What do allergies, food sensitivities, eczema, and headaches have in common? They can all be linked to a histamine intolerance.
Histamine intolerance is an imbalance in the body that can cause a range of uncomfortable symptoms. But there are ways to treat and manage this condition by addressing gut health, and using diet as a healing strategy.
Let’s examine the details behind histamine intolerance, symptoms, and how to clear histamine from the body and find relief.
What is Histamine?
Histamine is a chemical released from immune cells in response to an allergen or foreign substance. Once released, histamine triggers an inflammatory immune response to counter the perceived threat.1
Since these immune cells are found throughout your body, a histamine response can happen anywhere, which is why the symptoms of histamine intolerance can vary widely, making diagnosis challenging.2
Usually, histamine is broken down and metabolized by the enzymes diamine oxidase (DAO) and histamine n-methyltransferase (HNMT). For people with histamine intolerance, the production of these enzymes, especially DAO, can be lower than expected, so histamine levels build up. 2
Why is DAO Important?
DAO is the primary histamine-degrading enzyme outside of cells and inside the digestive tract. It’s needed to remove histamine from food, allergens, and bacteria.3
You need a healthy gut to produce enough DAO. Otherwise, histamine can build up in the body and cause problems. Certain foods and medications can also block the action of DAO.4
What is Histamine Intolerance?
Most people are familiar with lactose intolerance, where you are intolerant to dairy because you’re missing the enzyme (lactase) needed to digest lactose, the primary sugar in milk products.5
Histamine intolerance is slightly different from lactose intolerance because you aren’t actually intolerant to histamine. Instead, you either produce too much histamine or the body can’t break it down correctly. The build-up of histamine is what causes symptoms.2
Women are more likely to have histamine intolerance (possibly related to estrogen influencing the breakdown of histamine). It’s also closely related to other digestive disorders like irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease.6 3
Histamine Intolerance Symptoms
Since mast cells can travel throughout the body, histamine intolerance symptoms can manifest in many different ways (making diagnosis challenging), including: 3
- Headaches, including migraines.
- Rashes, hives, and eczema.
- Muscle and joint pain.
- Heart arrhythmias, palpitations, or racing.
- Asthma, wheezing, and coughing.
- Congestion and runny nose.
- Constipation, diarrhea, bloating, gas.
- Abdominal pain.
- Acid reflux.
- Menstrual cycle irregularities.
- Low blood pressure.
- Skin flushing.
While histamine intolerance can look like an allergic reaction, it’s important to note that it’s different because of the immune cells involved. Allergic reactions involve antigens, the body’s recognition of an offender, like pollen, dust, or pet dander. Histamine intolerance is due to excess histamine and the inability to break it down. 2
Also, unlike an allergic reaction which usually happens within minutes after contact, histamine intolerance symptoms can take hours to appear.
Think of the build-up of histamine in your body like water filling a bucket. To start, a little water (or histamine) isn’t a problem, but as the bucket fills up, the water will eventually spill over and cause symptoms.
What Causes a Histamine Intolerance?
The primary cause of histamine intolerance is the build-up of histamine related to low DAO or HNMT. But why does this happen?
Some reasons include: 3 2
- Medication use (including NSAIDS like ibuprofen).
- Alcohol intake (alcohol is high in histamines).
- Mast cell dysfunction.
- Higher than normal histamine production related to allergies.
- Genetics: Some people may naturally make less DAO or HMNT.7
But a big reason for histamine intolerance may be related to the health of your gut.
