Synephrine: from trace concentrations to massive consumption in weight-loss

Synephrine is cited as 'the active component' of plants and dietary supplements used in weight loss. It became one of the most popular stimulants present in weight-loss products after the US Food and Drug Administration had interdicted the use of ephedrine-containing dietary supplements. Synephrine is also a trace amine that can be found in vertebrates and invertebrates. Synephrine acts on several adrenergic and serotonergic receptors and its activity on trace-amine-associated receptors has long been discussed. Synephrine exists in three different positional isomers; however, only p- and m-synephrine have been described in weight-loss products. The alleged effectiveness of synephrine-containing supplements is attributed to the thermogenic effects arising from synephrine's adrenergic stimulation. The growing use of synephrine has raised concerns since it has been accompanied by reports of adverse effects. Cardiac adverse events, including hypertension, tachyarrhythmia, variant angina, cardiac arrest, QT prolongation, ventricular fibrillation, myocardial infarction, and sudden death, have been the most common adverse effects associated with synephrine intake. The mechanisms involved in synephrine-induced cardiotoxicity are still unknown since studies related to its safety are scarce. This review will address general aspects concerning the pharmacology of synephrine, but will focus on the efficacy and toxicity aspects related to the use of synephrine in weight-loss.