Bitter-Orange

BITTER ORANGE

Common Name: Bitter Orange

Scientific Name: Citrus × aurantium L.

History and Origin

Bitter orange is native to South Africa and the tropical regions of Asia. Today this tree grows across the Mediterranean region and some parts of the United States; orchards of bitter orange are found along the Mediterranean coast, particularly in Spain.

Arabs introduced bitter orange for the first time in the Mediterranean region in the early ninth century A.D.

Around the 17th century, the Italians, the Spaniards, and the French used this plant extensively. The application of this plant dates back to ancient times. Ancient Greeks used it for disinfection in Aromatherapy (smell therapy) and herbal therapy. This plant grew in Sicily (Sicilia) in the 11th century. In the late 12th century, bitter orange entered Spain, and during the Renaissance period, they dedicated some fields to its growth.

Bitter Orange Plant Structure

Bitter orange, also called Seville orange, marmalade orange, bigarade orange, and sour orange, refers to a citrus tree (Citrus × aurantium) and its fruit. It belongs to the order Geraniales and the Rutaceae family.

A tree or rarely a shrub that its young shoots are glabrous and greenish-white:

The leaflets are 7.5 – 15 cm, long, elliptic or ovate, obtuse, acute or acuminate. The petioles are naked or winged; the wings are often obovate and nearly as large as the blade.

The flowers are bisexual and pure white, with 20-30 stamens.

The fruit is globose, generally oblate, not mammillate, usually orange-colored, rind loose or adherent; the pulp is sweet, yellow, and rarely red. (1)

              The photo of Citrus × aurantium L.                                                                                                                The photo of bitter orange blossom

Bitter Orange Health Benefits

1. Regulating Irregular Heartbeat

In a research, the effect of different densities of this plant extract was studied on the Electrophysiological properties of the atrioventricular node with the help of the atrioventricular node model and the protecting role of bitter orange extract in arrhythmia (irregular heartbeat) in rabbits. (After passing through the corridors and reaching the ventricles, the electrical current in the heart must pass through a structure called an atrioventricular node).

They examined three groups of rabbits (6 rabbits in each group and 18 rabbits in total). The results showed a significant meaningful effect of different densities of the plant extract on increasing electrophysiological parameters of plant base (foundation, ventricular-corridor conduction time, functional in irritability time). As corridor-node conduction time showed a significant meaningful increase in 0.3 ML concentration from 32.6±3.6 millisecond (ms) to 40±6.08 ms and in the time of FRP (Functional refractory period) from 147.5±5.1 ms to 166.6±3.6 ms.

As a result, the research has suggested that bitter orange might help to regulate heartbeat.  (2)

2. Calming Anxiety and Stress

In a study, consuming 1g/kg of the bitter orange extract was compared to 10 mg/kg of chlordiazepoxide, 400 mg/kg of valproic acid or 1.2 mg/kg diazepam. The results showed that consuming this extract has a significant relaxing effect and decreases anxiety. (2)

In a clinical study, the bitter orange effect on stress was investigated in nulliparous women. The results of this experiment showed that smell therapy with bitter orange reduces the anxiety of childbirth. The oily extracts improve the mood and reduce the level of anxiety during childbirth by stimulating the routes in the limbic system of the brain. These extracts are absorbed through respiration; they can affect enzymes, ion channels and receptors and can lead to brain stimulation, anxiety relief, and cerebral blood flow increase. In addition, they have anti-depressant effects. These oily extracts can pass from the blood-brain barrier through breathing and interact with receptors in the central nervous system.

The research on mice showed that para-synephrine might have antidepressant activity.  (2)

Akhlaghi et al compared the effects of bitter orange to the effects of Diazepam in reducing anxiety before surgery. In this study, they selected 60 patients referring for surgery, aged 14 to 48 years, and randomly divided them into two groups of thirty people. Two hours before surgery, they gave 100 cc bitter orange to group 1, and oral solution of a 5 mg Diazepam pill in 100 cc water to group 2; and measured their anxiety and vital signs before medication and two hours after medication. The results showed that the amount of anxiety reduced in both groups; they both experienced lower levels of stress after taking the drug. As a result, bitter orange can be an effective premedication for reducing the patients’ anxiety before surgery.

