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- Diabetes – 5
- Fat loss - 5
- Tyramine should not be taken by those who are being treated with a monoamine oxidase inhibitor (MAOI).
- May increase blood pressure and heart rate, especially in higher amounts.
- Some people report unusual sensitivity to dietary tyramine. Although the scientific evidence does not presently support a link between dietary tyramine and adverse reactions in those who are not taking an MAOI, idiosyncratic reactions are always a possibility. For this reason, anyone choosing to take supplemental tyramine should start with a low dose to guage their reaction.
- Because there is little human research, tyramine does not have a well-established side effect profile.
Tyramine is a trace amine naturally found in the body and also found in multiple dietary sources. The highest concentrations of tyramine are found in aged cheeses and aged meat, but there are a multitude of dietary sources, including alcoholic beverages, some fruits and vegetables, chocolate, and many others. In insects, tyramine plays a similar role as a neurotransmitter to the role that epinephrine (adrenaline) plays in humans, while octopamine is seen as the insect equivalent of norepinephrine. Because it was only recognized as a neurotransmitter about a decade ago, comparatively little is known about tyramine [1]. In humans, tyramine either comes from dietary sources or is derived from the amino acid tyrosine. It is further metabolized into octopamine and ultimately synephrine. Like other trace amines, the biological actions of tyramine are generally attributed to its action as a "false neurotransmitter," and the relevance of its action at the trace amine receptor is not yet well known. This article discusses the biological actions of tyramine, possible supplemental uses, and possible side effects from both dietary and supplemental tyramine.
The primary established action of tyramine is increased release of norepinephrine (NE). Tyramine is actively transported into neurons and displaces NE, leading to intraneuronal release of NE [2]. After tyramine infusion in humans, blood levels of NE dose-dependently increase. Blood levels of epinephrine also increase, but the effect is very small [3]. The present experimental evidence indicates that tyramine is not a direct agonist or antagonist at any adrenoceptor subtype [4]. Because it increases NE, it is possible that tyramine increases fat loss, but no studies have yet examined this directly. An antidepressant effect could also be hypothesized.
Tyramine may also independently increase dopamine (DA) levels, but this effect is not yet well established. Tyramine can be enzymatically converted to dopamine in the liver via the enzyme CYP4502D6, but it is not yet clear if DA levels can be significantly increased in vivo through this mechanism. Another possibility is that tyramine causes DA release through the same mechanism through which it increases NE. IV administration of tyramine has been documented to increase blood DA levels [3]. However, multiple research teams have found that their tyramine samples were contaminated with dopamine, and although the degree of contamination was small (<1%), it was enough to significantly increase blood levels of DA. When the tyramine was stored properly, no clear effect on DA levels could be found. In vitro and animal studies also indicate that tyramine increases DA, but they may have been subject to the same contamination problems [5].
In addition to increasing neurotransmitter levels, tyramine also has biological actions through its interaction with monoamine oxidase (MAO). There are two isoforms of this enzyme, MAO-A and MAO-B, and tyramine is primarily oxidized by MAO-A [6]. This can result in the local production of hydrogen peroxide (H2O2), which can have an insulin-like effect on some cell types. In adipocytes (fat cells), tyramine stimulates glucose transport, stimulates lipogenesis (the creation of fat), and inhibits lipolysis (the breakdown of fat), an effect that can be blocked by inhibitors of MAO (MAOIs) or antioxidants such as glutathione and N-acetylcysteine, which prevent H2O2 formation [4, 6]. One study does contradict this, indicating that tyramine increases H2O2 in adipocytes but also increases forskolin-mediated cAMP generation (which is lipolytic) and beta-adrenergic mediated lipolysis [7]. The discrepancy may be explained by the different concentrations of tyramine used [4].
Although this may appear to be bad news, tyramine also stimulates glucose uptake in other insulin-sensitive tissues, such as cardiomyocytes and skeletal muscle. Although muscle tissue has relatively low MAO activity, it accounts for a significant proportion of body mass, and the total MAO content of skeletal muscle is the highest of any organ or tissue other than the liver [6]. Multiple studies have found that tyramine administration to diabetic rats increases glucose disposal and reduces hyperglycemia, an effect which occurs even at doses that have little effect on cardiovascular variables, and for this reason it has been suggested as a possible treatment for diabetes [6, 8]. However, it is unlikely that this avenue will be explored, as there are much more promising options for the treatment of diabetes.
As can be expected from a substance that increases NE, tyramine also affects cardiovascular variables when given in sufficient quantity. Systemic administration of tyramine leads to increased blood pressure and heart rate, and an excessive amount could ultimately lead to heart attack or stroke [9]. Tyramine was originally used as a model of naturally occuring sympathetic nervous system activation, but recent research suggests distinct differences between the effects of tyramine and natural sympathetic activation. Instead of being vasoconstrictive, tyramine leads to vasodilation. It increases systolic blood pressure but does not have a consistent effect on diastolic blood pressure, and heart rate is only moderately increased. This inconsistency has not yet been well explained, although an effect on DA release and epinephrine have both been suggested as possible explanations [3].
The cardiovascular effects of tyramine from dietary sources are unlikely to be significant, as the MAO system is highly efficient. Even moderate supplemental use will probably not have much of an effect on cardiovascular variables. The average fasted subject requires about 500 mg of tyramine orally for even a minimal increase in blood pressure, and taking tyramine with food decreases the bioavailability by approximately half. However, those who are being treated with some MAO inhibitors (primarily used as antidepressants) may get a hypertensive reaction with as little as 10 mg, while a high tyramine meal may contain as much as 20-40 mg [9].
Another reputed side effect from dietary tyramine is headaches, and for this reason low tyramine diets are often recommended to those who regularly experience headaches. Other than patients being treated with MAOI's, there is no direct evidence linking dietary tyramine with the occurence of headaches. Tyramine levels are increased in those with cluster headaches, but this does not establish a causal relationship [10]. A recent review of the available research on the subject of biogenic amines and food intolerance indicated that there was no evidence for a relationship between tyramine or other biogenic amines and food intolerance reactions, including headaches [11]. However, it is entirely possible that tyramine supplements containing higher amounts than those typically found in food could lead to headaches in susceptible individuals.
In conclusion, tyramine reliably increases NE, opening the door for a number of possible uses which have yet to be explored in the scientific literature. It is also very likely that it independently increases dopamine levels, as this is the best working explanation for the cardiovascular effects. While it should not be used by those taking some MAOI's, the possible dangers in normal individuals are very often overstated. For those who choose to use tyramine, a dose of 200 mg is recommended, as this is enough to significantly increase plasma levels [9], but is well within the safety range. As with any new stimulant, the starting dose should be very low and increased as tolerated.
No part of this article may be reproduced in any form without the permission of David Tolson or Mike McCandless.
