Bitter Orange Essential Oil

Bitter Orange Essential Oil is used in natural skin care products for its antiseptic and anti-inflammatory properties. Scientifically known as Citrus aurantium, bitter orange is an evergreen tree indigenous to the tropical parts of Asia and Africa.

Almost all the parts of this tree are used in extracting essential oils due its healing values. Essential oil extracted from the leaves and twigs of this tree is known as Petitgrain oil, the oil distilled from the flowers of this tree is the celebrated Neroli oil and the oil extracted from the peel of the bitter orange fruit is called as Bitter orange essential oil.

Unlike the sweet oranges, bitter oranges are not much favored mainly for its tart, astringent and acidic taste. Since the ancient times, bitter oranges and the essential oil cold pressed from the rind of these fruits have carried away the world of medicine with its enormous medicinal values. Known as Narange in Sanskrit, bitter orange is used in Ayurveda in the treatment of gout, gastrointestinal problems, lack of appetite, anxiety and digestive disorders.

Historical importance of Bitter Orange: The Traditional Chinese Medicine used bitter oranges as a natural carminative and tonic for treating dyspepsia. They also used dried bitter oranges in the treatment of diarrhea, ptosis of the anus and uterus, blood in feces and abdominal distention. The rind of bitter orange fruits were used in Homeopathy for relieving abdominal pain, headache, constipation, digestive disorders, weight loss and high blood pressure. Due to the presence of the active ingredient synephrine, bitter oranges are used in herbal medicinal system as an appetite suppressant and as a stimulant.

The Brazilian folklore medicine used bitter orange and its oil in treating insomnia and anxiety. The ancient Europeans used it as a prophylactic and as a sedative for curing nervous problems, gastrointestinal disorders, insomnia, sore throat and gout. This medicinal herb has been in use in various cultures across the globe in the treatment of cancer, anaphylactic shock, cardiac exhaustion, heartburn, fungal infections and certain other heart problems.

The native Latin Americans used it in the preparation of a tonic for treating insomnia, lessening anxiety and also as a laxative. It is also used in the United States as an effective aid in preventing colon, breast and skin cancer. In addition, bitter orange essential oil is used in flavoring baked goods, alcoholic beverages, gelatins, candies, puddings, meat products, frozen desserts and certain other condiments. It is also used as a marinade for meat in the Haitian, Cuban, Nicaraguan and Dominican cooking.

Therapeutic properties and constituents of Bitter orange essential oil: The remedial properties of this oil are antiseptic, carminative, sedative, stomachic, digestive, antidepressant, anti-hyper cholesterolemic, tranquilizer, anti-inflammatory, choleretic, antifungal and antibacterial. Synephrine, tyramine metabolites N-methyltyramine, pinene, carotenoids, limonene, cymene, camphene, octopamine, ocimene and few other alkaloids are its major chemical constituents.

Ayurvedic health benefits of Bitter orange essential oil: Ayurveda is the oldest of all the healing methodologies in the world and it still flourishes due to the simplicity it preaches and practices in its remedial rule. According to this ancient science, every individual is a part of nature and his/her poor health and good health depends upon their harmony with nature. Sickness in Ayurveda is a strong symbol that the individual’s system is out of balance with nature and needs immediate assistance with natural remedies like essential oils, herbal medications, yoga, healthy lifestyle and meditation.

Ayurvedic remedies aim at treating the actual root cause of an illness instead of treating the illness alone and suggests an Ayurvedic routine for preventing such illnesses in the future as well. Every human being according to Ayurvedic principle is unique with an individual constitution that comprises of three energy elements known as doshas, namely vata, pitta and kapha. The predominance of any one of these doshas determines the personality and characteristics of an individual and imbalance of any of these doshas leads to diseases.

Ayurvedic treatments vary from individual to individual based upon their dosha predominance and unique constitution. Bitter orange essential oil is said to increase vata and pitta doshas and pacify kapha dosha. The Ayurvedic health benefits of Bitter orange oil are:

Bitter orange essential oil has been proved effective in treating numerous skin problems with its antiseptic, antibacterial and antifungal properties. The rind of this fruit from which its essential oil is extracted contains non-bitter flavonoids, which is known to have considerable venotonic properties. It is for this reason; bitter orange essential oil is used in cosmetics for preventing capillary fragility. Bitter orange extracts are also used in the treatment of cellulites as it has the potent to normalize the affected parts and stimulate the cutaneous tone of the skin.

