Synephrine cardiovascular effects

There are limited animal and human data on the cardiovascular effects of C. aurantium. When administered to rats, C. aurantium and synephrine both raised blood pressure in a dose-dependent manner (31). In another study in rats, repeated oral C. aurantium extract led to dose-dependent cardiovascular toxicity and mortality (32). Two studies using synephrine or C. aurantium in rats with induced portal hypertension (by portal vein ligation) have been conducted (31,33). In these studies, both synephrine and C. aurantium significantly reduced portal venous pressure. Interestingly, C. aurantium had a greater effect on portal hypertension than synephrine alone. 

Penzak SR, Jann MW, Cold A, Hon YY, Desai HD, Gurley BJ. Seville (sour) orange juice synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol 2001 41 1059-1063. 

Many reports of adverse effects due to the use of bitter orange, as a replacement for ephedra, in weight-loss dietary supplements have reeently emerged. Some of the reported effects include ischemic colitis, angina, elevated blood pressure, and other cardiovascular effects. " Synephrine and/or octopamine are speculated to play a role in the advent of such effects. ... 

An article in the Canadian Adverse Reaction Newsletter published their reporting of adverse effects caused by products containing C. aurantium from January 1, 1998 to February 28, 2004 (46). The article lists 16 reports of synephrine associated with cardiovascular events including tachycardia, cardiac arrest, ventricular fibrillation, transient collapse, and blackout. In one case, bitter orange was the sole suspected culprit. In seven others the products also contained caffeine, and in eight cases the product contained both caffeine and ephedrine. Health Canada has issued an advisory stating that synephrine may have effects similar to ephedrine and caution should be used if taking it (47). 

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