Bitter orange
Bitter orange

Background

Bitter orange (Citrus aurantium) is a fruit-bearing tree native to Asia. It contains an active ingredient called synephrine that is similar to ephedra.

In 2004, the FDA banned ephedra due to serious effects on the heart. Since then, many weight loss and bodybuilding products have used bitter orange and caffeine in its place. Bitter orange contains many chemicals that affect the nervous system. These chemicals might cause heart problems in healthy adults.

Bitter orange is used for obesity, athletic performance, and many other purposes, but there is no good scientific evidence to support its use.

Bitter orange (synephrine) is considered a banned substance by the National Collegiate Athletic Association (NCAA). Don't confuse bitter orange with other orange species such as sweet orange and bergamot.
When taken by mouth: Bitter orange is likely safe when eaten in the amounts found in food. But bitter orange is possibly unsafe when taken in the larger amounts used as medicine. Bitter orange, taken by itself or with stimulants such as caffeine or caffeine-containing herbs, might increase the risk for high blood pressure, fainting, heart attack, stroke, and other serious side effects. There are also reports that bitter orange can trigger headaches in some people.

When applied to the skin: Bitter orange essential oil is possibly safe. The oil can cause sensitivity to the sun. Wear sunblock outside, especially if you are light-skinned.

When inhaled: Bitter orange essential oil is possibly safe when inhaled as aromatherapy.

Special Precautions & Warnings:

Pregnancy: Bitter orange is likely safe when eaten in the amounts found in food. But it is possibly unsafe when taken by mouth in medicinal amounts. Stay on the safe side and stick to food amounts during pregnancy.

Breast-feeding: There isn't enough reliable information to know if bitter orange is safe to use when breast-feeding. Stay on the safe side and avoid use.

Headache: Taking bitter orange might trigger headaches, including migraines and cluster headaches.

High blood pressure: Taking bitter orange, especially together with caffeine, might increase blood pressure in healthy people. Avoid using bitter orange, especially in combination with stimulants such as caffeine, if you have high blood pressure.

Glaucoma: Bitter orange might worsen glaucoma. Avoid using it if you have this condition.

Heart disease: Taking bitter orange, especially together with caffeine or other stimulants, might increase the risk of serious side effects in people with a particular heart problem called "long QT interval syndrome".

Irregular heartbeat (heart arrhythmia): Taking bitter orange, especially together with caffeine, can increase heart rate in healthy people. Avoid using bitter orange, especially with stimulants such as caffeine, if you have an irregular heartbeat.

Surgery: Bitter orange acts like a stimulant, so it might interfere with surgery by increasing heart rate and blood pressure. Stop taking bitter orange at least 2 weeks before a scheduled surgery.

Effectiveness

There is interest in using bitter orange for a number of purposes, but there isn't enough reliable information to say whether it might be helpful.
Likely effective Effectiveness definitions
Possibly effective Effectiveness definitions
Likely ineffective Effectiveness definitions
Possibly ineffective Effectiveness definitions
Insufficient evidence Effectiveness definitions

Dosing & administration

Bitter orange is available in supplements and topical oils. Supplements containing bitter orange are often marketed for athletic performance and weight loss. The active chemical in bitter orange, synephrine, can cause serious side effects, and products containing this ingredient have been shown to contain amounts much higher than what is listed on the product label. They've also been found to contain many other synthetic stimulants that are banned in supplements.

Interactions with pharmaceuticals

Caffeine

Interaction Rating=Moderate Be cautious with this combination.

Bitter orange is a stimulant. Caffeine is also a stimulant. Taking these products together can increase blood pressure and cause the heart to beat rapidly. This can cause serious adverse effects such as heart attack and stroke.

Colchicine

Interaction Rating=Moderate Be cautious with this combination.

Bitter orange might affect levels of colchicine. Using colchicine with bitter orange may reduce the benefits or increase the side effects of colchicine.

Dextromethorphan (Robitussin DM, and others)

Interaction Rating=Moderate Be cautious with this combination.

Bitter orange might decrease how quickly the liver breaks down dextromethorphan. Taking bitter orange along with dextromethorphan might increase the effects and side effects of dextromethorphan such as nervousness, drowsiness, and others.

