Seville (sour) Orange Juice: Synephrine Content and Cardiovascular Effects in Normotensive Adults

  title={Seville (sour) Orange Juice: Synephrine Content and Cardiovascular Effects in Normotensive Adults},
  author={Scott R. Penzak and Michael W. Jann and Julie A. Cold and Yuen Yi Hon and Hiral D. Desai and Bill J Gurley},
  journal={The Journal of Clinical Pharmacology},
The Seville orange extract Citrus aurantium contains m‐synephrine (phenylephrine) and octopamine; it causes cardiac disturbances in animals and is used by humans for weight loss. Juice from the orange (Seville orange juice [SOJ]) is used to “knock out” intestinal cytochrome P450 (CYP) 3A4 in bioavailability studies. The purpose of this study was to determine synephrine and octopamine concentrations in SOJ and SOJ's cardiovascular effects in normotensive humans. Subjects consumed 8 ounces of SOJ… 
Mass spectrometric determination of the predominant adrenergic protoalkaloids in bitter orange ( Citrus aurantium )
Seville orange (Citrus aurantium) extracts are being marketed as a safe alternative to ephedra in herbal weight-loss products, but C. aurantium may also have the potential to cause adverse health
Safety evaluation of p‐synephrine following 15 days of oral administration to healthy subjects: A clinical study
No significant changes occurred in heart rate, electrocardiograms, systolic blood or diastolic pressures, blood cell counts, or blood chemistries in either the control or p‐synephrine treated groups at any time point.
The acute effects of citrus aurantium extract on blood pressure and heart rate
To investigate the cardiovascular effects of CA ingestion, in an herbal blend, on mildly overweight individuals, 14 females and nine males (Mean +SD) volunteered in this placebo crossover, double-blind designed study.
Cardiovascular Safety of Oral p‐Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo‐Controlled Cross‐over Clinical Trial
This study assessed the cardiovascular (stimulatory) effects of bitter orange extract given to 18 healthy subjects in a double‐blinded, placebo‐controlled cross‐over study and found p‐synephrine does not act as a stimulant at the dose used.
Citrus aurantium, an Ingredient of Dietary Supplements Marketed for Weight Loss: Current Status of Clinical and Basic Research
There is little evidence that products containing C. aurantium are an effective aid to weight loss, and synephrine, which is structurally similar to epinephrine, has lipolytic effects in human fat cells only at high doses.
A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract.
Effect of Acute Administration of an Herbal Preparation on Blood Pressure and Heart Rate in Humans
The results of this study indicate that ingestion of a product containing bitter orange extract, caffeine and green tea extract does not lead to increased cardiovascular stress and that fat oxidation may increase in certain populations.
The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p‐Synephrine
The data indicate that based on current knowledge, the use of bitter orange extract and p‐synephrine appears to be exceedingly safe with no serious adverse effects being directly attributable to these ingredients.
Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine
  • S. Stohs
  • Biology
    Phytotherapy research : PTR
  • 2017
This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p‐synephrine are safe for use in dietary supplements and foods at the commonly used doses.


Pharmacokinetics of Oral Decongestants
Whereas PPA and PDE are not substantially metabolized, PE undergoes extensive biotransformation in the gut wall and the liver, and the agents should be used with caution in patients with renal impairment.
A comparison of the cardiovascular effects of phenylpropanolamine and phenylephrine containing proprietary cold remedies.
The cardiovascular effects of phenylpropanolamine, including vasoconstriction and an increase in cardiac performance, are consistent with its alpha- and beta 1-adrenoceptor agonist action, while it may help the symptoms of rhinitis, its use in patients with heart disease or hypertension is hazardous.
Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica (Ma-huang) as determined by high performance liquid chromatography.
A validated HPLC method for the determination of ephedrine-type alkaloids, commonly found in Ephedra supplements, is presented and may contribute to toxicity associated with these products.
Pharmacokinetics of 3H-phenylephrine in man.
Metabolism to phenolic conjugates mainly after oral ingestion, and to m-hydroxymandelic acid after i.v. injection, again demonstrated that m-Hydroxylated amines are predominantly conjugated during the "first-pass" metabolism.
Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors
Based upon the known selectivities of these isomers for α‐adrenoceptor subtypes, it is concluded that the rat aorta contains only α1‐ adrenoceptors while the rabbit saphenous vein possesses predominantly α2‐adereoisomer antagonists.
Use of Seville orange juice to "knock out
  • 1999
SF: Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica (Ma-huang) as determined by high performance liquid chromatography
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  • 1998