More than two thirds of Americans are overweight or obese, and each year they spend more than $2 billion on OTC weight-loss products and appetite suppressants. Products that promise “quick” weight loss are particularly popular. After numerous claims of illness and death resulted in the FDA banning of all supplements containing ephedra in 2003, the weight-loss industry was left scrambling to maintain the market for OTC products.1

One product that is filling the vacuum is bitter orange.

Background

Bitter orange, or Citrus aurantium, refers to both a citrus tree and its fruit. They are native to southern Vietnam but cultivated throughout much of the world.2 The spiny evergreen tree produces tiny, extremely tart fruit with thick, dimpled skin.2 The dried outer peel of the fruit is used medicinally.

For centuries, the flower of the tree has been used in folk medicine to treat numerous health problems, including GI disorders, nervousness, insomnia, gout, and sore throat. In Chinese medicine, the plant serves to cure poor appetite, stomach pain, and vomiting. However, it was always given in concert with other supporting herbs. In modern-day Latin America, a tonic made from the leaf of the plant is touted as a laxative as well as a sedative for insomnia and anxiety. In other cultures, the fruit’s peel is used as an antispasmodic.


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Mechanism of action

The basic concept of how bitter orange works is quite simple. Theoretically, thermogenesis of fat cells is chemically mediated through alpha-adrenergic stimulation, more specific to beta3 than beta1 or beta2.1 As a result, direct stimulation or agonist activity on the beta3 receptor should enhance the fat-burning process. However, problems can occur. Enhancing the beta system increases thermogenesis and up-regulates other important body functions, including heart rate and rhythm, BP, peripheral vasoconstriction, and respiratory rate.

The primary active alkaloid in bitter orange is synephrine, a stimulant very similar to ephedra.2 Because synephrine produces a sympathomimetic action, its beta3-agonist activity can cause high BP, cardiac arrhythmias, stroke, and even death. In addition, synephrine causes metabolic enzyme inhibition, which can hinder the hepatic breakdown of many prescription drugs, leading to dangerous levels of active medication in the system.3

Similar stimulants are thought to suppress appetite by having both serotoninergic and dopaminergic activity in the brain, giving a false sense of satiety and inducing a mild anorexia.

Scientific data

There are very few clinical trials investigating the safety and efficacy of bitter orange as a solitary agent for weight loss. One study that examined the weight-loss potential of bitter orange in a combination product found no statistically significant difference in weight loss in patients taking bitter orange compared with those taking placebo.4 At present, the National Center for Complementary and Alternative Medicine is not studying the use of bitter orange as a diet supplement. Reports by the German Commission E and the National Toxicology Program of the National Institutes of Environmental Health Sciences both documented the need for caution with the use of bitter orange as well as the plant’s potential for lipolytic effect.1 The FDA requests that any adverse reactions to products containing this supplement be reported.

Dosage

Dried bitter orange peel 1-2 g (with the white spongy backside removed) may be simmered for 10-15 minutes in water. Three cups daily are recommended for typical efficacy. Or, if a tincture is used, 2-3 mL t.i.d. isrecommended.5 Capsules containing powdered extract are also available.

Safety

Using bitter orange supplements for weight loss is controversial. Because the product is so similar to ephedra in its chemical action, there is significant concern about its safety. Approximately 155 deaths have been attributed to ephedra, which is now banned in the United States, and researchers fear a similar rise in mortality with the explosion in the popularity of bitter orange. Cardiovascular effects, agitation, and insomnia are frequent in patients taking bitter orange; these reactions can be lethal. Because at least seven deaths and 25 adverse events have been blamed on bitter orange within the past two years, the FDA has begun an investigation of it and other ephedra substitutes.

Drug interactions

Metabolically, serious interactions with other prescription drugs can occur, resulting in potentially toxic drug levels.6 Bitter orange is known to inhibit the cytochrome P450 3A4 enzyme system, so medications metabolized through this system could be significantly affected.6

Pregnant women or women who are nursing should never take any product containing bitter orange. Anyone on prescription medication of any kind should check with their health-care provider if considering this product.

Patients with histories of pollen or other plant-based allergies should use with caution. Bitter orange should not be given to children because no data exist on how the supplement reacts in immature systems.

How supplied and cost

Bitter orange powdered extract is available in capsule form; liquid tincture extract or teas may also be found. Depending on the type of product and vendor, the cost for 100 doses ranges from $5-$10.

Summary

The use of bitter orange supplements for appetite suppression and weight loss is highly controversial. Because of the lack of good clinical trials and the alarming number of reports of toxicity and adverse reactions, clinicians should not recommend this supplement to patients. The usual methods of lifestyle modification with conservative diet and exercise remain the most effective ways to manage weight.

Sherril Sego, MSN, FNP. Ms. Sego is a staff clinician at the Veterans Administration Hospital in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas.

References

1. American Botanical Council. Bitter Orange Peel and Synephrine. Available at www.herbalgram.org/default.asp?c=Bitter_Orange. Accessed December 6, 2006.

2. Wikipedia. Bitter Orange. Available at http://en.wikipedia.org/wiki/Bitter_orange. Accessed December 6, 2006.

3. Zeratsky K. Bitter orange: Helpful or harmful weight loss supplement. Available at www.mayoclinic.com/health/bitter-orange/AN01218. Accessed December 6, 2006.

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

5. NutraSanus. Bitter Orange. Available at www.nutrasanus.com/bitter-orange.html. Accessed December 6, 2006.

6. Skidmore-Roth L. Mosby’s Handbook of Herbs & Natural Supplements. 3rd ed. St. Louis, Mo.: Elsevier Mosby; 2006:132.