17 Histamine Health Effects: Cognition, Inflammation & Sleep

Is Histamine Wreaking Havoc in Your Body?

17 Histamine Health Effects: Cognition, Inflammation & Sleep

You may have heard that we’ve been hard at work here at Genius Labs, cooking up new features for SelfDecode, our sister company.

Recently, we announced that we have a brand NEW Personalized Genetics Blog! 

Anyone can read the blog, but only SelfDecode members with DNA files can see their personalized DNA analysis and recommendations the blog topic. We publish new topics regularly!

Today, we’re focusing on histamine levels related to the AOC1 and the HNMT gene. 

If you suffer from allergy- reactions after you eat, this is typically due to an inflammatory response. For me, amines in food, including histamines, can cause issues.

Too much histamine in your system can cause allergy- reactions even when you don’t have an allergic response to anything you’ve eaten. This is called histamine intolerance.

So, if you have too much histamine in your system already and you eat food with histamine in it, your body can’t process it, resulting in symptoms that resemble an allergic reaction.

The diamine oxidase enzyme helps to regulate your histamine levels by breaking down histamine in the gut. Your DAO gene determines how much of the enzyme your body makes naturally.

If you have one of the gene variations which results in lower DAO, you are more ly to have a surplus of histamine and histamine intolerance.

If you are at risk for histamine intolerance, you should examine your diet and try to eliminate some foods that are high in histamine.

Some of those include:

  • Legumes
  • Aged cheese
  • Spinach
  • Tomatoes
  • Wine
  • Chocolate
  • Canned foods

The simplest solution for reduced DAO activity is also the easiest: taking diamine oxidase, which is available as a supplement.

Before you start implementing solutions, it is important to find out if your symptoms are stemming from histamine or other issues (such as lectin sensitivity) so that you can effectively manage your allergy- symptoms and start to feel better!

However if you have more migraine- symptoms and it is not directly tied to your food, you may have a variation of the HNMT gene that results in low HNMT activity. HNMT is responsible for breaking down histamine and is most important in the brain.

This could mean that you have higher brain histamine than usual which can induce headaches or other issues such as hives or eczema. 

In those who have ADHD, an excess of histamine can worsen symptoms of children with ADHD. Therefore, increasing the HNMT gene is beneficial. 

If you aren’t a member of SelfDecode, you won’t be able to find out which variation of the gene you have.

What are you waiting for?

For only $59 a year, you can unlock more of what your genes can tell you about how to improve your health.

We’re publishing exciting new articles regularly! Don’t miss out on new information about your genetic health.

SelfHacked Posts on Histamine Intolerance:


The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease.

Information is shared for educational purposes only.

You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

Source: https://selfhack.com/blog/histamine-wreaking-havoc/

Histamine and migraine revisited: mechanisms and possible drug targets

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Histamine Pharmacology and New CNS Drug Targets

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17 Histamine Health Effects: Cognition, Inflammation & Sleep

17 Histamine Health Effects: Cognition, Inflammation & Sleep

Histamine is often cast as a villain for its role in inflammation and allergies, but this neurotransmitter regulates sleep, appetite, sexual behavior, and more. Read on to learn about the many vital functions of this inflammatory signal molecule.

What is Histamine?

You may have landed here from our previous post on histamine. If so, you know that this biogenic amine acts on four receptors (H1R, H2R, H3R, and H4R) to regulate sleep, appetite, motivation, learning, memory, and sexual behavior.

If not, you may want to read that post before continuing into this deep dive into the health effects of histamine.

Health Effects of Histamine

You may have heard some pretty bad things about histamine. It tends to be discussed in the context of bug bites, itching, and allergies, but histamine is extremely important to your body’s daily function.

1) Alertness and Wakefulness

Histamine sets your circadian clock. The first type of histamine receptor, H1R, helps you stay awake. Many antihistamine medications block this receptor, which is why they can make you drowsy [1, 2, 3].

H3R, by contrast, lowers histamine and promotes sleep. Neurons that release histamine are active during the day, stop working as you get drowsy in the evening, and start again after you wake up [4].

Low brain histamine can make you excessively sleepy during the day. It might also make waking up in the morning a struggle, even if you got enough sleep.

