“Most Comprehensive Ever” Bitter Orange Safety Review Published

In April, Phytotherapy Research published a safety review on bitter orangeCitrus aurantium), which Advantra Z bitter orange ingredient supplier Nutratech (West Caldwell, NJ) is calling “the most comprehensive review ever written about the safety of bitter orange.” The Stohs et. al review, “The safety of citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine,” is said to draw on evidence from 89 clinical research studies and other reference sources.

The researchers looked at the safety of bitter orange alone, as well as in combination with other ingredients, and concluded that the “preponderance of human clinical studies have reported that bitter orange extract (p-synephrine) either alone or in combination with caffeine and other ingredients has no effect on blood pressure or heart rate.”

Moreover, the review looked at whether m-synpherine, which unlike p-synephrine is an FDA-approved over-the-counter drug used in nasal decongestants and sprays and that can constrict blood vessels, and confirmed that m-synephrine is not naturally occurring as the protoalkaloids present in bitter orange, according to 19 separate analytical studies.

The researchers also clarify a study that is frequently cited as evidence of adverse cardiovascular effects, “Hemodynamic effects of ephedra-free weight-loss supplements in humans” (Haller et al.; September 2005. 

The Phytotherapy Research reviewers point out that Haller’s study clearly supports bitter orange’s safety. Haller reported that no significant effects on heart rate were recorded for three hours after subjects ingested two different the dietary supplements, one of which contained bitter orange. An increase in heart rate occurred only at the six-hour mark, after all subjects had consumed a meal. "After eating, an increase in heart rate occurred in the two treatment groups as well as in the control group.  The increase in heart rate does not coincide with the pharmacokinetics including blood levels and half-life of p-synephrine (Haller, et al., 2005, 2008) but does coincide with the thermic effect of food (Gougeon, et al., 2005)," wrote Stohs et al.