Bitter orange

The bitter orange (also known as bitter orange, Citrus aurantium L., bigarade, neroli or bitter orange) is a plant whose peel, blossom, fruit and fruit juice are used to make medicine. The bitter orange tree is similar to the lemon tree, a tree up to 5 m high with evergreen leaves and white, pleasantly fragrant flowers. In folk medicine, the flowers, the peel of the fruit and the unripe fruit are used. The bitter orange tree is native to tropical Asia, but is already cultivated in the Mediterranean region. Bitter orange oil is produced from the peel of the fruit.

What are the uses of bitter orange?

Bitter orange has a wide range of applications when taken orally or applied to the skin. So far, however, science has only shown that the oil, when applied to the skin, may be effective in treating fungal infections such as bark lichen and athlete's foot. The flowers contain essential oil, bitter substances and flavonoids and are said to help as a mild sedative for nervousness and sleep disorders. Other uses of the flowers and oil include digestive tract disorders including intestinal ulcers, constipation, diarrhea, blood in the stool and flatulence. These parts of the bitter orange plant are also used to regulate blood lipid levels, to reduce blood sugar in diabetics, to stimulate the heart and circulation, to "cleanse the blood", for liver and gallbladder disorders, for kidney and bladder disorders and as a sedative for insomnia.

Some people use the blossom and oil of the bitter orange for general weakness, anemia, skin blemishes, hair loss, cancer and frostbite, as well as a tonic. In addition to essential oil, the peel (and therefore also the fruit) contains mainly bitter substances and is used as an appetite stimulant and for digestive disorders such as bloating and flatulence. Other uses of the fruit and peel include weight loss support, nasal congestion and chronic fatigue syndrome. In Asian medicine, the whole dried unripe fruit is primarily used for digestive disorders. In addition, the peel of the bitter orange is applied to the skin to treat inflammatory swelling of the eyelids and the retina of the eye.

It is also used for bleeding in the retina, exhaustion accompanying a cold, headaches, nerve pain, muscle pain, joint pain, bruising, swollen veins and bedsores. In aromatherapy, the essential oil of bitter orange is applied to the skin as a painkiller and is also inhaled. In food, bitter orange oil is used as a flavoring agent. The fruit is used to make marmalade and liqueurs such as Triple Sec, Grand Marnier, Cointreau and Curacao. As the fruit of the bitter orange is so sour and bitter, it is rarely eaten except in Iran and Mexico. The dried peel of the fruit is also used as a spice. In industrial production, bitter orange oil is used in the manufacture of pharmaceuticals, cosmetics and soap. The essential oil is also used in perfume production.

How is bitter orange used in sports and weight loss?

Bitter orange, or the synephrine it contains, is often used in ephedra free supplements to aid weight loss since ephedra and ephedrine are no longer allowed to be sold freely in many countries due to serious side effects affecting the heart. Synephrine is extracted from the fruit of the bitter orange (citrus aurantium). As a rule, extracts added to food supplements contain 6 percent synephrine. According to analyses, synephrine is the active ingredient that is primarily responsible for fat mobilization. Synephrine is chemically closely related to ephedrine. Synephrine is not only found in plants, but also occurs naturally in the human body (which probably explains why they have not yet been banned).

Bitter orange and caffeine, a commonly used combination in bodybuilding and weight loss supplements, can also cause high blood pressure and increase heart rate in healthy adults with otherwise normal blood pressure. There is no evidence that bitter orange is safer than ephedra. Bitter orange, or the synephrine it contains, is considered a banned performance-enhancing substance by some sports organizations such as the National Collegiate Athletic Association (NCAA).

How does bitter orange work?

Bitter orange contains many chemicals that affect the nervous system. The concentrations and effects of these chemicals can vary depending on which parts of the plant are used and which method of processing is chosen. These chemicals can constrict blood vessels, increase blood pressure and cause a faster heartbeat. The synephrine contained in bitter orange increases energy and has a stimulating effect. It is very rich in flavonoids.

Together, these two compounds produce a stimulating and energizing effect in the body. Flavonoids are powerful antioxidants with properties to reduce blood clotting. Scientists believe that their positive effects of counteracting oxygen-induced damage in the body, such as fatty tissue buildup, can help prevent heart problems as well as promote better circulation and overall health by eliminating free radicals in the body.

