Cheese effect

Ordonez, A.I., Ibanez, F.C., Torre, P. and Barcina, Y. (1997). Formation of biogenic amines in Idiazabal ewe s-milk cheese Effect of ripening, pasteurization, and starter, J. Food Prot., 60, 1371. 

Figure 24. Swiss Cheese effect in GMC negative resist produced by shock rinsing after development.

The main limitation to the clinical use of the MAOIs is due to their interaction with amine-containing foods such as cheeses, red wine, beers (including non-alcoholic beers), fermented and processed meat products, yeast products, soya and some vegetables. Some proprietary medicines such as cold cures contain phenylpropanolamine, ephedrine, etc. and will also interact with MAOIs. Such an interaction (termed the "cheese effect"), is attributed to the dramatic rise in blood pressure due to the sudden release of noradrenaline from peripheral sympathetic terminals, an event due to the displacement of noradrenaline from its mtraneuronal vesicles by the primary amine (usually tyramine). Under normal circumstances, any dietary amines would be metabolized by MAO in the wall of the gastrointestinal tract, in the liver, platelets, etc. The occurrence of hypertensive crises, and occasionally strokes, therefore limited the use of the MAOIs, despite their proven clinical efficacy, to the treatment of atypical depression and occasionally panic disorder. 

The "cheese effect" is a well-established phenomenon whereby an amine-rich food is consumed while the patient is being treated with an irreversible MAOI. Foods which cause such an effect include cheeses, pickled fish, yeast products (red wines and beers, including non-alcoholic varieties), chocolate and pulses such as broad beans (which contain dopa). It appears that foods containing more than 10 mg of tyramine must be consumed in order to produce a significant rise in blood pressure. Furthermore, it is now apparent that there is considerable variation in the tyramine content of many of these foods even when they are produced by the same manufacturer. Therefore it is essential that all patients on MAOIs should be provided with a list of foods and drinks that should be avoided. 

Tranylcypromine ( rans-2-phenylcyclopropylamine, TCP, 8a) has close structural similarity to amphetamine (2-amino-1-phenylpropane) and is known as a nonhydrazine, nonselective, and irreversible inhibitor of both MAO A and B. It is also a potent reversible inhibitor of CAOs [36,37], Tranylcypromine has an important clinical use for treatment of certain depressive illnesses, particularly of nonendo-genous and atypical depressions and depressions associated with anxiety, agitation, phobias, and anergia [38-40], In combination with lithium, it is also applied for treatment of refractory depression [41], Recent reports also discussed MAO inhibitors as useful agents against neurodegenerative disorders such as Parkinson s or Alzheimer s diseases [42], Despite impressive clinical successes, clinical use of tranylcypromine and other MAO inhibitors is limited by various problems, including the cheese effect discussed in Section 1,... 

With the recognition in the late 1960s that there are two forms of MAO (Section 1.1.1), potential therapeutic implications related to isozyme selectivity needed to be considered in MAO inhibitor development. (The early literature also reveals some lack of distinction between copper-containing and flavin-containing MAOs.) An important case in point involves the clinical side effects associated with the cheese effect (Section 1.2.1) that made clear that there would be important clinical advantages to having available isozyme-selective inhibitors [115]. Follow-up studies with the well-known cyclopropylamine inhibitor trans-2-phenylcyclopropylamine (8a) demonstrated that this clinically useful compound is an irreversible inhibitor of MAO, but that it had no selectivity toward either MAO A or B [116]. 

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

Mills, O. E. and Thomas, T. D. 1980. Bitterness development in Cheddar cheese Effect of level of starter proteinase. N.Z. J. Dairy Sci. Technol. 15, 131-141. 

