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Diamine Oxidase Deficiency: Prevalence, Consequences, and Solutions

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 12021

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Special Issue Editor

Dr. Hilario Blasco-Fontecilla

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Department of Psychiatry, Puerta de Hierro University Hospital, Health Research Institute Puerta de Hierro-Segovia de Arana (IDIPHISA), Majadahonda, Madrid, Spain
Interests: suicidal behavior; personality disorders; ADHD; psychopharmacology; biomarkers; nutrition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are delighted to invite you to send a manuscript to this Special Issue focused on diamine oxidase (DAO) deficiency.

Diamine oxidase enzyme (DAO) is responsible for histamine gastro-intestinal degradation. DAO deficiency may implicate an excess of histamine (“histamine intolerance”), which has been linked to a growing number of diseases, such as migraines, gastro-intestinal and pseudo-allergic symptomatology, among others. However, data on the relationship between the DAO activity, and other disorders, including mental disorders such as attention deficit/hyperactivity disorder (ADHD), are scarce. In any case, there is increasing interest in the role of DAO deficiency with a wide array of medical diseases.

The goal of the present Special Issue is to reinforce the knowledge of DAO deficiency by gathering a complete scientific volume with world-renowned experts. We will include manuscripts addressing both diagnosis and treatment, and ongoing clinical studies across the globe. We are sure that DAO Deficiency represents a paradigm shift in medical nutrition.

Dr. Hilario Blasco-Fontecilla
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

DAO deficiency
histamine intolerance
nutrition
migraine
intestinal dysbiosis
gut micobiota
genetic profiles
ADHD
sleep disorders
fibromyalgia
allergy

Published Papers (6 papers)

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Research

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14 pages, 1623 KiB

Open AccessArticle

Exploring the Relationship between Diamine Oxidase and Psychotropic Medications in Fibromyalgia Treatment, Finding No Reduction in Diamine Oxidase Levels and Activity except with Citalopram

by Yaiza Tobajas, Marc Alemany-Fornés, Iris Samarra, Jordi Romero-Giménez, Jordi Cuñé-Castellana, Maria Tintoré, Antoni del Pino, Núria Canela, Josep M. del Bas, Nàdia Ortega-Olivé, Carlos de Lecea and Xavier Escoté

J. Clin. Med. 2024, 13(3), 792; https://doi.org/10.3390/jcm13030792 - 30 Jan 2024

Viewed by 1041

Abstract

Background: Histamine intolerance manifests when there is an imbalance between the production of histamine and the body’s capacity to metabolise it. Within the gastrointestinal tract, diamine oxidase (DAO) plays a pivotal role in breaking down ingested histamine. Insufficient levels of DAO have been linked to various diseases affecting the respiratory, cardiovascular, nervous, muscular, and digestive systems; some of these symptoms are evidenced in fibromyalgia syndrome. This underscores the crucial role of DAO in maintaining the histamine balance and highlights its association with diverse physiological systems and health conditions. The management of fibromyalgia commonly involves the use of psychotropic medications; however, their potential interactions with DAO remain not fully elucidated. Methods: This study delved into the influence of various psychotropic medications on DAO activity through in vitro experiments. Additionally, we explored their impact on the human intestinal cell line Caco-2, examining alterations in DAO expression at both the mRNA and protein levels along with DAO activity. Results: Notably, the examined drugs—sertraline, pregabalin, paroxetine, alprazolam, and lorazepam—did not exhibit inhibitory effects on DAO activity or lead to reductions in DAO levels. In contrast, citalopram demonstrated a decrease in DAO activity in in vitro assays without influencing DAO levels and activity in human enterocytes. Conclusions: These findings imply that a collaborative approach involving psychotropic medications and DAO enzyme supplementation for individuals with fibromyalgia and a DAO deficiency could offer potential benefits for healthcare professionals in their routine clinical practice. Full article

(This article belongs to the Special Issue Diamine Oxidase Deficiency: Prevalence, Consequences, and Solutions)

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11 pages, 2126 KiB

Open AccessArticle

Diamine Oxidase Interactions with Anti-Inflammatory and Anti-Migraine Medicines in the Treatment of Migraine

by Yaiza Tobajas, Marc Alemany-Fornés, Iris Samarra, Jordi Romero-Giménez, Maria Tintoré, Antoni del Pino, Núria Canela, Josep M. del Bas, Nàdia Ortega-Olivé, Carlos de Lecea and Xavier Escoté

