Copper and Diamine Oxidase (DAO): Is There a Link?

Some food supple­ments for hist­amine-into­le­rant or hist­amine-sensi­tive pati­ents contain copper, clai­ming to support the enzyme diamine oxidase (DAO for short). Diamine oxidase is an enzyme that is mainly found in the intes­tine, where it breaks down hist­amine and thus contri­butes to the regu­la­tion of hist­amine levels in the body.

How Does Copper Affect Diamine Oxidase (DAO)?

A defi­ci­ency of copper appears in animal models to cause diamine oxidase acti­vity or the level of diamine oxidase in blood plasma to be reduced.1,2 However, it is still ques­tion­able to what extent diamine oxidase acti­vity in the blood provides insight into the acti­vity of DAO in the intes­tine, where it is most abundant in the body and is essen­tial for the hist­amine degra­dation process. I have not yet found any clinical studies on this for humans.

This article is about a health issue. It is important that you have your symptoms examined and treated by medical profes­sio­nals. This article is not intended to be, and cannot be, a substi­tute for the care and advice of medical profes­sio­nals that may be avail­able to you.

Lack of Infor­ma­tive Value of DAO in the Blood (Serum/Plasma)?

Curr­ently, it is still contro­ver­sial how conclu­sive the level of diamine oxidase in the blood is. Some studies could not prove any signi­fi­cant DAO level diffe­rences between affected persons with hist­amine into­le­rance syndrome (HIS) and symptom-free persons who can eat hist­amine-rich foods.3

There­fore, the German Society for Allergy and Clinical Immu­no­logy (DGAKI) curr­ently rejects blood diamine oxidase as a marker for hist­amine into­le­rance syndrome, or HIS for short.3 However, there are indeed medical experts who view this differ­ently. For example, a constantly very low DAO level can also indi­cate a muta­tion in one of the DAO gene segments (see Causes of HIS).4

One reason for the partial lack of signi­fi­cance of the diamine oxidase value could be that it has not yet been conclu­si­vely clari­fied to what extent the DAO value in the blood is related to the actual diamine oxidase present in the intes­tine. It is mainly in the intes­tine that DAO is needed to break down the hist­amine produced from food.

For example, in patho­logy at the Univer­sity Hospital Erlangen, the DAO present in the intes­tine can be clas­si­fied by exami­ning biop­sies obtained during gastro­in­tes­tinal endoscopy.

The DAO present in the intes­tine also appears to be nega­tively affected by inflamma­tory and allergic processes of the intes­tinal mucosa.5 There­fore, treat­ment of the causes that may lead to hist­amine into­le­rance is critical.

Unfor­tu­n­a­tely, because studies of diamine oxidase in intes­tinal tissue have not been performed as stan­dard prac­tice to date, valu­able data that could benefit rese­arch on diamine oxidase defi­ci­ency are lacking.

Degra­dation of Biogenic Amines and Histamine

Copper Defi­ci­ency

Copper defi­ci­ency can be respon­sible for various symptoms and occurs, among other things, when the diet is too one-sided or when there are absorp­tion disor­ders. Causes that play a role, espe­cially in children, are protein defi­ci­ency or severe diar­rhea. These can also ensure that the intes­tine does not absorb enough copper.

In addi­tion, a high intake of zinc can block copper absorp­tion in the intes­tine.6 Pati­ents with hist­amine into­le­rance often take supple­ments with zinc — so it is advi­s­able to have both zinc and copper levels tested.

Should I Take Copper for Hist­amine Intolerance?

Due to the risk of getting side effects from too much copper or impai­ring zinc absorp­tion, it is best to take copper only after labo­ra­tory deter­mi­na­tion or get it from food. The daily requi­re­ment is 1–1.5mg/day.7

Symptoms of Copper Deficiency

Bei einem Kupfer­mangel können folgende Symptome auftreten:

  • Fatigue
  • Anemia, fewer red blood cells, called erythrocytes
  • Leuko­penia, a reduc­tion in white blood cells
  • Osteo­po­rosis
  • Nerve damage


In the case of a copper defi­ci­ency, the cause must be iden­ti­fied whether, for example, chronic inflamma­tory bowel disease is present that prevents the absorp­tion of copper. Also, as mentioned above, a very unba­lanced diet or arti­fi­cial nutri­tion through the vein (so-called paren­teral nutri­tion) can cause defi­ci­ency. one can remedy this by expan­ding the diet or a targeted supply through dietary supple­ments.8

In case of high oral zinc supple­men­ta­tion, one should make sure this is needed. If it is necessary to ensure normal zinc levels in the blood, one should take copper in addi­tion. Care should be taken to ensure that copper and zinc are then supple­mented sepa­r­ately — for example, zinc is taken in the morning, and copper is then taken in the evening.

