Unlike ephedrine, some of the alkaloids in bitter orange are believed to act specifically on beta-3 adrenergic receptors, which promote fat breakdown.
There are a limited number of published clinical trials examining the effects of bitter orange in humans, but there has been work done involving in vitro (experiments done in a laboratory dish), animal models, human studies described in patents, and even a few published human studies that generally support the idea that bitter orange is a safe ingredient for weight loss.
One study examined the effectiveness of bitter orange in combination with caffeine and St. John's Wort versus placebo in overweight men and women following a weight loss program that involved a low-fat reduced calorie diet (1800 kcal/day) and regular exercise (3 days/week).
Compared to the placebo group, subjects in the bitter orange group lost more body weight and body fat and increased their metabolic rate after just 6 weeks. There were no reported side effects or adverse responses in markers of renal, liver, and cardiovascular function.
Although this was a small study, the results do support the notion that the mild stimulants in bitter orange may offer benefits for weight loss.