Some limited research suggests that bitter orange supplements may increase blood pressure, while other research found no effect. A meta-analysis of small randomized controlled studies suggests that taking bitter orange extract alone or with other ingredients for 56–60 days increases systolic blood pressure by up to 6.4 mmHg compared to control; however, there was no significant effect on diastolic blood pressure. Acute administration of bitter orange extract tended to increase blood pressure over 3 hours, but this result was not statistically significant.[1] One randomized crossover trial of 15 healthy, young adults given a single dose of bitter orange supplement containing 108 mg of synephrine, which was included in the above meta-analysis, reported that the participants given synephrine experienced modestly increased blood pressure and heart rate for up to 5 hours compared to placebo.[2] In another small study, in which participants were given a single, smaller dose of 27 mg of synephrine and monitored for 8 hours, no significant difference from placebo was seen on t blood pressure or electrocardiogram (QT interval).[3] In a small study of healthy young adults sitting quietly for 3 hours after taking a single dose of 103 mg p-synephrine, alone or with 240 mg caffeine, blood pressure and heart rate were not affected compared to placebo.[4] These results suggest that caffeine and synephrine may not always have synergistic effects in the short term.
A small study of 10 healthy adults considered 2 different dietary supplements containing synephrine and compared heart rate and blood pressure results with placebo after a single dose (Advantra Z, containing 46.9 mg synephrine, and Xenadrine EFX, containing 5.5 mg synephrine). Interestingly, the Xenadrine EFX group experienced more blood pressure and heart rate elevations than the Advantra group, possibly due to other ingredients in the supplement.[5]
The longer-term effects of a 20 mg daily dose of synephrine were examined in an 8 week study of healthy, young, resistance-trained males; researchers found no changes in blood pressure or heart rate compared to control.[6].