Cardiovascular Toxicology

, Volume 13, Issue 3, pp 208–219 | Cite as

Cardiovascular Toxicity of Citrus aurantium in Exercised Rats

  • Deborah K. Hansen
  • Nysia I. George
  • Gene E. White
  • Ali Abdel-Rahman
  • Linda S. Pellicore
  • Daniel Fabricant


When safety concerns forced the removal of ephedra from the market, other botanicals, including Citrus aurantium or bitter orange (BO) were used as replacements. A major component of the BO extract is synephrine, a chemical that is structurally similar to ephedrine. Because ephedrine has cardiovascular effects that may be exacerbated during physical exercise, the purpose of this study was to determine whether extracts containing synephrine produced adverse effects on the cardiovascular system in exercising rats. Sprague–Dawley rats were dosed daily by gavage for 28 days with 10 or 50 mg of synephrine/kg body weight from one of two different extracts; caffeine was added to some doses. The rats ran on a treadmill for 30 min/day, 3 days/week. Heart rate, blood pressure, body temperature, and QT interval were monitored. Both doses of both extracts significantly increased systolic and diastolic blood pressure for up to 8 h after dosing. Effects on heart rate and body temperature appeared to be due primarily to the effects of caffeine. These data suggest that the combination of synephrine, caffeine, and exercise can have significant effects on blood pressure and do not appear to be effective in decreasing food consumption or body weight.


Bitter orange Citrus aurantium Cardiotoxicology Blood pressure Heart rate Weight loss 


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Copyright information

© Springer Science+Business Media New York (outside the USA) 2013

Authors and Affiliations

  • Deborah K. Hansen
    • 1
  • Nysia I. George
    • 2
  • Gene E. White
    • 3
  • Ali Abdel-Rahman
    • 4
  • Linda S. Pellicore
    • 5
  • Daniel Fabricant
    • 4
  1. 1.Division of Systems BiologyFood and Drug Administration (FDA)/NCTRJeffersonUSA
  2. 2.Division of Bioinformatics and BiostatisticsFood and Drug Administration (FDA)/NCTRJeffersonUSA
  3. 3.Toxicological Pathology AssociatesJeffersonUSA
  4. 4.Office of Nutrition, Labeling and Dietary SupplementsUS Food and Drug Administration (FDA)/Center for Food Safety and NutritionCollege ParkUSA
  5. 5.Office of New DrugsUS Food and Drug Administration (FDA)/Center for Drug Evaluation and ResearchSilver SpringUSA

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