Grapefruit is a citrus fruit with a thousand beneficial properties. It is rich in vitamin C, minerals, citric acid and pectins.
Despite all the beneficial properties of grapefruit, not everyone knows however that this fruit can interfere with some drugs, significantly affecting their biological activity through metabolic interactions.
Discovery
This information was made public as early as 1989, when by pure chance, grapefruit juice was used as an add-on to a placebo in a drug test in Canada.
In the placebo group with grapefruit juice, the plasma concentration of felodipine (a vasodilator drug used for hypertension) was unexpectedly high.
Since then, a myriad of research has started to confirm the "drug-grapefruit interaction. It was thus possible to discover that grapefruit interferes with numerous drugs including: statins, anti-rhythmics, immunosuppressive agents and calcium channel blockers (see table ).
There are, however, other classes of drugs that have not shown any toxic effect when taken with grapefruit juice, these drugs can therefore be used as an alternative therapy in those patients who show a high risk of drug interaction with grapefruit. Patients, however, they may choose to exclude grapefruit from their diet and consume other types of fruit, including other citrus fruits, in order to avoid a toxic interaction.
The increase in plasma levels of quinidine and disopyramide can be cardiotoxic and induce torsades de pointes.
Fibrates, nicotinic acid, bile acid sequestrants
Nephrotoxicity, hepatotoxicity and increased immunosuppressive effect.
Mechanism of action:
Investigations carried out on grapefruit juice have shown that some components of this fruit, such as bergamottin and naringin (Fig. 1) are potent inhibitors of cytochrome P450 3A4 (CYP3A4).
Fig.1 Chemical structure
This enzyme, expressed in the intestine and in the liver, is the main actor responsible for the detoxification of the organism from about 50% of the currently existing drugs.
The interaction of the drug with grapefruit juice occurs mainly by inhibition of intestinal CYP3A4, which causes a slower disposal of the drug and its excessive permanence in the organism (Fig. 2). For this reason, overdose phenomena are frequent following the intake of grapefruit and the drug.
Since inhibition of CYP3A4 occurs in the intestine, drug-grapefruit juice interactions occur only with oral formulations. Studies carried out on drugs metabolised by hepatic CYP3A4, administered intravenously, have shown that grapefruit juice does not modify their plasma levels.
Fig. 2 Pre-systemic metabolism of felodipine by CYP3A4 on enterocytes and in the liver. CYP3A4 metabolizes the drug until its bioavailability is reduced by 15%. Grapefruit, on the other hand, by inhibiting the enzyme increases the bioavailability of the drug by 45%.
Quantity and duration of the effect
Intestinal levels of CYP3A4 can be reduced by 47% within a couple of hours of taking grapefruit.
Furthermore, it has been shown that drug interactions can also occur with the intake of modest quantities of grapefruit juice or fresh fruit (250 g).
This enzymatic inactivation can last for a long period (about 3 days), therefore it would be advisable avoid ingesting grapefruit products at least 72 hours before taking a drug.
However, there is a large biological variability of intestinal CYP3A4 expression (genetic polymorphism), consequently it is difficult to be able to predict with certainty, from one patient to another, a possible drug interaction involving grapefruit juice. In any case. , the higher the intestinal content of this enzyme, the greater the risk of toxic effects.
Side effects
Grapefruit, causing the "increase in plasma levels of some drugs, creates a condition of overdose. This" increased concentration of the drug in our body is responsible for possible mild side effects, such as: headache, fatigue, gastrointestinal disorders, but sometimes also effects serious collateral, such as: kidney disease and heart disease. A sensational case of grapefruit drug interaction occurred in the USA, when a 29-year-old man died prematurely following the simultaneous intake of Terfenadine (an antihistamine) and grapefruit juice. The drug was immediately removed from the market. Since some drug interactions can be particularly serious, pharmaceutical companies, manufacturers for example of cyclosporine and simvastatin, have decided to add special warnings on the package leaflet about the use of grapefruit products. in patients being treated with these drugs.
Recommendations
The intent of this article of mine is not to cause alarmism or discourage the consumption of grapefruit, but to inform. It is therefore sufficient not to consume grapefruits or their derivatives when taking certain drugs!
Although to date there are no definitive data on this, it would seem that other types of citrus fruits such as oranges also Seville and the mapo (a hybrid between grapefruit and tangerine) can interfere, similarly to grapefruit juice, with the metabolism of some drugs.