Gut Health and Histamine Intolerance
As you learned above, multiple gut-related health conditions are associated with higher than normal histamine and lower DAO levels, including Crohn’s disease, ulcerative colitis, small intestinal bacterial overgrowth (SIBO), celiac, and IBS.8 9 10
Histamine receptors, the sites on the cell where histamine attaches and causes an effect, are found throughout your gut. Some research suggests that people with gut-related health conditions have more receptors than people without.11
Dysbiosis, the imbalance of bacteria in the gut, may also contribute to histamine intolerance. Scientists have found that certain types of bacteria make more histamine while others may help degrade it. SIBO, where bacteria overgrow in the small intestine, can add to the histamine-producing bacterial load while also damaging the gut lining.12 13
When the gut lining is inflamed or damaged, it can cause intestinal permeability (often called leaky gut). Intestinal permeability means the cells of the gut lining don’t seal together as tightly, allowing larger molecules like food particles through that can activate an immune response. If the gut lining is damaged, less DAO may also be produced and stored. 3 14
How is Histamine Intolerance Diagnosed?
Histamine intolerance has only started to be more accepted as a diagnosis in Western medicine, so it’s essential to find a health provider who is familiar with the condition. It’s partially a diagnosis of elimination, meaning it’s important to rule out other possible causes for symptoms, especially allergic reactions.
An allergist can provide tests to rule out an allergic reaction or mast cell disorders. A full GI work-up is also important and can help rule out other conditions like IBS, IBD, SIBO, and celiac.
Measuring DAO levels is possible, but not all practitioners offer this test. DAO levels could indicate an increased risk of histamine intolerance, but it isn’t necessary to diagnose the condition.15
The best way to confirm if you have histamine intolerance is through an elimination diet (as listed below) for at least three to four weeks. An elimination diet means you remove all foods high in histamine and other potential triggers to see if you get any relief. If symptoms improve while following the diet and return when eating high-histamine foods, then you likely have a histamine intolerance.
How is Histamine Intolerance Treated?
If gut issues are to blame for your histamine intolerance, it’s essential to address the root cause. Supporting symptoms through diet or supplements can help you feel better, but will only be a bandaid without working on restoring balance in the gut. In many cases, once the gut condition is addressed, histamine intolerance is no longer a problem.
You can use lifestyle to help calm the body and reduce symptoms while supporting your gut health. Diet is the primary treatment for histamine intolerance. Avoiding foods that are either high in histamine, trigger the body to release more histamine or block DAO are all helpful.
One study found that children with histamine intolerance symptoms reduced symptoms by more than 80% (and in some cases 100%) by following a low-histamine diet.16
Low histamine diets have also been shown to help increase DAO. They also may shift the composition of gut bacteria by reducing those that produce histamine and increasing the number of beneficial microorganisms.17 12
In some cases, your healthcare practitioner may also try supplements or occasionally medications to reduce symptoms, but addressing diet is a priority.
Diet for Histamine Intolerance
A diet for histamine intolerance may feel overwhelming at first. There are also several versions of high-histamine foods lists available that differ slightly. The key is consistency, so working with a dietitian is incredibly helpful here. Sometimes it can feel like trial and error to find what works best for you.
If you have many diet changes to make, starting with a foundational anti-inflammatory diet that includes the following can be a good place to start:
- Healthy fats.
- Lean protein.
- Fresh produce.
- Fiber-rich whole grains (if your digestion allows).
- Minimally processed or sugary foods.
Sometimes these changes can lead to improvement on their own. If not, you can take it a step further and follow the low-histamine diet. A low-histamine diet should be strictly followed for three to four weeks before foods are reintroduced and tested.16
If it feels restrictive, it’s because it is! But the goal is never to remain on such a challenging diet long-term but to help minimize histamine so you can find out what foods are a problem for you (or until your gut inflammation is improved).
Working with a dietitian as you move through the elimination and reintroduction phase can help you feel more confident and supported.
Foods on a Low Histamine Diet
Food should be as fresh as possible because histamine levels increase as food ages. Leftovers should be frozen immediately. If you get meat or poultry from the store, it should be as fresh as possible (ideally, you know your butcher and ask them).
Alcohol should also be avoided because it’s aged (high in histamine) and can impact DAO activity. Plus, alcohol can contribute to gut dysbiosis.18
You can include these foods on a low histamine diet:
- Fresh meat, poultry, and fish.