Desmethylselegiline is also an irreversible inhibitor of monoamine oxidase B in humans. There is evidence that the 1-stereoisomers of 1-amphetamine and 1-methamphetamine may have some qualitatively different actions from their d-isomer counterparts, which might result in beneficial clinical effects and could complement any beneficial clinical actions of selegiline itself. Food has no effect on the pharmacokinetics of desmethylselegiline, methamphetamine, and amphetamine. At a dose of 10 mg per day, selegiline is devoid of the cheese effect that is, it does not cause hypertension when taken with tyramine-containing foods such as cheese. 

Irreversible MAOIs + sympathomimetic amines, tyramine-containing foods ("cheese effect") and buspirone — hypertension, possibly leading to stroke. 

The search for selective inhibitors for the two forms of MAO (MAO A and MAO B) remains an important area of medicinal chemistry223. Mood-elevating effects of MAO inhibitors make them useful drugs for the treatment of depressive illness. Complications of MAO treatment include elevation of blood pressure due to blockade of the oxidative metabolism of tyramine, a pressor amine present in many foods (the cheese effect ). Since this inhibition has been attributed to the action of intestinal MAO A, the search for selective MAO B inhibitors has been particularly intense. 

Werner, S.A., Luedecke, L.O., Shultz, T.D. 1992. Determination of conjugated linoleic acid content and isomer distribution in three Cheddar-type cheeses Effects of cheese cultures, processing and aging. J. Agric. Food Chem. 40, 1817-1821. 

Lee, B.O., Kilbertus, G., Alais, C. 1981. Ultrastructural study of processed cheese. Effect of different parameters. Milchwissenschaft 36, 343-348. 

The monoamine oxidase inhibitors are associated with a number of undesirable side effects including weight gain, postural hypotension, sexual dysfunction, and insomnia. The most serious side effect is the risk of tyramine-re-lated hypertensive crisis, often referred to as the "cheese effect," which can be fatal. To avoid this situation patients taking MAOIs must limit their tyramine intake, and the restrictive diet required to accomplish this leads to low patient compliance. A similar interaction occurs when switching patients from MAOI to SSRI therapy, and a minimum 2-week washout period before commencement of SSRI therapy is essential to allow MAO levels to return to normal. The therapeutic effects of the TCAs derive from their inhibition of serotonin and norepinephrine uptake, al-... 

Elsworth JD, Glover V, Reynolds GP, Sandler M, Lees AJ, Phuapradit P, Shaw KM, Stern GM, Kumar P (1978) Deprenyl administration in man a selective monoamine oxidase B inhibitor without the cheese effect . Psychopharmacology 57 33-38... 

Sheehan, J.J., Hnppertz, T., Hayes, M.G., Kelly, A.L., Beresford, T.P., and Guinee, T.P. 2005. High pressnre treatment of rednced-fat mozzarella cheese Effects on functional and rheological properties. Innovative Food Science and Emerging Technologies 6 73-81. 

Monoamine oxidases (both MAO-A and MAO-B) also exist in peripheral tissue, specifically the gastrointestinal tract (GIT). In the GIT, they inhibit the first-pass metabolism of exogenous tyramine. Because of this property, treatment with non-selective irreversible MAOIs can result in the accumulation of tyramine and have the potential to precipitate a dangerous hypertensive crisis, the so-called cheese effect. This effect may occur more frequently in elderly than in younger patients, because the cardiovascular systems of the elderly are already compromised by age. Selective MAO-B inhibitors and reversible MAO-A inhibitors are free from this potentially fatal interaction. 

O Connor, C. B. (1974). The quality and composition of Cheddar cheese Effect of various rates of salt addition. Ir. Agric. Creamery Rev. 27(1), 11-13. 

Chlorgyline, like many other nonspecific and MAO A inhibitors, potentiates the pressor effect of tyramine on the cardiovascular system in humans and rodents and may result in hypertensive crises. This effect is probably due to inhibition of MAO A activity in the intestines which normally detoxify monoamines in food and beverages such as cheese and winei id 2 jg believed that only MAO A inhibitors (and mixed inhibitors) have this so-called cheese effect ... 

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