Find out if you have Tyramine Intolerance

Let me set the scene: You’re gathered ’round on Christmas Eve for a family get-together. 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. We will top it all off with your dad putting 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 fun gathering!

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!

For most people, this won’t happen. But it is a possibility if you have genetic variants that significantly decrease tyramine metabolism.  Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

What is tyramine intolerance? Symptoms, foods, and metabolism

High tyramine levels in meals can trigger a tyramine hypertensive crisis, commonly known as the ‘cheese effect.’ This is usually associated with taking an MAO inhibitor, and people on an MAOi are cautioned about the dietary interactions.

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

Let’s start with some basic information on tyramine, and then we’ll go 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 at trace levels in the human body.

Histamine, spermidine, dopamine, serotonin, epinephrine, and norepinephrine are all amines that we create naturally. Neurotransmitters such as dopamine, serotonin, adrenaline, and norepinephrine, as well as histamine, are known to cause allergic reactions.

Tyramine in low amounts can act to release catecholemine neurotransmitters. 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 as a reaction in people on MOAI drugs)

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, kimchi, 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)
Is it histamine intolerance 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 through this article on histamine intolerance to learn about genetic susceptibility and symptom differences.

How does the body get rid of tyramine?

Tyramine is absorbed in the intestines from foods and from certain gut microbes that produce tyramine from tyrosine.

Tyramine is mainly broken down (metabolized) in the body using these enzymes:

  • MAO-A (monamine oxidase A)
  • FMO3 (flavin-containing monooxygenase 3)
  • CYP2D6 (a CYP450 family detoxification enzyme)

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 (MAOi’s) can be used as antidepressants, although they usually aren’t the first choice due to the dietary interactions with tyramine.

Once tyramine is metabolized, utilizing one of the enzymes above in the reaction, it is eliminated from the body in the urine.[ref]

Tyramine reactions:

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 takes the place of other neurotransmitters, which trigger the body to release a bunch of norepinephrine, constricting blood vessels and raising blood pressure.[ref] 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 from 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 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 Florida?


Tyramine Metabolism Genotype Report

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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 causes 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 .

 


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 (tyramine containing foods list):

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Related Genes and Topics:

Histamine Intolerance
Excess histamine can cause allergy-type reactions in some people.

Serotonin
Your genes play a role in how much serotonin is made, how it is broken down, and how cells receive the serotonin signal.

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.

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.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.