Safety Update: Synephrine

March 16, 2011 By


There has been speculation that synephrine, a constituent naturally found in bitter orange (Citrus aurantium), may be associated with adverse cardiovascular or central nervous system effects. There are 2 main isoforms of synephrine: para-synephrine (p-synephrine) and meta-synephine (m-synephrine), the latter more commonly known as phenylephrine. m-synephrine is a common ingredient of over-the-counter nasal decongestants which may increase heart rate and blood pressure. Furthermore, scientific evidence has suggested that while p-synephrine is a natural constituent of bitter orange, m-synephrine is not.

Bitter orange fruit and fruit peel has been used in Traditional Chinese Medicine, but most recently has been included as an ingredient in weight management products. In a recent publication, Stohs (2010) reviewed 22 adverse events reported to the United States Food and Drug Administration (US FDA) between April 2004 and October 2009 and compiled a summary in an attempt to determine whether the adverse reactions may in fact be related to the consumption of bitter orange or p-synephrine. In many of the reports bitter orange was used in combination with various other alkaloid-containing ingredients in addition to other confounding factors outlined in the reports. Based on the pharmacological and biochemical evidence available for bitter orange and p-synephrine, and having taken into account the multi-ingredient products used in many of the reports, Mr. Stohs was not able to conclude that bitter orange was responsible for the reported adverse reactions.

Health Canada (2010) has set an upper limit of 30 mg synephrine daily in over-the-counter products, such as natural health products. Furthermore, the Natural Health Products Directorate (NHPD) considers synephrine in combination with caffeine as a high risk combination. Products containing high risk ingredients, such as this combination, are not eligible to receive an Exemption Number (EN), as per the Unprocessed Natural Health Products Regulations adopted in August 2010.

In summary, evidence has suggested that p-synephrine, the alkalaoid present in bitter orange, is safe for consumption in amounts up to 30 mg daily in Canada, but caution should be taken when consuming bitter orange with caffeine or other alkaloid-containing products.


1. Health Canada. Guidelines for the Use of Synephrine in Natural Health Products. January 2010.

2. Stohs SJ. The Safety of Bitter Orange (Citrus aurantium) and p-Synephrine. HerbalGram. 2010; American Botanical Council. 89:34-39.

3. Stohs SJ. Assessment of the adverse event reports associated with Citrus aurantium (bitter orange) from April 2004 to October 2009. J Funct Foods. Oct 2010; 2(4):235-8.