FDA Study Shows Bitter Orange Ups Blood Pressure

JEFFERSON, Ark.Synephrine, either as bitter orange extract or as pure synephrine, increased heart rate and blood pressure in rats, according to a new FDA study (Toxicol Appl Pharmacol. 2012 Jun 15;261(3):236-47). This study goes against previous studies that have shown bitter orange doesnt increase stress on the heart.

Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Bitter orange has been increasing popular as a dietary ingredient since ephedra-containing dietary supplements were banned from the U.S. market in 2004. As bitter orange's dominant amine, p-synephrine, a stable isomer of synephrine, it stimulates beta-3 receptors. Previous studies have shown these receptors increase fat burning, but do not affect blood pressure.

P-synephrine has structural similarities to ephedrine and nor-epinephrine, but research has shown it exhibits different pharmacokinetic and receptor binding properties (Oxid Med Cell Longev. 2011;2011:482973). Ephedrine contains m-synephrine, which affects alpha, beta-1 and beta-2 receptors, increasing blood pressure and heart rate. However, this study showed p-synephrine makes minimal contact with alpha-1, and -2, and beta-1 and -2 receptors, which are responsible for causing negative cardiovascular and central nervous systems side effects.

In 2010, HerbalGram, a publication from the American Botanical Council (ABC), published a review that determined bitter orange and bitter orange extract are safe for use as ingredients in foods and dietary supplements.

In this current study, female Sprague-Dawley rats received either bitter orange extract  (6-percent synephrine) or pure synephrine extract (95-percent synephrine) in doses of either 10 or 50 mg synephrine/kg body weight for 28 days. Additionally, caffeine was added to these doses because the authors noted many dietary supplements also contain caffeine.

The researchers reported animals treated with 95-percent synephrine showed minimal effects on heart rate and blood pressure; however, more significant effects were observed with the bitter orange extract, suggesting other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added, they reported.

Bob Green, president, Nutratech Inc., a company that markets Advantra Z bitter orange extract, noted the dosing in this study is 13 to 43 times the typical human dosage. "So the results of the study cannot be directly applied to the Citrus aurantium/p synephrine used in dietary supplements." Green said he got advice form Sidney J. Stohs, Ph.D., co-author of a scientific review on the safety of bitter orange in regards to the current study.

Green added that the increase in heart rate and blood pressure in the study participants ranged from 4  to 11.5 percent.  "Its important to understand that heart rate and blood pressure will increase 10 to 20 percent with moderate exercise or simply walking up a flight of stairs. So while statistically significant, the statistics in the study are not clinically significant or relevant to humans."

Green added the large amount of evidence supporting the safety of bitter orange ensures manufacturers can be confident about including it in their dietary supplements.