The cheese effect and your genes: tyramine intolerance

Subtitled: Let's all try not to have a heart attack this Christmas! 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. Your aunt from California brings in a tray of fermented foods along with an olive and antipasto tray.  Let's top it all off with your dad pulling out some anchovies, and your mom making a bowl of guacamole from some nice ripe avocados. Naturally, dark chocolate abounds in the chocolate covered peanuts and dried fruits. 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!  Unfortunately, you drew the short end of the genetic straw when it comes to the genes that break down tyramine.

What is tyramine intolerance?

A tyramine hypertensive crisis also called the 'cheese effect', is caused by overindulging in foods high in tyramine. This is usually associated with being on an MAO inhibitor. (People on MAOIs are usually well aware of the dietary restriction of tyramine.) The cheese effect basically is caused by too much tyramine causing a sudden increase in blood pressure. What are the genetic variants that can cause you to not break down tyramine as well as you should?

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 have lots of these biogenic amines produced in the body. Your body produced many of the amines in larger quantities, such as histamine, dopamine, epinephrine, norepinephrine, and these amines act mainly as neurotransmitters. 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) 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 a lot of neurotransmitters also, so inhibiting or decreasing MAO-A is one way to increase dopamine levels. Thus MAO-A inhibitors can be used as antidepressants, although they usually aren't the first choice due to the dietary interactions with 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.  (Some of the first studies on the pressor effect raising blood pressure were done in the early 1900s using rotting horse meat.[ref] So don't eat rotting horse meat...) You may be wondering why we all aren't dropping dead of a heart attack after eating a salami and cheese sandwich on sourdough. 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. 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 as well as they should.[ref] The vasoconstriction may be what is triggering the migraine.[ref][ref] One final interesting tidbit... 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. I'm not sure if this means that selling chocolate and cheese is a felony in FL or not.[ref]

Genetic variants that impair tyramine breakdown:

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