Diamine oxidase (DAO) is a critical enzyme in histamine metabolism. It is responsible for the oxidative deamination of histamine and other biogenic amines, producing imidazole acetaldehyde, ammonia, and hydrogen peroxide. DAO plays a pivotal role in mitigating histamine exposure—particularly from dietary sources—before it enters systemic circulation. While DAO is endogenously synthesized in the small intestine, kidneys, and placenta, its activity can be modulated significantly by diet, gut health, genetic factors, and cofactor availability. At Creative Enzymes, we provide a comprehensive guide on how to naturally support and enhance DAO levels and activity through targeted dietary strategies.

The Biological Significance of DAO

DAO belongs to the copper-containing amine oxidase (AOC) enzyme family and is encoded by the AOC1 gene. Its primary substrate is histamine, though it also acts on other polyamines such as putrescine and spermidine. Histamine is involved in multiple physiological processes—including gastric secretion, neurotransmission, and immune modulation—but when its degradation is compromised, symptoms resembling allergic responses may ensue.

Histamine intolerance arises when histamine intake or production exceeds the metabolic capacity of DAO (or histamine-N-methyltransferase), leading to adverse reactions. DAO deficiency may result from inherited polymorphisms, acquired factors such as gastrointestinal disease, or inhibition by certain medications.

Mechanisms to Enhance DAO via Diet

There are two primary dietary strategies to increase DAO availability:

• Include foods that contain DAO (exogenous sources).
• Consume nutrients that support endogenous DAO synthesis and activity.

Exogenous DAO-Rich Foods

Recent studies have identified several food sources containing measurable DAO activity:

• Raw legume sprouts: Pea shoots, lentil sprouts, and mung bean sprouts have been shown to exhibit significant DAO activity—up to 250 times that found in ungerminated seeds, when grown in darkness. Mung bean sprouts, for example, contain approximately 185 mU/mg protein.
  • Native plant origin diamine oxidase
  • Native pea sprouts diamine oxidase powder (food grade)
• Pork kidneys: Traditional sources of DAO also include pork kidneys, which remain available via butchers or specialty markets. They can provide a natural dietary supplement in cultures such as the United Kingdom.
  • Native porcine diamine oxidase
  • Native porcine diamine oxidase powder (food grade)
• Other legume sprouts and pulses: Alfalfa, broad bean, lentil, and common bean sprouts likewise exhibit endogenous DAO activity.
  • Alfalfa extract

Vegetarians or individuals seeking plant-based sources may prioritize legume and sprout consumption. Optimal DAO levels are achieved when sprouts are germinated in darkness for six to eight days, a process that may increase DAO enzymatic capacity by up to 250-fold.

Figure 1. Exogenous DAO-rich foods.

Nutrients Essential for Endogenous DAO

DAO is a metalloprotein that depends on several micronutrients as cofactors or structural elements. Ensuring adequate intake of these nutrients can optimize endogenous DAO function:

• Copper: DAO is copper-dependent. Copper serves as a central component of the enzyme's active site.
• Vitamin B6 (pyridoxal 5'-phosphate): Serves as a coenzyme in DAO-related pathways.
• Vitamin C: May enhance DAO function or reduce histamine load.
• Zinc, Magnesium, Phosphorus, Iron, Calcium, Vitamin B12: These micronutrients contribute either as cofactors or structural stabilizers for DAO.
• Omega-3 and oleic acid-rich fats: These may increase DAO release. For example, oleic acid from olive oil has been associated with up to a 500 % elevation in DAO secretion.

Dietary Patterns to Enhance DAO Activity

Incorporate Sprouts Intensively

Sprouted legumes—particularly from peas (Pisum sativum) and lentils—are among the richest natural sources of exogenous DAO. To maximize their enzyme activity:

• Germinate legume seeds in darkness for 6–8 days. Darkness encourages optimal sprouting and enzyme production.
• Add sprouts to salads, blend into smoothies, or lightly stir-fry—but avoid high-heat cooking methods, which rapidly degrade DAO enzymes.
• Store sprouts fresh and cool. Refrigeration helps preserve their enzymatic activity and slows histamine formation during storage.

Sprouts not only contribute natural DAO but also supply fiber and prebiotics that support gut health—a key component in regulating endogenous DAO activity.

Prioritize Clean, Nutrient-Dense Whole Foods

Boosting your body's own DAO production requires a steady supply of specific nutrients and foods that stimulate its secretion:

• Include organ meats (e.g., liver, kidney) in your diet several times a week. These are rich in vitamin B6, copper, and iron—essential cofactors for DAO function.
• Incorporate fatty fish (like salmon and sardines) and extra virgin olive oil regularly, both of which support anti-inflammatory pathways and enhance DAO secretion via intestinal health.
• Balance meals with nuts, seeds, legumes, and leafy greens to supply critical micronutrients, antioxidants, and fiber that promote both DAO expression and gut integrity.

