N Methyl Tyramine
Also known as: NMT, N-Methyltyramine
Overview
N-Methyltyramine (NMT) is a naturally occurring protoalkaloid found in various plants, including citrus species, and is often included in dietary supplements. Structurally related to tyramine, it is classified as a phenethylamine and acts as a trace amine. NMT is primarily marketed for its potential stimulant effects, particularly in weight management and sports performance supplements, due to proposed lipolytic and metabolic stimulation properties. It interacts with monoamine oxidase (MAO) enzymes and trace amine-associated receptors (TAARs), influencing neurotransmitter systems and metabolic pathways. While several in vitro and ex vivo studies exist, human clinical trials are limited, and no comprehensive systematic reviews or meta-analyses specifically on NMT supplementation in humans have been conducted.
Benefits
Research indicates that NMT can stimulate glucose uptake in human adipocytes, similar to tyramine, suggesting potential metabolic effects on fat cells, such as enhanced glucose transport. This effect has been observed in ex vivo studies, demonstrating a statistically significant cellular response. However, NMT is not considered a direct lipolytic agent capable of significantly promoting fat mobilization or oxidation in humans. Its potential secondary effects include indirect sympathomimetic activity via its role as an MAO substrate, leading to the production of hydrogen peroxide and activation of glucose transporter translocation. There is no robust clinical data to support specific benefits in human populations, and the observed cellular effects have not been translated into clinically significant outcomes or fat loss in human trials.
How it works
N-Methyltyramine primarily acts as a substrate for monoamine oxidase (MAO) enzymes. This interaction leads to oxidative deamination and the production of hydrogen peroxide, which subsequently triggers glucose transporter translocation in adipocytes, thereby stimulating glucose uptake. NMT may also interact with trace amine-associated receptors (TAARs), potentially influencing sympathetic nervous system activity, although direct evidence for this specific interaction with NMT is limited. Its influence on adipocyte glucose metabolism and possible sympathetic nervous system signaling are the main proposed mechanisms. The exact pharmacokinetics and bioavailability in humans are not well characterized, but it is assumed to have oral bioavailability.
Side effects
Comprehensive human safety data for N-Methyltyramine are lacking, but it is presumed to have a safety profile similar to other trace amines with potential sympathomimetic effects. Common side effects are not well documented, but there is a potential for cardiovascular stimulation due to its sympathomimetic activity. Uncommon and rare side effects are unknown due to the absence of clinical data. A significant concern is its potential interaction with MAO inhibitors (MAOIs), which could increase the risk of hypertensive crises, similar to interactions seen with tyramine-containing substances. Therefore, NMT is likely contraindicated for individuals taking MAOIs or other sympathomimetic drugs. Safety in pregnant, lactating, pediatric, or cardiovascular-compromised populations has not been established, and caution is advised.
Dosage
The minimum effective dose for N-Methyltyramine in humans has not been established. Consequently, optimal dosage ranges are also not defined. Doses used in in vitro studies are typically in the millimolar range, which are not directly translatable to human oral dosing. The maximum safe dose is unknown, and caution is strongly advised due to the potential for sympathomimetic effects. There are no established timing considerations for NMT supplementation. It is typically found in oral supplement formulations, but there is no data on alternative routes of administration. Absorption factors and required cofactors for its efficacy are also unknown.
FAQs
Is NMT a direct fat burner?
No, current evidence indicates NMT does not directly promote lipolysis or fat oxidation in humans, despite some cellular effects on glucose uptake.
Is NMT safe with MAO inhibitors?
No, there is a potential for dangerous interactions, including hypertensive crises, due to NMT's activity as an MAO substrate.
Does NMT improve athletic performance?
There is no clinical evidence to support claims that NMT improves athletic performance in humans.
How quickly does NMT act?
Cellular effects on glucose uptake occur rapidly in vitro, but the clinical relevance and onset of action in humans are unclear.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9370673/ – This ex vivo study on human adipocytes found that N-Methyltyramine significantly stimulated glucose uptake, similar to tyramine. However, it concluded that NMT was not a direct lipolytic agent, indicating it does not directly promote fat breakdown. The study provides robust cellular data but lacks human clinical translation.
- https://www.mypcnow.org/fast-fact/non-oral-pharmacotherapy-options-for-depression/?print=print – This systematic review/meta-analysis focuses on MAO inhibitors and highlights the risks associated with tyramine-like compounds when combined with MAOIs. While not directly about NMT, it provides crucial context for potential safety concerns regarding NMT's interaction with MAOIs due to its similar biochemical properties.
- https://pubmed.ncbi.nlm.nih.gov/25274429/ – This narrative review summarizes the receptor interactions and pharmacological effects of NMT and related amines. It provides an overview of NMT's biochemical properties but lacks the systematic methodology of a high-level evidence review and does not include human RCT data on NMT supplementation.