Positive Health Online

Histamine: What is it and What Effects Does it Have?

What is Histamine?

Histamine is an excitatory neuro-transmitter which is made from the amino acid histidine.[1] Extensive research has shown that "histamine is a major mediator of allergic inflammation" and plays a key role in inflammatory diseases.[2]

The Presence of Histamine

Histamine was first thought only to be present in mast cells, but modern research has proven that many other cells also produce histamine to varying degrees. These include white blood cells such as basophiles, platelets, certain types of gastric cells and neurons.[2] Furthermore, histamine has been found to be present in all tissues of the body.[3]

Different histamine producing cells play a role in different conditions. Mast cells have been found to be the main sources of histamine in the blood and the respiratory system. However, in asthma it is believed that basophiles also contribute to the presence of histamine in the airways.[2] This seems to be the consensus in other types of allergic inflammation, and not just asthma.[2] In relation to gastrointestinal disease, it has been found that mast cells play a major role in both functional (irritable bowel syndrome) and inflammatory bowel disease.[4]

What are the Effects of Histamine?

Histamine exhibits a vide range of effects on the body. Its effects vary depending on the receptor sites involved, but for the purpose of this article, the generalized effects of histamine will be mentioned in order to keep it simple.

Histamine has been found to:

• Stimulate acid secretion from the stomach;[3]
• Stimulate the smooth muscles of the respiratory system;[3] 
• Cause vasodilation;[3]
• Stimulate the heart to contract;[3]
• Stimulates the smooth muscles of the gastrointestinal system by exciting the nerves that supply this system;[4]
• Promotes wakefulness. Researchers have found that histamine promotes wakefulness by stimulating the basal forebrain;[5]
• Induce an inflammatory response.[6]

Histamine has also been found to causes blood pressure to fall and stay low for as long as it is around.[3]

Furthermore, it is thought that histamine plays a major role in Chronic Fatigue Syndrome (CFS). This is believed to be due to a hypersensitivity to the immune suppressing effects of histamine. Much of the symptomatology of this condition can be explained by this hypersensitivity, which can sometimes cause permanent changes in cell membranes.[7]

The Histamine/Stress Connection

It has been shown that mast cells are activated by stressors. These stressors can either be emotional, physical or environmental.[8] Once activated, they release an array of over 50 potent molecules, including histamine, which cause or further aggravate inflammation; among these molecules are cytokines.[6] Cytokines are proteins that either stimulate of inhibit immune cells.[9]

These chemicals play a major role in the development of chronic inflammatory diseases. Some of these diseases include psoriasis, alopecia areata, acne vulgaris, asthma, and inflammatory bowel disease (IBD), to name but a few. In fact, acute stress has been found to increase the histamine levels of mast cells in the colon, resulting in functional disturbances of the gastrointestinal system.[8]

The Autonomic Nervous System

The autonomic nervous system consists of two main subdivisions: the sympathetic and parasympathetic divisions.1 The sympathetic division is further divided into alpha sympathetic (α) and beta sympathetic (ßS). α activity relates to stress, so stress/stressors increase the activity of this subdivision. ßS activity is related to the part of the autonomic nervous system that produces cortisol (a potent anti-inflammatory hormone produced by the adrenal glands). Simply put, the ßS system is the release mechanism of the body. It is the way the body adapts to stress. The parasympathetic (PS) division, among other activities, increases the secretions of fluids and in this context is a congestive system.

As we have seen above, mast cells and to some degree other cells are activated by stress/stressors and histamine is released.[8] It is thought that histamine not only goes on to affect the body directly, but also prolongs the life of α activity, so a positive feedback cycle occurs. In this way, a vicious stress induced histamine cycle is put into motion.6 In addition to prolonging α activity; histamine has a blocking effect on ßS activity, so suppressing the action of the adrenal glands and the production of cortisol. (Please see Figure 1 below)[10]

Herbal Medicine in the Treatment of Excess Histamine.

When searching for anti-histamine compounds, researchers looked for preparations that could reduce both the sympathetic and parasympathetic nervous system.[3] A wide range of herbal medicines are available which work on the specific pathways shown in Figure 1 above.

Plant Adaptogens

Plant adaptogens are herbs that have a balancing, regulating and tonic effect.[11] As defined by Lazarev, adaptogens are; "substances which elicit in an organism a state of non-specifically raised resistance, allowing them to counteract stressor signals and to adapt to exceptional strain."[12] Rhodiola rosea (Golden Root) and Withania somnifera (Winter Cherry) are two such examples. Studies have shown that adaptogens, among them Rhodiola, increase stamina, concentration and endurance, and so help the body cope with fatigue. As well as adaptogenic effects, these herbs also posses many other therapeutic actions. With regards to Withania, studies on rats have shown that it has the ability to increase resistance to stress, increase stamina, have an immune modulating effect as well as having a significant anti-depressant effect.[12]

Rhodiola is also a potent antioxidant and this has been attributed to its high polyphenol content. In a study comparing a range of plant adaptogens, Rhodiola was found to have the highest polyphenol content and therefore, can help protect the body against oxidative stress.[11] In addition to this, Rhodiola has been found to have a potent anti-depressant activity. This is, in part, due to its ability to increase the level of 5-HT in the brain as well as its ability to save damaged neurons.[13] In another study, its anti-depressant activity was found to be due to its ability to inhibiting Monoamine oxidase-A (MAO-A). It is also believed that this herb may be effective in the control of senile dementia by inhibition of MAO-B.[14] This means that Rhodiola may help alleviate depression as well as other mental disorders.[13]

Studies also show that Rhodiola has a significant anti-inflammatory action and that this action is thought to be due to its membrane stabilising effect.[15] In a Pilot study carried out in 2008, to assess the use of Rhodiola in the treatment of anxiety disorders; it was shown that patients had significant improvement.[16]
 

Herbs that Reduce aS Activity

Lavandula officinalis (Lavender) and Tilia europea (Lime Flower). Among many other herbal medicines, Lavandula and Tilia are two common examples of herbs that are well known for their relaxing effect on the nervous system.