How is Synephrine different from ephedrine?

Similar to ephedrine, synephrine causes an increase in resting metabolic rate and body temperature. Like ephedrine, synephrine has an alpha-adrenergic effect, but unlike ephedrine it only contacts andrenergic beta-3 receptors. Ephedrine, on the other hand, interacts with beta-1, beta-2 and beta-3 receptors, whereby its interaction with beta-2 receptors is responsible for the majority of its fat-mobilizing effect. Its overlap with beta-1 receptors was to blame for its side effects, such as severe stress on the cardiovascular system. In reality, problems only occurred in users who had taken an overdose of ephedrine or had a medical history, such as cardiovascular disease.

A study by the University of Utah seems to support this conclusion. In a placebo-controlled study, both the ephedrine and synephrine groups showed an equal increase in resting metabolic rate and body temperature. However, only the ephedrine group showed an increase in respiratory rate as a sign of fat burning. It was concluded from the study that synephrine is clearly inferior in its effect. However, it is questionable to what extent the experimental approach can deliver comparable results. Neither substance was administered as the sole thermogenic agent. While both substances contained caffeine, yohimbe and quercetin as additives, two Chinese herbs were added to the synephrine-containing combination. The dosage also differed greatly. While one group received 24 mg of ephedrine, the synephrine group received only 10 mg of the active ingredient. In my opinion, this experimental setup is not capable of providing usable results for a direct comparison of the two substances. Both substances should have been administered at least in the same dosage.

Another frequently mentioned advantage of Synephrine over ephedrine is the absence of palpitations, shakiness and other cardiovascular symptoms that afflicted some ephedrine users. These symptoms were related to the activation of beta-2 receptors by ephedrine, which does not occur with synephrine. Unfortunately, another ephedrine-induced cardiovascular side effect has also been observed in association with synephrine: increased blood pressure (hypertension). Ketecholamines such as ephedrine and norepinephine contribute to a constriction of blood vessels that increases blood pressure. Due to its structural relationship with catecholamines, ephedrine also raises blood pressure slightly, but this is not a problem for most users. Synephrine is also similar in structure to catecholamines, which is why it can also have a blood pressure-raising effect. Synephrine shares a property with grapefruit juice that ephedrine does not: it contains at least two substances that inhibit the cytochrome P450 enzyme system in the liver. This system is responsible for the metabolism of more than 25 percent of all medications, and blocking it would lead to dangerously high concentrations of medications and drugs in the blood. This effect is even more pronounced with synephrine than with grapefruit juice.

What is the scientific evidence on the effects of bitter orange?

Bitter orange may be effective for the treatment of skin infections such as bark lichen and athlete's foot. There is not enough scientific data to evaluate the effectiveness of bitter orange for weight loss. The available data is contradictory. Some studies suggest that a combination of bitter orange, caffeine and St. John's wort in combination with a calorie-restricted diet and exercise could support weight loss. However, another study came to the conclusion that a combination of bitter orange, caffeine and several other ingredients did not help with weight loss.

There is also a lack of scientific information on the effectiveness of bitter orange for nasal congestion, allergies, flatulence, cancer, digestive upset, intestinal ulcers, diabetes, chronic fatigue syndrome, liver and gallbladder problems, swollen eyes, colds, headaches, nerve and muscle pain, bruising and mild sleep problems, as well as for stimulating the heart and circulation, regulating cholesterol levels and stimulating appetite. Further scientific research is needed in all these areas of application in order to evaluate the effectiveness of bitter orange.

Safety and side effects

Bitter orange is probably safe for children and adults when consumed in the amounts found in food. However, bitter orange may not be safe and harmless when used as a supplement for medicinal purposes such as weight loss support. Bitter orange - especially when combined with stimulants such as caffeine - increases the risk of high blood pressure, fainting, heart attack, stroke and other serious side effects. There are reports that bitter orange can trigger headaches, including migraines and cluster headaches, in some people. Bitter orange can also increase the skin's sensitivity to sunlight, so sunscreen should be used when outdoors, especially for fair-skinned people.