We can safely consume other citrus fruits such as: oranges, tangerines and lemons which instead have no effect on CYP3A4.
Bibliography
- Bailey DG, Spence JD, Edgar B, Bayliff CD, Arnold JM. Ethanol enhances the hemodynamic effects of felodipine. Clin Invest Med. 1989;12:357–62.
- Edwards DJ, Bellevue FH, Woster PM. Identification of 6 ', 7'-dihydroxybergamottin, a cytochrome P450, in grapefruit juice. Drug Metab Dispos. 1996; 24: 1287-1290.
- Kuhnau J. The flavonoids: a class of semi-essential food components; their role in human nutrition. World Rev Nutr Diet. 1976; 24: 117–191
- Dahan A, Altman H. Food-drug interaction: grapefruit juice augments drug bioavailabilitymechanism, extent and relevance. Eur J Clin Nutr 2004; 58: 1-9.
- Dresser GK, Bailey DG. The effects of fruit juices on drug disposition: a new model for druginteractions. Eur J Clin Invest 2003; 33: 10-6.
- Huang SM, et al. for the Center for Drug Evaluation and Research and Office of Regulatory Affairs, U.S. Food and Drug Administration. Drug interactions with herbal products and grapefruit juice: a conference report. Clin Pharmacol Ther 2004; 75: 1-12.
Select plant Fir Acacia Acerola Sorrel Yarrow Yarrow Yarrow Aconito Adatoda Garlic Agnocasto Agrimonia Alchemilla Alkekengi Aloe Altea Witch Hazel Ammi or Visnaga Pineapple Andrographis Anemone Pulsatilla Angelica Anise Star Anise Japanese Star Anise Bitter Orange Bitter Areca Arnica Harpagophytum Arpagophyte Artemisia Asteragus Basil Asparagus Asparagus Peruvian Asparagus Asparagus Asparagus Hawthorn Boldo Borage Shepherd's Purse Boswellia Bucco Butea superba Cocoa Coffee Cajeput Calamus Calamus Marigold Camedrio Chamomile Roman Chamomile Camphor Cinnamon Ceylon Maidenhair Capuchin Artichoke Cardamom Cardiac Thistle Asian Thistle Carvi Cascara Cassia Catecu Catha Cabbage Celandine Chicory Centaurea Cinnamon Cypress Celandine Chives Cypress Coca Cola Colchico Combreto Condurango Comfrey Coriander Cranberry Barberry American Chrysanthemum Cumin Turmeric Damiana Digital Dioscorea Drosera Dulcamara Dunalilella Echinacea Eder a Ephedra Elenio Eleutherococcus Helichrysum Evening primrose Horsetail Alfalfa Erica Euphrasia Erisimo Escolzia Eucalyptus Farfara Farfaraccio Calabar bean Fenugreek Fennel Phytolacca Frangola Ash Fumaria Japanese Mushrooms Galega Ganoderma lucidum Garcinia Cambogia Mulberry Gentian Broom Ginkgo Ginkgo Guipana Guipana Gynestra Ginkgo Hibelia Gymnasium Hibiscus Guarulp St. John's Wort Horse Chestnut Ispaghul Hyssop Jaborandi Kava kava Konjac Laminaria Cherry Laurel Lavender Lemongrass Lespedeza Lovage Icelandic Lichen Lemon Flax Lippia Licorice Lobelia Hops Maca Marjoram Maize Mallow Manna Marrubio Marrubio d "water Matè Melaleuca Meliloto American Lemon balm Myrtle Myrama Walnut Nutmeg Walnut vomica Olive tree Meadowsweet Ononide Opuntia Oregano Orthosiphon Nettle Poppy Papaya Parietaria Feverfew Passiflora Chilli Perilla Periwinkle Phyllanthus Plantain Picrorhiza Pilosella Pino Pisci dia Podofillo Polygala Grapefruit Parsley Psyllium Pueraria mirifica Butcher's Broom Pygeum Quassia Oak Rhubarb Ratania Rauwolfia currant CastorRhodiola Dog rose Rosemary Rue Willow Sarsaparilla Sage Elderberry Sassafras Sedum Ergot Senna Serenoa repens Soybean Solidago spirulina Tamarind Tansy Dandelion Badger Tea Linden Thyme Tormentilla Clover Fibrinous clover Tuia Uncaria Bearberry Valerian Vanilla Mullein Verbena Senna Viburnum Viburnum Vis Pumpkin Select disease Juvenile Acne Rosacea Acne Tinnitus Aerophagia Tendon Affections Aphonia Aphtas Algae Functional Halitosis Breastfeeding Allergy Anemia Anguish Anxiety Arteriosclerosis