- Dairy substitutes.
- Fresh vegetables and fruit (aside from those listed below).
- Gluten-free grains.
- Olive oil.
Foods High in Histamine
Foods high in histamine include those that are fermented or aged. Histamine also occurs naturally in some foods: 16 19
- Aged cheese.
- Aged or smoked meat like salami or sausages.
- Smoked, salted, or canned fish.
- Soy sauce.
Foods That Promote Histamine Release
Some foods don’t contain high amounts of histamine, but they may cause more histamine release. There isn’t a lot of research on whether these foods are a problem, so a dietitian could help you determine if removing them is a good idea for you.20
These foods include:
- Citrus fruits.
- Cow’s milk.
- Egg white (raw only).
Supplements for Histamine Intolerance
Supplements to support histamine intolerance are highly individualized and should be discussed and recommended by a healthcare practitioner who understands gut health and histamine intolerance.
Supplements for histamine intolerance that are supported in research include:
- Probiotics. Probiotic supplements are live microorganisms to add to the beneficial bacteria and restore balance in the gut. Studies show that certain probiotics may help lower histamine levels in the gut.21
Some argue that taking probiotics with histamine intolerance could worsen symptoms. There are two explanations for this. One is that someone may be taking the wrong strain of probiotics. The word “probiotics” is often used as a blanket term, but strain matters. So, taking a probiotic that includes bacteria that increase histamine production can worsen symptoms.
The other explanation is that if someone has SIBO, probiotics may also add to the bacterial load in the gut and increase symptoms. Before you start taking a probiotic, check with your dietitian or practitioner.
- DAO Supplements. Taking supplemental DAO could help address the root cause of histamine intolerance if it stems from a low production in the gut. It can be taken with meals to help limit the histamine effects on the body.
More studies are needed on DAO supplements, but the results are promising. Taking a DAO supplement could help degrade histamine and improve symptoms.22 23
- Vitamin C. Supplemental vitamin C could help degrade histamine by increasing the production of DAO. If possible, you want to find a source that isn’t derived from citrus. Since it’s usually recommended in high doses, you’ll want to work with your healthcare practitioner to determine the right amount for you.24
- Quercetin. A natural antihistamine and anti-inflammatory, quercetin is a polyphenol (a chemical found in food with health benefits) found in foods like apples and grapes and as a supplement. One study found that quercetin. One study found that quercetin effectively blocked histamine release from mast cells. 25 26
Other Support for Histamine Intolerance
Other lifestyle factors like addressing stress and any sleep disruptions are also important. Both affect the health of your gut.
Studies show that stress and lack of sleep adversely affect gut bacteria, which could contribute to dysbiosis, affecting histamine intolerance.27 28
A Dietitian Can Help Guide You Through the Healing Process
While helpful, it’s completely understandable if all this information feels overwhelming. Working with a dietitian can help you make sense of the available research and tailor a plan that works for your lifestyle—and Nourish can make it easy to find someone who is the right fit for you.
It’s so important to remember that the restrictive phase of a low-histamine diet should not be a long-term solution. A dietitian who understands gut health and histamine intolerance is essential if you have histamine intolerance. Histamine intolerance is individualized, but you can feel good again.
Click here to learn more about Nourish, and book an appointment today.
- Patel, R. H., & Mohiuddin, S. S. (2022). Biochemistry, Histamine. In StatPearls [Internet]. StatPearls Publishing.
- Zhao Y, Zhang X, Jin H, Chen L, Ji J, Zhang Z. Histamine Intolerance-A Kind of Pseudoallergic Reaction. Biomolecules. 2022;12(3):454. Published 2022 Mar 15.
- Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185-1196
- Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021;13(4):1262. Published 2021 Apr 12.
- Di Costanzo M, Berni Canani R. Lactose Intolerance: Common Misunderstandings. Ann Nutr Metab. 2018;73 Suppl 4:30-37.
