The MAOIs were introduced in the mid-1950s, and for the first decade of their use, nobody had an inkling that combining them with cheese (or any other high tyramine food) could be dangerous. Over this period of time, there were an awful lot of patients combining cheddar with Nardil and Parnate, but hypertensive emergencies associated with this combination were rare.
The first published report hinting at a problem with MAOIs appeared in the Lancet in 1963. Barry Blackwell, a psychiatric resident at Maudsley Hospital in London, reported on 12 patients who had hypertensive crises apparently related to the use of Parnate (11 of the patients) or Nardil (one of the patients). It took several years before an interaction with cheese was identified as the culprit and the mechanism was uncovered.
It turns out that cheese, and several other high protein foods, contain high amounts of the amino acid tyramine. While tyramine helps us build proteins, it causes a bit of mischief as well. Sometimes referred to as a “false neurotransmitter,” tyramine enters noradrenergic nerve terminals and displaces large amounts of norepinephrine, which enters the blood stream and causes vasoconstriction. In fact, when volunteers are given pure tyramine (available as a dietary supplement and marketed for body-builders), they usually experience a mild rise in blood pressure (J Clin Pharmacol 2003;43(6):604-609).
Nonetheless, dietary tyramine generally causes us no problems, because our GI tracts and our livers contain plenty of monoamine oxidase (MAO), which metabolizes tyramine, ensuring that any hypertensive effect is transient. But MAOIs cause a “double whammy” that can significantly increase blood pressure:
Whammy #1: MAOIs prevent the breakdown of tyramine in the gut, so lots of tyramine gets into the bloodstream and displaces NE from nerve terminals.
Whammy #2: These artificially higher levels of NE cannot be quickly lowered, because MAOI inhibits the
breakdown of NE (along with serotonin and dopamine) inside the neurons.
How do foods get to be high in tyramine? Via the action of bacteria on tyramine’s parent, tyrosine. Tyrosine is found in large amounts in many high protein foods. Bacteria such as Enterococcus and Lactobacillus contain tyrosine decarboxylase, which converts tyrosine to tyramine. Hence, foods that (1) contain amino acids (e.g., have protein); and (2) have a lot of bacteria in them, are precisely those foods that are likely to be loaded with tyramine. This is why we tell patients on MAOIs to eat foods when they are fresh. The longer cheese or meat is left in the fridge, the more bacteria, and hence the more tyramine.
The MAOI Diet
The forbidden foods on the MAOI diet used to read like a who’s who of all the things that our patients love to eat and drink: pizza, chocolate, brie, beer, fava beans with someone’s liver and a nice chianti (made famous by Anthony Hopkins in The Silence of the Lambs). But that list has been changing in recent years, largely due to the efforts of a group of researchers at the University of Toronto who have been measuring the tyramine content of foods commonly forbidden. To the delight of many patients, they found, for example, that major food-chain pizzas had safe quantities of tyramine, including a Domino’s double-cheese, double-pepperoni pizza (J Clin Psychiatry 1999;60(3):191-193). The serving sizes analyzed were by no means stingy: a half of a medium pizza. Because most pizzas are made with fresh mozzarella, which contains little tyramine, it appears that patients taking MAOIs can indeed enjoy pizza dinners, at least when they are made fresh to order and when the only cheese they contain is mozzarella. Note that some gourmet pizzas may contain aged cheeses that are higher in tyramine and thus should be avoided (J Clin Psychiatry [letter] 2000;61(2):145).