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Limited evidenceWeight management

Bitter Orange (Synephrine)

Bitter orange (Citrus aurantium) and its alkaloid p-synephrine became the post-ephedra fat burner ingredient, but a systematic review and meta-analysis found essentially no meaningful weight-loss effect while confirming measurable cardiovascular activity. The risk-to-benefit ratio is poor, especially in stimulant stacks.

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What the science says

  • Weight-loss effects are small to absent Limited evidence

    A systematic review and meta-analysis of Citrus aurantium extracts and p-synephrine found the evidence for body-weight reduction weak and inconsistent, with most trials small, short and confounded by co-administered caffeine. Earlier meta-analytic work reached the same conclusion: no clear evidence of clinically meaningful weight loss from bitter orange.

  • It does modestly raise fat oxidation during exercise Moderate evidence

    In randomised crossover work, 3 mg/kg p-synephrine raised maximal fat oxidation rate during graded cycling in trained cyclists (roughly a 7-11% increase in MFO in reported studies) without changing heart rate or blood pressure at that dose. Increased fat oxidation during a single session, however, does not translate to fat loss when energy balance is unchanged.

  • Cardiovascular effects are real, and worse in stimulant combinations Moderate evidence

    Meta-analytic data show p-synephrine can raise heart rate and blood pressure, and a review of case reports on pre-workout supplements containing synephrine documents arrhythmias, myocardial infarction, ischaemic stroke and hypertensive events — nearly all in products that also contained high-dose caffeine or other stimulants.

  • It interferes with drug metabolism Moderate evidence

    Bitter orange contains furanocoumarins and, like grapefruit, inhibits intestinal CYP3A4, raising blood levels of numerous medications. It has been shown to increase exposure to drugs such as felodipine and midazolam, a real interaction risk independent of any stimulant effect.

Dosage & safety

Studied doseStudied doses: 3 mg/kg p-synephrine (about 100-200 mg for a typical adult) acutely for fat-oxidation studies; weight-management trials generally used 10-50 mg/day p-synephrine, often with caffeine, for 6-12 weeks. Commercial labels commonly list 100-200 mg bitter orange extract standardised to 6-30% synephrine (roughly 6-60 mg synephrine). Because the reliably demonstrated effects are cardiovascular rather than weight-related, there is no dose we recommend for fat loss.
SafetyAdverse effects include increased heart rate and blood pressure, palpitations, headache and anxiety, amplified substantially by caffeine. Serious case reports include arrhythmia, angina, myocardial infarction, ischaemic colitis and stroke in otherwise young, healthy users of synephrine-containing pre-workouts and fat burners. Contraindicated in cardiovascular disease, hypertension, arrhythmia, glaucoma and hyperthyroidism, and with MAO inhibitors. Because of CYP3A4 inhibition, avoid with statins, calcium channel blockers, immunosuppressants, some benzodiazepines and many other drugs. Synephrine is on the WADA monitoring program and is banned by some sporting bodies; several national regulators (including Health Canada and authorities in the EU) restrict its dose in supplements. Avoid in pregnancy and breastfeeding.

How to take it

TimingMorning if used at all — it raises heart rate and blood pressure for hours.
With food?Either way.
Worth knowingRead the label for milligrams of p-synephrine, not extract weight: 200 mg of a 6% extract is 12 mg of the actual compound.

Interactions

With medications

  • MAO inhibitors

    Synephrine is a sympathomimetic and combining it with an MAOI risks a hypertensive crisis. do not combine

  • CYP3A4 substrates (statins, calcium channel blockers, ciclosporin, some benzodiazepines)

    Bitter orange furanocoumarins inhibit CYP3A4 much as grapefruit does, raising blood levels of these drugs. avoid it, or check every medication with a pharmacist first

  • blood-pressure medication and other stimulants (decongestants, ADHD medication)

    Additive rise in heart rate and blood pressure, against treatment. do not combine

With other supplements

  • caffeine

    Caffeine substantially amplifies synephrine's cardiovascular effects, and most products deliberately combine the two. avoid the combination if you have any cardiovascular risk

Well-established interactions only — this is not a complete list. Always tell your doctor and pharmacist what you take.

Frequently asked questions

Does bitter orange (synephrine) help you lose weight?

Bitter orange and its alkaloid p-synephrine have weak and inconsistent evidence for weight loss (limited evidence), with most trials small, short and confounded by added caffeine. There is no dose recommended for fat loss, because its reliably demonstrated effects are cardiovascular rather than weight-related.

Is synephrine safe for your heart?

Synephrine can raise heart rate and blood pressure, and case reports link synephrine-containing pre-workouts and fat burners to arrhythmias, heart attack and stroke, nearly all in products that also contained high-dose caffeine (moderate evidence). Bitter orange is contraindicated in cardiovascular disease, hypertension and arrhythmia.

Does bitter orange interact with medications?

Bitter orange inhibits intestinal CYP3A4 much as grapefruit does, raising blood levels of drugs such as statins, calcium channel blockers, ciclosporin and some benzodiazepines (moderate evidence). It must not be combined with MAO inhibitors because of the risk of a hypertensive crisis.

Does synephrine increase fat burning during exercise?

In trials in trained cyclists, 3 mg/kg p-synephrine raised maximal fat oxidation during exercise by roughly 7-11% (moderate evidence). Burning more fat during a single session does not translate into fat loss when your energy balance is unchanged.

Scientific references

Where to buy

Primaforce, Syneburn, 10 mg, 180 Capsules

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