Herbs & Botanicals · Herbs · Citrus peel and extract sold for weight loss and sport, with weak benefit evidence and real heart cautions

Bitter Orange

Q: Does bitter orange help you lose weight?

The latest meta-analysis of 18 placebo-controlled trials found no significant weight loss and no change in body composition. NCCIH says its effect on weight is unclear.

Q: Is bitter orange safe for the heart?

Not for everyone. Pooled trials found raised blood pressure after prolonged use. Case reports describe heart attacks, strokes, fast heart rhythm and fainting, mostly with multi-ingredient products. Single doses in 18 healthy volunteers did not change heart rate or ECG in one trial. If you have heart or blood pressure problems, ask a doctor first.

Q: Can bitter orange cause long QT or dangerous rhythms?

One dose of standardised extract did not change the QT interval in 18 healthy people. One young woman fainted with a QT of 516 ms after a multi-ingredient product. Whether bitter orange itself causes this is unproven.

Q: Is it safe with caffeine or pre-workout products?

Avoid the combination. The German BfR says synephrine with caffeine and exercise raises the risk, and a small trial found raised adrenaline-type markers with the pair.

Q: Does bitter orange interact with medicines like grapefruit does?

Seville orange juice is used in studies to switch off intestinal CYP3A4 and raised felodipine levels. One branded extract held very little furanocoumarin, but other products were not tested. Ask a pharmacist if your medicine has a grapefruit warning.

Q: Can I take it with an MAO inhibitor or decongestant?

The authors of a juice trial advise people on MAO inhibitors or decongestants to avoid it. Ask a pharmacist.

Q: Is it safe in pregnancy or breastfeeding?

NCCIH says it may not be safe, and animal data suggest it might reduce milk. Avoid supplements. A small trial of inhaled oil in pregnancy reported benefit, but that is a different use.

Q: Can athletes use it?

NCCIH says the NCAA bans synephrine. Octopamine was prohibited and synephrine monitored in older WADA documents; we could not confirm the current list, so check it yourself.

Q: Do supplements contain what the label says?

Often not. In an FDA test of 59 products, only 5 of 23 with a synephrine claim were within 80-120% of the label, and some had hidden synthetic amines.

Q: Does the essential oil help anxiety?

Three small trials found lower anxiety scores after inhaling the oil, but blinding was weak and some used flower oil. NCCIH says benefit is unclear. Do not swallow the oil.

Citrus aurantium L. · also called Bitter orange, Seville orange, sour orange, zhi shi (Chinese), p-synephrine supplement, neroli (flower oil), naranja amarga (Spanish)

Bitter orange is a citrus tree whose peel, fruit and flowers are used in cooking, perfume and herbal products. Its extract contains p-synephrine, a stimulant-type compound that was sold as an ephedra substitute for weight loss and sport. Research does not show clear benefit, and several reviews and case reports raise heart and blood pressure concerns, especially with caffeine.

General information, not medical advice. Last substantive update October 25, 2026 · Not medically reviewed. A named clinician has not signed off on this page. How this page is made

About Bitter Orange

Bitter orange (Citrus aurantium) is a sour citrus used in cooking and perfume. Its extract supplements, rich in p-synephrine, are sold for weight loss and sport but are not shown to work and carry heart and blood pressure cautions. Inhaled oil has some small positive trials.

What it is

Bitter orange (Citrus aurantium) is a citrus tree native to Southeast Asia, per NCCIH. The fruit is too sour to eat raw, but fruit, peel and oils are used in cooking, flavouring beer and spirits, and perfume.

The extract holds p-synephrine, a stimulant-type compound that looks a little like ephedrine but works differently. It became popular after the US banned ephedra alkaloids in supplements in 2004.

^{15 17}

Traditional and current uses

Today it is promoted as a supplement for weight loss and sport, and the oil is used on the skin and in aromatherapy.

NCCIH says bitter orange has not been clearly shown to help for any health purpose.

¹⁵

Four things that are not the same

p-Synephrine or extract supplements are the form linked to heart and blood pressure cautions. Inhaled oils (peel oil, neroli from flowers, petitgrain from leaves) are a separate use. Juice and marmalade are foods that can interact with some medicines. Peel or flower tea has no human trials.

Evidence for one form should not be applied to another.

^{15 14 21}

What the research shows

The best pooled analysis found no weight-loss benefit and a rise in blood pressure. Small lab trials show more fat burning during exercise after one dose but no sport performance gain. Some trials were industry-linked, which we flag.

Inhaled oil trials (three, small, Iranian) report lower anxiety scores, with weak blinding.

^{10 5 6 25 14}

At a glance

Traditional uses history, not proof

Fruit, peel and oils in cooking, drinks and perfume
Bitter peel and flower teas in herbal tradition (not verified here)
Aromatherapy with the oil for anxiety and sleep

Studied for research

Weight loss, low (no benefit in the latest pooled analysis)
Fat burning during exercise (one-dose lab trials), low
Sports performance, low (mostly no effect)
Anxiety with inhaled oil, low
Fungal skin infections and tea for digestion, insufficient

Main compounds

p-Synephrine (isolated or in extract)
Octopamine and related amines (in some products)
Limonene and other peel oil compounds
Flavonoids (naringin, hesperidin) and furanocoumarins (bergapten)

Common forms

Peel or fruit extract supplements (p-synephrine)
Combination weight-loss and pre-workout products, often with caffeine
Essential oil (peel, flower neroli) for skin or inhaling
Juice, marmalade and peel as food; teas and tinctures

Research links: NCCIH: Bitter Orange · Koncz 2022 meta-analysis (PubMed) · Research Library · Genes & Biomarkers Library

The plant and its history

Accepted scientific name: Citrus aurantium L.
Naming authority: GBIF backbone lists Citrus × aurantium L. (canonical Citrus aurantium) as ACCEPTED, usage key 8077391, exact match, confidence 97.
Synonyms: Citrus x aurantium L.
Common names: Bitter orange (English); Seville orange (English); Sour orange (English); Zhi shi (Chinese (pinyin))
Botanical family: Rutaceae (citrus family)
Classification: Plantae > Tracheophyta > Magnoliopsida > Sapindales > Rutaceae > Citrus > Citrus aurantium
Native range: NCCIH: the tree is native to Southeast Asia.
Habitat: Not verified in the sources read.
What the plant looks like: Roots: Not verified.; Stems: Not verified.; Leaves: Not verified; leaf oil is called petitgrain per Dosoky 2018.; Flowers: Flowers give neroli oil per the trial and review abstracts.; Fruit: NCCIH: fruit too sour to eat raw; fruit, peel and oils used in cooking, beer and spirits, perfume.
Cultivation: Not verified.
Harvest and processing: Not verified. Zhi shi (unripe fruit) is a traditional Chinese name from NCCIH.
Look-alikes and adulterants: Name: Sweet orange (Citrus sinensis); Note: A different species (sweet orange); not covered by this profile.; Name: Grapefruit (Citrus x paradisi); Note: Known for CYP3A4 and furanocoumarin drug interactions; Seville orange juice acts in a similar way in studies.; Name: Bergamot (Citrus bergamia); Note: A different citrus species with its own oil; not covered here.
Sustainability and conservation: Not assessed in the sources read.

Traditional use and history history, not clinical proof

Tradition or era	Documented use	Source
Cooking and perfumery	Fruit, peel and essential oils are used in cooking, as flavourings in beer and spirits, and in perfumes.	s-nccih-bitter-orange
After the 2004 US ephedra ban	Bitter orange became popular as an ephedra alternative in weight-loss and sport supplements.	s-nccih-bitter-orange
Aromatherapy	The oil is used topically and in aromatherapy, including for anxiety and insomnia, without clear proof of benefit.	s-nccih-bitter-orange
Chinese medicine (zhi shi)	Zhi shi is listed as a common name by NCCIH. Traditional uses were not read and are NOT verified.	s-nccih-bitter-orange
European herbal tradition	A secondary encyclopedia (found by web search) lists bitter peel for dyspepsia and poor appetite via Commission E and notes no EMA/HMPC monograph. NOT verified.	Altmeyer's encyclopedia via web search (secondary, not read in full)

Traditional use shows how a plant was used. It does not show that a supplement works or is safe today.

What is inside, and how it may work

What the plant contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.

Main compounds

Compound	Family	Where it is concentrated	Activity studied	Level of evidence
p-Synephrine PubChem 7172	protoalkaloid (phenethylamine)	Fruit and peel of C. aurantium Seville orange juice about 56.9 micrograms/ml in one trial	Stimulant-type amine, structurally similar to ephedrine but with different pharmacology (NCCIH); proposed adrenergic activity. ^{21 15}	Human data
Octopamine PubChem 4581	biogenic amine	Found in some products Not detected in Seville orange juice in one trial	Prohibited in sport per a 2012 paper; on FDA's advisory list per FDA authors. ^{21 28 20}	Human data
Limonene PubChem 22311	monoterpene	Peel essential oil Not given in sources read	Common citrus oil component; no activity verified here. ¹⁸	Laboratory research
Naringin PubChem 442428	flavanone glycoside	Citrus fruit Tested at 600 mg in one trial	Combined with p-synephrine in one trial that reported a larger metabolic-rate rise. ²⁵	Human data
Hesperidin PubChem 10621	flavanone glycoside	Citrus fruit Tested at 100 or 1000 mg in one trial	Combined with p-synephrine and naringin; response was non-linear. ²⁵	Human data
Bergapten PubChem 2355	furanocoumarin	Fruit and juice Under 20 micrograms/g total furanocoumarins in four branded extracts	Named by the authors as the main furanocoumarin in bitter orange; grapefruit-type furanocoumarins relate to CYP3A4. ²⁶	Laboratory research
Tyramine and N-methyltyramine PubChem 5610	amines	Found in some products Measured in FDA analysis	On the FDA advisory list (N-methyltyramine). ²⁰	Laboratory research

Mechanisms, receptors and pathways

Target or pathway	Gene or receptor	What was found	Level
Adrenergic (sympathetic) stimulation	Adrenergic receptors (as proposed)	p-Synephrine is proposed to act on adrenaline-type receptors. Human trials show mixed effects on blood pressure; animal studies in the BfR assessment show blood pressure rise and ventricular arrhythmia. ^{1 15}	Animal research
Fat oxidation during exercise	Not specified	p-Synephrine raised the maximal fat oxidation rate in healthy volunteers (human). ^{5 7}	Human data
Intestinal CYP3A4 inhibition	CYP3A4	Seville orange juice is used in studies to inhibit intestinal CYP3A4, and raised felodipine exposure per a review. ^{21 4}	Human data
Aroma and brain	Not studied	No mechanism is established for the anxiety-lowering effect of the inhaled oil. ^{14 12}	Human data

Absorption, metabolism and elimination

Absorption: Not studied in the abstracts read. Blood levels of p-synephrine were drawn in the 2016 safety trial but results are not in the abstract.
Distribution: Not studied.
Metabolism: Not covered in the abstracts read.
Elimination: Not studied; urinary octopamine did not rise after synephrine or supplements in a doping-control study.
Bioavailability: Unknown.