Felodipine (Plendil)

Interaction Rating=Moderate Be cautious with this combination.

The liver breaks down felodipine to get rid of it. Bitter orange might decrease how quickly the liver gets rid of felodipine. Taking bitter orange along with felodipine might increase the effects and side effects of felodipine.

Indinavir (Crixivan)

Interaction Rating=Moderate Be cautious with this combination.

The liver breaks down indinavir to get rid of it. Bitter orange might decrease how quickly the liver breaks down indinavir. Taking bitter orange along with indinavir might increase the effects and side effects of indinavir.

Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates)

Interaction Rating=Minor Be watchful with this combination.

Some medications are changed and broken down by the liver. Bitter orange might change how quickly the liver breaks down these medications. This could change the effects and side effects of these medications.

Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates)

Interaction Rating=Moderate Be cautious with this combination.

Some medications are changed and broken down by the liver. Bitter orange might change how quickly the liver breaks down these medications. This could change the effects and side effects of these medications.

Medications for depression (MAOIs)

Interaction Rating=Major Do not take this combination.

Bitter orange contains chemicals that stimulate the body. Some medications used for depression can increase these chemicals. Taking bitter orange with these medications might cause serious side effects including very fast heartbeat and very high blood pressure.

Some common MAOIs include phenelzine (Nardil), selegiline (Zelapar), and tranylcypromine (Parnate).

Medications for diabetes (Antidiabetes drugs)

Interaction Rating=Moderate Be cautious with this combination.

Bitter orange might lower blood sugar levels. Taking bitter orange along with diabetes medications might cause blood sugar to drop too low. Monitor your blood sugar closely.

Medications that can cause an irregular heartbeat (QT interval-prolonging drugs)

Interaction Rating=Moderate Be cautious with this combination.

Bitter orange might affect electrical currents in the heart. This can increase the risk of having an irregular heartbeat. Some medications can have this same effect. Taking bitter orange with these medications might increase the risk for a serious heart issue.

Midazolam (Versed)

Interaction Rating=Major Do not take this combination.

Bitter orange can decrease how quickly the body breaks down midazolam. Taking bitter orange along with midazolam might increase the effects and side effects of midazolam.

Sildenafil (Viagra)

Interaction Rating=Moderate Be cautious with this combination.

The body breaks down sildenafil to get rid of it. Bitter orange can decrease how quickly the body breaks down sildenafil. Taking bitter orange along with sildenafil might increase the effects and side effects of sildenafil.

Stimulant drugs

Interaction Rating=Moderate Be cautious with this combination.

Stimulants, such as amphetamines and cocaine, speed up the nervous system. By speeding up the nervous system, stimulant medications can increase blood pressure and speed up the heartbeat. Bitter orange might also speed up the nervous system. Taking bitter orange along with stimulant drugs might cause serious problems including increased heart rate and high blood pressure.

Interactions with herbs & supplements

Herbs and supplements that might cause an irregular heartbeat (QT interval-prolonging products): Bitter orange might change the electrical currents in the heart. This can increase the risk of having an irregular heartbeat. Taking bitter orange with other supplements with similar effects might increase the risk for a serious heart issue. Examples of supplements with this effect include ephedra, grapefruit, iboga, and Panax ginseng.
Herbs and supplements that might lower blood sugar: Bitter orange might lower blood sugar. Taking it with other supplements with similar effects might lower blood sugar too much. Examples of supplements with this effect include aloe, bitter melon, cassia cinnamon, chromium, and prickly pear cactus.
Herbs and supplements with stimulant properties: Bitter orange might have stimulant effects. Taking it with other supplements with similar effects might increase the chance of side effects, including rapid heartbeat and high blood pressure. Examples of supplements with this effect include 1,3-DMAA, caffeine-containing products, DMHA, and ephedra.

Interactions with foods

Taking bitter orange with caffeine-containing foods or beverages can increase blood pressure and heart rate in healthy adults. Avoid this combination.
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This monograph was last reviewed on 31/01/2024 11:00:00 and last updated on 30/03/2022 06:03:16. Monographs are reviewed and/or updated multiple times per month and at least once per year.
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