Locations of the four different types of histamine receptors throughout the body. Note how widespred they are, and note they are especially abundant in the nervous system.
Image from: Histamine: A Mediator of Intestinal Disorders - A Review (2022). Smolinska, S. et al. Metabolites.
Histamine intolerance/excess: symptoms, the connection with OCD and anxiety, and what you can do about it
Part 1: What is histamine, and common symptoms of histamine excess
Have you been experiencing any of the following?
Worsened OCD or anxiety after drinking alcohol (during a session OR the day after).
You can’t remember the last time you had a poo that wasn’t runny (very common symptom).
You’re constipated a lot (very common symptom).
Your abdomen is bloated, especially after eating (very common symptom).
You have seemingly random episodes of nausea, vomiting, and diarrhoea.
Reflux/heartburn.
Dreading your monthly period because OCD always gets much worse, and you just can’t sleep for a night or two (very common symptoms).
Sore breasts just before and maybe during your period.
Low mood for months even though you’re doing your best to look after yourself. And the lows get intense sometimes (especially before your period).
A chronically runny nose.
Heart palpitations.
Itchy skin.
Rosacea (when you never had it previously).
Headaches, migraines, or feeling dizzy (or all three). It can be especially bad just before your period.
Joint pain.
You've been diagnosed with ‘Irritable Bowel Syndrome’ (IBS) but given no real answers and eliminating certain foods or taking medications hasn’t helped.
Histamine intolerance/excess is a condition that affects multiple body systems. Each person will experience slightly different combinations of symptoms and symptom severity. The list above includes some of the most common symptoms, involving the nervous, cardiovascular, respiratory, reproductive, musculoskeletal and nervous systems, and skin.
So what is histamine?
Histamine itself is not bad. It’s produced by all humans and is an important signalling molecule in your body, constantly transmitting cellular information through your body. In the right amounts, it plays a key role in our functional health.
Some supportive roles of histamine in human health:
· makes stomach acid
· immune cell function (cytokines)
· inflammation (important in healing processes)
· contraction of smooth muscles (e.g., in the uterus, gastrointestinal tract)
· vasodilation
· neurotransmission, especially wakefulness, alertness, the sleep-wake cycle, and letting us know when we are too hot, dehydrated, etc.
The wide-ranging effects of histamine (both positive and negative) occur because so many different types of cells in your body can make and release histamine, and so many cells have receptors for histamine (see the image above). These receptors are known as H1, H2, H3, and H4.
H1 and H2 receptors in particular are widely distributed throughout the human body, in your neurons (nervous system cells), smooth muscle cells, liver cells (Hepatocytes), your heart, your intestines, and more.
Histamine only becomes problematic when we have too much of it.
If you are experiencing several of the symptoms listed above, and you have ruled out a food allergy (e.g., Coeliac disease), high/excess histamine is likely a factor. The next steps are to identify:
1) what is causing an excess of histamine, and
2) what is hampering the body’s ability to break down histamine?
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Part 2: Common causes of excess histamine
It is believed that an excess of histamine in the body is caused by inefficient histamine breakdown by specific enzymes. The diamine oxidase (DAO) enzyme and histamine-methyl-transferase (HNMT) enzyme are key for breaking down histamine, and will be compromised if:
· you have deficiencies of vitamin B6, vitamin C, magnesium, and zinc. All are necessary for DAO synthesis or limiting histamine release. Note: these are all VERY common deficiencies I have seen in clients with OCD.
· there's inflammation of or damage to your intestinal wall (as can occur with Coealiac disease) and dysbiosis of the gut (the intestinal lining is a key body tissue where DAO is secreted from).
· you have a history of endometriosis, with the associated inflammation and increased mast cell activity (mast cells release histamine).
· you have a genetic variant that affects DAO synthesis.
· you have a deficiency of vitamins B9, B12, and choline.
· you have compromised methylation owing to an MTHFR genetic variant (especially common in people of southern European ethnicity/ancestry, e.g., Spaniards, Italians, Hispanics).
Other factors in histamine excess include:
· a diet containing a lot of high-histamine foods and drinks (more on this below).
· high, chronic stress levels (so common with OCD…), because being in a state of chronic sympathetic activation (fight or flight) releases histamine.
· an infection of histamine-producing bacteria in the gut, such as Group A Streptococcus, Raoultella ornitholytica, H. Pylori, Klebisella, E. coli, Bacillus Coagulans, and many species of the Enterobacter genus and Enterococcus genus. (Note: this list does not include all known histamine-producing bacteria).
· taking medication known to have DAO-limiting effects, such as ibuprofen, aspirin, Cymbalta, Zoloft, Prozac, and Effexor. Antihistamine drugs such as Allegra, Zyrtec, and Benadryl will also impact DAO function, as will some antiarrhythmic drugs, H2 blockers, and immune modulator drugs.
But why do my symptoms get worse just before my period….?
Simply because many women have a too-high estrogen ratio (caused by stress and exposure to environmental estrogens, compromised liver detoxification, plus common deficiencies in nutrients needed to make progesterone, like zinc). Excess estrogen drives mast cell release, which leads to more histamine release, and histamine stimulates estrogen via H receptors. In other words, estrogen and histamine drive each other. In addition, estrogen downregulates the DAO enzyme.
