# Histamine

Category: Hormones

Histamine is a universal stress signal, produced by virtually any cell under sufficient duress, and should be thought of as one of the primary signals of danger or damage, corresponding to the catabolic phase of an infection. Peat argued that while mast cells and basophils are…

9 passages · 1 author · 2011–2022 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/histamine

## Synthesis

**Histamine** is a universal stress signal, produced by virtually any cell under sufficient duress, and should be thought of as one of the primary signals of danger or damage, corresponding to the catabolic phase of an infection. [Source 1, 2, 6] Peat argued that while mast cells and basophils are the usual main sources, energy deprivation activates histamine formation in all cells studied, where it functions as a basic organizing factor in immunity, promoting inflammation and coagulation. [Source 2, 6] He noted that histamine helps to rouse immune functions, but its effects must be blocked for the completion of immune processes; in a prolonged excess, it tends to **calcify soft tissues**, reducing their functions. [Source 1] Like serotonin, it activates **carbonic anhydrase**, and is activated by estrogen and a reducing environment. [Source 1]

The production and effects of histamine are deeply intertwined with systemic hormonal and metabolic states. Peat identified **estrogen** as the main promoter of mast cell overproduction and histamine release, while **progesterone** and **thyroid** have the opposite effect, reducing histamine formation and release from mast cells. [Source 7, 8] He explained that estrogen activates mast cells to produce more estrogen and histamine, creating a vicious cycle, whereas increased oxidative metabolism lowers histamine and inflammation systemically, for example by lowering the ratio of estrogen to progesterone. [Source 1, 7] This hormonal dysregulation can cause a local uptake of water, a shift to inefficient metabolism towards lactic acid production, and a change in protein conformation that makes the cell appear antigenic, causing the immune system to attack what looks like foreign material. [Source 5] Peat emphasized that the tissue damage from this inflammatory state is primary, and that restoring oxidative metabolism can return proteins to their natural conformation so they are no longer antigenic. [Source 5]

Histamine's role extends into chronic disease and immune dysfunction. Peat stated that mast cells and histamine are the problem that keeps the immune system from eliminating cancer, as these pro-inflammatory factors drive cancer and disrupt immune function, sometimes promoting tumor growth through specific blocking antibodies. [Source 4] He noted that antihistamines and aspirin could produce tremendous improvement in such conditions. [Source 4] In the context of COVID-19, Peat highlighted that the virus inactivates the ACE2 enzyme, which normally destroys the pro-inflammatory angiotensin II, making it a disease of inflammation and coagulation where histamine's role in promoting both processes is central. [Source 1, 2] He also connected histamine to the stress-organizing systems of the brain, noting that when anything goes wrong, the brain activates both the histamine and serotonin systems, with prolactin as one of the reacting stress hormones. [Source 9]

Several practical interventions can oppose histamine's effects. Peat pointed out that anything which energizes and restores cell function tends to prevent histamine production, specifically mentioning that **coffee** is a very effective signal to turn off histamine production, and that *sugar* definitely has the same effect. [Source 6] He also noted that some of the shorter chain saturated fats in coconut oil have an anti-histamine effect, and that local anesthetics are functional antihistamines. [Source 6, 8] Peat referenced V. W. Adamkiewicz's work showing that reducing blood glucose with insulin greatly intensified allergic reactions, while increasing blood glucose prevented deadly anaphylaxis, demonstrating that *energy metabolism governs the effectiveness of the immune process*. [Source 1] He dismissed the idea that histamine acts as a protective mechanism against high serotonin levels. [Source 3]

## People also ask

### How does estrogen promote histamine release?

Peat argued that estrogen is the main promoter of mast cell overproduction and histamine release, and that estrogen-activated mast cells produce more estrogen and histamine, creating a vicious cycle of inflammation.

### Why does Peat consider sugar protective against histamine?

The corpus describes that increasing blood glucose prevents deadly anaphylaxis and that sugar, like coffee, is a very effective signal to turn off histamine production, because energy metabolism governs the immune process.

