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Hordenine

  • Increase in energy levels
  • Supports healthy cognitive function
  • Noticeable improvement in mood 

 

Hordenine (N, N-dimethyltyramine) is a mildly energizing and mood-lifting phytochemical found in several plant species. It was first isolated from barley in the late 19th century and is known to occur in beer. Its benefits include a mild to moderate increase in physical energy, as well as noticeable improvements in mood and cognitive performance. It may also support a healthy metabolism. It also has a synergistic relationship with the energizing amine, Phenylethylamine (PEA).

The recommended serving size for this supplement is 50 – 200 mg, taken once to twice daily. It is not recommended to use this supplement up to 2 hours prior to sleep due to its energizing effect, nor to exceed the recommended serving size. This compound may interact with numerous medications. Speak to your doctor before using it if you have any underlying medical conditions, or are pregnant or breastfeeding.  

 

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Hordenine Reviews

Makes wonders with coffee in the morning or caffeine in general, in my opinion, it's even better than Phenibut, it makes me talk more with people and I’m happier, makes work really easy most of the time, it really is a great product! Makes your day even better with this, happier and not even one sad moment, really fantastic!” – Patrick, LiftMode review

 

I have been using Hordenine with PEA, and it's not just good- INCREDIBLE. It increases your wellbeing, slightly increases your sense of pleasure, and SERIOUSLY stimulates you. Oh, and did I forget to mention that weightlifters can lift more after using PEA and Hordenine!? If you're having a lazy morning, this combination works wonders as you can focus like no other. It's not addictive either.” – I feel awesome!, user review on LiftMode.com

 

  • A natural energizing compound found in several plant species, including the Bitter Orange fruit, barley, beer, and wheat.

  • Benefits include noticeable increases in physical energy and mental performance, as well as mood and metabolism-boosting effects.

  • The recommended serving size for this supplement is 50 – 200 mg, taken once or twice daily.

  • Side effects are mild and rare but larger servings may cause dizziness, headaches, increased heart rate, and anxiety. 

 

Background

 

Hordenine (also known as N, N-dimethyltyramine) is a naturally-occurring adrenergic compound found in a number of plant species, and especially in the Bitter Orange (also the natural source of Synephrine and Octopamine). It is chemically similar to the amino acid L-Tyrosine as well as the trace amines, tyramine and N-methyltyramine. It is touted to be a powerful energizing compound due to its association with tyramine, dopamine, and norepinephrine.

This supplement is a moderately energizing phytochemical with a fairly short duration of action (around 1-2 hours). It helps the brain to release extra norepinephrine, allowing for a host of energizing benefits, while being highly selective for the MAO-B enzyme. This allows it to have a synergistic relationship with similar energizing compounds like Phenylethylamine (PEA). It is effective at crossing the blood-brain barrier and is not known to cause noticeable adverse effects when used at the recommended serving size. [1]

In terms of its metabolism, this supplement is metabolized by the Monoamine Oxidase (MAO) enzyme, specifically the B-subset enzymes. It can be used as a reversible competitive ligand when taking other supplements that are metabolized by the same enzymes (for example, Phenylethylamine (PEA)). By using this supplement with PEA, the results are an increase in potency and duration of effects of both supplements.

This supplement acts on the adrenergic system and helps to stimulate the sympathetic nervous system (SNS), both of which are involved in the ‘fight or flight’ response – thus acting as a powerful energizing supplement. Research has shown that this supplement helps to increase levels of norepinephrine (a highly energizing neurotransmitter) in the brain.[2] This supplement is most often used for its benefits with regards to helping to support healthy cognitive function and a healthy metabolism, as well as to increase mood and physical energy levels.[3]

This compound was first isolated by a German chemist named Arthur Heffter, in 1894.[4] At the time, he named it ‘anhalin’. Later, an Austrian chemist named Ernst Späth proposed the correct molecular formula for this compound, which was isolated from barley, and named it ‘Hordenine’.[5] Interestingly, this energizing compound is found is a wide range of plants, including various cacti, as well as some algae and fungi. It is also found in high concentrations in cereal grains like barley, millet, and sorghum. [6]

hordenine-for-mood 

Hordenine Effects & Benefits

 

