545:
the histamine-degrading enzyme DAO caused a reduction of symptoms". In this study, neither major nor minor symptoms could be replicated in 39 patients who initially responded to an open challenge with 75 mg histamine in peppermint tea, using a double-blind, placebo-controlled challenge. Consequently, the primary endpoint of the study was not achieved, and the basis for the authors' conclusion that DAO supplementation intake resulted in a "statistically significant reduction in symptoms" remains unclear. The second study was purely observational, lacking a control group: it compared symptomatology with and without DAO use in 28 patients. The chosen design was not suitable to demonstrate causal effects and carried a high risk of attributing placebo effects. The effectiveness of DAO supplementation has not been scientifically validated and is not recommended by the medical associations in
Germany, Austria and Switzerland.
511:
uterine contractions, which can lead to premature labor. DAO in the placenta breaks down histamine to prevent its accumulation and maintain a healthy pregnancy. Low levels of DAO in the placenta may contribute to preeclampsia, a pregnancy-related disorder characterized by mother's high blood pressure and damage to mother's organs such as the liver and kidneys; the baby may also be affected if the condition is severe or left untreated, but it is not the primary target of the disorder.
554:
stimulate each other's release within the trigeminovascular system, potentially contributing to the onset of migraines, so that individuals with genetic variants in the DAO gene often experience migraines when consuming a diet high in histamine. As such, exploring the functional interplay between exogenous histamine and CGRP could provide valuable insights into the mechanisms underlying diet-induced migraines. This area of research continues to be actively investigated.
1527:
2223:
1486:"Guideline on management of suspected adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergology and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA) as well as the Swiss Society for Allergology and Immunology (SGAI) and the Austrian Society for Allergology and Immunology (ĂGAI)"
44:
553:
DAO is related on possible links to migraine conditions. During migraine episodes, there is a noted elevation in the plasma concentrations of both calcitonin gene-related peptide (CGRP) and histamine. These substances are known for their potent vasodilatory effects and have been observed to mutually
544:
In Europe, two investigations, financially backed by the manufacturer of the oral DAO supplementation, have posited that DAO supplementation could alleviate patient symptoms. The first study sought to "objectify and quantify histamine-associated symptoms and to analyze whether oral administration of
460:
DAO is involved in the physiology of digestion and other physiological processes, such as inflammation, immune response, and wound healing. Dysfunction of DAO has been associated with various diseases, including allergies, autoimmune disorders, and cancer. DAO also plays a role in healthy pregnancy
366:
These pathways highlight the complex and varied mechanisms through which histamine is metabolized in different organisms. Understanding these pathways is crucial for biomedical professionals as it can provide insights into the regulation of histamine levels and its role in various physiological and
510:
During pregnancy, DAO plays a crucial role in maintaining fetal growth and development by regulating histamine levels. DAO levels in the blood circulation increases vastly in pregnant women suggesting a protective mechanism against adverse histamine. Histamine is a potent vasodilator and can cause
361:
The third pathway involves the acetylation of histamine by an acetylase to form 4-(-acetylaminoethyl)imidazole. However, itâs important to note that this pathway is found exclusively in enterobacteria and has not been identified in mammals. This suggests a unique metabolic pathway for histamine in
350:), which also has some biological activity, albeit much weaker than that of histamine. Still, NMT, being a product in a reaction catalyzed by HNMT, may inhibit expression of HNMT in a negative feedback loop. This reaction is NÏ-methylation of histamine by the
1189:
Izquierdo-Casas J, Comas-Basté O, Latorre-Moratalla ML, Lorente-Gascón M, Duelo A, Soler-Singla L, et al. (February 2019). "Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial".
530:, and for the relief of other conditions, such as migraine or fibromyalgia. However, the results are inconclusive because studies to date have involved small study populations and short intervention periods.
1621:
1614:
2040:
358:(MAO). This two-step process effectively reduces the activity of histamine in the body and is particularly important for quick deactivation of histamine in the brain.
197:
1547:"Is calcitonin gene-related peptide (CGRP) the missing link in food histamine-induced migraine? A review of functional gut-to-trigeminovascular system connections"
2264:
216:
1607:
2077:
354:(HNMT) enzyme. The NÏ-methylhistamine, unless excreted by the kindney, is subsequently oxidized into NÏ-methylimidazoleacetic acid (NÏMIAA) by the enzyme
514:
Lowered diamine oxidase values in maternal blood in early pregnancy might be an indication for trophoblast-related pregnancy disorders like early-onset
343:
The first pathway (see the reaction illustrated below) involves the deamination of histamine by the enzyme diamine oxidase to form imidazoleacetic acid.
