Diamine oxidase supplementation improves symptoms in patients with histamine intolerance

Wolfgang J Schnedl, Michael Schenk, Sonja Lackner, Dietmar Enko, Harald Mangge, Florian Forster, Wolfgang J Schnedl, Michael Schenk, Sonja Lackner, Dietmar Enko, Harald Mangge, Florian Forster

Abstract

Histamine intolerance (HIT) is thought to be caused by a disproportionate amount of histamine in the body. The enzyme diamine oxidase (DAO) is considered for the gastrointestinal degradation of histamine. For this open-label interventional pilot study, we identified 28 patients with HIT. For 4 weeks, they were instructed to take DAO capsules before meals. Then, throughout a follow-up period, they were instructed not to take the DAO. We used a questionnaire that included 22 symptoms, which were divided into 4 categories, as well as a symptom severity score. All symptoms improved significantly during the oral supplementation of DAO. During the follow-up period, without DAO supplementation, the symptoms sum scores increased again. The symptom intensity score was reduced for all symptoms. We have demonstrated, a significant reduction of every HIT-related symptom and its intensity due to DAO oral supplements. The ClinicalTrials.gov identifier (NCT number) is NCT03298568.

Keywords: Diamine oxidase; Extra-intestinal; Gastrointestinal; Histamine; Malabsorption.

Conflict of interest statement

Conflict of interestM. Schenk, S. Lackner and H. Mangge declare no competing interests. W. J. Schnedl received speaking honoraria from Sciotec. F. Forster is employed by Sciotec. The authors are grateful for the free supply of DAOSIN® capsules from Sciotec. Study monitoring and analysis of the data with BioTeSys GmbH was remunerated by Sciotec.

© The Author(s) 2019.

Figures

Fig. 1
Fig. 1
Scatter-plot of symptoms sum-score of all 22 HIT-related symptoms throughout the study period of 8 weeks. Oral supplementation of DAO from visit 1 to visit 3 (V1 to V3); no oral DAO from visit 3 to visit 5 (V3 to V5)
Fig. 2
Fig. 2
Scatter-plot of symptoms sum-score of the most common and diagnostic 5 GI symptoms (bloating, postprandial fullness, abdominal pain, belching and diarrhea) for HIT throughout the study period of 8 weeks. Oral supplementation of DAO from visit 1 to visit 3 (V1 to V3); no oral DAO from visit 3 to visit 5 (V3 to V5)
Fig. 3
Fig. 3
Scatter-plot of symptoms sum-score of respiratory symptoms (rhinorrhea, nose congestion, sneezing and asthma) throughout the study period of 8 weeks. Oral supplementation of DAO from visit 1 to visit 3 (V1 to V3); no oral DAO from visit 3 to visit 5 (V3 to V5)
Fig. 4
Fig. 4
Mean intensity of GI symptoms (abdominal pain, intestinal colic, bloating, diarrhea, constipation, nausea, belching, emesis, postprandial fullness and dysmenorrhea) throughout the study period of 8 weeks. Oral supplementation of DAO from visit 1 to visit 3 (V1 to V3); no oral DAO from visit 3 to visit 5 (V3 to V5)
Fig. 5
Fig. 5
Scatter-plot of serum DAO values throughout the study period of 8 weeks. Oral supplementation of DAO from visit 1 to visit 3 (V1 to V3); no oral DAO from visit 3 to visit 5 (V3 to V5). Normal range for DAO in serum 0.5–10 U/mL

References

    1. Doeun D, Davaatseren M, Chung MS. Biogenic amines in foods. Food Sci. Biotechnol. 2017;26:1463–1474. doi: 10.1007/s10068-017-0239-3.
    1. Eisenbruch S, Enck P. Placebo effects and their determinants in gastrointestinal disorders. Nature Rev. Gastoenterol. Hepatol. 2015;12:472–485. doi: 10.1038/nrgastro.2015.117.
    1. Elmore BO, Bollinger JA, Dooley DM. Human kidney diamine oxidase: heterologous expression, purification, and characterization. J. Biol. Inorg. Chem. 2007;7:565–579. doi: 10.1007/s00775-001-0331-1.
    1. Izquierdo-Casas J, Comas-Basté O, Latorre-Moratalla ML, Lorente-Gascón M, Duelo A, Soler-Singla L, Vidal-Carou MC. Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial. Clin. Nutr. 2019;38:152–158. doi: 10.1016/j.clnu.2018.01.013.
    1. Jones BL, Kearns GL. Histamine: New thoughts about a familiar mediator. Clin. Pharm. Therap. 2011;89:189–197. doi: 10.1038/clpt.2010.256.
    1. Jumarie C, Séïde M, Marcocci L, Pietrangeli P, Mateescu MA. Diamine oxidase from white pea (Lathyrus sativus) combined with catalase protects the human intestinal Caco-2 cell line from histamine damage. Appl. Biochem. Biotechnol. 2017;182:1171–1181. doi: 10.1007/s12010-016-2390-3.
    1. Kacik J, Wróblewska B, Lewicki S, Zdanowski R, Kalicki B. Serum diamine oxidase in pseudoallergy in the pediatric population. Adv. Exp. Med. Biol. 2018;1039:35–44. doi: 10.1007/5584_2017_81.
    1. Komericki P, Klein G, Reider N, Hawranek T, Strimitzer T, Lang R, Kranzelbinder B, Aberer W. Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomized, double-blind, placebo-controlled cross-over study. Wien. Klin. Wochenschr. 2011;123:15–20. doi: 10.1007/s00508-010-1506-y.
    1. Lackner S, Malcher V, Enko D, Mangge H, Holasek S, Schnedl WJ. Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance. Eur. J. Clin. Nutr. 2019;73:102–104. doi: 10.1038/s41430-018-0260-5.
    1. Reese I, Ballmer-Weber B, Beyer K, Fuchs T, Kleine-Tebbe J, Klimek L, Lepp U, Niggemann B, Saloga J, Schäfer C, Werfel T, Zuberbier T, Worm M. 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 J. Int. 2017;26:72–79. doi: 10.1007/s40629-017-0011-5.
    1. Schnedl WJ, Lackner S, Enko D, Schenk M, Holasek SJ, Mangge H. Evaluation of symptoms and symptom combinations in histamine intolerance. Intest. Res. in press (2019)
    1. Sciotec. DAOSIN® product information (German). Available from: . Accessed October 20, 2018.
    1. Smolinska S, Jutel M, Crameri R, O’Mahony L. Histamine and gut mucosal immune regulation. Allergy. 2014;69:273–281. doi: 10.1111/all.12330.
    1. Wilder-Smith CH, Olesen SS, Materna A, Drewes AM. Predictors of response to a low-FODMAP diet in patients with functional gastrointestinal disorders and lactose or fructose intolerance. Aliment. Pharmacol. Ther. 2017;45:1094–1106. doi: 10.1111/apt.13978.
    1. Wollin A, Wang X, Tso P. Nutrients regulate diamine oxidase release from intestinal mucosa. Am. J. Physiol. 1988;275:R969–R975.
    1. Yacoub MR, Ramirez GA, Berti A, Mercurio G, Breda D, Saporiti N, Burastero S, Dagna L, Colombo G. Diamine oxidase supplementation in chronic spontaneous urticaria: A randomized, double-blind placebo-controlled study. Int. Arch. Allergy Immunol. 2018;26:1–4.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner