A recent comprehensive review in the September 2025 issue of the International Journal of Molecular Sciences pulls together the available evidence: histamine intolerance (HIT) is a plausible clinical entity with emerging evidence, rooted in the body's inability to properly break down histamine from food. It's not an allergy, but it can mimic one.
Let's break histamine intolerance down and separate the hype from the evidence, based on? this and other research.
Disclosure: The 2025 review was funded by Bioiberica S.A.U., a company that produces diamine oxidase (DAO) supplements purported to break down histamine. It’s a thorough piece of work, but since the funder helped prepare the paper, its conclusions particularly on supplements should be viewed in this context. I included independent research to give a balanced picture of the science.
What Is Histamine Intolerance?
Histamine is a natural chemical produced by the body and found in many foods. It plays key roles in immune responses, digestion, and even neurotransmission. But like many things in biology, balance is everything. Normally, an enzyme called diamine oxidase (DAO) in the gut breaks down excess dietary histamine, preventing it from building up and causing chaos.
In HIT, that breakdown falters. Either the body doesn't produce enough DAO, or something blocks its activity.
The 2025 review synthesizes data showing this imbalance allows too much histamine to get into the systemic circulation, triggering widespread symptoms. Not immune-mediated like a true allergy, but more of a metabolic glitch.
Independent reviews, including a 2007 overview in The American Journal of Clinical Nutrition and a later update by researchers based in Spain, support this biochemical basis but emphasize that prevalence and diagnostic criteria remain poorly defined.
The Symptoms: Not Just a Bad Hangover
Symptoms of HIT can strike within minutes to hours after eating trigger foods, and vary widely, which is why the condition often gets misdiagnosed. Common ones include:
- Gut troubles: Bloating, diarrhea, abdominal pain, or constipation. Bloating tops the list in studies.
- Skin reactions: Flushing, itching, hives, or urticaria.
- Head and neurological issues: Headaches, migraines, dizziness, fatigue.
- Respiratory symptoms: Runny nose, congestion, or sneezing.
- Other oddities: Heart palpitations or low blood pressure in severe cases.
These aren't unique to HIT—they overlap with allergies, IBS, and even anxiety. But the key clue is that they often follow meals rich in histamine, like aged cheese, fermented veggies, wine, or leftovers that have sat too long.
Why Does It Happen? Genetics, Gut, and Lifestyle Culprits
The 2025 review highlights several factors that can tank DAO activity. Genetics play a role: some people inherit variants in the gene that reduce DAO production, and studies have linked specific SNPs (single-nucleotide polymorphisms) to lower enzyme levels. Gut damage can also contribute — conditions that injure the small intestinal lining, such as celiac disease, gastrointestinal infections, or inflammatory bowel disease, may reduce DAO production.
Microbiome mischief is another factor. An overgrowth of histamine-producing bacteria may overwhelm the system, though whether this is cause or effect remains uncertain. A 2022 pilot study found that a low-histamine diet altered the abundance of gut bacteria, including reductions in histamine-secreting species, though a direct causal link to symptom improvement was not established.
Medications and other cofactors can also interfere. The reflux medicine cimetidine can inhibit DAO. Alcohol is a double whammy—it both increases histamine release and blocks DAO activity. Hormonal fluctuations and overlapping intolerances (like lactose malabsorption) may further modulate sensitivity, helping explain why symptoms vary so much between individuals.
Diagnosis: No Magic Test, But a Practical Process
Unfortunately, there’s no gold-standard lab test for HIT. Blood DAO levels vary too much to be reliable, skin-prick tests can’t distinguish it from allergies, and stool histamine is skewed by gut bacteria that secrete histamine. Clinical studies confirm that serum DAO levels vary widely and correlate poorly with symptoms.
In the absence of a reliable laboratory test, an evidence-based approach—as outlined in the 2025 review—is to:
- Take a detailed history: track symptoms, timing, and triggers.
- Rule out mimics: allergies, IBS, celiac disease, skin conditions.
- Try a short low-histamine diet trial, then reintroduce foods gradually.