People with narcolepsy have low brain histamine and uncontrollably fall asleep during the daytime. Tiprolisant is a drug that can increase their wakefulness and brain histamine by blocking H3R [3, 5].

2) Motivation and Exploration

Histamine increases motivation to meet goals. It also reduces the drive to eat, so you can focus on completing tasks [6].

Brain histamine also makes animals more ly to explore new things. Mice with low histamine or low H1R have less interest in novelty and explore less when they are placed into a new environment. They also have reduced emotional responses to these new environments [6].

In one study, patients with depression had reduced H1R binding. By the same token, loss of histamine or histamine receptors causesdepression in animals [6, 7].

This effect may have a dark side, however: people with anorexia have increased H1R activity, and mice with more H1R and less H2R activity are more ly to be anxious [8, 9].

3) Stress Management

Histamine is part of the body’s alarm system. Brain histamine increases alertness and focus and decreases pain and the desire to eat; these changes are part of the fight or flight response and prepare the body to respond to danger [6].

Various types of stress increase brain histamine; these include dehydration, loss of blood, severe infection, or emotional triggers [10].

4) Cognitive Performance

Histamine stimulates certain types of memory and learning, but inhibits others [11].

H1R antihistamines can impair cognitive performance in humans, possibly because of their sedating effect. By contrast, blocking H3R improves memory, attention, and cognitive performance in most (but not all) cases [12, 13].

H1R is important for memory, learning, and wakefulness. H1R-deficient mice have general learning and memory impairments. They also have poor spatial memory and fail to make sense of space- and time-related information [14, 15].

Activation of histamine receptors improves object recognition, an important measurement of cognitive function in rats. The object recognition test measures the amount of time the animal spends exploring a new object relative to an object it has seen before, indicating whether it recognizes and remembers the old object [13, 16].

Also in rats, histamine promotes memory consolidation, the process by which short term memories are stored as long term memories [17, 18].

5) Aging & Cognitive Decline

Some researchers believe that part of the cognitive decline inAlzheimer’s disease may be caused by low brain histamine and fewer histamine-releasing neurons [15].

People with Alzheimer’s tend to have lower H1R activity, the level of which correlates with the severity of cognitive symptoms. By contrast, they have higher blood histamine levels [15, 19].

The Alzheimer’s disease drug tacrine mostly inhibits acetylcholinesterase, but it also inhibits HNMT and thereby increases brain histamine [15, 20, 21].

6) Temperature Regulation

When the body heats up, neurons release histamine. Activated H1R then dilates the airways and increases breathing rate. This process decreases body temperature [22, 23].

Elevated histamine in the brain generally leads to hypothermia (below-normal body temperature). If needed, however, histamine can also raise body temperature by acting on other brain areas [24, 25, 22].

7) Preventing Seizures

Histamine protects against seizures by increasing the seizure threshold: when histamine levels are high, it takes more stimulation to induce a seizure [26].

Treatments that increase brain histamine may improve some forms of epilepsy, while histamine-blocking drugs worsen it. For example, H2R and H1R antihistamines (such as diphenhydramine and famotidine) have both been implicated in seizures (as rare side effects) [27, 28].

On the other hand, blocking H3R facilitated histamine release and protected against seizures in humans and rodents [29, 30, 31].

8) Alcohol Preference

Brain histamine may influence whether we have a preference for alcohol, and a variation in the HNMT gene has been linked to alcoholism, though this association is controversial [32, 33, 34, 35].

Mutations in rs11558538 may influence the degree to which people are vulnerable to dependence on alcohol. The common allele (C) may lower brain histamine, compared to the less common allele (T); people with the T allele (higher brain histamine) may be less vulnerable to alcoholism [34, 35].

9) Appetite Regulation

Brain histamine decreases appetite and helps control how often we eat, our circadian rhythm. Higher histamine suppresses appetite and decreases caloric intake, body weight, and blood triglycerides in rodents and monkeys [36].

In contrast, low histamine activity increases appetite, meal size, and duration of eating. Mice with low H1R activity eat at irregular times and are prone to metabolic syndrome and obesity. Similarly, histamine-deficient mice develop more stomach fat and insulin and have impaired glucose tolerance [37, 38].