- Zaitsu M, Narita S, Lambert KC, et al. Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx. Mol Immunol. 2007;44(8):1977-1985.
- Maintz L, Yu CF, Rodríguez E, et al. Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergy. 2011;66(7):893-902.
- Schmidt WU, Sattler J, Hesterberg R, et al. Human intestinal diamine oxidase (DAO) activity in Crohn's disease: a new marker for disease assessment?. Agents Actions. 1990;30(1-2):267-270.
- Raithel M, Matek M, Baenkler HW, Jorde W, Hahn EG. Mucosal histamine content and histamine secretion in Crohn's disease, ulcerative colitis and allergic enteropathy. Int Arch Allergy Immunol. 1995;108(2):127-133.
- Raithel M, Küfner M, Ulrich P, Hahn EG. The involvement of the histamine degradation pathway by diamine oxidase in manifest gastrointestinal allergies. Inflamm Res. 1999;48 Suppl 1:S75-S76.
- Sander LE, Lorentz A, Sellge G, et al. Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract. Gut. 2006;55(4):498-504.
- Sánchez-Pérez S, Comas-Basté O, Duelo A, et al. The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study. Front Nutr. 2022;9:1018463. Published 2022 Oct 21
- Park JH, Park DI, Kim HJ, et al. The Relationship between Small-Intestinal Bacterial Overgrowth and Intestinal Permeability in Patients with Irritable Bowel Syndrome. Gut Liver. 2009;3(3):174-179.
- Schink M, Konturek PC, Tietz E, et al. Microbial patterns in patients with histamine intolerance. J Physiol Pharmacol. 2018;69(4):10.26402/jpp.2018.4.09.
- Enko D, Meinitzer A, Mangge H, et al. Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption. Can J Gastroenterol Hepatol. 2016;2016:4893501.
- Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020;10(8):1181. Published 2020 Aug 14.
- Lackner S, Malcher V, Enko D, Mangge H, Holasek SJ, Schnedl WJ. Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance. Eur J Clin Nutr. 2019;73(1):102-104.
- Qamar N, Castano D, Patt C, Chu T, Cottrell J, Chang SL. Meta-analysis of alcohol induced gut dysbiosis and the resulting behavioral impact. Behav Brain Res. 2019;376:112196.
- Hrubisko M, Danis R, Huorka M, Wawruch M. Histamine Intolerance-The More We Know the Less We Know. A Review. Nutrients. 2021;13(7):2228. Published 2021 Jun 29.
- Vlieg-Boerstra BJ, van der Heide S, Oude Elberink JN, Kluin-Nelemans JC, Dubois AE. Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods: what is the evidence?. Neth J Med. 2005;63(7):244-249.
- Toh ZQ, Anzela A, Tang ML, Licciardi PV. Probiotic therapy as a novel approach for allergic disease. Front Pharmacol. 2012;3:171. Published 2012 Sep 21.
- Izquierdo-Casas J, Comas-Basté O, Latorre-Moratalla ML, et al. Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial. Clin Nutr. 2019;38(1):152-158.
- Kettner L, Seitl I, Fischer L. Toward Oral Supplementation of Diamine Oxidase for the Treatment of Histamine Intolerance. Nutrients. 2022;14(13):2621. Published 2022 Jun 24.
- Hagel AF, Layritz CM, Hagel WH, et al. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(9):789-793.
- Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and Its Anti-Allergic Immune Response. Molecules. 2016;21(5):623. Published 2016 May 12.
- Weng Z, Zhang B, Asadi S, et al. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 2012;7(3):e33805.
- Smith RP, Easson C, Lyle SM, et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One. 2019;14(10):e0222394. Published 2019 Oct 7.
- Geng S, Yang L, Cheng F, et al. Gut Microbiota Are Associated With Psychological Stress-Induced Defections in Intestinal and Blood-Brain Barriers. Front Microbiol. 2020;10:3067. Published 2020 Jan 15.
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