Benefits
Absorption and blood levels after oral intake in people
In two small studies, three volunteers took a single 100 mg dose of hordenine and four drank beer supplying about 0.075 mg/kg. Blood levels peaked within about an hour and fell with a half-life of about an hour. Both research teams judged these levels unlikely to act directly on the dopamine D2 receptor, the target identified in lab tests.
Strength and power with a pre-workout blend containing hordenine
In a randomized double-blind crossover trial in 23 resistance-trained men, a pre-workout drink with 150 mg barley-derived hordenine extract, 300 mg caffeine and nine other ingredients improved strength and sprint cycling power versus placebo. With that much caffeine in the formula, none of the effect can be attributed to hordenine.
Heart rate, blood pressure and noradrenaline in animal studies
In rats and dogs, hordenine raised blood pressure, strengthened heart contractions and slowed gut movement by releasing stored noradrenaline, but the effects were short, needed high doses and did not change mouse behavior. In horses, 2 mg/kg injected doubled heart rate, while the same dose by mouth changed nothing.
Fat breakdown (lipolysis) in laboratory fat cells
In isolated mouse fat cells, hordenine at up to 1 mM neither stimulated nor blocked fat breakdown, although the cells responded normally to isoprenaline, forskolin and insulin. Human fat tissue was used only for enzyme tests, not for lipolysis. The authors concluded hordenine is unlikely to increase fat mobilization from fat stores.
Interaction with monoamine oxidase (MAO) enzymes
In rat liver tissue, hordenine was broken down selectively by MAO-B and not by the MAO-A of the gut lining. In human fat tissue it competed with tyramine for MAO but was itself broken down slowly, so the authors called it a mixed substrate and inhibitor. Whether this matters at supplement doses in people has not been tested.
Mechanism of action
Noradrenaline release and reuptake (animal tissue)
In animal pharmacology experiments, hordenine behaved as an indirectly acting adrenergic compound that releases noradrenaline from stores, and its effect was very weak in isolated organs and in tissues with low adrenaline content. In isolated rat vas deferens it caused no contraction itself but boosted responses to added noradrenaline and blocked responses to tyramine, which those authors read as inhibition of noradrenaline reuptake.
Dopamine D2 receptor activity in cell assays
In receptor assays, hordenine bound the dopamine D2 receptor (Ki 13 μM) and activated its G protein signaling with about 76% of the efficacy of dopamine, while blocking beta-arrestin recruitment. Blood levels measured after oral hordenine in people were well below the concentrations at which this activity was seen.
Monoamine oxidase substrate and inhibitor
Hordenine is a selective substrate of MAO-B in rat liver. In human abdominal fat tissue it competed with tyramine for MAO while producing little breakdown product itself, and it was neither a substrate nor an inhibitor of semicarbazide-sensitive amine oxidase. Which MAO form it acts on in human tissue was not determined.
Gut and blood brain barrier transport (laboratory models)
In a gut cell model hordenine crossed quickly, but it was also pumped back toward the gut side and partly metabolized inside the cells, which may limit oral bioavailability. In a pig brain capillary cell model it crossed the blood brain barrier rapidly; the authors said a dopamine effect would need a route other than oral intake. In people it is converted mainly to sulfate and glucuronide forms.
No direct fat breakdown in fat cells
Unlike synephrine, hordenine did not trigger lipolysis in isolated mouse fat cells, and unlike tyramine it did not block it. Any effect on body fat would have to come indirectly, for example through the sympathetic nervous system, and no human study has measured body weight or body fat with hordenine.
Clinical trials
Randomized, double-blind, placebo-controlled crossover trial with a familiarization visit and two testing sessions seven days apart; one 9.6 g drink (Knockout 2.0, Olimp Laboratories) taken about 40 minutes before testing, containing 150 mg barley-derived hordenine extract, 300 mg anhydrous caffeine, 200 mg guarana extract, 3 g L-citrulline, 2 g beta-alanine and six other ingredients. The authors reported no external funding. (Kaczka et al. 2020, Int J Environ Res Public Health)
23 resistance-trained men.
Compared with placebo, the drink increased knee flexor and extensor torque and power on isokinetic testing (p=0.001 to 0.005), three-repetition maximum strength (p=0.001) and Wingate mean power (8.7 vs 8.5 W/kg, p=0.038). The formula supplied 300 mg of caffeine plus guarana, so no part of the result can be attributed to hordenine.
Pharmacokinetic study within an analytical methods paper: one oral 100 mg dose of hordenine in starch capsules after an overnight fast, with blood sampled for 4 hours; no placebo and no health outcomes. (Sobiech et al. 2020, J Agric Food Chem)
Three healthy nonsmoking volunteers weighing 80 to 105 kg.
Plasma hordenine peaked at 16.4 ± 7.8 μg/L about 65 minutes after the dose and fell with a half-life of about 54 minutes. The authors judged a direct effect on the dopamine D2 receptor unlikely at these levels, since activation in lab tests needs about 610 μg/L. A very large apparent volume of distribution pointed to low bioavailability or wide tissue distribution.
Pilot biokinetic study: volunteers drank beer supplying 0.075 mg hordenine per kg body weight, and plasma and urine were analyzed; no health outcomes. (Sommer et al. 2020, J Agric Food Chem)
Four volunteers.
Free hordenine in plasma peaked at 12.0 to 17.3 nM within 0 to 60 minutes and had a half-life of 52.7 to 66.4 minutes. It was converted first mainly to a sulfate and later to a glucuronide, and 9.9% of the dose appeared in urine within 24 hours. The authors judged these levels too low for a direct dopamine D2 receptor effect.
Veterinary pharmacology and pharmacokinetic study: 2.0 mg/kg hordenine by rapid intravenous injection to 10 horses, and the same dose by mouth. (Frank et al. 1990, Equine Vet J)
Horses (10 given the intravenous dose).
Intravenous hordenine raised breathing rate about 250%, roughly doubled heart rate and caused sweating and respiratory distress, all resolving within 30 minutes, with no remaining stimulant or depressant effect on behavior testing. The same dose by mouth produced no change in heart rate, breathing rate, body temperature or behavior.
Animal pharmacology study in intact animals and isolated organs, published in German with an English abstract. (Hapke and Strathmann 1995, Dtsch Tierarztl Wochenschr)
Rats, dogs and mice, plus isolated organ preparations.
Hordenine strengthened heart contractions, raised systolic and diastolic blood pressure and peripheral blood flow, and slowed gut movement, acting by releasing stored noradrenaline. It had no effect on mouse behavior, its effect was very weak in isolated organs and tissues with low adrenaline content, and all effects were short and seen only at high doses. The authors judged a performance effect in racehorses from feed quite improbable.