Grapefruit juice
Encyclopedia
Grapefruit juice is the fruit juice from grapefruit
s. It is rich in Vitamin C
and ranges from sweet-tart to very sour. It is considered by some cultures to be a mystical tonic which promotes health and vigor. Certain civilizations have had holy men who live on Grapefruit juice alone. Variations include white grapefruit, pink grapefruit and ruby red grapefruit juice.
enzyme, which can impact the metabolism of a variety of drugs, increasing their bioavailability
. In some cases, this can lead to a fatal interaction with drugs like astemizole
or terfenadine
. The effect of grapefruit juice with regard to drug absorption was originally discovered in 1989. However, the effect became well-publicized after being responsible for a number of deaths due to overdosing on medication. However, the first published report on grapefruit drug interactions was in 1991 in the Lancet entitled "Interactions of Citrus Juices with Felodipine and Nifedipine." and was the first reported food-drug interaction clinically.
Recently some researchers have shown that furanocoumarin
s rather than flavonoid
s are the ingredients causing the various drug interactions.
Drugs that may be affected include oxycodone
, diazepam
, alprazolam
, lorazepam
, midazolam
, carbamazepine
(Tegretol), ciclosporin
, lovastatin
, methadone
, dextromethorphan
, simvastatin
, pravastatin
, felodipine
, ketamine
, sildenafil
(Viagra), and caffeine
, as well as a number of antihistamine
s including astemizole and terfenadine.
Grapefruit juice has also been reported to increase both the bioavailability of some benzodiazepine
s, (such as diazepam) and greatly slow the rate of metabolisation.
An easy way to tell if a medication may be affected by grapefruit juice is by researching whether another known CYP3A4 inhibitor drug is already contraindicated with the active drug of the medication in question. Examples of such known CYP3A4 inhibitor
s include cisapride
(Propulsid), erythromycin
, itraconazole
(Sporanox), ketoconazole
(Nizoral), and mibefradil
(Posicor).
The flavonoid existing in highest concentration in grapefruit juice is naringin
, which in humans is metabolised to naringenin
. Other flavonoids exist in grapefruit juice in lower concentrations as well. Orange juice
does not contain naringin in as high a concentration, instead containing hesperetin
. It is sometimes recommended as a substitute. Juice of lime
s and Seville oranges can also inhibit drug metabolism, however, as can apple
juice with some drugs.
reported that eating grapefruit every day could raise the risk of developing breast cancer by almost a third. The study found that in the test subjects, 50,000 post-menopausal women, eating just a quarter of a grapefruit daily raised the risk by up to 30%. It is believed that the fruit boosts the levels of estrogen, which in turn increases the risk of developing the disease. However, a 2008 study has shown that grapefruit consumption does not increase breast cancer risk and has found a significant decrease in breast cancer risk with greater intake of grapefruit in women who never used hormone therapy
.
Grapefruit
The grapefruit , is a subtropical citrus tree known for its sour fruit, an 18th-century hybrid first bred in Barbados. When found, it was named the "forbidden fruit"; it has also been misidentified with the pomelo or shaddock , one of the parents of this hybrid, the other being sweet orange The...
s. It is rich in Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
and ranges from sweet-tart to very sour. It is considered by some cultures to be a mystical tonic which promotes health and vigor. Certain civilizations have had holy men who live on Grapefruit juice alone. Variations include white grapefruit, pink grapefruit and ruby red grapefruit juice.
Drug interactions
Grapefruit juice, and grapefruit in general, is a potent inhibitor of the cytochrome P450 CYP3A4CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
enzyme, which can impact the metabolism of a variety of drugs, increasing their bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
. In some cases, this can lead to a fatal interaction with drugs like astemizole
Astemizole
Astemizole was a second generation antihistamine drug which has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977...
or terfenadine
Terfenadine
Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel and marketed under various brand names including Seldane in the United States, Triludan in the United Kingdom, and Teldane in Australia...
. The effect of grapefruit juice with regard to drug absorption was originally discovered in 1989. However, the effect became well-publicized after being responsible for a number of deaths due to overdosing on medication. However, the first published report on grapefruit drug interactions was in 1991 in the Lancet entitled "Interactions of Citrus Juices with Felodipine and Nifedipine." and was the first reported food-drug interaction clinically.
Recently some researchers have shown that furanocoumarin
Furanocoumarin
Furanocoumarins, or furocoumarins, are a class of organic chemical compounds produced by a variety of plants. They are biosynthesized partly through the phenylpropanoid pathway and the mevalonate pathway, which is biosynthesized by a coupling of dimethylallyl pyrophosphate and 7-hydroxycoumarin...
s rather than flavonoid
Flavonoid
Flavonoids , are a class of plant secondary metabolites....
s are the ingredients causing the various drug interactions.
