What is N-Methyltyramine?

Beer pong. It’s derailed many of our college ambitions. What you may not know is that garden variety suds contain N-Methyltyramine – a prohibited substance in sport and also an ingredient on the FDA’s Dietary Supplement Ingredient Advisory List. N-methyltyraminehas also gained prominence as a pre-workout and fat burner in dietary supplements. Say it isn’t so, even beer is banned in sport??? Well yes and no. We try to unravel the facts on N-Methyltyramine.

Where does N-Methyltyramine come from?

N-Methyltyramine is also known as 4-hydroxy-N-methylphenethylamine or NMT for short. It can befound naturally in plants such as cacti, acacia, and bitter orange, but it was first discovered in 1950 in the same barley used to make beer. One publication in 1977 outlined hundreds of plant species that contain phenethylamine derivatives, including 57 that contained N-methyltyramine. NMT is present at about 2mg/g in malted barley.A pint of beer contains around 2.3 – 3.8 mg/pint of N-Methyltyramine. Milligram quantities mean these are relatively high amounts, not trace levels. It is likely that the NMT found in many dietary supplements has been synthesized. N-methyltyramine is also a human trace amine, meaning you can find it naturally in the human body.

N-methyltyramine stimulant pre-workout and fat burner supplements.

As a stimulant and pre-workout ingredient N-methyltyramine is typically found in the 20-200 mg range. It is often included in proprietary blends with no specific amount listed making it hard to figure out exactly what you are getting. Despite N-methyltyramine appearing on the FDA Dietary Supplement Ingredient Advisory List it still shows up in 53 products on the NIH Dietary Supplement Label Database as of July 2022.

Is N-Methyltyramine a legal Dietary Supplement Ingredient?

Theoretically NMT could be a legal dietary supplement ingredient if it is present in a natural extract of a plant, or if it is demonstrated to be a component of something used prior to 1994 as an old Pre-DSHEA Dietary Ingredient. On its own as a synthesized chemical N-Methyltyraminedoes not appear to qualify as a legal dietary supplement ingredient. The U.S. FDA lists N-Methyltyramine on the Dietary Supplement Ingredient Advisory List.

N-MethyltyramineClaims and Potential Benefits

N-Methyltyramine is naturally present in barley and bitter orange (citrus aurantium). The latter also contains other stimulants like synephrine and octopamine. Citrus aurantium and synephrine have been popular stimulant and weight loss ingredients in supplements for years. So, the theory is that N-Methyltyramine, being a phenethylamine derivative, makes it a perfect ingredient for anyone looking to improve athletic performance and lose weight. It’s marketed as helping with the following:

– Increased focus
– Heightened concentration
– Improved mood
– Helps regulate appetite
– An improve ability to breakdown fat
– Amplified energy levels

Whether N-Methyltyramine will produce these effects is unclear. Results may be significantly different due to varying amounts of NMT usedin different supplements, and everyone may react in a unique way to this ingredient. While the amount of NMT in beer is likely not enough to have much of a stimulant effect the higher amounts used in supplements are designed to make the user feel the ingredient’s effects.

Is N-Methyltyramine a fat burner?

Will N-Methyltyraminework as a stimulant or fat burner?The short answer is, not really.
All the potential benefitsas a stimulant or fat burner were recorded in rodents. They have not been replicated in human trials. In humans, it’s only been explored to treat ailments such as hypotension and gastrointestinal disorders. This means itmay not offer the touted benefits to the user.

N-Methyltyramineis somewhat under-studied so it can be tough to detail exactly what benefits, or negatives, you’ll actually receive if you supplement with it. In animal research, it’s reported to stop fats from breaking down and even increase mice’s urge to eat. Oddly, these effectswouldn’t be ideal if the same effect was replicated in a human who wanted to lose weight. One study noted ironically, “NMT may promote weight gain rather than weight loss through enhanced appetite and increased absorption of foods.” You might want to think twice if you are thinking about using NMT as a fat burner especially if you are a drug tested athlete, as NMT is prohibited in sport.

N-Methyltyramine Side Effects

While there might be purported benefits there are also N-methyltyramineside effects to consider. Sites that promote NMT also note some of the side effects and issues with the substance.

