Histamine is a naturally occurring signaling molecule, or biogenic amine, that plays several roles in the body beyond its association with seasonal allergies. It functions as a neurotransmitter, modulating sleep-wake cycles and cognitive function, and is also involved in the digestive process by triggering stomach acid release. Histamine is stored in mast cells and released as part of the immune response to foreign pathogens or injury. Histamine intolerance is not a true allergy, but a condition where the body accumulates more histamine than it can efficiently process. This imbalance leads to a range of uncomfortable, allergy-like symptoms. Reducing the total histamine burden is the primary goal of intervention.
Why Histamine Levels Rise
The body employs two primary enzymes to manage histamine levels, each handling histamine in different locations. Diamine Oxidase (DAO) is the main enzyme responsible for metabolizing extracellular histamine, which includes the histamine ingested through food or produced by gut bacteria. DAO is predominantly produced in the intestinal lining, acting as a defense barrier against dietary histamine before it enters the bloodstream.
The other enzyme, Histamine N-methyltransferase (HNMT), is responsible for breaking down intracellular histamine, primarily in tissues like the liver, kidneys, and central nervous system. A deficiency in DAO activity is the most common cause of adverse reactions to dietary histamine, leading to its accumulation in the digestive tract and eventually the bloodstream.
External and internal factors can directly inhibit the function of the DAO enzyme, causing histamine levels to spike. Alcohol, particularly red wine, is a known inhibitor of DAO activity, as are certain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and some acid-blocking drugs. Gastrointestinal disorders and genetic variations can also impair the body’s ability to produce adequate amounts of DAO.
Immediate Dietary Intervention
A low-histamine diet provides the fastest way to reduce the body’s histamine load by eliminating the main external sources. High-histamine foods are typically those that are aged, fermented, or cured, as these processes involve microbial action that produces histamine from the amino acid histidine.
Foods to strictly avoid include:
- Aged cheeses
- Fermented foods like sauerkraut and yogurt
- Cured meats
- Alcohol
- Histamine liberators such as spinach, eggplant, tomato, avocado, and citrus fruits
The most critical element of this dietary intervention is food freshness, as histamine levels in meats and fish increase rapidly as they age, even under refrigeration. Prioritizing fresh, unprocessed, and quickly cooked foods helps maintain a low histamine intake. Freshly prepared meat, poultry, and fish that is flash-frozen or cooked shortly after purchase are generally well-tolerated. The goal is not a permanent, overly restrictive diet, but a temporary tool to bring the body’s histamine burden down to a manageable level.
Supporting Histamine Breakdown with Supplements
Supplemental diamine oxidase (DAO) enzymes offer a direct way to assist the breakdown of dietary histamine in the gut. These supplements are typically derived from porcine kidney extract and are taken immediately before meals to help process the histamine contained in the food before it can be absorbed. DAO supplementation acts as a temporary enzyme replacement therapy, directly addressing the processing deficit.
The body’s own histamine-processing enzymes require specific micronutrients to function optimally, known as cofactors. Vitamin B6, copper, and Vitamin C are essential cofactors for the DAO enzyme. Copper is a component of the DAO molecule itself, while Vitamin B6 is necessary for DAO activity.
Vitamin C also acts as an antioxidant and may assist in the degradation of histamine in the blood, while zinc further supports DAO function. Natural compounds like Quercetin and Bromelain can also be beneficial. Quercetin, a flavonoid found in many plants, helps stabilize mast cells, which reduces the release of the body’s endogenous histamine. Bromelain, an enzyme complex derived from pineapple, is often combined with Quercetin to enhance its effects as a natural mast cell stabilizer.
Long-Term Histamine Management Through Gut Health
While dietary changes and supplements provide immediate relief, long-term management requires addressing the health of the digestive tract, where the DAO enzyme is produced. DAO is synthesized by the cells lining the small intestine, meaning any damage to this mucosal barrier directly compromises the body’s ability to produce the enzyme. Conditions like inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or a “leaky gut” (increased intestinal permeability) all contribute to reduced DAO production.
Strategies for gut repair focus on reducing inflammation and restoring the integrity of the intestinal lining. Identifying and removing specific food sensitivities, such as gluten or dairy, can significantly lower gut inflammation. Nutrient deficiencies that impact mucosal repair, such as zinc and the amino acid L-glutamine, must also be addressed.
Managing the gut microbiome is another critical component, as certain bacteria strains produce histamine from the amino acid histidine, adding to the total body burden. Conversely, other strains, such as Bifidobacterium longum and Lactobacillus rhamnosus, have been shown to degrade histamine. A targeted approach is necessary, selecting specific probiotic strains that degrade histamine while avoiding those known to produce it.