J. Clin. Med. 2023, 12(23), 7502; https://doi.org/10.3390/jcm12237502 - 4 Dec 2023

Cited by 2 | Viewed by 1773

Abstract

Histamine intolerance arises when there is a disparity between the production of histamine and the body’s ability to break it down. In the gastrointestinal tract, the primary enzyme responsible for metabolizing ingested histamine is diamine oxidase (DAO), and a shortage of this enzyme has been associated with some diseases related to the respiratory, cardiovascular, nervous, muscular, and digestive systems, in addition to migraines. The treatment of migraines typically revolves around the utilization of both anti-migraine and anti-inflammatory drugs, but their interaction with DAO is not thoroughly understood. In this study, we examined the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-migraine medications on DAO activity through in vitro experiments. We also investigated their effects on the human intestinal cell line Caco-2, assessing changes in DAO expression (both at the mRNA and protein levels) as well as DAO activity. The tested drugs, including ibuprofen, acetylsalicylic acid, paracetamol, a combination of acetylsalicylic acid with paracetamol and caffeine, zolmitriptan, and sumatriptan, did not inhibit DAO activity or reduce their levels. However, naproxen reduced DAO protein levels in human enterocyte cultures while not affecting DAO activity. These results suggest that combining anti-inflammatory and anti-migraine drugs with DAO enzyme supplementation for migraine patients with DAO deficiency could be beneficial for healthcare professionals in their daily practice. Full article

(This article belongs to the Special Issue Diamine Oxidase Deficiency: Prevalence, Consequences, and Solutions)

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13 pages, 795 KiB

Open AccessArticle

Lower Urinary Tract Symptoms (LUTS) as a New Clinical Presentation of Histamine Intolerance: A Prevalence Study of Genetic Diamine Oxidase Deficiency

by Jose Ponce Díaz-Reixa, Marcos Aller Rodríguez, Sara Martínez Breijo, Jorge Suanzes Hernández, Eva Ruiz Casares, Teresa Perucho Alcalde, Manuel Bohorquez Cruz, Teresa Mosquera Seoane, Jose M. Sánchez Merino, Jacobo Freire Calvo, Paula Fernández Suárez and Venancio Chantada Abal

J. Clin. Med. 2023, 12(21), 6870; https://doi.org/10.3390/jcm12216870 - 31 Oct 2023

Cited by 2 | Viewed by 1259

Abstract

Lower urinary tract symptoms (LUTS) are highly prevalent, and their treatment is mainly focused on the control of symptoms. Histamine intolerance (HIT) has been related to a variety of systemic symptoms. DAO deficiency has been identified as a significant factor contributing to histamine intolerance (HIT). Preclinical evidence indicates the involvement of histamine in the lower urinary tract. This study aimed to assess the prevalence of diamine oxidase deficiency (DAO) in a prospective cohort of 100 patients with at least moderate LUTS. A genetic study of four single nucleotide polymorphisms (SNPs) (c.-691G>T, c.47C>T, c.995C>T, and c.1990C>G) was performed. HIT was found in 85.9% of patients. The prevalence of at least one minor allele in the SNPs analyzed was 88%, without gender differences. Storage symptoms were more intense in the presence of HIT as well as asthenia and neurological and musculoskeletal symptoms. The presence of minor alleles of the AOC1 gene was associated with a higher intensity of symptoms. Minor alleles from c.-691G>T and c.47C>T SNPs were also associated with a greater severity of obstructive symptoms. Thirty-one percent of patients presented the four SNPS with at least one associated minor allele. The relationship between HIT and LUTS in a mixed population of men and women found in this study supports further investigations to define the pathophysiology of histamine in LUTS. Full article

(This article belongs to the Special Issue Diamine Oxidase Deficiency: Prevalence, Consequences, and Solutions)

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12 pages, 1409 KiB

Open AccessArticle

Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial

by Gülşah Okutan, Guerthy Melissa Sánchez Niño, Ana Terrén Lora, Sara López Oliva and Ismael San Mauro Martín