### What role does histamine play in COVID-19 pathology?

Peat highlighted that the virus inactivates the ACE2 enzyme, which normally destroys pro-inflammatory angiotensin II, making COVID-19 a disease of inflammation and coagulation where histamine's role in promoting both processes is central.

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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Immunology, Ideology, Power

Ray Peat · Newsletter · 2021

> Histamine should probably be thought of as one of the signals of danger or damage. It seems to correspond to the catabolic phase of an infection. Although inflammation can occur without infection, its presence is generally thought to indicate infection. The coronavirus infections inactivate the ACE2 enzyme, whose functions include destroying angiotensin II, a basic promoter of inflammation, so, more than other kinds of infection, it is a disease of inflammation. Since inflammation activates the clotting system, it is a disease of inflammation and coagulation. Before the WHO declared the pandemic, China was treating covid infections with anti-inflammatories and anticoagulants. Outside of China, governments have ordered doctors not to treat early cases of covid, until their symptoms were serious enough to require hospitalization and oxygen treatment. On October 22, 2020, the FDA approved the use of remdesivir in covid patients, but remdesivir is neither anti-inflammatory nor anticoagulant; inflammation is one of its side effects. Histamine helps to rouse the immune functions, and promotes inflammation and coagulation. In a prolonged excess, it tends to calcify soft tissues, reducing their functions. Like serotonin, it activates carbonic anhydrase, and is activated by estrogen and a reducing environment. While histamine is a basic organizing factor in immunity, its effects have to be blocked for completion of the immune processes. Increased oxidative metabolism lowers histamine and inflammation systemically, for example by lowering the ratio of estrogen to progesterone. Although anaphylaxis is usually thought of as something separate from the immune response, I think it just represents a quick entry into the high-histamine state, because of low energy reserves and slow mobilization of the hormones of homeostasis. In the 1960s, V. W. Adamkiewicz showed that reducing blood glucose with insulin greatly intensified allergic reactions, while increasing blood glucose prevented deadly anaphylaxis, but weakened resistance to infection. Energy metabolism governs the effectiveness of the immune process, including the avoidance of autoimmunity (Gaber, et al., 2017). Metabolic energy is involved in every aspect of the covid infection, but that has been denied or ignored because of a traditional, ideological understanding of immunity.

### Source 2 — Immunology, Ideology, Power

Ray Peat · Newsletter · 2021

> When a cell is damaged, it releases internal components including DNA, RNA, and ATP, and these are recognized by cells that promote repair of the damage, under the guidance of systemic interactions. Unfamiliar antigens will be eliminated along with the damaged tissue, by a combination of many factors, from phagocytes to antibodies. A few people had been recognizing the failure of the clonal deletion theory for a long time. At an international meeting of immunologists in 1969 at the University of Oregon, a young teacher had demonstrated that the deleted clones could be restored, giving the original repertoire of antibodies, if the immune cells were simply cultured at a higher density than Burnet and Nossal had used, allowing the cells to interact with each other, forming a network that was able to detect, and repair, the deletions. Although his lecture was attended by only a few people, and the main speakers acted as though it hadn’t happened, Niels Jerne apparently noticed it, because he later presented an alternative to clonal deletion based on his idea of an “idiotype-antiidiotype network” (Jerne, 1974). By itself, it wasn’t an adequate theory, but it moved in the right direction. The damage and danger theories have provided a way to discard the various Nobel Prize winning theories of antibodies and their functions, and to begin seeing immunity and resistance as holistic processes of the organism.
>
> The nature of protective reactions has been obscured by thinking in terms of “the immune system,” as something distinct from metabolic and adaptive processes. The various “-phylaxes,” starting with skeptophylaxis (lightning or quick protection), have made it clear that the endocrine system and metabolic systems are deeply involved in the adaptive protections. Although mast cells and basophils are usually the main sources of histamine, experiments have shown that under the most extreme conditions, all of the cells studied produced histamine. Energy deprivation activates the formation of histamine, which activates many “immune” functions, including increasing the TLRs, and production of cytokines and antibodies. Histamine should probably be thought of as one of the signals of danger or damage. It seems to correspond to the catabolic phase of an infection. Although inflammation can occur without infection, its presence is generally thought to indicate infection.

