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Hordenine

Hordeum vulgare (barley) — primary source
Evidence Level
Preliminary
3 Clinical Trials
5 Documented Benefits
1/5 Evidence Score

Phenethylamine alkaloid (N,N-dimethyltyramine) found in sprouted barley, bitter orange, and cacti. Marketed as fat burner and stimulant in pre-workout supplements via MAO-B inhibition and indirect adrenergic activity. Human RCT evidence is essentially absent — most evidence is rat/horse pharmacology with short-lived effects requiring high doses. Adipocyte studies show NO direct lipolytic effect.

Studied Dose TYPICAL: 25-100 mg per serving in pre-workouts/fat burners. Often combined with caffeine, synephrine, PEA, yohimbine. 30 min pre-training. NO well-established human dose-finding studies. FDA NDI.
Active Compound Hordenine (N,N-dimethyltyramine) — phenethylamine alkaloid related to tyramine. Found in: sprouted barley (Hordeum vulgare — name origin), bitter orange (Citrus aurantium), Lophophora williamsii, various cacti, Senecio scandens, and red algae

Benefits

Stimulant/sympathomimetic effects (animal evidence)

Hapke 1995 (, Dtsch Tierarztl Wochenschr) demonstrated in dogs and rats that hordenine produced positive inotropic effect on heart, increased systolic and diastolic BP, and increased peripheral blood flow. Effects via indirect adrenergic activity (norepinephrine release). CRITICAL CAVEAT: effects were short-lived and required HIGH DOSES — performance enhancement in racehorses unlikely. Human translation has not been rigorously demonstrated.

Supported by Trial 2

Weak MAO-B inhibitor (potentiates other PEAs)

Hordenine is a selective substrate for MAO-B with weak inhibitory activity (Km = 479 μM, Vmax = 128 nM/mg protein/h in rat liver). Theoretical mechanism for potentiating phenylethylamine (PEA) and other monoamines that are MAO-B substrates. Combined with PEA in some pre-workouts to extend duration. NOT a clinically meaningful MAOI like prescription drugs (selegiline, etc.) — far weaker effect.

Supported by Trial 2, Trial 3

NO direct lipolytic activity (Haj Ahmed 2021)

Haj study directly tested hordenine effects on adipocyte lipolysis. RESULT: hordenine does NOT activate or inhibit lipolysis in fat cells. Adipocytes were responsive to standard stimulants (isoprenaline, forskolin) and inhibitors (insulin) but unresponsive to hordenine. Authors concluded: 'Hordenine consumption cannot likely increase lipid mobilization from fat depots since this plant alkaloid is lacking noticeable lipolytic effect.' Direct evidence against fat-burner marketing claims.

Supported by Trial 3

Indirect adrenergic activity (norepinephrine release)

Hordenine acts as indirect adrenergic agonist by promoting norepinephrine release from sympathetic nerve terminals. Mechanism similar to (but weaker than) tyramine and amphetamines. Theoretical contribution to focus and energy through SNS activation — but actual clinical effects in humans are minimal at safe doses.

Supported by Trial 2

Bronchodilation (traditional Chinese use)

Used in Traditional Chinese Medicine as 'mao gen' for respiratory conditions including asthma — bronchodilator activity via β-adrenergic indirect effects. Mechanism plausible but rigorous clinical evidence in respiratory conditions absent. Modern bronchodilators (β2-agonists) far more effective.

Supported by Trial 1

Mechanism of action

1

Indirect adrenergic activity via norepinephrine release

Hordenine, like tyramine and amphetamines, is an indirect-acting sympathomimetic — it promotes release of stored norepinephrine from sympathetic nerve terminals. Mechanism does NOT involve direct receptor binding (unlike epinephrine). Effects depend on existing sympathetic tone and norepinephrine stores. Tachyphylaxis can develop with repeated use.

2

Selective MAO-B inhibition (weak)

Selectively inhibits MAO-B isoenzyme over MAO-A. In context of PEA potentiation: PEA is rapidly metabolized by MAO-B; hordenine slows this metabolism. However, hordenine itself is also an MAO-B substrate at low concentrations — making it a 'mixed substrate/inhibitor.' Inhibitory activity is weak relative to selective MAOI drugs.

3

Crosses blood-brain barrier

Lipophilic structure allows penetration into CNS. Theoretically supports nootropic/focus claims, but actual brain levels achieved at oral supplement doses are likely low. CNS effects in humans have not been rigorously characterized via PET imaging or microdialysis studies.

4

NO direct β-adrenergic agonism in adipocytes

Despite weight loss marketing, hordenine does NOT bind β-adrenergic receptors directly in adipocytes (Haj Ahmed 2021). Cannot stimulate lipolysis directly. Any weight management effects would have to come from indirect mechanisms (SNS activation generally) — which are modest at safe doses.

Clinical trials

1
Frank 1990 — Hordenine Pharmacology in Horses
PubMed

Veterinary pharmacology study (Frank M, Weckman TJ, Wood T, Woods WE, Tai CL, Chang SL, Ewing A, Blake JW, Tobin T 1990, Equine Vet J 22(6):437-441, doi:10.1111/j.2042-3306.1990.tb04313.x).

Horses given oral and intravenous hordenine. Pharmacokinetics (plasma concentration), behavioral effects, vital signs, and respiratory effects measured.

Intravenous administration caused immediate behavioral changes and significant respiratory distress, but symptoms subsided within 30 minutes. Oral administration showed NO noticeable changes — consistent with poor oral bioavailability. Pharmacokinetic analysis revealed rapid plasma clearance, with no lasting stimulant or depressive effects post-dosing. Foundational evidence that oral hordenine produces minimal systemic effects.