The effects and unique properties of bitter orange essential oil in the Aromatherapy Workbook by Shirley Price states bitter orange essential oil “help restore an acne skin to normal and is prophylactic against the signs of ageing”. When applied to the affected area after blending 2 drops of bitter orange oil with coconut oil, the antifungal properties of this oil help in treating fungal infections like athlete’s foot and ringworm.

Bitter orange oil also acts as a natural antiseptic and aids in clearing acne, cold sores, wounds, psoriasis, eczema and certain other skin problems due to excessive stagnation of oil. You can add 2 drops of bitter orange oil with refreshing carrier oil like jojoba oil or to your skin care creams and lotions and gently massage onto the affected parts for quicker effects.

For more than thousands of years, bitter orange has been used in the world of Complementary medicine for treating digestive problems like flatulence, dyspepsia, constipation, sluggish digestion, loss of appetite, intestinal gas, nausea and indigestion. Gently massaging your stomach with 2 drops of bitter orange oil blended with sesame oil can help you enhance the entire process of digestion. You can also add 2 drops of this oil to your bath tub to help with digestive disorders.

Weight loss supplements with bitter orange formula are the most popular and the recent use of bitter oranges in the therapeutic world. Numerous researches have proved the effectiveness of bitter orange supplements in treating obesity. “At present, Citrus aurantium may be the best thermogenic substitute for Ephedra” reveals the Georgetown University Medical Center study on ‘Citrus aurantium as a thermogenic, weight-reduction replacement for Ephedra’.

A recent research on ‘The safety of Citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine’ states “The data indicate that based on current knowledge, the use of bitter orange extract and p-synephrine appears to be exceedingly safe with no serious adverse effects being directly attributable to these ingredients”. It also notes that bitter orange extract and its principal protoalkaloidal constituent p-synephrine are extensively used in weight management, weight loss and products promoting sports performance.

A 2006 study on ‘Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity’ by Johns Hopkins University School of Medicine, MD, USA states that there are certain promising evidences that Citrus aurantium containing several compounds including synephrine alkaloids is a safe alternative to Ephedra, which is a weight-loss supplement banned in US for its adverse health effects.

To boost your metabolism and lessen energy absorption, you can massage your body with 2 to 3 drops of bitter orange oil blended with coconut oil or add 3 drops of this oil to your bath tub.

Bitter orange oil has a much similar aroma to that of fresh tangy oranges. Inhaling the energizing and enlivening fragrance of this oil especially during the early hours of the day promises a serene atmosphere and instills complete calmness in your mind. This is why Ayurvedic healing suggests the use of bitter orange oil during your meditation practice. Add 1 drop of bitter orange oil to your diffuser or air freshener and start your deep meditation after which you will feel a never before freshness and increase in your confidence level.

Bitter orange essential oil is also used in treating chronic fatigue syndrome, intestinal ulcers, lowering blood sugar level in diabetic patients, sleep disorders, joint pain, muscular aches, bruises, cold and certain other liver and gall bladder problems. It is also used in making soaps, cleaning products, disinfectants, cosmetics, perfumes, pharmaceuticals, eau de colognes and certain other household cleaners. Bitter orange oil is also used as a commercial flavoring agent in foods and beverages in many countries.

Pure and organic essential oils are highly concentrated liquids so always use it after diluting in suitable carrier oils. Never use essential oils internally. Citrus oils in general have a photo-toxic effect so avoid going out in the sun immediately after using it on your skin. Pregnant women, nursing mothers, children and people suffering from hypertension and glaucoma should avoid using bitter orange oil. Always consult your Ayurvedic practitioner before choosing the right essential oils for your unique individual constitution.

Pharmacological actions for Citrus aurantium include the following: antispasmodic, sedative, tranquilizer, cholagogue, demulcent, eupeptic, tonic, and vascular stimulant; as an anti-inflammatory, antibacterial, and antifungal agent; and for reducing cholesterol;

however, clinical data is limited. Most medical literature focuses on the safety and efficacy of its use in over-the-counter weight-loss supplement formulations. Studies examining this use have used small sample sizes and often focus on combination products.

Because of the potential for additive effects, synephrine use is best avoided in patients with hypertension, tachyarrhythmia, or narrow angle glaucoma.

Pregnancy/Lactation

Avoid use due to lack of clinical data regarding safety and efficacy during pregnancy and lactation.

Bitter orange may inhibit intestinal CYP3A4 and intestinal efflux and may interact with numerous drugs, including anxiolytics, antidepressants, antiviral agents, calcium channel blockers, dextromethorphan, GI prokinetic agents, vasoconstrictors, and weight-loss formulas.

