Tyramine Intolerance: Metabolism of tyramine

Key takeaways:
~ Tyramine can build up and result in serious difficulties like heart palpitations, spiking blood pressure, stroke-like symptoms, nausea, gastrointestinal issues, migraines, and brain fog.
~ Genetic variants in three key pathways impact how well you break down and eliminate tyramine.
~ Medications, especially MAOIs, also impact 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 by their doctor about the dietary interactions.

The hypertensive crisis is caused by too much tyramine, causing a sudden blood pressure increase leading to other symptoms.

I’ll start with some background on tyramine and then explain the genetic implications.

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 catecholamine 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 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)
How do you know if you have 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 this histamine intolerance article to learn about genetic susceptibility and symptom differences.

How does the body get rid of tyramine?

Tyramine is absorbed in the intestines from foods. Additionally, certain gut microbes can produce tyramine from tyrosine.

Tyramine is mainly broken down (metabolized) in the body using these three 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 (MAOIs) 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 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.[ref]

Interestingly, some of the first studies on the pressor effect of raising blood pressure were done in the early 1900s using rotting horse meat.[ref]

You may wonder 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. The change from typically not eating foods high in tyramine to suddenly chowing down on them 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 migraines.[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

Members: Log in to see your data below.
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the members only information in the Lifehacks sections.

Let me be clear: 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 three 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 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: typical FMO3 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]

Several genetic variants decrease or eliminate the CYP2D6 enzyme, and these variants can also influence your ability to metabolize certain medications. (Read more about CYP2D6)

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[ref]
  • 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 rs5030867 (23andMe v4, v5 ):

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

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
  • DD (or -/ – ): carrier of two CYP2D6*9, non-functioning[ref]

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: decreased or possibly non-functioning[ref]

Members: Your genotype for rs28371706 is .

Check your genetic data for rs16947 (23andMe v4, v5, AncestryDNA):

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

Members: Your genotype for rs16947 is .


Lifehacks: Natural solutions for tyramine

Riboflavin for tyramine intolerance:

Vitamin B2 (riboflavin) is important for people with FMO3 genetic variants.[ref][ref] Make sure you get 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):

The rest of this article is for Genetic Lifehacks members only.  Consider joining today to see the rest of this article.

Member Content:

An active subscription is required to access this content.

Join Here for full access to this article, genotype reports, and much more!


Already a member? Log in below.


Related Articles 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 by 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.

References:

“Avoid the Combination of High-Tyramine Foods and MAOIs.” Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/depression/expert-answers/maois/faq-20058035. Accessed 16 Nov. 2022.

Barger, G., and G. S. Walpole. “Isolation of the Pressor Principles of Putrid Meat.” The Journal of Physiology, vol. 38, no. 4, Mar. 1909, pp. 343–52. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533642/.

Bushueva, Olga, et al. “The Flavin-Containing Monooxygenase 3 Gene and Essential Hypertension: The Joint Effect of Polymorphism E158K and Cigarette Smoking on Disease Susceptibility.” International Journal of Hypertension, vol. 2014, Aug. 2014, p. e712169. www.hindawi.com, https://doi.org/10.1155/2014/712169.

Cronometer: Eat Smarter. Live Better. https://cronometer.com/. Accessed 16 Nov. 2022.

D’Andrea, G., et al. “Biochemistry of Neuromodulation in Primary Headaches: Focus on Anomalies of Tyrosine Metabolism.” Neurological Sciences, vol. 28, no. 2, May 2007, pp. S94–96. Springer Link, https://doi.org/10.1007/s10072-007-0758-4.

Hotamisligil, G. S., and X. O. Breakefield. “Human Monoamine Oxidase A Gene Determines Levels of Enzyme Activity.” American Journal of Human Genetics, vol. 49, no. 2, Aug. 1991, pp. 383–92.

How a Migraine Happens. 26 Nov. 2019, https://www.hopkinsmedicine.org/health/conditions-and-diseases/headache/how-a-migraine-happens.

Kashyap, A. S., and Surekha Kashyap. “Fish Odour Syndrome.” Postgraduate Medical Journal, vol. 76, no. 895, May 2000, pp. 318–318. pmj.bmj.com, https://doi.org/10.1136/pmj.76.895.318a.

Koukouritaki, Sevasti B., et al. “Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants.” Molecular Pharmacology, vol. 68, no. 2, Aug. 2005, pp. 383–92. PubMed, https://doi.org/10.1124/mol.105.012062.

Manning, Nigel J., et al. “Riboflavin-Responsive Trimethylaminuria in a Patient with Homocystinuria on Betaine Therapy.” JIMD Reports, vol. 5, 2012, pp. 71–75. PubMed, https://doi.org/10.1007/8904_2011_99.

Niwa, Toshiro, et al. “Human Liver Enzymes Responsible for Metabolic Elimination of Tyramine; a Vasopressor Agent from Daily Food.” Drug Metabolism Letters, vol. 5, no. 3, Aug. 2011, pp. 216–19. PubMed, https://doi.org/10.2174/187231211796905026.

NM_006894.5(FMO3):C.913G>T (p.Glu305Ter) AND Trimethylaminuria – ClinVar – NCBI. https://www.ncbi.nlm.nih.gov/clinvar/RCV000017697.30/. Accessed 16 Nov. 2022.

NM_001002294.3(FMO3):C.589_590TG[1] (p.Cys197_Asp198delinsTer) AND Trimethylaminuria – ClinVar – NCBI. https://www.ncbi.nlm.nih.gov/clinvar/RCV000490504.1/. Accessed 16 Nov. 2022.

Rafehi, Muhammad, et al. “Highly Variable Pharmacokinetics of Tyramine in Humans and Polymorphisms in OCT1, CYP2D6, and MAO-A.” Frontiers in Pharmacology, vol. 10, Oct. 2019, p. 1297. PubMed Central, https://doi.org/10.3389/fphar.2019.01297.

Sathyanarayana Rao, T. S., and Vikram K. Yeragani. “Hypertensive Crisis and Cheese.” Indian Journal of Psychiatry, vol. 51, no. 1, 2009, pp. 65–66. PubMed Central, https://doi.org/10.4103/0019-5545.44910.

tammy-lrome. “Low-Tyramine Diet Essentials.” Migraine.Com, https://migraine.com/blog/low-tyramine-diet-essentials. Accessed 16 Nov. 2022.

Walker, S. E., et al. “Tyramine Content of Previously Restricted Foods in Monoamine Oxidase Inhibitor Diets.” Journal of Clinical Psychopharmacology, vol. 16, no. 5, Oct. 1996, pp. 383–88. PubMed, https://doi.org/10.1097/00004714-199610000-00007.

Xu, Meijuan, et al. “Genetic and Nongenetic Factors Associated with Protein Abundance of Flavin-Containing Monooxygenase 3 in Human Liver.” The Journal of Pharmacology and Experimental Therapeutics, vol. 363, no. 2, Nov. 2017, pp. 265–74. PubMed, https://doi.org/10.1124/jpet.117.243113.

Xu, Xiaohui, et al. “Association Study between the Monoamine Oxidase A Gene and Attention Deficit Hyperactivity Disorder in Taiwanese Samples.” BMC Psychiatry, vol. 7, Feb. 2007, p. 10. PubMed, https://doi.org/10.1186/1471-244X-7-10.

Zubiaur, Pablo, et al. “SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability.” Journal of Personalized Medicine, vol. 11, no. 3, Mar. 2021, p. 204. PubMed, https://doi.org/10.3390/jpm11030204.


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.