Synephrine
Synephrine (p-synephrine) is a sympathomimetic alkaloid from bitter orange (Citrus aurantium), widely used in weight-loss and pre-workout supplements after the ephedra ban. It has mild stimulant and thermogenic effects, and while less potent than ephedrine, cardiovascular concerns rise when it is combined with caffeine and other stimulants.
01 Overview
p-Synephrine is the principal active alkaloid of bitter orange extract and is marketed as a "safer" replacement for banned ephedra in fat-burner and energy products. It has modest adrenergic activity and small measured effects on metabolic rate and heart rate.
Used alone at supplement doses, p-synephrine appears to have a relatively modest cardiovascular profile in the available human studies. The main safety concern is combination: most products stack it with caffeine and other stimulants, which can raise blood pressure and heart rate more than any single ingredient. Evidence for meaningful weight loss is limited.
02 Mechanism
Sympathomimetic adrenergic agonist (relatively selective for beta-3 and with modest alpha activity), modestly increasing metabolic rate and cardiovascular tone.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Common (supplement) | 10–50 mg | Oral | Typical amounts in fat-burner/pre-workout products; often combined with caffeine. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Mild thermogenesisSmall measured increases in resting metabolic rate and fat oxidation in short human studies. | Clinical | ||
| Stimulation and appetite suppressionPerceived energy and reduced appetite, marketed for weight management. | Anecdotal | ||
| Raised heart rate and blood pressureModest cardiovascular stimulation, amplified when combined with caffeine. | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Anxiety, jitteriness and insomniaRestlessness, anxiety and disturbed sleep typical of stimulants. | Mild | Common | Anecdotal | |
| Interactions and adulterationVariable extract content and potential interactions (e.g. with MAO inhibitors or other sympathomimetics). | Mild | Uncommon | Observational | |
| Cardiovascular stimulationIncreased heart rate and blood pressure, palpitations; more pronounced in stimulant stacks. | Moderate | Common | Observational |