Let’s Talk Nutrition With Nico Episode 1: Why Histamine Intolerance Remains Difficult to Diagnose

The first episode of “Let’s Talk Nutrition With Nico,” a collaborative video series between Lana Pine of The Educated Patient and Nicholas Saraceno of Nutritional Outlook, explored emerging research surrounding histamine intolerance (HIT), a condition estimated to affect between 1% and 3% of the global population. During the discussion, Saraceno highlighted a 2025 scientific review examining current evidence related to histamine intolerance, diamine oxidase (DAO) activity, gut health, and dietary management strategies.

He explained that histamine intolerance may occur when DAO—an enzyme responsible for breaking down histamine in the gut—does not function efficiently, potentially allowing histamine to accumulate and contribute to symptoms such as bloating, headaches, flushing, congestion, abdominal discomfort, fatigue, and skin irritation. Researchers cited in the review also explored the possible role of the gut microbiome, suggesting that individuals with HIT may harbor elevated levels of histamine-producing bacteria that could worsen inflammation and impair histamine metabolism.

A major focus of the conversation centered on the challenges surrounding diagnosis. According to Saraceno, there is currently no universally accepted diagnostic test or biomarker for histamine intolerance. While DAO blood testing is frequently discussed in clinical and consumer conversations, the review found that its reliability remains inconsistent. As a result, healthcare professionals often rely on symptom tracking, elimination diets, and food reintroduction protocols to identify potential triggers.

The episode also discussed observational research involving DAO supplementation. One 2023 study involving 82 participants reported symptom improvement after subjects consumed DAO supplements before meals for 28 days. However, Saraceno emphasized that much of the available evidence remains preliminary, with several studies observational in nature rather than large-scale randomized clinical trials. He also noted that some researchers involved in the review were affiliated with Bioiberica, a company that markets DAO-related ingredients.

Overall, the discussion framed histamine intolerance as a complex and evolving area of research involving interactions among gut health, enzyme activity, genetics, and dietary patterns rather than a condition solely managed through food avoidance.

A transcript of Pine’s and Saraceno’s conversation can be found below.

Lana Pine: I’m Lana Pine, senior editor of The Educated Patient, and welcome to our very first episode of “Let’s Talk Nutrition with Nico,” a collaborative video series featuring The Educated Patient and Nutritional Outlook. Having said that, I’m joined by Nico Saraceno, senior editor of NO. Thanks for being here, Nico!

Nicholas Saraceno: Of course Lana, super excited for this! This has been months in the works, so thank you for having me.

Pine: Our worlds intersect quite a bit. As you know, one of our goals with The Educated Patient is to help patients—people in general—feel more confident making health-based decisions.

Saraceno: The same goes for Nutritional Outlook, in the sense that we aim to inform finished product manufacturers of the latest happenings in the nutraceutical industry. But those manufacturers are also consumers.

Pine: Definitely. So what’s on your mind today?

Saraceno: Well, with this week being Food Allergy Awareness Week, I thought it’d be worth re-visiting an observational study that I recently came across.

Let me start out by saying that I am by no means an expert on any of these topics—such as MD, an RD, a nurse, a registered dietician, any of that— I'm just merely reporting the findings or the facts of what I came across. I wanted to focus on histamine intolerance (HIT), a condition estimated to affect 1–3% of the global population. Histamine is a chemical released by the immune system during an allergic reaction, causing symptoms like itching, swelling, runny nose, and hives.

So, a 2025 scientific review^1,2 from researchers examined the current evidence around HIT. The review explored how reduced activity of the enzyme diamine oxidase (DAO), which helps break down histamine in the gut, may allow histamine to accumulate and trigger symptoms like bloating, headaches, congestion, flushing, abdominal pain, and fatigue, so all the fun things that you probably don't want to be experiencing with HIT. It’s pretty mind-blowing stuff.

Pine: Oh no!

Saraceno: Researchers also pointed to the gut microbiome as a possible factor in histamine intolerance. Basically, people with HIT may have higher levels of bacteria that produce histamine, which could contribute to inflammation and make it harder for the body to break histamine down properly.

One of the biggest takeaways from the review was that histamine intolerance is still difficult to diagnose. There’s currently no universally accepted test or biomarker for it. Even DAO blood testing, which is commonly discussed, has shown inconsistent reliability. Because of that, healthcare providers often rely on symptoms, elimination diets, and food reintroduction to help identify potential triggers.

The review also looked at research on personalized low-histamine diets and DAO supplements. One observational study³ from 2023 involving 82 participants found that people reported significant symptom improvement after taking DAO supplements before meals for 28 days.

Pine: Did you come across any limitations?

Saraceno: I did actually. Much of the evidence is still early-stage, some studies were observational instead of large randomized clinical trials, and histamine intolerance itself is still debated in parts of the medical community because diagnostic standards aren’t consistent. Several researchers were also affiliated with Bioiberica, a company that markets DAO ingredients.

Overall, the review suggests that histamine intolerance may be more complicated than just avoiding certain foods. Gut health, genetics, enzyme activity, and overall diet may all play a role together.

Pine: Well, thank you so much for that break down! I know you’re busy working on future content for NO, so I’ll let you go, but thanks for taking the time today!

Saraceno: Of course, Lana! Looking forward to doing this again soon!

References

1. Jackson K, Busse W, Gálvez-Martín P, Terradillos A, Martínez-Puig D. Evidence for dietary management of histamine intolerance. Int J Mol Sci. 2025;26(18):9198

2. Bioiberica. Histamine intolerance: new review summarizes key insights dietary management. Accessed May 26, 2026. https://www.bioiberica.com/en/inspiring-insights/histamine-intolerance-new-review-summarizes-key-insights-dietary-management

3. O’Connor ME, Terradillos-Guillén A, Gálvez-Martín P, Martínez-Puig D. Observational study to assess the efficacy and safety of diaminooxidase (DAO) supplementation in patients with histamine intolerance (HIT). Clin Nutr ESPEN. 2023;58:741.