J. Clin. Med. 2023, 12(20), 6449; https://doi.org/10.3390/jcm12206449 - 10 Oct 2023

Cited by 1 | Viewed by 2053

Abstract

Fibromyalgia (FM) is characterized by chronic musculoskeletal pain, muscle tension, joint mobility loss, and several psychological symptoms severely affecting patient well-being. Histamine is naturally degraded in the small intestine by diamine oxidase (DAO). Hereditary or acquired DAO deficiency causes extracellular histamine accumulation, leading to symptoms similar to those of individuals diagnosed with FM. Thus, this study aimed to assess the efficacy of adding DAO supplementation for 8 weeks to their standard therapy. We randomly assigned 100 women with FM (age: 33–61 years) to the supplementation and control groups. The Fibromyalgia Impact Questionnaire (FIQ), the Pain Catastrophizing Scale (PCS), and intensity scales were applied for a series of clinical symptoms together with the Bristol scale to assess the added value of DAO supplementation. Patients in both groups were receiving complete pharmacological support but some differences in the number of subjects receiving analgesics, antidepressants, and anxiolytics was noted. Patients in both study groups experienced favorable changes during the evaluation period as indicated by their final FIQ and PCS scores, particularly in the DAO group in the latter questionnaire. Qualitatively, the patients assigned to the DAO treatment group had lower scores for fatigue, anxiety, depression, burning and for rumination, magnification, and helplessness. Full article

(This article belongs to the Special Issue Diamine Oxidase Deficiency: Prevalence, Consequences, and Solutions)

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12 pages, 2047 KiB

Open AccessArticle

Interaction of Diamine Oxidase with Psychostimulant Drugs for ADHD Management

J. Clin. Med. 2023, 12(14), 4666; https://doi.org/10.3390/jcm12144666 - 13 Jul 2023

Cited by 4 | Viewed by 1757

Abstract

Histamine intolerance occurs when there is an imbalance between histamine production and the capacity for histamine degradation. Diamine oxidase (DAO) is the main enzyme for the catabolism of ingested histamine degradation in the gastrointestinal tract and its deficiency has been linked to allergy-like symptoms. Psychostimulant drugs are commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD), but their interaction with DAO is not well characterized. In this work, we evaluated the effects of psychostimulant drugs (methylphenidate and lisdexamfetamine) on in vitro DAO activity and in the human cell line of enterocytes (Caco-2), evaluating DAO expression (mRNA and protein) and DAO activity. Methylphenidate and lisdexamfetamine did not repress the in vitro DAO activity. In addition, in Caco-2 cells, lisdexamfetamine promoted a strong upregulation of DAO mRNA levels, whereas methylphenidate tended to induce DAO activity. To sum up, methylphenidate and lisdexamfetamine treatments do not reduce DAO activity. These findings could be useful for physicians prescribing these two drugs to ADHD patients affected by DAO deficiency. Full article

(This article belongs to the Special Issue Diamine Oxidase Deficiency: Prevalence, Consequences, and Solutions)

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Other

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23 pages, 941 KiB

Open AccessHypothesis

Is Histamine and Not Acetylcholine the Missing Link between ADHD and Allergies? Speer Allergic Tension Fatigue Syndrome Re-Visited

by Hilario Blasco-Fontecilla

J. Clin. Med. 2023, 12(16), 5350; https://doi.org/10.3390/jcm12165350 - 17 Aug 2023

Cited by 2 | Viewed by 3325

Abstract

Speer allergic tension-fatigue syndrome (SATFS) is a classic allergy syndrome characterized by allergy-like symptoms, muscle tension, headaches, chronic fatigue, and other particular behaviors that were initially described in the fifties. The particular behaviors displayed include symptoms such as hyperkinesis, hyperesthesia (i.e., insomnia), restlessness, and distractibility, among others. Interestingly, these symptoms are very similar to descriptions of attention deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder worldwide, which is characterized by inattention, hyperactivity, and impulsivity. The clinical description of SATFS precedes the nomination of ADHD in 1960 by Stella Chess. In this conceptual paper, we stress that there is a gap in the research on the relationship between ADHD and allergic pathologies. The hypotheses of this conceptual paper are (1) SATFS is probably one of the first and best historical descriptions of ADHD alongside a common comorbidity (allergy) displayed by these patients; (2) SATFS (ADHD) is a systemic disease that includes both somatic and behavioral manifestations that may influence each other in a bidirectional manner; (3) The role of neuroinflammation and histamine is key for understanding the pathophysiology of ADHD and its frequent somatic comorbidities; (4) The deficiency of the diamine oxidase (DAO) enzyme, which metabolizes histamine extracellularly, may play a role in the pathophysiology of ADHD. Decreased DAO activity may lead to an accumulation of histamine, which could contribute to core ADHD symptoms and comorbid disorders. Further empirical studies are needed to confirm our hypotheses. Full article

(This article belongs to the Special Issue Diamine Oxidase Deficiency: Prevalence, Consequences, and Solutions)

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