Clinical Abstracts

With Comments by Adriane Fugh-Berman, MD

Citrus aurantium for Weight Loss

November 2000; Volume 2; 85-86

Source: Colker CM, et al. Effects of Citrus aurantium extract, caffeine, and St. John’s wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res 1999;60:145-153.

Design/Setting/Subjects: A double-blind, randomized, placebo-controlled, three-armed study of 23 subjects with a body mass index more than 25 kg/m2. Subjects were divided into three groups; one group received treatment, one group received a maltodextrin placebo, and one group received nothing. All were counseled by a dietitian on how to follow an 1,800 calorie American Heart Association Step 1 diet and performed a weight circuit training exercise program three days a week under the direction of an exercise physiologist.

Treatment/Dose/Route/Duration: A product containing 975 mg Citrus aurantium extract (containing 6% synephrine alkaloid), 528 mg caffeine, and 900 mg St. John’s wort (3% Hypericum [sic]) daily for six weeks.

Outcome Measures: Weight, fat loss, mood (Profile of Mood States questionnaire), blood lipids, blood pressure (BP), heart rate, EKG findings, serum chemistries, urinalysis.

Results: Twenty subjects completed the six-week study (nine in the treatment group, seven in the placebo group, and four in the control group). Subjects in the treatment group lost a significant amount of weight (1.4 kg) compared to the placebo group (which lost 0.9 kg) and control group (which lost 0.04 kg). The treated group lost 2.9% of fat while no significant changes in percent body fat lost were seen in the placebo or control groups. No significant changes were seen in any group in the profile of mood states questionnaire, blood lipids, BP, heart rate, EKG, serum chemistries, or urinalysis. The treated group had a significant increase in basal metabolic rate while the placebo group had a significant decrease in basal metabolic rate; there was no change in the control group. No side effects were reported.

Funding: Twin Laboratories, Inc. Hauppage, NY.

Comments: This very small study found an additive effect of a Citrus aurantium product in short-term weight loss. No justification is given for having both a placebo and an untreated control group, and the latter comprised only four subjects. It was difficult for me to believe that the difference in weight loss between the treated group (1.4 kg) and the placebo group (0.9 kg) was significant; half a kilo equals 1.1 pounds. I’m still not convinced. Although the text states that the treated group lost a significant amount of weight compared to the placebo and untreated groups, the table appears to indicate that the difference is significant compared to baseline but not in comparison to the other groups.

There is no evidence that St. John’s wort has any effect on weight loss or appetite suppression (although there is clear evidence of efficacy for depression). And since dieting can be depressing, maybe this is not an unreasonable addition. I assume that the "3% hypericum" is a typo (hypericum is the same as St. John’s wort) and actually means 3% hypericin, in which case the dose of St. John’s wort in this product would be a therapeutic antidepressant dose. It should be kept in mind that St. John’s wort interacts with a number of drugs, including cyclosporine, digoxin, theophylline, and SSRIs.1 There is a lot of caffeine in this product; the equivalent of about four cups of coffee or 10 cups of tea. Caffeine has a thermogenic effect, and this effect is synergistic with other sympathomimetic agents. Even 100 mg caffeine has a thermogenic effect lasting one to two hours; dosages higher than 600 mg/d increase 24-hour energy expenditure under respiratory chamber conditions.2

Citrus aurantium contains synephrine and octopamine, which are phenolamines found in mammalian organs and sympathetic nerve fibers—in the same region as adrenaline and noradrenaline. Synephrine is structurally similar to adrenaline, and octopamine is similar in structure to noradrenaline (they differ only in the number of hydroxyl groups on the aromatic ring).3 P-synephrine has antidepressant effects in mice; in oral doses from 1-10 mg/kg, p-synephrine decreased the duration of immobility in the tail suspension test and forced swimming test (doses of 30 mg/kg were ineffective).4 Administration of an alpha-1 adrenoreceptor antagonist blocked the effect. Besides modulating the activation of alpha adrenoreceptors, both synephrine and octopamine appear to inhibit cyclic adenosine monophosphate production.3 Beta-3 adrenoreceptors also are activated by synephrine and octopamine. Beta-3 adrenoreceptor agonists are full lipolytic agents in rats, hamsters, and dogs, but are much less active in humans and guinea pigs. Synephrine is partially active in stimulating lipolysis in rats, hamsters, dogs, guinea pigs, and humans.5 Of agents tested, octopamine was more potent; of several amines, only octopamine fully stimulated lipolysis in rats, hamsters, and dogs; it was inefficient in humans and guinea pigs.

Sympathomimetic agents in sufficient doses speed metabolism and may result in weight loss. Given growing concerns with ephedra, products containing synephrine and octopamine are apt to be the next wave in "natural" weight loss products. However, any sympathomimetic agent taken in sufficient dosages to cause weight loss cannot be presumed to be safe, especially in those with cardiovascular disease.


1. Fugh-Berman A. Herb-drug interactions. Lancet 2000;355:134-138.

2. Dulloo AG, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. An J Clin Nutr 1999;70:1040-1045.

3. Airriess CN, et al. Selective inhibition of adenylyl cyclase by octopamine via a human cloned a2A-adrenoceptor. Br J Pharmacol 1997;122:191-198.

4. Song DK, et al. Antidepressant-like effects of p-synephrine in mouse models of immobility tests. Neurosci Lett 1996;214:107-110.

5. Carpene C, et al. Selective activation of beta3-adrenoreceptors by octopamine: Comparative studies in mammalian fat cells. Naunyn Schmiedebergs Arch Pharmacol 1999;359:310-321.