Tyramine intolerance: MAOA, Migraines, and Cheese

Let me set the scene: You’re gathered ’round on Christmas Eve for a get together with all of your family, having traveled from far and wide. Your uncle brings his “special family recipe” of summer sausage to share, paired with a plate of all kinds of fancy aged cheeses. Your hipster cousin contributes some home-brew beer to the party, and you sop up all the alcohol with sourdough bread rounds stacked with sausage and cheese. Let’s top it all off with your dad pulling out an olive tray, and your mom making a bowl of guacamole from some nice ripe avocados. Naturally, dark chocolate and dried fruit to nibble on for dessert.

Delicious and wonderful family fun.

Until… all the tyramine in those foods spikes your blood pressure, causing a severe headache, difficulty thinking, blurred vision, chest pain, nausea, and stroke-like symptoms!  But this is only a problem if you have genetic variants that decrease tyramine metabolism.

This article digs into the genetic reasons for tyramine intolerance and explains how to know if it applies to you.

What is tyramine intolerance?

A tyramine hypertensive crisis, also called the ‘cheese effect’, is caused by high tyramine levels in foods. This is usually associated with being on an MAO inhibitor, and people on MAOi’s are cautioned about the food interactions.

The cheese effect  is caused by too much tyramine causing a sudden increase in blood pressure which leads to other symptoms.

First, let’s go through some of the background information on tyramine, and then we will dig into the genetics.

What is tyramine?

Tyramine is a biogenic amine, which refers to its chemical structure with nitrogen at its base. It is naturally found in trace levels in the body.

We naturally produce several kinds of biogenic amines including histamine, dopamine, serotonin, epinephrine, and norepinephrine. Dopamine, serotonin, epinephrine and norepinephrine act as neurotransmitters, and histamine is well known for allergic reactions.

Tyramine is found in trace amounts in the body. It can cross the blood-brain barrier and act as a neuromodulator in the brain.

Tyramine can also be found in foods – especially fermented foods or foods that are close to spoiling. This is where the ‘cheese effect‘ comes into play. (Read the background on how it was discovered)

Which foods are high in tyramine?

A quick list of foods high in tyramine include:

  • aged, smoked, or fermented meats (salami, pepperoni, cured sausages, bacon, corned beef, beef jerky, etc)
  • aged cheeses (cheddar, gouda, Swiss, parmesan, feta, Brie, etc)
  • sourdough bread and some homemade yeast bread
  • marmite and other yeasty things
  • fermented veggies and dried fruits (sauerkraut, kimchee, tofu, soy sauce)
  • some beers and wines (especially unpasteurized beer such as homemade or tap)
  • medium sources include: olives, chocolate, snow peas, edamame, avocados, bananas, pineapple, eggplant, figs, yogurt, sour cream, peanuts, Brazil nuts, fava beans (broad beans)

Breaking down tyramine:

Tyramine that is absorbed in the intestines (from food and your microbiome) mainly is broken down in the body using the enzymes MAO-A, FMO3, and CYP2D6.

MAO-A is the enzyme that metabolizes several neurotransmitters, including dopamine. Inhibiting or decreasing MAO-A is one way to increase dopamine levels. Thus, drugs that act as MAO-A inhibitors can be used as antidepressants, although they usually aren’t the first choice due to the dietary interactions with tyramine.

Effects of too much tyramine

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 30 mmHg or more.

This is called the ‘tyramine pressor response’.  Tyramine is taking the place of other neurotransmitters, which triggers the body to release a bunch of norepinephrine, constricting blood vessels and raising blood pressure. Interestingly, some of the first studies on the pressor effect raising blood pressure were done in the early 1900s using rotting horse meat.[ref]

You may be wondering why we all aren’t dropping dead of a heart attack after eating a salami and 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.

Tyramine Sensitivity and Migraines

For people susceptible to migraines, the list of foods high in tyramine may correspond to your list of ‘triggers’.

  • Many people with either cluster headaches or migraines don’t break down tyramine well.[ref]
  • Researchers think that the vasoconstriction triggered by tyramines initiates the migraine.[ref][ref]

Fun fact

Tyramine is chemically similar to amphetamine and methamphetamine, although it doesn’t produce the same effects. The state of Florida banned tyramine as a schedule I drug in 2012. [ref] Does this mean that selling chocolate and cheese is a felony in Forida?