Management: Diet First
The cornerstone of management is dietary—an elimination–rechallenge plan that reduces histamine load. Several small studies report symptom reductions with a low-histamine diet, but placebo-controlled trials are scarce. One small randomized crossover trial found significant improvements in gastrointestinal and skin symptoms after three weeks on a low-histamine diet compared to a mixed diet in patients with HIT. However, DAO levels did not significantly change, and the sample size of just 18 subjects limits broader applicability.
A four-phase approach is recommended:
- Four-week strict restriction of foods high in histamine or which may trigger its release, to establish a baseline.
- One to two-week gradual reintroduction of small portions of these foods.
- Increase portions if tolerated.
- Maintain tolerance level and reassess periodically.
High-histamine foods include tomatoes, spinach, fermented vegetables, eggplant, avocado, cured meats, smoked fish, aged cheeses, wine, and beer. Yet histamine levels vary widely with fermentation, aging, handling, and storage conditions.
Older literature often lists “histamine liberators” (e.g., citrus, pineapple, kiwi, papaya, egg whites, milk, seafood, chocolate, nuts) and “DAO blockers” (e.g., bananas, strawberries, tea, coffee, energy drinks). However, most well-evidenced clinical guidelines find no robust, reproducible proof that specific foods consistently “liberate” histamine or block DAO in the body. These are speculative ideas, drawn only from small in-vitro studies or anecdotal reports.
The practical takeaway is to treat histamine food lists as short-term hypotheses for cautious, professionally guided elimination and reintroduction. Alcohol is a notable exception: it interferes with histamine metabolism and is consistently flagged as a potential aggravating factor.
Working with a registered dietitian is recommended to avoid nutrient gaps and to help identify signs of disordered eating or excessive food fear, which sometimes develop when dietary changes are self-directed.
Most importantly, a low-histamine diet isn’t forever—regularly re-testing your tolerance helps prevent unnecessary long-term restriction.
DAO Supplements: Potentially Helpful, Not a Panacea
If DAO is the weak link, why not replace it? That’s the idea behind oral DAO supplements, usually derived from pigs’ kidneys, which aim to break down dietary histamine in the gut before it is absorbed. The 2025 review summarizes several small studies suggesting these supplements—typically taken before meals and sometimes paired with vitamin C or catalase—may ease symptoms such as migraines, fatigue, urticaria, and digestive discomfort.
It’s worth a quick reminder that this review was funded by a DAO supplement manufacturer—and even then, the authors still describe the evidence as preliminary and inconsistent. Most studies are small (around 20–100 participants), short-term, and vary in diagnostic criteria, dosing, and formulations. Importantly, oral DAO works only within the gut; it doesn’t influence histamine produced elsewhere in the body.
If you try a DAO supplement, take it shortly before meals and treat it as an adjunct—not a substitute—for dietary management. It may be most useful when eating out or during supervised reintroduction of higher-histamine foods.
Other Options: Antihistamines for Flare-Ups
H1 and H2 blockers—the same meds used for heartburn—can help take the edge off a histamine flare. They don’t boost DAO activity (in fact, cimetidine, an older H2 blocker, is known to reduce it), so they’re best used for short-term relief rather than daily management.
Non-dietary factors often matter more than food lists. Stress, alcohol, medications, and hormonal shifts (especially premenstrual) can all heighten sensitivity to ingested histamine. These variables—not just diet—drive symptom flares and should be addressed as priority.
As for probiotics or “microbiome therapy”? There’s no firm evidence yet—interesting, yes, but not ready for prime time.
The Bottom Line: Evidence Is Evolving, But Actionable Now
Histamine intolerance isn’t a myth and independent research over the past few years supports the concept while underscoring that most findings are still preliminary and patchy.
Neither is histamine intolerance a blanket ban on your favorite foods; personalization is key, as is avoiding internet “cure-alls” and consulting a professional to sidestep pitfalls like nutrient deficiencies or food fears.
If you’re having repeated reactions to aged or fermented foods, start a symptom diary and talk with your doctor or a dietitian. Relief is possible, without turning your diet into a prison sentence.
