By Elaine Watson Nutra Ingredients USA
Nutratech - the firm behind patented bitter orange (Citrus aurantium) extract Advantra Z - has seen a surge in enquires from manufacturers looking for alternatives to DMAA in the wake of the FDA’s crackdown on the controversial stimulant.
Bitter orange is 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 supplements, increasingly as a replacement for DMAA.
Nutratech president Bob Green told NutraIngredients-USA: “Sales were already up in the double digits before the DMAA issue really hit the headlines, but since then we have seen a surge in interest as companies look for an alternative.”
‘Frustrating’ to see ‘erroneous’ claims about p-synephrine resurface
However, it has been frustrating to see some firms continue to make “erroneous” claims about the risks of p-synephrine, the predominant amine in bitter orange, despite the fact it is supported by reams of safety data, he said.
For example, in a class action lawsuit filed against supplement maker Nutrex Research and retailer Vitamin Shoppe on June 18 in Illinois, plaintiff Rochelle Ibarolla argues that “Synephrine – sometimes referred to as bitter orange – may be safe for consumption when taken in the small amounts found in food.
“But when taken as a supplement for weight loss, it poses a serious health risk. This is particularly true when it is taken with another stimulant, such as caffeine or caffeine-containing herbs. Then, it can greatly increase the risk for high blood pressure, fainting, heart attack, stroke, and other severe side effects.”
But this was “simply wrong”, said Green.
Tens of millions of doses without serious adverse event reports
He added: “Some years ago, someone from the FDA made an erroneous statement about bitter orange and p-synephrine that was eventually recanted. But unfortunately, with today’s technology, people are able to regurgitate what they have read without any substance behind it.”
He added: “Because it is structurally similar to ephedra, some people assumed that it increases the heart rate and blood pressure. But it doesn’t. Tens of millions of doses of bitter orange extract/p-synephrine-containing products have been consumed in recent years without the report of serious adverse events.”
The safety of p-synephrine has been extensively researched said Green, citing a paper co-authored by Dr. Sidney J. Stohs, dean of Creighton University Medical Center School of Pharmacy and Health Professions, entitled ‘The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p Synephrine’ published in the Phytotherapy Research last April .
Calorie burning, energy, and weight management
This concluded that “based on current knowledge, the use of bitter orange extract and p-synephrine appears to be exceedingly safe with no serious adverse effects being directly attributable to these ingredients”.
Just because there were “structural similarities” to DMAA and ephedra did not make p-synephrine dangerous, noted Stoh: “You cannot extrapolate the properties of other biogenic amines to p-synephrine based on some structural similarities.
“The structural differences in p-synephrine relative to biogenic amines as epinephrine, nor-epinephrine, ephedrine, m-synephrine (phenylephrine), pseudoephedrine, and DMAA result in markedly different adrenergic receptor binding and pharmacokinetic characteristics, and as a consequence markedly different pharmacological properties.
“P-Synephrine does not exhibit increases in heart rate and blood pressure or other adverse cardiovascular effects that occur with epinephrine, nor-epinephrine, m-synephrine, DMAA, and related compounds.”
His findings were supported by a toxicology study from scientists at the FDA published in Birth Defects Research Part B: Developmental and Reproductive Toxicology (doi: 10.1002/bdrb.20308).
Doping, p-synephrine and banned lists
P-Synephrine is not banned by WADA, the FDA or Health Canada (which recently changed its guidelines and concluded that 1 to 50 mg per day is “not likely to cause any adverse health consequences”), said Green.
While it is still on the banned list at the NFL, Nutratech is confident that this could change, said Green.
“We’re in ongoing discussions with the NFL and are hoping that once they review all the data they too will get it deleted [from their banned list].”
Background to Advantra Z
The intellectual property around Advantra Z was developed by ZhiShin, LLC and licensed to New Jersey-based Nutratech, which is its exclusive global distributor.
Advantra Z - which contains a combination of citrus amines from unripe bitter orange including p-synephrine - is protected by a suite of patents filed in the US, Canada and Europe said Green, who said Nutratech is currently working on research looking at the synergistic effects of Advantra Z used in combination with other ingredients.
The US Patents 6,224,873 ; 6,316,499 ; 6,340,481 ; 6,340,482 cover its ability to stimulate thermogenesis, reduce weight, increase lean muscle mass, improve athletic performance and suppress the appetite.