{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:59Z","timestamp":1787028659078,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Generalitat de Catalunya","award":["2021-SGR-00861"],"award-info":[{"award-number":["2021-SGR-00861"]}]},{"name":"Generalitat de Catalunya","award":["PID2020-117670RB-C21"],"award-info":[{"award-number":["PID2020-117670RB-C21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Diamine oxidase (DAO) deficiency can lead to excessive histamine absorption at the intestinal level, triggering symptoms that affect the gastrointestinal, neurological, dermatological, respiratory, circulatory, and musculoskeletal systems. This condition, known as histamine intolerance, is more prevalent in women. While serum DAO levels have been observed to increase during pregnancy in healthy women, there is a lack of in-depth studies evaluating the relationship between pregnancy, DAO activity, and histamine intolerance symptoms. This is the first study to assess serum DAO activity before, during, and after pregnancy, as well as the evolution of histamine intolerance symptoms in women diagnosed with this condition. Due to low histamine, diets are quite restrictive, no dietary intervention was considered for pregnant women. Methods: This prospective observational study used an assessment questionnaire to evaluate the presence or absence of histamine-related symptoms in 30 adult women with histamine intolerance before, during, and after pregnancy. Serum DAO activity was also measured at the three time points. Results: Nearly all women (27 out of 30) experienced symptom improvement during pregnancy (p &lt; 0.001). Specifically, at least 77% of women reported a marked reduction in flatulence, bloating, headache, rhinorrhea, flushing, pruritus, hypotonia, or muscle pain. Concurrently, the DAO activity significantly increased 11-fold from the baseline, coinciding with symptom relief. At two months postpartum, symptoms tended to reappear, accompanied by a significant decrease in DAO activity in all participants. Conclusions: This first-of-its-kind observational study demonstrates an improvement in histamine intolerance symptoms and an increase in serum DAO activity during pregnancy. The pronounced symptom relief suggests that restrictive diets, such as low-histamine diets, may not be necessary during pregnancy. Further research is required to confirm these novel findings.<\/jats:p>","DOI":"10.3390\/jcm14134573","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T13:06:17Z","timestamp":1751288777000},"page":"4573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Improvement of Histamine Intolerance Symptoms in Pregnant Women with Diamine Oxidase Deficiency: An Exploratory Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-1289","authenticated-orcid":false,"given":"Adriana","family":"Duelo","sequence":"first","affiliation":[{"name":"Departament de Nutrici\u00f3, Ci\u00e8ncies de l\u2019Alimentaci\u00f3 i Gastronomia, Campus de l\u2019Alimentaci\u00f3 de Torribera, Universitat de Barcelona (UB), 08921 Santa Coloma de Gramenet, Spain"},{"name":"Institut de Recerca en Nutrici\u00f3 i Seguretat Aliment\u00e0ria (INSA\u00b7UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain"},{"name":"International Institute of DAO Deficiency, C\/Escoles Pies 49, 08017 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4818-2224","authenticated-orcid":false,"given":"S\u00f2nia","family":"S\u00e1nchez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Institut de Recerca en Nutrici\u00f3 i Seguretat Aliment\u00e0ria (INSA\u00b7UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), c\/Rossell\u00f3 149, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0266-9245","authenticated-orcid":false,"given":"Salvador","family":"Pellicer-Roca","sequence":"additional","affiliation":[{"name":"Departament de Nutrici\u00f3, Ci\u00e8ncies de l\u2019Alimentaci\u00f3 i Gastronomia, Campus de l\u2019Alimentaci\u00f3 de Torribera, Universitat de Barcelona (UB), 08921 Santa Coloma de Gramenet, Spain"},{"name":"Institut de Recerca en Nutrici\u00f3 i Seguretat Aliment\u00e0ria (INSA\u00b7UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"S\u00e1nchez-Buxens","sequence":"additional","affiliation":[{"name":"International Institute of DAO Deficiency, C\/Escoles Pies 49, 08017 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-0395","authenticated-orcid":false,"given":"Oriol","family":"Comas-Bast\u00e9","sequence":"additional","affiliation":[{"name":"Departament de Nutrici\u00f3, Ci\u00e8ncies de l\u2019Alimentaci\u00f3 i Gastronomia, Campus de l\u2019Alimentaci\u00f3 de Torribera, Universitat de Barcelona (UB), 08921 Santa Coloma de Gramenet, Spain"},{"name":"Institut de Recerca en Nutrici\u00f3 i Seguretat Aliment\u00e0ria (INSA\u00b7UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-7180","authenticated-orcid":false,"given":"M. Luz","family":"Latorre-Moratalla","sequence":"additional","affiliation":[{"name":"Departament de Nutrici\u00f3, Ci\u00e8ncies de l\u2019Alimentaci\u00f3 i Gastronomia, Campus de l\u2019Alimentaci\u00f3 de Torribera, Universitat de Barcelona (UB), 08921 Santa Coloma de Gramenet, Spain"},{"name":"Institut de Recerca en Nutrici\u00f3 i Seguretat Aliment\u00e0ria (INSA\u00b7UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-8626","authenticated-orcid":false,"given":"M. Carmen","family":"Vidal-Carou","sequence":"additional","affiliation":[{"name":"Departament de Nutrici\u00f3, Ci\u00e8ncies de l\u2019Alimentaci\u00f3 i Gastronomia, Campus de l\u2019Alimentaci\u00f3 de Torribera, Universitat de Barcelona (UB), 08921 Santa Coloma de Gramenet, Spain"},{"name":"Institut de Recerca