There are numerous case reports of adverse cardiac reactions associated with C. aurantium extract use. Medical literature primarily documents cardiovascular toxicity, especially due to the stimulant amines synephrine, octopamine, and N-methyltyramine, which may cause vasoconstriction as well as increased heart rate and blood pressure.

The Spanish and Portuguese brought bitter oranges to the Americas in the 1500s. In Chinese folk medicine, bitter orange was used as a tonic and carminative to treat dyspepsia. Dried bitter orange was used to treat ptosis of the uterus and anus, to relieve abdominal distention and diarrhea, and for blood in feces

In Europe, bitter orange flowers and oil have been used as a sedative and as a prophylactic for GI complaints, nervous conditions, gout, sore throat, and insomnia. The plant has been used to treat toxic and anaphylactic shock, heart conditions, cardiac exhaustion, and cancer. In Brazilian folk medicine it was used as an anticonvulsant and to treat anxiety and insomnia.

Bitter orange oil is used extensively to flavor many food products, alcoholic and nonalcoholic beverages, frozen dairy desserts, candy, baked goods, gelatins and puddings, meat and meat products, and condiments and relishes.

Its purported uses in the United States include prevention of skin, breast, and colon cancer. In Haiti the plant has been used as an antiseptic and purgative and in Turkey it has been used as a narcotic, sedative, and treatment for scurvy. The plant has been used as a remedy for treatment-resistant fungal skin diseases, and the tincture or extract has been used for treating heartburn.

Powdered extracts of the dried immature fruit or peel are used as an alternative to ephedra in many dietary supplements and herbal weight-loss products. On April 11, 2004, the Food and Drug Administration banned the sale of dietary supplements containing ephedrine alkaloids because of the safety concerns. Many manufacturers of weight-loss supplement formulations now offer ephedra-free products containing bitter orange extract. Because bitter orange extract contains a sympathomimetic, the safety and efficacy of these formulations is monitored closely.

Uses and Pharmacology

There are numerous pharmacological actions recognized for C. aurantium . The leaf and flower have been studied for anticancer activity and as an antispasmodic, sedative, and tranquilizer. The peel has been studied as a cholagogue, demulcent, eupeptic, tonic, and vascular stimulant, as well as an anti-inflammatory, antibacterial, and antifungal agent, and for reducing cholesterol.

The most current literature focuses on the plant’s safety and efficacy in over-the-counter weight-loss supplement formulations. Patients should be aware when taking over-the-counter formulations that synephrine content may vary and that manufacturer dosage guidelines should be followed.

Synephrine alkaloids increase energy expenditure and decrease food intake through activation of alpha- and beta-adrenergic receptors. Synephrine alkaloids may also decrease food intake by reducing gastric motility.

Several studies have demonstrated that synephrine alkaloids reduce food intake and white fat cells in rats, hamsters, and dogs. Synephrine also promotes lipolysis in adipocytes through beta-adrenergic stimulation.

Synephrine content of bitter orange products varies widely. Review manufacturers’ dosage guidelines because of the numerous commercially available synephrine products. There is evidence for effective weight loss at a synephrine dose of 32 mg/day synephrine in treating obesity.

Adverse Reactions

There are numerous case reports of adverse reactions associated with bitter orange.

Cardiovascular system

A 38-year-old man suffered an ischemic stroke after taking a dietary supplement containing synephrine daily for 1 week. The patient had no medical history or atherosclerotic risk factors and took no medications. Other possible causes of ischemic stroke proved to be unremarkable.

A 52-year old woman developed unremitting tachycardia after consuming a daily dose of C. aurantium extract 500 mg (synephrine 30 mg/day). She had been taking thyroxine 50 mcg/day for hypothyroidism for about 10 years.

Another case report documents a 55-year-old woman with an acute-lateral-wall myocardial infarction. The patient was taking a dietary supplement containing C. aurantium 300 mg for weight loss for 1 year. She had numerous risk factors for myocardial infarction.

A 28-year-old man suffered a massive myocardial infarction after abusing synephrine tablets (dose not provided). An overdose of synthetic synephrine in children caused nausea, vomiting, irritation, tachycardia, and a rapid increase in blood pressure.
There is also a case report on variant angina with bitter orange.
Muscular system

A 22-year-old man developed rhabdomyolysis after consuming a synephrine-containing weight-loss formula. While exercising, the patient developed fatigue, dehydration, and myalgias.