Genetic variants that could cause tyramine intolerance:

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Let me be clear up-front: There aren’t any specific research studies that specify that the combination of these variants cause tyramine intolerance.

Instead, the variants below have been studied in reference to their impact on enzyme activity in the molecules that metabolize tyramine. 

Reduced enzyme activity in just one gene is not likely to cause you a whole lot of problems with high tyramine foods since there are multiple ways your body can break it down. But reduced activity in a couple of the genes theoretically could cause problems with tyramine metabolism. Again, this all depends on your diet and how often you eat foods high in tyramine.

Tyramine taken in from food is mainly broken down in the liver using the enzymes MAOA, FMO3, and CYP2D6.[ref]

MAO-A genetic variants:

The monoamine oxidase A (MAOA) enzyme 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.

Check your genetic data for rs6323 (23andMe v4 only):

  • G/G or G: typical
  • G/T: somewhat reduced MAOA activity
  • T/T or T: reduced MAOA activity[ref][ref]

Members: Your genotype for rs6323 is .

 

FMO3 genetic variants:

This is one of the main liver enzymes for breaking down tyramine (as well as other biogenic amines). FMO3, or flavin-containing monooxygenase 3, is dependent on FAD and FMN as cofactors.

These first four variants are more significant reductions in enzyme activity and are linked to TMAU (fish odor or strong body odor). Note that 23andMe doesn’t cover all the FMO3 variants that decrease the function.

Check your genetic data for rs28363581 (23andMe v5; AncestryDNA):

  • C/C: decreased FMO3 function
  • C/T: decreased FMO3 function
  • T/T: typical FMO3 function

Members: Your genotype for rs28363581 is .

Check your genetic data for rs3832024 (23andMe v5):

  • DD or -/-: decreased FMO3 function[ref]
  • DI or -/TG: decreased FMO3 function
  • II or TG/TG: typical FMO3 function

Members: Your genotype for rs3832024 is .

Check your genetic data for rs61753344 (23andMe v4, v5; AncestryDNA):

  • T/T: decreased FMO3 function[ref]
  • G/T: decreased FMO3 function
  • G/G: typical FMO3 function

Members: Your genotype for rs61753344 is .

Check your genetic data for rs1736557 (23andMe v4, v5; AncestryDNA):

  • A/A: decreased FMO3 function[ref]
  • A/G: decreased FMO3 function
  • G/G: typical FMO3 function

Members: Your genotype for rs1736557 is .

Check your genetic data for rs2266780 (23andMe v4, v5; AncestryDNA):

  • G/G: somewhat decreased FMO3 function[ref]
  • A/G: somewhat decreased FMO3 function
  • A/A: typical FMO3 function

Members: Your genotype for rs2266780 is .

Check your genetic data for rs2266782 (23andMe v4, v5):

  • A/A: decreased FMO3 function[ref][ref] increased risk of hypertension, especially in smokers[ref]
  • A/G: somewhat decreased FMO3 function
  • G/G: typicalFMO3 function

Members: Your genotype for rs2266782 is .

Check your genetic data for rs909530 (23andMe v4; AncestryDNA):

  • T/T: somewhat decreased FMO3 function[ref] (probably mild)
  • C/T: somewhat decreased FMO3 function
  • C/C: typical FMO3 function

Members: Your genotype for rs909530 is .

Check your genetic data for rs909531 (23andMe v4):

  • C/C: somewhat decreased FMO3 function[ref]
  • C/T: somewhat decreased FMO3 function
  • T/T: typical FMO3 function

Members: Your genotype for rs909531 is .

 

CYP2D6 genetic variants:

Inhibiting CYP2D6 causes tyramine elimination rates to decrease.[ref] There are several genetic variants that decrease or eliminate the CYP2D6 enzyme. These variants are not all that common and carrying a variant that decreases the CYP2D6 enzyme can decrease your ability to break down tyramine as well as quite a few other drugs.

Check your genetic data for rs3892097 (23andMev4 only):

  • T/T: CYP2D6*4 – poor metabolizer
  • C/T:  typically an intermediate metabolizer
  • C/C: extensive metabolizer

Members: Your genotype for rs3892097 is .

Check your genetic data for rs5030655 (23andMe v4, v5):

  • DD (or -/- ) : CYP2A6*6 – deletion, poor metabolizer
  • DI (or – /A ):  intermediate metabolizer
  •  II (or A/A): typical

Members: Your genotype for rs5030655 is .

