez MA, Toxicological effects of dietary biogenic amines. Current Nutrition in Food Sciences. 2010;6:145–156.
10. 10. Akbulut G. ed. Besin Alerjisi, Besin İntoleransı Durumlarında Beslenme ve Test Diyetleri. Ankara. Nobel Tıp Kitabevleri;2016.
11. 11. Hrubisko M, Danis R, Huorka M, Wawruch M. Histamine intolerance-the more we know the less we know. a review. Nutrients. 2021;13(7):2228.
12. 12. Sánchez-Pérez S, Comas-Basté O, Veciana-Nogués MT, Latorre-Moratalla ML, Vidal-Carou MC. Low-histamine diets: is the exclusion of foods justified by their histamine content? Nutrients. 2021;13(5):1395.
13. 13. San Mauro Martin I, Brachero S, Garicano Vilar E. Histamine intolerance and dietary management: A complete review. Allergologia et Immunopathologia. 2016;44(5):475–483.
14. 14. Comas-Basté O, Latorre-Moratalla ML, Bernacchia R, Veciana-Nogués MT, Vidal-Carou MC. New approach for the diagnosis of histamine intolerance based on the determination of histamine and methylhistamine in urine. Journal of Pharmaceutical and Biomedical Analysis. 2017;145:379-385.
15. 15. Maintz L, Novak N. Histamine and histamine intolerance. American Journal of Clinical Nutrition. 2007;85(5):1185–1196.
16. 16. Boehm T, Reiter B, Ristl R, et al. Massive release of the histamine-degrading enzyme diamine oxidase during severe anaphylaxis in mastocytosis patients. Allergy. 2019;74(3):583-593.
17. 17. Manzotti G, Breda D, Di Gioacchino M, Burastero SE. Serum diamine oxidase activity in patients with histamine intolerance. International Journal of Immunopathology and Pharmacology. 2016;29(1):105–111.
18. 18. Kucher AN. Association of polymorphic variants of key histamine metabolism genes and histamine receptor genes with multifactorial diseases. Russian Journal of Genetics. 2019;55:794–814.
19. 19. Maintz L, Yu CF, Rodríguez E, et al. Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Eur. J. The Journal of Allergy and Clinical Immunology. 2011;66:893–902.
20. 20. Schnedl WJ, Enko D. Considering histamine in functional gastrointestinal disorders. Critical Reviews in Food Science and Nutrition. 2021;61(17):2960-2967.
21. 21. McGrath AP, Hilmer KM, Collyer CA, et al. Structure and inhibition of human diamine oxidase. Biochemistry. 2009;48(41):9810-22.
22. 22. Leitner R, Zoernpfenning E, Missbichler A. Evaluation of the inhibitory effect of various drugs / active ingredients on the activity of human diamine oxidase in vitro. Clinical and Translational Allergy. 2014;4:23.
23. 23. Finney J, Moon HJ, Ronnebaum T, Lantz M, Mure M. Human copper-dependent amine oxidases. Archives of Biochemistry and Biophysics. 2014;546:19-32.
24. 24. Schnedl WJ, Lackner S, Enko D, Schenk M, Holasek SJ, Mangge H. Evaluation of symptoms and symptom combinations in histamine intolerance. Intestinal Research. 2019;17(3):427–433.
25. 25. Giera B, Straube S, Konturek P, Hahn EG, Raithel M. Plasma histamine levels and symptoms in double blind plasebo controlled histamine provocation. Inflammation Research. 2008;57(1):73-74.
26. 26. Tuck CJ, Biesiekierski JR, Schmid-Grendelmeier P, Pohl D. Food intolerances. Nutrients. 2019;11(7):1684.
27. 27. Buczyłko K, Bartnicka A, Kruszewski J, et al. Guidelines for the diagnosis and management of histamine intolerance. Polish Journal of Allergology. 2023;10(3):141-151.
28. 28. Zia JK, Chung CF, Schroeder J, et al. The feasibility, usability, and clinical utility of traditional paper food and symptom journals for patients with irritable bowel syndrome. Neurogastroenterology & Motility. 2017;29(2).