Toxicology

Animal studies document the following potential cardiac toxicity: N-methyltyramine increased renal and cerebral resistance in dogs; synephrine induced dose-dependent portal hypotensive effects and ventricular arrhythmias with enlargement of QRS complex in rats. C. aurantium contains the stimulant amines synephrine, octopamine, and N-methyltyramine. These amines may cause vasoconstriction as well as increased heart rate and blood pressure.

Because of the potential for additive effects, synephrine use should be avoided in patients with hypertension, tachyarrhythmia, or narrow-angle glaucoma.

Ephedrine and synephrine are banned by many sports agencies. A single dose of a commercially available synephrine product did not cause a false-positive response in an amphetamine assay.

People Use This For:

Orally, bitter orange peel is used as an appetite stimulant and for dyspepsia. Bitter orange fruit and peel are also used orally for weight loss, increasing lean body mass, body building, improving athletic performance, nasal congestion, allergic rhinitis, chronic fatigue syndrome (CFS). The bitter orange flower and its oil are used orally for gastrointestinal (GI) disturbances, duodenal ulcers, constipation, regulating blood lipid levels, lowering blood sugar in diabetes, hyperlipidemia, blood purification, functional disorders of liver and gallbladder, stimulation of the heart and circulation, frostbite, as a sedative for sleep disorders, for kidney and bladder diseases, general feebleness, anemia, imbalances of mineral metabolism, impurities of the skin, hair loss, as a tonic, antiflatulent, and for cancer. Other uses include prolapsed uterus, prolapsed anus or rectum, diarrhea, and blood in the stools.

Topically, bitter orange peel is used for inflammation of the eyelid, conjunctiva, and retina. It is also used for retinal hemorrhage, exhaustion accompanying colds, headaches, neuralgia, muscular pain, rheumatic discomfort, bruises, phlebitis, and bed sores.
In aromatherapy, the essential oil of bitter orange is used topically and by inhalation as an analgesic.
In foods, bitter orange oil is used as a flavoring agent.
In manufacturing, bitter orange oil is used in pharmaceuticals, cosmetics, and soaps.

Safety:

LIKELY SAFE …when used orally in amounts commonly found in foods. Bitter orange has Generally Recognized as Safe (GRAS) status in the US.

POSSIBLY SAFE …when bitter orange essential oil is used topically or by inhalation as aromatherapy.

POSSIBLY UNSAFE …when used orally for medicinal purposes. Bitter orange juice and extract have been safely used, short-term in healthy adults in small controlled trials. But there is concern that bitter orange can cause potentially severe adverse effects in some patients due to its stimulant effects. There are case reports of ischemic stroke, and cardiotoxicity including tachyarrhythmia, cardiac arrest, syncope, angina, myocardial infarction, ventricular arrhythmia, and death in otherwise healthy patients who have taken bitter orange extract alone or in combination with other stimulants such as caffeine.

CHILDREN: LIKELY SAFE …when used orally in the amounts found in foods. Bitter orange has Generally Recognized as Safe (GRAS) status in the US.

POSSIBLY UNSAFE …when used orally for medicinal purposes. There are case reports of cardiotoxicity including tachyarrhythmia, syncope, and myocardial infarction in otherwise healthy adults who have taken bitter orange extract in combination with other stimulants such as caffeine.

PREGNANCY AND LACTATION: LIKELY SAFE …when used orally in the amounts found in foods. Bitter orange has Generally Recognized as Safe (GRAS) status in the US.

POSSIBLY UNSAFE …when used orally for medicinal purposes. There are case reports of cardiotoxicity including tachyarrhythmia, syncope, and myocardial infarction in otherwise healthy adults who have taken bitter orange extract in combination with other stimulants such as caffeine. The effects of bitter orange on a fetus or in a breast-feeding infant are not known; avoid using.

Effectiveness:

Obesity. There is contradictory evidence about the effects of bitter orange on weight. Some preliminary clinical research suggests that a combination of bitter orange, caffeine, and St. John’s wort might help for weight reduction when used with caloric restriction and exercise. However, other preliminary clinical research suggests that a different specific combination product (Charge, Labrada) containing bitter orange 150 mg, providing 9 mg synephrine, plus caffeine and several other ingredients taken twice daily does not significantly reduce weight; More evidence is needed to rate bitter orange for this use.

The applicable parts of bitter orange are the peel, flower, leaf, and fruit. Bitter orange has numerous active constituents and pharmacological effects; however, the amount of each constituent can vary depending on the plant part and preparation method used.
The flavonoid content is higher in the flowers than the leaves. The flavonoids are also present in the peel. These flavonoids include limonene, hesperidin, neohesperidin, naringin, and tangaretin.

