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The Journal of Orthomolecular Medicine Vol. 13, 4th Quarter 1998

Article

Histamine Levels in Health and Disease

James A. Jackson, Ph.D., BCLD; Hugh D. Riordan, M.D.;Sharon Neathery, M.T.; Chris Revard, B.S., CLS

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Histamine is a biologically active amine compound formed in the body by removal of an acid group from histidine. It is most often associated with Type 1 IgE hypersensitive reactions.

When released from basophils and tissue mast cells, the biological effects of histamine include increased vascular permeability of small venules; contraction of bronchial and other smooth muscle; increased gastric, nasal, and lacrimal secretions. A function not normally associated with histamine is the role of neurotransmitter in the brain.1,2 Elevated histamine levels may also be related to certain forms of headache and schizophrenia.3,4,5 A list of the characteristics of patients with low or high blood histamine levels are shown in Table 1 (p.237).

The first accurate and convenient method for measuring blood histamine levels was first described by Dr. Carl C. Pfeiffer in 1968. This fluorescent method is performed on two milliliters of venous blood mixed with five milliliters of 10% trichloracetic acid. Histamine and the polyamines, spermidine and spermine, are separated by ion-exchange techniques using cation cellulose. The solution is reacted with a chemical to induce fluorescence, which is then read in a spectrofluorometer. The reference range for histamine by the method used at the BioCenter Laboratory is 25 to 65 ng/mL.6,7

Clinical Cases

Laboratory records were reviewed for patients having a blood histamine level requested by one of The Center’s physicians. Fifty-five patients were randomly selected from the records. The histamine level and physician diagnosis were then compared. If a urine pyrrole level was also requested, it was included in the data. Elevated pyrroles are said to be associated with physiological and/or psychological stress.8 Table 2 (p.237) lists patients with elevated histamine, diagnosis and pyrrole levels. Table 3 (p.238) lists patients with low histamine, diagnosis and pyrroles levels. Table 4 (p.238-39) lists patients with normal histamine, diagnosis and pyrrole levels.

As Table 2 shows, eight patients out of the 55 examined (14.5%), had high histamine levels. All patients had one or more of the symptoms of histadelia listed in Table 1. Three of the patients also had high urine pyrrole levels. Note the histamine and pyrrole level in the 49 year old male with OCD. He has had obsessive compulsive disorder for many years. During his visits at The Center, blood histamine and urine pyrroles were measured. The results obtained were as follows: August 18, 1992 histamine 83 ng/dL, pyrroles 20 ug/dL June 16, 1994 histamine 117 ng/dL, pyrroles 32 ug/dL January 17, 1997 histamine 107 ng/dL, pyrroles 33 ug/dL.

This patient continues to have significant problems with his OCD behavior. It will be interesting to follow this patient and to see if there is any correlation between the levels of histamine and pyrroles with any improvement in the patient’s condition. The histamine levels of 117 and 107 ng/mL are among the highest seen in our laboratory. As Table 3 shows, five out of 55 patients (9.0%, and all females) had low histamine levels. Four of the patients also showed an elevated pyrrole level. These patients had one or more symptoms of histapenia.

Histamine Levels in Health and Disease

Table 1. Characteristics of blood histamine levels

Low blood histamine (histapenia) High blood histamine (histadelia)

Paranoia Obsession and compulsion Overstimulation: low productivity Overstimulation, with productivity Excessive need for sleep Less than average need for sleep High tolerance for pain Low tolerance for pain Low tolerance for drugs Low tolerance for drugs Low libido; slow sexual response High libido; fast sexual response Easy frustration; mild depression Exaggerated depression Few allergic reactions Frequent allergic reactions Non-addictive nature High addictive potential Slow metabolizer of food Rapid metabolizer of food Tension headaches Migraine-type headaches Cry easily Has chronic muscle-spasm syndrome Steatopygous body type-hirsute Tend to be thin-little body hair

Table 2. Comparison of diagnosis with elevated histamine and urine pyrrole levels

Blood Urine Histamine Pyrrole Age/Sex Diagnosis Normal= 25-65ng/mL Normal= < 20ug/dL

42/M bipolar, organic brain syndrome 76 25 30/F headache, PMS, back pain, easy

bruising 25 49/M obsessive compulsive disorder 107* 33 47/M headache, allergies 77 7 50/F depression, headache, anxiety, back

pain, easy bruising 65 17 51/F headaches, obesity, Candiasis 70 0 51/M migraine headache, memory loss

diabetes 71 18 39/F depression, back pain, PMS, arthritis 68 3

Forty two patients (Table 4) had normal histamine levels. Some of these patients also showed symptoms of histapenia pyrroles serve as a good indicator and di-and/or histadelia. It is interesting to note agnostic aid for patients suffering physi-that 21 (50%) of these patients had elevated ological and psychological stress.8 urinary pyrroles. Patients with elevated The BioCenter Laboratory serves as a pyrroles (Table 2, 3, and 4) confirms the national reference laboratory and performs results published previously by the authors histamines and pyrroles on specimens which showed that elevated urinary from many different clinical facilities

