The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p‐Synephrine

@article{Stohs2011TheSO,
  title={The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p‐Synephrine},
  author={Sidney J Stohs and Harry G Preuss and Mohd A. Shara},
  journal={Phytotherapy Research},
  year={2011},
  volume={25}
}
Citrus aurantium (bitter orange) extract and its principal protoalkaloidal constituent p‐synephrine are widely used in weight loss and weight management as well as in sports performance products. However, questions are raised frequently regarding the safety of these ingredients. The potential inherent dangers associated with the use of products containing C. aurantium extract are frequently touted, while conversely, millions of doses of dietary supplements have been consumed by possibly… 
Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine
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  • Biology
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  • 2017
TLDR
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.
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TLDR
It is concluded that both the extract and isolated compounds have no unwanted effects in human at therapeutic doses and, therefore, can confidently be used in various dietary formulations.
A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine
TLDR
Bitter orange extract alone and in combination with other herbal ingredients did not produce significant adverse events as an increase in heart rate or blood pressure, or alter electrocardiographic data, serum chemistry, blood cell counts or urinalysis, and p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure.
Effects of Citrus aurantium (Bitter Orange) Fruit Extracts and p-Synephrine on Metabolic Fluxes in the Rat Liver
TLDR
The fruit extracts of Citrus aurantium are traditionally used as weight-loss products and as appetite supressants and can be partly attributed to its content in p-synephrine, which is structurally similar to the adrenergic agents.
A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract.
Questionable Conclusions in the Article “Cardiovascular Toxicity of Citrus aurantium in Exercised Rats”
  • S. Stohs
  • Medicine
    Cardiovascular Toxicology
  • 2013
TLDR
The authors failed to adequately discuss human clinical relevance and significance, failed to review the current scientific literature regarding C. aurantium (bitter orange) and p-synephrine, and did not appropriately relate their doses in rats to commonly used doses in humans.
Cardiovascular Safety of Oral p‐Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo‐Controlled Cross‐over Clinical Trial
TLDR
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.
Investigating herb-drug interactions: the effect of Citrus aurantium fruit extract on the pharmacokinetics of amiodarone in rats.
  • M. Rodrigues, G. Alves, A. Falcão
  • Biology, Medicine
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2013
Citrus aurantium L. Active Constituents, Biological Effects and Extraction Methods. An Updated Review
TLDR
This paper intends to provide an in-depth understanding of the biological activities and medicinal uses of active constituents existing in C. aurantium, and presents an overview of the most recent studies done on the matter.
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