Check your genetic data for rs1065852 (23andMe v4 only):

  • A/A: decreased or non-functioning
  • A/G:  somewhat decreased
  • G/G: typical

Members: Your genotype for rs1065852 is .

Check your genetic data for rs1135824 (23andMe v4, v5):

  • T/T: typical
  • C/T:  one copy of CYP2D6*3
  • C/C: two copies of CYP2D6*3, non-functioning

Members: Your genotype for rs1135824 is .

Check your genetic data for rs5030867 (23andMe v4, v5 ):

  • T/T: typical
  • G/T:  carrier of one CYP2D6*7 allele
  • G/G: carrier of two CYP2D6*7, non-functioning

Members: Your genotype for rs5030867 is .

Check your genetic data for rs5030656 (23andMe v4, v5):

  • II (or C/T/T / C/T/T): typical
  • DI (or -/C/T/T):  carrier of one CYP2D6*9 allele
  • II (or  -/ – ): carrier of two CYP2D6*9, non-functioning

Members: Your genotype for rs5030656 is .

Check your genetic data for rs28371706 (23andMe v4 only):

  •  G/G: typical
  •  A/G:  carrier of one decreased or non-functioning allele
  •  A/A: possibly decreased or non-functioning

Members: Your genotype for rs28371706 is .

Check your genetic data for i4001479 (23andMe v4 only) or other genetic data for rs72549354 :

  • DD (or -/- ): typical
  • DI (or -/C ): reduced enzyme activity
  • II (or C/C): no enzyme activity CYP2D6*20

Members: Your genotype for i4001479 is .


Lifehacks:

Riboflavin for tyramine intolerance:

Vitamin B2 (riboflavin) is important for people with FMO3 genetic variants.[ref][ref]  Make sure you are getting enough riboflavin via your diet, or consider supplementing with riboflavin.

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

Low tyramine diet:

Foods to avoid that are high in tyramine include:[ref][ref][ref]

Highest:

  • dried and aged sausages (salami, pepperoni, cacciatore, summer sausage)
  • soy sauce, fish sauce
  • sauerkraut, kimchi
  • aged chicken liver

High:

  • fava beans (broad beans)
  • Aged cheeses (Parmesan, blue cheese, aged cheddar, Swiss)
  • smoked or processed meats (hot dogs, bologna, corned beef, smoked fish)
  • tap beer or any beer that is unpasteurized
  • Marmite (yeast extract)
  • tofu and other soy products (not including soy milk)
  • supplements that contain tyramine

Lifestyle tips for tyramine intolerance:

Eat fresh foods: In addition to being found in fermented and aged food, tyramine builds up in leftovers. So if you aren’t going to eat your leftover dinner the next morning, go ahead and put it in the freezer.

Tracking: If you get a lot of migraines, keep track of what you are eating either in a journal or through an app like Cronometer.com. This can show whether your migraines are related to tyramine-containing foods.

Stomach sensitivity: Receptors for tyramine (TAAR1) are also found in the stomach, specifically in the pylorus, which is where the stomach dumps into the small intestines. Activation of the tyramine receptors in the pylorus cause gastric secretion – e.g. stomach acid secretion. This may cause some people to have a stomach that is sensitive to tyramine in foods.

Medication interactions: Note that FMO3 and CYP2D6 are also involved in the metabolism of many other drugs. You should check out the list of substrates for FMO3 and CYP2D6 if you have variants that significantly affect their function.


Related Genes and Topics:

Your need for riboflavin (B2): MTHFR and other genetic variants
Riboflavin (Vitamin B2) is a water-soluble vitamin that is a cofactor for many enzymes in the body.  To put it in simpler terms: riboflavin is vitally important! Riboflavin is a ribose sugar bound to a flavin molecule.

Detoxification: Phase I and Phase II Metabolism
Our body has an amazing capacity to rid itself of harmful substances. We take in toxins daily through eating natural plant toxins. We are exposed to toxicants (man-made toxins) through pesticide residue, air pollution, skincare products, and medications.

Trimethylaminuria: Genetic variants that cause a malodorous body odor
Often referred to as ‘fish odor disease’, trimethylaminuria causes a strong odor in sweat, urine, and breath. It is caused by mutations in the FMO3 gene.




Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.