Bitter orange extract and p-synephrine safety and effects
What it found
In about 30 human studies, bitter orange extract and p-synephrine did not cause heart or blood pressure effects at commonly used doses.
Animal and lab studies suggest it may help with fat breakdown and appetite, but animal results do not always apply to people.
What they found
Studies in people
Heart and blood pressure in people
About 30 human studies found that p-synephrine and bitter orange extracts did not cause cardiovascular effects at commonly used doses. Some small increases in heart rate or blood pressure were reported in a few subjects, but these were not confirmed by other studies.
Weight and appetite in people
Some human studies found that p-synephrine increased energy and appetite control. It also increased fat oxidation during exercise in one study.
Drug interactions
Bitter orange extract did not affect major drug-metabolizing enzymes in people. It contains very low levels of furanocoumarins, which are the compounds in grapefruit juice that can cause drug interactions.
Animal and lab studies
Animal safety studies
In rats and mice, high doses of p-synephrine or bitter orange extract did not cause serious adverse effects. Some small cardiovascular effects were seen in rodents, but these may not apply to humans because p-synephrine binds more strongly to rodent receptors.
Lab tests on cells
In lab tests, p-synephrine increased glucose consumption in muscle cells and reduced glucose production in liver cells. It also showed anti-inflammatory and antioxidant effects in cells and animal tissues.
Mutagenicity tests
Bitter orange extract and p-synephrine did not cause mutations in bacterial or cell tests. One test found a small increase in DNA damage at a high concentration, but not at a lower concentration.
What the authors conclude
“This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p-synephrine are safe for use in dietary supplements and foods at the commonly used doses.”
Also in their conclusions
- They conclude that bitter orange extract and p-synephrine are safe for use in dietary supplements and foods at commonly used doses.
- They state that p-synephrine does not act as a stimulant and does not produce cardiovascular effects at commonly used doses.
- They advise that additional studies are needed to determine at what dosage levels adverse effects might occur.
How it was done
Questions have been raised about the safety of p-synephrine because it has some structural similarity to ephedrine, and it is widely referred to as a stimulant and assumed to exhibit cardiovascular activity.
The authors reviewed human, animal, and lab studies on bitter orange extract and p-synephrine. Human studies involved over 600 subjects, with doses up to 100 mg per day, and some studies lasted up to 60 days.
What it can’t tell you
- Animal and lab results cannot be directly extrapolated to people because p-synephrine binds more strongly to rodent receptors.
- The studies reviewed cannot show whether bitter orange extract or p-synephrine cause any long-term health effects.
- The exact dose at which adverse effects might start in people is not known.
Who paid
- Authors work at
- Creighton University Medical Center, USA
The paper
- Title
- Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine
- Type
- ReviewThe authors read earlier studies and describe what they found. It isn’t a new study.
- Evidence
- Studies in people · animals · lab
- Summarised from
- Full text
- Licence
- CC BY. Words in quotation marks are the authors’; the rest is our summary.
- Cite
- Stohs SJ (2017). Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine. Phytotherapy research. doi:10.1002/ptr.5879Free full textPubMed 28752649DOI
Summary written 30 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error