Tyramine-Containing Foods

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References

Bieck PR. [Hypertensive crises with reversible inhibitors of monoamine oxidases? Results of tyramine interaction studies]. Psychiatr Prax 1989 Aug;16 Suppl 1:25-31. [Article in German]
Abstract: Healthy ambulatory subjects took 6 different MAO inhibitors (MAOIs) orally for 2 to 4 weeks. The new reversible MAO-A inhibitors brofaromine and moclobemide were compared with the irreversible MAOIs clorgyline, selegiline, phenelzine and tranylcypromine. Pressor responsiveness to oral tyramine was assessed before, during and after treatment. In unmedicated subjects, doses of tyramine to raise systolic blood pressure by at least 30 mmHg (PD30) ranged between 200 and 800 mg. During treatment with MAOIs, the PD30 decreased. The ratio of median effective doses (ED50) of tyramine (pre- vs post-treatment) was: selegiline 5, moclobemide 7, brofaromine 10, clorgyline 10, phenelzine 13 and tranylcypromine 55. Pressor responsiveness normalized within 8 days after stopping the reversible MAOIs and 30 days after tranylcypromine. The increased sensitivity after phenelzine persisted for longer than 8 weeks and after clorgyline for longer than 15 weeks. The results suggest that the two reversible MAO-A inhibitors moclobemide and brofaromine carry a much reduced liability to tyramine-related hypertensive reactions.

Brown C, Taniguchi G, Yip K. The monoamine oxidase inhibitor-tyramine interaction. J Clin Pharmacol 1989 Jun;29(6):529-532.
Abstract: Reports of hypertensive reactions from monoamine oxidase inhibitors (MAOI) began to proliferate in the early 1960s. Asatoor did extensive research and found that the combination of an MAOI and a food containing tyramine resulted in the hypertensive interaction ("the cheese reaction"). Because of the risk of intracerebral hemorrhage and death, clinicians were hesitant to use the MAOIs. Although progress on the metabolic effects of MAOIs has been slow, use of clinical information in addition to analysis of bioactive amine content of foods has allowed the formulation of dietary recommendations, which are thought to be useful clinically in the administration of MAOIs. This has resulted in the gradual return to use of these psychotropic compounds.

Buist RA. Drug-nutrient interactions - an overview. Intl Clin Nutr Rev 1984;4(3):114. (Review)

Cole AF, et al. Pharmacokinetic and metabolic aspects of the moclobemide-food interaction. Psychopharmacology (Berl). 1992;106 Suppl:S37-39.

Da Prada M, Zurcher G, Wuthrich I, Haefely WE. On tyramine, food, beverages and the reversible MAO inhibitor moclobemide. J Neural Transm Suppl 1988;26:31-56.
Abstract: The pathways for the biosynthesis and metabolism of tyramine are described as a basis for the discussion of the interaction between MAO inhibitors and tyramine. While a role of endogenous tyramine in the antidepressant action of MAO inhibitors remains purely hypothetical at this time, the mechanisms leading to the potentiation of the tyramine pressor effect ("cheese effect") are well known. Experiments in animals and man have provided concordant quantitative information on the effect of irreversible and some novel reversible MAO inhibitors on the presystemic disposition of orally ingested tyramine and on the noradrenaline-releasing action of tyramine in noradrenergic nerve terminals. There is a profound difference in the magnitude of tyramine potentiation between the irreversible inhibitor tranylcypromine and the reversible inhibitor moclobemide. A systematic analysis of the tyramine content of current European food and beverage is reported and serves as a rational basis for providing advice to patients on moclobemide. Most of the food and beverages analyzed contain less tyramine than previously reported and a few rules concerning rare cheeses with high tyramine content are sufficient to eliminate the risk of hypertensive crises.

Dyck LE, Dewar KM. Inhibition of aromatic L-amino acid decarboxylase and tyrosine aminotransferase by the monoamine oxidase inhibitor phenelzine. J Neurochem 1986 Jun;46(6):1899-1903.
Abstract: The concentration of p-tyramine in the rat striatum was increased significantly by intraperitoneal injection of phenelzine (5 or 100 mg/kg). Unlike other monoamine oxidase (MAO) inhibitors, phenelzine had no effect on p-tyramine levels in the first 1-2 h following injection. The high dose of phenelzine increased the p-tyramine levels much more than the low dose. In addition, the high dose of phenelzine increased striatal p-tyrosine levels significantly 12 h after injection. Further studies showed that phenelzine inhibited the tyrosine aminotransferase activity of rat liver homogenates; the IC50 was 50 microM. Phenelzine also inhibited the aromatic L-amino acid decarboxylase activity of rat brain homogenate with an IC50 of 25 microM. Following intraperitoneal injection of 100 mg/kg phenelzine, the initial concentration of phenelzine in the striatum appears to be high enough to inhibit aromatic L-amino acid decarboxylase. It is suggested that the multiple enzyme inhibition caused by administration of high doses of phenelzine accounts for its unusual effects on striatal p-tyramine levels compared with other MAO inhibitors, i.e., its initial lack of effect on p-tyramine levels followed later by very large increases in p-tyramine levels.

