Histamine Articles 7


Effect Of Pyridoxine Deficiency On Intestinal Histaminase In The Rat.
            (Abdel-Aziz and Boullin, 1964) Download
Histaminase is one of the major enzymes responsible for inactivation of histamine in the rat and the small intestine has high enzyme activity. It is generally considered to be a flavoprotein with pyridoxal as the coenzyme. It might therefore be supposed that pyridoxine-deficient animals would show diminished histaminase activity, which would be restored by administering pyridoxine to the intact animal or by adding pyridoxal phosphate to isolated enzyme systems in vitro. The present experiments are further evidence that FAD and pyridoxal are prosthetic groups of histaminase, and their failure here was possibly due to an effect of the deficiency state on the apoenzyme.

An evaluation of histamine as a therapeutic agent in some allergic disorders
            (Blue, 1956)  Download
A series of 191 cases treated with histamine by the intravenous and iontophoretic methods is presented. It is concluded that this tpe of histamine therapy is very beneficial in acute urticaria, acute serum-sickness-like disease, chronic uriticaria, allergic headache, migraine, vertigo, traumatic headaches, multiple sclerosis and psoriasis diseases.

Effect of ascorbic acid on histamine metabolism in scorbutic guinea-pigs.
            (Chatterjee et al., 1975) Download
1. In guinea-pigs fed an ascorbic-acid-free diet, as the ascorbic acid levels decreased the histamine levels in blood and urine rose steadily to maxima in about 10-12 days. The elevated histamine levels persisted in the blood and urine of scorbutic guinea-pigs and the histamine levels in lung, gastric mucosa and spleen also increased. The increased histamine content of the urine, blood and other tissues in the ascorbic-acid-depleted condition could be brought back to normal levels by administration of a single dose of ascorbic acid 5 mg/100 g body wt. guinea-pig. 3. The drop in the elevated histamine level was not due to an indirect effect of ascorbic acid on histamine forming capacity, histaminase activity or histamine release.


The role of histidine in the anemia of folate deficiency.
            (Cooperman and Lopez, 2002) Download
The amino acid histidine is metabolized to glutamic acid in mammalian tissue. Formiminoglutamic acid (FIGLU) is an intermediary in this reaction, and tetrahydrofolic acid is the coenzyme that converts it to glutamic acid. A test for folate deficiency concerns the measurement of urinary FIGLU excretion after a histidine load. It was observed that folate-deficient individuals receiving the histidine for the FIGLU test made hematological response that alleviated the anemia associated with this deficiency. This was unusual in that a biochemical test to determine the deficiency results in a beneficial effect for one aspect of the deficiency. The studies reported in this paper give a metabolic explanation for this phenomenon. Urine was collected for 24 hr from 25 folate-deficient subjects, 10 vitamin B(12)-deficient subjects, and 15 normal controls. Urinary excretion of histidine was a mean of 203 mg with a range of 130-360 mg for the folate-deficient subjects; 51.5 mg with a range of 30-76.6 mg for normal subjects; and 60.0 mg with a range of 32.3-93.0 mg for the vitamin B(12)-deficient subjects. All the folate-deficient subjects subsequently made a hematological response to the histidine administered for the FIGLU test. No hematological response was observed in the vitamin B(12)-deficient individuals. When folic acid was given to folate-deficient subjects who received no histidine, urinary histidine levels returned to normal levels rapidly and this was followed by a hematological response. Others have shown that volunteers fed a histidine-free diet developed anemia. In normal subjects, histidine is excreted much more in the urine than other essential amino acids are. Hemoglobin protein contains 10% histidine. Under normal conditions, dietary histidine can supply sufficient histidine to prevent anemia. When the dietary intake is diminished or the urinary excretion is greatly increased, anemia results. It is concluded that folate deficiency causes histidine depletion through increased urinary excretion of this amino acid. Feeding histidine replenishes tissue levels of histidine, resulting in hemoglobin regeneration. Folic acid administration results in return of histidine to normal urinary levels. Thus, a combination of folic acid histidine would be beneficial for folate deficient individuals.

Histamine in the nervous system.
            (Haas et al., 2008) Download
Histamine is a transmitter in the nervous system and a signaling molecule in the gut, the skin, and the immune system. Histaminergic neurons in mammalian brain are located exclusively in the tuberomamillary nucleus of the posterior hypothalamus and send their axons all over the central nervous system. Active solely during waking, they maintain wakefulness and attention. Three of the four known histamine receptors and binding to glutamate NMDA receptors serve multiple functions in the brain, particularly control of excitability and plasticity. H1 and H2 receptor-mediated actions are mostly excitatory; H3 receptors act as inhibitory auto- and heteroreceptors. Mutual interactions with other transmitter systems form a network that links basic homeostatic and higher brain functions, including sleep-wake regulation, circadian and feeding rhythms, immunity, learning, and memory in health and disease.

