Histamine intolerance is a hot topic at the moment within the holistic and functional medicine field. Research is still emerging, however with the current research at hand, we are starting to get a solid understanding of the exact mechanisms behind this interesting food intolerance, which is often misdiagnosed and underestimated due to its multifaceted symptom presentation.
Approximately 1% of the population has histamine intolerance and 80% of those patients are middle-aged. Most are also female due to a strong connection between estrogen levels and histamines.
Research is starting to show that a disrupted gut microbiome may be one of the main drivers behind histamine intolerance, which is no surprise due to what we already know about the role of the gut flora in food allergies and intolerances. This once again highlights the significant connection between the gut microbiome and our health.
What is histamine intolerance?
Histamines are naturally produced in the body by specialised cells called mast cells. They play important roles in immune function, brain function, sleep, skin health, libido, estrogen balance and digestive function. They also play important roles in mood and alertness, which is why anti-histamine medication causes drowsiness. Mast cells are located in high amounts within these various body systems, which makes them very widespread in the body.
Most people know about histamines due to their role in allergic reactions. The release of histamines in response to allergens such as pollen, is what causes symptoms like a runny nose, watering eyes, sneezing, throat and face swelling, itchy skin and hives. This is why antihistamines are prescribed for things like hay fever and other types of allergies. Histamine release in response to allergens that are harmless to the body such as pollen, is a result of an over reactive, hyper-sensitive immune system, which is usually due to genetics and a disrupted gut microbiome. A disrupted gut microbiome is driven by various diet, lifestyle and environmental factors. .
Mast cells on a daily basis produce histamine as part of normal physiological functions, which are mentioned above. Also, histamines are naturally occurring molecules that are contained within our foods. Moreover, some foods are not necessarily high in histamines, but when they are consumed, they can cause the release of histamines from mast cells.
High concentrations of histamine can be found in the foods products listed below. Some of these foods may not contain histamines, but once ingested, they increase the release of histamines from mast cells.
Protein: Eggs, seafood (shellfish and finfish – particularly smoked or canned seafood), Greek yoghurt, kefir yoghurt, bone broth, processed, cured and smoked meat/fish (e.g. bacon, meatballs, patties, sausages, salami etc)
Vegetables: Tomato, spinach, eggplant and microbially fermented food like pickled vegetables, kimchi, natto, tempeh, kombucha and sauerkraut.
Carbs: Citrus fruits like pineapple, orange, grapefruit, mandarin, lemon, lime, papaya, paw paw, kiwi, grapes, plums, passion fruit, berries (except blueberries/blackberries), yeast (i.e. gluten) products, dried fruits, beans, legumes, lentils, peas, soy milk, tofu (i.e. soy products), pumpkin and processed carbs, such as deep fried food, pizza, pasta/noodles, breads, desserts, baked goods, chips, chocolate, confectionary and lollies.
Fats: Dairy products like milk cream, sour cream, cheese and butter. And vegetable oils (e.g. canola, safflower, soybean and sunflower oil) used in takeout, cafe and restaurant food, as well as processed/packaged food.
Herbs and spices and flavours: Cinnamon, chili powder, cloves, anise, nutmeg, curry powder, cayenne, soy sauce, ketchup, mustard, vinegars, salad dressings, relishes, tomato-based sauces, lemon/lime juice, stocks, jams, condiments, curry pastes, as well as artificial flavours, preservatives, additives and colours (i.e. processed food).
Drinks: Herbal teas, milk, alcohol (especially beer, cider and wine), drinks with added sugar and fermented drinks like kombucha and kefir milk.
Most people can breakdown the histamines consumed via food and the ones produced naturally in the body. However, those with histamine intolerance can’t effectively break down histamines taken in via the diet and may have trouble breaking down histamines produced in the body. This leads to the accumulation of histamines in the blood, which can then manifest in the symptoms of histamine intolerance.
Essentially, histamine intolerance results from a disequilibrium of accumulated histamines in the blood due to increased intake of histamine high foods, combined with the decreased ability for histamine degradation. Because histamines are naturally produced in the body for physiological functions on a daily basis, when someone can’t effectively break down histamines ingested via their diet or that are produced in the body, it leads to excess histamines in the blood. Exacerbating this is the fact that inflammation in the body and excess estrogen can also cause the release of histamines from mast cells, which is why histamine intolerance is more common in females, especially those on the contraceptive pill and those with hormonal disruption issues that result from excess estrogens. Such as endometriosis, heavy periods, painful periods and fibroids. Interestingly, while estrogens increase histamine release, increased histamines can cause excess estrogen production from the ovaries, which can therefore be a driving factor behind estrogen dominant hormonal issues.