1.     Energizing & Metabolism Boosting Benefits

 

Hordenine is well-known for its potent energizing benefits, which are sometimes compared to those of Caffeine. It functions as a compound to help release norepinephrine, and also works to inhibit the reuptake of this neurotransmitter.[7]

Norepinephrine is an important neurotransmitter that is released by the sympathetic nervous system and is active in helping to boost energy levels and to stimulate the metabolism. It is used in the body’s response to stress, where it plays a vital role in the ‘flight-or-fight’ response. Norepinephrine has several important functions in the body, where it:

-        Increases the amount of oxygen sent to the brain, allowing for faster and clearer thinking

-        Increases the heart rate, allowing for more efficient movement and action

-        Increases the release of sugar (glucose), which can be burnt for more energy

-        Increases the rate of breathing, to allow more oxygen to circulate through the body

-        Slows processes like digestion and cell repair, so that more energy can be used on the task at hand [8]

By increasing the release of norepinephrine and by limiting is reuptake (a process that is involved in maintaining the homeostasis of neurotransmitters), this supplement allows for a greater concentration of the neurotransmitter to accumulate in the brain, increasing physical energy and boosting the metabolism. This is why it is often thought of as a weight-loss supplement. Taking this supplement before or during exercise should noticeably increase your energy levels.

 

2.     Mood-Lift

 

There are two important mechanisms through which Hordenine helps to support a healthy and positive mood. Firstly, by binding to MAO-B enzymes, it competes at these receptors against other compounds that are usually metabolized there. For example, dopamine, norepinephrine, and several other trace amines are also metabolised by MAO enzymes. While this supplement is acting on the enzymes, it allows a greater concentration of adrenergic compounds, including dopamine, to build in the brain. Dopamine and serotonin long been associated with an improvement in mood and is considered to be of greater importance in regulating emotions and stress.[9]

Secondly, research has indicated that this supplement not only competes at MAO enzyme binding sites to prevent the reuptake of amines, but that it also binds to, and activates, dopamine receptors. In a complex study, using state-of-the-art technology, researchers used radio-ligand assays to determine the binding affinities of several thousand phytochemicals at dopamine D2 receptor binding sites. The results showed that Hordenine binds to, and activates dopamine D2 receptors, through the process of D2R-promoted G-protein activation. [10] 

In layman’s terms, the results show that this supplement can activate dopamine receptors, while simultaneously preventing the reuptake of dopamine, resulting in a noticeable improvement in mood reductions in feelings of stress. 

 

3.     Supports Healthy Cognition

 

This supplement can also be used to promote a sharp and clear mind, again through its effects on the adrenergic system. By helping to increase the concentration of norepinephrine in the brain, this supplement allows greater oxygen and blood flow to the brain which, in turn, promotes healthy cognitive performance. These benefits have long been known to people who use this great energizing dietary supplement. However, there is still room for further research and publications with objective data relating to its effects on cognitive performance in humans.

Interestingly, people who have difficulties with maintaining focus and attention have been known to typically have low levels of norepinephrine and dopamine in circulation. In fact, the association between norepinephrine, dopamine, and attention is so strong that most pharmaceuticals used to help promote focus and attention target the adrenergic system to increase levels of these neurotransmitters.[11] Hordenine supplements are able to increase the circulating levels of these transmitters naturally and without the risk of dangerous adverse effects, albeit for a shorter period of time.

 

4.     Can Be Used with Phenylethylamine

 

One great benefit of this supplement is its synergistic relationship with Phenylethylamine (PEA) – an energizing compound found in red wine and dark chocolate, and often associated with the ‘runner’s high’.[12] When taken as a dietary supplement, PEA is quickly metabolized by MAO enzymes and has a rapid duration of effects of around 45 minutes to 1 hour. However, because Hordenine is able to bind to MAO-B enzymes, it prevents the metabolism of PEA, allowing the duration of effects to last up to twice as long!