^{24 28 4 26}

Isolated compounds versus whole extracts

Peel, whole extract, isolated p-synephrine, juice and essential oil differ. p-Synephrine supplements are the focus of heart and blood-pressure concerns. The oil (neroli from flowers, peel oil) is used by inhalation. Whole peel and juice carry furanocoumarins relevant for medicines. Branded standardised extracts may be low in furanocoumarins.

Nutritional composition

Bitter orange fruit is too sour to eat raw; peel and juice are used as flavouring (NCCIH). Marmalade and juice are food uses, but see the Safety tab if you take medicines affected by grapefruit.

8benefits and uses looked at

30studies and sources checked

Low certaintybest evidence rating found

7lab markers tracked in trials

4 low certainty2 very low certainty2 not enough evidence

What is Bitter Orange good for?

The main proposed uses and how strong the human evidence is for each. Read the Safety tab before the benefits.

Weight loss (p-synephrine or bitter orange extract)Low certaintyA 2022 meta-analysis of 18 placebo-controlled trials found weight loss after prolonged use was not significant and body composition did not change, and the authors say there is no evidence it helps weight loss. A 2004 review found one trial of 20 people with no significant benefit. NCCIH says its effect on body weight is unclear. Many trials were small or used combination products. Calories burned at restVery low certaintyOne small industry-linked trial (about 10 per group) reported a rise of 65 kcal at 75 minutes after p-synephrine alone, and larger with citrus flavonoids. It was a single dose and not a weight-loss result. Fat burning during exerciseLow certaintyIn two small lab crossover trials (18 and 13 people), p-synephrine raised the maximal fat oxidation rate during cycling without changing heart rate. It did not add to caffeine. It is unknown whether it works over weeks. Sports performanceLow certaintyIn 13 sprinters, p-synephrine did not change jumps or 60 m and 100 m sprint speed. NCCIH says most studies did not show benefit. Check anti-doping rules; the NCAA bans synephrine. Bitter orange with caffeine (a caution, not a benefit)Very low certaintyIn 10 active men a Citrus aurantium plus caffeine capsule raised heart rate, epinephrine and norepinephrine. The German BfR warns the pair is riskier, especially with exercise. Anxiety (inhaled Citrus aurantium oil)Low certaintyThree small trials in Iran (140, 80 and 68 people) found lower anxiety scores after inhaling the oil, one with neroli flower oil. Blinding was weak and the plant part was unclear. A 2025 corrigendum exists for the pregnancy trial. Fungal skin infections (oil on skin)Not enough evidenceNCCIH says the one study had no comparison group, so it is not possible to tell if the oil helps. Digestion (peel or flower tea)Not enough evidenceWe found no human trial of bitter orange tea or tincture. Traditional use is described in secondary sources that we did not verify.

Benefits, one by one

Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.

Weight loss and body composition (p-synephrine or bitter orange extract)

Low certainty

The main reason people buy bitter orange extract. The best pooled analysis found no evidence that it helps weight loss, and it found raised blood pressure.

3 studiesTrials used extract or p-synephrine, alone or inside combination prod…

Studies, doses and limits

What the trials found

A 2022 systematic review and meta-analysis of 18 placebo-controlled human trials found weight loss after prolonged use was not significant and body composition did not change. The authors state there is no evidence synephrine helps weight loss. A 2004 review found only one eligible trial (20 people, 6 weeks), with no significant benefit. NCCIH says effects on body weight are unclear because studies were small, often of combination products, and conflicting.

Results

No reliable weight-loss benefit shown.

Effect sizes as reported

Weight loss not significant; body composition unchanged (Koncz 2022).

Why this rating

The latest pooled analysis is null for weight, but the trials are small, mixed in product and design, and many tested multi-ingredient products. Certainty that it helps weight loss is low, and the evidence leans against a benefit.

Form and dose studied

Trials used extract or p-synephrine, alone or inside combination products; amounts are not given here.

Who was studied

Adults in short trials of weeks, mostly healthy or overweight volunteers.

Limits

Many trials were small and some were industry-linked. Combination products make the bitter orange effect impossible to isolate.

Why researchers looked

Bitter orange extracts were sold as 'ephedra-free' fat burners after the US banned ephedra alkaloids in supplements in 2004. p-Synephrine is a stimulant-type compound that looks a little like ephedrine.

Traditional use

Peel is used in cooking and flavouring. A traditional role as a slimming aid is not documented in the sources we read.

Proposed mechanism Pharmacological theory

p-Synephrine is thought to act on adrenaline-type receptors to raise energy use and fat breakdown. This is a proposal; the human results below do not confirm it for weight loss.

A proposed mechanism does not show that the effect happens in people.

See the Safety tab first: p-synephrine products can raise blood pressure and heart rate, and reports of heart attack, stroke and abnormal rhythm exist.

^{10 2 15}

Resting metabolic rate (calories burned at rest)

Very low certainty

One small single-dose trial reported a rise in calories burned at rest after p-synephrine, especially with citrus flavonoids. It was industry-linked and very short.

1 studies50 mg p-synephrine, alone or with naringin and hesperidin, in juice.

Studies, doses and limits

What the trials found

A 2011 randomised, placebo-controlled trial gave about 10 people per group 50 mg p-synephrine alone or with the flavonoids naringin and hesperidin and measured at 75 minutes. Synephrine alone raised the metabolic rate 65 kcal versus placebo; with naringin and 100 mg hesperidin the rise was 183 kcal (p<0.02); with 1000 mg hesperidin only 79 kcal. Heart rate and blood pressure did not change. One author was a Nutratech employee and two were Nutratech consultants.

Results

A short-lived rise in resting calorie burn in one small trial.

Effect sizes as reported

+65 kcal (synephrine alone); up to +183 kcal (with naringin and hesperidin); measured 75 minutes after one dose.

Why this rating

One tiny, single-dose, industry-linked trial. A rise in metabolic rate over 75 minutes is not weight loss.

Form and dose studied

50 mg p-synephrine, alone or with naringin and hesperidin, in juice.

Who was studied

Healthy adults.

Limits

Very small groups, one dose, funded by or tied to a supplement maker, and not repeated.

Why researchers looked

A higher resting metabolic rate is the idea behind 'thermogenic' supplements.

Traditional use

Not applicable.

Proposed mechanism Pharmacological theory

p-Synephrine is proposed to stimulate adrenaline-type receptors; not shown by this trial.

A proposed mechanism does not show that the effect happens in people.

See the Safety tab first: p-synephrine products can raise blood pressure and heart rate, and reports of heart attack, stroke and abnormal rhythm exist.

²⁵

Fat burning during exercise (acute lab trials of p-synephrine)

Low certainty

In a few small lab studies, a single dose of p-synephrine raised the rate at which people burn fat while cycling. This is not the same as losing weight.

3 studiesp-Synephrine 3 mg per kg body weight, single dose, in the trials read.

Studies, doses and limits

What the trials found

In 18 healthy people, p-synephrine (3 mg/kg) raised maximal fat oxidation during cycling from 0.29 to 0.40 g/min (P=0.01) with no change at rest. In 13 people, caffeine, p-synephrine and the two together each raised maximal fat oxidation (about 0.43 to 0.45 vs 0.30 g/min on placebo) without changing total energy use or heart rate; the combination was not additive. A 2021 narrative review says the effect is seen at 2-3 mg/kg and low to moderate intensity, and that it is not known whether it lasts with repeated use.

Results

Higher fat burning during exercise after one dose.

Effect sizes as reported

Maximal fat oxidation +0.11 g/min (n=18); about +0.13 to +0.15 g/min (n=13).

Why this rating

Consistent small crossover trials but from one research group, single doses, small numbers and a lab outcome rather than weight lost.

Form and dose studied

p-Synephrine 3 mg per kg body weight, single dose, in the trials read.

Who was studied

Healthy, active adults.

Limits

Acute dose only; effect on body fat over months is unknown; same group ran most trials.

Why researchers looked

A Spanish research group tested whether p-synephrine shifts the body towards burning fat during exercise.

Traditional use

Not applicable.

Proposed mechanism Preliminary mechanism

Proposed action on adrenaline-type receptors that raises fat breakdown.

A proposed mechanism does not show that the effect happens in people.

See the Safety tab first: p-synephrine products can raise blood pressure and heart rate, and reports of heart attack, stroke and abnormal rhythm exist. These trials did not see heart-rate changes, but the same compound raised blood pressure in pooled trials.

^{5 7 23}

Sports performance (sprinting, jumping, strength)

Low certainty

Most studies found no clear boost to athletic performance. Check the sport-rules note on the Safety tab.

3 studiesp-Synephrine 3 mg/kg single dose.

Studies, doses and limits

What the trials found

In 13 experienced sprinters, 3 mg/kg of p-synephrine did not change jump heights or 60 m and 100 m sprint speed (for example 100 m 8.8 vs 8.8 m/s) and did not raise side-effect reports. The 2021 review says acute intake does not change running sprint performance, jumping capacity or aerobic capacity. NCCIH says results across studies were inconsistent and most did not show benefit.

Results

No performance benefit in sprinters.

Effect sizes as reported

No change in jumps or sprints.

Why this rating

Small randomised trials agree on null performance results, but few trials and mostly one research group.

Form and dose studied

p-Synephrine 3 mg/kg single dose.

Who was studied

Experienced sprinters; healthy adults.

Limits

Only acute doses; other sports and long-term use not tested.

Why researchers looked

Sold in pre-workout products as a stimulant.

Traditional use

Not applicable.

Proposed mechanism Pharmacological theory

Proposed stimulant effect; not shown in these performance tests.

A proposed mechanism does not show that the effect happens in people.

See the Safety tab first: p-synephrine products can raise blood pressure and heart rate, and reports of heart attack, stroke and abnormal rhythm exist.

^{6 23 15}

Bitter orange plus caffeine (how the combination acts)

Very low certainty

This is a safety topic more than a benefit. With caffeine, bitter orange raised adrenaline-system activity in one small trial.

3 studies100 mg Citrus aurantium + 100 mg caffeine capsule in the trial.

Studies, doses and limits

What the trials found

In 10 active men who use caffeine, 100 mg Citrus aurantium plus 100 mg caffeine raised heart rate, sympathetic markers of heart-rate variability and plasma epinephrine and norepinephrine compared with placebo. In the cycling trial above, p-synephrine plus caffeine did not raise heart rate during exercise. The German BfR notes animal studies where caffeine and exercise made synephrine's cardiovascular effects stronger.

Results

Raised sympathetic activity with the combination in one trial; mixed on heart rate.

Effect sizes as reported

Epinephrine, norepinephrine and heart rate rose with the combination only.

Why this rating

A very small crossover study; the BfR statement rests on animals plus case reports.