Histamines are inflammatory in nature, therefore an excessive accumulation of them in the blood can cause widespread inflammation in body tissues where mast cells are densely located (i.e. skin, gut, urinary tract, uterus, ovaries, immune system, nervous system, endocrine system).
Increased histamines in the blood also activate histamine receptors on mast cells to release more histamines. As mentioned above, mast cells are densely located in the skin, gut, uterus, ovaries, urinary tract, immune system, nervous system and endocrine system. Therefore, once mast cells are activated to release more histamines in these tissues, it causes inflammation in them.
Inflammation from high histamine levels in these tissues, as a result of over stimulation of histamine receptors, can manifest in a wide variety of symptoms relating to the organ systems mentioned that have high amounts of mast cells, as well as flaring up existing health issues relating to these body systems. These include:
- Hay fever symptoms like itchy eyes, watery eyes, runny nose, sneezing, blocked sinuses etc. People with hay fever tend to also have histamine intolerance, which is why decreasing histamines via the diet seems to improve reactions to pollens due to the decreased amounts of histamines in the blood.
- Hormonal imbalances in females like heavy periods, painful periods, irregular periods, and PMS (e.g. food cravings, mood disturbances – anxiety and depression, fluid retention, bloating, changes in bowel motions, breast tenderness, nausea, fatigue, acne, a flare in skin issues). These issues are driven by excess estrgoen and low progesterone. Histamines increase the production of estorgen and estrogen increases histamines, which is why histamine intolerance can manifest in hormonal issues.
- Fatigue, mood disturbances and mental health issues (e.g. anxiety and depression).
- Digestive issues like reflux, nausea, gas, bloating, constipation and diarrhea.
- Hives and exacerbation of existing skin issues like acne, dermatitis and eczema etc.
- Cognitive issues like brain fog.
- Chronic fatigue and fibromyalgia.
- Bladder symptoms like increased frequency and urgency.
- Decreased immune function and increased risk of infection.
- Flare up of symptoms relating to a specific health condition. Most chronic health conditions are driven by and exacerbated by inflammation. Excess histamines increase inflammation.
Note: Interestingly, pharmaceutical drugs that increase histamine release from mast cells or block histamine breakdown in the body often have side effects similar to what is mentioned above.
Histamine intolerance is hard to diagnose:
Histamine intolerance can be hard to diagnose because histamine intolerance is a dose dependent food intolerance, which means the more the amounts of histamine accumulate in the blood, the worse symptoms get. Or, a certain threshold needs to be reached that overwhelms the body’s ability to degrade histamines, therefore causing symptoms due to histamine excess.
For one person, only a small amount needs to accumulate in their blood to trigger symptoms, which results from increased intake, increased production and decreased breakdown of histamines. For someone else, it may need the consistent intake of high amounts of histamine containing food/s.
Everyone has a different sized “cup” in regard to the amount of histamines they can tolerate in the body, as well as different abilities to effectively break down ingested histamines. Some people have a small cup and very ineffective mechanisms of breaking down histamines, therefore it only takes a small amount of histamine ingestion and histamine accumulation to make the cup overflow and cause symptoms. While others have a larger cup and more effective mechanisms to break down histamines.
This is why a person with a large cup and somewhat effective histamine breakdown mechanisms, may consume a lot of histamine food/s in one day. Then at the end of the day, they eat a particular food high in histamines and it results in symptoms relating to histamine intolerance, therefore causing them to pinpoint this particular food as an issue for them. This is often without them realizing that it was all the other histamine foods preceding this particular food that contributed to their cup filling up over the day and then eventually overflowing.
Maybe if they consumed this particular food at the beginning of the day, it may not have triggered an allergic reaction because it wasn’t enough to overflow their cup. In saying that, some foods are very high in histamines and can cause an overflow of a person’s cup in one hit, even if they have a large cup, therefore leading to histamine intolerance symptoms.
People with smaller cups and less effective breakdown mechanisms are obviously more reactive to smaller amounts of ingested histamines, as these people will easily have a sharp increase in excess histamines after the ingestion of histamine foods.
As mentioned above, because everyone has different sized cups, different efficacies of breakdown mechanisms, as well as different thresholds for histamine amounts in the blood – diagnosing histamine intolerance can be quite a challenge.
All of these factors makes pinpointing a particular food culprit quite difficult and people often don’t recognise the commonalities behind all the foods they are reacting to. This is why this intolerance is often undiagnosed and can be mistaken for other allergies and intolerances such as foods high in FODMAPs and dair, which can also be high in histamines.
Also, because clinical symptoms and their provocation by certain foods and beverages appear similar in other diseases, such as food allergies and intolerance to sulphites or other biogenic amines (e.g. tyramine), this further makes histamine intolerance hard to diagnose.
High histamine foods are often very healthy foods for most people, which is why this intolerance can often be frustrating for the individual because they are eating foods that are supposed to be healthy for them, but they keep getting reactions that appear quite random and sporadic.