Arthritis Gouty Arthritis Rheumatoid Arthrosis Asthenia Asthenia Sex Man Asthenia Sex Woman Blepharitis and Conjunctivitis Calculus Renal bags Bronchitis Brittle hair Caries Headache Cellulitis Motion sickness Cystitis Climacteric Cholecystopathy High cholesterol Ulcerative colitis Colonoscopy Bruises Hematoma Convalescence Couperose Depression Dermatitis Dermatitis and Diaper Diabetes Diarrhea Erectile dysfunction Dyslipidemia Dysmenorrhea Dyspepsia Disturbances of vision Hemorrhoids Epistaxis Cardiac erethism Fever Fibromyalgia Flatulence Phlebitis Gastritis Chilblains Gingivitis Herpes Loss of appetite Urinary infections Influenza Insomnia Hypersomnia Irritable intestine Malthritis Hypertension Hypertension Hypertension Prosth Mononucleosis Alzheimer's disease Crohn's disease Nausea Vomiting Obesity Dark circles Onychomycosis Osteoporosis Dry skin Periarthritis Piorea Low blood pressure Prostatitis Psoriasis Colds Breast fissures Anal fissures Gastroesophageal reflux Nasopharyngitis Wrinkles (abdominal fat) Salmonella Sinus syndrome Smashing Premenstrual stacks Cough High triglycerides Ulcer Burns Fragile nails Hot flashes Warts Dizziness Herbal properties Abortive tanning Adaptogens Aphrodisiacs Bittering analgesic anesthetic anorectics analgesic antacid anti-allergic anti-asthmatic Antibiotic catarrh Anticellulitiche anticonvulsant Antidiaforetiche antidiarrheal edematous anthelmintic antiemetic Antiemorroidarie antiphlogistic Antiidrotiche Antinevrotiche Antioxidants antipyretic antirheumatic antiscorbutic Antiseptic antispasmodic anti-uric Aperitive Flavoring Astringent Balsamic Bechiche Capillarotrope cardiotonic Carminative Cathartic caustics Cicatrizant cholagogue choleretic Dyes Decongestants Deodorants purifying Detergents diaphoretic Disinfectants Detox Refreshing Diuretics Exciting Emetics Emmenagoghe Emollients Hemostatic Energy Hepatoprotective Expectorants Eupepticics Photosensitizers Galactophores Galactofuges Galactogogues Moisturizers Immunostimulants Hypertensive Hypnotic Hypoglycemic Hypotensive Irritants Laxatives Soothing Narcotic Nervous ti Revulsive Remineralizing Refreshing Rubefacenti Scialagoghe Sedative Soporifera Sneezing Stomachic Stomatics Narcotic Tonic tenifugas Vasoconstrictors Vasodilators Wormers Vescicators Vulnerary Vitamins Other Foods - Fruits Apricots Amarene Chestnuts Anacilis Watermelon Watermelon Strawberry Persimmon Strawberry Persimmon Strawberry Persimmon Strawberry Persimmon Strawberry Persimmon Strawberry Kaffi Passion fruit (Maracujà, Granadilla) Jujube Kiwi Raspberries Coconut milk Almond milk Lime Lemons Mandarrants Mango Apples Quinces Pomegranate Melon Blackberries Mustard Medlar Olives Taggiasca olives Fermented Papaya Pears Peaches Plane (Cooking Bananas) Pomelo Grapefruit Pink grapefruit Prunes, prunes Fruit juices and fruit juices Grape juice Plums Grapes Sultanas and Raisins OTHER FRUIT ITEMS Categories Alcoholic foods Meat Cereals and derivatives Sweeteners Sweets Offal Fruit Dried fruit Milk and derivatives The gumi Oils and fats Fish and fishery products Cold cuts Spices Vegetables Health recipes Appetizers Bread, Pizza and Brioche First courses Second courses Vegetables and salads Sweets and desserts Ice creams and sorbets Syrups, liqueurs and grappas Basic Preparations ---- In the Kitchen with Leftovers Carnival recipes Christmas recipes Light diet recipes Women's, mom's and dad's day recipes Functional recipes International recipes Easter recipes Celiac recipes Diabetic recipes Holiday recipes Valentine's Day recipes Vegetarian recipes Protein recipes Regional recipes Vegan recipes