Synephrine, fruit

Citrus aurantium (Christen.) Swingle var. amara Suan Cheng (Bitter orange) (unripe fruit) Synephrine, N-methyltyramine, flavones including tangeratin and nobiletin.33 Treat indigestion, relieve abdominal distension, ptosis of the anus or uterus. 

Crude (minimally processed) dried bitter orange immature fruit and nearly mature fruit are used in traditional Chinese medicine. The content of synephrine in dried bitter orange fruit ranges from 0.012 to 0.25% (Rossato et al. 2011), and p-synephrine is reported to be the primary protoalkaloid present in bitter orange (Stohs et al. 2011). Extracts of the fruit with an increased concentration of synephrine (usually 4 to 6%) are also available in the marketplace (see next entry). 

Information on the safety of bitter orange fruit concentrated extract in pregnancy is limited. A study of bitter orange fruit concentrated extract in pregnant rats showed no adverse effects on mothers or fetuses (Hansen et al. 2006). In a subsequent study, administration of oral doses of synephrine of up to 100 mg/kg body weight to pregnant rats for 20 days resulted in no developmental toxicity and no adverse effects on fetal development (Hansen et al. 2011). 

No significant effects of bitter orange fruit concentrated extract (700 mg daily with 28 mg synephrine) were observed on CYP3A4 (Gurley et al. 2004). 

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). 

Conversely, a single dose of bitter orange fruit concentrated extract containing 46.9 mg synephrine was reported to be associated with an increased heart rate of 11.4 10.8 beats per minute after 6 hours, while blood pressure remained unchanged (Haller et al. 2005). In another study of a bitter orange fruit concentrated extract (900 mg with 54 mg... 

In rats administered 2.5 to 20 mg/kg bitter orange fruit concentrated extract daily (4 or 6% synephrine) for 7 or 15 days, mortality was observed in a dose-dependent manner in animals receiving extracts with either 4 or 6% synephrine. No differences in blood pressure were observed as compared to the control group (Calapai et al. 1999). 

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). 

No changes in the QT, interval or blood pressure were observed after a single dose of bitter orange fruit concentrated extract (450 mg with 27 mg synephrine) (Min et al. 2005). No increases in systolic or diastolic blood pressure or heart rate occurred in fasting volunteers 45 minutes after oral consumption of bitter orange fruit concentrated extract containing 50 mg p-synephrine with or without the flavo-noids naringin and hesperidin (Stohs et al 2011). 

The dried rinds of the fruits of Citrus unshiu and C. aurantium var. daidai are known as Chin-pi or Toh-hi in Japan, respectively, and the immature fruits of these plants are called Ki-jitsu. These are also used in Kampo medicine, and from them, the phenylethylamine-type alkaloids N-methyl-tyramine and synephrine were isolated [6,7]. 

Synephrine and N-methyltyramine were extracted from citrus fruit and separated on a C,g column (electrochemical detector, -(-1.2V vs. Ag/AgCl) using a 70/30 aqueous 20 mM citric acid with 20 mM NaH2P04 at pH 3 mobile phase [1573]. 

Arbo MD, Larentis ER, Linck VM, Aboy AL, Pimentel AL, Henriques AT, Dallegrave E, Garcia SC, Leal MB, Limberger RP (2008) Concentrations of p-synephrine in fruits and leaves of Citrus species (Rutaceae) and the acute toxicity testing of Citrus aurantium extract and p-synephrine. Food Chem Toxicol 46(8) 2770-2775... 

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