Answer:
Histamine intolerance is a concept more than a proven disease based upon evidence. The major mechanisms for histamine degradation are N-methyltransferase enzymes for intracellular histamine and diamine oxidases for extracellular histamine. The latter enzyme is more important for metabolism of histamine in food (Maintz). I have copied a question from Ask the Expert archives that provides some additional information.
The utilization of supplements of diamine oxidase are promoted as a potential solution for patients with symptoms suggestive of excessive histamine. However, there is no definitive test for the syndrome (Reese). There are publications discussing measurement of urinary histamine and methylhistamine as a means of making a diagnosis, but the predictive value of such testing is not established (Comas-Baste). Therefore, evidence-based medicine confirming efficacy for replacement therapies or appropriate dosing of histamine decarboxylase is not available due to inability to prove the diagnosis. I am not aware of any proven risk in supplemental diamine oxidase.
I have discussed the diamine oxidase, over the counter supplement for adults with symptoms suggestive of histamine excess, such as headache, flushing, diarrhea, light-headed feeling, nausea. I emphasize that the concept is controversial that there is a specific condition associated with diamine oxidase deficiency. Since diamine oxidase is a nutritional supplement, there are limited regulations for manufacturers. Commercial products are not labeled with standard terminology, some state supplement, some provide units of histamine neutralization and others mg of enzyme. There is no recommendation of weight based dosing, suggesting that body size has limited if any effect on side effects.
I regret I cannot provide a specific recommendation for you related to pediatric diamine oxidase supplementation.
1. Maintz, Laura, and Natalija Novak. "Histamine and histamine intolerance." The American journal of clinical nutrition 85.5 (2007): 1185-1196.
2. Comas-Basté, Oriol, et al. "New approach for the diagnosis of histamine intolerance based on the determination of histamine and methylhistamine in urine." Journal of pharmaceutical and biomedical analysis 145 (2017): 379-385.
3. Reese, Imke, et al. "German guideline for the management of adverse reactions to ingested histamine." Allergo journal international 26.2 (2017): 72-79.
10/16/2015: Histamine intolerance
Question: I have a pt that wants to know if there is any "test" for histamine intolerance.
Answer: Histamine is a natural substance produced by basophils and mast cells. There is an unproven concept that a variety of symptoms result from excessive histamine due to a deficiency of histamine degradation enzymes such as diamine oxidase and histamine N-methyl transferase. The contention is that this condition results in allergic like symptoms such as abdominal complaints, rhinitis, itching, urticaria, dizziness, migraine headaches and hypotension. The source of histamine is said to be from both endogenous production and absorption from histamine in foods. A review in the medical literature may be of interest to you and a quote from this article summarizes the situation, “…a lot more is alleged and stated than is substantiated by scientific evidence.” (Schwelberger) The tests that are most often suggested are quantification of histamine N-methyl transferase or diamine oxidase, red wine ingestion with assessment of symptoms or plasma histamine concentration (Wantke, Maintz). Diamine oxidase is felt to be more important for GI metabolism of ingested histamine. Histamine challenge, either orally or intravenously, has been suggested as a strategy to identify histamine intolerance. However, the nature of the symptoms are variable and double-blind challenge data do not confirm the existence of the syndrome (Komericki).
In summary, there is insufficient information to validate the concept of histamine intolerance. Tests that are suggested include histamine infusion, histamine oral ingestion, red wine provocation; plasma histamine quantification; and measurement of the enzymes involved in the degradation of histamine. None of these can be recommended due to lack of information proving the predictive value of the tests.
1. Schwelberger, H. G. "Histamine intolerance: a metabolic disease?."Inflammation Research 59.2 (2010): 219-221.
2. Komericki, Peter, et al. "Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study." Wiener Klinische Wochenschrift 123.1-2 (2011): 15-20.
3. Maintz, Laura, et al. "Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema." Journal of Allergy and Clinical Immunology 117.5 (2006): 1106-1112.
4. Wantke, Felix, Manfred Götz, and Reinhart Jarisch. "The red wine provocation test: intolerance to histamine as a model for food intolerance."Allergy and Asthma Proceedings. Vol. 15. No. 1. OceanSide Publications, Inc, 1994.
5. Wöhrl, Stefan, et al. "Histamine intolerance-like symptoms in healthy volunteers after oral provocation with liquid histamine." Allergy and Asthma Proceedings. Vol. 25. No. 5. OceanSide Publications, Inc, 2004.
I hope this information is of help to you and your patient.
All my best.
Dennis K. Ledford, MD, FAAAAI