The fruit and peel of bitter orange contain the adrenergic agonists synephrine and octopamine. Synephrine is structurally similar to epinephrine. Octopamine is similar to norepinephrine.

There are at least 6 isomers of synephrine. Different isomers of synephrine can have somewhat different pharmacological effects. It is unclear which isomer or isomers are contained in bitter orange. Some references suggest that bitter orange contains only p-synephrine. Other references suggest that it contains only m-synephrine, which is also known as phenylephrine. Phenylephrine (m-synephrine) is the alpha-adrenergic agent used as an over-the-counter nasal decongestant (Neosynephrine). Some bitter orange product labels indicate that the product contains both p-synephrine and m-synephrine. In laboratory analysis, both of these isomers have been detected in at least one commercial bitter orange product. But it is unknown if this commercial bitter orange product may be spiked with one or more synthetic synephrine isomers. More research is needed to determine which isomer(s) of synephrine occur naturally in bitter orange extracts in order to better understand the pharmacological effects of bitter orange products.

Synephrine and octopamine naturally occur in the human body. Trace amounts are part of the pool of circulating amines in humans.

In the body tyramine is converted to octopamine, which then gets converted to synephrine. Like tyramine, octopamine and synephrine are substrates of monoamine oxidase.

The exact physiological function of octopamine and synephrine is unclear. They were once referred to as “false neurotransmitters,” but it is now thought that they might act as true neurotransmitters.

Octopamine and synephrine might have a role in fat cell lipolysis. Octopamine seems to have an insulin-like effect on glucose uptake by fat cells. Preliminary research suggests that migraine and cluster headaches might be related to excess levels of synephrine and octopamine.

Bitter orange peel seems to have beta-1 adrenergic activity. Both synephrine and octopamine are selective beta-3 adrenoreceptor agonists. Synephrine also appears to be an alpha-1 agonist. Octopamine appears to also affect alpha-2 receptors.
Fresh bitter orange fruit contains approximately 0.02% synephrine. The concentration tends to be smaller in larger fruits, and higher in smaller fruits. In freshly squeezed bitter orange juice, the synephrine concentration is 57 mcg/mL. Drying the fruit seems to increase synephrine concentrations to approximately 0.35%. Dried extracts contain approximately 3% synephrine. Octopamine levels are much lower, usually less than 0.03 percent. Since octopamine concentration is so low, it’s not known if its effects in humans is significant.

Commercially available bitter orange extracts usually contain 1% to 6% synephrine. But some manufacturers boost synephrine content to as much as 30%. These preparations are often promoted for weight loss due to purported thermogenic effects (4800). In animal models, synephrine causes weight loss, but also increases cardiovascular toxicity.
Studies evaluating the effect of bitter orange on cardiovascular parameters have been mixed. Some clinical research suggests that bitter orange, in combination with caffeine, can increase systolic and diastolic blood pressure and heart rate in otherwise healthy normotensive adults.

Taking a single dose of bitter orange 900 mg, standardized to 6% synephrine (54 mg), seems to increase diastolic and systolic blood pressure and heart rate for up to 5 hours in young, healthy adults. But using half that dose of bitter orange and providing half as much synephrine, does not seem to significantly effect blood pressure or QT interval in healthy adults. A manufacturer-sponsored study found no significant changes in blood pressure, heart rate, or electrocardiogram measurements in normotensive patients after 6 weeks of use; however, frequent hemodynamic monitoring was not performed.

Synephrine given intravenously in men increases systolic blood pressure, but does not seem to increase diastolic blood pressure or heart rate. Animal models suggest that bitter orange can cause vasoconstriction and increase mean arterial pressure (MAP), but reduce portal pressure.

Bitter orange plus a synthetic preparation of the active components synephrine and N-methyltyramine have been used successfully to treat infectious shock in preliminary research. N-methyltyramine seems to increase blood pressure by increasing norepinephrine release.

Preliminary research suggests that synephrine might have antidepressant effects, possibly by promoting norepinephrine release. Bitter orange peel is also commonly used for dyspepsia due to its spasmolytic effects. Bitter orange peel might also have anti-inflammatory activity, which might be due to the flavonoids naringin and nobiletin.
Bitter orange preparations have a variety of antimicrobial properties. The oil of the bitter orange peel seems to have insecticidal activity.

