"Tyramine is an amino acid which is found in various foods, and is an indirect sympathomimetic that can cause a hypertensive reaction in patients receiving MAOI therapy.
Monoamine oxidase is found in the gastrointestinal tract and inactivates tyramine; when drugs prevent the catabolism of exogenous tyramine, this amino acid is absorbed and displaces norepinephrine from sympathetic nerve ending and epinephrine from the adrenal glands. If a sufficient amount of pressor amines are released, a patient may experience a severe occipital or temporal headache, diaphoresis, mydriasis, nuchal rigidity, palpitations, and the elevation of both diastolic and systolic blood pressure may ensue (Anon, 1989; Da Prada et al, 1988; Brown & Bryant, 1988).
On rare occasions, cardiac arrhythmias, cardiac failure, and intracerebral hemorrhage have developed in patients receiving MAOI therapy that did not observe dietary restrictions (Brown & Bryant, 1988).
Therefore, dietary restrictions are required for patients receiving MAOIs. Extensive dietary restrictions previously published were collected over a decade ago and due to changes in food processing and more reliable analytical methods, new recommendations have been published (Anon, 1989; McCabe, 1986).
The tyramine content of foods varies greatly due to the differences in processing, fermentation, ripening, degradation, or incidental contamination. Many foods contain small amounts of tyramine and the formation of large quantities of tyramine have been reported if products were aged, fermented, or left to spoil. Because the sequela from tyramine and MAOIs is dose-related, reactions can be minimized without total abstinence from tyramine-containing foods. Approximately 10 to 25 mg of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild reaction. Foods that normally contain low amounts of tyramine may become a risk if unusually large quantities are consumed or if spoilage has occurred (McCabe, 1986).
Three lists were compiled (foods to avoid, foods that may used in small quantities, and foods with insufficient evidence to restrict) to minimized the strict dietary restrictions that were previously used and improve compliance and safety of MAOI therapy. The foods to avoid list consists of foods with sufficient tyramine (in small or usual serving sizes) that would create a dangerous elevation in blood pressure and therefore should be avoided (McCabe, 1986).
Foods to Avoid
ALCOHOLIC BEVERAGES - avoid Chianti wine and vermouth. Consumption of red, white, and port WINE in quantities less than 120 mL present little risk (Anon, 1989; Da Prada et al, 1988; McCabe, 1986). BEER and ALE should also be avoided (McCabe, 1986), however other investigators feel major domestic (US) brands of beer is safe in small quantities (1/2 cup or less than 120 mL) (Anon, 1989; Da Prada, 1988), but imported beer should not be consumed unless a specific brand is known to be safe. WHISKEY and LIQUEURS such as Drambuie(R) and Chartreuse(R) have caused reactions. NONALCOHOLIC BEVERAGES (alcohol- free beer and wines) may contain tyramine and should be avoided (Anon, 1989; Stockley, 1993).
BANANA PEELS - a single case report implicates a BANANA as the causative agent, which involved the consumption of whole stewed green banana, including the peel. Ripe banana pulp contains 7 mcg/gram of tyramine compared to a peel which contains 65 mcg/gram and 700 mcg of tyramine and dopamine, respectively (McCabe, 1986).
BEAN CURD - fermented bean curd, fermented soya bean, soya bean pastes contain a significant amount of tyramine (Anon, 1989).
BROAD (FAVA) BEAN PODS - these beans contain dopa, not tyramine, which is metabolized to dopamine and may cause a pressor reaction and therefore should not be eaten particularly if overripe (McCabe, 1986; Anon, 1989; Brown & Bryant, 1988).
CHEESE - tyramine content cannot be predicted based on appearance, flavor, or variety and therefore should be avoided. CREAM CHEESE and COTTAGE CHEESE have no detectable level of tyramine (McCabe, 1986; Anon, 1989, Brown & Bryant, 1988).