Fankhauser C, Charieras T, Caille D, Rovei V. Interaction of MAO inhibitors and dietary tyramine: a new experimental model in the conscious rat. J Pharmacol Toxicol Methods 1994 Dec;32(4):219-224.
Abstract: The aim of this study was to assess a new model for tyramine-induced pressor effects in the rat. The predictivity of the test is improved by simulating the real clinical situations where tyramine is ingested with food and beverages containing the amine. The pressor effect was investigated after oral administration of tyramine in a feed preparation or in a water solution by continuously recording blood pressure just above the aorta junction via a left-carotid catheter. The response was quantified by measurement of peak systolic blood pressure and as the percentage of tyramine-sensitive rats (TSR) in which the maximal pressor response to the amine was higher than 30 mm Hg (clinical risk threshold). Tyramine elicited, after oral administration (by gavage), a statistically significant dose-dependent increase in blood pressure from the dose of 10 mg/kg in solution (i.e. 23 +/- 3 mm Hg, N = 36) and 40 mg/kg in feed preparation (i.e., 20 +/- 2 mm Hg, N = 26). Almost all rats showed a systolic blood pressor increase higher than 30 mm Hg after oral administration of tyramine at a dose of 80 mg/kg p.o. in solution (TSR = 96%). Administration of tyramine in food (80 mg/kg) significantly delayed the time of the peak blood pressure (13 +/- 2 min instead of 7 +/- 0.5 min in solution, p < .001). Under these conditions, the tyramine threshold dose of TYR 30 (dose inducing an average response equivalent to the clinical risk threshold) was 14 mg/kg p.o. in solution and 67 mg/kg p.o. in feed preparation, respectively.

Gardner DM, Shulman KI, Walker SE, Tailor SA. The making of a user friendly MAOI diet. J Clin Psychiatry 1996 Mar;57(3):99-104. (Review)
Abstract: BACKGROUND: Many monoamine oxidase inhibitor (MAOI) diets are considered to be excessively restrictive and founded on poor scientific evidence. We present a safe and practical MAOI diet based on the related clinical and analytic data. METHOD: We used a critical review of the literature and our own tyramine assay results to categorize foods to be restricted absolutely, taken in moderation only, or unrestricted. RESULTS: We recommend that users avoid aged cheese; aged or cured meats (e.g., air-dried sausage); any potentially spoiled meat, poultry, or fish; broad (fava) bean pods; Marmite concentrated yeast extract; sauerkraut; soy sauce and soy bean condiments; and tap beer. Wine and domestic bottled or canned beer are considered safe when consumed in moderation. Other foods not mentioned are considered unrestricted. CONCLUSION: The concerns about perpetuating an overly restrictive MAOI diet include the avoidance by prescribers of a potentially useful treatment option, excessive limitations on lifestyle for patients, and increased risk to patients secondary to noncompliance with the diet. We propose an MAOI diet that has a solid scientific and clinical basis and that is, above all, practical.

Holt GA. Food and Drug Interactions. Chicago: Precept Press, 1998.