3. Regulating Blood Pressure

In a research published in Evidence-Based Complementary and Alternative Medicine journal, the effects of inhalation of bitter orange essential oil on high blood pressure and salivary cortisol levels were investigated in 83 people with high blood pressure for 24 hours.

Based on this study, inhalation of neroli essential oil significantly reduces systolic and diastolic blood pressure, and the density of salivary cortisol (cortisol hormone secrets in response to stress). This study showed that smelling bitter orange essential oil has positive effects on blood pressure and decreasing stress. (3)

4. Anti-Microbial

According to researches, the bitter orange extract has anti-microbial and anti-oxidant properties. A research published in Pakistan Journal of Biological Sciences suggests that bitter orange has anti-microbial properties against all bacteria tested (especially pseudomonas aeruginosa bacteria, except for Staphylococcus aureus), two types of yeast, and three types of fungus tested. The strong antifungal activity of this plant is equal to antibiotics such as Nystatin. (4)

What Are Bitter Orange Side Effects?

No health hazards or side effects have been known in conjunction with the proper administration of designated therapeutic dosages but to be on the safe side, note the following:  (5)

1. Pregnancy and Breast-Feeding

Bitter orange is Likely SAFE during pregnancy when used in reasonable amounts found in food. However, it is POSSIBLY UNSAFE and NOT RECOMMENDED when taken orally in medicinal amounts. The effects of bitter orange on breast-feeding infants are not known.

Thus, stay on the safe side and do NOT use bitter orange during pregnancy or breast-feeding.

2. Diabetes

Some evidence shows that bitter orange may interfere with blood sugar control in patients with type 2 diabetes.

Diabetic patients should use it with caution and monitor their blood sugar levels closely.

3. High Blood Pressure

Some studies suggest that bitter orange can increase blood pressure in healthy people, especially when taken with caffeine. However, other studies have found no such blood pressure elevation. Furthermore, to date, there have not been any studies looking at the effect of taking bitter orange orally in people with high blood pressure.

If you have high blood pressure, avoid using bitter orange, especially in combination with stimulants such as caffeine.

4. Glaucoma

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

5. Heart Disease

Consumption of bitter orange, especially in combination with caffeine or other stimulants, might increase the risk of serious side effects in people with long QT syndrome, a particular heart disorder.

6. Irregular Heartbeat (Heart Arrhythmia)

Although, some studies suggest that bitter orange, especially when taken with caffeine, may increase heart rate in healthy people. However, other studies have found no evidence of such an effect on heart rate. Furthermore, there have been no studies shown any effects of bitter orange on people who have an irregular heartbeat.

Avoid using bitter orange, if you have an irregular heartbeat, especially in combination with stimulants such as caffeine.

7. Surgery

Bitter orange acts like a stimulant. Thus, it may interfere with surgery by increasing heart rate and blood pressure. Stop the consumption of bitter orange at least 2 weeks prior to a scheduled surgery. (6)

Nutritional Information

Food value per 100 g of the edible portion of bitter orange is moisture, protein, fat, carbohydrates, fiber, ash, calcium, iron, phosphorus, vitamin A, thiamine, riboflavin, niacin, ascorbic acid. (7)

Bitter Orange Daily Dosage

Follow the manufacturer’s dosage guidelines because synephrine content may vary in supplement formulations. (2)

Bioactive Compounds

Bitter orange contains monoterpenes, flavonoid, synephrine, adenosine, asparagine, tyrosine, valine, ‎isoleucine, alanine, and beta-sitosterol.

The dried flower contains Steroid- Desmosterol, Ergosterol, β-Sitosterol, Stigmasterol, and ‘O’ Saponins (unspecified type or hemolytic absent).

Alkaloid caffeine was reported in the extract of dried flower.

Flower essential oil contains Monoterpene- b-limonene, Linalool, Linalool acetate.

Best Time to Consume

2 hours before or after meals.

Possible Drug Interactions

1. Medications for Depression (MAOIs)

Bitter orange contains chemicals that stimulate the body. Some anti-depression drugs, including phenelzine (Nardil) and tranylcypromine (Parnate), taken with bitter orange may increase these chemicals, which might cause serious side effects including fast heartbeat, high blood pressure, nervousness and even result in seizures.