1759:
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623:"Determination of NÏ-methylimidazoleacetic acid (A histamine metabolite) in urine by gas chromatography using nitrogen-phosphorus detection"
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Peters LJ, Kovacic JP (2009). "Histamine: Metabolism, physiology, and pathophysiology with applications in veterinary medicine".
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1085:"Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia"
160:
136:
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1779:
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445:
351:
2018:
484:, including humans, the highest levels of DAO expression are observed in the digestive tract (intestinal mucosa) and the
2250:
1853:
1245:"Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial"
538:
955:
571:
Wolvekamp MC, de Bruin RW (1994). "Diamine oxidase: an overview of historical, biochemical and functional aspects".
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Exogenous DAO (supplements) are being studied as complementary treatment for the relief of symptoms associated with
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2191:
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979:"The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs"
154:
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404:
257:
59:
728:
BĂ€hre H, Kaever V (2017). "Analytical
Methods for the Quantification of Histamine and Histamine Metabolites".
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141:
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1883:
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In case of a shortage or low enzymatic activity of diamine oxidase in the human body, it may appear as an
221:
2149:
2002:
1928:
534:
527:
469:
368:
129:
1345:
Comas-Basté O, Sånchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MC (August 2020).
660:
Mohammed T (2010). "Biological and
Pharmacological Aspects of Histamine Receptors and Their Ligands".
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Reese I, Ballmer-Weber B, Beyer K, Dölle-Bierke S, Kleine-Tebbe J, Klimek L, et al. (2021).
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Histamine, a biogenic amine, undergoes metabolism through three distinct enzymatic pathways:
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Okutan G, SĂĄnchez Niño GM, TerrĂ©n Lora A, LĂłpez Oliva S, San Mauro MartĂn I (October 2023).
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Velicky P, Windsperger K, Petroczi K, Pils S, Reiter B, Weiss T, et al. (April 2018).
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AgĂșndez JA, Ayuso P, Cornejo-GarcĂa JA, Blanca M, Torres MJ, Doña I, et al. (2012).
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1530: This article incorporates text from this source, which is available under the
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In the second pathway, histamine is metabolized into NÏ-methylhistamine (also known as
192:
2222:
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2277:
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2131:
1955:
1810:
1175:
1041:"Effects of histamine and diamine oxidase activities on pregnancy: a critical review"
875:"Serum diamine oxidase (DAO) activity as a diagnostic test for histamine intolerance"
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638:
284:
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951:
775:"Evaluation of Serum Diamine Oxidase as a Diagnostic Test for Histamine Intolerance"
1920:
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Journal of
Veterinary Emergency and Critical Care (San Antonio, Tex. : 2001)
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176:
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507:, express the enzyme and secrete it into the blood stream of a pregnant woman.
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In humans, a certain subtype of cells of the placenta, namely the extravillous
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826:"Serum diamine oxidase activity in patients with histamine intolerance"
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100:
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621:
Keyzer J, Wolthers B, Breukelman H, Kauffman H, De Monchy J (1982).
1398:"Histamine Intolerance-The More We Know the Less We Know. A Review"
2096:
824:
Manzotti G, Breda D, Di
Gioacchino M, Burastero SE (March 2016).
1932:
1039:
Maintz L, Schwarzer V, Bieber T, van der Ven K, Novak N (2008).
488:. DAO expression is also observed in kidney of various species.
319:
311:
112:
2022:
1603:
43:
263:) involved in the metabolism, oxidation, and inactivation of
873:
Music E, Silar M, Korosec P, Kosnik M, Rijavec M (2011).
830:
International
Journal of Immunopathology and Pharmacology
773:
Arih K, ÄorÄeviÄ N, KoĆĄnik M, Rijavec M (October 2023).
2238:
444:
Imidazole-4-acetaldehyde is then further oxidized by a
1396:
Hrubisko M, Danis R, Huorka M, Wawruch M (June 2021).
1347:"Histamine Intolerance: The Current State of the Art"
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In the United States, DAO supplements are available
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302:gene. This gene is highly conserved across the
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2258:
2034:
1615:
1296:"Histamine Intolerance Originates in the Gut"
8:
1448:"regulations.gov search for diamine oxidase"
918:"Histaminase release from human eosinophils"
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2041:
2027:
2019:
1960:
1819:
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367:pathological processes. DAO catalyzes the
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1592:at the U.S. National Library of Medicine
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563:
1760:Phenylethanolamine N-methyltransferase
916:Zeiger RS, Colten HR (February 1977).