A tell tale sign of histamine intolerance is someone who is eating a good, wholefood diet and their health issues are not improving as they still feel reactive to various foods, which appear to be quite random. One day a particular food may set them off and other days it might not. If their diet is good, they may be reacting to certain wholefoods high in histamines.
Lastly, the diverse number of symptoms of histamine intolerance in various body systems makes histamine intolerance hard to diagnose as well.
What causes impaired breakdown of histamines leading to histamine accumulation?
Diamine oxidase (DAO) is the main enzyme required for the metabolism and breakdown of ingested histamine. In healthy people, dietary histamine can be rapidly detoxified by DAO, whereas those with low DAO activity are at risk of excess histamine accumulation in the blood, which over time (not always immediately) may result in numerous histamine intolerance symptoms and the mimicking of an allergic reaction. These are the people who develop histamine intolerance.
Research has shown that reducing histamine-rich foods in the diet dramatically reduces symptoms. However, as a functional medicine practitioner, I am always concerned about treating the underlying cause(s) of health issues. While symptomatic treatment is necessary, it is imperative to address the causes in order to achieve long-term health. This is especially true for histamine intolerance because foods high in histamine tend to be nutrient dense foods such as fish, seafood, various fermented foods and some varieties of fruits and vegetables. Therefore, removing them from the diet permanently may not be ideal for long-term health. This means that as a practitioner, one potential question I need to ask is, why are DAO enzymes not being produced in sufficient amounts? Looking to the gut might give some answers.
The gut microbiome and histamine intolerance
The fact that histamine intolerance is a food intolerance, it should come as no surprise that the gut microbiome has a large role to play in its pathogenesis.
DAO enzymes are synthesised and stored within the cells lining the small intestine walls and colon. Upon histamine ingestion, these enzymes work to metabolise histamines and therefore reduces the amount of histamines absorbed into the bloodstream. Decreased DAO production leads to increased histamine absorption, resulting in excess histamine accumulation. As mentioned above, this is exacerbated by increased histamine production from mast cells in the body due to normal physiological functions, as well as increased estrogen levels and increased inflammation – inflammation in the body is usually driven by poor diet and lifestyle habits and chronic health issues.
Decreased DAO production is usually a result of inflammation within the lining of the gut walls and this is likely driven by an overgrowth of “bad” bacteria in the gut lining, which release inflammatory molecules that increase inflammation in the digestive tract.
Within the gut there are billions of colonies of bacteria, both good bacteria and bad bacteria. The good keep the bad in check. It is all about balance in the gut.
Poor diet and lifestyle habits, alcohol, smoking, being born via a C-section, decreased breastfeeding as a child, a history of gastroenteritis (i.e. food poisoning), as well as the overuse of medications such as antibiotics, NSAIDs (e.g. ibuprofen), opioids, the oral contraceptive pill – estrogens in the pill increase histamine release and block DAO function and ant-acids for reflux, are all significant risk factors that increase the likelihood of bad bacteria overgrowing in the gut and overrunning the good bacteria.
Once this happens, the bad bacteria release inflammatory molecules that cause inflammation in the digestive system, thus affecting proper digestion and absorption of food, which through various mechanisms can cause digestive symptoms like gas, bloating, reflux and stool issues. Inflammatory molecules from the gut can also travel into the blood and cause inflammation elsewhere in the body, hence exacerbating other symptoms. It also leads to decreased DAO function as mentioned above.
Digestive disorders/diseases like Crohn’s disease, ulcerative colitis, celiac disease and irritable bowel syndrome (IBS) are characterised by inflammation in the digestive tract and are associated with overgrown bad bacteria in the gut, which is likely driving the inflammation associated with these conditions. This is why these people tend to commonly suffer from food intolerances like histamine intolerance and have been shown to have worsening of symptoms with histamine rich foods in some cases. The inflammation resulting from these conditions in the gut lining impairs DAO function.
Another enzyme worth mentioning in regard to histamine intolerance is HMNT. This enzyme is produced in the liver and breaks down histamines that are absorbed into the blood once they make their way through the gut lining. People who have compromised liver function or liver diseases, which tend to coincide with gut issues, may have decreased function of this enzyme. Poor functioning of this enzyme will impair the breakdown of histamines absorbed via the gut, as well as produced in the body.
While there is a genetic predisposition to histamine intolerance and a genetic predisposition to the malfunctioning of DAO and HMNT, these genetic predispositions are more likely to manifest in the backdrop of the risk factors for poor gut health.
Based on all of this, it seems quite clear that excessive production and intake of histamines, combined with decreased degradation of histamines from impaired DAO activity, is the likely driver behind histamine intolerance. And more specifically, the inflammation resulting from a disrupted gut microbiome may be an underlying driving factor behind histamine intolerance.