2. Midazolam (Versed)

The body breaks down midazolam (Versed) very quickly in order to get rid of it. However, bitter orange can slow down liver functionality to break down midazolam (Versed). Thus, taking bitter orange along with midazolam (Versed) might increase the effects and side effects of midazolam (Versed).

3. Caffeine (Excedrin, Anacin, Vivarin, and others)

Bitter orange is a stimulant just like Caffeine. When consumed simultaneously, it may result in higher blood pressure as well as an increase of heartbeats, which can lead to some serious adverse side effects such as heart attack and stroke.

4. Dextromethorphan (Robitussin DM, and others)

The body breaks down dextromethorphan (Robitussin DM, others) very quickly in order to get rid of it. However, bitter orange can slowdown liver functionality to break down dextromethorphan (Robitussin DM, others). Thus, taking bitter orange along with dextromethorphan (Robitussin DM, others) might increase the effects and side effects of dextromethorphan (Robitussin DM, others).

5. Felodipine (Plendil)

Felodipine (Plendil) is used to lower blood pressure. The body breaks down felodipine (Plendil) very quickly in order to get rid of it. However, bitter orange can slowdown liver functionality to break down felodipine (Plendil). Thus, taking bitter orange along with felodipine (Plendil) might increase the effects and side effects of felodipine (Plendil).

6. Indinavir (Crixivan)

Indinavir (Crixivan) is used to treat HIV/AIDS. The body breaks down indinavir (Crixivan) very quickly in order to get rid of it. However, bitter orange can slowdown liver functionality to break down indinavir (Crixivan). Thus, taking bitter orange along with indinavir (Crixivan) might increase the effects and side effects of indinavir (Crixivan).

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

Taking bitter orange along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking bitter orange, talk to your healthcare provider if you are taking any medications that are changed by the liver.

Some medications changed by the liver include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra) and triazolam (Halcion).

8. Stimulant drugs

Taking bitter orange along with stimulant drugs might cause serious problems including increased heart rate and high blood pressure.

It is highly recommended NOT to consume stimulant drugs such as diethylpropion (Tenuate), epinephrine, phentermine (Ionamin), and pseudoephedrine (Sudafed) along with bitter orange. (6)

Traditional Use

Bitter orange has a warm nature. Its leaves were traditionally tonic and laxative and were used to cure insomnia and calm nerves in Mexico and South America. People of Euskal Herria (a state in Spain) knew bitter orange as an anti-spasm and used it to cure stomach diseases, palpitations, and headaches. In China, they used this plant to cure stomachache and diarrhea.

Bitter Orange is traditionally relaxing and anti-anxiety. It reduces the tension headache and migraine. It is used to relieve the weakness of the nerves and sleeping problems, reduce menopausal symptoms, regulate blood pressure, improve cold, remove hiccup, constipation and dizziness.

Some Questions about Bitter Orange

Is bitter orange good for weight loss?

Clinical trials have examined the effects of bitter orangeproducts alone or in combination with other ingredients on body weight and body composition.

The anti-obesity effect of bitter orangecontains synephrine, which is a stimulant. Furthermore, bitter orange is believed to increase your basal metabolic rate, which results in weight loss and calorie burn while our body is at rest by stimulating fat breakdown and suppressing appetite.

Does bitter orange suppress appetite?

Bitter orange contains synephrine, a compound that may be effective in reducing appetite.

Is bitter orange dangerous?

Decoctions of bitter orange substantially increase blood levels of cyclosporine, causing toxicity. Bitter orange contains synephrine and octopamine; these chemicals may cause high blood pressure (hypertension) and heart rhythm disturbances (arrhythmias) which can lead to heart attack, stroke, and even death.

For more information on possible side effects of “Bitter Orange”, see the “What Are Bitter Orange Side Effects?” section.

Is bitter orange a stimulant?

Some sources recognize bitter orange as a stimulant. On the other hand, many sources suggest that it is not a stimulant if consumed in appropriate doses.

However, the National Collegiate Athletic Association (NCAA) has stated synephrine (bitter orange) in their list of banned drugs, which acts as a stimulant.

References

1. https://www.researchgate.net/

2- https://www.drugs.com/

3- https://draxe.com/

4- https://scialert.net/abstract/

5- (2000). PDR for herbal medicines. 2nd ed. Montvale, NJ: Medical Economics Company.

6- https://www.webmd.com/

7- https://hort.purdue.edu/

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