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Are Synephrine, Higenamine and Hordenine the Best Pre-workout Stims?

A good pre-workout product should supercharge the senses and prepare the body to work harder than ever before. Bodybuilders have traditionally used various stimulants such as high-doses of caffeine and, before it was banned, ephedrine combined with aspirin and caffeine to awaken every neuron to the possibility of sustained and intense muscular overload. The best pre-workouts, on the other hand, create the same massive surge of energy, prepare the body for action and enable stored bodyfat to be used for fuel, but without the inevitable stimulant-crash and jitters associated with massive heapings of caffeine and little else. The new breed of pre-workout is energy-sustaining. Rather than peaking at a certain point before leaving the user feeling tired, lethargic and anxiety-riddled, it’ll support intensity increases and heighten mental awareness throughout the entire workout.

An effective pre-workout combines an adequate dose of caffeine with an array of additional performance ingredients, all designed to work synergistically to produce a sustained stimulant effect that’ll have you firing on all cylinders right through to the final rep. 


Energy, Im
proved Focus, and More
Three ingredients that’ll uniquely increase energy, stimulate both mind and body and improve one’s ability to use fat for fuel are Synephrine, Higenamine, and Hordenine. Collectively known as Beta-adrenergic agonists, or Beta agonists, each functions on its own as a low-level stimulant but when combined (together and with various forms of caffeine) produce an immensely powerful and long-lasting stimulant effect.

Due to their effectiveness in relaxing and widening the airways and assisting normal breathing, the Beta agonists are often used to treat respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD).2, 4 Acting on the beta adrenoceptors (G protein-coupled receptors: targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline)), the Beta agonists have the opposite function of Beta Blockers (competitive antagonists which block the receptor sites for the endogenous catecholamines and thus weaken the effects of these key stress hormones).2, 4, 9 Compounds like Synephrine, Higenamine and Hordenine, which act upon the Beta adrenoceptors, mimic the actions of the major neurotransmitter catecholamines (notably epinephrine and norepinephrine) to ready the body for intense activity (the famed fight-or-flight response which mobilizes energy reserves, focuses the mind, and stimulates action). Beneficial heart rate increases, enhanced metabolism of lipids (fats) and heightened mental awareness are among the benefits to be experienced. However, unlike potent and potentially dangerous stimulants such as straight epinephrine (with side effects including anxiety, apprehensiveness, restlessness, tremor, weakness, dizzinesssweating, palpitations, pallor, nausea and vomiting, and headaches), Beta agonists have few adverse effects (in some cases and with certain compounds the user may experience mild to moderate anxiety, increased heart rate, and insomnia). While Synephrine, Higenamine, and Hordenine, in Beta agonistic fashion, are known to synergistically engage the mind and body when action is required, each has specific functions which make them uniquely beneficial. Let’s take a closer look at each to assess how they’ll put you in fight, not flight, mode in the lead-up to your next workout. 

Functioning both as an Alpha receptor antagonist and a Beta receptor agonist, the net effect of Synephrine intake is an increased rate of lipolysis (the breakdown of fats for energy) along with its stimulant effects. Synephrine is considered a much safer stimulant alternative to the more powerful, and illegal, ephedrine (which it’s often compared to), itself a Beta agonist/Alpha antagonist. Indeed, Synephrine is known to greatly increase energy and metabolic rate, without significantly increasing heart rate or blood pressure as with the more potent stimulants.3

On a cellular level Synephrine, an alkaloid which naturally occurs in some plants and animals, promotes the breakdown of fats for energy by activating the beta-3 adrenergic receptors located on fat cells. It increases the metabolic rate by increasing lipolysis and basal (resting) metabolic rate, effects which are independent of nutrient consumption.7, 15 Synephrine’s stimulant effects replicate those of the ubiquitous caffeine but without the jitters typically associated with heavily caffeinated pre-workout products. 

