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

Intestinal Dysbiosis in Patients with Histamine Intolerance

New study published about microbiota, histamine intolerance and DAO deficiency by the research team of the University of Barcelona (Dr. Mª Carmen Vidal). Adding clinical and scientific evidence every day.

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Abstract: An underlying cause of histamine intolerance is diamine oxidase (DAO) deficiency, which leads to defective homeostasis and a higher systemic absorption of histamine. Impaired DAO activity may have a genetic, pharmacological or pathological origin. A recent proposal also suggests it can arise from an alteration in the gut microbiota, although only one study has explored this hypothesis to date. A greater abundance of histamine-secreting bacteria in the gut could lead to the development of histamine  ntolerance. Thus, the aim of this study was to characterize the composition of the intestinal microbiota of patients with histamine intolerance symptoms and compare it with that of healthy individuals. The study was performed by sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database. Dysbiosis of the gut microbiota was observed in the histamine intolerance group who, in comparison with the healthy individuals, had a significantly lower proportion of Prevotellaceae, Ruminococcus, Faecalibacterium and Faecablibacterium prausnitzii, which are bacteria related to gut health. They also had a significantly higher abundance of histaminesecreting bacteria, including the genera Staphylococcus and Proteus, several unidentified genera belonging to the family Enterobacteriaceae and the species Clostridium perfringens and Enterococcus faecalis. A greater abundance of histaminogenic bacteria would favor the accumulation of high levels of histamine in the gut, its subsequent absorption in plasma and the appearance of adverse effects, even in individuals without DAO deficiency.

Sònia Sánchez-Pérez 1,2,3 , Oriol Comas-Basté 1,2,3 , Adriana Duelo 1,2,3, M. Teresa Veciana-Nogués 1,2,3 ,
Mercedes Berlanga 4 , M. Luz Latorre-Moratalla 1,2,3,† and M. Carmen Vidal-Carou 1,2,3,*,†

1 Department de Nutrició, Ciències de l’Alimentació i Gastronomía, Facultat de Farmàcia i Ciències de l’Alimentació, Campus de l’Alimentació de Torribera, Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain; soniasanchezperez@ub.edu (S.S.-P.); oriolcomas@ub.edu (O.C.-B.); aduelo@ub.edu (A.D.); veciana@ub.edu (M.T.V.-N.); mariluzlatorre@ub.edu (M.L.L.-M.)
2 Institut de Recerca en Nutrició i Seguretat Alimentària (INSA
UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain
3 Xarxa d’Innovació Alimentària (XIA), C/Baldiri Reixac 4, 08028 Barcelona, Spain
4 Departament de Biologia, Sanitat i Mediambient, Secció de Microbiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain; mberlanga@ub.edu

• Correspondence: mcvidal@ub.edu
  † These authors contributed equally to this work.

Citation: Sánchez-Pérez, S.; Comas-Basté, O.; Duelo, A.; Veciana-Nogués, M.T.; Berlanga, M.; Latorre-Moratalla, M.L.; Vidal-Carou, M.C. Intestinal Dysbiosis in Patients with Histamine Intolerance. Nutrients 2022, 14, 1774. https://doi.org/10.3390/nu14091774

New Regulatory Approvals Support DAO Deficiency Solution Expansion

In February 2022, the active ingredient diamine oxidase – or DAO – produced by AB Biotek’s DR Healthcare division, as well as the solutions derived from it, have obtained the GRAS (Generally Recognized As Safe, per sections 201(s) and 409 of the U.S. Food & Drug Act) qualification from the U.S. Food & Drug Administration.  This allows for the upcoming launch in the U.S. marketplace.

From the FDA regulations 21 CFR 170.3 and 21 CFR 170.30, the use of a food substance may be GRAS through scientific procedures and scientific evidence and is based on in published studies.

Additionally, at the same time, the Directorate-General for Hygiene, Food Safety & Nutrition in Rome, Italy, and the Ministry of Finance, Economy & Recovery in Paris, France, both approved the launch of DAO products in those two countries.

These three steps represent new support for continued international expansion of DR Healthcare’s solution portfolio targeting consumers with DAO deficiency.

DAO – an enzyme naturally secreted by the human body – is frequently used as a nutritional supplement to treat disorders from histamine accumulation including migraines, fibromyalgia, irritable bowel syndrome (IBS), atopic skin or even attention deficit hyperactivity disorder (ADHD). Approximately 15 percent of the population suffers from a DAO deficiency, both genetic and acquired.

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 also produces DAO for both human and animal use and offers proprietary solutions for the food, veterinary and animal health industries. More information is available at www.dr-healthcare.com/en.

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.

