A daily dose of about 100 milligrams of a patented bitter orange extract (Advantra Z, Nutratech), alone or in combination with the other citrus flavonoids naringin and hesperidin did not produce any significant changes in systolic or diastolic blood pressures, blood chemistries or blood cell counts.
“This 60-day study is the longest study with the highest dose conducted to date involving bitter orange extract as a single entity product,” wrote the researchers in Food and Chemical Toxicology.
The study was performed by Gilbert Kaats from Integrative Health Technologies, Inc. (San Antonio), Howard Miller from Nutratech Inc. (New Jersey), Harry Preuss from Georgetown University Medical Center (Washington, DC), and Sidney Stohs from Creighton University Medical Center (Omaha).
Nutratech has been very active in supporting science about its patented bitter orange extract Advantra Z, and the New Jersey-based company funded the new study.
Commenting on the study's findings, Bob Green, Nutratech's president, told NutraIngredients-USA: "Most bitter orange safety studies, until now, have been short‑term, often based on a single dose. That’s why Nutratech welcomed the opportunity to fund a 60-day study.
"Dr. Kaats’ research not only corroborates previous safety studies, it confirms that p‑synephrine dosages (98 mg daily) even higher than those recently supported by Health Canada (50 mg) and Intertek Cantox (60 mg) can be tolerated without negative side effects.”
Growing presence in the market
Bitter orange 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 inquiries 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”.
For the new study, Dr Kaats and his co-workers recruited 75 healthy men and women with an average age of 51 to participate in their study. The participants were randomly assigned to receive supplements of the bitter orange extract, or the extract plus naringin and hesperidin, or placebo for 60 days.
The researchers reported no significant changes in blood pressures, blood chemistries or blood cell counts in any of the groups. A small increase in heart rates was observed in the combination group, but this was deemed to be clinically insignificant.
“The lack of cardiovascular effects agree with previous studies where bitter orange extract was administered as a single dose and when it has been used in combination with caffeine and other ingredients that have been administered for varying periods of time,” wrote the researchers.
“Longer term studies are required to determine weight loss and the effectiveness of bitter orange (p-synephrine) as well as long term safety,” they added.
Source: Food and Chemical Toxicology
Published online ahead of print, 25 January 2013, doi: 10.1016/j.fct.2013.01.013
“A 60 Day Double-Blind, Placebo-Controlled Safety Study involving Citrus aurantium (Bitter Orange) Extract”
Authors: G.R. Kaats, H. Miller, H.G. Preuss, S.J. Stohs