Journal of Orthomolecular Medicine Vol. 13, No. 4, 1998

Table 3. Comparison of diagnosis with low histamine and urine pyrrole levels

Blood Urine

Histamine Pyrrole Age/Sex Diagnosis Normal= 25-65ng/mL Normal= < 20ug/dL

42/F depression, anxiety, headache,

allergies 25 14 41/F depression, headaches, CFS,

obesity 23 5 30/F allergies 22 4 38/F insomnia, irritable bowel syndrome,

fibromyalgia 19 93 49/F headaches, gastritis, PMS 17 32

Table 4. Comparison of diagnosis, normal histamine, and urine pyrrole levels

Blood Urine

Histamine Pyrrole Age/Sex Diagnosis Normal= 25-65ng/mL Normal= <20ug/dL

59/F hair loss, constipation 58 5

allergies, CFS, sinusitis, hypertension 41 NA 48/M back pain, edema 53 21* 31/F headache, gastritis, PMS 42 11 51/M depression, anxiety, fatigue, tinnitus,

muscle spasms, arrhythmias 43 5 27/F depression, insomnia 37 0 34/F diabetes 32 26* 48/F migraine headache 33 30* 72/M depression, leukopenia, hypothyroid 61 36* 43/F depression, headache, recurrent cough 63 21* 50/F insomnia, CFS, myositis 35 20* 43/F fatigue, constipation, hyperlipidemia 55 13 65/M allergies, myalgia, hypertension 46 31* 61/F bipolar, headache, edema 55 24* 41/M bipolar, allergies, constipation 44 2 51/F allergies, sinusitis, CFS, hypothyroid 31 22* 70/M depression, Parkinson’s disease 49 20* 29/M bipolar, depression, CFS 52 18 34/F depression, schizophrenia, headache,

allergies, sinusitis, easy bruising 36 15 cont’d

Histamine Levels in Health and Disease

Table 4. (cont’d) Comparison of diagnosis, normal histamine, and urine pyrrole levels

Blood Urine

Histamine Pyrrole Age/Sex Diagnosis Normal= 25-65ng/mL Normal= <20ug/dL

37/F headache, CFS, insomnia, easy bruising 47 26* 40/F headache, insomnia, acne, PMS 59 28* 52/F allergies, dermatitis, arthritis, back pain 61 39* 28/F depression, fatigue, edema 53 35* 45/F headache, insomnia, dermatitis,

hypertension, fibromyalgia 45 22* 21/F headache, fatigue, acne, easy bruising 54 6 42/M bipolar, organic brain syndrome 31 NA 37/M depression, memory loss, easy bruising 45 19 49/M depression, anxiety, tachycardia, dermatitis 48 9 15/F headaches 29 4 15/F anxiety, fatigue, asthma 39 22* 13/M Down Syndrome, alopecia 45 32* 66/M fatigue, hypertension 34 22* 17/F easy bruising, hair loss, dermatitis, acne 39 6 66/F easy bruising, migraine, anemia 58 31* 51/M depression, headaches, hearing loss 54 56* 48/M headache, memory loss, allergies 48 2 73/F depression, anxiety, migraine, easy

bruising, hypertension 34 7 43/M allergies, tinnitus, easy bruising, obesity 47 9 29/F headache, IBS, PMS 30 151* 51/F depression, insomnia, allergies, fatigue 62 3 40/F anxiety, CSF, Epstein Barr, gastritis 43 19 60/M depression 37 16

*= elevated pyrroles

across the United States and Canada. In reviewing results from 50 blood histamines and urine pyrroles received from one clinical facility, two patients had low histamine levels while seven had high histamines levels. Eleven patients (22%) had elevated urine pyrroles. According to the director of the facility (an alcohol dependency nutrition treatment center), the information received from urine pyrrole levels is helpful in treating their patients.9,10

It must be noted that patients seen at The Center are chronically ill. Many of them have been seen by two or more physicians in the past and still present with a chronic illness. The protocol used at The Center include many tests not normally performed in the usual clinical laboratory. These “unusual” tests often allow the physicians at the Center to diagnose and successfully treat these patients. Blood histamine and urine pyrrole are examples of these tests.

References

1. Pfeiffer CC: Blood histamine, basophil counts and trace elements in the schizophrenias. Rev

Can Biol, 1972b; 31:73.

  1. Schwartz JC: Histamine as a transmitter in brain. Life Sci, 1975; 17: 503-517.

  2. Pfeiffer CC, Smyrl EG, Iliev V: Extreme basophil counts and blood histamine levels in schizophrenic patients as compared to normals. Res Commun Chem Pathol Pharmacol, 1972a; 4: 51.

  3. Rauscher FP, Nasrallah HA, Wyatt RJ: Histamine and schizophrenia. In eds.Usdin E, Hamburg DA, Barchas JD: Neuroregulators and Psychiatric Disorders, 1977; New York: Oxford University Press.

  4. Green JP, Johnson CL, Weinstein H: Histamine as a neurotransmitter. In eds. Lipton MA, DiMascio A, Killam KF: Pharmacology: a generation of progress, 1978; New York: Raven Press.

  1. Lorenz W, et al: A sensitive and specific method for the determination of histamine in human whole blood. Hoppe-Seyler’s Z Physiol Chem, 1972; Bd. 353: 911-920.

  2. Pfeiffer CC, et al: Blood histamine, polyamines and the schizophrenias. Res Commun Chem Pathol Pharmcol, 1970a; 1: 247.

  3. Jackson JA, Riordan HD, Neathery S, Riordan NH: Urinary pyrroles in health and disease. J Orthomol Med, 1997; 12; 2: 96-98.

  4. Mathews-Larson J: Seven Weeks to Sobriety, 1997; Fawcett Columbine, New York.

  5. Mathews-Larsen J: Bio-Recovery Times Newsletter, Health Recovery Center, 3255 Hennepin Ave S., Minneapolis, MN 55408.


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