Form and dose studied

100 mg Citrus aurantium + 100 mg caffeine capsule in the trial.

Who was studied

Ten active men who use caffeine.

Limits

Cannot separate the bitter orange part from caffeine's.

Why researchers looked

Many weight-loss and pre-workout products combine the two.

Traditional use

Not applicable.

Proposed mechanism Preliminary mechanism

Both stimulate the sympathetic nervous system, so effects could add up.

A proposed mechanism does not show that the effect happens in people.

See the Safety tab first: p-synephrine products can raise blood pressure and heart rate, and reports of heart attack, stroke and abnormal rhythm exist.

^{9 1 7}

Anxiety before procedures and in pregnancy (inhaled Citrus aurantium oil)

Low certainty

Small trials in Iran found lower anxiety scores after inhaling the oil. This is aromatherapy, not a swallowed supplement, and the oil in some trials is neroli (from flowers).

4 studiesInhaled oil: 30% flower oil in paraffin; oil on a mask; or inhaled fo…

Studies, doses and limits

What the trials found

In 140 people with acute coronary syndrome, inhaled 30% neroli (C. aurantium flower oil) gave a lower anxiety score than paraffin placebo (34.66 vs 42.36 on STAI, p<0.0001) with no side effects seen. In 80 patients before coronary angiography, inhaling the oil lowered STAI from 53.30 to 42.37 (water control unchanged; single-blind). In 68 pregnant women, five drops twice daily for a month lowered depression (-4.80 vs +1.03) and anxiety (-3.37 vs +0.79) compared with almond oil, but stress was not significantly different (p=0.166). A 2025 corrigendum exists for that paper.

Results

Lower anxiety scores on inhalation in three small trials.

Effect sizes as reported

STAI 34.66 vs 42.36 (n=140); STAI 53.30 to 42.37 (n=80); DASS-21 anxiety -3.37 vs +0.79 (n=68).

Why this rating

Three small, same-region trials with subjective scores, weak blinding (a water or odourless control) and unclear plant part. No large or independent trials.

Form and dose studied

Inhaled oil: 30% flower oil in paraffin; oil on a mask; or inhaled for 15-20 minutes, as each trial reports.

Who was studied

Hospital patients and pregnant women in Iran.

Limits

Subjective outcomes, small samples, blinding doubtful, flower oil is not the same as peel oil; photosensitivity of the peel oil was not checked in the sources read.

Why researchers looked

Bitter orange oil is used in aromatherapy for anxiety and sleep; NCCIH says it is unclear whether that helps.

Traditional use

Bitter orange oil is used in aromatherapy (NCCIH).

Proposed mechanism Preliminary mechanism

Not established; smell and expectation may play a part, and an odourless control cannot hide the scent.

A proposed mechanism does not show that the effect happens in people.

NCCIH says the oil is generally well tolerated in aromatherapy. Pregnancy: see Safety. Do not swallow the oil.

^{14 12 13 15}

Fungal skin infections (oil on the skin)

Not enough evidence

Only one uncontrolled study exists, so it is not possible to say if the oil helps.

1 studiesOil on skin.

Studies, doses and limits

What the trials found

NCCIH reports that the one study of bitter orange oil for these infections did not compare it with other treatments or a placebo, so its results are hard to interpret.

Results

Unknown.

Effect sizes as reported

Not available.

Why this rating

One uncontrolled study, summarised by NCCIH; we did not read the study itself.

Form and dose studied

Oil on skin.

Who was studied

Not applicable.

Limits

No control group.

Why researchers looked

The oil has been tried on ringworm, athlete's foot and jock itch.

Traditional use

Traditional topical use is not documented in the sources read.

Proposed mechanism Preliminary mechanism

Not studied in the sources read.

A proposed mechanism does not show that the effect happens in people.

Citrus oils can irritate skin; patch test and sun cautions are in Safety.

¹⁵

Peel or flower tea and digestive complaints

Not enough evidence

Peel and flowers are used as bitter teas for the stomach in European tradition. We found no human trial of the tea.

1 studiesTea or tincture of dried peel or flower; no amounts studied.

Studies, doses and limits

What the trials found

No randomised trial of bitter orange peel or flower tea was found for digestion, sleep or anything else. NCCIH does not mention tea or tincture.

Results

Unknown.

Effect sizes as reported

No trial data.

Why this rating

No human trials found.

Form and dose studied

Tea or tincture of dried peel or flower; no amounts studied.

Who was studied

Not studied.

Limits

No evidence beyond tradition.

Why researchers looked

Bitter orange peel is a classic bitter used in flavouring and in some European herbal books; a secondary encyclopedia describes a German Commission E use for dyspepsia and poor appetite, which we did not verify.

Traditional use

European herbal tradition (secondary source, not verified).

Proposed mechanism Pharmacological theory

Bitter-tasting compounds are thought to prompt digestive juices; not tested here.

A proposed mechanism does not show that the effect happens in people.

Peel tea is a different exposure from p-synephrine supplements, but the furanocoumarins in peel may still matter with medicines (see Safety).

¹⁵

Connections to the rest of health

How Bitter Orange connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.

Explore every connection: goals, body systems, organs, symptoms, genes

Kind of connection Connected to Search

A. Wellness goals

Connected to	Kind of connection	Evidence status	Context	Studies
Weight Management	Potential benefit	Low certainty	Weight loss and body composition (p-synephrine or bitter orange extract): The main reason people buy bitter orange extract. The best pooled analysis found no evidence that it helps weight loss, and it found raised blood pressure. Fat burning during exercise (acute lab trials of p-synephrine): In a few small lab studies, a single dose of p-synephrine raised the rate at which people burn fat while cycling. This is not the same as losing weight.	^{10 2 15 5 7 23}
Metabolic Health	Potential benefit	Low certainty	Weight loss and body composition (p-synephrine or bitter orange extract): The main reason people buy bitter orange extract. The best pooled analysis found no evidence that it helps weight loss, and it found raised blood pressure. Fat burning during exercise (acute lab trials of p-synephrine): In a few small lab studies, a single dose of p-synephrine raised the rate at which people burn fat while cycling. This is not the same as losing weight.	^{10 2 15 5 7 23}
Metabolic Health	Preliminary mechanism	Very low certainty	Resting metabolic rate (calories burned at rest): One small single-dose trial reported a rise in calories burned at rest after p-synephrine, especially with citrus flavonoids. It was industry-linked and very short.	²⁵
Energy Boost	Preliminary mechanism	Very low certainty	Resting metabolic rate (calories burned at rest): One small single-dose trial reported a rise in calories burned at rest after p-synephrine, especially with citrus flavonoids. It was industry-linked and very short.	²⁵
Endurance Support	Potential benefit	Low certainty	Fat burning during exercise (acute lab trials of p-synephrine): In a few small lab studies, a single dose of p-synephrine raised the rate at which people burn fat while cycling. This is not the same as losing weight.	^{5 7 23}
Peak Performance	Potential benefit	Low certainty	Sports performance (sprinting, jumping, strength): Most studies found no clear boost to athletic performance. Check the sport-rules note on the Safety tab.	^{6 23 15}
Physical Stamina	Potential benefit	Low certainty	Sports performance (sprinting, jumping, strength): Most studies found no clear boost to athletic performance. Check the sport-rules note on the Safety tab.	^{6 23 15}
Energy Boost	Biological association	Very low certainty	Bitter orange plus caffeine (how the combination acts): This is a safety topic more than a benefit. With caffeine, bitter orange raised adrenaline-system activity in one small trial.	^{9 1 7}
Anxiety Support	Potential benefit	Low certainty	Anxiety before procedures and in pregnancy (inhaled Citrus aurantium oil): Small trials in Iran found lower anxiety scores after inhaling the oil. This is aromatherapy, not a swallowed supplement, and the oil in some trials is neroli (from flowers).	^{14 12 13 15}
Calm Relaxation	Potential benefit	Low certainty	Anxiety before procedures and in pregnancy (inhaled Citrus aurantium oil): Small trials in Iran found lower anxiety scores after inhaling the oil. This is aromatherapy, not a swallowed supplement, and the oil in some trials is neroli (from flowers).	^{14 12 13 15}
Mood Balance	Potential benefit	Low certainty	Anxiety before procedures and in pregnancy (inhaled Citrus aurantium oil): Small trials in Iran found lower anxiety scores after inhaling the oil. This is aromatherapy, not a swallowed supplement, and the oil in some trials is neroli (from flowers).	^{14 12 13 15}
Healthy Skin	Traditional use	Not enough evidence	Fungal skin infections (oil on the skin): Only one uncontrolled study exists, so it is not possible to say if the oil helps.	¹⁵
Digestive Support	Traditional use	Not enough evidence	Peel or flower tea and digestive complaints: Peel and flowers are used as bitter teas for the stomach in European tradition. We found no human trial of the tea.	¹⁵

B. Body systems

Connected to	Kind of connection	Evidence status	Context	Studies
Cardiovascular system	Adverse effect or risk	Moderate certainty	Raised blood pressure and heart rate in pooled trials; heart rhythm, heart attack and stroke case reports. Raised blood pressure and heart rate; heart attack, stroke and rhythm case reports. Preparation or compound: Bitter orange extract / p-synephrine supplements	^{10 30}
Nervous system	Adverse effect or risk	Low certainty	Stimulant-type sympathetic activation. Preparation or compound: p-Synephrine with caffeine	⁹
Metabolism and weight	Potential benefit	Low certainty	Acute fat-burning during exercise; no proven weight loss. Preparation or compound: p-Synephrine	^{10 5}
Liver	Drug or supplement interaction	Not enough evidence	Seville orange juice used to inhibit intestinal CYP3A4; felodipine exposure up. Preparation or compound: Bitter orange juice or peel with CYP3A4 medicines	^{21 4}
Metabolism Weight	Biological association	Low certainty	Studied for: Weight loss and body composition (p-synephrine or bitter orange extract) Studied for: Resting metabolic rate (calories burned at rest)	^{10 2 15 25 5 7 23}
Musculoskeletal System	Biological association	Low certainty	Studied for: Fat burning during exercise (acute lab trials of p-synephrine) Studied for: Sports performance (sprinting, jumping, strength)	^{5 7 23 6 15}
Cardiovascular System	Biological association	Very low certainty	Studied for: Bitter orange plus caffeine (how the combination acts)	^{9 1 7}
Nervous System	Biological association	Very low certainty	Studied for: Bitter orange plus caffeine (how the combination acts) Studied for: Anxiety before procedures and in pregnancy (inhaled Citrus aurantium oil)	^{9 1 7 14 12 13 15}
Integumentary System	Biological association	Not enough evidence	Studied for: Fungal skin infections (oil on the skin)	¹⁵
Digestive System	Biological association	Not enough evidence	Studied for: Peel or flower tea and digestive complaints	¹⁵