33:
730:Handbook of Experimental Pharmacology
242:"amine oxidase, copper-containing, 1"
7:
2219:
2217:
1454:from the original on 29 October 2023
446:NAD-dependent aldehyde dehydrogenase
1903:Acetylserotonin O-methyltransferase
616:
614:
612:
610:
608:
606:
604:
602:
2237:. You can help Knowledge (XXG) by
879:Clinical and Translational Allergy
352:histamine N-methyltransferase
14:
1590:Amine+Oxidase+(Copper-Containing)
1294:Schnedl WJ, Enko D (April 2021).
958:from the original on 8 March 2024
281:amine oxidase (copper-containing)
2221:
1898:Aralkylamine N-acetyltransferase
1545:De Mora F, Messlinger K (2024).
1525:
707:10.1111/j.1476-4431.2009.00434.x
42:
662:Biomedical Aspects of Histamine
298:. The enzyme is encoded by the
1:
1780:Catechol-O-methyl transferase
1695:Histamine N-methyltransferase
664:. Springer. pp. 61â100.
1854:4-aminobutyrate transaminase
1564:10.1016/j.drudis.2024.103941
1004:10.1371/journal.pone.0047571
639:10.1016/0009-8981(82)90247-9
279:. The enzyme belongs to the
48:Diamine oxidase dimer, Human
892:10.1186/2045-7022-1-S1-P115
670:10.1007/978-90-481-9349-3_4
499:The role in human pregnancy
290:The enzyme is expressed in
2315:
2216:
2201:D-amino acid dehydrogenase
2104:Glutamate synthase (NADPH)
2062:amino acid oxidoreductases
1204:10.1016/j.clnu.2018.01.013
1140:Hakl R, Litzman J (2023).
1109:10.1038/s41598-018-24652-0
935:10.4049/jimmunol.118.2.540
20:
1975:Choline acetyltransferase
1893:-amino acid decarboxylase
1755:Dopamine beta-hydroxylase
1750:-amino acid decarboxylase
491:DAO is also expressed in
395:Reaction catalyzed by DAO
182:
41:
1594:Medical Subject Headings
842:10.1177/0394632015617170
405:imidazole-4-acetaldehyde
375:, such as histamine and
294:, a biological group of
21:Not to be confused with
2182:Glycine cleavage system
2087:Glutamate dehydrogenase
1834:Glutamate decarboxylase
1675:Histidine decarboxylase
1142:"Histamine intolerance"
450:imidazole-4-acetic acid
1884:Tryptophan hydroxylase
461:in placental mammals.
2003:Butyrylcholinesterase
1929:Nitric oxide synthase
1159:10.36290/vnl.2023.005
1058:10.1093/humupd/dmn014
922:Journal of Immunology
528:histamine intolerance
470:histamine intolerance
369:oxidative deamination
335:Histamine metabolites
306:group which includes
2299:Oxidoreductase stubs
2127:D-amino acid oxidase
1999:Acetylcholinesterase
1741:Tyrosine hydroxylase
1551:Drug Discovery Today
1364:10.3390/biom10081181
627:Clinica Chimica Acta
23:D-amino acid oxidase
2206:Amine dehydrogenase
1262:10.3390/jcm12206449
1101:2018NatSR...8.6342V
995:2012PLoSO...747571A
742:10.1007/164_2017_22
549:Research directions
248:), formerly called
27:D-aspartate oxidase
1415:10.3390/nu13072228
1313:10.3390/nu13041262
1089:Scientific Reports
792:10.3390/nu15194246
573:Digestive Diseases
2246:
2245:
2214:
2213:
2194:: other acceptors
2154:Flavin-containing
2136:Copper-containing
2060:1.4) - primarily
2016:
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2011:
1911:
1910:
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1785:Monoamine oxidase
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1635:neurotransmission
1502:10.5414/ALX02269E
1045:Hum Reprod Update
751:978-3-319-58192-7
679:978-90-481-9348-6
585:10.1159/000171432
482:placental mammals
385:hydrogen peroxide
356:monoamine oxidase
348:1-Methylhistamine
330:Chemical activity
326:, to name a few.
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885:(Suppl 1): 115.
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362:these bacteria.
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37:Diamine oxidase
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1198:(1): 152â158.
