Caffeine Bitter orange

Like other stimulants, bitter orange can speed up a person s heart and raise his or her blood pressure. According to the National Center for Complimentary and Alternative Medicine (NCCAM), part of the National Institutes of Health, there have been reports of fainting, heart attack, and stroke in people taking either bitter orange alone or in combination with caffeine. People should stay away from this supplement, especially if... 

One case of an acute lateral wall myocardial infarction (MI) was reported in a woman after daily ingestion of Edita s Skinny Pill (containing 300 mg bitter orange plus caffeine and guarana) for 1 year (44). The 55-year-old Caucasian woman developed chest discomfort after eating Chinese food. After workup at the hospital, the woman was diagnosed with acute lateral-wall MI and smoking addiction. Her ejection fraction was 0.45. Prior to this incident, she had no known coronary artery disease, hypertension, or hyperlipidemia. 

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). 

Bitter orange does not alter the metabolism of caffeine, chlorzoxazone, debrisoquine, or midazolam, and is therefore unlikely to interact with drugs that are metabolised by CYP1A2, CYP2E1, CYP2D6 or CYP3A4. 

Bitter orange fruit concentrated extract combined with caffeine or caffeine-containing herbs is not recommended for excessive or long-term use or for use by persons with heart irregularities, hypertension, insomnia, or anxiety (Haller 2005). 

No adverse events were reported in a clinical trial of adults taking a supplement containing bitter orange fruit concentrated extract (975 mg with 58 mg synephrine), caffeine, and St. John s wort (Hypericum peiforatum) for 6 weeks (Colker et al. 1999). 

A previously healthy 22-year-old woman, who had recently resumed use of a combination product with numerous caffeine-containing ingredients along with standardized bitter orange extract, experienced a syncopal episode while running. An electrocardiogram revealed sinus tachycardia and QT prolongation (Nasir et al. 2004). 

In the six-year period from 1998 to 2004, Health Canada received 16 reports of cardiovascular adverse reactions associated with products containing bitter orange or synephrine. One of these products was reported to contain neither caffeine nor ephedrine, while the others contained one or both of these alkaloids (Jordan et al. 2004). 

No teratogenic or other adverse effects were found in fetuses of rats administered up to 100 mg/kg daily by gavage of bitter orange concentrated extract (6% synephrine). In combination with caffeine (25 mg/kg), however, a decrease in the number of implanted eggs was observed (Hansen et al. 2006). 

A stroke was reported in a 38-year-old man with a one-week history of taking a supplement containing bitter orange fruit concentrated extract (6-12 mg synephrine daily) and caffeine (200-400 mg daily) (Bouchard et al. 2005). 

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