Korn A, Da Prada M, Raffesberg W, Gasic S, Eichler HG. Effect of moclobemide, a new reversible monoamine oxidase inhibitor, on absorption and pressor effect of tyramine. J Cardiovasc Pharmacol 1988 Jan;11(1):17-23.
Abstract: We determined in healthy subjects the pressor effect and the plasma level of free tyramine in response to intravenous and oral tyramine doses before and after therapeutic doses (3 X 100 mg/day) of moclobemide, a new reversible, preferential type A monoamine oxidase (MAO) inhibitor. In fasting subjects moclobemide increased the pressor effect of intravenously and orally administered tyramine; the tyramine dose-pressor curve was shifted to the left by factors of 2.4 and 4.1, respectively. No increase in systolic blood pressure occurred at free plasma tyramine concentrations lower than 70 ng/ml before, and 20 ng/ml after, moclobemide. Peak plasma tyramine concentrations increased dose-dependently after oral tyramine; after moclobemide similar peak plasma concentrations of tyramine were obtained with 2.6 times smaller doses of tyramine. Thus, the potentiation by moclobemide of the pressor effect of oral tyramine appears to be due to inhibition of tyramine first-pass metabolism, as well as to inhibition of tyramine catabolism by MAO within adrenergic nerve terminals. The peak concentrations of free tyramine in plasma and the concomitant increase of systolic blood pressure were significantly (p less than 0.01) smaller when tyramine was administered with a meal (before or after moclobemide) than when given with tap water. We conclude that at doses of 3 X 100 mg/day moclobemide induces only a mild potentiation of the pressor effect of tyramine. This potentiation is virtually absent under natural conditions when tyramine is given with a meal.

Livingston MG, et al. Monoamine oxidase inhibitors. An update on drug interactions. Drug Saf. 1996 Apr;14(4):219-27. (Review)
Abstract: After initial enthusiasm, the use of monoamine oxidase inhibitors (MAOIs) has been limited by the wide range of MAOI-drug and MAOI-food interactions that are possible, particularly with sympathomimetic medications or tyramine-containing foods, resulting in hypertensive reactions. Despite their clinical benefits, this has led to a reduction in use of such medications. Discovery of the 2 main subgroups of monoamine oxidase, types A and B, led to the synthesis of MAOIs selective for one or other of these isoenzymes. Consequently, selegiline (deprenyl), a selective MAO-B inhibitor, was developed for the treatment of idiopathic Parkinson's disease. This drug is useful in the treatment of the early stages of the disease and later on as an adjunct to other drug therapies. Although the selective MAO-A inhibitor, clorgiline (clorgyline), was found to be effective in the treatment of depression, it still retained the potential to cause hypertensive reactions. Recently, agents that are not only selective, but reversible in their inhibition of MAO-A (RIMAs) have been synthesised (e.g. moclobemide and toloxatone), and have proven antidepressant efficacy. While they are less likely to induce hypertensive reactions with the concomitant administration of sympathomimetic drugs or with tyramine-rich foodstuffs, it still seems wise to advocate care in co-prescribing potentially interacting medications and to advise a degree of caution with regard to the dietary intake of foodstuffs likely to contain a high tyramine content. Although these newer drugs represent an advance in safety, their use has, as yet, only been established in the treatment of depression. RIMAs also retain a potential for adverse interaction with other drugs. Concomitant prescription of serotonin-enhancing drugs should only be undertaken with caution for patients on moclobemide, toloxatone or selegiline. Coprescription of sympathomimetic drugs should also be avoided with these newer MAOIs and patients should be advised against purchasing over-the-counter preparations that may contain sympathomimetic drugs.

Muller T, Gieschke R, Ziegler WH. Blood pressure response to tyramine-enriched meal before and during MAO-inhibition in man: influence of dosage regimen. J Neural Transm Suppl 1988;26:105-114.
Abstract: In an open study oral tyramine in variable doses was administered to six healthy volunteers under three different conditions: 1) without moclobemide, 2) under moclobemide steady-state conditions (3 X 200 mg moclobemide daily) one hour after moclobemide intake and 3) under moclobemide steady-state conditions simultaneously with moclobemide. It was shown that the amount of tyramine effecting 30-50 mmHg systolic blood pressure increase was roughly doubled when moclobemide was administered together with tyramine instead of one hour before tyramine intake. The time interval between tyramine ingestion and maximal blood pressure increase did not differ significantly between conditions 2) and 3). The conclusion of this study is that moclobemide should always be taken at the end of a meal, which is anyway the usual time for drug intake.

Pohl R, Balon R, Berchou R. Reaction to chicken nuggets in a patient taking an MAOI. Am J Psychiatry 1988 May;145(5):651. (Letter)

Pronsky, Zaneta. Powers and Moore's Food-Medications Interactions. Ninth Edition. Food-Medication Interactions. Pottstown, PA, 1991.

Rafaelsen OJ. Cheese effects and new reversible MAO A inhibitors: summary. J Neural Transm Suppl 1988;26:123-124.

Roe DA. Diet and Drug Interactions. New York: Van Nostrand Reinhold, 1989.