Two flavonoids of the bitter orange fruit, neohesperidin and hesperidin, also seem to have antiviral activity against rotavirus infection. Preliminary research indicates that bitter orange constituents auraptene, marmin, tangeretin, nobiretin, and a psoralen compound, might have antitumor effects.

Although bitter orange is often included in muscle development products, preliminary research suggests bitter orange does not affect muscle precursor cells called satellite cells, which are thought to cause muscular hypertrophy.

Bitter orange also contains furocoumarins. The furocoumarins bergapten and oxypeucedanin in bitter orange oil are photosensitizing. The furocoumarins bergamottin, dihydroxybergamottin, and bergapten in the fruit and juice can inhibit the cytochrome P450 3A4 (CYP3A4) isoenzyme. Bitter orange appears to selectively inhibit intestinal CYP3A4, but not hepatic CYP3A4. These are the same constituents found in grapefruit that are responsible for numerous drug interactions. However, grapefruit juice contains a significantly higher concentration of these constituents than bitter orange juice. Research on the effects of bitter orange on P-glycoprotein is conflicting. Dihydroxybergamottin appears to inhibit CYP3A4, but not P-glycoprotein.

Orally, bitter orange, which contains the adrenergic agents synephrine and octopamine, might theoretically cause hypertension and cardiovascular toxicity.
Synephrine is similar to phenylephrine and the ephedrine contained in the herb ephedra. Theoretically, synephrine might cause similar side effects such as myocardial infarction (MI), stroke, seizure, and other serious side effects.

Studies evaluating the effect of bitter orange on cardiovascular parameters have been mixed. Some clinical research suggests that bitter orange in combination with caffeine can increase systolic and diastolic blood pressure and heart rate in otherwise healthy normotensive adults. Taking a single dose of bitter orange 900 mg, standardized to 6% synephrine (54 mg), seems to increase diastolic and systolic blood pressure and heart rate for up to 5 hours in young, healthy adults. But using half that dose of bitter orange and providing half as much synephrine, does not seem to significantly effect blood pressure or QT interval in healthy adults. A manufacturer-sponsored study found no significant changes in blood pressure, heart rate, or electrocardiogram measurements in normotensive patients after 6 weeks of use; however, frequent hemodynamic monitoring was not performed.

Case reports suggest that bitter orange might have significant adverse cardiovascular effects in some patients. From 1998 to 2004, Health Canada has received 16 reports of serious adverse cardiovascular reactions such as tachycardia, cardiac arrest, ventricular fibrillation, blackout, and collapse. In two of these cases, the patient died. In almost all of these cases, bitter orange was combined with another stimulant such as caffeine or ephedrine, or both.

There are also several published cases of adverse cardiovascular reactions. Myocardial infarction occurred in a patient without a history of cardiovascular disease who took supplements containing bitter orange 300 mg for a year. The supplement also contained guarana and green tea, both of which are sources of caffeine.

In another case, a woman experienced unremitting tachycardia after taking a bitter orange extract 500 mg containing 6% synephrine (30 mg). The patient discontinued bitter orange extract for one month and then took it again. Upon this re-challenge, the patient experienced another episode of unremitting tachycardia. Tachycardia resolved when the bitter orange was discontinued.

There is also a case report of syncope, tachyarrhythmia, and QT prolongation in a young, healthy woman who took a specific combination product containing bitter orange (Xenadrine EFX) just prior to exercising. This product also contained other stimulants including caffeine, theobromine, phenylethylamine, tyramine, and others. The tachyarrhythmia and QT interval normalized within 24 hours of discontinuing the product.

The bitter orange tree is small and produces an extremely sour and bitter citrus fruit. It’s generally not considered an edible fruit, but it is eaten in Iran and Mexico. Due to the fruit’s acidity it is popular for making marmalades and liquors such as triple sec, grand marnier, cointreau, and curacao. The dried peel of the fruit is also used as a seasoning.
In Asian medicine, the entire dried unripe fruit is used primarily for digestive disorders. In Western countries the dried peel of the fruit has historically been used to stimulate appetite. This is in surprising contrast to bitter orange’s primary use today, as a component of weight loss products. Bitter orange (synephrine) is considered a banned substance by the National Collegiate Athletic Association (NCAA).

Bitter orange is frequently used in “ephedra-free” products since the FDA banned ephedra in 2004 for serious adverse cardiovascular effects. Bitter orange and caffeine, a frequent combination in weight loss and bodybuilding products, can cause hypertension and increased heart rate in otherwise healthy normotensive adults. There is no evidence to suggest that bitter orange is any safer than ephedra.

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