Serum Diamine Oxidase Values, Indicating Histamine Intolerance, Influence Lactose Tolerance
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Abstract: Lactose intolerance (LIT) is one of the major causes of irritable bowel syndrome (IBS) spectrum complaints. Differences in inadequate lactose digestion are described as various LIT phenotypes with basically unknown pathophysiology. In LIT patients, we retrospectively assessed the effect of histamine intolerance (HIT) on expiratory hydrogen (H2) during H2 lactose breath tests. In a retrospective evaluation of charts from 402 LIT patients, 200 patients were identified as having only LIT. The other 202 LIT patients were found to additionally have diamine oxidase (DAO) values of <10 U/mL, which indicates histamine intolerance (HIT). To identify HIT, standardized questionnaires, low serum DAO values and responses to a histamine-reduced diet were used. Patients were separated into three diagnostic groups according to the result of H2 breath tests: (1) LIT, with an H2 increase of >20 parts per million (ppm), but a blood glucose (BG) increase of >20 mg/dL, (2) LIT with an H2 increase of 20 ppm in combination with a BG increase of <20 mg/dL, and (3) LIT with an exhaled H2 increase of <20 ppm and BG increase of <20 mg/dL. Pairwise comparison with the KruskalWallis test was used to compare the areas under the curve (AUC) of LIT and LIT with HIT patients. Exhaled H2 values were significantly higher in H2 > 20 ppm and BG < 20 mg/dL patients with LIT and HIT (p = 0.007). This diagnostic group also showed a significant higher number of patients (p = 0.012) and a significant higher number of patients with gastrointestinal (GI) symptoms during H2 breath tests (p < 0.001). Therefore, low serum DAO values, indicating HIT, influence results of lactose tolerance breath tests.
Citation: Schnedl,W.J.; Meier-Allard, N.; Michaelis, S.; Lackner, S.; Enko, D.; Mangge, H.; Holasek, S.J. Serum Diamine Oxidase Values, Indicating Histamine Intolerance, Influence Lactose Tolerance Breath Test Results. Nutrients 2022, 14, 2026. https://doi.org/10.3390/nu14102026
Wolfgang J. Schnedl 1,* , Nathalie Meier-Allard 2, Simon Michaelis 3 , Sonja Lackner 2 , Dietmar Enko 3,4 , Harald Mangge 4 and Sandra J. Holasek 2
1 Practice for General Internal Medicine, Dr. Theodor Körnerstrasse 19b, 8600 Bruck an der Mur, Austria
2 Division of Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz, Heinrichstrasse 31a, 8010 Graz, Austria; nathalie.allard@medunigraz.at (N.M.-A.); sonja.lackner@medunigraz.at (S.L.); sandra.holasek@medunigraz.at (S.J.H.)
3 Institute of Clinical Chemistry, Laboratory Medicine, Hospital Hochsteiermark, Vordernberger Straße 42, 8700 Leoben, Austria; simon.michaelis@kages.at (S.M.); enko.dietmar@gmx.at (D.E.)
4 Clinical Institute of Medical, Chemical Laboratory Diagnosis, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria; harald.mangge@klinikum-graz.at
- Correspondence: w.schnedl@dr-schnedl.at; Tel.: +43-3612-55833; Fax: +43-3612-55833-22
AB Biotek Acquires Spanish Biomedical DR Healthcare
Respective leaders in fermentation science and DAO-based medical nutrition join together to focus on innovative enzyme-based solutions for the human nutrition & health market.
PETERBOROUGH, U.K. 26 may 2021 – AB Biotek, a global business division of Associated British Foods plc – today announces that it has acquired DR Healthcare, a biomedical company focused on the dietary management of chronic diseases based in Barcelona, Spain.
This acquisition enables AB Biotek to boost its growing portfolio of differentiated microbiome modulating solutions for human nutrition and health. The acquisition adds diamine oxidase (DAO), an important intestinal enzyme, that will expand AB Biotek’s already strong commercial portfolio of probiotic yeast strains.