I. Biomarkers

Connected to	Kind of connection	Evidence status	Context	Studies
Body weight and body composition	Biological association	Low certainty	Measured in trials: no-change. A lab change is not the same as a health benefit.	¹⁰
Resting metabolic rate	Biological association	Very low certainty	Measured in trials: raised. A lab change is not the same as a health benefit.	²⁵
Maximal fat oxidation rate during exercise	Biological association	Low certainty	Measured in trials: raised. A lab change is not the same as a health benefit.	^{5 7}
Blood pressure (systolic and diastolic)	Biological association	Mixed findings	Measured in trials: mixed. A lab change is not the same as a health benefit.	^{10 24 11}
Heart rate	Biological association	Mixed findings	Measured in trials: mixed. A lab change is not the same as a health benefit.	^{10 7 9}
Anxiety score (State-Trait Anxiety Inventory)	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{14 12}
DASS-21 (depression, anxiety and stress scales)	Biological association	Low certainty	Measured in trials: mixed. A lab change is not the same as a health benefit.	¹³

J. Genes, receptors and enzymes

Connected to	Kind of connection	Evidence status	Context	Studies
CYP3A4	Preliminary mechanism	Human	Intestinal CYP3A4 is inhibited by Seville orange juice in studies.	^{21 4}
Adrenergic receptors	Preliminary mechanism	Animal	Proposed targets of p-synephrine; not shown in the abstracts read.	¹

L. Active compounds

Connected to	Kind of connection	Evidence status	Context	Studies
p-Synephrine	Biological association	Human	Stimulant-type amine, structurally similar to ephedrine but with different pharmacology (NCCIH); proposed adrenergic activity. Preparation or compound: Fruit and peel of C. aurantium	^{21 15}
Octopamine	Biological association	Human	Prohibited in sport per a 2012 paper; on FDA's advisory list per FDA authors. Preparation or compound: Found in some products	^{21 28 20}
Limonene	Biological association	In vitro	Common citrus oil component; no activity verified here. Preparation or compound: Peel essential oil	¹⁸
Naringin	Biological association	Human	Combined with p-synephrine in one trial that reported a larger metabolic-rate rise. Preparation or compound: Citrus fruit	²⁵
Hesperidin	Biological association	Human	Combined with p-synephrine and naringin; response was non-linear. Preparation or compound: Citrus fruit	²⁵
Bergapten	Biological association	In vitro	Named by the authors as the main furanocoumarin in bitter orange; grapefruit-type furanocoumarins relate to CYP3A4. Preparation or compound: Fruit and juice	²⁶
Tyramine and N-methyltyramine	Biological association	In vitro	On the FDA advisory list (N-methyltyramine). Preparation or compound: Found in some products	²⁰

Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 25, 2026).

Evidence at a glance: what changed in 7 lab markers

Tap a number to show only those markers. Counts are markers, not people.

Metabolic1 Other123

The evidence

The research centre for Bitter Orange. Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.

Evidence by outcome

Weight loss and body composition (p-synephrine or bitter orange extract) 3 studies Low certainty Resting metabolic rate (calories burned at rest) 1 studies Very low certainty Fat burning during exercise (acute lab trials of p-synephrine) 3 studies · 31 people in trials Low certainty Sports performance (sprinting, jumping, strength) 3 studies · 13 people in trials Low certainty Bitter orange plus caffeine (how the combination acts) 3 studies · 23 people in trials Very low certainty Anxiety before procedures and in pregnancy (inhaled Citrus aurantium oil) 4 studies · 288 people in trials Low certainty Fungal skin infections (oil on the skin) 1 studies Not enough evidence Peel or flower tea and digestive complaints 1 studies Not enough evidence

Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).

How we rate evidence

High certainty

Several well-run trials or reviews agree; further research is unlikely to change the picture much.

Moderate certainty

Good trials point the same way, but some doubt remains.

Low certainty

Small, short or inconsistent trials. The finding could change with better research.

Very low certainty

Very little or very weak human data. Treat as a possibility only.

Mixed findings

Trials or reviews disagree with each other.

Not enough evidence

Not enough human research to say either way.

Evidence against

Good research found no benefit, or found harm.

We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We searched PubMed, read the abstract of every PubMed study cited, read the NCCIH bitter orange page, and checked the plant name in GBIF and NCBI Taxonomy and compounds in PubChem. Not verified: EMA/HMPC, FDA, LiverTox, LactMed and current WADA lists could not be opened or confirmed. Most studies were read as abstracts only. Certainty ratings are the compiler's reading. Some trials are industry-linked and are flagged in the study notes.

