Data from over 20 studies involving about 360 people concluded: “The results involving both published and un-published clinical studies indicate 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,”
“p-Synephrine/bitter orange extract alone as well as in combination with other ingredients results in signifi-cant increases in resting metabolic rate, and when taken for periods of time up to 12 weeks may result in modest weight loss,” added Sidney Stohs from Creighton University Medical Center, Harry Preuss from Georgetown University Medical Center, and Mohd Shara from Jordan University of Science and Technology in Jordan.
The review is published in the International Journal of Medical Sciences. All of the authors have worked as consultants for Nutratech, Inc. - the firm behind patented bitter orange extract Advantra Z.
Growing presence in the market
Bitter orange (Citrus aurantium) and p-synephrine, the predominant amine in bitter orange, are claimed to increase energy expenditure, facilitate the breakdown of fat and increase glucose uptake by muscles, and is widely used in weight management and sports nutrition supplement.
The ingredient’s profile increased following the FDA ban on ephedra in 2004 as it contains similar compounds and was favored by dietary supplements manufacturers as an ephedra substitute.
Some suppliers have also reported a surge in enquires from manufacturers looking for alternatives to controversial ingredient DMAA in the wake of the FDA’s recent crackdown on the stimulant.
P-synephrine is not banned by WADA, the FDA or Health Canada, and the latter recently changed its guidelines and concluded that 1 to 50 mg per day is “not likely to cause any adverse health consequences”.
Despite this, concerns continue to be raised that p-synephrine may increase blood pressure and heart rate, particularly when taken in combination with other stimulants such as caffeine. Indeed, as reported recently by NutraIngredients-USA, scientists from the FDA reported that a multi-component extract of bitter orange could raise blood pressure and heart rate in lab animals (Toxicology and Applied Pharmacology, Vol. 261, pp. 236-247).
However, such claims have been dismissed by suppliers. In addition, Dr Stohs’ 2010 review on the subject concluded that safety concerns and adverse events associated with bitter orange and p-synephrine are ‘unwarranted and unjustified’ (Journal of Functional Foods, Vol. 2, pp. 235-238).
For their new review Drs Stohs, Preuss and Shara found that over 50% of the subjects from the 20 studies were overweight or obese, and about 65% consumed caffeine ranging from 132 to 528 milligrams per day in conjunction with doses of p-synephrine ranging from 10 to 53 milligrams per day.
In addition, about 44 % of the subjects consumed products containing only bitter orange/p-synephrine, while the rest consumed products with multiple ingredients.
“The data accumulated to date do not sup-port hypothesized concerns regarding potential adverse effects of p-synephrine particularly with respect to the cardiovascular system due to a paucity of binding to alpha-, beta-1 and beta-2 adrenergic receptors while exhibiting modest binding to beta-3 adrenergic receptors,” they explained.
“However, a need exists for additional well con-trolled, long term human efficacy and safety studies involving p-synephrine/bitter orange extract.”
Source: International Journal of Medical Sciences
September 2012, Volume 9, Number 7, Pages 527-538, doi: 10.7150/ijms.4446
“A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine”
Authors: S.J. Stohs, H.G. Preuss, M. Shara