Polish Society for Histamine Research
Popular science miscellany
Miscellaneous about histamine
Histamine is one of the most fascinating molecules in the human body. While most people associate it only with bothersome allergies and hay fever, it is actually a versatile messenger—regulating sleep, stimulating digestion, and even guarding our immune system. Discover the history of its discovery and learn why it is often called the body’s “molecular alarm.”
From Chemical Curiosity to Medical Breakthrough
The history of histamine began in a laboratory, not a clinic.
- 1907: German chemists Adolf Windaus and Walter Vogt first synthesized histamine chemically. At the time, no one suspected that this simple compound occurred naturally in living organisms.
- 1910: Sir Henry Dale and Patrick Laidlaw observed that histamine triggered reactions in animals that mimicked anaphylactic shock—a sudden drop in blood pressure and bronchial constriction. This discovery shifted the perception of histamine from a “curiosity” to a powerful biological agent.
- “Substance H”: For years, doctors knew that scratching the skin caused redness and swelling (known as the Lewis triple response). Sir Thomas Lewis proved that this was caused by “Substance H” released from the tissues—which turned out to be histamine.
How Does Histamine Work? The Four Keys to the Body
Histamine doesn’t act on its own; it must bind to specific “docking stations” (receptors) on the cell surface. We have four main types of these receptors, each responsible for different functions:
H1 Receptor
(Allergy & Alertness)
Found in blood vessels and the brain. It is responsible for itching, runny nose, and airway constriction. In the brain, histamine acts like “natural coffee,” keeping us awake (which is why older allergy medications that block H1 receptors caused drowsiness).
H2 Receptor
(Digestion)
Located primarily in the stomach. When histamine binds to it, the stomach begins producing the hydrochloric acid necessary for digestion.
H3 Receptor
(Balance)
Acts like a thermostat in the brain. It regulates the release of other neurotransmitters, influencing mood and concentration.
H4 Receptor
(Immunity)
The most recently discovered, found on immune cells (such as in bone marrow and the spleen), directing white blood cells to sites of inflammation.
FOOD AND HISTAMINE
All foods produced using lactic acid fermentation, such as yogurt, fermented foods, wine, beer, cheese, pickled fish, and dried sausages, contain significant concentrations of histamine. It is produced from the amino acid L-histidine by bacterial histidine decarboxylase. When the human digestive tract is functioning properly, diamine oxidase, present in the mucosa of the intestinal villi, effectively breaks down the amine and prevents adverse symptoms. No adverse symptoms have been observed with oral administration of even 500 mg of histamine. However, when the structure of the intestinal villi is damaged (celiac disease, Crohn’s disease, food allergies, intestinal ulcers, and others), excess histamine absorbed in the intestines enters the systemic circulation.
Histamine in Numbers: When Does It Become Dangerous?
In healthy conditions, histamine concentration in human plasma is very low (averaging about 0.7 ng/ml). The body possesses precise mechanisms to neutralize it. However, if levels rise, the body reacts in a cascading fashion:
| Plasma Concentration | Physiological Reaction |
| 1–2 ng/ml | Increased gastric acid secretion |
| 3–5 ng/ml | Increased heart rate (tachycardia) |
| 6–8 ng/ml | Significant drop in arterial blood pressure |
| 7–12 ng/ml | Bronchospasm (breathing difficulties) |
| approx. 100 ng/ml | Risk of cardiac arrest |
The DAO Barrier: Why Some People Can’t Handle Red Wine
The key to safely consuming histamine is the enzyme DAO (Diamine Oxidase), found in the intestines. It acts as a gatekeeper, breaking down histamine in food before it can enter the bloodstream.
When does the gatekeeper fail?
- Intestinal Diseases: Conditions like Celiac disease, Crohn’s disease, or ulcers damage the intestinal villi where the DAO enzyme is produced.
- Enzyme Blockers: Certain medications (e.g., Isoniazid) and toxins from fungi (e.g., the False Morel mushroom) can completely “deactivate” DAO. In such cases, even an ordinary meal can become toxic.
- Unfortunate Combinations: It is particularly risky to combine red wine with aged or pickled products (like marinated mushrooms) if the intestinal barrier is weakened.
Where is Histamine Found?
In food, histamine is primarily formed through fermentation and the aging process. The longer a product “matures,” the higher its histamine content may be.
| Product Group | Histamine Level (mg/kg) | Fun Fact |
| Cheeses (e.g., Emmental) | 0.1 – 2000 | Fresh cottage cheese has trace amounts; aged yellow cheeses are “histamine bombs.” |
| Red Wine | 0.1 – 14 | Contains significantly more histamine than white wine. |
| Fish (e.g., Smoked Mackerel) | 0.1 – 1788 | Non-fresh fish is the most common cause of histamine poisoning. |
| Cured Meats (e.g., Salami) | 0.1 – 279 | The meat fermentation process promotes the accumulation of amines. |
| Fresh Meat (Beef) | approx. 0.7 – 2 | The safest choice for those with histamine intolerance. |