Lastly, some research suggests that there are some species of bacteria in our gut that once overgrown (e.g. E.coli) can release histamines into the gut, further exacerbating the issue. Many of these species are also found in fermented foods and dairy, which is why these foods can exacerbate the symptoms of histamine intolerant individuals. These strains can be found in probiotic supplements too, therefore caution must be taken when prescribing probiotics in those who are histamine intolerant. It is necessary to prescribe probiotics with species that degrade histamines, rather than contribute to their production.
Note: While some people may have a disrupted gut microbiome, their imbalance may not manifest in digestive issues.
What does this all mean?
In patients with histamine intolerance symptomatology that are triggered by histamine foods, and who have a negative diagnosis of allergy or other disorders, histamine intolerance should be considered as an underlying mechanism. Especially if the person is already eating a wholefood diet with lots of healthy foods that they think should be helping their health but seem to be hindering it instead.
Furthermore, if a person has got histamine intolerance symptoms or health issues that could be helped by a low histamine diet (e.g. gut, skin, hormone and allergy symptoms), but they are eating a diet high in processed food, the first goal should be to increase the intake of wholefoods, regardless of histamines. By doing this, it is likely their symptoms will improve. To then take it a step further, a low histamine diet can be introduced to improve their symptoms.
The good thing about a low histamine diet is that it is anti-inflammatory in nature. It is high in anti-inflammatory and antioxidant nutrients, it decreases the intake of pro-inflammatory foods and it helps people increase the nutrient density of a person’s diet due to increased wholefood intake. This is going to help most people with inflammatory health conditions, regardless of histamines or a histamine intolerance. Therefore, a low histamine diet can be used to decrease symptoms of chronic, inflammatory, health issues.
A low histamine diet also removes foods, which contain proteins, that in some people, especially people with a disrupted gut microbiome and therefore a disrupted immune system, can be pro-inflammatory. This is aside from their histamine content, such as gluten, dairy and soy.
Histamine levels can be measured in plasma or urine. Serum DAO levels can also be measured. Elevated histamine concentrations and reduced DAO levels are both classically found in histamine intolerance and can be used as diagnostic tools. However, the gold standard for diagnosing histamine intolerance is via a food elimination diet. If a person presents with potential symptoms linked to histamine intolerance and the removal of histamine containing foods improves their symptoms, it is likely that histamine intolerance may be an underlying cause.
Typical treatment for histamine intolerance obviously involves a low histamine diet and focussing on what can be eaten rather than what cannot. This will decrease symptoms by decreasing inflammation and excess histamines in the blood, as well as lowering the threshold of histamines in the blood. Supplementing with nutrients that help support DAO function, as well as using natural antihistamine herbs/nutrients that stabilise mast cells is effective too. Also, any drugs that decrease DAO activity should be avoided (e.g. NSAIDS and antibiotics).
Also, supplementing with probiotic strains that degrade histamines may be beneficial. These include bifidobacteria species (particularly Bifidobacterium infantis), L. plantarum, L. rhamnosus, L. salivarius and L. gasseri.
It is also important to address the underlying causes of histamine intolerance. Therefore, addressing imbalances of the gut flora is crucial. This can be done by adjusting diet and lifestyle risk factors that lead to bacterial overgrowth in the gut, as well as herbal and nutritional supplementation. Furthermore, improving liver function, estrogen balance and the inflammatory status of the body through diet, lifestyle and supplemental interventions will also be useful.
After addressing the underlying causes of histamine intolerance and ultimately improving DAO (as well as HMNT) activity, small amounts of histamine foods can be re-introduced in a scheduled, dose dependent way. Once this is done, it is important to monitor symptoms to see how much of certain food flares up symptoms.
It is likely that by going on a low histamine diet, improving gut health, improving liver function, balancing hormones and decreasing inflammation in the body will allow a person to be able to re-add foods in certain amounts they once reacted to.
Tolerance to once problematic foods should increase if the underlying causes of histamine excess are addressed and if they are eaten in the backdrop of a low histamine diet. This is due to a lowered threshold and less histamines in the person’s “cup.” A person should start with re-introducing foods they once craved, regularly enjoyed eating and foods that are good for their health.
It becomes up to the individual in the re-introduction phase to find out how much histamine food/s (one or combined amounts) can be added (and how regularly they can be eaten) without causing symptoms. By going on a strict low histamine diet and with symptoms clearing, the re-introduction period can give a person a clear picture as to what foods, what combinations of food and in what amounts they actually react to. Individual sensitivity varies tremendously.
If the information in this blog post resonated with you, call Oak Health today or book an appointment online.
For more information on Oak Health’s approach to using a low histamine diet as a therapeutic tool, check out the treatment page here.