Editor's note: This article is a reprint. It was originally published on October 30, 2017.
Bitter orange, a flowering evergreen native to Asia, is now a widely cultivated fruit in the Mediterranean region. However, it is not an edible fruit, but the outer “zest” of the fruit, excluding the white flesh, and the oil from the leaves and branches are used medicinally. Bitter orange, which is said to have arrived in America with Spain and Portugal in the 1500s, has many different names depending on the country you are talking about it in.
Herb Resources1 There are several listed, including amara, hua chu heng, citrus bergamia, citrus bigaradia, citrus vulgaris, seville orange, zishi, petit grain, chong chao, bigarade orange, and sour orange. Notable compounds contained in bitter orange peel include flavones, the alkaloid synephrine, octopamine, N-methyltyramine, and carotenoids.2
Like many other ancient Asian plants, the leaves and flowers of Citrus aurantium have been used in traditional folk medicine, and the small fruits, while still “green”, are the flavoring for a drink known as curacao. Ayurvedic oil3 Bitter orange is called “orange bitter oil” and is said to help with stomach upsets, gout, loss of appetite, and anxiety. The peel has also been used to treat indigestion, stomachaches, headaches, constipation, and high blood pressure.
According to Brazilian folklore, bitter orange helps to relieve insomnia and anxiety. Likewise, traditional European applications mention it as useful for stomach problems, as a sedative, and for treating “nervous problems” and sore throats. In China and some parts of the Amazon, the list of diseases for which bitter orange is used includes nasal congestion and bladder problems.
Hordenine – an adrenergic agent in bitter orange that releases epinephrine
One of the most potent compounds in bitter orange is hordenine, also known as N,N-dimethyltyramine, an alkaloid found only in a few plants, including barley and bitter orange. The action of this alkaloid is adrenergic, causing nerve cells to release the neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline).
Both are said to increase focus and the “fight or flight” response. Hordenine increases the response to norepinephrine, and one animal study reported increased energy and focus after exposure.4 Self Hacked notes in another study on hordenine:5
“Hortenine itself does not cause any physical changes, meaning it does not directly increase alertness, but rather indirectly increases alertness by blocking the clearance of norepinephrine.”
Additionally, hortenine has been shown to reduce melanin production by 30%, which is helpful for people who have excessive skin pigmentation, which leads to freckles, age spots, and other hyperpigmentation.6 The compound became famous many years ago when shady horse racing managers fed their racehorses food containing hordenine to boost their performance.
Because the energy effect is short-lived and requires high doses to induce the desired reaction, many countries believed that performance improvement was impossible.7 And they didn't consider the practice “cheating.” But after testing, Canada banned hordenine for horses.
Although a short-term stimulating effect occurred within two minutes, side effects such as excessive sweating and immediate bowel movements were reported when injected directly into the bloodstream.8
Bitter orange may help with weight loss, but be careful with bitter orange supplements for this purpose.
Bitter orange is probably best known for its ephedra-like substance that “activates” metabolism, which is why it is often used in weight loss supplements, sometimes in combination with caffeine. It contains the alkaloid synephrine, which is chemically similar to ephedrine and is banned by the National Collegiate Athletic Association (NCAA).9
Studies have shown that taking products containing bitter orange extract or synephrine for 6 to 12 weeks slightly increases weight loss.10 Although no serious side effects have been reported yet, you should be cautious with weight loss supplements containing this ingredient.
When taken in large doses or combined with other stimulants such as caffeine, bitter orange, or its stimulating alkaloids, side effects such as fainting, heart attack, and stroke may occur.
Some experts believe these supplements may cause similar problems to supplements containing ephedra, which were banned in 2004.11,12 On the other hand, some claim that bitter orange is different or milder than ephedra, and that it has side effects when taken with caffeine or certain medications.13
Also, be aware that the hordenine in bitter orange can cause false positives in opioid drug tests, including tests for morphine, oxymorphone, hydromorphone, and apomorphine. However, most cases of false positives in drug tests due to high hordenine levels are due to people drinking beer made from barley.14 According to Self Hacked, there are a number of other potential side effects to watch out for when taking hordenine.15 These include:
- Hordenine can decrease the way other neurotransmitters are broken down. For example, monoamine oxidase-B essentially inactivates hordenine and other neurotransmitters like dopamine and phenylethylamine. While you are “focusing” on breaking down hordenine, other neurotransmitters like dopamine may increase, increasing your reactivity to stress.16
- Experiments on cats have shown that blood pressure levels can fluctuate, initially decreasing and then suddenly increasing dramatically, followed by similar fluctuations.17
- It can cause seizures. The study above also notes that hordenine, a cholinesterase inhibitor, prevents the cholinesterase enzyme from breaking down acetylcholine. Acetylcholine transmits signals in nerve cells, causing things like movement. “By preventing cholinesterase from breaking down acetylcholine, the body may not stop moving naturally, and may continue to cause seizures.”18
- Hordenine can lower your protection against UV rays. Melanin protects your skin by absorbing free radicals and protecting it from excessive UV exposure, but hordenine's ability to reduce melanin production leaves your skin vulnerable to damage.19
- Consistently eating large amounts of foods containing hordenine can cause kidney damage, including tubular degeneration, in which kidney cells fill with water. In animal studies, diabetes, a disease in which glucose is released from the kidneys into the urine, occurred in 62% of rats fed high doses of foods containing hordenine.20
Bitter Orange Usage and Precautions
Bitter orange is used in foods such as syrups, marmalades, spicy fruit chatneys, and candied fruits, especially because of its high pectin content, which creates a gel-like consistency. It is also used in cosmetics and aromatherapy, especially for its energy boosting, anxiety relief, digestion, and skin health. The essential oil known as bitter orange is extracted from the peel of the fruit (the oil extracted from the tree’s flowers is called neroli oil) and has been used for a long time in Ayurveda.
Modern studies have shown that the oil acts as an effective antifungal agent when applied topically, and bitter orange has also been found to have anticancer properties.21,22
According to a study published in the Journal of Pharmacology, drinking two 8-ounce glasses of bitter orange juice over an 8-hour period appears to be safe for people with normal blood pressure, but people with heart rate abnormalities, uncontrolled high blood pressure, narrow-angle glaucoma, or those taking decongestants or MAO inhibitors as antidepressants should avoid the juice.23
Also, be careful with supplements containing high levels of bitter orange, hordenine or synephrine, especially if you have heart disease or high blood pressure, and be careful not to take them with caffeinated beverages or MAO inhibitors, which are medications used to treat depression.24 Additionally, bitter orange inhibits enzymes in the small intestine, which can affect their blood levels, which may affect how certain medications work.
These include antidepressants, anti-ulcer drugs, HIV, anti-nausea and anti-fungal drugs, anti-anxiety drugs, statins, some calcium channel blockers, weight loss supplements, and antivirals.25 Herbal Supplement Resource notes that consuming large amounts of bitter orange peel can cause abdominal pain, cramps, and even death in children.26 Therefore, children and pregnant and breastfeeding women should avoid it.
In conclusion, bitter orange and bitter orange essential oil have valuable medicinal properties, but they should be used with caution, ideally under the guidance of a knowledgeable natural health practitioner who can help you with proper dosage and administration. Weight loss supplements containing bitter orange or related ingredients are dangerous and should be avoided.