The use of histamine in the treatment of allergic diseases.
            (Jonez, 1952) Download
During the past seven years, giving 75,000 doss intravenously and at least an equal number by the repository method. We had over 1,500 patients on self-administration. With this experience, we believe that in the field of allergy, histamine is proving itself to be the closest approach to an over-all hypo-sensitizer without any dleterious side reations.

Is there a diet for histamine intolerance
            (Kohn, 2014) Download
After food allergies have been ruled out, a low-histamine diet is often rec- ommended, and a favorable response to it can help aid in the diagnosis of a histamine intolerance. Dietary sources that are high in hista- mine include many aged and fermented foods and beverages (eg, cheeses, yogurt, processed meats, alcoholic beverages, sauerkraut, soy, some fish, especially frozen, smoked, and canned varieties; fruits, such as strawberries and cherries; vegetables, including spinach, tomatoes, and eggplant; and seasonings, such as chili powder, cinnamon, cloves, and vinegar.

Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity.
            (Luk et al., 1980) Download
Diamine oxidase (histaminase) is an enzyme found in high concentrations in the intestinal mucosa of humans and other mammalian species. We investigated whether plasma and mucosal levels of diamine oxidase activity reflect both the maturational status of the mucosa during its development in the newborn rate and the degree of mucosal damage during its injury in the adult rat. Litter mates were reared under identical conditions and killed at different ages from day 0 to day 40 after birth. Diamine oxidase in the small intestine was low at birth, increased gradually with age, reached a peak at 22 d, and then remained at normal adult levels, similar to the developmental patterns of maltase and sucrase. Plasma diamine oxidase rose in parallel with intestinal levels (n = 500, r = 0.84, P less than 0.001), reached a peak at 24 d, and then remained at normal adult levels. Diamine oxidase activity in 15 nonintestinal tissues was less than 5% of ileal mucosal activity, and no nonintestinal activities showed increase with age. Adult rat intestinal loops were perfused with hyperosmolar sodium sulfate solutions to produce selective damage to villus mucosa. With increasing mucosal damage, there was a progressive decrease in the enzyme activities studied; first, lactase levels fell, then maltase and sucrase, and finally mucosal and plasma diamine oxidase activity levels fell. The decrease in plasma diamine oxidase reflected the degree of mucosal damage (n = 29, P less than 0.04). Diamine oxidase activity is thus unique among intestinal mucosal enzymes studied to date in that circulating levels can serve as a marker of mucosal maturation and integrity.

Vitamin B-6 nutriture and plasma diamine oxidase activity in pregnant Hispanic teenagers.
            (Martner-Hewes et al., 1986) Download
Vitamin B-6 status was assessed by measuring erythrocyte glutamic-pyruvic transaminase (EGPT) indices in 122 pregnant Hispanic teenagers. Seventeen percent were vitamin B-6 deficient (EGPT indices greater than 1.25) at the initial interview (first or second trimester). A daily supplement of 5 mg vitamin B-6, beginning at initial interview, did not reduce prevalence of vitamin B-6 deficiency at final interview (third trimester). No association was found between EGPT indices greater than 1.25 and the outcome of pregnancy. The activity of diamine oxidase (DAO), a vitamin B-6-dependent enzyme produced by the placental decidua, was measured in maternal plasma. At initial and final interviews, plasma-DAO activity was increased by in vitro addition of pyridoxal-5'-phosphate. The activity in early pregnancy was positively associated with dietary vitamin B-6 intake and was lower in teenagers with EGPT indices greater than 1.25 at the final interview. Findings suggest that plasma-DAO activity is influenced by vitamin B-6 status.

Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options.
            (Molderings et al., 2011) Download
Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient's presentation.


Effect of ascorbic acid on detoxification of histamine under stress conditions.
            (Nandi et al., 1974) Download
A variety of stress conditions, namely, administration of vaccines, toxoids and dietary and physical stress in rats and guinea pigs led to an enhanced histamine formation or release in the system. Administration of large doses of ascorbic acid in any of the stressful situations resulted in a marked decrease in the urinary histamine level indicating detoxification of histamine in vivo. In the guinea pig, the utilization of ascorbic acid was significantly increased in different histamine forming or histamine releasing stress conditions.

Localization of histaminase to the specific granule of the human neutrophil.
            (Ringel et al., 1984) Download
The release of histaminase, a diamine oxidase of the human neutrophil, is initiated by soluble secretagogues. Histaminase is simultaneously inactivated by the reactive oxygen intermediates generated by the respiratory burst. Thus, quantitative assessment of histaminase release relative to other granule markers is best achieved in the presence of superoxide dismutase and catalase. Human neutrophils activated with secretagogues preferential for the specific granule, such as calcium ionophore A23187 in a limited concentration, phorbol myristate acetate (PMA), formyl-methionyl-leucylphenylalanine (fMLP), and concanavalin A, release vitamin B12-binding protein, lysozyme, and histaminase but not beta glucuronidase. PMA activation in the presence of cytochalasin B augments the release of lysozyme and initiates the release of beta glucuronidase through recruitment of the azurophilic granule but has no incremental effect on the release of vitamin B12-binding protein and histaminase observed with PMA alone. Subcellular fractionation of resting neutrophils by sucrose density gradient centrifugation to separate specific granules from two classes of azurophilic granules selectively distributes vitamin B12-binding protein and histaminase to the specific granule fractions.