Histamine Intolerance—A Kind of Pseudoallergic Reaction

Biomolecules 2022, 12, 454. https://doi.org/10.3390/biom12030454

Ying Zhao 1,2,† , Xiaoyan Zhang 1,2,† , Hengxi Jin 2 , Lu Chen 1,2, Jiang Ji 1,2,* and Zhongwei Zhang 3,*

1 Department of Dermatology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China;
nanjjzhaoying@126.com (Y.Z.); hiohikari@163.com (X.Z.); chenlu1275@163.com (L.C.)
2 Department of Dermatology and Venereology, Suzhou Medical College of Soochow University,
Suzhou 215000, China; jinhengxi1995@163.com
3 Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University,
Nantong 226001, China

*Correspondence: jijiang@suda.edu.cn (J.J.); zhangzwei22@gmail.com (Z.Z.); Tel.: +86-0512-6778-3484 (J.J.)
† These authors contributed equally to this work.

Download th review here

Abstract:

Histamine intolerance (HIT) is a common disorder associated with impaired histamine metabolism. Notwithstanding, it is often misdiagnosed as other diseases because of its lack of specific clinical manifestations. HIT did not gain traction until the early 21st century. In this review, we will focus on the latest research and elaborate on the clinical manifestations of HIT, including its manifestations in special populations such as atopic dermatitis (AD) and chronic urticaria (CU), as well as the latest understanding of its etiology and pathogenesis. In addition, we will explore the latest treatment strategies for HIT and the treatment of specific cases.

International Congress of DAO Deficiency 2021

You are invited to map a new future in managing DAO Deficiency attending the International Congress on DAO Deficiency.

Sign up here

SAVE THE DATE: November 4th 2021

At DR HEALTHCARE, we are pioneers in DAO Deficiency. Since our beginnings, scientific evidence and research have driven each one of our steps. The time has come to share this knowledge with the scientific and medical community, nutrition specialists, and patients who suffer from this metabolic deficiency’s different recurring symptoms.

Together, we can go farther.

Which is why we are delighted to invite you to the International Congress of DAO Deficiency, to be held 4 November 2021, in virtual format.

Our end goal:

is to reinforce knowledge of DAO Deficiency through a complete programme of scientific sessions, with experts of worldwide renown. With a forward-looking approach, we will address both diagnosis and treatment, as well as how knowledge of DAO Deficiency has led to a paradigm shift in the field of medical nutrition.

The event will be held entirely online:

as required by this exceptional situation caused by the pandemic. However, this way we will also be able to make our shared knowledge and experiences available to professionals all around the world, saving on costs and travel, and reducing our ecological footprint.

Technology will make it possible:

for guests to attend all conferences through an immersive, comprehensive experience. In addition to the extensive medical and scientific programme, the exhibition with 3D stands, and online interaction with guests, congress participants and speakers will provide a one-of-a-kind stage with services just like at a face-to-face event. All in real time.

We eagerly await you.

Warm regards,

Gerald Dard                                             Juanjo Duelo

    Managing Director ABBiotek                   Global Business Development Director Enzymes

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.  

FOR MORE INFORMATION:

Patrick Barry +1.314.540.3865

patrick@byrnepr.net

LLYC

Tina Díaz adiaz@llorenteycuenca.com

Míriam Cusí mcusi@llorenteycuenca.com

Cristina Vilà cvila@llorenteycuenca.com

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

Download the paper here

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.

Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population

Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population

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Sukhvinder Kaura,⁎, Arif Alib, Yaser Siahbalaeic, Uzair Ahmadc, Fazila Nargisc, A.K. Pandeyd,
Balkirat Singhe

a UGC-PDF, Gene Expression Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
b UGC-BSR-FF, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
c Department of Biosciences, Jamia Millia Islamia, New Delhi, India
d Head, Department of Physiology, ESIC Medical College & Hospital, Faridabad, India
e NC Medical College & Hospital, Panipat, India

A B S T R A C T

Background: Migraine is a common neurovascular disorder affected by various levels of neurotransmitters. Low histamine metabolism is also related with pathophysiology of migraine. As diamine oxidase (DAO) gene variants are linked with higher levels of histamine in migraine patients, we investigated the possible relationship of two variants rs2052129 and rs10156191of this gene with migraine risk in North Indian population.

Methods: A case-control study for 250 migraine patients and 250 matched healthy controls was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: We found statistically significant differences in allelic frequencies of rs2052129 (p = .009, OR = 1.462; 95% CI: 1.098–1.947) and rs10156191 (p = .019, OR = 1.430; 95% CI: 1.060–1.928) variants in DAO gene. For rs1015691, we were able to show statistically significant association at all genotypic, dominant and allelic levels in both MA (for T allele, p = .020; OR = 1.662, 95% CI: 1.083–2.551) as well as in female subgroup (for T allele, p = .025, OR = 1.460; 95% CI: 1.049–2.033). But no such significant association was found in clinical sub grouping of migraine in rs2052129 as p > .05. However in gender analysis, protective effect of T allele in male migraine patients for rs2052129 (OR < 1) was found.

Conclusions: Our findings clearly indicated that female patient with rs10156191T allele and in MA subgroup showed an increased risk for migraine. Our data also indicated that rs2052129T variant showed a significant role in migraine susceptibility of this population.