Tyramine Intolerance: Symptoms, High-Tyramine Foods, and Genetics

Key takeaways:

Tyramine is a naturally occurring biogenic amine that can cause blood vessels to constrict and act as a norepinephrine mimetic.
Excess tyramine can result in serious symptoms, such as heart palpitations, spiking blood pressure, stroke-like symptoms, nausea, gastrointestinal issues, migraines, cluster headaches, and brain fog.
Genetic variants in key enzymes (MAOA, FMO3, CYP2D6, and DAO) impact how well you break down and eliminate tyramine.
Medications, especially MAO-A inhibitors, can also significantly impact tyramine metabolism.

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What is tyramine intolerance? Symptoms, foods, and breaking it down

Tyramine intolerance is a sensitivity where eating foods high in tyramine (like aged cheese, cured meats, or leftovers) triggers symptoms such as severe migraines, blood pressure spikes, or gut problems because your body cannot break tyramine down efficiently.

Tyramine is a biogenic amine that is derived from the amino acid tyrosine when it is broken down by bacteria. Higher tyramine levels cause the release of norepinephrine in the body, which then increases blood pressure. High tyramine content is often found in aged, fermented, or slightly spoiled foods.

Genetic variants in the genes related to tyramine metabolism cause a large inter-individual variability in the response to tyramine.[ref]

High tyramine levels in meals can trigger a hypertensive crisis, commonly known as the cheese effect from tyramine. This is usually associated with taking a drug type called an MAO-A inhibitor (MAOI), a class of drugs that includes phenelzine, tranylcypromine, and isocarboxazid. People on an MAOI are cautioned by their doctor about the dietary interactions, such as with aged cheeses. The hypertensive crisis is caused by too much tyramine, causing a sudden blood pressure increase and leading to other symptoms.

In addition to medication interactions with MAOIs, genetic variants play a role in how well the body handles tyramine. I’ll start with some background on tyramine and then explain the genetic variants that can decrease your ability to metabolize and eliminate tyramine.

What is tyramine, and why does it cause symptoms?

Tyramine is a biogenic amine, which refers to its chemical structure with nitrogen at its base. Other biogenic amines include histamine, spermidine, dopamine, serotonin, epinephrine, and norepinephrine, which are all amines that we create naturally. Structurally, tyramine is a monoamine, similar to norepinephrine, dopamine, and serotonin.

It is naturally found at trace levels in the human body. Tyramine, even in low amounts, causes the release of catecholamine neurotransmitters. It can cross the blood-brain barrier and act as a neuromodulator in the brain. It can also take the place of norepinephrine, binding to the receptors that cause blood vessel constriction.[ref][ref]

Bacteria convert the amino acid tyrosine into tyramine, and fermented foods, aged cheeses, and foods close to spoiling can have very high amounts of tyrosine. This is where the term ‘cheese effect‘ comes into play, because researchers first discovered the hypertensive effects of tyrosine when people on MAOI drugs ate aged cheeses. [ref]

In addition, certain gut microbes can also produce tyramine, adding to the body’s overall tyramine levels. Tyramine is absorbed in the intestines and transported by the OCT1 transporter.

How does the body get rid of tyramine?

In the intestines, tyramine is absorbed from foods and from gut microbial production. From there, it enters the circulation and is then broken down primarily in the liver. Tyramine is mainly broken down (metabolized) in the body using the MAO-A (monoamine oxidase) enzyme, but three other enzymes, CYP2D6, FMO3, and DAO, can also act on tyramine.