### Source 3 — Ray Peat Email Advice Depository — Post 866

Ray Peat · Email · Dec 3, 2022

> **Question:** Hello Dr. Peat This study found that when mice were injected with LPS brain serotonin levels dropped while staying the same in the control group. While also stating that histamine rose in the brain - to block the effect of serotonin. Do you think that histamine acts as a protective mechanism against high levels of serotonin? [Histamine could be a key player in depression, according to study in mice](https://www.imperial.ac.uk/news/228353/histamine-could-player-depression-according-study/)
>
> **Ray Peat:** No.

### Source 4 — KMUD - October 15, 2021

Ray Peat · Interview · Oct 17, 2021

> **Ray Peat:** I think that mast cells and mostly histamine are the problem that keeps the immune system from going ahead and getting rid of the cancer. These particular pro-inflammatory things are driving cancer and disrupting the immune function so that some of the antibodies formed in reaction to the abnormal tissue in the cancer some of the antibodies specifically block other immune reactions and promote the tumor growth.
>
> **Andrew Murray:** So antihistamines and other compounds that would stop mast cell degranulation to release and liberate histamine would also be useful.
>
> **Ray Peat:** Yeah, definitely. And if you mention taking aspirin and antihistamines, for cancer. Until just recently, everyone would ridicule the idea, but now there's enough foundation for it that you can see tremendous improvement just in a couple of days with good antihistamines and aspirin.
>
> **Andrew Murray:** Good. Let's hold it there. I want to ask you more questions about aspirin when we get back from this caller, but we've got a caller on the air. So you're on the air. Caller, where are you from? What's your question?

### Source 5 — One Radio Network: Ray Peat with Patrick Timpone — December 20, 2021

Ray Peat · Interview · Dec 20, 2021

> **Ray Peat:** My current newsletter has a little bit about that. The histamine, for example, activated by estrogen and many other things, But histamine and estrogen and endotoxin, each of those tends to make your tissues take up water, get inflamed, start producing more histamine or analogous things, release endotoxin from your intestine to circulate through your bloodstream. endotoxin makes things more inflamed, leakier, and the histamine effect in cells is causing a local uptick of water, a change of the protein relation to the surrounding water, an activation of the cell, excitation, shift to inefficient metabolism towards lactic acid production for example and that damage these transmitters that change the metabolism are changing the antigenic properties of the cell it doesn't take a powerful chemical reaction just a stretching or excess bending or swelling of a tissue can change the protein conformation enough that it becomes antigenic. Your immune system sees what looks like a foreign antigen because of these intrinsic pro-inflammatory signals. The cell is swelling up and getting deranged. And to the immune system, at an extreme, that looks like a foreign material. So the immune system comes in and tries to clean up the damage the way it would with a bacteria or fungal infection. It kills the cells and carries away the debris as far as possible. So although these same components, histamine and estrogen, for example, will shift, your immune system, knocking out the brain of your immune system, the thymus cells, suppressing them and releasing the antibody-forming B cells, and at the same time activating an enzyme that creates actual genetic change, a genomic destabilization. enzyme, they call it AID, that produces novel antibodies. So you're generating more and more antibodies under the influence of estrogen and histamine.

### Source 6 — Digestion and Emotion KMUD January 2015

Ray Peat · Interview · 2015 · https://www.youtube.com/watch?v=nFxqSK5DC8Y

> **Caller:** Could you explain briefly the mechanisms of histamines and the good ways to correct that [histamine responses]?
>
> **Ray Peat:** Since I was mentioning the saturated fats...some of the shorter chain saturated fats in coconut oil have an anti-histamine effect. Coffee is very effective signal to turn off histamine production. Anything that energizes and restores cell function tends to prevent the production of histamine.
>
> **Andrew Murray:** How about sugar?
>
> **Ray Peat:** Oh, definitely! A person wrote a book about histamine about 40 years ago and he demonstrated that histamine is produced in every kind of cell in the organism when it's sufficiently stressed. That was before nitric oxide was known, but histamine turns on nitric oxide, so those are the two probably universal stress injury signals.
>
> **Caller:** On the last show, you had mentioned that tetracycline destroys harmful intestinal bacteria while preserving the good bacteria. Do we know that for sure? How does it selectively spare the "beneficial" bacteria? I've always heard there is a symbiotic relationship with certain intestinal bacteria that help to absorb certain nutrients. So, I'm assuming that would be considered a beneficial bacteria, if that is true...