Shulman KI, Walker SE, MacKenzie S, Knowles S. Dietary restriction, tyramine, and the use of monoamine oxidase inhibitors. J Clin Psychopharmacol 1989 Dec;9(6):397-402.
Abstract: The aim of this study is to provide clearer guidelines for rational, safe, and practical dietary restriction for use with monoamine oxidase inhibitors. Tyramine levels were assayed in over 100 of the controversial foods that have been associated with hypertensive reactions or reported to contain high levels of tyramine. Only a very limited number of foods appear to require absolute restriction. These include all aged cheeses, concentrated yeast extracts (e.g., Marmite), sauerkraut, and broad bean pods. Alcoholic beverages, including Chianti wine consumed in moderation, appear to be safe. Some aged meats contain relatively high levels of tyramine and require closer investigation.

Shulman KI, Tailor SA, Walker SE, Gardner DM. Tap (draft) beer and monoamine oxidase inhibitor dietary restrictions. Can J Psychiatry 1997 Apr;42(3):310-312.
Abstract: OBJECTIVE: Traditional monoamine oxidase inhibitors (MAOIs) continue to play an important role in the management of a wide variety of clinical conditions. Accordingly, a practical and safe approach to MAOI dietary restrictions remains an essential component of patient management. METHOD: In an effort to refine MAOI dietary recommendations, we report a case of hypertensive crisis following the consumption of a modest amount of tap beer. RESULTS: A well-documented case report involving tap (draft) beer consumed while on an MAOI supports an earlier study, which recommended that all tap beers be restricted on MAOI diets. The 2 cases were remarkably similar in terms of the offending substance, quantity consumed, and subsequent reaction. CONCLUSIONS: As a result of recent tyramine analyses and 2 well-documented case reports, all tap (draft) beers should now be absolutely restricted on MAOI diets because they represent a very significant risk at modest levels of consumption.

Sullivan EA, Shulman KI. Diet and monoamine oxidase inhibitors: a re-examination. Can J Psychiatry 1984 Dec;29(8):707-711. (Review)
Abstract: Monoamine oxidase inhibitors (MAOIs) are attracting renewed attention as effective antidepressants for refractory depressions, particularly among the elderly. However, widespread fears concerning the interactions of MAOIs with tyramine-containing foods have led to the development of long and complicated diets. These diets have served as an obstacle to the ready use of MAOIs, yet very little systematic or critical review of the basis for food restriction has been undertaken. An international survey of MAOI diets was conducted and from the diets collected, foods were categorized according to frequency of restriction on the diet lists. On the basis of this survey and a critical review of the literature it was determined that only four foods clearly warrant absolute prohibition: aged cheese, pickled fish (herring), concentrated yeast extracts and broad bean pods. While there is insufficient evidence to prohibit alcohol completely (even chianti wine) true moderation must apply. It is suggested that a radically simplified diet should be investigated on a prospective basis.

Thom, Dickson. Surviving the Nineties: Coping With Food Intolerances. Portland, OR, 1992.

Threlkeld DS, ed. Central nervous system drugs, antidepressants, monoamine oxidase inhibitors. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1997.

Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991 Nov;44(5):1651-1658.(Review)

Walker SE, Shulman KI, Tailor SA, Gardner D. Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. J Clin Psychopharmacol 1996 Oct;16(5):383-388.
Abstract: Traditional monoamine oxidase inhibitors (MAOIs) remain an important class of drugs for a variety of psychiatric conditions, including depressive illnesses, anxiety, and eating disorders. It was the objective of this study to refine the MAOI diet by determining the tyramine content of a variety of untested and "controversial" foods that continue to appear on MAOI diet-restricted food lists. A secondary objective of the study was to evaluate the effect of freshness on the tyramine content of some foods. Fifty-one food samples were evaluated for tyramine content by liquid chromatography. Food samples included a selection of sausages, beverages, sliced meat products, including chicken liver, and some fruits, including raspberries, bananas, and banana peels. Foods that were found to have dangerously high concentrations of tyramine (> or = 6 mg/serving) included chicken liver aged 9 days (63.84 mg/30 g), air-dried sausage (7.56 g/30 g), soy sauce (0.941 mg/ml), and sauerkraut (7.75 mg/250 g). Of the foods analyzed in this study, only those with high tyramine content per serving should continue to be absolutely restricted. All other foods are either safe for consumption or safe in moderation. The data provided should be combined with the data from other similar analytical studies to develop a list of foods that should be absolutely restricted. A more accurate list of restricted foods may enhance patient dietary compliance.

Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997. (Review).