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J Diet Suppl. 2014 Sep;11(3):288-93. doi: 10.3109/19390211.2014.937047. Epub 2014 Jul 15.

Absence of furanocoumarins in Advantra Z® (Citrus aurantium, bitter orange) extracts.

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1School of Pharmacy and Health Professions, Creighton University Medical Center , Omaha, NE , USA.


Grapefruit (Citrus paradisi) juice is known for its ability to alter drug metabolism through inhibition of the cytochrome P450-3A4 (CYP3A4) system, and result in drug-food interactions that may be life threatening. The primary active ingredients in grapefruit responsible for these effects are the furanocoumarins bergapten, bergamottin, and 6',7'-dihydroxybergamottin (DHB). Bergamottin and DHB appear to be the most important in terms of adverse drug interactions. Furanocoumarins are present in the juices and fruits of other Citrus species including C. aurantium (bitter oranges). Bergapten is the predominant furanocoumarin in bitter orange. Bitter orange extracts are widely used in products associated with weight loss, sports performance, and energy production. Questions have been raised about the potential of bitter orange extracts to cause drug interactions. This study examined the furanocoumarin content of four standardized bitter orange extracts (Advantra Z®) by liquid chromatography-mass spectroscopy. The results indicated that the total furanocoumarin content of each of the four extracts was less than 20 μg/g, amounts insufficient to exert significant effects on the metabolism of susceptible drugs in human subjects at the doses commonly used for these extracts.


6′; 7′-dihydroxybergamottin; Advantra Z®; bergamottin; bergapten; bitter orange extract; citrus aurantium

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