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MAOI Diet Addendum

Posted by SalArmy4me on August 4, 2001, at 22:53:48

Walker, Scott E. MScPhm. Shulman, Kenneth I. MD, SM, FRCP(C). Tailor, Sandra A.N. PharmD. Gardner, David BScPhm. Tyramine Content of Previously Restricted Foods in Monoamine Oxidase Inhibitor Diets. Journal of Clinical Psychopharmacology. 16(5):383-388, October 1996"

"It has been clearly demonstrated that individuals who are taking MAOIs are more sensitive to the pressor effects of tyramine. [15] A critical issue in dietary restriction relates to the amount of tyramine that will produce an increase in blood pressure. Both Blackwell and Mabbitt [16] as well as Horowitz and associates [17] have observed increases in blood pressure with the ingestion of only 6 mg of tyramine. However, Blackwell and Mabbitt [16] were unable to reproduce these results on rechallenge with 6 mg in the same subject. Bieck and Antonin [15] demonstrated that an 8-mg oral dose of tyramine is sufficient to increase systolic pressure by 30 mm Hg in 50% of subjects receiving tranylcypromine. However, they also demonstrated a wide intra-individual variation in responses in some patients that may be due to variability in both the rate and extent of absorption. Furthermore, many foods have been reported to contain variable amounts of other pressor agents [18-21] that may also increase blood pressure, possibly contributing to variable response. [15,16] Therefore, we have used a conservative upper limit of 6 mg of tyramine as a guideline for safe ingestion. This is identical to the limit that we have used previously. [7,8,11]

In this study, we again analyzed an Italian Chianti wine and found no tyramine. This is in agreement with the low or negligible levels reported by others. [8,13] Chianti wine has been widely restricted for many years based on a single report of a tyramine concentration of 25.4 mg/liter. [17] However, case reports of hypertensive crises associated with this or other wines are lacking.

It is of interest to note that in our assay, if we eliminate sodium lauryl sulfate (which acts as a counter ion) from our mobile phase, a compound in Chianti wine coelutes with tyramine. Liquid chromatographic columns can separate this coeluting peak with varying degrees of success. Therefore, it seems possible that the long-standing restriction of Chianti wine may have been due to analytical interference that led to an overestimation of the tyramine content. This points out the need to carefully validate the analytical method before reporting tyramine concentrations.

By far, most reported fatal and nonfatal MAOI-related hypertensive reactions have been associated with the ingestion of cheese. [8] The restriction of all aged cheeses is universally accepted. However, not all cheeses should be banned. In this study, we analyzed mozzarella cheese and found extremely low amounts (0.01 mg/g), even when stored at room temperature for 5 days. The content of this part-skim mozzarella cheese is much lower than the 0.16 mg/g observed in our previous report of mozzarella cheese (28% milk fat). [8] Nevertheless, both concentrations would be regarded as safe when less than 30 g of cheese is ingested. Furthermore, the tyramine content provided in the current report is similar to the low concentrations reported for other mild and fresh varieties of cheeses such as cottage cheese, cream cheese, ricotta, and processed cheeses. [8,19,13,16] In this study, we also analyzed the tyramine content of the packaged cheese powder found in a Kraft Macaroni & Cheese Dinner (Kraft Foods, Inc., Glenview, IL) and found no tyramine.

In this study, we analyzed only one beer, a bottled German beer (Beck's, Brauerei Beck & Co., Bremen, Germany) and found it to contain small amounts of tyramine (1.0 mg/liter). This is in agreement with the results of the analysis of other bottled beers analyzed by our group [8,11] and others. [17,22,23] However, we have previously reported alarmingly high tyramine concentrations of tyramine (27.05-112.91 mg/liter) in four tap beers [11] and suggest that storage and contamination of the hose from the keg to the tap may provide conditions conducive to the production of tyramine. We recommend that tap beers be avoided by patients who are taking MAOIs, and because no bottled or canned beers from North American breweries have been identified as containing dangerous amounts of tyramine, we acknowledge that these can be consumed in moderation.

A number of investigators have reported that banana pulp is safe, [8,24] although the peel has been observed to contain moderate to high amounts of several vasoactive substances, including serotonin, dopamine, and noradrenaline in addition to tyramine. [25] In this study, we observed the skin of a blackened banana to contain 2.58 mg of tyramine, whereas the pulp of each of two blackened bananas contained less than half this amount. Both of these bananas had been stored at room temperature for more than 1 week beyond the time when they were a ripened yellow. In our previous study, the tyramine content of a fresh banana was below the limit of detection and one whole peel was observed to have 1.42 mg of tyramine. [8] Although the tyramine content does appear to have increased with storage, this could easily be due to the variability in content between bananas. Furthermore, the bananas tested in this study, even after prolonged storage, did not contain dangerous amounts of tyramine. Therefore, we conclude that the pulp of an overripe banana is safe.

Coffin [24] reported that raspberries contain 0.048 mg/g of tyramine (range: 0.013-0.093 mg/g). Our own analysis of raspberries with different presentations (e.g., stored at room temperature or refrigerated for 4 days, with or without mold, in jam, and frozen) yielded tyramine concentrations ranging from 0 to 0.001 mg/g for berries and 0.021 mg/g for a frozen berry product. Based on our results and those of Coffin as well as the observation that there are no reports linking raspberries to hypertensive episodes, we conclude that raspberries are safe.