Study library: every study we checked 30

Design Research type Plant part Year from Search

Study	Design	People	Product, dose, length	Result
Bakhyia 2017 [Risk assessment of synephrine in dietary supplements]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz · PMID 28058460 · DOI	Narrative review mixed	Animal and human data reviewed by the German BfR	Synephrine in supplements, often Citrus aurantium extract with caffeine fruit extract Not stated in the abstract Not stated in the abstract · vs Not applicable	In animals, oral synephrine raised blood pressure and caused ventricular arrhythmias, more so with caffeine and exercise. Some human studies and case reports point to cardiovascular effects. BfR concluded high intakes, especially with caffeine and exercise, raise the risk, and that daily intake from supplements should not exceed the median intake from ordinary foods. Risk assessment, not an effect size (None) Methods, limits and funding Outcomes: Cardiovascular risk Limitations: Article in German; abstract read only. Funding and conflicts: Government risk-assessment institute (BfR); no commercial funding stated Read: abstract
Bent 2004 Safety and efficacy of citrus aurantium for weight loss. Am J Cardiol · PMID 15541270 · DOI	Systematic review	20 Adults in the one eligible randomised trial	Citrus aurantium (product not named in the abstract) unspecified Not stated in the abstract 6 weeks · vs Placebo	Only one eligible randomised placebo-controlled trial was found. It followed 20 people for 6 weeks, showed no statistically significant weight-loss benefit and gave limited safety information. No significant weight-loss benefit (None) Methods, limits and funding Outcomes: Weight loss, safety Limitations: Very small evidence base; 2004 search. Funding and conflicts: Not stated in the abstract Read: abstract
Bouchard 2005 Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc · PMID 15819293 · DOI	Case report	1 38-year-old man without major risk factors	Stacker 2 Ephedra-Free (synephrine and caffeine) unspecified 1 or 2 capsules a day 1 week · vs Not applicable	Brain scans showed new infarctions in the thalamus and cerebellum. Other causes were negative; a spasm of the arteries was thought most likely. He nearly fully recovered after leaving hospital. Possible association (None) Methods, limits and funding Outcomes: Stroke Limitations: One person; product also contained caffeine. Funding and conflicts: Not stated in the abstract Read: abstract
Chen 2018 Food-drug interactions precipitated by fruit juices other than grapefruit juice: An update review. J Food Drug Anal · PMID 29703387 · DOI	Systematic review	46 randomised trials of juice-drug combinations	Fruit juices including Seville orange juice juice Not stated in the abstract Not stated in the abstract · vs Not applicable	Among the juice-drug pairs with possible clinical relevance, Seville orange juice increased felodipine bioavailability. The authors say that, unlike furanocoumarin-rich grapefruit juice, other juices did not cause severely harmful interactions despite sporadic case reports. Seville orange juice raised felodipine exposure (size not given) (None) Methods, limits and funding Outcomes: Drug bioavailability Limitations: About juice, not supplements; abstract read only. Funding and conflicts: Authors declare no conflicts Read: abstract
Gutiérrez-Hellín 2016 Acute p-synephrine ingestion increases fat oxidation rate during exercise. Br J Clin Pharmacol · PMID 27038225 · DOI	Controlled trial	18 18 healthy people	p-Synephrine 3 mg/kg, single dose isolated p-synephrine 3 mg per kg body weight Single dose · vs Placebo (cellulose), crossover	No change in energy use or fat burning at rest. During cycling maximal fat oxidation was higher (0.29 vs 0.40 g/min, P=0.01). Maximal fat oxidation +0.11 g/min (None) Methods, limits and funding Outcomes: Fat oxidation during cycling Limitations: One dose in a lab; not weight loss. Funding and conflicts: Not stated in the abstract Read: abstract
Gutiérrez-Hellín 2016 Acute consumption of p-synephrine does not enhance performance in sprint athletes. Appl Physiol Nutr Metab · PMID 26673246 · DOI	Controlled trial	13 13 experienced sprinters	p-Synephrine 3 mg/kg, single dose isolated p-synephrine 3 mg/kg Single dose · vs Placebo, crossover	No change in jumps (e.g. countermovement 37.4 vs 36.7 cm) or sprint speed (60 m 9.0 vs 9.0 m/s; 100 m 8.8 vs 8.8 m/s). Headache, stomach upset, muscle pain and insomnia did not increase. The authors note it was on the WADA monitoring program. No performance change (None) Methods, limits and funding Outcomes: Jump height, 60 m and 100 m sprint speed, side effects Limitations: 13 athletes, one dose. Funding and conflicts: Not stated in the abstract Read: abstract
Gutiérrez-Hellín 2018 Effects of p-Synephrine and Caffeine Ingestion on Substrate Oxidation during Exercise. Med Sci Sports Exerc · PMID 29727404 · DOI	Controlled trial	13 13 healthy people	p-Synephrine 3 mg/kg, caffeine 3 mg/kg, or both isolated p-synephrine 3 mg/kg each Single dose · vs Placebo, 4 crossover trials	Caffeine, p-synephrine and the combination each raised maximal fat oxidation compared with placebo (about 0.43 to 0.45 vs 0.30 g/min). No change in total energy use or heart rate during exercise. Combining them was not additive. Maximal fat oxidation about +0.13 to +0.15 g/min (None) Methods, limits and funding Outcomes: Fat oxidation, energy use, heart rate during cycling Limitations: Small, one dose, lab exercise test. Funding and conflicts: Not stated in the abstract Read: abstract
Hansen 2011 Developmental toxicity of Citrus aurantium in rats. Birth Defects Res B Dev Reprod Toxicol · PMID 21594979 · DOI	Animal research animal	Pregnant Sprague-Dawley rats	Synephrine or bitter orange extract by gavage, some with caffeine extract / synephrine Up to 100 mg synephrine/kg Daily during pregnancy · vs Vehicle	No developmental toxicity up to 100 mg synephrine/kg. Maternal weight dropped with the 6% extract plus caffeine, and with caffeine alone. No fetal harm in rats at the doses tested (None) Methods, limits and funding Outcomes: Fetal survival, weight, malformations Limitations: Rats; says nothing certain about women. Funding and conflicts: US FDA authors Read: abstract
Kliszczewicz 2018 The influence of citrus aurantium and caffeine complex versus placebo on the cardiac autonomic response: a double blind crossover design. J Int Soc Sports Nutr · PMID 30041682 · DOI	Controlled trial	10 10 active men who use caffeine	Citrus aurantium 100 mg plus caffeine 100 mg capsule extract (part not stated) 100 mg Citrus aurantium + 100 mg caffeine Single dose with exercise · vs Placebo (dextrose), crossover	Heart rate, sympathetic markers, epinephrine and norepinephrine rose after the combination only, not placebo. Recovery after exercise was similar. Increased sympathetic activity at rest with the combination (None) Methods, limits and funding Outcomes: Heart rate, heart-rate variability, epinephrine and norepinephrine Limitations: Combination with caffeine, so the part due to bitter orange cannot be separated; 10 men. Funding and conflicts: Authors declare no competing interests Read: abstract
Koncz 2022 The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients · PMID 36235672 · DOI	Meta-analysis	Adults in 18 placebo-controlled human trials of synephrine	p-Synephrine or Citrus aurantium extract (some products multi-ingredient) fruit extract / isolated p-synephrine Not stated in the abstract Not stated in the abstract · vs Placebo	After prolonged use systolic pressure rose 6.37 mmHg and diastolic 4.33 mmHg. Weight loss was not significant and body composition did not change. The authors say synephrine tends to raise blood pressure and heart rate and there is no evidence it helps weight loss. SBP +6.37 mmHg; DBP +4.33 mmHg (SBP 95% CI 1.02 to 11.72; DBP 0.48 to 8.18) Methods, limits and funding Outcomes: Weight, body composition, blood pressure, heart rate Limitations: Mixed products and designs; the authors call for further studies. Funding and conflicts: Authors declare no conflict of interest Read: abstract
Min 2005 Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects. Pharmacotherapy · PMID 16305290 · DOI	Controlled trial	18 18 healthy volunteers	Bitter-orange dried-fruit extract, 450 mg standardised to 27 mg m- or p-synephrine dried fruit extract 450 mg extract (27 mg synephrine), once Single dose, measured to 8 hours · vs Placebo (crossover)	QTc 402 vs 403 msec (p=0.653), systolic 114 vs 115 mmHg, diastolic 68 vs 68 mmHg. No significant change after one dose. No change in QTc or blood pressure after one dose (None) Methods, limits and funding Outcomes: QTc interval, blood pressure Limitations: Single dose only; the authors say multiple-dose safety needs study. Funding and conflicts: Not stated in the abstract Read: abstract
Moradi 2021 Essential Oil from Citrus aurantium Alleviates Anxiety of Patients Undergoing Coronary Angiography: A Single-Blind, Randomized Controlled Trial. Chin J Integr Med · PMID 32572778 · DOI	Controlled trial	80 80 patients before coronary angiography, Iran	Inhaled Citrus aurantium essential oil essential oil (part not stated) Inhaled 15-20 minutes, about 60 minutes before the procedure Single session · vs Distilled water	In the oil group STAI fell from 53.30 to 42.37 and blood pressure and pulse also fell; the water group did not change. No adverse reactions. STAI 53.30 to 42.37 (oil) vs no change (None) Methods, limits and funding Outcomes: Anxiety (STAI), blood pressure, pulse Limitations: Single-blind; one pre-procedure session; water placebo has no smell. Funding and conflicts: Not stated in the abstract Registration: IRCT2016040816797N2 (registered retrospectively) Read: abstract
Moradi 2025 The effect of aromatherapy with Citrus Aurantium essential oil on depression, stress and anxiety in pregnant women; a randomized controlled clinical trial. Taiwan J Obstet Gynecol · PMID 40368523 · DOI	Controlled trial	68 68 pregnant women (about 29 weeks)	Citrus aurantium essential oil, five drops on a face mask essential oil (part not stated) Five drops, twice a day, inhaled 20 minutes 1 month · vs Odourless sweet almond oil	Depression fell more with oil (-4.80 vs +1.03, p<0.001) and anxiety too (-3.37 vs +0.79, p<0.001); stress did not differ significantly (p=0.166). The authors call it safe. A 2025 corrigendum exists; the abstract shown for it lists only author details. Depression and anxiety lower; stress not significant (None) Methods, limits and funding Outcomes: DASS-21 depression, anxiety, stress Limitations: Small; almond-oil control is odourless so blinding is doubtful; corrigendum content not read in full. Funding and conflicts: Not stated in the abstract Read: abstract
Moslemi 2019 Citrus aurantium Aroma for Anxiety in Patients with Acute Coronary Syndrome: A Double-Blind Placebo-Controlled Trial. J Altern Complement Med · PMID 31211612 · DOI	Controlled trial	140 140 hospitalised patients with acute coronary syndrome, Iran	Inhaled 30% essential oil of Citrus aurantium flowers (neroli) in paraffin flower essential oil Three times a day Not stated in the abstract · vs Paraffin placebo	After treatment anxiety was 34.66 vs 42.36 on the STAI (p<0.0001). No side effect was observed. STAI 34.66 vs 42.36 (None) Methods, limits and funding Outcomes: Anxiety (STAI) Limitations: Single country; the oil is from the flower, not the peel; subjective outcome. Funding and conflicts: Not stated in the abstract Read: abstract
NCCIH 2024 NCCIH: Bitter Orange: Usefulness and Safety Web page · Source	Authoritative guidance	Not applicable	Not applicable Not applicable Not applicable Not applicable · vs Not applicable	Not clearly shown to help any health use. Likely safe in food amounts; oil generally well tolerated on skin or in aromatherapy. Serious events (abnormal rhythms, heart attacks, strokes) reported with supplements, mostly multi-ingredient. May not be safe in pregnancy or breastfeeding; animal data suggest it might reduce milk production. Talk to a provider about medicines. NCAA lists synephrine as banned. Cites the FDA analysis of 59 products. Not applicable Methods, limits and funding Outcomes: Guidance Limitations: Read on 2026-10-25; page date not shown. Read: full-text
Nasir 2004 Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc · PMID 15301335 · DOI	Case report	1 Healthy 22-year-old woman	Xenadrine EFX (ephedra-free; notable phenylephrine content) unspecified Second dose taken 1 hour before the event Single exposure · vs Not applicable	She fainted during exercise an hour after the second dose. The corrected QT interval was 516 ms and normalised within 24 hours. Heart tests and 9 months of loop-recorder monitoring off the product showed no arrhythmia. Possible association with QT prolongation (None) Methods, limits and funding Outcomes: Fainting, QT interval Limitations: One person; product has many ingredients; the report is about phenylephrine content rather than bitter orange by name. Funding and conflicts: Not stated in the abstract Read: abstract
Not applicable GBIF backbone: Citrus x aurantium L. (Citrus aurantium) Web page · Source	Database record	Not applicable	Not applicable Not applicable Not applicable Not applicable · vs Not applicable	GBIF matches Citrus aurantium (usage key 8077391, Citrus × aurantium L.) as ACCEPTED, family Rutaceae, genus Citrus. NCBI Taxonomy search returns taxid 43166. Not applicable Methods, limits and funding Outcomes: Guidance Limitations: API response read 2026-10-25. Read: full-text
Not applicable PubChem compound records (synephrine, octopamine, limonene, bergapten, naringin, hesperidin, tyramine, N-methyltyramine) Web page · Source	Database record	Not applicable	Not applicable Not applicable Not applicable Not applicable · vs Not applicable	CIDs checked by name lookup on 2026-10-25: synephrine 7172, octopamine 4581, limonene 22311, bergapten 2355, naringin 442428, hesperidin 10621, tyramine 5610, N-methyltyramine 9727. Not applicable Methods, limits and funding Outcomes: Guidance Limitations: API lookups by name. Read: full-text
Nykamp 2004 Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother · PMID 15026566 · DOI	Case report	1 55-year-old woman with an undetected left main coronary lesion and smoking history	Multi-ingredient weight-loss supplement with 300 mg bitter orange, taken for a year unspecified 300 mg bitter orange in a combination product About 1 year · vs Not applicable	Acute lateral-wall heart attack. The authors rate bitter orange as a possible cause on the Naranjo scale and say more reports are needed. Possible association (Naranjo) (None) Methods, limits and funding Outcomes: Heart attack Limitations: One person, hidden artery disease, smoker, multi-ingredient product. Funding and conflicts: Not stated in the abstract Read: abstract
Pawar 2020 Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC-MS/MS. Drug Test Anal · PMID 32497396 · DOI	Laboratory analysis in-vitro	59 59 US products labelled to contain bitter orange	Bitter orange supplements peel / extract / amines Not stated in the abstract Not stated in the abstract · vs Not applicable	Of 23 products with a synephrine claim, only 5 (22%) were within 80-120% of the label. Six products held methylsynephrine (up to 240 mg per serving) and one held isopropyloctopamine (up to 76 mg per serving), synthetic amines not permitted in supplements. 5 of 23 within 80-120% of label (None) Methods, limits and funding Outcomes: Amine content versus label Limitations: US market sample from before 2020; not every brand. Funding and conflicts: US FDA authors Read: abstract
Penzak 2001 Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol · PMID 11583473 · DOI	Controlled trial	Normotensive adults (number not given in the abstract)	Seville orange juice, 8 ounces twice, 8 hours apart juice 8 ounces, repeated after 8 hours Same day · vs Water (crossover)	Heart rate and blood pressure did not differ from water. Juice held about 56.9 micrograms/ml synephrine and no octopamine was detected. The authors note the juice is used to knock out intestinal CYP3A4 in studies and advise people with severe hypertension, fast heart rhythms, narrow-angle glaucoma, MAO-inhibitor use or decongestant use to avoid it. No hemodynamic difference from water (None) Methods, limits and funding Outcomes: Heart rate and blood pressure; synephrine content of juice Limitations: Juice, not supplement; sample size not in the abstract. Funding and conflicts: Not stated in the abstract Read: abstract
Plaitis 2026 Unexplained Supraventricular Tachycardia and Myocardial Injury After Bitter Orange Supplement Use in a Young Woman. JACC Case Rep · PMID 42132724 · DOI	Case report	1 38-year-old woman without cardiovascular risk factors	Weight-loss supplement containing bitter orange (p-synephrine) unspecified Not stated in the abstract 1 week · vs Not applicable	Palpitations, chest pain and vomiting after a week; supraventricular tachycardia ended with 6 mg intravenous adenosine. Troponin I rose from 17.9 to 1,395.7 ng/L. Coronary angiography showed no blockage. The authors suggest a possible link, likely through sympathetic stimulation. Possible association (None) Methods, limits and funding Outcomes: Fast heart rhythm, heart-muscle injury Limitations: One person; the supplement's full contents are not given in the abstract. Funding and conflicts: Authors report no relevant relationships Read: abstract
Ruiz-Moreno 2021 Effects of p-Synephrine during Exercise: A Brief Narrative Review. Nutrients · PMID 33467423 · DOI	Narrative review	Exercise studies of p-synephrine	p-Synephrine isolated / extract Not stated in the abstract Acute doses · vs Not applicable	Acute p-synephrine did not change sprint speed, jumping or aerobic capacity. At 2-3 mg/kg it raised fat oxidation during exercise at 30-80% of peak oxygen uptake without changing heart rate. The authors say it is unknown whether this lasts with repeated use. Narrative (None) Methods, limits and funding Outcomes: Fat oxidation, performance Limitations: Narrative review; most included trials come from the same research group as the authors. Funding and conflicts: Authors declare no conflict of interest Read: abstract
Shara 2016 Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial. Phytother Res · PMID 26948284 · DOI	Controlled trial	18 18 healthy adults (9 men, 9 women)	Bitter orange extract giving 49 mg p-synephrine, single dose fruit extract 49 mg p-synephrine, once Single dose, measured over 8 hours · vs Placebo (crossover)	No significant changes in ECG, heart rate, systolic pressure, blood chemistry or blood counts. Diastolic pressure fell 4.5 mmHg at 60 minutes. No adverse effects reported. Caffeine intake varied between people. No stimulant effect at this dose (None) Methods, limits and funding Outcomes: Heart rate, blood pressure, ECG, blood tests Limitations: One dose, 18 healthy people, 8 hours. Co-author Stohs has declared consultancy for a maker of bitter orange extract in another paper (p21537493); funding not stated in this abstract, so treat as possibly industry-linked. Funding and conflicts: Not stated in the abstract; co-author Stohs consultant for Nutratech (see p21537493) Read: abstract
Stohs 2011 Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med Sci · PMID 21537493 · DOI	Controlled trial	About 10 people per group	p-Synephrine 50 mg alone or with naringin and hesperidin, single dose fruit extract components 50 mg p-synephrine (alone) +/- 600 mg naringin +/- 100 or 1000 mg hesperidin Single dose, measured at 75 minutes · vs Placebo in V-8 juice	Resting metabolic rate rose 65 kcal with p-synephrine alone versus placebo; up to 183 kcal with synephrine plus naringin and 100 mg hesperidin (p<0.02), but only 79 kcal with 1000 mg hesperidin. No change in heart rate or blood pressure. RMR +65 kcal (synephrine alone vs placebo) (None) Methods, limits and funding Outcomes: Resting metabolic rate, blood pressure, heart rate Limitations: Tiny groups, one dose, 75 minutes. Industry-linked. Funding and conflicts: One author an employee of Nutratech; two others consultants for Nutratech, Inc. Read: abstract
Stohs 2014 Absence of furanocoumarins in Advantra Z (Citrus aurantium, bitter orange) extracts. J Diet Suppl · PMID 25026202 · DOI	Laboratory analysis in-vitro	4 Four batches of one branded extract (Advantra Z)	Standardised bitter orange extract fruit extract Not stated in the abstract Not applicable · vs Not applicable	Furanocoumarins in each of four extracts were below 20 micrograms per gram, which the authors say is too little to affect drug metabolism at common doses. They note bergapten is the main furanocoumarin in bitter orange and that other citrus juices and fruits contain them. Less than 20 micrograms/g (None) Methods, limits and funding Outcomes: Furanocoumarin content Limitations: One branded extract only; juice, peel and other brands were not tested. Industry-linked authors. Funding and conflicts: Not stated in the abstract; authors have declared ties to a bitter orange extract supplier in other papers (see p21537493) Read: abstract
Sultan 2006 Ischemic colitis associated with use of a bitter orange-containing dietary weight-loss supplement. Mayo Clin Proc · PMID 17165643 · DOI	Case report	1 One woman with no other predisposing factors	Bitter orange-containing weight-loss supplement unspecified Not stated in the abstract 1 week before symptoms · vs Not applicable	Ischaemic colitis developed 1 week after starting; symptoms improved immediately and resolved after stopping. Possible association (None) Methods, limits and funding Outcomes: Ischaemic colitis Limitations: One person; multi-ingredient product. Funding and conflicts: Not stated in the abstract Read: abstract
Thevis 2012 Analysis of octopamine in human doping control samples. Biomed Chromatogr · PMID 21932383 · DOI	Laboratory analysis	Urine after supplements or drugs	Octopamine and synephrine products supplements / drugs Not stated in the abstract Not stated in the abstract · vs Not applicable	The abstract states octopamine is prohibited in sport and that synephrine was not banned but was being monitored. Synephrine and supplements did not raise urinary octopamine. Not applicable (None) Methods, limits and funding Outcomes: Urine octopamine Limitations: 2012 statement; current lists must be checked. Funding and conflicts: German anti-doping lab Read: abstract
Thomas 2009 STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature. Tex Heart Inst J · PMID 20069086	Case report	1 Healthy 24-year-old man with no risk factors found	Nutrex Lipo-6x (synephrine-containing, ephedra-free) unspecified Within hours of taking the product Single exposure · vs Not applicable	ST-elevation heart attack with extensive clot in the left anterior descending artery within hours of the product. The authors propose a direct association. Authors propose an association (None) Methods, limits and funding Outcomes: Heart attack Limitations: One person; product has many ingredients. Funding and conflicts: Not stated in the abstract Read: abstract
de Jonge 2023 Review of Case Reports on Adverse Events Related to Pre-workout Supplements Containing Synephrine. Cardiovasc Toxicol · PMID 36639595 · DOI	Case series	35 35 patients in 30 case reports	Pre-workout supplements containing synephrine unspecified Not stated in the abstract Not stated in the abstract · vs Not applicable	30 case reports (35 people) were found. Chest pain, palpitations, syncope and dizziness were most common. Ischaemic heart disease, arrhythmias and cerebrovascular disease were commonly raised diagnoses. Five people were left disabled or stayed on medication. Caffeine and other ingredients cannot be excluded. Association only (None) Methods, limits and funding Outcomes: Adverse events Limitations: Case reports; confounded by caffeine and other ingredients; no rate can be calculated. Funding and conflicts: Authors declare no conflict of interest Read: abstract

