The longest safety test yet of bitter orange on its own suggests that the compound is safe after two months of daily use. A new study published in Food & Chemical Toxicology was noted in the American Botanical Council's most recent Herbclip.
Bitter orange (Citrus aurantium) became popular with dieters and weight-loss supplement manufacturers after the the Food and Drug Administration banned ephedra. A compound in bitter orange, p-synephrine, is a stimulant similar to ephedra. The safety of p-synephrine hasn't been established, though there have been no direct adverse event reports made for it, writes Risa Schulman in HerbClip. P-synephrine's similar in structure to ephedrine, norepinephrine and m-synephrine, which have been known to have have detrimental cardiovascular effects.
Because bitter orange is often taken in combination with other supplements like caffeine, it has not been clear what role bitter orange has had in adverse events reported for the combination. To gain some clarity, researchers designed a double-blind, placebo-controlled study to evaluate the safety of bitter orange alone and in combination with the citrus flavonoids naringin and hesperidin, in healthy adults.
For 60 days, researchers gave 75 healthy adults (average age, 51.6 years; 15 males and 60 females) two daily doses of either 49 mg of p-synephrine alone, 49 mg of p-synephrine with 576 mg of naringin and 100 mg of hesperidin or a placebo. None of the subjects reported adverse events, according to the HerbClip article. There were no statistically significant changes from baseline in the blood chemistry, systolic or diastolic blood pressure, resting heart rate, heart, liver, kidneys or quality of life in any of the groups. There was a small, but statistically significant, difference in the increase of the average resting heart rate between the combination group (3 beats per minute) and the p-synephrine-only (0.1 beat per minute) and placebo groups (P < 0.05 for both). However, they weren't considered clinically significant.
“This study indicates that a daily dose of nearly 100 mg of p-synephrine taken for up to 60 days is safe in healthy male and female adults. Efficacy studies need to be done to determine if there would be any effects on weight loss,” writes Schulman. HerbClip notes, however, that “the combination of p-synephrine and caffeine is still a major concern among some health professionals and researchers, and this paper did not address this issue.”