DAO, naturally secreted by the human body, is widely known as a critical enzyme at the core of reducing symptoms of many of today’s ailments, including migraine, food intolerances and attention deficit hyperactivity disorder, prevalent in millions of people around the world.
Juanjo Duelo, the founder of DR Healthcare, will remain with the business.
“With the acquisition of DR Healthcare, we now have the next stepping stone in shaping our science-based organization to serve the fast-growing human nutrition and health space,” said Gerald Dard, global managing director, AB Biotek. “DR Healthcare has a strong track record in this area, and we welcome our new colleagues who are equally passionate about the health and wellness of today’s consumers.”
“I am very excited about this new chapter as our companies have many shared values, from advanced health solutions and deep science to an extreme passion for what we do,” said Juanjo Duelo. “The future is bright under the good ownership of AB Biotek, and the timing is perfect to bring new, innovative technologies to improve the wellbeing of those people who suffer from various pathologies associated with the deficiency of DAO.”
About AB Biotek
AB Biotek contributes to the success of customers through the delivery of customized fermentation-based, sustainable solutions containing proprietary and/or purposefully sourced microorganisms to created differentiated food, beverage, health & nutrition business opportunities. Science and advanced microorganism fermentation technology are core enablers. AB Biotek has commercial scale production and research development facilities located around the world. For more information about our product applications and unmatched technical service capabilities, please visit www.abbiotek.com.
About DR Healthcare
Founded in Barcelona, Spain, in 2007, DR Healthcare is a biomedical company specialized in medical nutrition and dedicated to the research, development, innovation, marketing and licensing of new nutraceuticals, functional foods, active ingredients and customized solutions. Our medical nutrition products are aimed at dietary management of chronic diseases, physiological dysfunctions and/or metabolic diseases, mainly associated with metabolic disorders caused by a deficiency of the intestinal enzyme diamine oxidase (DAO). DR Healthcare produces DAO for both human and animal use and offers proprietary solutions for the food, pharmaceutical, veterinary and animal health industries. More information is available at www.dr-healthcare.com/en.
Patrick Barry +1.314.540.3865
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Histamine Intolerance Originates in the Gut
Nutrients 2021, 13, 1262. https://doi.org/10.3390/nu13041262
Wolfgang J. Schnedl 1,* and Dietmar Enko 2
1 General Internal Medicine Practice, Dr. Theodor Körnerstrasse 19b, A-8600 Bruck, Austria
2 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz,
Auenbruggerplatz 15, A-8036 Graz, Austria; enko.dietmar@gmx.at
- Correspondence: w.schnedl@dr-schnedl.at; Tel.: +43-3612-55833; Fax: +43-3612-55833-22
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Abstract:
Histamine intolerance (HIT) is assumed to be due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO) and, therefore, the food component histamine not being degraded and/or absorbed properly within the GI tract. Involvement of the GI mucosa in various disorders and diseases, several with unknown origin, and the effects of some medications seem to reduce gastrointestinal DAO activity. HIT causes variable, functional, nonspecific, non-allergic GI and extra-intestinal complaints. Usually, evaluation for HIT is not included in differential diagnoses of patients with unexplained, functional GI complaints or in the here-listed disorders and diseases. The clinical diagnosis of HIT is challenging, and the thorough anamnesis of all HIT-linked complaints, using a standardized questionnaire, is the mainstay of HIT diagnosis. So far, DAO values in serum have not been established to correlate with DAO activity in the gut, but the diagnosis of HIT may be supported with determination of a low serum DAO value. A targeted dietary intervention, consisting of a histamine-reduced diet and/or supplementation with oral DAO capsules, is helpful to reduce HIT-related symptoms. This manuscript will present why histamine should also be taken into account in the differential diagnoses of patients with various diseases and disorders of unknown origin, but with association to functional gastrointestinal complaints. In this review, we discuss currently increasing evidence that HIT is primarily a gastrointestinal disorder and that it originates in the gut.