What we do not know yet

No long-term controlled trial of p-synephrine safety for heart, blood pressure or QT in people with heart risk.
No human drug-interaction trial of bitter orange supplements; juice data and one extract analysis only.
Pregnancy and breastfeeding: no human data for supplements; LactMed not read.
EMA/HMPC, FDA and current WADA status not confirmed from agency sites.

How new research is added

New studies are found by a saved PubMed search and placed in a review queue. A person reads each one before it changes any rating or safety wording.

Lab markers

What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".

Metabolic 1

●

Body weight and body composition

No clear change in trials

Weight on the scale and the share of fat and lean tissue.

Low certainty

Results and what it means

Why it was measured

The main goal of weight-loss use.

Statistical vs. clinical meaning

A null pooled result for weight.

Safety implication

A product that does not help weight loss still carries its heart and blood-pressure cautions.

Study	Result	People	Product
¹⁰	Weight loss non-significant after prolonged use; body composition parameters unchanged	Adults, 18 placebo-controlled trials	Synephrine or bitter orange extract (some combination products)

¹⁰

Other 6

▲

Resting metabolic rate

Raised in trials

Calories the body burns at rest, measured by breath analysis.

Very low certainty

Results and what it means

Why it was measured

Used to test 'thermogenic' claims.

Statistical vs. clinical meaning

A short-term lab change, not weight loss.

Safety implication

Industry-linked, one dose.

Study	Result	People	Product
²⁵	+65 kcal vs placebo at 75 minutes after 50 mg p-synephrine alone; up to +183 kcal with naringin and 100 mg hesperidin	About 10 people per group	50 mg p-synephrine in V-8 juice

²⁵

▲

Maximal fat oxidation rate during exercise

Raised in trials

The most grams of fat per minute the body burns during a graded exercise test.

Low certainty

Results and what it means

Why it was measured

Tests whether p-synephrine shifts fuel use.

Statistical vs. clinical meaning

A lab measure, not a health outcome.

Safety implication

No heart-rate change in these trials.

Study	Result	People	Product
⁵	0.29 to 0.40 g/min (P=0.01)	18 healthy people	p-Synephrine 3 mg/kg vs placebo
⁷	About 0.43 vs 0.30 g/min placebo for p-synephrine alone (P<0.01); combination with caffeine 0.45 g/min	13 healthy people	p-Synephrine 3 mg/kg, caffeine 3 mg/kg or both

^{5 7}

↕

Blood pressure (systolic and diastolic)

Mixed results in trials

The force of blood on artery walls, in mmHg.

Mixed findings

Results and what it means

Why it was measured

Main safety outcome for a stimulant-type compound.

Statistical vs. clinical meaning

Single doses in healthy people show no rise, but pooled prolonged-use trials show a rise.

Safety implication

A rise is what a stimulant-type compound is expected to do; relevant for anyone with high blood pressure or heart disease.

Study	Result	People	Product
¹⁰	Systolic +6.37 mmHg (95% CI 1.02 to 11.72) and diastolic +4.33 (0.48 to 8.18) after prolonged use	Adults, 18 trials	Synephrine or extract
²⁴	No change in systolic; diastolic fell 4.5 mmHg at 60 minutes after one dose	18 healthy adults	Extract giving 49 mg p-synephrine
¹¹	Systolic 114 vs 115, diastolic 68 vs 68 mmHg	18 healthy volunteers	450 mg extract (27 mg synephrine), one dose

^{10 24 11}

↕

Heart rate

Mixed results in trials

Beats per minute.

Mixed findings

Results and what it means

Why it was measured

Stimulants can speed the heart.

Statistical vs. clinical meaning

Results differ by dose, product and caffeine.

Safety implication

Fast heart rhythms and supraventricular tachycardia have been reported with bitter orange supplements.

Study	Result	People	Product
¹⁰	The authors say synephrine tends to raise heart rate	Adults, 18 trials	Synephrine or extract
⁷	No change in heart rate during exercise	13 healthy people	p-Synephrine, caffeine or both
⁹	Heart rate rose with Citrus aurantium plus caffeine only	10 active men	100 mg C. aurantium + 100 mg caffeine

^{10 7 9}

▼

Anxiety score (State-Trait Anxiety Inventory)

Lowered in trials

A questionnaire score of how anxious a person feels; higher means more anxious.

Low certainty

Results and what it means

Why it was measured

The main outcome in two inhalation trials.

Statistical vs. clinical meaning

A self-rated score; a lower number is not proof of treatment benefit.

Safety implication

None reported in the abstracts.

Study	Result	People	Product
¹⁴	34.66 vs 42.36 (p<0.0001) after treatment	140 patients with acute coronary syndrome	Inhaled neroli oil (flower) vs paraffin
¹²	53.30 to 42.37 in the oil group; no change in water group	80 patients before angiography	Inhaled C. aurantium oil vs water

^{14 12}

↕

DASS-21 (depression, anxiety and stress scales)

Mixed results in trials

A 21-item questionnaire scoring depression, anxiety and stress.

Low certainty

Results and what it means

Why it was measured

Primary outcome in the pregnancy trial.

Statistical vs. clinical meaning

Two of three scales improved; a corrigendum was published in 2025.

Safety implication

The authors call it safe, from a small trial; pregnancy cautions still apply to supplements.

