“A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p‑Synephrine,” published in the September 2012 issue of International Journal of Medical Sciences, concludes that "bitter orange extract and p-synephrine increase metabolism and energy expenditure" and "when taken for periods of time up to 12 weeks may result in modest weight loss." The review also finds that "p-synephrine alone or in combination with caffeine does not appear to produce significant adverse cardiovascular effects or pose a risk to human health at doses commonly ingested orally."
Authored by two of the country’s foremost researchers of natural performance-enhancing ingredients—Sidney J. Stohs, PhD, and Harry G. Preuss, MD—in conjunction with Mohd Shara, PharmD, PhD, the article provides an in-depth scientific analysis of the chemistry, efficacy and safety of bitter orange drawn from 56 clinical research studies and other reference sources.
This review of the most current research and knowledge available on bitter orange summarizes the results of more than 20 studies involving a total of approximately 360 subjects who consumed bitter orange/p-synephrine alone or in combination with other ingredients. More than half of the subjects involved in these studies were overweight, and approximately two-thirds consumed 132 mg to 528 mg of caffeine per day.
The summary also contains a detailed discussion of p-synephrine receptor binding and the reasons for the absence of negative cardiovascular side effects, noting that "Properties possessed by m-synephrine are inappropriately attributed to bitter orange extract and p-synephrine, and clinical case study reports and reviews involving bitter orange extract frequently make inappropriate references to m-synpephrine." m-Synephrine (phenylephrine)—which is often found in nasal decongestants and sprays - has the potential for raising blood pressure in humans.