Ergogenic and Sympathomimetic Effects of Yohimbine: A Review

Abstract

The purpose of this review is to compile and discuss available evidence in humans on the efficacy of YHM supplementation on performance in different exercise modalities. Yohimbine (YHM) is a naturally occurring alkaloid that induces increases in sympathetic nervous system (SNS) activation effectively initiating "fight or flight" responses. In supplement form, YHM is commonly sold as an isolated product or combined into multi-ingredient exercise supplements and is widely consumed in fitness settings despite the lack of empirical support until recently. YHM primarily acts as an α2-adrenergic receptor antagonist effectively increasing norepinephrine release from sympathetic neurons. YHM has been implicated in improving or altering cardiovascular function, blood flow, lactate metabolism, and muscle function. Emerging evidence has suggested that YHM may have the potential to improve performance in a wide range of exercise modes including endurance, sprint, and resistance exercise. Performance enhancement with YHM is mediated by mechanistic underpinnings of physiological and psychological alterations to exercise responses including increased sympathetic activation, adaptive hemodynamic changes, increased alertness, and decreased fatigue. However, YHM use is not without risk as it has high interindividual variability in bioavailability, can be deceptively potent, lacks widely accepted dosing recommendations, and, when taken in large doses, has been empirically documented to result in serious side effects. Despite this, the evidence presented in this review suggests low doses of YHM are tolerable and may serve as an ideal exercise training aid due to acute enhancement of physical performance. However, safety concerns remain outstanding and temperance should be used when using YHM and similar sympathomimetics.

Keywords: catecholamines; dietary supplement; stimulant; sympathetic nervous system.

Figure 1

Primary mechanism of action of Yohimbine (YHM) via α₂-adrenergic receptor antagonism. YHM competes for norepinephrine (NE) binding sites on α₂-adrenergic receptors, which serve as negative feedback regulators of NE release at the pre-synaptic neuron. Inhibition of a₂-adrenergic receptor activation results in exacerbation of NE release and NE spillover. The phenomenon of NE spillover leads to the propagation of catecholamine release and sympathetic activation systemically. This influences multiple organ systems including the adrenal glands, heart, vasculature, skeletal muscle, and neural activity. Alterations in skeletal muscle performance, cardiovascular function, hemodynamics, and metrics linked to psychological arousal have been implicated as underlying effects mediating the ergogenic effects of YHM.

Figure 2

Chemical structure of Yohimbine (YHM). Chemical formula: C₂₁H₂₆N₂O₃. Molecular weight: 354.4 g/mol. Classification: indole alkaloid.

Figure 3

Physiological and psychological factors contributing to improved exercise ability with acute Yohimbine (YHM) ingestion. YHM HCl results in physiological and psychological alterations to mediators of performance. Physiological improvements that have been reported in the literature include greater oxygen uptake (VO2), catecholamine release, and metabolism, as reflected by hypoxanthine. Lower post-exercise lactate levels have also been reported by multiple studies. Psychologically, there have been reports of increased motivation, alertness, and feelings of energy with YHM ingestion. Subjective feelings of fatigue have also been suggested as an underlier to improved performance.