Primary routes of tyramine metabolism. Screenshot from https://pmc.ncbi.nlm.nih.gov/articles/PMC6831736/

Enzyme	Role
MAO-A	Primary enzyme, breaks down neurotransmitters; inhibited by MAOIs, increasing risk
FMO3	Supports tyramine breakdown
CYP2D6	Liver enzyme, detoxifies various compounds, including tyramine
DAO	Intestinal enzyme, breaks down histamine in the intestines along with other biogenic amines (including tyramine)

The MAO-A enzyme is the primary way the body breaks down tyramine. It also metabolizes (breaks down) several neurotransmitters, including dopamine. Thus, inhibiting MAO-A is one way to increase dopamine levels. Drugs that act as MAO-A inhibitors (MAOIs) can be used as antidepressants, although they usually aren’t the first drug choice due to the interactions with tyramine in foods. In addition to drug interactions, genetic variants in the MAOA gene affect the metabolism of tyramine and the blood pressure response.[ref]

CYP2D6 is a detoxification enzyme produced primarily in the liver and in the brain. It breaks down toxins, medications, and some substances produced in the body, such as serotonin. In tyramine metabolism, the CYP2D6 enzyme acts as a catalyst to convert tyramine to dopamine.[ref]

FMO3 (flavin-containing monooxygenase 3) is another enzyme produced in the liver that can metabolize tyramine. Specifically, FMO3 oxidizes tyramine, converting it into trans-oxime.[ref]

The DAO (diamine oxidase) enzyme is responsible primarily for breaking down histamine in foods. Recent studies show that it can also be a backup route for metabolizing other biogenic amines, including tyramine.[ref] Genetic variants in the AOC1 gene, which encodes the DAO enzyme, are also found in histamine intolerance. Some of the symptoms of histamine intolerance, such as gastrointestinal issues and headaches, overlap with tyramine intolerance, making it difficult to distinguish the two conditions.

Tyramine reactions:

Tyramine is similar to norepinephrine in structure, and it can activate norepinephrine receptors at high levels.

Tyramine intolerance symptoms include:

migraines
BP spikes
gastrointestinal issues
brain fog
heart palpitations

Let’s take a look at some of these effects in detail:

Tyramine causes migraines or cluster headaches:
Research shows that for people susceptible to migraines, a list of foods high in tyramine often corresponds to their list of ‘triggers’. Many people with either cluster headaches or migraines don’t break down tyramine well.[ref]

Why headaches from tyramine? Researchers think that vasoconstriction triggered by high tyramine levels initiates the migraine.[ref][ref]

Related article: Migraines, genetic causes

Blood pressure spike:
If you get too much tyramine due to eating foods high in tyramine and not breaking down the tyramine (e.g., when taking an MAO-A inhibitor), it can throw your body into a hypertensive crisis, raising systolic blood pressure by 30 mmHg or more.

This is called the ‘tyramine pressor response’. Tyramine takes the place of other neurotransmitters, triggering the body to release a bunch of norepinephrine, constricting blood vessels, and raising blood pressure. Tyramine can also take the place of norepinephrine in activating receptors.[ref]

You may wonder why everyone doesn’t have a stroke or heart attack after eating a salami and aged cheese sandwich on sourdough bread. There are a couple of reasons for this:

First, most people break down tyramine fairly well. There are three different enzyme pathways to take care of it.
Second, repeated exposure to tyramine will decrease the tyramine pressor response. It’s the change from typically not eating foods high in tyramine to suddenly chowing down on them that can cause a response. For instance, eating a healthy diet full of fresh foods — and then hitting the holiday buffet and having salami, cheese, and olives, chased with a glass of red wine.

Gut activation:
In addition to blood vessel constriction, when tyramine levels are high, it can activate the ADRA2A (alpha-2A adrenergic receptor), which is a norepinephrine receptor that regulates insulin secretion, anxiety, sympathetic neurons, and also neurons in the gut. In the intestines, certain gut bacteria can produce tyramine, and this can activate ADRA2A. In an animal model of IBD (Crohn’s, ulcerative colitis), it was recently shown that this tyramine –> ADRA2A activation pathway suppresses the intestinal stem cells that can repair and maintain the gut barrier.[ref]

Related article: Inflammatory Bowel Diseases

Fatty liver:
Tyramine from the gut microbiome may also play a role in fatty liver disease (NAFLD). A study involving children with obesity showed that their gut microbiome had more Enterococcus faecium, which produces tyramine. The increased tyramine activated PPAR-gamma, leading to lipid accumulation and NAFLD.[ref]

Related article: Fatty liver disease (NAFLD, MAFLD)

Notable/Interesting Points:

Tyramine is chemically similar to amphetamines but does not have the same effects.[ref]
Florida banned tyramine in 2012 as a Schedule I drug. (Does this make aged cheese illegal in Florida?)