A clean, unprocessed, nutrient-dense diet forms the foundation for supporting long-term DAO efficiency and reducing histamine-related symptoms.

Manage Histamine Load Simultaneously

Supporting DAO is only half the strategy—it's equally important to reduce histamine intake from dietary sources to prevent overloading the enzyme system:

• Avoid high-histamine foods, including aged cheeses, fermented products (e.g., sauerkraut, soy sauce), cured meats, alcohol, aged or smoked fish, and processed or leftover foods. These contribute to cumulative histamine burden.
• Prioritize freshness by consuming freshly prepared meals and storing leftovers for minimal time. Cooking and eating foods promptly help limit histamine buildup.
• Limit histamine-releasing foods, even if they are not high in histamine themselves. These include tomatoes, eggplant, chocolate, nuts, shellfish, and strawberries, which can trigger histamine release in sensitive individuals.

By simultaneously enhancing DAO activity and minimizing dietary histamine exposure, individuals with histamine intolerance or related symptoms may experience significant relief and improved quality of life.

Lifestyle and Supplementation Considerations

Gut Health is Paramount

Since DAO is primarily synthesized in intestinal enterocytes—the absorptive cells lining the small intestine—preserving the integrity of the gut lining is critical for optimal DAO production. A compromised gastrointestinal environment can drastically reduce DAO levels and contribute to histamine intolerance.

• Address underlying gastrointestinal conditions such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or small intestinal bacterial overgrowth (SIBO). These disorders can damage the intestinal lining and impair DAO production. Management should include individualized dietary strategies (e.g., low-FODMAP or anti-inflammatory diets) alongside appropriate medical treatment.
• Nourish the gut microbiome with a high-fiber diet rich in prebiotics, and consider probiotic supplementation, particularly with strains like Bifidobacterium, which are associated with improved mucosal health and histamine degradation.
• Incorporate gut-friendly fermented foods like kefir, yogurt, or small amounts of properly prepared sauerkraut—if tolerated—while avoiding those high in histamine.
• Reduce chronic inflammation by limiting processed foods, refined sugars, and alcohol. Chronic low-grade inflammation can impair enterocyte function, hinder nutrient absorption, and downregulate DAO synthesis.

Potential Benefits of DAO Supplementation

For individuals with low endogenous DAO levels or persistent symptoms despite dietary interventions, DAO supplementation may offer practical, short-term enzymatic support—particularly around meals.

• Oral DAO supplements can help break down dietary histamine before it crosses the intestinal barrier.
• Clinical observations and preliminary studies suggest that DAO supplements may help reduce symptoms such as migraines, gastrointestinal discomfort, skin rashes, and urticaria (hives). However, many studies are limited in size and quality, so outcomes can be variable.
• Regulatory note: DAO supplements are currently classified as dietary supplements and not regulated by the U.S. FDA as therapeutic agents. This means that product quality, potency, and efficacy can vary widely between brands.

Cofactor Supplementation

Micronutrient supplements can support DAO when diet alone is insufficient:

• Copper and zinc, when taken in appropriate balance, play a vital role in histamine metabolism. Zinc supports gut lining repair and immune modulation, while copper is directly involved in DAO enzymatic function.
• Magnesium contributes to overall metabolic function and may assist in regulating histamine release and degradation. When paired with zinc and copper, its effects may be synergistic.
• Vitamin B6 (pyridoxine) is a critical coenzyme in amino acid metabolism and has been associated with improved DAO activity.
• Vitamin B12 and vitamin C also support DAO production indirectly through immune and metabolic pathways. Vitamin C, in particular, has natural antihistamine properties and may help reduce histamine levels in circulation.

In summary, effective modulation of histamine metabolism involves more than just avoiding histamine-rich foods. By strategically incorporating DAO- and cofactor-rich foods into the diet, supporting gut health, and managing histamine intake, individuals may enhance their endogenous and exogenous DAO presence. This comprehensive nutritional approach can help individuals maintain histamine equilibrium, potentially reducing the prevalence and severity of intolerance symptoms.

While further research—particularly robust clinical trials—is required to fully quantify the impact of these dietary strategies, the existing body of scientific evidence provides a solid foundation for nutritionally informed support of DAO activity.

Creative Enzymes provides premium-grade diamine oxidase sourced from pea sprouts and porcine kidney. Food-grade options are also available to meet a wide range of research, nutritional, and industrial needs. Have questions or specific requirements? Contact our team today—we're here to help.