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Histamine Intolerance-Like Symptoms in Healthy Volunteers after Oral Provocation with Liquid Histamine

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Histamine in food at non-toxic doses has been proposed to be a major cause of food intolerance causing symptoms like diarrhea, hypotension, headache, pruritus and flush ("histamine intolerance"). Histamine-rich foods such as cheese, sausages, sauerkraut, tuna, tomatoes, and alcoholic beverages may contain histamine up to 500 mg/kg. We conducted a randomized, double-blind, placebo-controlled cross-over study in 10 healthy females (age range 22–36 years, mean 29.1 ± 5.4) who were hospitalized and challenged on two consecutive days with placebo (peppermint tea) or 75 mg of pure histamine (equaling 124 mg histamine dihydrochloride, dissolved in peppermint tea). Objective parameters (heart rate, blood pressure, skin temperature, peak flow) as well as a total clinical symptom score using a standardized protocol were recorded at baseline, 10, 20, 40, 80 minutes, and 24 hours. The subjects received a histamine-free diet also low in allergen 24 hours before hospitalization and over the whole observation period. Blood samples were drawn at baseline, 10, 20, 40, and 80 minutes, and histamine and the histamine-degrading enzyme diamine oxidase (DAO) were determined. After histamine challenge, 5 of 10 subjects showed no reaction. One individual experienced tachycardia, mild hypotension after 20 minutes, sneezing, itching of the nose, and rhinorrhea after 60 minutes. Four subjects experienced delayed symptoms like diarrhea (4×), flatulence (3×), headache (3×), pruritus (2×) and ocular symptoms (1×) starting 3 to 24 hours after provocation. No subject reacted to placebo. No changes were observed in histamine and DAO levels within the first 80 minutes in non-reactors as well as reactors. There was no difference in challenge with histamine versus challenge with placebo. We conclude that 75 mg of pure liquid oral histamine—a dose found in normal meals— can provoke immediate as well as delayed symptoms in 50% of healthy females without a history of food intolerance.
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Document Type: Research Article

Publication date: September 1, 2004

More about this publication?
  • Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.

    The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma and by having the potential to directly impact the quality of patient care. AAP welcomes the submission of original works including peer-reviewed original research and clinical trial results. Additionally, as the official journal of the Eastern Allergy Conference (EAC), AAP will publish content from EAC poster sessions as well as review articles derived from EAC lectures.

    Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.

    Articles marked "F" offer free full text for personal noncommercial use only.

    The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
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