Drugs that may be affected include oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
, alprazolam
Alprazolam
Alprazolam is a short-acting anxiolytic of the benzodiazepine class of psychoactive drugs. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor...
, lorazepam
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
, midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...
, carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
(Tegretol), ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
, lovastatin
Lovastatin
Lovastatin is a member of the drug class of statins, used for lowering cholesterol in those with hypercholesterolemia and so preventing cardiovascular disease...
, methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
, dextromethorphan
Dextromethorphan
Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
, simvastatin
Simvastatin
Simvastatin is a hypolipidemic drug used to control elevated cholesterol, or hypercholesterolemia. Simvastatin is a member of the statin class of pharmaceuticals, is a synthetic derivate of a fermentation product of Aspergillus terreus.-Medical uses:The primary uses of simvastatin is for the...
, pravastatin
Pravastatin
Pravastatin is a member of the drug class of statins, used for lowering cholesterol and preventing cardiovascular disease. Initially known as CS-514, it was originally identified in a bacterium called Nocardia autotrophica by researchers of the Sankyo Pharma Inc....
, felodipine
Felodipine
Felodipine is a calcium channel blocker , a drug used to control hypertension . It is marketed under the brand name Plendil by AstraZeneca and Renedil by Sanofi-Aventis...
, ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
, sildenafil
Sildenafil
Sildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...
(Viagra), and caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, as well as a number of antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
s including astemizole and terfenadine.
Grapefruit juice has also been reported to increase both the bioavailability of some benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s, (such as diazepam) and greatly slow the rate of metabolisation.
An easy way to tell if a medication may be affected by grapefruit juice is by researching whether another known CYP3A4 inhibitor drug is already contraindicated with the active drug of the medication in question. Examples of such known CYP3A4 inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
s include cisapride
Cisapride
Cisapride is a gastroprokinetic agent, a drug which increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous...
(Propulsid), erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
, itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
(Sporanox), ketoconazole
Ketoconazole
Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
(Nizoral), and mibefradil
Mibefradil
Mibefradil is a drug for the treatment of hypertension and chronic angina pectoris. It belongs to a group known as calcium channel blockers.It is nonselective....
(Posicor).
The flavonoid existing in highest concentration in grapefruit juice is naringin
Naringin
Naringin is a flavanone glycoside. It is a major flavonoid in grapefruit and gives the grapefruit juice its bitter taste. It is metabolized to the flavanone naringenin in humans...
, which in humans is metabolised to naringenin
Naringenin
Naringenin is a flavanone, a type of flavonoid, that is considered to have a bioactive effect on human health as antioxidant, free radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, and immune system modulator. It is the predominant flavanone in grapefruit.-Biological...
. Other flavonoids exist in grapefruit juice in lower concentrations as well. Orange juice
Orange juice
Orange juice is a popular beverage made from oranges. It is made by extraction from the fresh fruit, by desiccation and subsequent reconstitution of dried juice, or by concentration of the juice and the subsequent addition of water to the concentrate...
does not contain naringin in as high a concentration, instead containing hesperetin
Hesperetin
Hesperetin is a bioflavonoid and, to be more specific, a flavanone. Hesperidin is water-soluble due to the presence of the sugar part in its structure, so on ingestion it releases its aglycone, i.e, hesperetin....
. It is sometimes recommended as a substitute. Juice of lime
Lime (fruit)
Lime is a term referring to a number of different citrus fruits, both species and hybrids, which are typically round, green to yellow in color, 3–6 cm in diameter, and containing sour and acidic pulp. Limes are a good source of vitamin C. Limes are often used to accent the flavors of foods and...
s and Seville oranges can also inhibit drug metabolism, however, as can apple
Apple
The apple is the pomaceous fruit of the apple tree, species Malus domestica in the rose family . It is one of the most widely cultivated tree fruits, and the most widely known of the many members of genus Malus that are used by humans. Apple grow on small, deciduous trees that blossom in the spring...
juice with some drugs.
Breast cancer link
A study published in the July 2007 edition of the British Journal of CancerBritish Journal of Cancer
The British Journal of Cancer a twice-monthly professional medical journal of Cancer Research UK , published on their behalf by the Nature Publishing Group ....
reported that eating grapefruit every day could raise the risk of developing breast cancer by almost a third. The study found that in the test subjects, 50,000 post-menopausal women, eating just a quarter of a grapefruit daily raised the risk by up to 30%. It is believed that the fruit boosts the levels of estrogen, which in turn increases the risk of developing the disease. However, a 2008 study has shown that grapefruit consumption does not increase breast cancer risk and has found a significant decrease in breast cancer risk with greater intake of grapefruit in women who never used hormone therapy
Hormone therapy
Hormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...
.