PEA is a modulator of catecholamine emissions in the brain. It acts to help the brain release dopamine and norepinephrine and thereby to improve energy and mood, as well as suppress appetite and promote a healthy metabolism. It is found in high levels in especially dark chocolate and pure cocoa. A recent study found that healthy men who had undergone an intense 60-minute exercise programme had significantly increased levels of PEA. It is also thought to be one of the key chemical components of post-workout euphoria.[13]

Although Hordenine is often considered to be a little less potent at its energizing benefits than PEA, taking the two supplements together is a great way to get the best of both. Hordenine is known as a mild-moderate energizing and mood-lifting supplement, while PEA is known for its powerful mood-lift and increase in physical and mental energy, but the effects are generally short-lived. Using both supplements in combination allows an extension of effects and an increase in potency.

 

5.     Safety First!    

 

This relates more to safety than to an experienced physiological or psychological effect. There are many supplements and synthetic compounds available today that target MAO enzymes. These are often used to help promote and support a healthy mood and to reduce feelings of stress. They may also be used to help promote mental focus and clarity at times. However, most compounds that are metabolized by MAO enzymes, or that inhibit their action, come with a long list of warnings.

By increasing adrenergic neurotransmitters, these compounds help to increase energy, mood, and metabolism. However, at high dosages, or when used together with similar compounds, there tends to be a risk of excessive concentrations of adrenergic neurotransmitters accumulating in the brain (called the ‘cheese-effect’). The cheese effect draws its name from a chemical called tyrosine (structurally similar to this supplement) that occurs in high concentrations in many kinds of cheese. It is metabolised by the MAO enzyme and was the first chemical found to be a substrate of that enzyme. The cheese effect refers to the risk of developing a hypertensive crisis when consuming stimulant-like compounds with MAO substrates or inhibitors (like tyrosine, for example).[14]

Luckily, new research has shown that substances which are metabolised by MAO-B enzymes (like Hordenine) pose far less risk for adverse effects, even when taken in large servings or when used in combination with similar energizing compounds (natural or synthetic). Recent research has shown that the ‘cheese-effect’ is associated with selective inhibition of the MAO-A enzyme subtype, while Hordenine is known to be a substrate for the MAO-B enzyme.[15]

What this means is that Hordenine supplements can be used as a relatively safe and natural energizing compound, with much less risk associated when compared to many similar compounds (especially synthetic ones) that tend to have similar benefits.[16]

hordenine-energizing-compound

 

Hordenine Recommended Usage

 

The recommended serving size for this dietary supplement is 50 – 200 mg, taken once or twice per day. It is an energizing supplement and is not recommended to be taken before sleep. Mornings or 30 - 45 minutes before a workout are the ideal times.

If taking this supplement with Phenylethylamine, ensure that you use a smaller serving size for both supplements as the potency increases in combination. Do not exceed the recommended serving size for this supplement.

 

Hordenine Side Effects & Warnings

 

When used at the correct serving size, this supplement is relatively free from adverse effects. Mild side effects may be experienced, even at the recommended serving size. These could include headaches, sweating, restlessness, twitching, nausea, and/or dry mouth. Any adverse effects will increase in severity with larger serving sizes. Always use the smallest serving size required to feel beneficial effects, so as to avoid the possibility of experiencing any side effects of larger servings.

Do not use this supplement if you are taking any medication as there is a potential for dangerous interactions. This is especially important for people taking antidepressants, MAOIs, central nervous system stimulants, blood pressure medication, alpha-blockers, beta-blockers, as well as asthma or allergy medication. If you have any underlying medical conditions, speak to your doctor before taking this supplement. This supplement may interact with surgery. Do not use this supplement up to 2 weeks prior to surgery.