N-methyltyramine side effects have been reported among users including:
– Stomach aches
– Headaches
– Accelerated heart rate
– High blood pressure

Is N-Methyltyramine Banned in Sport?

N-Methyltyramine is technically banned in sport even though it is isn’t listed by name and there hasn’t been a positive drug test reported for it yet. In 2015, the World Anti-Doping Agency (WADA) added “Phenethylamine and its derivatives” to the WADA Prohibited List that governs Olympic sport. They did so in response to a novel phenethylamine derivative being found in a pre-workout supplement called Crazethat had caused a positive drug test. The substance found was a close cousin to amphetamine and WADA called a positive drug test based on the substance having a ‘similar chemical structure or similar biological effect’ as others on the list, only the second time this had been done with DMAA being the first. The significance of the phenethylamine ban was vast as it now placed hundreds of natural products and plant extracts like n-methyltyramine that are phenethylamine derivatives in a grey area as they could now be interpreted as prohibited.Phenethylamine itself is present in soybeans, peas, and even chocolate.

The Global Drug Reference Online is a “partnership between UK Anti-Doping (UKAD), the Canadian Centre for Ethics in Sport (CCES) and the United States Anti-Doping Agency (USADA). The Japan Anti-Doping Agency (JADA) and the Australian Sports Anti-Doping Authority (ASADA) are official Global DRO licensees.” The Global DRO “provides athletes and support personnel with information about the prohibited status of specific substances under the rules of sport based on the current World Anti-Doping Agency (WADA) Prohibited List.”The Global DRO indicates that N-Methyltyramineis prohibited under the S6 – Stimulant category, even though NMT is not actually listed by name on the WADA Prohibited List. This would make NMT prohibited in competition, but not out of competition for most drug tested athletes.

Will N-Methyltyramine Make You Fail a Drug Test?

N-Methyltyramine as a phenethylamine derivative clearly qualifies as a banned substance but it does not appear to be targeted yet in sport drug testing. This is supported by the statistics on adverse analytical findings in the WADA system that do not show any findings for N-Methyltyramine from 2006-2020. N-Methyltyramineappears to fall into a unique category. A drug banned by interpretation of the list language, but not actually in practice. Many naturallypresent compoundsshare a similar predicament.

If it were to be targeted in sport drug testing urine thresholds would apply to avoid positives from environmental presence. S6 – Stimulants have a reporting threshold of 50 ng/ml in urine drug testing under the WADA Technical Document TD2022MRPL. Could beers on the night of a cycling race, or three beers a week before a swim-meet potentially impact a drug test? It’s unclear, but possible given that you ingest low milligram quantities of NMT in just one pint and drug testing labs can easily detect parts per billion or nanogram levels in urine. This example illustrates one of the main challenges faced by anti-doping testing, namely that you must be able to distinguish natural or environmental presence of a substance from purposeful doping if you are going to operate a fair system.

N-MethyltyraminevDMAA

The battle for supremacy in stimulant pre-workout ingredients has been raging since at least 2012 pitting N-Methyltyramine versus DMAA. Interest in N-Methyltyramine surged as companies looked for alternative ingredients for popular stimulants like DMAA (dimethylamylamine, or methylhexaneamine). DMAA has been used for weight loss and to enhance performance as stimulant. DMAA was often disguised as natural geranium oil extract in an effort to legitimize the substance and throw off regulators. Thisconnection led some people to believe geranium oil is banned (it’s not). Geranium oil has been used for centuries to treat anxiety, depression and even has anti-inflammatory properties. In its natural form, it has been used for centuries.

Instead of geranium oil, supplement makers were using the synthetic chemical, DMAA, in significant amounts. It wasn’t long before DMAA became perhaps the most popular stimulant pre-workout ingredient ever. It ran into trouble after serious adverse events and even deaths prompting the U.S. FDA and other authorities to address DMAA in 2013 and remove it from the market. It is now an illegal supplement ingredient although it can still be found in some dietary supplements and can be easily purchased.At the peak of popularity in 2012, DMAA was the most common stimulant reported and the third most reported drug in the WADA system with 320 adverse analytical findings.N-Methyltyramine was offered as replacement for DMAA and is still found today in supplements.