### Source 7 — One Radio Network: Ray Peat with Patrick Timpone — October 18, 2021

Ray Peat · Interview · Oct 18, 2021

> **Ray Peat:** That's the basic idea. The mast cell isn't the only source of histamine, but it's a major source. and it's one that has been studied the most, and estrogen activates the mast cells to produce more estrogen, more histamine, and progesterone has the opposite effect, reducing histamine formation and release from the mast cells. And so for such things as the... bladder oversensitivity, you can pretty much just turn that off by increasing your thyroid and progesterone because of their effect on the estrogen.
>
> **Patrick Timpone:** And we want to get that TSH 0.5, right?
>
> **Ray Peat:** Around that, 0.2 or 0.3 or 0.4.
>
> **Patrick Timpone:** That low, that low. So now I'm going to do this little test I told you about. I've been taking the piggy thyroid, you know, for a couple months. And so if I get this guy and it says my test, my TSH is maybe one or two. It used to be three. Hopefully it will be down. I'm feeling great. Would I just increase the piggy and just keep it until I get to 0.5? Is that how you do it?
>
> **Ray Peat:** What about your temperature?
>
> **Patrick Timpone:** Temperature, when I wake up in the morning, like 91, 98.1, something like that?

### Source 8 — Iodine, Spider Veins, Oxalates, Fat Loss

Ray Peat · Interview · Aug 4, 2020 · https://www.youtube.com/watch?v=6uTJLfQUJOs

> **Jodelle Fitzwater:** A lot of people use a glutamine for the intestines, like for leaky gut. What do you think about that?
>
> **Ray Peat:** Any of the manufactured so-called pure chemicals are risky because in the manufacturing process, every stage it goes through, it can pick up some foreign material in trace amounts. And all it takes for an allergic that analysis would almost always be invisible. It would take an ultrafine analysis to guarantee the purity of something like glutamine or glutathione or any of the things sold as purity.
>
> **Jodelle Fitzwater:** All righty, Amanda asks, what can one do for histamine mast cell issues? I've had a spot on my foot for the longest time that will just not stop itching, usually when warm from wearing shoes. It used to blister and contain clear liquid that has stopped after a few months following Ray Peat's protocols. I'm about a year and a half in now. I was originally diagnosed with a form of eczema. I've also discovered I have issues with vibration using a percussion massager. So I was told it was due to high histamine levels. Is that true and what can I do?

### Source 9 — EastWest Healing: Estrogen vs Progesterone

Ray Peat · Interview · Mar 15, 2011

> ## Prolactin, Serotonin, and Osteoporosis
>
> **Josh Rubin:** Let's talk about prolactin and its correlation with osteoporosis, cortisol, and histamine.
>
> **Ray Peat:** Many people have been taught that mast cells are the only cells that produce histamine, but any cell seems to be able to produce it. There is a network in the brain that specializes in histamine signaling, and it seems to be a stress-organizing influence. Serotonin is the other general stress signaling system. When anything goes wrong, your brain activates the histamine and serotonin systems. Prolactin is one of the stress-reacting hormones. It tends to increase steadily with aging. The normal range for prolactin was lowered about 30 years ago because they saw that the top number was increased by women using birth control pills. There was an epidemic of prolactin-secreting pituitary tumors resulting from contraceptive estrogen exposure. Just a few years ago, the top number was raised again in some labs because the average person is now in a stressed, hyperprolactinemic condition. Don't feel reassured if your prolactin is "normal" by today's standards; everything is under stress when it's that high. It has been known for many years that prolactin is a major factor in bone loss. Estrogen increases prolactin, yet people are told that estrogen prevents osteoporosis. Men also develop osteoporosis progressively with age as estrogen creeps up, pushing prolactin up. When progesterone falls at menopause, that is when bone loss really picks up.

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