Side-Effects of Copper Supplementation

Copper intake in case of defi­ci­ency is usually without side effects. People who are very sensi­tive may possibly expe­ri­ence minor gastro­in­tes­tinal symptoms, such as mild nausea.

Care should be taken to ensure that there are no incom­pa­tible dyes or addi­tives in the chosen form of copper supplementation.

Copper Poiso­ning?

Acute copper poiso­ning occurs after ingestion of more than 1 gram and can lead to death. Symptoms of copper poiso­ning include:

  • Mucosal blee­ding, vomi­ting blood
  • Blue-green feces
  • Gastro­in­tes­tinal symptoms
  • Strong feelings of thirst
  • Headache
  • Dizzi­ness
  • Epileptic seizures
  • Jaun­dice
  • Acute hemo­lysis (break­down of red blood cells)9

Prolonged exces­sive intake can also lead to copper poisoning.


1. Legleiter LR, Spears JW. Plasma diamine oxidase: a biomarker of copper defi­ci­ency in the bovine. J Anim Sci. 2007;85(9):2198–2204. doi:10.2527/jas.2006–841

2. Kehoe CA, Faughnan MS, Gilmore WS, Coulter JS, Howard AN, Strain JJ. Plasma diamine oxidase acti­vity is greater in copper-adequate than copper-marginal or copper-defi­cient rats. J Nutr. 2000;130(1):30–33. doi:10.1093/jn/130.1.30

3. Reese I, Ballmer-Weber B, Beyer K, et al. German guide­line for the manage­ment of adverse reac­tions to inge­sted hist­amine: Guide­line of the German Society for Aller­go­logy and Clinical Immu­no­logy (DGAKI), the German Society for Pediatric Aller­go­logy and Envi­ron­mental Medi­cine (GPA), the German Asso­cia­tion of Aller­go­lo­gists (AeDA), and the Swiss Society for Aller­go­logy and Immu­no­logy (SGAI). Allergo J Int. 2017;26(2):72–79. doi:10.1007/s40629-017‑0011‑5

4. Hist­amin­in­to­le­ranz: IMD Institut für medi­zi­ni­sche Diagnostik, Labor. Accessed February 17, 2019. https://www.imd-berlin.de/spezielle-kompetenzen/nahrungsmittelunvertraeglichkeiten/histaminintoleranz.html

5. Raithel M, Küfner M, Ulrich P, Hahn EG. The invol­ve­ment of the hist­amine degra­dation pathway by diamine oxidase in mani­fest gastro­in­tes­tinal aller­gies. Inflamm Res. 1999;48 Suppl 1:S75-76. doi:10.1007/s000110050414

6. Brzozowska A. [Inter­ac­tion of iron, zinc and copper in the body of animals and humans]. Rocz Panstw Zakl Hig. 1989;40(4–6):302–312.

7. Wazir SM, Ghobrial I. Copper defi­ci­ency, a new triad: anemia, leuco­penia, and myelo­neu­ro­pathy. J Commu­nity Hosp Intern Med Perspect. 2017;7(4):265–268. doi:10.1080/20009666.2017.1351289

8. Water NRC (US) C on C in D. Health Effects of Excess Copper. National Acade­mies Press (US); 2000. Accessed August 1, 2021. https://www.ncbi.nlm.nih.gov/books/NBK225400/

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Natur­o­path, hypno­the­ra­pist, owner of an immune system gone crazy with various auto­im­mune special effects. She likes reading through medical papers and is an avid learner of all things regar­ding the human immune system. When her joints and body allow it: enthu­si­astic do-it-your­selfer around the house.

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