And so it becomes a vicious cycle of excess estrogen and excess histamine.
The late luteal phase of our monthly cycle (the week or so just before we get our period) is when excess estrogen tends to affect us most. Hence, we feel the symptoms of excess histamine more at this time, too.
But why would high histamine make my OCD worse?
As you've been learning, histamine receptors are widely found throughout your body. There are thousands of them in your nervous system, which includes your brain.
We know from research that histamine acts as a neurotransmitter in the brain, and some of the effects of excess histamine on the brain include problems getting to sleep and inflammation. One 2022 study conducted in mice found that when histamine levels were higher, serotonin levels were lower, and that lowering histamine was levels was important to restoring serotonin levels. There is also research going all the way back to 1988 which found a link between histamine and the inhibition of serotonin in rat brains. These findings have been replicated in ongoing studies, and a 2021 study done on mouse brains found that when brain histamine is high, the SSRI escitalopram was less effective because its ability to increase serotonin didn't work as well.
While studies on rats and mice aren't considered as robust as studies on humans, the fact that numerous animal studies have found a possible link between HIGH histamine and LOW serotonin is significant.
So a combination of increased difficulty sleeping, neuroinflammation, and reductions in serotonin may all play a role in the relationship between high histamine and worsened symptoms of OCD.
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PART 3: A list of high-histamine foods and drinks
Anything aged, fermented, or vinegar-containing, such as:
· alcoholic drinks (especially wine and beer)
· black tea and green tea
· cheese, cured meats like bacon, ham, and salami, hot dogs
· yoghurt, kefir
· kombucha, sauerkraut
· pickles, olives, mayonnaise, vinegar, soy sauce
· dried fruits such as raisins, dates, apricots
· smoked fish
· walnuts, cashews, and peanuts
· spinach, tomatoes, and eggplant
· food that has been sitting in the fridge more than two days, canned and tinned foods.
Bananas, strawberries, pineapple, papaya, chocolate, cow’s milk, and many preservatives do not contain histamine, but they impact the action of DAO, so are sometimes listed as ‘high histamine foods’.
Low-histamine foods
· freshly cooked meat and poultry
· freshly caught fish
· rice, potatoes, quinoa
· eggs
· fresh vegetables other than tomatoes, spinach, and eggplant
· coconut, hemp, almond, oat and rice milk
· butter
· coconut oil
· leafy herbs such as parsley, mint, basil, coriander, chives, Thai basil, sage, rosemary.
· herbal teas
· almond butter
· freshly prepared, home-cooked foods.
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PART 4: So, what can you do to reduce excess histamine?
First steps
Two things will be absolutely vital for reducing the symptoms of histamine excess: reducing stress and treating any infection/dysbiosis in the gut.
If you have a history (more than two months) of digestive symptoms (bloating, diarrhoea, constipation, pain, excessive belching) which allergen elimination diets haven’t helped, I strongly recommend seeing a nutritionist or naturopath for professional guidance with rebuilding the microbiome, healing the intestinal lining, and eliminating any pathogens if needed.
Additionally:
· Start going to be by 9:30 as often as you can.
· Ensure adequate hydration (water) for regular bowel motions if constipation has been a factor.
· Take a break from alcohol for three months or more.
· Take a break from as many high-histamine foods as you can for two months (refer to the list above). Especially cheeses, salami, bacon, peanut butter, tomatoes, yoghurt, kefir, kombucha, sauerkraut, pickles, olives, mayonnaise, and vinegars.
· See your nutritionist to obtain professional-grade supplements to support DAO production and estrogen elimination, and for advice on how much to take, when, and for how long.
· Support your liver health.
· Enjoy more fresh veges and herbs. If you are in a cold climate, vegetable soups such as pumpkin, squash, and chicken and vegetable soup are good choices
· Keep meat frozen and thaw it only the day or day before you are going to eat it.
· Eat leftover food the next day, otherwise freeze it after it has been cooked and cooled.
· Daily movement: yoga, walking.
Second steps
Work with your naturopath or nutritionist to review any test results, your current symptom levels, and supplements. There are specific probiotics, fibres, herbs, and supplements that research shows can help reduce histamine, help clear estrogen from the body, rebalance the microbiome and crowd out pathogens, and support our overall gut and nervous system health.
Continue following a low-histamine diet. Once you are feeling better/many symptoms are gone, you can gradually re-introduce histamine foods (but not in excess).
Want more information or support? Find out more about booking your appointment, or get my ebook.
References
Histamine Intolerance—A Kind of Pseudoallergic Reaction - PMC (nih.gov)
DAO Deficiency and Histamine: The Unlikely Connection | MTHFR Support Australia
Histamine Producing Gut Bacteria (alisonvickery.com)
A tale of two transmitters: serotonin and histamine as in vivo biomarkers of chronic stress in mice | Journal of Neuroinflammation | Full Text (biomedcentral.com)
Histamine Disrupts Serotonin and May Impede How SSRIs Work | Psychology Today
Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex | Naunyn-Schmiedeberg's Archives of Pharmacology (springer.com)