Monoamine oxidase inhibitors (MAOIs) were first introduced in the 1950s to treat depression.1,2 They are a separate class from other antidepressants, treating different forms of depression as well as other nervous system disorders.3 However, relatively soon after their introduction, MAOIs were quickly associated with a potentially fatal interaction with foods containing tyramine. Why is the interaction between tyramine and MAOIs relevant to a blog on soyfoods? Because there is erroneous information that all soyfoods need to be avoided by patients on MAOIs. This is simply not the case.
MAOIs inhibit the activity of monoamine oxidase, an enzyme which is responsible for degradation of brain neurotransmitters such as norepinephrine, serotonin, dopamine, and tyramine. Inhibiting degradation leads to higher brain levels of neurotransmitters, allowing them to continue to influence the cells that have been affected by depression.4
Patients that take MAOIs and consume tyramine-containing foods or drinks will exhibit high serum tyramine levels.5,6 A high level of tyramine can cause a sudden increase in blood pressure, called the tyramine pressor response.7 Even though it is rare, a high tyramine level can trigger a cerebral hemorrhage, which can even result in death. Initially, the low-tyramine diets patients were prescribed was very restrictive and based on limited scientific evidence;8 that diet has evolved to be more focused and less restrictive.9 In terms of intake recommendations, researchers have observed increases in blood pressure in response to 6 mg of tyramine.10,11 Bieck and Antonin12 demonstrated that an 8 mg oral dose of tyramine is sufficient to increase systolic pressure by 30 mm Hg in 50% of subjects receiving the MAOI, tranylcypromine. Most researchers use a conservative upper limit of 6 mg of tyramine as a guideline for safe ingestion.13
More than 20 years ago, Shulman and Walker14 advised patients taking MAOIs to avoid all soy products. Much more recently, a 2018 article from the Mayo Clinic listed soybeans and soy products as foods high in tyramine.15 Soy sauce was also listed as being high in tyramine, which as will be discussed, is consistent with the literature. However, in contrast to the literature, tofu, which was classified as a pickled or fermented food, was also said to be high in tyramine.
A 1986 position paper of the Academy of Nutrition and Dietetics recommended that patients taking MAOIs use soy sauce with caution.16 One year later, a case reported described the hypertensive effects of miso in a MAOI patient.17 Since these reports were published, other investigators have also reported significant concentrations of tyramine in miso and soy sauce, and natto,18 although the amounts can be quite variable.13,14,18-20 Miso, natto and soy sauce are fermented foods. Tyramine is present in extremely limited amounts in fresh foods; it results from the degradation of amino acids present in aging or deteriorating foods or fermented foods. But what about non-fermented soyfoods?
More than 20 years ago, it was reported that soymilk (250 ml) and tofu (100 g) contained 0.5 and 0.8 mg tyramine, respectively.13 Much more recently, Toro-Funes et al.20 reported values in the literature for the tyramine content of a variety of foods. Tofu was found not to contain tyramine, as did one sample of soymilk, although another sample contained 0.4 mg/250 ml. The evidence indicates that unfermented soyfoods contain at most extremely low levels of tyramine. So, why do some sources list tofu as a high tyramine food? Because although most tofu around the world is consumed in unfermented form, fermented tofu is also consumed (often referred to as “stinky tofu”). It is the fermented tofu that contains tyramine.21,22
Finally, no data on the tyramine content of soy protein isolate or concentrate was identified. However, given that soy protein isolate and concentrate are not fermented, and that soy protein has a long shelf-life, indicating it is relatively stable, it is reasonable to speculate that tyramine content of these products is extremely low.
In summary, for those on a low-tyramine diet, it may be prudent to avoid some fermented soy products. In contrast, the evidence indicates unfermented products do not pose a problem for MAIO patients.
- Culpepper L. Reducing the burden of difficult-to-treat major depressive disorder: Revisiting monoamine oxidase inhibitor therapy. Prim Care Companion CNS Disord. 2013;15.
- Rapaport MH. Dietary restrictions and drug interactions with monoamine oxidase inhibitors: the state of the art. J Clin Psychiatry. 2007;68 Suppl 8:42-6.
- Thase ME. The role of monoamine oxidase inhibitors in depression treatment guidelines. J Clin Psychiatry. 2012;73 Suppl 1:10-6.
- Baker GB, Coutts RT, McKenna KF, et al. Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review. J Psychiatry Neurosci. 1992;17:206-14.
- Flockhart DA. Dietary restrictions and drug interactions with monoamine oxidase inhibitors: an update. J Clin Psychiatry. 2012;73 Suppl 1:17-24.
- Brown C, Taniguchi G, Yip K. The monoamine oxidase inhibitor-tyramine interaction. J Clin Pharmacol. 1989;29:529-32.
- Sathyanarayana Rao TS, Yeragani VK. Hypertensive crisis and cheese. Indian J Psychiatry. 2009;51:65-6.
- Sullivan EA, Shulman KI. Diet and monoamine oxidase inhibitors: a re-examination. Can J Psychiatry. 1984;29:707-11.
- Gardner DM, Shulman KI, Walker SE, et al. The making of a user friendly MAOI diet. J Clin Psychiatry. 1996;57:99-104.
- Blackwell B, Marley E, Mabbitt LA. Effects of yeast extract after monoamine-oxidase inhibition. Lancet. 1965;1:940-3.
- Horowitz D, Lovenberg W, Engelman K, et al. Monoamine oxidase inhibitors, tyramine and cheese. JAMA. 1964;188:1108-10.
- Bieck PR, Antonin KH. Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs: comparison of brofaromine and tranylcypromine in healthy subjects. J Clin Psychopharmacol. 1988;8:237-45.
- Walker SE, Shulman KI, Tailor SA, et al. Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. J Clin Psychopharmacol. 1996;16:383-8.
- Shulman KI, Walker SE. Refining the MAOI diet: tyramine content of pizzas and soy products. J Clin Psychiatry. 1999;60:191-3.
- Hall-Flavin DK. MAOIs and diet: Is it necessary to restrict tyramine? (Accessed February 4, 2021). In; 2018.
- McCabe BJ. Dietary tyramine and other pressor amines in MAOI regimens: a review. J Am Diet Assoc. 1986;86:1059-64.
- Mesmer RE. Don’t mix miso with MAOIs. JAMA. 1987;258:3515.
- Mah JH, Park YK, Jin YH, et al. Bacterial production and control of biogenic amines in Asian fermented soybean foods. Foods. 2019;8.
- Shulman KI, Walker SE, MacKenzie S, et al. Dietary restriction, tyramine, and the use of monoamine oxidase inhibitors. J Clin Psychopharmacol. 1989;9:397-402.
- Toro-Funes N, Bosch-Fuste J, Latorre-Moratalla ML, et al. Biologically active amines in fermented and non-fermented commercial soybean products from the Spanish market. Food Chem. 2015;173:1119-24.
- Yang J, Ding X, Qin Y, et al. Safety assessment of the biogenic amines in fermented soya beans and fermented bean curd. J Agric Food Chem. 2014;62:7947-54.
- Wing YK, Chen CN. Tyramine content in Chinese food. J Clin Psychopharmacol. 1997;17:227; author reply -8.