FDA Study Shows Bitter Orange Safety

JEFFERSON, Ark.Despite recent concerns with the safety of bitter orange (Citrus aurantium), an FDA-funded study found doses of up to 100mg p-synephrine/kg body weight, the  major component in bitter orange extract, did not produce developmental toxicity in Sprague-Dawley rat fetuses (Birth Defects Res B Dev Reprod Toxicol. 2011 May 18. DOI: 10.1002/bdrb.20308). This and other recent studies on the safety of bitter orange can put weight management product makers at ease that including this ingredient wont cause consumer harm.

Researchers from FDA and the National Center for Toxicological Research (NCTR)  reported doses up to 100 mg p-synephrine/kg body weight did not cause increased fetal death, or gross, visceral or skeletal abnormalities. The dose also did not produce adverse effects on fetal weight

 There was a decrease in maternal weight at 50 mg p-synephrine/kg body weight when given as a 6-percent p-synephrine extract with 25 mg caffeine/kg body weight; there was also a decrease in maternal weight in the caffeine-only group. However, the researchers reported this decrease in body weight may have been due to decreased food consumption, which was also observed in these two groups.

Nutratech Inc., maker of Advantra Z, a patented bitter orange extract, noted the dosages used in the study represent 60 to 200 times the daily amount of bitter orange or p-synephrine typically found in dietary supplements. 

In this study, Sprague-Dawley rats were dosed daily by gavage with one of several different doses of p-synephrine from one of two different extracts. Caffeine was added to some doses. Animals were sacrificed 20 days after they became pregnant, and fetuses were examined for the presence of various developmental toxic endpoints. NCTR also helped fund this study.

The concern of bitter orange comes from p-synephrines resemblance to the active compound in ephedra, which was been banned for use by FDA due to health risks.