What is Hordenine?
Hordenine – Get the Facts
Hordenine can be a common ingredient in stimulant-based pre-workout supplements. Curiously, it is also a chemical found in beer, which is similar its cousin N-Methyltyramine (NMT). Hordenine was named after barley as the name stems from the Latin species Hordeum. It is an alkaloid, part of the phenethylamine class with a chemical name of N,N-Dimethyl-p-hydroxyphenethylamine. Phenethylamine derivatives are now banned on the World Anti-Doping Agency (WADA) Prohibited List.
Amazingly, beer contains not just one compound banned in sport, but two in the form of NMT and Hordenine. Gulp! Hordenine also appears on the FDA’s Dietary Supplement Ingredient Advisory List. This means it is a not a legal dietary supplement ingredient and neither is NMT. So, if you see either of these on your supplement’s ingredient list then you could be at risk of failing a drug test.
Where does Hordenine come from?
You can thank nature for creating Hordenine, also known as N,N-Dimethyl-p-hydroxyphenethylamine, which can be found naturally in a variety of plants including barley, cacti and citrus like bitter orange, and even marine algae. A 1977 study of phenethylamines that can be found in plants discovered as many as 91 plant species that contain Hordenine.
It was originally extracted from a cactus species in 1894 and given the name Anhalin. In 1906 it was isolated from barley and given the more common name of Hordenine, which is used today. A study in 1983 reported there is 12-24 mg/L of Hordenine in beer. So, it is natural but only if it is extracted from one of the natural sources. It can also be synthesized.
Hordenine in Stimulant Pre-workout Supplements
As a stimulant and pre-workout dietary supplement ingredient, Hordenine can often be found as part of proprietary blends. This means it can be hard to know exactly how much is used in these products. In products that do list the amount it is commonly found in the 20-50 mg range.
Despite Hordenine being on the FDA Dietary Supplement Ingredient Advisory List it still appears in 359 products on the NIH Dietary Supplement Label Database. Being on the FDA Dietary Supplement Ingredient List doesn’t necessarily mean it is unsafe. Rather, it means that according to the FDA the ingredients do not appear to be lawful dietary supplement ingredients.
Hordenine Marketing Claims
Hordenine may have effects that are both expected and unexpected. Hordenine is most often used as a stimulant or mood enhancer in dietary supplements. It has been studied as a Monoamine Oxidase Type B (MAO-B) inhibitor and is suggested to have some anti-depressant and mood benefits. It is common to find it stacked with other stimulants or nootropic cognitive enhancers because it may be more beneficial in the presence of other stimulants. Some sources suggest that it may have fat burning properties, but this hasn’t been conclusively proven.
It’s marketed as helping with the following:
– Attention and alertness
– Fat burning
– Antibiotic and antimicrobial properties
– Skin protection
Does it really work as a stimulant?
Most of the studies on Hordenine have been on animals. It came to fame in the horse racing realm in 1990 because it had the potential to impact horse racing as an injected stimulant. However, when taken by mouth, these same stimulant properties did not seem to apply.
It seems clear that Hordenine does have some stimulant properties as early research in 1989 noted it “is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.” It has been shown to work as an MAO-B inhibitor. This enzyme breaks down brain chemicals, such as dopamine.
One source enhancetech.eu that specializes in performance enhancement, concludes that “while it is clear that Hordenine is a cardiovascular, nervous system and metabolism stimulant, nootropic properties are debatable – while it might be mildly nootropic, the opposite may be true, instead.”
As with many supplements there are potential Hordenine side effects to think about. These are relatively unknown in human studies and are suggested by animal studies thanks to the stimulant nature of Hordenine.
Potential Hordenine side effects include:
– Possible interaction with MAOI drugs
– Accelerated heart rate
– Increased blood pressure
– Increased breathing rate
These side effects are thought to be because it stimulates your nervous system. It appears these side-effects may be brief and only when someone takes very high doses.
Is Hordenine Banned in Sport?
Technically yes, but there hasn’t been a positive drug test reported for it yet based on WADA adverse analytical finding statistics from 2006-2020. Phenethylamine derivatives were added to the WADA Prohibited List in 2016. The phenethylamine ban was significant because there are hundreds of natural products and plant extracts that are phenethylamine derivatives that could now be interpreted as prohibited.
While it would qualify as a prohibited substance as a phenethylamine derivative, it is not specifically listed in any banned substance lists used in sport, except the NCAA Banned Substances List where it is included as an example of a stimulant. The absence of Hordenine on most banned substance lists is surprising given its prevalence in pre-workout supplements.
The Global Drug Reference Online (Global DRO), a cooperative among several anti-doping agencies, does not yet have a record on Hordenine. The Global DRO does have a record for N-methyltyramine, saying this related stimulant is banned. This suggests Hordenine would also be interpreted as prohibited by the Global DRO.
Will It Make You Fail a Drug Test?
Hordenine could make you fail a drug test in sport, at least in theory. The lack of WADA adverse analytical findings suggest that it has not yet been targeted in sport drug testing. If it is targeted urine thresholds would apply with the category S6 – Stimulants having a reporting threshold of 50 ng/ml in urine according to the WADA Technical Document TD2022MRPL. Hordenine, along with N-Methyltyramine, appear to fall into a strange category in sport drug testing. They are drugs banned by interpretation of the list, but apparently not in practice.
Hordenine may impact workplace drug tests that use immunoassay testing. These tests usually give a color or signal in the presence of a category of drugs whereas mass spectrometry fingerprints the specific drug in question. Hordenine has been known to appear like morphine in immunoassay tests. If confirmed by mass spectrometry, it should be distinguishable from morphine.
Is Hordenine a Legal Dietary Supplement Ingredient?
It is possible in our view that it could be a legal dietary supplement ingredient if it was in the form of a legitimate natural extract of a plant. However, on its own as a synthesized chemical it does not appear to qualify as a legal dietary supplement ingredient.
The U.S. FDA lists Hordenine on the Dietary Supplement Ingredient Advisory List, or at least they did, it was removed in October of 2021. It still appears below a note that suggests, “the following ingredients have been removed from the Ingredient Advisory List because, based on available information, the ingredients fall into one of the three categories described above.” Above it says that, “an ingredient may not lawfully be in dietary supplements for reasons including, “one of the three categories. This circular logic creates apparent confusion on whether it is or is not a legal ingredient. While the language may be confusing FDA actions confirm that it is illegal in their eyes as they took action against multiple companies in a slate of warning letters in May of 2022.