Massive release of the histamine‐degrading enzyme diamine oxidase during severe anaphylaxis in mastocytosis patients
Thomas Boehm, 1 Birgit Reiter, 2 Robin Ristl, 3 Karin Petroczi, 1 Wolfgang Sperr, 4 Thomas Stimpfl, 2 Peter Valent, 4 and Bernd Jilma 1
Allergy. 2019 Mar; 74(3): 583–593.
Published online 2019 Jan 1. doi: 10.1111/all.13663 PMCID: PMC6590243 PMID: 30418682
Abstract
Background
Histaminolytic activity mediated by diamine oxidase (DAO) is present in plasma after induction of severe anaphylaxis in rats, guinea pigs, and rabbits. Heparin released during mast cell degranulation in the gastrointestinal tract might liberate DAO from heparin‐sensitive storage sites. DAO release during anaphylaxis has not been demonstrated in humans.
Methods
Plasma DAO, tryptase, and histamine concentrations of four severe anaphylaxis events were determined at multiple serial time points in two patients with systemic mastocytosis. The histamine degradation rates were measured in anaphylaxis samples and in pregnancy sera and plasma with comparable DAO concentrations.
Results
Mean DAO (132 ng/mL) and tryptase (304 ng/mL) concentrations increased 187‐ and 4.0‐fold, respectively, over baseline values (DAO 0.7 ng/mL, tryptase 76 ng/mL) during severe anaphylaxis. Under non‐anaphylaxis conditions, DAO concentrations were not elevated in 29 mastocytosis patients compared to healthy volunteers and there was no correlation between DAO and tryptase levels in mastocytosis patients. The histamine degradation rate of DAO in plasma from mastocytosis patients during anaphylaxis is severely compromised compared to DAO from pregnancy samples.
Conclusion
During severe anaphylaxis in mastocytosis patients, DAO is likely released from heparin‐sensitive gastrointestinal storage sites. The measured concentrations can degrade histamine, but DAO activity is compromised compared to pregnancy samples. For accurate histamine measurements during anaphylaxis, DAO inhibition is essential to inhibit further histamine degradation after blood withdrawal. Determination of DAO antigen levels might be of clinical value to improve the diagnosis of mast cell activation.
The colorimetric assay of diamine oxidase activity with high sensitivity based on calixarene derivative-capped gold nanoparticles
The colorimetric assay of diamine oxidase activity with high sensitivity based on calixarene derivative-capped gold nanoparticles
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Abstract
Diamine oxidase (DAO) is involved in regulating ingested or endogenous histamine, several types of human cancer, and the cell mass during embryonic development. Furthermore, DAO is a potential indicator of intestinal mucosa damage in inflammatory and neoplastic diseases or after chemotherapy. Therefore, developing a biosensor is urgently needed to assay DAO activity. In this work, a simple but sensitive colorimetric biosensor is developed for DAO assay and inhibitor screening. The biosensor is based on host-guest interactions between the amine group on the terminal of 1,6-hexanediamine (HMD) and p-sulfonatocalix[6]arene (pSC6). These interactions may aggregate pSC6 modified gold nanoparticles (AuNPs) and induce the corresponding color change of the test solution. Specifically, AuNP aggregation is affected because coordination reactivity does not exist between oxidized HMD and pSC6 during HMD oxidation by DAO. Therefore, a simple colorimetric method with high sensitivity for the assay of DAO activity is proposed. A linear relationship is presented under optimized experimental conditions in a range of 0.15 mU mL−1 to 4.5 mU mL−1 with the lowest detection limit of 0.062 mU mL−1. Moreover, the inhibition effect of guanidine on DAO activity is tested with the IC50 value of 2.4 μM using the proposed biosensor. Therefore, this biosensor has great potential not only for the detection of DAO activity but also for inhibitor screening in future.
DOI:10.1039/C7AY00227K