Synephrine is a naturally occurring protoalkaloid compound (precursor of an alkaloid), commonly found in bitter orange, that is used as a fat-burner and may also have antioxidant and anti-inflammatory properties.
The extracts from the fruit and peel of bitter orange have long been used in traditional Chinese medicine to treat stomach problems (constipation, nausea and indigestion) and allergies.
Synephrine is similar to the main chemical in the herb ephedra (but less potent). Ephedra is banned by the U.S. Food and Drug Administration because it raises blood pressure and is linked to heart attack and stroke.
Synephrine is considered a banned substance by the National Collegiate Athletic Association (NCAA).
Synephrine may aid weight loss. In a 2016 study, researchers set out to determine the effects that different doses of p-synephrine had on maximal fat oxidation during exercise. Seventeen healthy participants volunteered for the study. On four trials separated by 72 hours, participants ingested a placebo or 1, 2 or 3 mg/kg of p-synephrine.
After resting for 60 minutes to allow substance absorption, participants performed an exercise test of increasing intensity on a stationary bicycle.
At the end of the study, researchers concluded that although all p-synephrine increased the maximal rate of fat oxidation during exercise, the highest effects were found with 2 and 3 mg/kg (1).
Reduced rates of fat oxidation have been shown to predict weight gain. Exercise acutely increases fat oxidation, and endurance training increases the capacity to oxidize fat (2).
In another study, twelve healthy men performed repetitions of squats and were randomly assigned to one of three groups: p-synephrine, p-synephrine and caffeine, or a placebo.
The results showed increased fat burning at rest and up to 30 minutes after exercise in men given synephrine, or a combination of synephrine and caffeine compared to placebo. No heart rate changes were observed unless caffeine was added (3).
While early evidence is promising, researchers conclude that larger and more rigorous clinical trials are necessary to draw adequate conclusions regarding the safety and efficacy of synephrine for promoting weight loss.
Synephrine has anti-inflammatory properties. Researchers of a recent study who set out to evaluate whether p-synephrine exerts potent anti-inflammatory effects against acute lung injury, were met with promising results.
Using an animal study to induce acute lung injury, researchers found that p-synephrine significantly reduced the number of inflammatory cells, the lung wet-to-dry weight ratio, reactive oxygen species, myeloperoxidase activity (biomarkers of inflammation) and enhanced superoxide dismutase (an enzyme that helps break down potentially harmful oxygen molecules in cells).
In cell studies, synephrine stopped the production of eotaxin-1. Elevated eotaxin-1 levels have been described in various pathologic conditions, ranging from airway inflammation, to Hodgkin lymphoma, obesity and coronary artery disease (4,5).
Synephrine may improve athletic performance. In a 2015 study, researchers examined the effects of supplementation with p-synephrine alone and in combination with caffeine on free-weight resistance exercise performance.
Twelve healthy, college-aged men performed a control resistance exercise protocol consisting of 6 sets of squats for up to 10 repetitions per set with 2 minutes of rest in between sets.
Each was randomly assigned to one of the following: p-synephrine (100 mg), p-synephrine and caffeine (100 mg of p-synephrine plus 100 mg of caffeine), or a placebo.
The p-synephrine and p-synephrine and caffeine groups augmented resistance exercise performance (total repetitions and volume load). The addition of caffeine increased mean power and velocity of squat performance (6).
Further studies are warranted as another study showed that three sprinters given p-synephrine failed to show improvement in sprint velocity or jumping heights compared to placebo (7).
Synephrine may have antidepressant-like effects. Researchers studied the effects of p-synephrine on the immobility behaviors and on the spontaneous motor activity in mice (in vivo tests that are used to screen antidepressant activity).
p-Synephrine at oral doses from 1 to 10 mg/kg significantly decreased the duration of immobility in the tail suspension test and the forced swimming test in mice (8).
Due to questions being raised about the safety of p-synephrine due to its structural similarity to banned ephedra, several studies have been done on its safety and efficacy.
According to a 2017 issue of Phytotherapy Research, a review of approximately 30 human studies indicates that p-synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses — up to 100 mg (9).
The review, as well as several other assessments published in recent years, has concluded that p-synephrine is safe for use in dietary supplements and foods at the commonly used doses (10).
In one study, researchers found that a patented blend of P-synephrine known as Xenadrine EFX (containing just 5.5 mg synephrine) was linked to an increase in blood pressure; however, in another patented blend, Advantra-Z (which contains a significantly higher dose of synephrine at 46.9 mg along with active bioflavonoids such as naringen and hesperidin) did not (11).
More studies are needed to gain a better understanding of what side effects are caused by short-term and long-term supplementation.
Early evidence shows that consumption of up to 50 mg per day of p‐synephrine alone in healthy adults is not likely to cause any adverse health consequences. In combination with up to 320 mg of caffeine, it is only recommended to take up to 40 mg of synephrine per day (12).
Before taking bitter orange or synephrine supplementation, talk with your healthcare professional.
Synephrine is a naturally occurring protoalkaloid compound commonly found in bitter orange, that is used as a fat-burner and may also have antioxidant and anti-inflammatory properties. It is structural similarity to ephedra, which has been banned by the FDA, yet is less potent and studies show that it does not cause the same adverse reactions as ephedra.
It is, however, a banned substance by the National Collegiate Athletic Association (NCAA).
According to a review of several human studies, synephrine does not result in cardiovascular effects and does not act as a stimulant at commonly used doses.
Early studies show its potential to also improve athletic performance and treat depression. Further studies and clinical trials are necessary to draw clear conclusions regarding the safety and efficacy of synephrine for promoting weight loss and other health benefits.
The safety of long-term use is also not yet known.