Bent RK, Kugler C, Faihs V, Darsow U, Biedermann T, Brockow K. The Journal of Allergy and Clinical Immunology: In Practice 2023;11(12):3724–3731 · Single-blind placebo-controlled challenge study · 59 patients
When 59 people with suspected histamine intolerance were given histamine and a placebo without being told which was which, 37 of them reacted to the placebo — and the diagnosis was ruled out in 50.
What the researchers did
A team at the allergy department of the Technical University of Munich tested 59 patients with suspected histamine intolerance, most of them middle-aged women (84.7%). Each patient was given histamine on one occasion and a placebo on another without knowing which was which. The researchers also compared blood levels of diamine oxidase (DAO) — the enzyme that breaks down histamine in the gut — and histamine skin-prick test results between those who reacted and those who did not.
What they found
- Placebo reactions were common: 37 of the 59 patients (62.7%) developed symptoms after the placebo.
- Histamine intolerance was ruled out in 50 patients (84.7%).
- Only 4 (6.8%) had objective symptoms after histamine but not after placebo. The authors classed these as “plausible” histamine intolerance, because a chance reaction could not be excluded. Another 5 (8.5%) were classed as “possible” after case-by-case review.
- Three-quarters of the patients had reported feeling better, though never symptom-free, on a low-histamine diet — and those with plausible or possible intolerance had responded to the diet no better than the rest.
- The plausible and possible cases had reported more digestive symptoms. Their DAO levels tended to be lower, but DAO varied so widely among the others that it could not be used to make the diagnosis. Skin-prick results did not differ.
- The challenge was safe: one patient needed an antihistamine.
What it means
For most people in this study, symptoms blamed on histamine were not reproduced by histamine given blind, and many reacted to a placebo — which is why the authors conclude that placebo-controlled challenges are needed. Feeling better on a low-histamine diet did not separate the two groups, and a DAO blood test was not specific enough on its own. The study does not show that histamine intolerance never exists: 9 of the 59 had a plausible or possible reaction.
Limitations
This is a small study at a single specialist centre, and it was single-blind (the patients did not know which challenge they received) rather than double-blind. The “plausible” and “possible” categories rest partly on clinical judgement.
Read the abstract on PubMed → · Full text at the publisher →
More on this: histamine in food and foods high in histamine.
Summary in our own words; follow the links for the source and full abstract.
