Histamine is a substance found in many foods, such as meats, spinach, fermented foods, avocadoes, nuts, tomatoes and chocolate. An estimated 1-3% of the population cannot digest dietary histamine efficiently, often because of low intestinal diamine oxidase (DAO), an enzyme in the GI tract that normally breaks down histamine. These individuals often experience gastrointestinal discomfort, headache, skin sensitivity or flushing after consuming histamine-containing foods. Supplementation with DAO enhances DAO activity in the GI tract, promoting breakdown of dietary histamine and reducing gastrointestinal discomfort (occasional diarrhea, bloating and gas) associated with sensitivity to histamine-rich foods. DAO may also reduce skin symptoms associated with high intestinal histamine levels. In an open-label pilot study, individuals with low DAO levels (< 10 U/ml) who received DAO (10,000 HDU) up to 3 times per day reported significant improvements in gastrointestinal, respiratory and skin symptom scores after 4 weeks. Subjects reported significant improvement in gastrointestinal comfort, including occasional diarrhea, bloating and gas, headache, respiratory and skin discomfort. In a double-blind, placebo-controlled, crossover investigation of 22 patients, supplementation of 10,000 HDU DAO twice daily for 30 days improved dietary histamine-associated skin discomfort.