Herbs that Increase ßS Activity

Ribes nigrum (Blackcurrant) bud and leaf stimulate ßS activity and have a potent anti-inflammatory effect. Ribes supports the adrenal glands and is capable of stimulating cortisol production.10 A study carried out demonstrates that the leaves of Ribes have a marked anti-inflammatory action and this was found to be due to the proanthocyanidins within the herb.[17]

Another herb capable of increasing ßS activity is Glycyrrhiza glabra (liquorice) root. It is a potent anti-inflammatory. Part of the way it exhibits its anti-inflammatory action is by prolonging the life of cortisol.[18] Indeed, its anti-inflammatory action has been likened to that of hydrocortisole.[19]

Reduce PS Activity

Thymus vulgaris (Thyme), Gentiana lutea (Gentian) and Chamomila recutita (German Chamomile).[10]

Herbs that Reduce Histamine

Albizzia lebeck (Pit Shirish) and Scutellaria baicalensis (Baikal Skullcap) are two herbs that exhibit a marked anti-histamine action.

Albizzia has been shown to exhibit a mast cell stabilizing effect on the mast cells of rats.[20] In further animal studies, Albizzia has been shown to have a potent effect on asthma, and began to work within 1 hour of administration. It reached its most potent action after 4 hours, and even after 24 hours it still exhibited a protective effect. It was found to have a significant protective effect against histamine-induced bronchospasm. In addition to this, in clinical trials involving asthma patients, significant relief was observed using Albizzia lebeck.[21] Also, it has been shown to have a protective effect on the adrenal glands against histamine.[22]

Scutellaria baicalensis has been traditionally used in China to treat a wide range of inflammatory and allergic conditions. It has been shown to have antioxidant and sedative properties as well as a potent anti-histamine action.[23] Baicalein, an active chemical found in Scutellaria baicalensis has been found to inhibit the production of inflammatory cytokins and the degranulation of human mast cells.[24]

In addition to these two herbal medicines mentioned, Plantago major (Common Plantain) through clinical trials has also proven effective in reducing raised histamine levels.[10]

Case Study

Patient Summary

Patient with Chronic Fatigue Syndrome, female aged 42 years old. Condition started with streptococcal throat infection and then developed reactive arthritis two weeks later. The patient developed severe fatigue and the symptoms included pain in the hips and fingers, abdominal pain, soft stools (diarrhoea-like), insomnia and bad sweet cravings. The patient had severe allergic reactions to insect bites, dust mites and pollen. An ongoing facial allergy was present.

There was a history of recurrent sinusitis and sore throats. Before the Chronic Fatigue Syndrome started she was under a lot of chronic stress. She was so fatigued even talking made her tired. The patient could not work properly and when she got tired she would develop a temperature. Her mind was very active and she could not relax easily. Blood pressure was 110/70 and pulse 63 bpm.

Treatment Plan

Advised to eliminate sugar from the diet, increase water intake and to cut out wheat for a while. The prescription consisted of anti-histamine herbal medicines as well as adaptogens and herbs that reduce α activity. An Endobiogenic blood analysis was undertaken (see end of article for more information). An Endobiogenic blood analysis is very different to a conventional blood analysis and allows one to evaluate the state of the nervous and hormonal systems. The results can be seen in Table 1.

After 2 weeks

Initially the patient felt much better. She had a lot more energy at the start of treatment  but then over exerted herself with too much walking and felt fatigued again. At the same time she had a lot of stress from work as a deadline was approaching. When the patient started her treatment, the facial allergy improved significantly, but when the pressure at work got too much the allergy returned. No major change in the insomnia.

One Month Later

Was sleeping very well and felt rested. Digestion was fine and able to cycle up the steepest hill in the area. Still had sinus congestion and allergic symptoms.

Two Months Later

Had a lot more energy and was able to work 3 days a week in the office and 2 days at home. She was able to cycle more often and felt she could now lead a pretty normal life. Exercise also included 1/2 hour walk every day. However she would get tired in the afternoons.

6 Months Later

Immunity had improved vastly. The patient did not have any bad colds or infections. She felt that it was now possible to have a normal life and to do everything she wanted to. Working every day was no longer a problem. Even though the hay fever season was present, there were no allergic symptoms.

As seen from Table 1, the patient's initial results show that the circulating cortisol and adrenal function were severely low. Also, the histamine levels were over 100 times the normal range. After 6 months of treatment there was over 50% improvement in histamine levels, and significant improvement in adrenal and cortisol activity.

Conclusion

As seen from this article, histamine exhibits a wide range of effects on both the mind and the body. Its release is stimulated by the α division of the autonomic nervous system, and it also has the effect of further stimulating α activity, thus setting up a vicious cycle. Further more; histamine has a blocking effect on ßS activity. Therefore, in order to treat allergic conditions successfully, one must take a global view and the different pathways involved in the specific condition must identified if treatment is to be successful.

References:

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10. Dr Lapraz JC. Personal communication.
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