2
Hapke 1995 — Hordenine Pharmacology in Dogs and Rats
PubMed

Animal pharmacology study (Hapke HJ, Strathmann W 1995, Dtsch Tierarztl Wochenschr 102(6):228-232, PMID 8542915).

Dogs and rats given hordenine orally and intravenously. Cardiovascular, gastrointestinal, and CNS effects assessed; isolated tissue experiments to elucidate mechanism.

Hordenine produced positive inotropic effect, increased BP, increased peripheral blood flow, inhibited GI movements. Effects characterized as INDIRECTLY ACTING ADRENERGIC mechanism via norepinephrine release. CRITICAL CAVEAT: effects were short-lived and required HIGH DOSES to be observed. Animal findings do not translate directly to human supplement doses.

3
Haj Ahmed 2021 — Hordenine NOT a Lipolysis Activator
PubMed

Adipocyte study (Haj Ahmed W et al. 2021, Integr Food Nutr Metab 8:302).

Mouse fat cells (adipocytes) and human subcutaneous adipose tissue homogenates exposed to hordenine and assessed for lipolytic and antilipolytic responses, plus interaction with monoamine oxidase.

DIRECT EVIDENCE that hordenine does NOT activate or inhibit lipolysis in adipocytes. Cells were responsive to standard agents (isoprenaline, forskolin, insulin) but unresponsive to hordenine. Confirmed weak MAO interaction (substrate/inhibitor) but no direct fat-cell stimulation. Authors concluded: 'Hordenine consumption cannot likely increase lipid mobilization from fat depots.' Foundational counter-evidence against fat burner marketing claims.

Side effects and drug interactions

Common Potential side effects

Hypertension at high doses or in those with cardiovascular conditions.
Tachycardia, palpitations.
Anxiety, jitteriness, insomnia (typical stimulant effects).
DRUG TEST INTERFERENCE: causes FALSE POSITIVES for opiates in ELISA and RIA immunoassays — important practical concern.
Pregnancy/lactation: AVOID — insufficient safety data, sympathomimetic activity.
Hypertension/heart disease: AVOID.
FDA NDI status — many products technically adulterated.

Important Drug interactions

MAOIs (selegiline, phenelzine): SIGNIFICANT INTERACTION RISK — hypertensive crisis potential.
Stimulants (caffeine, ephedrine, ADHD medications): additive sympathomimetic effects, cardiovascular risk.
Antihypertensives: theoretical opposition to BP-lowering effects.
Tyramine-containing foods: theoretical additive effects (clinically usually mild).
Sympathomimetic decongestants (pseudoephedrine): additive effects.
Drug screening: causes immunoassay FALSE POSITIVES for opiates.

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Frequently asked questions about Hordenine

What is Hordenine?

Phenethylamine alkaloid (N,N-dimethyltyramine) found in sprouted barley, bitter orange, and cacti.

What does Hordenine do?

Hordenine, like tyramine and amphetamines, is an indirect-acting sympathomimetic — it promotes release of stored norepinephrine from sympathetic nerve terminals. Mechanism does NOT involve direct receptor binding (unlike epinephrine). In clinical research, Hordenine has been studied for stimulant/sympathomimetic effects (animal evidence), weak mao-b inhibitor (potentiates other peas), no direct lipolytic activity (haj ahmed 2021).

Who should take Hordenine?

Hordenine may be most relevant for people interested in energy, weight management. It has been clinically studied for stimulant/sympathomimetic effects (animal evidence), weak mao-b inhibitor (potentiates other peas), no direct lipolytic activity (haj ahmed 2021). As with any supplement, consult your healthcare provider before starting, especially if you have medical conditions or take prescription medications.

How long does Hordenine take to work?

Most clinical trial effects appear over weeks of consistent use; individual response varies. Acute or same-day effects (where applicable) typically appear within hours, but most cumulative benefits — particularly those affecting biomarkers, mood, sleep quality, or chronic symptoms — require 4-12 weeks of regular use to fully assess. If you don't notice benefit after 12 weeks at the appropriate dose, it may not be your responder.

When is the best time to take Hordenine?

For performance or energy goals, Hordenine is typically taken 30-60 minutes before exercise or in the morning. Some people take it with food to reduce GI sensitivity; others prefer empty-stomach timing for faster absorption. Always check product labeling and follow personalized guidance from your healthcare provider.

Is Hordenine worth taking?

Hordenine has preliminary clinical evidence (Evidence Level 1/5 on NutraSmarts) — based largely on traditional use or early research. Consider this an experimental option. Whether it's worth taking depends on your specific goals, what you've already tried, your budget, and your overall supplement strategy. The honest framing: no supplement is essential for most people, and lifestyle factors (sleep, exercise, diet, stress management) typically produce larger effects than any single supplement. Hordenine is most worth trying if its evidence-supported uses align with your specific goals.

What is the recommended dosage of Hordenine?

The clinically studied dose for Hordenine is TYPICAL: 25-100 mg per serving in pre-workouts/fat burners. Often combined with caffeine, synephrine, PEA, yohimbine. 30 min pre-training. NO well-established human dose-finding studies. FDA NDI.. Always follow product labeling and consult a healthcare provider for personalized dosing recommendations.

What is Hordenine used for?

Hordenine is studied for stimulant/sympathomimetic effects (animal evidence), weak mao-b inhibitor (potentiates other peas), no direct lipolytic activity (haj ahmed 2021). Hapke 1995 (, Dtsch Tierarztl Wochenschr) demonstrated in dogs and rats that hordenine produced positive inotropic effect on heart, increased systolic and diastolic BP, and increased peripheral blood flow.