Abstract

Histamine can induce headaches by s.c. and i.v. injections, oral intake and inhalative administration. The aim of the study was to eliminate headache by following a histamine-free diet in histamine-intolerant patients. A pilot study was performed in 35 patients (29 female, six male, average age 35 years) with an average frequency of headache of 14 days a month. Besides, headache patients reported of diarrhea (16 times), dermatological problems, mostly urticarial reactions (16 times), cardial arrhythmias (9 times) and bronchial asthma (4 times). Twelve out of 29 female patients suffered from menstrual pain. Patients were put on a histamine-free diet for four weeks; then case history concerning severity and frequency of headaches was taken again. Plasma histamine levels and serum diamine oxidase (DAO) activity were determined on both visits. Histamine was assessed by radioimmunassay (Immunotech, Marseille, France). Levels lower than 0.3 ng/ml were considered as normal, levels between 0.3 and 0.5 as borderline and levels above 0.5 as elevated. Diamine oxidase (DAO) was determined by the C14 putrescine method as described by Tufvesson and Tryding (1969). At the first visit, plasma histamine was found elevated in 9 of 30 patients, whereas DAO was decreased in 23 of 27 patients. At the second visit, average headache frequency dropped from 14 - 2 days per month; 22 patients were completely free of symptoms, five reported a reduction of more than 50%. Add-on medication with antihistamines prescribed to half of the patients in a randomized manner had no additional effect. While plasma histamine levels did not fall significantly (p = 0.07), a significant rise in DAO activity was noted (p < 0.0001). A subsequent telephone survey 3 to 12 months later revealed deterioration of headaches in three cases and amelioration in five. Thus, only five of the 35 patients did not benefit from the diet at the end of the study. Diet errors were reported by 26 patients, leading to headaches in 20 of them. Culprit foods were chocolate, wine, wine vinegar and salami. This dietary intervention study, although not double-blind and placebo-controlled, shows that avoidance of histamine-rich food may lead to a complete remission of headaches in 63% of the patients and a reduction in headache frequency in another 23%. Due to long-lasting case histories, patients served as their own controls. Performance of a double-blind diet study is difficult. Since placebo success rates rarely exceed 30%, the very high success rate of 86% observed in this study and the reported effects of incidental diet errors strongly argue for a causative role of dietary histamine and other biogenic amines as important headache triggers. The increase in DAO even in four of five non-responders parallels the effect of the histamine-free diet and indicates that causes other than histamine seem to play a role in these patients. Headaches associated with recurrent diarrhea, postprandial rhinitis and other characteristic symptoms of histamine intolerance, should be considered as candidates of choice for a histamine-free diet. Preferentially, however, double-blind placebo-controlled studies should be initiated in specialized headache divisions.

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