Study	Result	People	Product
¹³	Depression -4.80 vs +1.03 and anxiety -3.37 vs +0.79 (both p<0.001); stress -3.77 vs +1.39, p=0.166 (not significant)	68 pregnant women	Five drops C. aurantium oil on a mask twice daily for a month vs almond oil

¹³

Safety

What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.

Main points to know 8

Heart, blood pressure and stroke: the main concern. A 2022 meta-analysis of 18 placebo-controlled trials found prolonged use of synephrine raised systolic pressure by 6.37 mmHg and diastolic by 4.33 mmHg, and the authors say it tends to raise heart rate. A review of 30 case reports (35 people) found chest pain, palpitations, fainting and dizziness most often, with heart disease, abnormal rhythms and stroke among the diagnoses; five people were left disabled or stayed on medication. Single doses in healthy volunteers did not change blood pressure or ECG in two small trials. NCCIH says serious events including abnormal rhythms, heart attacks and strokes have been reported, but most products had several ingredients so the cause is unclear. Meta-analysis ^{10 30 24 11 15}
Case reports: heart attack, stroke, fainting with long QT, fast rhythm, bowel ischaemia. Individual reports include a heart attack in a 55-year-old woman with hidden artery disease (Naranjo: possible), a stroke in a 38-year-old man after a synephrine-caffeine product, fainting with a corrected QT of 516 ms in a 22-year-old after Xenadrine EFX, ischaemic colitis one week after a bitter orange weight-loss product, a heart attack in a 24-year-old with a clot in a main artery, and in 2026 a supraventricular tachycardia with heart-muscle injury in a 38-year-old woman. All used multi-ingredient products, often with caffeine. They show possible harm, not how often it happens. Case report ^{19 3 16 27 29 22}
QT interval: one dose of standardised extract did not change it. In 18 healthy volunteers one 450 mg dose of bitter orange extract (27 mg synephrine) did not change the QTc (402 vs 403 ms). The one case of QT prolongation we found involved a combination product with notable phenylephrine content. Repeated dosing, other drugs, and people with heart conditions were not tested. Controlled trial ^{11 16}
Caffeine and other stimulants add up. The German BfR says in animals caffeine and exercise made synephrine's blood pressure and rhythm effects stronger, and warns that high amounts of synephrine, especially with caffeine and exercise, raise the risk of cardiovascular harm. In 10 active men, Citrus aurantium plus caffeine raised heart rate, epinephrine and norepinephrine; but a cycling trial of p-synephrine plus caffeine saw no heart-rate rise. Avoid stacking with other stimulants. Authoritative guidance ^{1 9 7}
Product contents often do not match the label, and hidden drugs were found. The FDA analysed 59 US bitter orange products: only 5 of 23 with a synephrine claim were within 80-120% of the label, and six held methylsynephrine (up to 240 mg per serving) and one isopropyloctopamine, which are not permitted in supplements. Laboratory research ^{20 15}
Medicines: stimulants, MAOIs, decongestants, heart and blood pressure drugs, and CYP3A4 medicines. The Seville orange juice trial authors advise people with severe hypertension, fast heart rhythms, narrow-angle glaucoma, MAO-inhibitor use or decongestant use to avoid the juice. Seville orange juice raised felodipine exposure in trials. A branded standardised extract held very little furanocoumarin, but juice and peel were not covered. See Interactions. Controlled trial ^{21 4 26}
Pregnancy and breastfeeding: avoid supplements. NCCIH says it may not be safe in pregnancy or breastfeeding, and animal data suggest it might decrease milk production. Rats given up to 100 mg synephrine/kg showed no developmental toxicity, but that does not clear it for women. No human pregnancy safety data for supplements were found. A small trial of inhaled oil in 68 pregnant women reported benefit and called it safe. Authoritative guidance ^{15 8 13}
Sport rules: banned by the NCAA; octopamine banned; current WADA status not verified. NCCIH says the NCAA lists synephrine (bitter orange) as a banned stimulant. A 2012 paper says octopamine is prohibited in sport and that synephrine was not banned but monitored. A 2016 trial also says synephrine was in WADA's monitoring programme. We could not open the current WADA list, so the present status for each is NOT verified. Athletes should check the current list before use. Authoritative guidance ^{15 28 6}

Side effects 5

Effect	How often	Severity and recovery	Evidence
Raised blood pressure and heart rate Single-dose trials in healthy people found no rise.	Not stated as a rate; pooled increase systolic 6.37 and diastolic 4.33 mmHg after prolonged use	mild to serious Not stated	Meta-analysis ¹⁰
Chest pain, palpitations, fainting, dizziness Case reports only; caffeine and other ingredients are confounders.	Not available	moderate to severe Five of 35 reported patients left disabled or on ongoing medication	Case series ³⁰
Heart attack, stroke, ischaemic colitis, supraventricular tachycardia and QT prolongation Each in a person using a multi-ingredient product.	Not available	severe Some recovered fully (stroke, colitis, QT), others were hospitalised	Case report ^{19 3 16 27 29 22}
Fewer side effects with single doses in healthy volunteers Small trials; they do not rule out rare serious events.	No adverse effects reported in the 18-person trial	none reported Not applicable	Controlled trial ^{24 6}
Oil on skin or inhaled: generally well tolerated No adverse reactions reported in three small inhalation trials.	Not available	mild Not stated	Authoritative guidance ^{15 14}

Liver

We found no LiverTox entry for bitter orange and no human case of liver injury in the sources read (NCCIH, the trials and case reports). This does not prove safety: contaminated or multi-ingredient weight-loss products can harm the liver for other reasons, and our search was limited. ¹⁵

How often. No frequency data. LiverTox entry not found by web search (not verified).

Monitoring. No agency monitoring advice found. People with liver disease should ask a clinician before using weight-loss supplements.

This is a safety connection. It is not evidence that Bitter Orange supports liver health.

Medicines and supplements 6

With	Why it matters	Importance	Evidence	What to do
Caffeine and other stimulants (pre-workout, fat-burner, energy products, decongestants) stimulant	Both raise sympathetic activity; the BfR describes stronger blood pressure and rhythm effects with caffeine in animals; epinephrine rose in a small human trial.	Possibly large for blood pressure and heart rhythm; no controlled safety trial.	Authoritative guidance Low certainty ^{1 9 21}	Avoid combining; ask a doctor or pharmacist.
MAO inhibitors (some antidepressants, Parkinson's and anti-infective drugs) prescription	Theory only: the juice-trial authors advise MAOI users to avoid it, presumably because synephrine is an amine; no mechanism is stated in the abstract.	Unknown in people; the authors advise MAOI users to avoid Seville orange juice.	Pharmacological theory Very low certainty ²¹	Avoid unless a prescriber agrees.
Blood pressure, heart-rhythm and heart-failure medicines prescription	Synephrine can raise blood pressure and heart rate, working against these drugs.	Unknown for people on these medicines; pooled trials in mostly healthy adults show a rise in blood pressure.	Meta-analysis Low certainty ^{10 21}	Ask a prescriber; do not stop medicine yourself.
Drugs cleared by CYP3A4 or P-glycoprotein (for example felodipine, cyclosporine, some statins and others) prescription	Seville (bitter) orange juice is used in studies to switch off intestinal CYP3A4, and raised felodipine exposure. This is the same kind of effect as grapefruit, which is blamed on furanocoumarins.	The juice and likely the whole peel can interact. A review says other juices are less severe than grapefruit.	Controlled trial Low certainty ^{21 4}	If you take a medicine with a grapefruit warning, treat Seville orange juice, marmalade and peel products the same until a pharmacist says otherwise.
Standardised p-synephrine extracts versus grapefruit effect prescription	Four batches of one branded extract (Advantra Z) had under 20 micrograms/g of furanocoumarins, which the authors (industry-linked) say is too little to affect drug metabolism at usual doses.	Reassuring only for that extract; other brands, peel powders and juice are not covered. No human drug-interaction trial of the extract was found.	Laboratory research Very low certainty ²⁶	Do not assume every product is low in furanocoumarins; ask a pharmacist.
Decongestants and diet pills over-the-counter	Similar stimulant action.	Unknown; the juice trial authors say people on decongestant cold medicines should avoid the juice.	Pharmacological theory Very low certainty ²¹	Avoid combining.

Who should check first 5

Situation	Advice	Evidence
High blood pressure, fast or irregular heartbeat, heart disease, stroke history, or QT problems	Avoid p-synephrine supplements; ask a clinician.	Authoritative guidance ^{10 30 15}
Pregnancy or breastfeeding	Avoid supplements (NCCIH: may not be safe; may reduce milk in animals).	Authoritative guidance ¹⁵
Narrow-angle glaucoma	Avoid, per the authors of the Seville orange juice trial; glaucoma is also named for juice only.	Pharmacological theory ²¹
Taking MAO inhibitors, decongestants, other stimulants or medicines with a grapefruit warning	Do not use without asking a pharmacist.	Pharmacological theory ^{21 4}
Competitive athletes	Check current anti-doping lists; NCAA lists synephrine as banned.	Authoritative guidance ^{15 28}

Overdose, product quality and regulators

Summary. p-Synephrine is a stimulant-type compound. The main toxic concern is cardiovascular, from reports and the BfR assessment; the BfR suggests supplement intake should not exceed the median intake from ordinary foods.

Animal. In animals oral synephrine raised blood pressure and caused ventricular arrhythmias, more so with caffeine and exercise (BfR). In pregnant rats up to 100 mg synephrine/kg caused no developmental toxicity.

Human doses studied. Single doses around 27 to 50 mg synephrine, or 3 mg/kg, in healthy volunteers; amounts are not recommendations.

High dose or long term signals. Prolonged-use trials pooled a rise in blood pressure; no long-term safety trial found.

Overdose response. No overdose series found. Unlabelled synthetic amines (methylsynephrine up to 240 mg a serving) were found in some products, so the dose in a product may not be what is on the label.

Genotoxicity. Not covered by the sources read.

Toxic plant parts. Fruit and peel extracts are the source of p-synephrine. Bergapten, a furanocoumarin, is named in bitter orange by one source; photosensitivity of bitter orange peel oil is NOT verified in the sources we read.

The FDA found large label mismatches and hidden synthetic amines.

Label accuracy. Only 5 of 23 products claiming a synephrine amount were within 80-120% of the label. ²⁰

Hidden synthetic amines. Methylsynephrine (up to 240 mg/serving) in six products and isopropyloctopamine (up to 76 mg/serving) in one; hordenine, N-methyltyramine and octopamine are on FDA's Dietary Supplement Ingredient Advisory List. ²⁰

Body	Action	Date
NCCIH (US National Institutes of Health) (United States)	Not clearly shown to help any health purpose; serious cardiovascular events reported; may not be safe in pregnancy or breastfeeding; NCAA bans synephrine. source
German BfR (Germany)	Risk assessment: supplement intake of synephrine should not exceed the median intake from conventional foods. source
NCAA (United States)	Lists synephrine (bitter orange) as a banned stimulant, per NCCIH. source

When to get medical help

Chest pain or pressure, a racing or irregular heartbeat, fainting, or shortness of breath: stop and call emergency services.
Sudden weakness, trouble speaking or seeing, confusion, severe headache or loss of balance (possible stroke): call emergency services.
Severe belly pain or bloody stool.
Very high blood pressure readings or severe headache.
Swollen face or lips, hives or trouble breathing.