Role of L-ascorbic acid on detoxification of histamine.
            (Subramanian et al., 1973) Download
We considered that the production of excess L-ascorbic acid in response to an elevated histamine level might be a natural defence mechanism for detoxicating the excess histamine. To trace this, we examined the effect of ascorbic acid on histamine both in vitro and in vivo. It would appear that any beneficial effect of ascorbic acid is due to its detoxication of excess histamine produced in response to the stress.


Update on the "Dutch hypothesis" for chronic respiratory disease.
            (Vestbo and Prescott, 1998) Download
BACKGROUND:  Many patients with chronic obstructive lung disease show increased airways responsiveness to histamine. We investigated the hypothesis that increased airways responsiveness predicts the development and remission of chronic respiratory symptoms. METHODS:  We used data from 24-year follow-up (1965-90) of 2684 participants in a cohort study in Vlagtwedde and Vlaardingen, Netherlands. Increased airways responsiveness was defined as a PC10 value (concentration of histamine for which challenge led to a 10% fall in forced expiratory volume in 1 s) of less than 8 mg/ml. Information on respiratory symptoms was collected by means of a standard questionnaire every 3 years. Logistic regression was used to control for age, area of residence, cigarette smoking status, and sex. FINDINGS:  Participants with increased airways responsiveness (1281 observations) were more likely than those without increased airways responsiveness (5801 observations) to develop the following symptoms during any 3-year follow-up interval: chronic cough (odds ratio 1.9 [95% CI 1.2-2.9]), chronic phlegm (2.0 [1.3-3.0]), dyspnoea (2.3[1.5-3.5]), asthmatic attacks (3.7[2.2-6.1]), and persistent wheeze (2.7[1.7-4.4]). The estimate of the odds ratio for the development of any of the six symptoms was 1.7 (1.2-2.3). Participants with increased airways responsiveness were less likely than those without this characteristic to show remission of these respiratory symptoms. The estimate of the odds ratio for the remission of any of the six symptoms was 0.42 (0.28-0.61). INTERPRETATION:  These prospective analyses show that increased airways responsiveness is positively associated with the development of chronic respiratory symptoms and negatively associated with the remission of these symptoms in adults.



Abdel-Aziz, AM and DJ Boullin (1964), ‘Effect Of Pyridoxine Deficiency On Intestinal Histaminase In The Rat.’, Biochem Pharmacol, 13 803-5. PubMed: 14184030
Blue, J. A. (1956), ‘An evaluation of histamine as a therapeutic agent in some allergic disorders’, South Med J, 49 (6), 636-40. PubMed: 13324460
Chatterjee, IB, et al. (1975), ‘Effect of ascorbic acid on histamine metabolism in scorbutic guinea-pigs.’, J Physiol, 251 (2), 271-79. PubMed: 52707
Cooperman, JM and R Lopez (2002), ‘The role of histidine in the anemia of folate deficiency.’, Exp Biol Med (Maywood), 227 (11), 998-1000. PubMed: 12486209
Haas, HL, OA Sergeeva, and O Selbach (2008), ‘Histamine in the nervous system.’, Physiol Rev, 88 (3), 1183-241. PubMed: 18626069
Jonez, HD (1952), ‘The use of histamine in the treatment of allergic diseases.’, Ann Allergy, 10 (4), 454-64. PubMed: 14944098
Kohn, JB (2014), ‘Is there a diet for histamine intolerance’, J Acad Nutr Diet, 114 (11), 1860. PubMed: 25439083
Luk, GD, TM Bayless, and SB Baylin (1980), ‘Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity.’, J Clin Invest, 66 (1), 66-70. PubMed: 6772669
Martner-Hewes, PM, et al. (1986), ‘Vitamin B-6 nutriture and plasma diamine oxidase activity in pregnant Hispanic teenagers.’, Am J Clin Nutr, 44 (6), 907-13. PubMed: 3098085
Molderings, GJ, et al. (2011), ‘Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options.’, J Hematol Oncol, 4 10. PubMed: 21418662
Nandi, BK, et al. (1974), ‘Effect of ascorbic acid on detoxification of histamine under stress conditions.’, Biochem Pharmacol, 23 (3), 643-47. PubMed: 4132605
Ringel, EW, NA Soter, and KF Austen (1984), ‘Localization of histaminase to the specific granule of the human neutrophil.’, Immunology, 52 (4), 649-58. PubMed: 6430792
Subramanian, N, et al. (1973), ‘Role of L-ascorbic acid on detoxification of histamine.’, Biochem Pharmacol, 22 (13), 1671-73. PubMed: 4147115
Vestbo, J and E Prescott (1998), ‘Update on the “Dutch hypothesis” for chronic respiratory disease.’, Thorax, 53 Suppl 2 S15-9. PubMed: 10193342