353 ]. Milk Food Techno[. Vol. 39, No. 5, Pages 353-358 (Jvfay, 1976) Copyright @ 1976, International Association of Milk, Food, and Environmental Sanitarians Biologically Active Amines in Food: A Review S. L. RICE, R. R. EITENMILLER, and P. E. KOEHLER Department ofFood Science University ofGeorgia, Athens, Georgia 30602 (Received for publication November 11. 1975} Downloaded from http://meridian.allenpress.com/jfp/article-pdf/39/5/353/2397438/0022-2747-39_5_353.pdf by guest on 27 September 2021 ABSTRACT psychiatric patients. Hypertensive attacks during MAOI Biologically active amines are normal constituents of many foods and treatment were first reported in 1955 (49). Blackwell (7) have been found in cheese; sauerkraut; wine; and putrid, aged, or tirst observed an association between hypertension crises fermented meats. These low molecular weight organic bases do not of patients on MAOI (tranylcypromine) and possible represent any hazard to individuals unless large quantities are ingested dietary precipitants (cheese). Asatoor et al. (3) implicated or natural mechanisms for their catabolism are inhibited or genetically tyramine in cheese as the primary causative agent. deficient. Tyramine, histamine, and phenethylamine. which can arise from enzymatic decarboxylation of the corresponding amino acids, are During the early 1960's many reports of hypertension strongly vasoactive. Histamine, a capillary dilator. produces crises of patients on MAOI were reported in the hypotensive effects while tyramine and phenethylamine cause a rise in literature. The principle foods implicated in these first blood pressure. Phenethylamine has been implicated in the onset of attacks included cheese and yeast extract. In addition to migraine headache attacks. The occurrence, mechanism of formation, the reports of hypertension crises in the literature, there and catabolism of these compounds is reviewed. are reports connecting tyramine, serotonin, and phenethyamine to migraine headaches (1. 2). The role of INTRODUCTION amines in migraines is presently being investigated. Since Asatoor et al. (3) associated tyramine in cheese to Biologically active amines (biogenic amines) have been pressor attacks in MAOI patients, considerable research defined as aliphatic, alicyclic, or heterocyclic organic has been completed dealing with the appearance of bases of low molecular weight which arise as a biologically active amines in foods. The objective of this consequence of metabolic processes in animals, plants, and microorganisms (28). Biogenic amines are generally review is to present information on the physiological effects of various biologically active amines, to either psychoactive or vasoactive. Psychoactive amines summarize the quantitative data that are available in the act on the neural transmitters in the central nervous literature, and to discuss factors that lead to amine system, while vasoactive amines act, either directly or formation. indirectly, on the vascular system (43). Pressor amines are vasoactive amines that cause a rise in blood pressure. In 1901, Barger and Walpole (5) first identified tyramine, TYRAMINE AND HYPERTENSIVE CRISES phenethylamine, and isoamylamine as the pressor Hypertension attacks during treatment with ipron­ principles of putrid meat. Tyramine was the most active iazid, a monoamine oxidase inhibitor (MAOI), were of the pressor amines. It is now well known that first reported by Ogilvie in 1955 (49). Initially. MAOI phenethylamine derivatives including tyramine, do­ were used to treat patients with pulmonary tuberculosis pamine, and norepinephrine cause a marked increase in and later for general treatment of depression in blood pressure when injected intravenously into psychiatric patients. With increased use of the drugs, mammals. Serotcmin and histamine are also strongly more pressor attacks were reported. Davies (19) reported vasoactive (30). Histamine, in contrast to tyramine, is a hypertension attacks in patients on nialamide and Clark strong capillary dilator and can produce hypotensive (1 7) and Blackwell (6) observed cases of hypertension effects. crises in patients on tranylcypromine. Up until this time Biologically active amines are normal constituents of no connection betwen the attacks and dietary factors had rnany foods, but they usually do not r<epresent ,,_ny hazard beer: observed. Blackwell in 1963 (7) first reported that ches~c; may be the dietary precipitant in the hypertensive 354 RICE, EITENMILLER, AND KOEHLER (3) Asatoor et a!. examined several cheeses for tyramine TABLE 2. Histamine and tyramine contents o{ cheesesa and found concentrations up to 2 mg of tyramine/g of Cheese Hil>t<.tmi!:t: Re!"rren~e~ cheese and 25.4 f..lg/g of wine. Controlled studies of a Cheddar 0-1,300 0-1,500 3. 8,23,35,55. 