29. 29. Teresa P, Carla B, Beltran-Ortiz C, Magdalena D. Histamine intolerance: clinical characterization and determination of serum diamine oxidase ( DaO ) in a series of cases and controls. Research Square. 2020:1–13. doi: 10.21203/rs.3.rs-60226/v1.
30. 30. Schnedl WJ, Schenk M, Lackner S, Enko D, Mangge H, Forster F. Diamine oxidase supplementation improves symptoms in patients with histamine intolerance. Food Science and Biotechnology. 2019;28(6):1779–1784.
31. 31. García-Martín E, Ayuso P, Martínez C, Agúndez JAG. Improved analytical sensitivity reveals the occurrence of gender-related variability in diamine oxidase enzyme activity in healthy individuals. Clinical Biochemistry. 2007;40:1339–1341.
32. 32. Rosell-Camps A, Zibetti S, Pérez-Esteban G, Vila-Vidal M, Ferrés-Ramis L, García-Teresa-García E. Histamine intolerance as a cause of chronic digestive complaints in pediatric patients. Revista Española de Enfermedades Digestivas. 2013;105(4):201–207.
33. 33. Hoffmann KM, Gruber E, Deutschmann A, et al. Histamine intolerance in children with chronic abdominal pain. Archives of Disease in Childhood. 2013;98:832-833.
34. 34. Mayo-Yáñez M, Díaz-Díaz A, Calvo-Henríquez C, Chiesa-Estomba C, Figueroa A, Martín-Martín CS. Usefulness of the histamine intolerance assessment questionnaire for diagnosis. Revue Francaise d’Allergologie. 2020;61(2):87-91.
35. 35. Schnedl WJ, Enko D. Histamine intolerance originates in the gut. Nutrients. 2021;13(4):1262.
36. 36. Shulpekova YO, Nechaev VM, Popova IR, et al. Food intolerance: The role of histamine. Nutrients. 2021;13(9):3207.
37. 37. Cornillier H, Giraudeau B, Samimi M, et al. Effect of diet in chronic spontaneous urticaria: A systematic review. Acta Dermato-Venereologica. 2019;99(2):127–132.
38. 38. Wantke F, Gotz M, Jarisch R. Histamine-free diet: Treatment of choice for histamine-induced food intolerance and supporting treatment for chronical headaches. Clinical and Experimental Allergy. 1993;23(12):982–985.
39. 39. Tobajas Y, Alemany-Fornés M, Samarra I, et al. Diamine oxidase interactions with anti-inflammatory and anti-migraine medicines in the treatment of migraine. Journal of Clinical Medicine. 2023;12(23).
40. 40. Lackner S, Malcher V, Enko D, Mangge H, Holasek SJ, Schnedl WJ. Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance. European Journal of Clinical Nutrition. 2019;73(1):102–104.
41. 41. Music E, Silar M, Korosec P, Kosnik M, Rijavec M. Serum diamine oxidase (DAO) activity as a diagnostic test for histamine intolerance. Clinical and Translational Allergy. 2013;1(1):2011.
42. 42. Cucca V, Ramirez GA, Pignatti P, et al. Basal serum diamine oxidase levels as a biomarker of histamine intolerance: A retrospective cohort study. Nutrients. 2022;14(7):1-8.
43. 43. Arih K, Đorđević N, Košnik M, Rijavec M. Evaluation of serum diamine oxidase as a diagnostic test for histamine intolerance. Nutrients. 2023;15(19):1-9.
44. 44. van Odijk J, Weisheit A, Arvidsson M, Miron N, Nwaru B, Ekerljung L. The use of DAO as a marker for histamine intolerance: measurements and determinants in a large random population-based survey. Nutrients. 2023;15(13).
45. 45. Bent RK, Kugler C, Faihs V, Darsow U, Biedermann T, Brockow K. Placebo-controlled histamine challenge disproves suspicion of histamine intolerance. Journal of Allergy and Clinical Immunology: In Practice. 2023;11(12):3724-3731.e11.