Metabolic and Mental Health
Histamine: The Many Hats of a Paradoxical Biochemical for the Body and Mind
Explore this neurotransmitter’s versatile role in the brain, nervous, immune, and cardiovascular systems to balance it.
Paradoxically histamine is a tiny yet complex and potent molecule that amazes scientists and health practitioners because of its hormonal and neurotransmitter effects on the body and mind.
Histamine’s impact and implications on our physiology and psychology are phenomenal. However, the psychoactive properties of histamine are not yet well understood. Over a century, details of histamine research require a multi-volume book, with around 93,000 medical reports stored in PubMed.
Covering the details in an article is impossible and also unnecessary. Therefore, I only provide a high-level perspective with critical points for the awareness of this crucial molecule for our health and well-being.
To explore it further, you might check the links I provide from credible sources, covering its multiple aspects.
Histamine might be a new term in your vocabulary, but you may have heard about or used antihistamine medication for allergic conditions to relieve discomfort. They are so popular that they hit the top of the OTC list.
These medications might give you a clue about histamine’s role in the immune system. But this multifaceted neurotransmitter or hormone has more effects on the body and mind. I unfold them succinctly in this article, highlighting the essential points for your health and well-being.
What is histamine?
Histamine is a molecule produced by various body cells. As a neurotransmitter and hormone, it involves many physiological processes. For example, it regulates the immune, nervous, and cardiovascular systems.
After 1910 when Nobel Laureate, Sir Henry Dale, identified it, scientists classified histamine as a neurotransmitter and biogenic amine. Histamine is originated from the amino acid histidine with the help of an enzyme called l-histidine decarboxylase.
By the way, histidine is one of the nine essential amino acids the body cannot create by itself. Therefore, we need to take it from protein-rich food or supplements.
Histamine is complex but a tiny molecule. Therefore, it can easily cross cell membranes, diffuse quickly, and interact with various target tissues as a hormone.
As documented in this paper, “histamine and its receptors represent a complex system of immunoregulation with distinct effects.”
“Several host factors and genetic factors may influence histamine/receptor effects, including the microbiota, gender, aging, autoimmune diseases, inflammatory skin, cancer, gut, and pulmonary diseases.”
Histamine has four receptors: H1, H2, H3, and H4. These receptors are involved in various physiological and psychological processes. You can learn the scientific and technical details from this paper.
Histamine is a heavily researched molecule for various reasons. As concluded by this scientific paper, “histamine research is an attractive perspective for the potential therapeutic exploitation of new drug targets.”
Histamine can be tested via blood or urine, as described in this source.
The Role of Antihistamines for the Body
As informed by this paper, “the seminal work on histamine was published in 1910, but histamine was not identified as a mediator of anaphylactic reactions until 1932. Research later showed that histamine is a significant mediator responsible for the symptoms of allergic rhinitis.”
Allergic rhinitis is inflammation inside the nose caused by allergens, such as dust, pollen, animal hairs, or mold.
Over-the-counter antihistamine drugs mainly block the histamine receptors (H1 receptors) on cells, preventing histamine from binding and triggering an immune response.
Some antihistamine drugs can cause drowsiness, making a sedative effect. Therefore some people use them as a sleep aid. One of the most common ones is promethazine.
I emphasize this point as (in addition to its antihistamines effects) some qualified healthcare professionals also use it for other purposes as it has soothing, antipsychotic, and antiemetic effects.
Promethazine is sold under the brand name Phenergan in Australia and is available without a prescription. However, pharmacists always discuss its impact and side effects before providing this medication to their clients.
Antihistamine medication might have side effects such as fatigue, drowsiness, headache, dry mouth, blurred vision, agitation, irregular heartbeats, nausea, and constipation. Therefore, it is essential to use them with guidance and support from qualified healthcare professionals.
Histamine’s Role in the Brain and Nervous System
Histamine modulates neural activities in the prefrontal cortex, the hypothalamus, and the amygdala. Therefore, it plays a crucial role in cognitive and mental health.
From a functional perspective, as a neurotransmitter, histamine regulates mood, various cognitive functions, and sleep. Thus, it can affect wakefulness, alertness, learning, and appetite.
Histamine’s role in regulating the circadian rhythm is noteworthy as it has sleep and memory implications. For example, histamine balance can impact REM sleep and is associated with memory consolidation.
Handbook of Clinical Neurology informs that “histamine cells fire rapidly during states of wakefulness, slowly during states of rest, and do not fire during REM sleep. Blocking histamine is a well-known pharmacological approach used to induce sleep.”
Therefore, histamine balance is crucial for restorative sleep as it is critical in sleep onset and maintenance.
In addition, as documented in this paper, histamine also interacts with other neurotransmitters like dopamine, serotonin, and acetylcholine, contributing to their release in the brain.
The paper informs that “histamine is released into some synapses, and also into the bloodstream where it acts as a hormone. It is also broken down by an enzyme and may be removed from the synapse through reuptake.”
As informed by this review paper by the American Physiological Society, “histamine in the nervous system signals the gut, the skin, and the immune system. Histaminergic neurons in the mammalian brain are located exclusively in the tuberomammillary nucleus of the posterior hypothalamus and send their axons all over the central nervous system.”