Precautions and warnings

Pregnancy and breastfeeding: Bitter orange is probably safe during pregnancy when used in the amounts found in food. However, the use of medicinal dosages may not be safe and harmless. The effects of bitter orange on breastfed infants are not known. For these reasons, pregnant and breastfeeding women should refrain from using bitter orange to be on the safe side.

High blood pressure: Some studies suggest that bitter orange - especially in combination with caffeine - can increase blood pressure in healthy people. Other studies have not observed such increases in blood pressure. To date, no studies have investigated the effect of bitter orange on blood pressure in people who already suffer from high blood pressure. You should therefore not take any risks and avoid bitter orange - especially in combination with caffeine - if you suffer from high blood pressure.

Glaucoma: Bitter orange can aggravate glaucoma, so people who suffer from this condition should not use bitter orange.

Heart disease: Using bitter orange - especially in combination with caffeine or other stimulants - could increase the risk of serious side effects in people who suffer from a heart condition known as "long QT interval syndrome."

Cardiac arrhythmias: Some studies suggest that bitter orange - especially when combined with caffeine - may increase heart rate in healthy people. Other studies have found no such effects on heart rate. To date, no study has investigated the effects of bitter orange in people with cardiac arrhythmias. For this reason, people who suffer from cardiac arrhythmias should not use bitter orange - especially in combination with caffeine.

Operations: Bitter orange acts as a stimulant, which is why it can have undesirable effects such as an increase in heart rate and blood pressure during surgery. For this reason, the use of bitter orange should be discontinued at least two weeks before planned operations.

Interactions

Bitter orange should not be used in combination with the following medications:

Medications for depression (monoamine oxidase inhibitors MAOI).

Bitter orange contains chemicals that stimulate the body. Some medications used for depression can increase the levels of these chemicals. Taking bitter orange with these medications can lead to serious side effects including rapid heartbeat, high blood pressure, seizures, nervousness and more.

Midazolam

The body breaks down midazolam in order to excrete it. Bitter orange can reduce the rate at which the body breaks down midazolam. Taking bitter orange in combination with midazolam could increase the effects and side effects of midazolam.

Care should be taken when combining bitter orange with the following medications:

Caffeine

Bitter orange is a stimulant. Caffeine is also a stimulant. In combination, these two substances can increase blood pressure and speed up the heart rate. This can lead to serious effects such as a heart attack or stroke.

Dextromethorphan

The body breaks down dextromethorphan in order to excrete it. Bitter orange may reduce the rate at which the body breaks down dextromethorphan. Taking bitter orange in combination with dextromethorphan could increase the effects and side effects of dextromethorphan.

Felodipine

Felodipine is used to lower blood pressure. The body breaks down felodipine in order to excrete it. Bitter orange may reduce the rate at which the body excretes felodipine. Taking bitter orange in combination with felodipine could increase the effects and side effects of felodipine.

Indinavir

Indinavir is used to treat HIV/AIDS. The body breaks down indinavir in order to be able to excrete it. Bitter orange may reduce the rate at which the body breaks down indinavir. Taking bitter orange in combination with indinavir could increase the effects and side effects of indinavir.

Drugs that are broken down by the liver (cytochrome P450 3A4 (CYP3A4) substrates)

Some drugs are broken down by the liver. Bitter orange may reduce the rate at which the liver breaks down certain drugs. Taking bitter orange in conjunction with medications that are broken down by the liver may increase the effects and side effects of some medications. For this reason, you should consult your doctor before taking bitter orange if you are taking medication that is broken down by the liver.

Medication that can cause irregular heartbeat (QT interval prolonging medication)

Bitter orange could increase the speed of the heartbeat. Taking bitter orange in combination with medications that can cause an irregular heartbeat could lead to serious side effects including cardiac arrhythmias.

Stimulants

Stimulants accelerate the function of the nervous system. By accelerating the function of the nervous system, stimulants can cause restlessness and speed up the heart rate. Bitter orange can also accelerate the function of the nervous system. Taking bitter orange in combination with stimulants can lead to serious side effects including accelerated heart rate and increased blood pressure. For this reason, bitter orange should not be combined with stimulants.

Dosages

The following dosages have been investigated in scientific studies:

Applied to the skin: For the treatment of fungal infections of the skin: Pure bitter orange oil was applied to the affected areas of skin once a day for 1 to 3 weeks.