Measurement and Characterization of Histamine and Methylhistamine in Human Urine under Histamine-Rich and Histamine-Poor Diets

Abstract

A radioimmunoassay for histamine was used to measure histamine and 1-methylhistamine (MH) in human urine samples. The detection limit of this assay was 2 ng/ml for histamine and 0.5 ng/ml for MH. Cation exchange high performance liquid chromatography (HPLC) on a Bio-Gel TSK SP-5 PW column with gradient elution was capable of separating histamine from its precursor L-histidine and its metabolites MH and 1-methylimidazole acetic acid (MIAA). The concentration of MH-immunoreactive material in healthy volunteers with no dietary restrictions was 202 ± 92 μg/24 h (mean ± SD; n = 14). The excretion of MH-like material, expressed as micrograms of MH per 24 h, was not significantly different before or after the intake of histamine-rich food: 217 ± 88 vs. 276 ± 135 μg/24 h (n = 10). However, in urine samples collected in individual fractions, the levels of MH immunoreactivity were significantly increased after a histamine-rich meal in comparison to the corresponding fractions which were taken a day earlier at the same time intervals after a histamine-low diet (p < 0.03). HPLC characterization of MH immunoreactivity revealed the presence of histamine, MH and a compound with the same retention time as MIAA. The ratio of histamine, MH and MIAA in controls without dietary restrictions, as determined by HPLC analysis, was 50 ± 6, 47 ± 5 and 3 ± 1%, respectively. After a histamine-rich meal the ratio was 97 ± 2% for histamine, 1% for MH and 2 ± 1% for MIAA.

Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet

“…Compared to controls who ingested also staple foods during unrestricted diet at day 1 and 2, patients with GMA exhibited significantly more symptoms than normal individuals under an unrestricted diet, and UH and UMH excretion were found to be highly significantly increased in allergic individuals. Although in the past, earlier attempts to diagnose GMA by histamine mediator excretion failed to show such clear results [ 14 , 19 ], these highly significant results may be the result of a strong standardization of this functional mediator test as described above (food ingestion up to 2 p.m., urine collection period from 6 p.m. to 6 a.m., each diet 2 days, fluid volume, water only etc. [ 4 , 13 , 15 ]) and an appropriate diagnostic work up for patient selection (Figure 1 ).…”

“…While GMA patients remained with their UMH levels mostly above 6.2 μg UMH/mmol creatinine x m2 BSA, controls were clearly below this differentiation level of 6.2 μg UMH/mmol creatinine x m2 BSA (Figure 3 ). The decline of UMH in controls may further indicate that the quantity of UMH excretion in humans reflects not only the rate of allergic effector cell degranulation and/or mast cell number or activity, respectively, but also several other intervening factors, like nutrient intake, protein content of the diet etc., resulting in a different extent of gastric acid stimulation by endogenous histamine dependent mechanisms [ 6 , 12 - 16 , 19 ].…”

“…However, UMH excretion was found to be highly significantly enhanced in both IgE- and non-IgE type of GMA patients than in controls under both diet forms, showed lower rates of intraindividual variation and it has been reported to reflect more precisely alterations of the histamine metabolism than histamine itself [ 12 - 14 , 21 , 22 ]. UMH presents as a possible indicator of systemic histamine production and it was found to increase in urine during early and late phase allergic asthmatic reactions [ 12 , 19 , 21 - 23 ]. The distribution of individual UMH levels in GMA and controls showed a considerable overlap, but in controls most patients (86.4%) were found to have UMH excretion rates lower than 6.2 (mean + 1SD).…”

“…However, increased excretion rates of UH and UMH are not specific for GMA, because several other diseases may be accompanied by persistently increased excretion of UMH like mastocytosis, active Inflammatory Bowel Disease, lymphoma, hematologic disorders etc. [ 6 , 14 - 16 , 19 , 25 - 28 ]. But compared to these diagnoses with persistently enhanced excretion of histamine and its metabolites, GMA patients were found to show a clear nutritive modulation of their UMH excretion within two consecutive days of elimination diet.…”

Separation assay of histamine and its metabolites in biological specimens

“…Intact HA and the metabolites without derivatization are simultaneously separated by a cation-exchange column (Yamatodani et al, 1985;Itoh et al, 1991;Mine et al, 1986;Houdi et al, 1987;Hermann et al, 1993). Although the other types of columns such as the octadesylsilyl column (ODS; Itoh et al, 1992;Allenmark et al, 1985;Ronnberg et al, 1984;Harsing et al, 1986a,b;Tsikas et al, 1993;Hui and Taylor, 1984;van Haaster et al, 1993;Saito et al, 1992;Skofitsch et al, 1981;Devalia et al, 1985;Kasziba et al, 1988) and the cyanopropylsilyl column (Siegel et al, 1990a,b) can be used for the separation, not only is the separation efficiency not very high, but also peak tailing based on adsorption by the resins sometimes occurs.…”