What Is Bitter Orange?


Editor’s Note: This article is a reprint. It was originally published October 30, 2017.

A flowering evergreen tree native to Asia, bitter orange is a fruit now widely cultivated in Mediterranean regions. But rather than a fruit for eating, the outer “zest” of the fruit, sans the white pulp, as well as the oil from the leaves and branches, are used as a medicinal. Bitter orange, which purportedly arrived in the Americas with the Spanish and Portuguese in the 1500s, has many other names, depending on the country talking about it.

Herbal Resource1 lists several — amara, hua chu hung, citrus bergamia, citrus bigaradia, citrus vulgaris, Seville orange, zhi shi, petit grain, chongcao, bigarade orange and sour orange. Compounds of note contained in bitter orange peel include flavones, the alkaloids synephrine, octopamine, and N-methyltyramine and carotenoids.2

As many other ancient Asian plants have been, the leaves and flowers of the Citrus aurantium have been used in traditional folk remedies, and the small fruit while still “green” is the flavor in a liquor known as Curacao. Ayurveda Oils3 refers to bitter orange as “orange bitter oil” and notes it may be helpful for stomach troubles, gout, low appetite and anxiety. The rind has also been used to remedy digestive disorders and abdominal pain, as well as headache, constipation and high blood pressure.

In Brazil, folklore has it that bitter orange can help relieve insomnia and anxiety. Similarly, traditional applications in Europe noted its usefulness for stomach disorders, as a sedative and to treat “nervous problems” and sore throat. In China and certain Amazon regions, the list of maladies bitter orange is said to be used for includes nasal congestion and bladder problems.

Hordenine — An Adrenergic in Bitter Orange That Releases Epinephrine

One of the most powerful compound bitter orange contains is hordenine, aka N, N-dimethyltyramine, which is an alkaloid found in only a few plants such as barley and bitter orange. The function it serves is adrenergic, which means it causes nerve cells to release the neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline).

Both are cited for increasing focus as well as the “fight or flight” response. Hordenine increases response to noradrenaline, and increased energy and focus was reported in one animal study following exposure.4 Self Hacked notes that in another study of hordenine:5

“The hordenine did not produce any bodily changes by itself. This means that it does not increase alertness directly, but in an indirect manner by keeping noradrenaline from being removed.”

In addition, hordenine was found to decrease melanin production by 30%, which is helpful for people with an overproduction of skin pigment, which can cause freckles, age spots and other evidences of hyperpigmentation.6 This compound gained a name for itself years ago when dodgy managers in the horse racing world gave food containing hordenine to racehorses to increase their performance.

Because the energy effects are considered short lived and high doses were necessary to induce the desired response, many countries believed any increases in performance were improbable7 and did not consider the practice “cheating.” However, after testing, Canada banned hordenine for horses.

Although, it increased short-term alertness within two minutes, side effects including profuse sweating and immediate defecation were reported when it was injected straight into their bloodstream.8

Bitter Orange May Aid Weight Loss, but Be Wary of Bitter Orange Supplements for This Purpose

Bitter orange is perhaps most widely known as an ephedra-like substance to “rev up” your metabolism, which is why it’s often used in weight loss supplements, sometimes in combination with caffeine. It contains the alkaloid synephrine, which is chemically similar to ephedrine, and is a banned substance by the National Collegiate Athletic Association (NCAA).9

Research has shown modest increases in weight loss when bitter orange extract or synephrine-containing products were taken for six to 12 weeks,10 without any significant adverse events reported, but be wary of weight loss supplements that contain it.

In high amounts, or when combined with other stimulants like caffeine, bitter orange or its stimulatory alkaloids could lead to side effects such as fainting, heart attack or stroke.

Some experts believe such supplements may cause problems similar to the ephedra-containing supplements that were banned in 2004,11,12 while others have suggested bitter orange to be different, or milder, than ephedra, with side effects blamed on combining it with caffeine or certain medications.13

Be aware also that the hordenine in bitter orange can cause false positives in opioid drug testing, including tests for morphine, oxymorphone, hydromorphone and apomorphine. Most cases of false positives in drug testing due to elevated hordenine are due to people drinking beer made with barley, however.14 There are also several other potential side effects of hordenine ingestion you should be aware of, as listed by Self Hacked.15 These include:

  • Hordenine may reduce how other neurotransmitters break down. An example is monoamine oxidase-B, which essentially inactivates it, as well as other neurotransmitters such as dopamine and phenylethylamine. While focusing its “attention” on breaking down hordenine, other neurotransmitters like dopamine may become elevated, possibly increasing reactivity to stress.16
  • It may make your blood pressure reading fluctuate, which, in testing on cats, first caused a decrease, then a huge spike, followed by similar fluctuations.17
  • It may cause convulsions. The above study also notes that as a cholinesterase inhibitor, hordenine keeps the enzyme cholinesterase from breaking down acetylcholine, which carries signals from your nerve cells to cause things like movement. “By blocking cholinesterase from breaking down acetylcholine, your body would naturally not stop moving and may keep convulsing.”18
  • Hordenine may lower your protection against UV radiation. Melanin protects your skin by both absorbing free radicals and protecting your skin from excessive exposure to UV rays, but due to hordenine’s ability to reduce production of melanin, your skin may be more susceptible to damage.19
  • Continuously ingesting large quantities of foods containing hordenine could cause kidney damage, including tubular hydropic degeneration, in which kidney cells overfill with water. In an animal study, a disease called glycosuria, in which glucose is released from the kidneys to the urine, occurred in 62% of voles fed high doses of hordenine-containing foods.20

Bitter Orange Uses and Precautions

Bitter orange is used in foods such as syrup, marmalade, spicy fruit chutneys and candied fruits, especially since the high pectin content creates a gel-like consistency. It’s also used in cosmetics and for aromatherapy, especially for energy boosting, anxiety relief, digestion and skin health. The essential oil known as bitter orange comes from the peel of the fruit (oil from the flowers of the tree is known as neroli oil) and has a long history of Ayurvedic use.

Modern research has also found the oil is an effective antifungal agent when applied topically and even that bitter orange may have anticancer properties.21,22

A study published in the Journal of Pharmacology found that drinking 8 ounces of bitter orange juice twice over an eight-hour period appeared to be safe in people with normal blood pressure, but advised anyone with heart rhythm abnormalities, uncontrolled high blood pressure, narrow-angle glaucoma and those who take decongestants or MAO inhibitors as an antidepressant to avoid the juice.23

Further, be careful of supplements containing high levels of bitter orange, hordenine or synephrine, especially if you have heart problems or high blood pressure, and avoid taking them with caffeinated beverages or MAO inhibitors for depression.24 In addition, bitter orange inhibits an enzyme in the small intestine that can affect the amount in your blood, which can influence how certain medications work.

This includes antidepressants, ulcer, HIV, antinausea and fungal medications, antianxiety drugs, statins, some calcium channel blockers, weight loss supplements and antiviral drugs.25 Herbal Supplement Resource notes that large amounts of bitter orange peel can cause colic, convulsions and even death in children,26 so it should be avoided in children and pregnant or breastfeeding women.

In conclusion, bitter orange and bitter orange essential oil have valuable medicinal properties, but must be used with caution and, ideally, with the guidance of a knowledgeable natural health care practitioner who can help with proper dosage and administration. Weight loss supplements containing bitter orange or related components are risky and better off avoided.



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