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381:aminoaldehydes
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240:), also known
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79:
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2268:
2263:
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2254:
2249:
2248:
2242:
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2236:
2233:article is a
2232:
2227:
2224:
2220:
2207:
2204:
2202:
2199:
2198:
2196:
2193:
2189:
2183:
2180:
2179:
2177:
2174:
2170:
2166:
2159:
2155:
2151:
2150:Primary-amine
2148:
2146:
2143:
2141:
2137:
2133:
2132:Amine oxidase
2130:
2128:
2125:
2124:
2122:
2119:
2115:
2111:
2105:
2102:
2098:
2095:
2093:
2090:
2089:
2088:
2085:
2084:
2082:
2079:
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2071:
2067:
2063:
2059:
2055:
2044:
2039:
2037:
2032:
2030:
2025:
2024:
2021:
2004:
2000:
1996:
1993:
1992:
1990:
1987:
1982:
1976:
1973:
1972:
1970:
1967:
1962:
1959:
1957:
1956:Acetylcholine
1953:
1949:
1942:
1938:
1934:
1930:
1927:
1926:
1924:
1922:
1918:
1914:
1904:
1901:
1899:
1896:
1894:
1887:
1885:
1882:
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1879:
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1869:
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1855:
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1474:
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1098:
1094:
1090:
1086:
1079:
1077:
1073:
1068:
1064:
1059:
1054:
1051:(5): 485â95.
1050:
1046:
1042:
1035:
1033:
1029:
1024:
1020:
1015:
1010:
1005:
1000:
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992:
988:
984:
980:
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898:
893:
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880:
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869:
866:
861:
857:
852:
847:
843:
839:
836:(1): 105â11.
835:
831:
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512:
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506:
498:
496:
494:
489:
487:
483:
475:
473:
471:
467:
462:
455:
453:
451:
448:, leading to
447:
428:â RâCHO + NH
410:
409:
408:
406:
402:
394:
392:
390:
386:
382:
379:, to produce
378:
374:
370:
360:
357:
353:
349:
345:
342:
341:
340:
334:
329:
327:
325:
321:
317:
313:
309:
305:
301:
297:
293:
288:
286:
285:amine oxidase
282:
278:
274:
270:
266:
262:
259:
255:
251:
247:
243:
239:
235:
223:
220:
218:
214:
211:
208:
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202:
199:
196:
194:
190:
185:
181:
178:
174:
171:
169:
168:Gene Ontology
165:
162:
159:
156:
153:
150:
146:
143:
140:
138:
134:
131:
128:
126:
122:
119:
116:
114:
110:
107:
106:NiceZyme view
104:
102:
98:
95:
92:
90:
86:
83:
80:
78:
74:
69:
66:
63:
61:
57:
52:
45:
40:
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32:
28:
24:
19:
2239:expanding it
2228:
2144:
1985:
1965:
1844:
1824:
1770:
1731:
1699:
1685:
1665:
1633:involved in
1554:
1550:
1540:
1524:
1493:
1489:
1456:. Retrieved
1442:
1405:
1401:
1391:
1354:
1351:Biomolecules
1350:
1340:
1303:
1299:
1289:
1255:(20): 6449.
1252:
1248:
1238:
1195:
1191:
1184:
1152:(1): 37â40.
1149:
1145:
1135:
1092:
1088:
1048:
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982:
972:
960:. Retrieved
928:(2): 540â3.
925:
921:
911:
882:
878:
868:
833:
829:
819:
785:(19): 4246.
782:
778:
768:
733:
729:
723:
698:
694:
688:
661:
655:
630:
626:
576:
572:
566:
552:
543:
537:but are not
532:
525:
516:preeclampsia
513:
509:
505:trophoblasts
502:
490:
479:
463:
459:
443:
398:
365:
338:
299:
289:
249:
245:
241:
237:
233:
232:
94:BRENDA entry
31:
18:
1986:catabolism:
1845:catabolism:
1771:catabolism:
1722:epinephrine
1686:catabolism:
1496:: 305â314.
1408:(7): 2228.
1357:(8): 1181.
1306:(4): 1262.
1213:2445/162978
1095:(1): 6342.
579:(1): 2â14.
541:-approved.
