Histamine Articles 9

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Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases.
(Hagel et al., 2013) Download
Histamine plays an important role in the development of symptoms in allergic, infectious, neoplastic and other diseases. Empirical findings have suggested beneficial effects of ascorbic acid supplementation in those diseases, and these effects are assumed to be related to a possible decrease in systemic histamine concentration. In the present study, we systematically investigated for the first time the effect of 7.5 g of intravenously administered ascorbic acid on serum histamine levels (as detected by ELISA) in 89 patients (19 with allergic and 70 with infectious diseases). When all patients were grouped together, there was a significant decline in histamine concentration from 0.83 to 0.57 ng/ml×m2 body surface area (BSA, p<0.0001). The decrease in serum histamine concentration in patients with allergic diseases (1.36 to 0.69 ng/ml×m2 BSA, p=0.0007) was greater than that in patients with infectious diseases (0.73 to 0.56 ng/ml×m2 BSA, p=0.01). Furthermore, the decline in histamine concentration after ascorbic acid administration was positively correlated with the basal, i.e. pre-therapeutic, histamine concentration. Intravenous infusion of ascorbic acid clearly reduced histamine concentrations in serum, and may represent a therapeutic option in patients presenting with symptoms and diseases associated with pathologically increased histamine concentration.

Impact of oral vitamin C on histamine levels and seasickness.
            (Jarisch et al., 2014) Download
BACKGROUND:  Seasickness is a risk aboard a ship. Histamine is postulated as a causative agent, inversely related to the intake of vitamin C. Persons with mastocytosis experienced improvement of nausea after the intake of vitamin C. OBJECTIVE:  To determine whether vitamin C suppresses nausea in 70 volunteers who spent 20 minutes in a life raft, exposed to one-meter-high waves in an indoor pool. METHOD:  Double-blind placebo-controlled crossover study. Two grams of vitamin C or placebo was taken one hour before exposure. Blood samples were taken one hour before and after exposure to determine histamine, diamine oxidase, tryptase, and vitamin C levels. Symptom scores were noted on a visual analog scale. On the second day the test persons were asked which day they had felt better. RESULTS:  Seven persons without symptoms were excluded from the analysis. Test persons had less severe symptoms after the intake of vitamin C (p < 0.01). Scores on the visual analog scale were in favor of vitamin C, but the difference was not significant. Twenty-three of 63 persons wished to leave the raft earlier: 17 after the intake of placebo and 6 after the intake of vitamin C (p < 0.03). Women (p < 0.02) and men below 27 years of age (p < 0.02) had less pronounced symptoms after the intake of vitamin C. Histamine (p < 0.01) and DAO levels were increased after the intake of vitamin C (p < 0.001) and after placebo (n.s.). The fact that the second test day was rated less stressful by most volunteers is indicative of habituation. CONCLUSIONS:  Some of the data show that vitamin C is effective in suppressing symptoms of seasickness, particularly in women and men younger than 27 years of age, and is devoid of side effects. Histamine levels were initially increased after the test persons had been exposed to waves.

Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind study.
            (Millán-Guerrero et al., 2007) Download
Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. The objective of this study was to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of sodium valproate, in an open clinical trial. Ninety-two patients with migraine were selected under criteria established by the International Headache Society and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week; n = 46) compared with oral administration of sodium valproate (500 mg daily dose; n = 46). The variables studied were headache intensity, frequency, duration, analgesic intake and migraine disability assessment (MIDAS). Two-tailed Student's t- test was used to compare means and the Mann-Whitney U and anova tests were used. The data collected during the 4th, 8th and 12th weeks of treatment revealed that histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS. The present study provides evidence of the superior efficacy of histamine applied subcutaneously in migraine prophylaxis when compared with sodium valproate taken orally. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study.
            (Millán-Guerrero et al., 2008) Download
BACKGROUND:  Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. OBJECTIVE:  To evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate. METHODS:  Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment. RESULTS:  The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%). CONCLUSION:  The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double-blind study.
            (Millán-Guerrero et al., 2009) Download
OBJECTIVES:  To compare the efficacy and tolerability of the subcutaneous administration of histamine and botulinum toxin type A (BoNTA) in migraine prophylaxis. BACKGROUND:  Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. METHODS:  One hundred patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) n = 50, compared with administration of 50 U of BoNTA (one injection cycle) n = 50. RESULTS:  The data collected during the 4th week of treatment revealed a significant decrease in all parameters studied, in histamine and BoNTA (P < 0.001). After 4 weeks of treatment, but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy. CONCLUSIONS:  This randomized study demonstrated that both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis. Low doses of histamine applied subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and lay the clinical and pharmacological groundwork for the use of H3 agonist in migraine prophylaxis.


