Histamine Sensitivity: How DAO Supplements Can Help

Who doesn't love a nice charcuterie board: those savory meats, creamy cheeses, a slice of fresh citrus fruit, all enjoyed with a glass of your favorite vino?

Well, your gut might not be a fan. For some people, occasional bloating, gas and stomach upset can accompany these tasty treats, and the culprit isn't always overeating (although that doesn't help).

Instead, the blame may belong to histamine sensitivity, a type of food intolerance that's due to the body's insufficiency at breaking down histamines in food. (Even though they are bite-sized, those cocktail party favorites are particularly high in histamine.)

Fortunately, you can supplement with diamine oxidase (DAO) to help alleviate this unpleasantness. Let's talk about how DAO supplements can help you make friends with your favorite foods again.

What is histamine?

Histamine is a signaling molecule produced by certain cells in your body, mainly the cells of your immune system. It plays a role in various functions, including cognition, digestion, healthy inflammatory responses and the dilation of blood vessels.

Histamine also is in a number of foods. When histamine binds to H2 receptors, it stimulates the stomach to secrete gastric acid, which is essential for digestion. But the more histamine there is, the more challenging it is for your body to break it down during digestion, and in some people, histamine in excess can cause discomfort.

You'll find the most histamine in certain plant- and animal-based foods (particularly fish), as well as aged and fermented foods, due to their bacterial content. People who are sensitive to dietary histamine often struggle with:

• Cured meats and sausages and deli meats
• Canned or preserved fish such as tuna and sardines
• Alcoholic beverages like beer and red wine
• Aged, smoked and blue cheeses
• Shellfish
• Fermented foods like sauerkraut and kefir
• Certain fruits and vegetables like tomato and eggplant

What is diamine oxidase (DAO)?

Similar to digestive enzymes that help break down the foods we eat into nutrients we can use for energy, the diamine oxidase (DAO) enzyme helps break down excess histamine in the body.

DAO is the main enzyme our bodies use to support the healthy breakdown of intestinal histamine, and it also helps promote gastrointestinal comfort after high-histamine meals.

When histamine is ingested from food or drinks, it makes its way through the digestive system to the small intestine, where DAO is mainly found. DAO breaks down the histamine, ultimately acting as a system of checks and balances to regulate the amount we get from our diet with what our bodies produce naturally. Healthy DAO activity like this not only supports digestive comfort, helping to alleviate occasional gas and upset stomach, but is also important for overall gut microbiome health.

People with diminished DAO activity may be sensitive to ingested histamine because their bodies cannot digest it fast enough, so the histamine can accumulate.

What are the benefits of DAO supplements?

Many people take digestive enzyme supplements to help them process a meal better, especially after hearty holiday feasts or all-you-can-eat buffets. These enzymes help break down the nutrients in food—mainly protein, fats and carbohydrates.

DAO supplements deliver digestive enzymes specific to the breakdown of histamine. For those with histamine sensitivity, supplementation can help your body process digestive histamine better, thus helping alleviate discomfort occasionally caused by certain foods. Many DAO supplements are derived from pig kidney, but DAO enzyme can also be sourced from some plants, including pea sprout (which is good news for vegetarians and vegans).

DAO supplements are still a relatively new area of research. Clinical trials have supported DAO supplementation for those with histamine sensitivity, but more research is needed.

In a randomized clinical trial, participants who took DAO supplements 20 minutes before a main meal for eight weeks reported relief from occasional gastrointestinal discomfort. Other clinical studies have also found DAO supplementation to effectively relieve occasional discomfort from foods. The supplement should label its histamine-degrading units (HDU), or how much histamine the enzyme can break down. Most clinical studies provided about 20,000 HDU before meals.

How do you know if you have histamine intolerance?

There's no single definitive test for histamine sensitivity. Usually food intolerances are identified through repeated exposures. One sign of insufficient histamine breakdown in your body is post-meal digestive discomforts, including:

• Occasional gas
• Occasional stomach upset
• Occasional bloating

Keep a food diary for a few weeks, noting what you eat and how you feel afterward. If you notice discomfort after eating certain foods, try eliminating them to see how you feel. Working with a nutritionist or healthcare provider can help you keep track of your diet and the effects of certain foods on your body.

Also keep in mind that several factors can affect DAO activity in your body:

• Alcohol.

  Alcohol and its metabolites can inhibit DAO activity.

• Stress.

  There is some limited evidence that stress might indirectly affect DAO activity.

• Hormone levels.

  There is also some limited evidence that hormonal fluctuations may affect DAO.

• Nutrition.

  DAO needs copper to carry out its enzymatic function, so not having enough copper can reduce DAO activity. Another mineral, magnesium, is required to make the DAO enzyme in the first place. There is also limited data that vitamin C may help support DAO activity.

• Gastrointestinal health.

  A healthy gut barrier and healthy small intestine are needed for proper DAO activity and expression.

How to time DAO supplements for best results

Most clinical trials of DAO supplements studied 20,000 HDU taken before heavy meals or before each meal, but always follow the directions on your supplement label. Many DAO supplements are recommended to take right before your meal so the DAO enzyme can make it to your digestive tract in time to play a role in breaking down the histamine that comes in with your food and minimize its absorption.

What about taking it after a meal? It's less likely that a DAO supplement would help in these cases. Digestive discomfort supplements that help with bloating are a better option after you've eaten.

References

• Alemany-Fornés M, et al. "Diamine oxidase deficiency implications for health, current management, and future directions in the treatment of histamine intolerance: A review." Biological Macromolecules. October 2025. https://www.sciencedirect.com/science/article/pii/S0141813025076871
• Holecek M. "Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement." Nutrients. March 2020. https://www.researchgate.net/publication/340097863_Histidine_in_Health_and_Disease_Metabolism_Physiological_Importance_and_Use_as_a_Supplement
• Izquierdo-Casas J, et al. "Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial." Clin Nutr. February 2019. https://pubmed.ncbi.nlm.nih.gov/29475774/
• Jackson K, et al. "Evidence for Dietary Management of Histamine Intolerance." Int J Mol Sci. September 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12470264/
• Jochum C. "Histamine Intolerance: Symptoms, Diagnosis, and Beyond." Nutrients. April 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC11054089/
• Okutan G, et al. "Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial." J Clin Med. October 2023. https://pubmed.ncbi.nlm.nih.gov/37892588/
• Sánchez-Pérez S, et al. "Intestinal Dysbiosis in Patients with Histamine Intolerance." Nutrients. April 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9102523/