Stop the supplement and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.

General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.

Frequently asked questions

Does bitter orange help you lose weight?

The latest meta-analysis of 18 placebo-controlled trials found no significant weight loss and no change in body composition. NCCIH says its effect on weight is unclear.

^{10 15}

Is bitter orange safe for the heart?

Not for everyone. Pooled trials found raised blood pressure after prolonged use. Case reports describe heart attacks, strokes, fast heart rhythm and fainting, mostly with multi-ingredient products. Single doses in 18 healthy volunteers did not change heart rate or ECG in one trial. If you have heart or blood pressure problems, ask a doctor first.

^{10 30 24 15}

Can bitter orange cause long QT or dangerous rhythms?

One dose of standardised extract did not change the QT interval in 18 healthy people. One young woman fainted with a QT of 516 ms after a multi-ingredient product. Whether bitter orange itself causes this is unproven.

^{11 16}

Is it safe with caffeine or pre-workout products?

Avoid the combination. The German BfR says synephrine with caffeine and exercise raises the risk, and a small trial found raised adrenaline-type markers with the pair.

^{1 9}

Does bitter orange interact with medicines like grapefruit does?

Seville orange juice is used in studies to switch off intestinal CYP3A4 and raised felodipine levels. One branded extract held very little furanocoumarin, but other products were not tested. Ask a pharmacist if your medicine has a grapefruit warning.

^{21 4 26}

Can I take it with an MAO inhibitor or decongestant?

The authors of a juice trial advise people on MAO inhibitors or decongestants to avoid it. Ask a pharmacist.

²¹

Is it safe in pregnancy or breastfeeding?

NCCIH says it may not be safe, and animal data suggest it might reduce milk. Avoid supplements. A small trial of inhaled oil in pregnancy reported benefit, but that is a different use.

^{15 13}

Can athletes use it?

NCCIH says the NCAA bans synephrine. Octopamine was prohibited and synephrine monitored in older WADA documents; we could not confirm the current list, so check it yourself.

^{15 28}

Do supplements contain what the label says?

Often not. In an FDA test of 59 products, only 5 of 23 with a synephrine claim were within 80-120% of the label, and some had hidden synthetic amines.

²⁰

Does the essential oil help anxiety?

Three small trials found lower anxiety scores after inhaling the oil, but blinding was weak and some used flower oil. NCCIH says benefit is unclear. Do not swallow the oil.

^{14 12 13 15}

Is there a difference between synephrine, the extract and tea?

Yes. Supplements with p-synephrine drive the safety concerns. No human trials exist for peel or flower tea.

¹⁵

Does it harm the liver?

We found no LiverTox entry and no case of liver injury in the sources read. That is not proof of safety, especially for contaminated blended products.

¹⁵

Explore by health goal

Metabolic Health Weight Management Energy Boost Endurance Support Peak Performance Physical Stamina Anxiety Support Calm Relaxation Mood Balance Healthy Skin Digestive Support

Editorial transparency

Written by: AlternativeMed editorial team. Research compiled with AI assistance, then checked against PubMed records.
Medical review: None. This page has not been reviewed by a physician or pharmacist.
First published: 2026-10-25
Last substantive update: 2026-10-25
How we research: We searched PubMed, read the abstract of every PubMed study cited, read the NCCIH bitter orange page, and checked the plant name in GBIF and NCBI Taxonomy and compounds in PubChem. Not verified: EMA/HMPC, FDA, LiverTox, LactMed and current WADA lists could not be opened or confirmed. Most studies were read as abstracts only. Certainty ratings are the compiler's reading. Some trials are industry-linked and are flagged in the study notes.
How we rate evidence: See "How we rate evidence" in the Evidence tab.
Independence: No product is promoted on this page. No affiliate links are shown.

Sources 30

Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.

Bakhyia N, Dusemund B, Richter K, et al.. [Risk assessment of synephrine in dietary supplements].. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2017. PMID 28058460. DOI 10.1007/s00103-016-2506-5. (abstract)
Bent S, Padula A, Neuhaus J. Safety and efficacy of citrus aurantium for weight loss.. Am J Cardiol. 2004. PMID 15541270. DOI 10.1016/j.amjcard.2004.07.137. (abstract)
Bouchard NC, Howland MA, Greller HA, et al.. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine.. Mayo Clin Proc. 2005. PMID 15819293. DOI 10.4065/80.4.541. (abstract)
Chen M, Zhou SY, Fabriaga E, et al.. Food-drug interactions precipitated by fruit juices other than grapefruit juice: An update review.. J Food Drug Anal. 2018. PMID 29703387. DOI 10.1016/j.jfda.2018.01.009. (abstract)
Gutiérrez-Hellín J, Del Coso J. Acute p-synephrine ingestion increases fat oxidation rate during exercise.. Br J Clin Pharmacol. 2016. PMID 27038225. DOI 10.1111/bcp.12952. (abstract)
Gutiérrez-Hellín J, Salinero JJ, Abían-Vicen J, et al.. Acute consumption of p-synephrine does not enhance performance in sprint athletes.. Appl Physiol Nutr Metab. 2016. PMID 26673246. DOI 10.1139/apnm-2015-0299. (abstract)
Gutiérrez-Hellín J, Del Coso J. Effects of p-Synephrine and Caffeine Ingestion on Substrate Oxidation during Exercise.. Med Sci Sports Exerc. 2018. PMID 29727404. DOI 10.1249/MSS.0000000000001653. (abstract)
Hansen DK, Juliar BE, White GE, et al.. Developmental toxicity of Citrus aurantium in rats.. Birth Defects Res B Dev Reprod Toxicol. 2011. PMID 21594979. DOI 10.1002/bdrb.20308. (abstract)
Kliszczewicz B, Bechke E, Williamson C, et al.. The influence of citrus aurantium and caffeine complex versus placebo on the cardiac autonomic response: a double blind crossover design.. J Int Soc Sports Nutr. 2018. PMID 30041682. DOI 10.1186/s12970-018-0240-0. (abstract)
Koncz D, Tóth B, Bahar MA, et al.. The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis.. Nutrients. 2022. PMID 36235672. DOI 10.3390/nu14194019. (abstract)
Min B, Cios D, Kluger J, et al.. Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects.. Pharmacotherapy. 2005. PMID 16305290. DOI 10.1592/phco.2005.25.12.1719. (abstract)
Moradi K, Ashtarian H, Danzima NY, et al.. Essential Oil from Citrus aurantium Alleviates Anxiety of Patients Undergoing Coronary Angiography: A Single-Blind, Randomized Controlled Trial.. Chin J Integr Med. 2021. PMID 32572778. DOI 10.1007/s11655-020-3266-5. (abstract)
Moradi M, Niazi A, Mohammadi Payandar F, et al.. The effect of aromatherapy with Citrus Aurantium essential oil on depression, stress and anxiety in pregnant women; a randomized controlled clinical trial.. Taiwan J Obstet Gynecol. 2025. PMID 40368523. DOI 10.1016/j.tjog.2024.10.020. (abstract)
Moslemi F, Alijaniha F, Naseri M, et al.. Citrus aurantium Aroma for Anxiety in Patients with Acute Coronary Syndrome: A Double-Blind Placebo-Controlled Trial.. J Altern Complement Med. 2019. PMID 31211612. DOI 10.1089/acm.2019.0061. (abstract)
NCCIH. NCCIH: Bitter Orange: Usefulness and Safety. Web page. 2024. (full-text)
Nasir JM, Durning SJ, Ferguson M, et al.. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine.. Mayo Clin Proc. 2004. PMID 15301335. DOI 10.4065/79.8.1059. (abstract)
Not applicable. GBIF backbone: Citrus x aurantium L. (Citrus aurantium). Web page. . (full-text)
Not applicable. PubChem compound records (synephrine, octopamine, limonene, bergapten, naringin, hesperidin, tyramine, N-methyltyramine). Web page. . (full-text)
Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement.. Ann Pharmacother. 2004. PMID 15026566. DOI 10.1345/aph.1D473. (abstract)
Pawar RS, Sagi S, Leontyev D. Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC-MS/MS.. Drug Test Anal. 2020. PMID 32497396. DOI 10.1002/dta.2871. (abstract)
Penzak SR, Jann MW, Cold JA, et al.. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults.. J Clin Pharmacol. 2001. PMID 11583473. DOI 10.1177/00912700122012652. (abstract)
Plaitis A, Grigoraki E, Karakosta M, et al.. Unexplained Supraventricular Tachycardia and Myocardial Injury After Bitter Orange Supplement Use in a Young Woman.. JACC Case Rep. 2026. PMID 42132724. DOI 10.1016/j.jaccas.2026.108361. (abstract)
Ruiz-Moreno C, Del Coso J, Giráldez-Costas V, et al.. Effects of p-Synephrine during Exercise: A Brief Narrative Review.. Nutrients. 2021. PMID 33467423. DOI 10.3390/nu13010233. (abstract)
Shara M, Stohs SJ, Mukattash TL. Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.. Phytother Res. 2016. PMID 26948284. DOI 10.1002/ptr.5590. (abstract)
Stohs SJ, Preuss HG, Keith SC, et al.. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes.. Int J Med Sci. 2011. PMID 21537493. DOI 10.7150/ijms.8.295. (abstract)
Stohs SJ, Miller H, Romano F. Absence of furanocoumarins in Advantra Z (Citrus aurantium, bitter orange) extracts.. J Diet Suppl. 2014. PMID 25026202. DOI 10.3109/19390211.2014.937047. (abstract)
Sultan S, Spector J, Mitchell RM. Ischemic colitis associated with use of a bitter orange-containing dietary weight-loss supplement.. Mayo Clin Proc. 2006. PMID 17165643. DOI 10.4065/81.12.1630. (abstract)
Thevis M, Koch A, Sigmund G, et al.. Analysis of octopamine in human doping control samples.. Biomed Chromatogr. 2012. PMID 21932383. DOI 10.1002/bmc.1705. (abstract)
Thomas JE, Munir JA, McIntyre PZ, et al.. STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature.. Tex Heart Inst J. 2009. PMID 20069086. (abstract)
de Jonge MLL, Kieviet LC, Sierts M, et al.. Review of Case Reports on Adverse Events Related to Pre-workout Supplements Containing Synephrine.. Cardiovasc Toxicol. 2023. PMID 36639595. DOI 10.1007/s12012-022-09777-z. (abstract)

Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.