A component of bitter orange, sprouted barley and other plant products, Hordenine has similarities to stimulant compounds such as Synephrine and is thus believed to assist with fat reduction and promote mental arousal when taken in supplemental form.6, 13 It’s known to boost the metabolic rate while significantly reducing appetite, both useful when seeking to shred. Though not strictly a Beta agonist (like Synephrine and Higenamine), Hordenine has been found to increase the chemical release of noradrenaline while helping to prevent its metabolic destruction.1 Thus it functions as a Beta-2 adrenergic agonist to dramatically increase cellular metabolism. Ineffective as a standalone stimulant, Hordenine can however enhance and prolong the effects of other stimulants due to its ability to block the reuptake of noradrenaline and other monoamines. 1, 12 In fact, via this very action Hordenine is known to stabilize mood, reduce anxiety and prolong feelings of wellbeing, important attributes when preparing to battle the iron.

Hordenine is able to cross the blood brain barrier where it acts as a monoamine oxidase inhibitor (MAO) upon attaching to specific neuronal receptor sites. Enzymes within cells that use oxygen to destroy beneficial amino acids and hormones, the MAOs, when accumulated in excess, can create an imbalance that leads mental instability, a loss of focus and reduced energy levels. Hordenine controls and prevents the excessive accumulation of MAOs, thus optimizing hormonal balance and producing beneficial levels of natural energy. Specifically, Hordenine acts upon the neurotransmitter dopamine, to ensure more of it remains available to promote feelings of mental sharpness and pleasure. 

Higenamine (also referred to as Norcoclaurine), like Synephrine and Hordenine, has implications as a performance enhancing stimulant and fat burning agent. Used within traditional Chinese medicine (TCM) for thousands of years, and derived from a variety of plants (specifically fruits, orchids and the Nandina plant), it’s a Beta-2 adrenergic agonist which has traditionally been and is still commonly used as an anti-asthmatic medication.5, 14 Higenamine is also known for being a mild stimulant when taken independent of other stimulants. However, when combined with other stimulant compounds (such as Synephrine, Hordenine and caffeine) it can help produce a powerful stimulant effect.

As a Beta receptor agonist it increases the production of noradrenaline, to stimulate the actions associated with the fight of flight response (more mental alertness and focus and muscles primed for action). Also, by stimulating the Beta adrenergic receptors it enhances lipolysis, to burn fat at a faster rate.8, 11


 Higenamine is used a fat burner due to having similar mechanisms to ephedrine.11 Indeed, its desirable pharmacokinetic and pharmacodynamic characteristics (movement of drugs within the body and effects of drugs and their mechanisms of action respectively) are largely attributable to its ability to increase the thermogenic effects of exercise and other supplements by making the heart work harder.10 However, despite its effects on the heart, Higenamine is considered very safe if taken in proper dosages.


 It’s a given that pre-workout supplementation should produce energy above and beyond that provided by regular nutrition and unmitigated mental fortitude alone. However, there is a point where stimulation (when produced in excess) can become detrimental to your training. What the perfect pre-workout supplement should provide is steady, balanced mental and physical energy. Certain pre-workout products do live up to the hype by supercharging the senses and producing intense mental focus. User beware! Many so-called “extreme” pre-workout products that focus too heavily stims alone can result in short-lived and excessive stimulation and just when the workout is reaching its most productive phase the energy levels that got you through the first few sets come crashing down, rendering you fatigued and ready to call it quits. What is needed is a well-balanced combination of stimulants that work synergistically to extend workout performance by keeping energy levels consistent. With Synephrine, Hordenine and Higenamine, along with other select performance compounds, a good pre-workout will do just that. For balanced energy, intense focus and prolonged fat burning look for a product that will give you the edge in workout intensity.

ALLMAX IMPACT IGNITER - IFBB Physique Pro Dr. Brett Khan

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  14. Tsukiyama, M., et al. 2009). Beta2-adrenoceptor-mediated tracheal relaxation induced by higenamine from Nandina domestica Thunberg. Planta Medica. 75 (13): 1393–9.
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