493:eosinophils
250:histaminase
82:IntEnz view
54:Identifiers
2278:Categories
1966:anabolism:
1868:tryptophan
1825:anabolism:
1732:anabolism:
1666:anabolism:
1458:29 October
1249:J Clin Med
558:References
476:Expression
377:putrescine
373:polyamines
277:spermidine
273:putrescine
269:polyamines
267:and other
151:structures
118:KEGG entry
2289:Histamine
2173:disulfide
2158:Monoamine
1889:Aromatic
1876:melatonin
1872:serotonin
1811:glutamate
1746:Aromatic
1656:histamine
1652:histidine
1643:monoamine
1532:CC BY 4.0
1402:Nutrients
1300:Nutrients
1192:Clin Nutr
1176:257604532
1146:Vnitr Lek
779:Nutrients
401:histamine
304:bilateria
292:bilateria
287:enzymes.
265:histamine
71:Databases
2284:EC 1.4.3
2175:acceptor
2120:acceptor
2080:acceptor
1917:arginine
1718:dopamine
1714:tyrosine
1573:38447930
1534:license.
1520:34651098
1452:Archived
1434:34209583
1383:32824107
1332:33921522
1281:37892588
1272:10607251
1222:29475774
1168:36931880
1127:29679053
1067:18499706
1023:23152756
983:PLOS ONE
956:Archived
952:36128339
860:26574488
811:37836530
802:10574399
760:28321587
736:: 3â19.
715:25164630
486:placenta
316:reptiles
271:such as
261:1.4.3.22
252:, is an
222:proteins
210:articles
198:articles
155:RCSB PDB
65:1.4.3.22
2145:Diamine
1952:choline
1631:Enzymes
1511:8511827
1425:8308327
1374:7463562
1323:8069563
1230:3511305
1118:5910386
1097:Bibcode
1014:3495953
991:Bibcode
902:3354134
851:5806734
647:6955073
593:8200121
466:allergy
389:ammonia
324:insects
308:mammals
296:animals
177:QuickGO
142:profile
125:MetaCyc
2192:1.4.99
2118:oxygen
1596:(MeSH)
1571:
1518:
1508:
1432:
1422:
1381:
1371:
1330:
1320:
1279:
1269:
1228:
1220:
1174:
1166:
1125:
1115:
1065:
1021:
1011:
962:2 July
950:
944:402420
942:
899:
858:
848:
809:
799:
758:
748:
713:
676:
645:
591:
387:, and
254:enzyme
205:PubMed
187:Search
173:AmiGO
161:PDBsum
101:ExPASy
89:BRENDA
77:IntEnz
60:EC no.
16:Enzyme
2229:This
2169:1.4.4
2140:Lysyl
2114:1.4.3
2097:GLUD2
2092:GLUD1
2070:1.4.1
2049:CH-NH
1557:(4).
1226:S2CID
1172:S2CID
948:S2CID
424:O + O
403:into
312:birds
137:PRIAM
2235:stub
2152:)) (
2078:NADP
1941:NOS3
1937:NOS2
1933:NOS1
1815:GABA
1569:PMID
1516:PMID
1460:2023
1430:PMID
1379:PMID
1328:PMID
1277:PMID
1218:PMID
1164:PMID
1123:PMID
1063:PMID
1019:PMID
964:2016
940:PMID
856:PMID
807:PMID
756:PMID
746:ISBN
711:PMID
674:ISBN
643:PMID
589:PMID
412:RâCH
322:and
320:fish
300:AOC1
246:AOC1
217:NCBI
158:PDBe
113:KEGG
2160:)))
2074:NAD
1559:doi
1506:PMC
1498:doi
1420:PMC
1410:doi
1369:PMC
1359:doi
1318:PMC
1308:doi
1267:PMC
1257:doi
1208:hdl
1200:doi
1154:doi
1113:PMC
1105:doi
1053:doi
1009:PMC
999:doi
930:doi
926:118
897:PMC
887:doi
846:PMC
838:doi
797:PMC
787:doi
738:doi
734:241
703:doi
666:doi
635:doi
631:121
581:doi
539:FDA
480:In
468:or
432:+ H
420:+ H
416:âNH
371:of
275:or
238:DAO
193:PMC
149:PDB
25:or
2280::
2171::
2116::
2072::
2058:EC
2001:,
1939:,
1935:,
1921:NO
1654:â
1567:.
1555:29
1553:.
1549:.
1514:.
1504:.
1492:.
1488:.
1468:^
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1326:.
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1103:.
1091:.
1087:.
1075:^
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1007:.
997:.
985:.
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881:.
877:.
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672:.
641:.
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625:.
601:^
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577:12
575:.
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407::
391:.
383:,
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314:,
310:,
258:EC
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