 

Effect of antioxidants on histamine receptor activation and sustained postexercise vasodilatation in humans.
            (Romero et al., 2015) Download
NEW FINDINGS:  What is the central question of this study? Is exercise-induced oxidative stress the upstream exercise-related signalling mechanism that leads to sustained postexercise vasodilatation via activation of H1 and H2 histamine receptors? What is the main finding and its importance? Systemic administration of the antioxidant ascorbate inhibits sustained postexercise vasodilatation to the same extent as seen previously with H1 and H2 histamine receptor blockade following small muscle-mass exercise. However, ascorbate has a unique ability to catalyse the degradation of histamine. We also found that systemic infusion of the antioxidant N-acetylcysteine had no effect on sustained postexercise vasodilatation, suggesting that exercise-induced oxidative stress does not contribute to sustained postexercise vasodilatation. An acute bout of aerobic exercise elicits a sustained postexercise vasodilatation that is mediated by histamine H1 and H2 receptor activation. However, the upstream signalling pathway that leads to postexercise histamine receptor activation is unknown. We tested the hypothesis that the potent antioxidant ascorbate would inhibit this histaminergic vasodilatation following exercise. Subjects performed 1 h of unilateral dynamic knee extension at 60% of peak power in three conditions: (i) control; (ii) i.v. ascorbate infusion; and (iii) ascorbate infusion plus oral H1 /H2 histamine receptor blockade. Femoral artery blood flow was measured (using Doppler ultrasound) before exercise and for 2 h postexercise. Femoral vascular conductance was calculated as flow/pressure. Postexercise vascular conductance was greater for control conditions (3.4 ± 0.1 ml min(-1) mmHg(-1) ) compared with ascorbate (2.7 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05) and ascorbate plus H1 /H2 blockade (2.8 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05), which did not differ from one another (P = 0.9). Given that ascorbate may catalyse the degradation of histamine in vivo, we conducted a follow-up study, in which subjects performed exercise in two conditions: (i) control; and (ii) i.v. N-acetylcysteine infusion. Postexercise vascular conductance was similar for control (4.0 ± 0.1 ml min(-1) mmHg(-1) ) and N-acetylcysteine conditions (4.0 ± 0.1 ml min(-1) mmHg(-1) ; P = 0.8). Thus, the results in the initial study were due to the degradation of histamine in skeletal muscle by ascorbate, because the histaminergic vasodilatation was unaffected by N-acetylcysteine. Overall, exercise-induced oxidative stress does not appear to contribute to sustained postexercise vasodilatation.

Histamine-induced vasodilatation in the human forearm vasculature.
            (Sandilands et al., 2013) Download
AIM:  To investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature. METHODS:  Three studies were conducted to assess changes in forearm blood flow (FBF) using venous occlusion plethysmography in response to intra-brachial histamine. First, the dose-response was investigated by assessing FBF throughout a dose-escalating histamine infusion. Next, histamine was infused at a constant dose to assess acute tolerance. Finally, a four way, double-blind, randomized, placebo-controlled crossover study was conducted to assess FBF response to histamine in the presence of H1 - and H2 -receptor antagonists. Flare and itch were assessed in all studies. RESULTS:  Histamine caused a dose-dependent increase in FBF, greatest with the highest dose (30 nmol min(-1) ) infused [mean (SEM) infused arm vs. control: 26.8 (5.3) vs. 2.6 ml min(-1)  100 ml(-1) ; P < 0.0001]. Dose-dependent flare and itch were demonstrated. Acute tolerance was not observed, with an increased FBF persisting throughout the infusion period. H2 -receptor antagonism significantly reduced FBF (mean (95% CI) difference from placebo at 30 nmol min(-1) histamine: -11.9 ml min(-1)  100 ml(-1) (-4.0, -19.8), P < 0.0001) and flare (mean (95% CI) difference from placebo: -403.7 cm(2) (-231.4, 576.0), P < 0.0001). No reduction in FBF or flare was observed in response to the H1 -receptor antagonist. Itch was unaffected by the treatments. Histamine did not stimulate vascular release of tissue plasminogen activator or von Willebrand factor. CONCLUSION:  Histamine causes dose-dependent vasodilatation, flare and itch in the human forearm. H2 -receptors are important in this process. Our results support further exploration of combined H1 - and H2 -receptor antagonist therapy in acute allergic syndromes.

 


References

Hagel, AF, et al. (2013), ‘Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases.’, Naunyn Schmiedebergs Arch Pharmacol, 386 (9), 789-93. PubMed: 23666445
Jarisch, R, et al. (2014), ‘Impact of oral vitamin C on histamine levels and seasickness.’, J Vestib Res, 24 (4), 281-88. PubMed: 25095772
Millán-Guerrero, RO, et al. (2007), ‘Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind study.’, Eur J Neurol, 14 (10), 1079-84. PubMed: 17880560
Millán-Guerrero, RO, et al. (2008), ‘Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study.’, Eur Neurol, 59 (5), 237-42. PubMed: 18264012
Millán-Guerrero, RO, et al. (2009), ‘Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double-blind study.’, Eur J Neurol, 16 (1), 88-94. PubMed: 19087155
Romero, SA, et al. (2015), ‘Effect of antioxidants on histamine receptor activation and sustained postexercise vasodilatation in humans.’, Exp Physiol, 100 (4), 435-49. PubMed: 25664905
Sandilands, EA, et al. (2013), ‘Histamine-induced vasodilatation in the human forearm vasculature.’, Br J Clin Pharmacol, 76 (5), 699-707. PubMed: 23488545