Some Questionable Conclusions in the Article “Dietary Supplements and Hypertension: Potential Benefits and Precautions”


Several questionable conclusions exist in the article “Dietary Supplements and Hypertension: Potential Benefits and Precautions” by Rasmussen and colleagues.1 The authors note that synephrine and octopamine are the primary ingredients in bitter orange and are thought to be the cause of blood pressure increases. The authors failed to adequately review current information regarding bitter orange and p-synephrine and, as a consequence, several issues are clearly inaccurate in this statement.

Octopamine is present in trace amounts or absent in bitter orange while p-synephrine comprises approximately 90% of the total protoalkaloids.2p-Synephrine exhibits poor binding to cardioresponsive α, β1, and β2 adrenoreceptors compared with ephedra and phenylephrine.3 Thus, increases in heart rate and blood pressure at common doses are not expected.

A recent review has summarized the results of more than 20 human studies involving bitter orange-containing products.4 The majority of these studies have not demonstrated cardiovascular effects. Five published studies and two unpublished studies reported no cardiovascular effects when using products that contained only bitter orange. Five published and five unpublished studies using p-synephrine with other ingredients reported no cardiovascular effects (total of 170 patients).

Small (3–7 mm Hg) and clinically questionable increases in blood pressure were reported by Bui and colleagues5 (15 patients) using a 50-mg dose of p-synephrine. These effects were not replicated in 5 studies (total of 91 patients) using a similar dose.4 Only Bui and colleagues was cited by the authors.5 Small cardiovascular effects have been reported for two studies that involved a total of 20 patients who consumed p-synephrine plus caffeine.4 The results of one of these studies have been questioned due to issues with regard to experimental design.4

Various orange juices deliver up to 25 to 40 mg p-synephrine per 8-ounce glass.6 Millions of individuals unknowingly consume p-synephrine daily in juices and orange food products as marmalades without adverse events. Furthermore, tens of millions of doses of bitter orange products have been consumed by millions of individuals without report of serious incidents.2

Finally, literature reviews indicate that no cardiovascular effects have ever been directly attributable to bitter orange extract and p-synephrine,2,4 contrary to widely held beliefs. The possibility exists that someone may experience hypertension in response to p-synephrine; however, the categorization of bitter orange as a supplement for which there is “evidence of harm” with respect to hypertension is not supported by the current research data.