Histamine’s Role in the Immune System
Histamine is involved in innate and acquired immunity and affects allergies, inflammation, and autoimmune responses.
Histamine is synthesized and stored in mast cells, basophils, and enterochromaffin-like cells. These cells release histamine in response to stimuli such as allergens, irritants, and bodily infections, triggering an immune response in the body.
As documented in this paper, “mast cells are multifunctional bone marrow-derived tissue-dwelling cells that are the primary producer of histamine in the body.”
Mast cells are involved in immunity and allergic responses by storing and releasing histamine and other signaling molecules in response to various stimuli, such as allergen/irritant exposure and tissue injuries.
Immune signals control the levels and functions of histamine. Some studies associate deficient histamine levels with elevated proinflammatory cytokines and a higher susceptibility to autoimmune diseases.
As most of us must have experienced, excessive histamine release in the body can lead to unpleasant symptoms such as itching, redness, and swelling.
In addition, elevated and prolonged histamine levels might also lead to allergic conditions and asthma for some people.
Histamine’s Paradoxical Role in the Cardiovascular System
Besides the immune system, histamine is critical in the cardiovascular system.
From a cardiovascular perspective, histamine’s activity can regulate blood pressure, improve oxygen delivery to the tissues, and increase cardiac output.
Histamine serves as a vasodilator, relaxing the walls of blood vessels and increasing blood flow. Vasodilators are natural substances or medications that dilate blood vessels.
Previously I introduced nitric oxide, a potent vasodilator improving cardiovascular health. Magnesium is another neuroprotective vasodilatory agent with various experimental and clinical profiles, as documented in this paper.
Besides acting as a vasodilator, histamine might also act as a vasoconstrictor. Vasoconstriction means the constriction of blood vessels by small muscles in their walls.
So, depending on its biochemical interactions, histamine might tighten the walls of blood vessels and reduce blood flow, contributing to conditions such as high blood pressure, heart disease, and stroke.
Impact and Implications of Histamine Imbalance
There is growing literature highlighting the importance of histamine homeostasis (balance) for physical and mental health.
Apart from its impact on the brain, nervous system, and cardiovascular system, the most critical issue regarding histamine imbalance can manifest in immune reactions leading to severe conditions such as allergies and chronic inflammation.
As histamine is a mediator of inflammation, it contributes to developing an inflammatory response. Therefore, when the body is exposed to a harmful stimulus, such as an allergen or infection, it releases histamine and triggers the inflammation response.
The critical point is that when released, histamine signals the surrounding cells and increases blood flow, allowing more immune cells to reach the site of infection or injury.
Therefore, excessive histamine release might lead to excessive inflammation. This condition is evident in allergic reactions and food intolerances when the body overproduces histamine and shows symptoms such as itching, redness, swelling, asthma attacks, and difficulty breathing.
It is also possible to accumulate excessive histamine from some foods. When the amount passes the threshold, the body can create histamine intolerance. However, like excessive histamine, too little histamine can also be a problem for the body.
Deficiencies of histamine might lead to susceptibility to infection, gastrointestinal and cardiovascular issues, sleep disturbances, irritability, anxiety, depression, and schizophrenia.
As documented in the Handbook of Clinical Neurology, “histamine also plays a role in sexual dysfunction, and supplementation with folic acid and niacin (used together), as well as L-histidine (an enzyme that metabolizes histamine from histidine), is effective in addressing histamine deficiencies.”
Histamine imbalances might lead to hormonal imbalances, skin conditions, gastrointestinal issues, food intolerances, and migraines. Therefore, maintaining a proper balance of histamine levels is crucial for health and overall well-being.
There is also a condition called histamine intolerance or sensitivity to dietary histamine. It is a disorder associated with an impaired ability to metabolize ingested histamine. Histamine intolerance also refers to a high level of histamine in the body when it cannot break down histamine.
This paper states, “although interest in histamine intolerance has grown considerably in recent years, more scientific evidence is still required to help define, diagnose, and clinically manage this condition.”
This 2021 paper informs that “Histamine intolerance (HIT) is assumed to be due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO) and, therefore, the food component histamine not being degraded and/or absorbed properly within the GI tract.”
It is essential to choose healthy lifestyle habits to optimize histamine levels, similar to the optimization of other biochemicals in the body. Gut health is critical for balance.
The fundamentals are a balanced diet, regular exercise, restorative sleep, rest, fun, and stress management approaches such as mindfulness and meditation.
Takeaways
1 — Understand the critical role of histamine for the body and mind.
2 — See histamine as a friend rather than a foe.
3 — Balance histamine levels by eating nutritious and clean food.
4 — Refrain from toxins, allergens, and pathogens.
5 — Detoxify the body naturally by initiating autophagy and mitophagy.
6 — Use antihistamine medication only when needed with guidance from qualified healthcare professionals.
7— When you experience food intolerance or allergies, obtain support from qualified healthcare professionals like your family physicians, dieticians, nutritionist, allergy specialists, and gastroenterologists.
Balancing our hormones, neurotransmitters, and other biochemicals via healthy lifestyle choices is crucial as they play a critical role in our health and well-being.
I introduced the intricacies of hormones in various articles before. I also wrote about other neurotransmitters such as dopamine, serotonin, oxytocin, GABA, acetylcholine, norepinephrine, and adrenalin,
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