FISH - fresh fish (Anon, 1989; McCabe, 1986) and vacuum- packed pickled fish or CAVIAR contain only small amounts of tyramine and are safe if consumed promptly or refrigerated for short periods; longer storage may be dangerous (Anon, 1989). Smoked, fermented, pickled (Herring) and otherwise aged fish, meat, or any spoiled food may contain high levels of tyramine and should be avoided (Anon, 1989; Brown & Bryant, 1988).
GINSENG - some preparations have resulted in a headache, tremulousness, and manic-like symptoms (Anon, 1989).
PROTEIN EXTRACTS - three brands of meat extract contained 95, 206, and 304 mcg/gram of tyramine and therefore meat extracts should be avoided (McCabe, 1986). Avoid liquid and powdered PROTEIN DIETARY SUPPLEMENTS (Anon, 1989).
MEAT, nonfresh or liver - no detectable levels identified in fresh chicken livers; high tyramine content found in spoiled or unfresh livers (McCabe, 1986). Fresh meat is safe, caution suggested in restaurants (Anon, 1989; Da Prada et al, 1988).
SAUSAGE, BOLOGNA, PEPPERONI and SALAMI contain large amounts of tyramine (Anon, 1989; Da Prada et al, 1988; McCabe, 1986). No detectable tyramine levels were identified in country CURED HAM (McCabe, 1986).
SAUERKRAUT - tyramine content has varied from 20 to 95 mcg/gram and should be avoided (McCabe, 1986).
SHRIMP PASTE - contain a large amount of tyramine (Anon, 1989).
SOUPS - should be avoided as protein extracts may be present; miso soup is prepared from fermented bean curd and contain tyramine in large amounts and should not be consumed (Anon, 1989).
YEAST, Brewer's or extracts - yeast extracts (Marmite) which are spread on bread or mixed with water, Brewer's yeast, or yeast vitamin supplements should not be consumed. Yeast used in baking is safe (Anon, 1989; Da Prada et al, 1988; McCabe, 1986).
The foods to use with caution list categorizes foods that have been reported to cause a hypertensive crisis if foods were consumed in large quantities, stored for prolong periods, or if contamination occurred. Small servings (1/2 cup, or less than 120 mL) of the following foods are not expected to pose a risk for patients on MAOI therapy (McCabe, 1986).
FOODS TO USE WITH CAUTION
(1/2 cup or less than 120 mL)
Alcoholic beverages - see under foods to avoid.
AVOCADOS - contain tyramine, particularly overripe (Anon, 1989) but may be used in small amounts if not overripened (McCabe, 1986).
CAFFEINE - contains a weak pressor agent, large amounts may cause a reaction (Anon, 1989).
CHOCOLATE - is safe to ingest for most patients, unless consumed in large amounts (Anon, 1989; McCabe, 1986).
DAIRY PRODUCTS - CREAM, SOUR CREAM, cottage cheese, cream cheese, YOGURT, or MILK should pose little risk unless prolonged storage or lack of sanitation standards exists (Anon, 1989; McCabe, 1986). Products should not be used if close to the expiration date (McCabe, 1986).
NUTS - large quantities of PEANUTS were implicated in a hypertensive reaction and headache. COCONUTS and BRAZIL NUTS have also been implicated, however no analysis of the tyramine content was performed (McCabe, 1986).
RASPBERRIES - contain tyramine and small amounts are expected to be safe (McCabe, 1986).
SOY SAUCE - has been reported to contain large amounts of tyramine and reactions have been reported with teriyaki (Anon, 1989), however analysis of soy sauce reveals a tyramine level of 1.76 mcg/mL and fermented meat may have contributed to the previously reported reactions (McCabe, 1986).
SPINACH, New Zealand prickly or hot weather - large amounts have resulted in a reaction (Anon, 1989; McCabe, 1986).
More than 200 foods contain tyramine in small quantities and have been implicated in reactions with MAOI therapy, however the majority of the previous reactions were due to the consumption of spoiled food. Evidence does not support the restriction of the following foods listed if the food is fresh (McCabe, 1986).
