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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 2004–2022.
Based on 12 studies · 2 meta-analyses · 6 RCTs
Confidence
HighBy outcome
Synephrine has an evidence score of 4.8/10 — emerging evidence based on 12 indexed studies, including 2 meta-analyses. 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.
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Last reviewed June 2026 · evidence from 12 studies · how we score
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.
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.
10-20mg p-synephrine 1-2x daily (≤50mg/day); avoid or minimize combining with caffeine/other stimulants
Can be taken without food
| Form | Type |
|---|---|
| 💊Standardized p-synephrine (stated dose) | Recommended |
| 💊Bitter orange extract | Alternative |
Prefer products with a labeled p-synephrine amount and minimal added stimulants.
Minimum: 4 weeks
Optimal: 12 weeks
Cycling: Use intermittently; avoid continuous high-dose stimulant use.
Note: Earlier in the day; limit caffeine co-ingestion.
Dose-response data unavailable. The current published research for Synephrine does not provide sufficient dose-specific outcome data to generate reliable dose-response curves.
Refer to the Dosage & Timing section above for recommended dose ranges based on available evidence.
Modestly raises fat-oxidation rate, especially during exercise.
A mild 'energy'/alertness effect, often amplified by caffeine in the same product.
Can increase heart rate and blood pressure, especially when stacked with caffeine or other stimulants.
Despite the thermogenic effect, randomized evidence for meaningful weight loss is weak.
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.
Tip: Use low isolated doses; avoid caffeine stacks
Tip: Reduce dose; avoid stimulant combinations
Tip: Reduce dose
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. The most commonly reported side effects are 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.
Enhances mitochondrial energy production and acts as a lipid-soluble antioxidant — critical for heart health and depleted by statins.
Bitter orange can inhibit CYP3A4, raising levels of some drugs (similar concern to grapefruit).