Which foods are high in tyramine?

Foods high in tyramine include:

High Sources	Medium Sources
Aged/smoked meats (salami, bacon, jerky)	Olives
Aged cheeses (cheddar, Swiss, Parmesan, feta)	Chocolate
Sourdough, homemade yeast bread	Snow peas, edamame
Marmite, fermented veggies, dried fruits	Avocados, bananas
Some beers/wines (esp. unpasteurized)	Pineapple, eggplant
	Figs, yogurt, sour cream
	Peanuts, Brazil nuts
	Fava beans

Is it histamine or tyramine intolerance?

Many foods that are high in tyramine are also high in histamine. You may find it difficult to know whether you’re reacting to histamine or tyramine in foods. Read this histamine intolerance article to learn about genetic susceptibility, similarities, and symptom differences.

One significant difference in tyramine intolerance vs. histamine intolerance is the hypertensive crisis. A spike in blood pressure is associated with high tyramine levels and not histamine intolerance.

Tyramine Metabolism Genotype Report

This is a SNP-based nutrigenomics framework to help you identify if you are likely to have reduced enzyme activity for tyramine metabolism. The variants below have been studied in reference to their impact on enzyme activity in the biochemical pathways that metabolize tyramine.

Reduced enzyme activity in just one gene is not likely to cause significant problems with high tyramine foods, since there are multiple pathways for the metabolism of tyramine. However, reduced activity in a couple of the genes theoretically could cause problems with tyramine metabolism. Keep in mind that tyramine intolerance depends on your intake of high tyramine foods, your gut microbiome, and any medication interactions.

Tyramine from food is mainly broken down in the liver using the enzymes MAOA, FMO3, and CYP2D6.[ref] In addition, the DAO enzyme produced in the intestines to break down histamine can also metabolize tyramine and other biogenic amines.

MAO-A gene: Encodes monoamine oxidase A (MAOA) enzyme, which breaks down tyramine, serotonin, dopamine, epinephrine, and norepinephrine. It is located on the X chromosome, so males will only have one copy of the gene.

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Lifehacks: Natural solutions for tyramine intolerance

Let’s take a look at how to support tyramine metabolism, which foods to avoid, and which supplements are likely to impair tyramine breakdown.

Supporting tyramine metabolism:

Riboflavin for tyramine intolerance:
Vitamin B2 (riboflavin) is important in two ways for the breakdown of tyramine.

Riboflavin is a cofactor for the MAO-A enzyme.[ref]
Riboflavin is necessary for FMO3 function.[ref][ref]

This may be one reason that riboflavin works to prevent migraines in some people.

Make sure you get enough riboflavin via your diet or consider supplementing with riboflavin. The RDA for riboflavin is 1.3 mg daily for adult men and 1.1 mg daily for adult women. Foods high in riboflavin include milk, yogurt, cheese, eggs, meats, and green leafy vegetables.

Related article: Riboflavin genetic variants

NAD+ for MAO-A support:
MAO-A is also dependent on NAD+ levels, and NAD+ levels decline with age. To support NAD+, consider NMN or NR if you are older.

Related article: NAD+, NR, and NMN

DAO enzyme supplements:
Diamine oxidase is the enzyme that breaks down histamine and tyramine in the intestines. DAO supplements are available and may be helpful for someone with DAO variants (AOC1 gene).

Related article: DAO Enzyme Supplement Research

Avoiding high tyramine foods:

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Tyramine Intolerance: Symptoms, High-Tyramine Foods, and Genetics

What is tyramine intolerance? Symptoms, foods, and breaking it down

What is tyramine, and why does it cause symptoms?

How does the body get rid of tyramine?

Tyramine reactions:

Which foods are high in tyramine?

Is it histamine or tyramine intolerance?

Tyramine Metabolism Genotype Report

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Lifehacks: Natural solutions for tyramine intolerance

Supporting tyramine metabolism:

Avoiding high tyramine foods:

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Related Articles and Topics:

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