Ephedra-free weight loss supplements aren't risk-free, a study in humans shows.
The study looked at supplements containing bitter orange, also known as Seville orange or Citrus aurantium. The herb contains a compound known as synephrine. Synephrine is chemically similar to ephedrine, the active compound in ephedra. In April 2004, the FDA banned ephedra-containing supplements.
But similar doesn't mean the same. Is synephrine really dangerous? University of California, San Francisco researchers Christine A. Haller, MD, and colleagues took a look. Their bottom line: Bitter orange supplements carry risks that outweigh their unproven benefits.
"It does seem these drugs affect blood pressure and heart rate at the same level we saw with ephedra," Haller tells WebMD. "I stop short of saying our study shows adverse events. Certainly overweight people with high blood pressure or heart problems should avoid these products."
Haller is quick to note that the pure bitter-orange product she tested — Advantra Z, from Nutratech, Inc. — did not raise blood pressure.
"I'm quite pleased with the results of the Haller study," Nutratech president Bob Green tells WebMD. "They clearly show there is no increase in blood pressure, and an insignificant increase in heart rate after ingesting our product at doses that are more than most consumers would take in a day."
Green says that this kind of increase in heart rate could be dangerous for people with heart trouble. Haller notes that people who take supplements promising weight loss are overweight — exactly the people who tend to have heart trouble.
"We encourage anyone taking any kind of supplement to go to a doctor first," Green says.
That's a good idea — but it's no guarantee of safe bitter-orange use, Haller says.
"It is hard to identify who may react real badly to the heart stimulation effects," she says. "Even if people ask their doctor, we don't know who might develop heart rhythm problems or have a stroke."
Bitter Orange + Caffeine = Raised Blood Pressure
The researchers enrolled 10 healthy adults who took, in turn, single doses of Advantra Z, Xenadrine EFX from Cytodyne Technologies, and an inactive placebo under hospital-controlled conditions. Neither the researchers nor the volunteers knew which supplement they were taking. Before and after taking the pills, the volunteers’ blood was tested.
Xenadrine EFX contains bitter orange, caffeine (as much as in three cups of coffee), and several other ingredients. Its single-dose heart effects were similar to those seen with ephedra.
The combination supplement raised the volunteers' blood pressure by 7 percent to 12 percent. That effect was seen two hours after taking the drug.
It's not clear why Xenadrine increased blood pressure. Its large caffeine dose may be the culprit. Indeed, Green warns people who take any kind of supplement not to consume too much caffeine.
Bitter Orange and Heart Rate: Synephrine Not to Blame?
Haller's team found that heart rate increased by 17 beats per minute with Xenadrine EFX and by 11 beats per minute with Advantra Z. This effect was seen six hours after taking the pills — long after blood levels of synephrine peaked. Patients who took Xenadrine EFX got about 8.5 times less synephrine than those who took Advantra Z.
"We think the heart rate increase may be related to bitter orange, but probably it is not the synephrine that is doing that," Haller says. "We think it is something in the product, because this didn't happen with placebo. There is something compelling here that merits investigation."
Bitter Orange Benefit Debated
Green says several studies show that bitter orange supplements help people lose weight. But Haller says the medical literature reveals little evidence that bitter orange really works.
"These products may be dangerous for some people," Haller says. "Because they are not proven effective, it really is not worth taking a risk. They do nothing for you and may harm you. I look at the risk/benefit analysis, and there isn't any perceived benefit at this point."
Green agrees that more research is needed, but he defends his product's safety.
"There have been more than 50 million doses of Advantra Z sold over the last seven years without any adverse events," he says.
Although Haller's team obtained Advantra Z for their study, Green says the product is intended as a "supplement ingredient" and is not sold directly to consumers.
But Haller sees untested multi-ingredient supplements as a nightmare.
"The products out there are so varied," she says. "Some contain ephedra-like compounds, and some have ingredients we have never heard of. So don't think they are all safe now that ephedra is gone. We just don’t have enough data to say they are safe or that they work."
SOURCES: Haller, C. The American Journal of Medicine, September 2005; vol 118. Christine A. Haller, MD, assistant professor of medicine, University of California, San Francisco. Bob Green, president, Nutratech Inc., Wayne, N.J.