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Synephrine (p-Synephrine; Bitter Orange, Citrus aurantium)
A mild stimulant from bitter orange marketed for fat loss; it modestly raises fat oxidation but clinical weight-loss evidence is weak and cardiovascular risk rises sharply when stacked with caffeine.
What the evidence says
Most Synephrine studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2004–2025.
Based on 18 studies · 1 meta-analysis · 11 RCTs
Confidence
Moderate confidenceBy outcome
Acute trials consistently show a small rise in fat oxidation, but the meta-analysis found no weight-loss benefit and a blood-pressure rise, so clinical evidence stays weak.
17 rigorous studies
16 randomized trials · 1 meta-analyses · 1 systematic reviews
Our evidence rating for Synephrine is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
2 trials ongoing or recruiting · 8 completed on ClinicalTrials.gov
1 of the completed trials have posted results
Registered trials show research momentum for Synephrine, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Sep 2026
Synephrine (p-synephrine) is a protoalkaloid from bitter orange (Citrus aurantium), widely used in 'fat-burner' and pre-workout supplements after ephedra was banned. It is a mild sympathomimetic that can modestly increase metabolic rate and fat oxidation, especially around exercise.
However, randomized evidence for actual weight loss is weak, and most reported adverse events occur in multi-ingredient products that combine it with caffeine and other stimulants — which is where cardiovascular risk (raised heart rate and blood pressure, palpitations) climbs.
On its own at low doses it appears milder than ephedra, but it remains a use-with-caution stimulant, particularly for anyone with cardiovascular risk.
p-Synephrine weakly activates beta-3 (and to a lesser extent other) adrenergic receptors, nudging metabolic rate and lipolysis upward.
Increases energy expenditure and fat oxidation, most measurably around exercise.
Avoid — sympathomimetic effects raise cardiovascular load.
Avoid.
Avoid stacking with caffeine; use the lowest dose if at all.
Risk of dangerous blood-pressure elevation — do not combine.
Additive cardiovascular stimulation — the main driver of reported adverse events; avoid high-caffeine stacks.
May counteract or interact with cardiovascular drugs.
Bitter orange can inhibit CYP3A4, raising levels of some drugs (similar concern to grapefruit).
Tip: Use low isolated doses; avoid caffeine stacks
Tip: Reduce dose; avoid stimulant combinations
Tip: Reduce dose
Synephrine has an evidence score of 4.8/10 — emerging evidence based on 12 indexed studies, including 1 meta-analysis. A mild stimulant from bitter orange marketed for fat loss; it modestly raises fat oxidation but clinical weight-loss evidence is weak and cardiovascular risk rises sharply when stacked with caffeine. Representative study: PMID 36235672.
The commonly studied dose of Synephrine is 10-20mg p-synephrine 1-2x daily (≤50mg/day); avoid or minimize combining with caffeine/other stimulants. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take Synephrine is in the morning. It can be taken on an empty stomach. Taken earlier in the day for its stimulant/thermogenic effect (often pre-exercise); avoid late-day dosing and high-caffeine stacks.
Synephrine should be used with caution — talk to a healthcare provider before taking it. Reported side effects are uncommon and include increased heart rate / blood pressure, palpitations, jitteriness, anxiety, headache. Use caution if any of these apply to you: Hypertension or cardiovascular disease; Arrhythmia or palpitations; Pregnancy and breastfeeding.
Caffeine
Likely helpsBlocks adenosine receptors to boost alertness, reaction time, and endurance — one of the most proven ergogenic aids.
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Urolithin A
Likely helpsPostbiotic that triggers mitophagy — the cleanup of damaged mitochondria — to support muscle health and cellular energy.
Theacrine
Mostly mechanism / observationalCaffeine-like purine alkaloid from kucha tea. Small RCTs suggest subjective energy and mood benefits and good safety, but objective performance gains are inconsistent.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 18 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.