en Nutrici\u00f3 i Seguretat Aliment\u00e0ria (INSA\u00b7UB), Universitat de Barcelona (UB), Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/ajcn\/85.5.1185","article-title":"Histamine and histamine intolerance","volume":"85","author":"Maintz","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.coi.2017.08.011","article-title":"Immune regulation by histamine and histamine-secreting bacteria","volume":"48","author":"Barcik","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-P\u00e9rez, S., Comas-Bast\u00e9, O., Duela, A., Veciana-Nogu\u00e9s, M.T., Berlanga, M., Latorre-Moratalla, M.L., and Vidal-Carou, M.C. (2022). Intestinal Dysbiosis in Patients with Histamine Intolerance. Nutrients, 14.","DOI":"10.3390\/nu14091774"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Comas-Bast\u00e9, O., S\u00e1nchez-P\u00e9rez, S., Veciana-Nogu\u00e9s, M.T., Latorre-Moratalla, M.L., and Vidal-Carou, M.C. (2020). Histamine intolerance: The current state of the art. Biomolecules, 10.","DOI":"10.3390\/biom10081181"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Duelo, A., Comas-Bast\u00e9, O., S\u00e1nchez-P\u00e9rez, S., Veciana-Nogu\u00e9s, M.T., Ruiza-Casares, E., Vidal-Carou, M.C., and Latorre-Moratalla, M.L. (2024). Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance. Nutrients, 16.","DOI":"10.3390\/nu16081142"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/j.1398-9995.2011.02548.x","article-title":"Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities","volume":"66","author":"Maintz","year":"2011","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1097\/FPC.0b013e328012b8e4","article-title":"Genetic variability of human diamine oxidase: Occurrence of three nonsynonymous polymorphisms and study of their effect on serum enzyme activity","volume":"17","author":"Ayuso","year":"2007","journal-title":"Pharmacogenet. Genom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00508-010-1506-y","article-title":"Histamine intolerance: Lack of reproducibility of single symptoms by oral provocation with histamine: A randomised, double-blind, placebo-controlled cross-over study","volume":"123","author":"Komericki","year":"2011","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1177\/0394632015617170","article-title":"Serum diamine oxidase activity in patients with histamine intolerance","volume":"29","author":"Manzotti","year":"2016","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.clnu.2018.01.013","article-title":"Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial","volume":"38","author":"Duelo","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1159\/000488142","article-title":"Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study","volume":"176","author":"Yacoub","year":"2018","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s10068-019-00627-3","article-title":"Diamine oxidase supplementation improves symptoms in patients with histamine intolerance","volume":"28","author":"Schnedl","year":"2019","journal-title":"Food Sci. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Okutan, G., S\u00e1nchez Ni\u00f1o, G.M., Terr\u00e9n Lora, A., L\u00f3pez Oliva, S., and San Mauro Mart\u00edn, I. (2023). Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial. J. Clin. Med., 12.","DOI":"10.3390\/jcm12206449"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kettner, L., Seitl, I., and Fischer, L. (2022). Toward Oral Supplementation of Diamine Oxidase for the Treatment of Histamine Intolerance. Nutrients, 14.","DOI":"10.3390\/nu14132621"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.clnesp.2023.09.892","article-title":"Observational study to assess the efficacy and safety of diaminooxidase (DAO) supplementation in patients with histamine intolerance (HIT)","volume":"58","year":"2023","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1111\/j.1365-2222.1993.tb00287.x","article-title":"Histamine-free diet: Treatment of choice for histamine-induced food intolerance and supporting treatment for chronical headaches","volume":"23","author":"Wantke","year":"1993","journal-title":"Clin. Exp. Allergy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/s41430-024-01448-2","article-title":"Measurement of diamine oxidase (DAO) during low-histamine or ordinary diet in patients with histamine intolerance","volume":"78","author":"Rentzos","year":"2024","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_18","first-page":"426","article-title":"Gestational and postpartum plasma diamine oxidase values","volume":"39","author":"Carrington","year":"1972","journal-title":"Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0002-9378(16)34688-9","article-title":"Serial plasma diamine oxidase (DAO) assays in first and second trimester complications of pregnancy","volume":"96","author":"Southren","year":"1966","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1210\/jcem-30-1-59","article-title":"Serum Diamine Oxidase in Pregnancy and in Trophoblastic Diseases","volume":"30","author":"Torok","year":"1969","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1136\/jcp.34.2.187","article-title":"Plasma Diamine Oxidase Levels in Pregnancy Complicated by Threatened Abortion","volume":"34","author":"Legge","year":"1981","journal-title":"J. Clin. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1471-0528.1982.tb03614.x","article-title":"Maternal serum diamine oxidase in fetal death and low-birth-weight infants","volume":"89","author":"Gahl","year":"1982","journal-title":"Br. J. Obstet. Gynaecol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Velicky, P., Windsperger, K., Petroczi, K., Pils, S., Reiter, B., Weiss, W., Vondra, S., Ristl, R., Dekan, S., and Fialaet, C. (2018). Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-24652-0"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/humupd\/dmn014","article-title":"Effects of histamine and diamine oxidase activities on pregnancy: A critical review","volume":"14","author":"Maintz","year":"2008","journal-title":"Hum. Reprod. Update"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1134\/S102279541907010X","article-title":"Association of Polymorphic Variants of Key Histamine Metabolism Genes and Histamine Receptor Genes with Multifactorial Diseases","volume":"55","author":"Kucher","year":"2019","journal-title":"Russ. J. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/head.12493","article-title":"Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine","volume":"55","author":"Serrador","year":"2015","journal-title":"Headache"},{"key":"ref_27","unstructured":"National Library of Medicine (US) (2025, February 26). dbSNP: Short Genetic Variations. Bethesda (MD). National Center for Biotechnology Information (NCBI), Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/?term=aoc1."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.recesp.2011.07.009","article-title":"El coraz\u00f3n durante el embarazo","volume":"64","author":"Hall","year":"2011","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_29","first-page":"559","article-title":"S\u00edntomas y signos digestivos durante la gestaci\u00f3n: N\u00e1useas y v\u00f3mitos\/hiperemesis grav\u00eddica","volume":"37","year":"2011","journal-title":"Med. Fam. Semer."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1038\/s41593-024-01741-0","article-title":"Neuroanatomical changes observed over the course of a human pregnancy","volume":"27","author":"Pritschet","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1447-0756.1986.tb00224.x","article-title":"Maternal serum diamine oxidase activity in the third trimester","volume":"12","author":"Legge","year":"1986","journal-title":"Asia Ocean. J. Obstet. Gynaecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.5217\/ir.2018.00152","article-title":"Evaluation of symptoms and symptom combinations in histamine intolerance","volume":"17","author":"Schnedl","year":"2019","journal-title":"Intest. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/all.13361","article-title":"Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls","volume":"73","author":"Pinzer","year":"2018","journal-title":"Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cucca, V., Ramirez, G.A., Pignatti, P., Asperti, C., Russo, M., Della-Torre, E., Breda, D., Burastero, S.E., Dagna, L., and Yacoub, M.R. (2022). Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study. Nutrients, 14.","DOI":"10.3390\/nu14071513"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Arih, K., \u0110or\u0111evi\u0107, N., Ko\u0161nik, M., and Rijavec, M. (2023). Evaluation of Serum Diamine Oxidase as a Diagnostic Test for Histamine Intolerance. Nutrients, 15.","DOI":"10.3390\/nu15194246"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00508-013-0354-y","article-title":"Serum diamine oxidase activity as a diagnostic test for histamine intolerance","volume":"125","author":"Rijavec","year":"2013","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1016\/j.jaip.2023.08.030","article-title":"Placebo-Controlled Histamine Challenge Disproves Suspicion of Histamine Intolerance","volume":"11","author":"Bent","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/jdv.13966","article-title":"A Popular myth\u2014Low-histamine diet improves chronic spontaneous urticaria\u2014Fact or fiction?","volume":"31","author":"Wagner","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"164","DOI":"10.5021\/ad.2018.30.2.164","article-title":"A histamine-free diet is helpful for treatment of adult patients with chronic spontaneous urticaria","volume":"30","author":"Son","year":"2018","journal-title":"Ann. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.jaci.2005.11.041","article-title":"Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema","volume":"117","author":"Maintz","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-P\u00e9rez, S., Comas-Bast\u00e9, O., Veciana-Nogu\u00e9s, M.T., Latorre-Moratalla, M.L., and Vidal-Carou, M.C. (2021). Low-histamine diets: Is the exclusion of foods justified by their histamine content?. Nutrients, 13.","DOI":"10.3390\/nu13051395"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0002-9378(84)80138-6","article-title":"Diamine oxidase activity in human decidua and endometrium","volume":"150","author":"Holinka","year":"1984","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.clinbiochem.2012.10.013","article-title":"Effect of the menstrual cycle on serum diamine oxidase levels in healthy women","volume":"46","author":"Hamada","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.placenta.2006.05.003","article-title":"Differential Activity of Histidine Decarboxylase in Normal and Pre-eclamptic Placentae","volume":"28","author":"Brew","year":"2007","journal-title":"Placenta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e13757","DOI":"10.1111\/eci.13757","article-title":"Increased serum diamine oxidase activity in nonallergic patients with migraine","volume":"52","author":"Amo","year":"2022","journal-title":"Eur. J. Clin. Investig."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4573\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:12Z","timestamp":1760032812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":45,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14134573"],"URL":"https:\/\/doi.org\/10.3390\/jcm14134573","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}