62 hospital patient given tyramine and cheese containing Camembert 0-480 20-2.000 3. 35, 55,62 tyramine showed that there was only a minor response to Emmenthaler 225-1,000 3. 35 the cheese or tyramine in the absence of MAOI. This Brie 0 0-260 35,55. 62 Stilton blue 0 460-2.170 35.55. 62 individual, after MAO inhibition with paraglyline, Processed 0 0-50 35.55. 62 showed a marked increase in blood pressure, Gruyere 516 35 accompanied by headache with ingestion of both cheese Gouda 0-850 20-670 23.55.62 Brick, natural 524 55 and tyramine. Mozzarella 0 0-410 55. 57,62 Tyramine acts pharmacologically by releasing Blue or Roquefort 0-2.300 27-1,100 55, 62 norepinephrine from tissue stores which in turn causes a Boursault 0 110-1,116 55,62 Parmesan 0-58 4-290 55. 57,62 Downloaded from http://meridian.allenpress.com/jfp/article-pdf/39/5/353/2397438/0022-2747-39_5_353.pdf by guest on 27 September 2021 rise in blood pressure (28). Tyramine has 1/20-1/50 of Romano 0-161 80-238 55. 57.62 the ability of epinephrine to increase blood pressure (3). Provolone 10-525 J8.J50 55,57 MAO inhibitors increase the tissue stores of Swiss 0 0-1.800 62 Colby 0-500 100-560 62 norepinephrine and thus potentiate the action of Edam 0 300-320 62 tyramine. Symptoms of hypertensive crisis include high Cottage 0 0 62 blood pressure, headache, fever, and sometimes Others 0-2.600 0-660 62 perspiration and vomiting (11, 30). MAO inhibitors still 3 Table adapted from Lovenberg (43). being used as antidepressants include isocarboxazid, b A dash means the cheese was not tested for this amine and 0 indicates that the level of the amine was below the detection threshold. Values nialamide, phenelzine sulfate, and tranylcypromine represent ranges or quantities present in the selected samples and sulfate (50). should not be interpreted as averages. Numerous other reports of hypertensive crises occur in the literature. Foods that have been implicated include chocolate (39), yeast extract (10), beef liver (12), chicken of tyramine than do fruits and vegetab!t~ and are livers (32), broad beans (34), and pickled herring (48). It considerably more dangerous to the tyramine-susceptible appears that tyramine is the major offender in individual. Of the other foods, yeast extract, salted dried precipitating hypertensive crises. In man, 20-80 mg of fish, pickled herring and the meat samples indicated in tyramine injected intraveneously or subcutaneously Table 3 could possibly be dangerous. cause a marked elevation of blood pressure (3). In individuals on MAOI, as little as 6 mg taken orally can HISTAMINE cause a rise in blood pressure. The tyramine contents of Histamine has been implicated in several outbreaks of fruits, vegetables, cheese, and other foods are given in food poisoning. Ferencik et a!. (26) showed that several Tables l, 2, and 3. It appears unlikely that tyramine in samples of tuna fish, which gave intoxication symptoms fruits and vegetables could precipitate hypertension in people after consumption, contained considerable attacks unless large quantities are consumed. Cheeses quantities of histamine (204-464 mg/100 g). Doeglas et and some sausages contain much higher concentrations al. (22) indicated histamine to be the cause of TABLE 1. Vasoactive amines in Apple Avocado 10 23 4-5 0 Banana (peel) 50-150 0 65 700 122 Banana (pulp) 28 0 7 8 2 Egg plant 0 0 Grape 0 0 0 0 0 Grapefruit juice 0 55 Orange 0 0.1 10 0 + 59 Passion fruit 1-4 27 Pawpaw 1-2 27 Pineapple juice 25-35 0.36 13,55 Plantain 45 59 Potato 0 0 0 0.1-0.2 59 Blue plum 0 5 59 Red plum 10 0-2 6 0 + 59 Red blue plum 8 2 59 Raspberry 13-93 4 Spinach 0 0 1 0 0 59 Tomato 12 4 4 0 0 59 aFrom Lnvenberg (43) b A dash m:ans the food was not tested for this amine, 0 means that the level of the amine was below the detection threshold. and + indicates the J!!atcrial contained a trace of the amine. AfvtiNES IN FOOD 355 TABLE 3. Histamine and tyramine contents of foods other than oxidase, may potentiate effects of histamine-containing cheesea foods on the patients involved. References 35. 55 Wines 0-22 35.45.51,55,58 /CH2 COOH /CH2 CH2NH2 Yeast extracts 210-2,830 9,35, 55 r=l =-r"l ,r----1 Fish Tuna 2.040-5,000 26, 36,37 N~NH N~NCH 5 Salted dried lmidaroleocetle ocld 1-Mothylhlstamlno tlsh 0-470 55 Pickled herring 3,000 48 Meat Meat extracts 95-304 55 Beef liver 274 12 Chicken liver 100 32 Downloaded from http://meridian.allenpress.com/jfp/article-pdf/39/5/353/2397438/0022-2747-39_5_353.pdf by guest on 27 September 2021 Sausage 0.74-410 0-1237 14,21.52 Miscellaneous /CH CH NH Soya sauce 1.76 55 \I2 2 2 Sauerkraut 7-200 20-95 44 1,-------('1 aTable adapted from Lovenberg (43). N~NH b A dash means the food was not tested for this amine, and 0 indicates that the level of the amine was below the detection threshold.