Certain behaviors, lifestyle factors, and disorders change histamine activity in the brain. Chewing your food well releases histamine, activates H1R in the brain, and may help reduce appetite. Leptin, the “satiety hormone,” increases brain histamine activity as well [39, 38].

During pregnancy, histamine levels drop; this helps increase appetite and food consumption [6].

People with anorexia have more H1R receptors in the brain; they respond more strongly to histamine and have low appetite [6].

10) Water Intake Regulation

High histamine brain levels increase thirst and encourage you to drink more water. Prolonged dehydration (24 to 48 hours) triggers histamine release in the brain. In turn, histamine also increases the hormone vasopressin, which tells the kidneys to reabsorb more water and keep it in the blood [40, 41, 42].

11) Sexual Behavior and Reproduction

Histamine and its receptors play a role in sexual function. Histamine deficiency prevented male mice from mating and shrank their testicles [43].

In humans, histamine promotes erections (and may prevent erectile dysfunction), while H2R antihistamines reduce sexual function [44, 45].

Histamine may also increase the release of hormones such asestradiol, prolactin, andLH, though this has only been confirmed in animals [46, 47, 48].

12) Hormone Release

Histamine helps regulate the release of several hormones. It:

Immunity & Inflammation

Histamine’s role in immunity and inflammation is complex and double-edged. Properly regulated, histamine is required for a healthy immune response, but too much can easily cause harm.

13) Bacterial Infection

Histamine is involved in the immune response to bacterial infection. Blocking its receptors (H2R or H3R/4R) can impair the immune response in mice; H2R inhibition may also worsen a bacterial infection of the lymph nodes [58, 59].

On the other hand, histamine deficiency in mice increased cytokine release, which helped them fight off tuberculosis in the early stages [59].

Histamine may either support or impair the immune response to infection, depending on the location and type of pathogen. Some bacteria and parasites even produce histamine themselves, hijacking the body’s inflammatory response [59].

14) Food Allergy

People with food allergies have increased histamine production and more mast cells in their gut. Taking DAO can help in food allergies by degrading gut histamine [60].

However, some histamine activity is beneficial: People who take H2R antihistamines produce more IgE against food antigens. That is, H2R activity may protect against the development of food allergy [60].

15) Pain Perception

Increasing brain histamine or inhibiting H3R has analgesic effects. Accordingly, drops in brain histamine levels and activating H3R increases pain [61, 62].

However, H1R and H2R activity outside the brain increase sensitivity to pain. Mice deficient in these receptors are less sensitive to pain; blocking these receptors also relieved pain in animals. Blocking H4R also decreased pain sensitivity in animals [63, 59, 61].

In humans, blocking H1R improves pelvic pain, and H2R inhibition improves painful bladder syndrome [61].

16) Complex Relationship with Cancer

Histamine has a complex relationship with cancer; it may promote or restrict cancer growth in different circumstances [64].

Positive Effects

Cancer patients tend to have lower blood histamine. Also, a treatment combining IL-12 and histamine may prevent relapse in people with leukemia [64, 65].

In mice, histamine deficiency increases susceptibility to skin and colon cancer, while elevated histamine reduced lymphoma growth [64, 66].

Furthermore, histamine in the blood merges withcholesterol to produce dendrogenin A (DDA), a compound with antitumor properties. DAA prevents breast cancer and melanoma in mice [67].

Negative Effects

Cimetidine, an H2R blocker, may be helpful in controlling one type of brain cancer (glioblastoma), while H3R blockers may help control another type (glioma) [68].

H4R blockers can slow the growth of colon cancer cells; this effect has not yet been reproduced in animal or human studies [33].

On the other hand, histamine in general shifts the immune system from Th1 to Th2 dominance, which may be relevant because Th1 cells fight cancer [69].

Histamine production is increased in tumor tissues, such as breast cancer, colon cancer, and melanoma. Histamine within tumors can enhance tumor growth by suppressing Th1 responses (LT-α, TNF-α, and IFN-γ) via the H2R [70, 71, 72].

More About Histamine

This is the second post in a six-part series on histamine, histamine intolerance, and how to manage it. To learn more, click through the links below.

Source: https://selfhacked.com/blog/histamine-health-effects/