FOODS WITH INSUFFICIENT EVIDENCE FOR RESTRICTION (McCabe, 1986)
anchovies - cream cheese - raisins
beetroot - cucumbers - salad dressings
chips with vinegar - egg, boiled - snails
Coca Cola (R) - figs, canned - tomato juice
cockles - fish, canned - wild game
coffee - junket - worcestershire sauce
corn, sweet - mushrooms - yeast-leavened bread
cottage cheese - pineapple, fresh
Any protein FOOD, improperly stored or handled, can form pressor amines through protein breakdown. Chicken and beef liver, liver pate, and game generally contain high amine levels due to frequent mishandling. Game is often allowed to partially decompose as part of its preparation. Ayd (1986) reported that the freshness of the food is a key issue with MAOIs and that as long as foods are purchased from reputable shops and stored properly, the danger of a hypertensive crisis is minimal. Some foods should be avoided, the most dangerous being aged cheeses and yeast products used as food supplements (Gilman et al, 1985).
With appropriate dietary restrictions, the incidence of hypertensive crises has decreased to approximately 4% (Zisook, 1985). Treatment of a hypertensive reactions includes the=7F administration of phentolamine (Anon, 1989) 2.5 to 5 milligrams intravenously (slow) titrated against blood pressure (Zisook,=7F 1985; Lippman & Nash, 1990). One report has suggested that the use of sublingual nifedipine 10 milligrams was effective in treating 2 hypertensive reactions following the ingestion of a tyramine-containing food in a patient receiving MAOI therapy (Clary & Schweizerr, 1987). Chlorpromazine also has alpha-blocking properties and has been recommended as an agent for discretionary use (patient-initiated treatment) in the setting of dietary indiscretion (Lippman & Nash, 1990).
Dietary restrictions are required for individuals receiving monoamine oxidase inhibitor therapy to prevent a hypertensive crisis and other side effects.
The foods listed in the dietary restrictions have been categorized into those foods that must be avoided, foods that may be ingested in small quantities, and those foods that were previous implicated in reactions but upon analyses of fresh samples only a small tyramine content was identified and should be safe to consume if freshness is considered.
1. Anon: Foods interacting with MAOI inhibitors. Med. Lett. Drug Ther. 1989; 31:11-12.
2. Ayd FJ: Diet and monoamine oxidase inhibitors (MAOIs): an update. Int. Drug Ther. Newsletter 1986; 21:19-20.
3. Brown CS & Bryant SG: Monoamine oxidase inhibitors: safety and efficacy issues. Drug Intell. Clinical Pharmacy 1988; 22:232-235.
4. Clary C & Schweizer E: Treatment of MAOI hypertensive crisis with sublingual nifedipine. Journal Clinical Psychiatry 1987; 48:249-250.
5. Da Prada M, Zurcher G, Wuthrich I et al: On tyramine, food, beverages and the reversible MAO inhibitor moclobemide. J. Neural Transm. 1988; 26
6. Gilman AG, Goodman LS & Rall TW et al (Ed): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 7th ed., Macmillan Publishing,
New York, NY, 1985.
7. Lippman SB & Nash K: Monoamine oxidase inhibitor update. Potential adverse food and drug interactions. Drug Safety 1990; 5:195-204.
8. McCabe BJ: Dietary tyramine and other pressor amines in MAOI regimens: a review. J. Am. Diet Assoc. 1986; 86:1059-1064.
9. Stockley I: Alcohol-free beer not safe for MAOI patients. Pharm. J. 1993; 250:174. 10. Zisook S: A clinical overview of monoamine oxidase
inhibitors. Psychosomatics 1985; 26:240-251.
Theodore G. Tong, Pharm D/C Hansen
Assistant Clinical Professor of Pharmacy
University of California
San Franscisco, California 94143
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Stephen R. Saklad, Pharm.D. - firstname.lastname@example.org
Psychiatric Pharmacy Program
The Univ Texas College of Pharmacy
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