Health Canada
Symbol of the Government of Canada

Common menu bar links

Drugs and Health Products

ARCHIVED - Notice - Guidelines for the Use of Synephrine in Natural Health Products

Warning This content was archived on June 24 2013.

Archived Content

Information identified as archived on the Web is for reference, research or recordkeeping purposes. It has not been altered or updated after the date of archiving. Web pages that are archived on the Web are not subject to the Government of Canada Web Standards. As per the Communications Policy of the Government of Canada, you can request alternate formats on the "Contact Us" page.

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

January 2010

The Natural Health Products Directorate (NHPD) has conducted a review of the safety of synephrine, a substance which has structural resemblance to epinephrine and ephedrine.

Based on the potential for cardiovascular toxicity, the NHPD has adopted the following guidelines for the use of synephrine in Natural Health Products.

  • A limit of 30 mg/day has been adopted as the maximum allowable dose for total synephrine and octopamine, which is related chemically and pharmacologically to synephrine. Sources of these substances include Citrus speciessuch as C. aurantium, as well as certain species of some other genera (e.g. Evodia rutaecarpa), and synthetic sources. The above limit is consistent with that adopted by the Australian Therapeutic Goods Administration for synephrine in over-the-counter products (NDPSC 2003).
  • Given that there is currently insufficient published clinical evidence to establish a safe level for synephrine + caffeine combinations, caffeine or caffeine sources (e.g. coffee, tea, cola, matÚ, guarana) will not be permitted in synephrine-containing products without submission of sufficient clinical evidence in humans.
  • As there is insufficient information to establish the safety of long-term use of synephrine-containing products, a duration-of-use statement is required:
    Consult a health care practitioner for use beyond 8 weeks (Greenway et al. 2006).

Risk Information:

  • No risk information is required for products providing ≤ 3 mg synephrine + octopamine in a daily dose. This is based on a long history of safe use of bitter orange in Traditional Chinese Medicine at doses that provide approximately 3 mg/day synephrine.
  • Risk information is required for those products providing >3 mg synephrine + octopamine in a total daily dose:

Cautions and warnings:

  • Consult a health care practitioner prior to use if you have cardiovascular disease or hypertension (Sweetman 2007Based on risk information for sympathomimetics.; Haller et al. 2005; Bui et al. 2006), diabetes (Sweetman 2007Based on risk information for sympathomimetics.), prostate disorders (Sweetman 2007Based on risk information for sympathomimetics.) or are taking prescription medication (Sweetman 2007Based on risk information for sympathomimetics.; Genpharm 2005; Firenzuoli et al. 2005; Malhotra et al. 2001). Optional: prescription medications may be specified, e.g. antihypertensives, thyroid hormones, Monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants.
  • Consumption with caffeine-containing products (e.g. medications, guarana, matÚ, coffee, tea) is not recommended as it may increase the risk of adverse effects (Haller et al. 2005).
  • Consult a health care practitioner prior to use if you are pregnant (Sweetman 2007Based on risk information for sympathomimetics.) or breastfeeding.

Contraindications:

  • Do not consume if you are taking decongestant-containing cold preparations (i.e. phenylephrine or pseudoephedrine) (Penzak et al. 2001; NDPSC 2003), products containing ephedra or ephedrine (FDA 2004), or other medications which increase blood pressure.

References

Bui LT, Nguyen DTT, Ambrose PJ. 2006. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother 40(1):53-7.

FDA: USA Department of Health and Human Services: Food and Drug Administration. 2004. Next link will take you to another Web site Sales of supplements containing ephedrine alkaloids (Ephedra) prohibited. [Accessed 2007-10-10].

Firenzuoli F, Gori L, Galapai C. 2005. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 12(3):247-8.

Genpharm. 2005. Gen-levothyroxine (levothyroxine) [product monograph]. Toronto: Genpharm Inc.

Greenway F, de Jonge-Levitan L, Martin C, Roberts A, Grundy I, Parker C. 2006. Dietary herbal supplements with phenylephrine for weight loss. J Med Food 9(4): 572-578.

Haller CA, Benowitz NL, Jacob P. 2005. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 118(9): 998-1003.

Malhotra S, Bailey DG, Paine MF, Watkins PB. 2001. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 69: 14-23.

NDPSC (National Drugs and Poisons Schedule Committee). Next link will take you to another Web site Record of the Reasons, 37th meeting, February 25-26; 2003. [Accessed 2007-09-13].

Penzak SR, Jann MW, Cold JA, Yi Y, Desai HD, Gurley BJ. 2001. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol 41:1059-63.

Sweetman SC. 2007. Martindale: The Complete Drug Reference, 33rd ed. London (GB): Pharmaceutical Press.

Footnotes

Footnote 1

Based on risk information for sympathomimetics.