This supplement is not for use by people under the age of 18 years. It should not be used by pregnant or nursing women. Do not exceed the recommended serving size.

 

Conclusion

 

In summary, this supplement is an energizing and mood-lifting compound with beneficial effects on cognition and physical energy. It is found in a number of plant species, including the bitter orange and a variety of grains, including barley and sorghum.

The key benefits of a Hordenine supplement include its energizing and metabolism-boosting effects, a noticeable improvement in mood, and support for healthy cognitive performance. It is said to act as an MAO-B substrate, where it binds competitively against other amine compounds, including Phenylethylamine (PEA). This allows the two compounds to have a synergistic relationship, where Hordenine lengthens and increases the effects of PEA.

The recommended serving size for this supplement is 50 – 200 mg, taken once to twice daily, and no later than 2 hours prior to sleep. This compound may interact with numerous medications and there is limited research into its effects in pregnant and nursing women. Do not use this supplement if you are taking any medication. Speak to your doctor if you have any underlying medical conditions.

 

hordenine-chemical-structure

 

Medical Disclaimer: 

Not intended to treat, diagnose, or cure any disease or ailment. Please read and fully understand potential adverse effects before using this product. These statements have not been reviewed by the FDA and are not written by a medical professional. Please consult your doctor before using any supplements, especially if you have any medical conditions.

 

References

 



[1]Hordenine”, HerbPedia, available online from http://herbpedia.wikidot.com/hordenine [Accessed May 8, 2018]

[2] Hapke HJ, Strathmann W. [Pharmacological effects of hordenine]. (Article in German). Dtsch Tierarztl Wochenschr. 1995 Jun;102(6):228-32.

[3] “Hordenine” Examine.com, available online from https://examine.com/supplements/hordenine/ [Accessed May 7, 2018]

[4] A. Heffter. "Ueber Pellote." Arch. exp. Path. Pharmakol. (1894). 34 65-86.

[5] E. Späth. "Über die Anhalonium-Alkaloide. I. Anhalin und Mezcalin." Monatschefte für Chemie (1919). 40 129-154.

[6] T. A. Smith "Phenethylamine and related compounds in plants." Phytochemistry. (1977). 16 9-18.

[7] Barwell CJ, Basma AN, Lafi MA, Leake LD. “Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat.” J Pharm Pharmacol. 1989 Jun;41(6):421-3.

[8]What Is Norepinephrine? - Effects, Function & Definition”. Chapter 34 / Lesson 14: Transcript. Study.com. Available online from https://study.com/academy/lesson/what-is-norepinephrine-effects-function-definition.html [Accessed May 8, 2018]

[9] Jaber M, Robinson SW, Missale C, Caron MG. “Dopamine receptors and brain function.Neuropharmacology. 1996;35(11):1503-19.

[10] Sommer T, Hübner H, El Kerdawy A, Gmeiner P, Pischetsrieder M, Clark T. “Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database.” Sci Rep. 2017 Mar 10;7:44201

[11]Norepinephrine”, Rice University online notes, available online from http://www.caam.rice.edu/~cox/wrap/norepinephrine.pdf [Accessed May 7, 2018]

[12] Irsfeld M, Spadafore M, Prüß BM. “β-phenylethylamine, a small molecule with a large impact.” WebmedCentral. 2013;4(9):4409.

[13] “Pharmacological effects of hordenine” Hapke HJ, Strathmann W, Dtsch Tierarztl Wochenschr. 1995 Jun;102(6):228-32.

[14] Sathyanarayana Rao TS, Yeragani VK. “Hypertensive crisis and cheese.” Indian Journal of Psychiatry. 2009;51(1):65-66.

[15] Youdim MB, Finberg JP. “Monoamine oxidase B inhibition and the "cheese effect".J Neural Transm Suppl. 1987;25:27-33.

[16] Finberg JP1, Gillman K. “Selective inhibitors of monoamine oxidase type B and the "cheese effect".Int Rev Neurobiol. 2011;100:169-90. 

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