Prepared and sliced meat products
Fresh, sliced cold meat and other meat products were analyzed in this study and generally found to contain low amounts of tyramine per 30-g serving. This is in agreement with our previous report. [8] We also chose to analyze some canned meat and pasta products (Chef Boyardee, American Home Products, Inc., Madison, NJ) and found them to contain safe amounts of tyramine per serving.

The freshness of meat, specifically chicken livers, has been identified as a factor affecting the amount of tyramine. [26] In this study, we observed fresh chicken liver to contain very small amounts of tyramine. However, after 9 days' storage at room temperature, the tyramine content had soared to 2.13 mg/g. Although the chicken liver stored for 9 days at room temperature could not have been mistaken as fresh, and would not likely have been prepared and eaten by anyone, it does illustrate a point about freshness. A previous evaluation of chicken liver indicated that storage in the refrigerator for 5 days increased the tyramine concentration from 0 to 0.051 mg/g. [8] The current method adjusted the storage conditions only to create a definitive test of freshness on tyramine in chicken liver.

As for cheeses, the degree of aging and variety of cured meats (e.g., salami, mortadella, pastrami) are tremendous and tyramine content can range from low and safe amounts to dangerously high levels. [8,9,21] Of most concern are the air-dried sausages, for example, salami. As sausages dry, an increase in the liberation of free amino acids has been observed to occur. [27] Because sausage can contain microorganisms with decarboxylase activity, [28] tyrosine can be converted to tyramine during the drying process. In this study, we tested a variety of air-dried sausages, analyzing samples taken both from the core and outer rim (next to the skin). In three of the four samples, the sample nearest the skin contained 20 to 360% more tyramine, whereas in the fourth sample the concentration in the center of the sausage was sevenfold higher than the sample taken from the area next to the skin. Of the 10 sausages tested, 2 were observed to contain more than 6 mg of tyramine per 30-g serving, and 2 others were observed to contain between 4 and 6 mg. Therefore, although there are no case reports associating air-dried sausages with hypertensive episodes, we recommend that air-dried sausages continue to be a dietary restriction for patients receiving MAOIs because of the variability in tyramine content among sausages and because of the likelihood that a serving will be greater than 30 g. However, as was pointed out previously, this restriction does not include fresh sliced-meat products, such as sliced cooked ham.

In this study, sauerkraut was observed to have a significant tyramine content per serving, (0.031 mg/g). This amount is lower than previously reported by Shulman and colleagues [8] (0.055 mg/g) but still within the range (0.020-0.095 mg/g) reported by Lovenberg [25] and Da Prada and associates. [9] All of these reports suggest a potentially dangerous tyramine content per serving, yet there are no case reports linking sauerkraut to hypertensive episodes. It is possible that the tyramine in sauerkraut may not be completely bioavailable or that the rate of absorption of tyramine from sauerkraut is slow, producing little change in blood pressure. However, in view of the confirmed high tyramine concentration per serving of sauerkraut, we recommend that it be restricted in patients on a regimen of MAOIs.

Improperly stored or spoiled food can create an environment where tyramine concentrations may increase. These foods must have either free tyrosine or tyrosine liberated on storage, which is then converted to tyramine by microorganisms with decarboxylase enzymes. [27] This was shown to occur with the chicken livers stored at room temperature for 9 days and is the postulated mechanism for production of tyramine in air-dried sausages and tap beers. [11] However, for a number of other foods (raspberries, mozzarella cheese, and bananas), improper or prolonged storage did not increase the tyramine content to unsafe levels. In these later cases, although conditions of growth were present, it is likely that either tyrosine was not liberated, was liberated in only small quantities, or decarboxylation activity was lacking.

Our analysis of a single chocolate bar (Toblerone, Kraft General Foods Canada Inc., Don Mills, Ontario, Canada; 35-g bar) failed to demonstrate measurable quantities of either tyramine or phenylethylamine, yet we did observe significant quantities of theobromine (2.78 mg/g) and caffeine (1.07 mg/g). The choice of a Toblerone chocolate bar arose from a case in which a young woman maintained on tranylcypromine (Parnate, SmithKline Beecham Pharmaceuticals, Oakville, Ontario, Canada) reported symptoms of dizziness, light-headedness, blurred vision, and headache 45 min after ingesting an unspecified amount of a Toblerone chocolate bar. The patient arrived at a hospital emergency department and was found to have normal blood pressure and heart rate, although she demonstrated slurred speech and pallor. We believe that many case reports, with only subjective findings that are not validated by objective measures, have led to the restriction of many foods. Headaches, which can occur for a variety of reasons, can also occur with chocolate ingestion in patients who are not taking MAOIs. In these cases, the cause does not appear to be related to either tyramine or phenylethylamine. We would suggest that this reaction may have been due to the stimulant effects of the methylxanthines (theobromine and caffeine).

Soy sauce and other soy bean preparations have been found to contain tyramine in significant concentrations, [9,10,29] whereas others have reported low concentrations. [8,13] From an analysis of Far Eastern cuisine, Da Prada and Zurcher [10] reported tyramine concentrations of 293 mg/liter and 878 mg/liter in two samples of soy sauce. Similarly, high concentrations (941 mg/liter) of tyramine were observed in the single soy product tested in this study. As with some other foods, the variation in tyramine content reported in various studies and between different soy sauce products creates a potential hazard. We recommend that soy sauce be avoided by patients taking MAOIs but acknowledge that patients may be able to ingest some brands without serious consequences...."




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