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- The grapefruit was first described in the 1750s as the “forbidden fruit” of Barbados. It was introduced to Florida in the 1820s. Most grapefruit in the United States is still grown in Florida. Grapefruit juice has been used in folk medicine for the treatment of diabetes as well as to strengthen the immune system. Grapefruit is also added to cosmetics and hair care products as a fragrance.
- Grapefruit has been suggested as a treatment for several conditions, but there is currently insufficient scientific evidence to support the use of grapefruit for any medical disorder. The use of supplemental grapefruit pectin in the prevention of cardiovascular disease and the use of grapefruit seed extract in atopic eczema warrants further scientific investigation before a strong recommendation can be made. There is conflicting research regarding the use of grapefruit for kidney stones.
- Grapefruit juice alters the way some drugs are broken down in the liver. Grapefruit may increase the effects of calcium channel blockers, benzodiazepines, immunosuppressants, and HMG-CoA reductase inhibitors.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
There is early, but inconclusive evidence to support the use of grapefruit seed extract in the treatment of atopic eczema. Additional study is needed to confirm these findings.
Early studies suggest grapefruit may have some benefit in the management of metabolic syndrome. More studies are needed to understand this relationship.
Grapefruit pectin supplementation may inhibit high cholesterol. There is promising but inconclusive human evidence to support the use of grapefruit pectin in the prevention of heart disease. Additional study is needed in this area.
There is limited and mixed research regarding the use of grapefruit for kidney stones. Further research is needed to clarify these results.
*Key to grades:
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
Adults (over 18 years old)
- There is no proven effective dose for grapefruit. Grapefruit is typically taken as a fruit, seed extract, or pectin by mouth. It has also been applied on the skin as a disinfectant for skin wounds. For atopic eczema, 150 milligrams of grapefruit seed extract has been taken by mouth three times daily for one month. For heart disease, 15 grams of grapefruit pectin in divided doses with meals for 16 weeks has been used. For metabolic syndrome, grapefruit capsules, fresh grapefruit, or 8 oz. of grapefruit juice three times daily before each meal has been studied for 12 weeks.
Children (under 18 years old)
- There is no proven effective dose for grapefruit in children. Grapefruit is likely safe when used in amounts commonly found in foods by individuals not on concurrent drug therapy.
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
- Avoid in individuals with a known allergy or hypersensitivity to grapefruit.
Side Effects and Warnings
- Grapefruit appears to be well-tolerated. Grapefruit is likely safe when used in amounts commonly found in foods by individuals not on concurrent drug therapy. Grapefruit has Generally Recognized as Safe (GRAS) status in the United States. Adverse effects from grapefruit juice have been reported only rarely and have been limited to those in combination with drug therapy. The severity of the interaction may depend on how much and how often the grapefruit juice is consumed, the timing of the grapefruit juice, the specific brand of juice, and the medication dose.
- Experts report that topically applied grapefruit seed extract can be irritating to the skin.
- High doses may cause pseudohyperaldosteronism (Liddle’s syndrome), increases in potassium clearance, mineralocorticoid excess, lowered elevated hematocrits, the development of kidney stones, or increases in enamel loss and tooth surface loss.
- Use cautiously in patients who drink red wine. Red wine in combination with grapefruit juice appears to have an additive inhibitory effect on the way liver breaks down some agents, theoretically increasing the risk for interactions with other drugs.
- Use cautiously in patients who drink tonic water or smoke.
- Use cautiously in patients with liver cirrhosis, at risk for kidney stones, or who have undergone gastric bypass surgery.
Pregnancy and Breastfeeding
- Grapefruit is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Interactions with Drugs
- Grapefruit juice may interfere with the way the body breaks down certain drugs in the liver. As a result, the levels of some drugs may be increased in the blood, and may cause increased effects or potentially serious adverse reactions. Patients using medications such as amitriptyline, clomipramine, clozapine, cyclobenzaprine, haloperidol, naproxen, ondansetron, propranolol, theophylline, and verapamil should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
- Grapefruit juice may also interact with nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., diclofenac, ibuprofen, meloxicam, piroxicam), oral antidiabetic agents (tolbutamide, glipizide), and angiotensin II blockers (e.g., losartan).
- Caution is advised when mixing grapefruit juice with proton pump inhibitors (e.g., lansoprazole, omeprazole, pantoprazole), anti-epileptics (e.g., diazepam, phenytoin), carisoprodol, citalopram, and nelfinavir.
- Grapefruit juice may increase drug levels and the risk of adverse effects when taken with macrolide antibiotics (e.g., erythromycin, clarithromycin), anti-arrhythmics (e.g., quinidine), benzodiazepines (e.g., alprazolam, midazolam, diazepam, triazolam), immune modulators (e.g., cyclosporine, tacrolimus), protease inhibitors (e.g., ritonavir, saquinavir), prokinetic agents (e.g., cisapride), antihistamines (e.g., terfenadine), calcium channel blockers (e.g., amlodipine, felodipine, diltiazem), HMG-CoA reductase inhibitors (e.g., atorvastatin, lovastatin), alfuzosin, etc.
- Although not well studied in humans, numerous other potential interactions with grapefruit juice may occur with acebutolol, alfentanil, alprazolam, amlodipine, amprenavir, anthelmintics (e.g., praziqauntel), antiarrhythmics (e.g., amiodarone, propafenone, quinidine), anticonvulsants (e.g., carbamazepine), antifungal agents (e.g., itraconazole), antimalarial agents (e.g., halofantrine, artemether, quinine), antineoplastic agents, aripiprazole, atorvastatin, beta-blocking agents, benzodiazepines, budesonide, celiprolol, digoxin, eplerenone, etoposide, felodipine, fentanyl, hormone replacement, imatinib, indinavir, lovastatin, levothyroxine, oral contraceptives (e.g., estradiol, progesterone), methylprednisolone, mifepristone, nifedipine, nimodipine, nitrendipine, opioids, pranidipine, ranolazine, scopolamine, selective serotonin reuptake inhibitors (e.g., sertraline), simvastatin, sufentanilbuspirone, sunitinib, talinolol, tolterodine, trazadone, triazolam, and zolpidem. Check with a qualified healthcare professional, including a pharmacist, for any interactions.
- Grapefruit may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (“blood thinners”) such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
- Grapefruit has been shown to modestly increase the absorption of sildenafil, an erectile dysfunction agent. Theoretically, grapefruit may have similar effects if used with other erectile dysfunction agents, such as tadalafi or vardenafil.
- Clinical studies show that the ingestion of grapefruit juice should not cause any pharmacokinetic or pharmacodynamic interactions when coadministered with caffeine.
- Grapefruit may reduce the effectiveness of antihistamines such as fexofenadine.
- Theoretically, grapefruit juice may inhibit the hepatic metabolism of oxybutynin leading to increased drug levels and associated adverse events.
- Grapefruit juice was found to have no significant effect on the metabolism of prednisone or prednisolone in one study of kidney transplant patients.
- Based on laboratory study, grapefruit may inhibit the absorption of vinblastine or alter the permeation of vincristine across the blood-brain barrier.
Interactions with Herbs and Dietary Supplements
- Theoretically, grapefruit may increase the adverse effects associated with antiarrhythmic, anticonvulsant, antihistamine, immunosuppressant, anti-cancer, beta-blocking, or estrogen-containing herbs and supplements. Concomitant use of grapefruit and green tea may increase caffeine levels leading to an increased risk of cardiovascular and central nervous system stimulatory effects, along with other caffeine-related adverse effects due to caffeine in green tea. However, currently, this effect has not been reported in humans.
- In theory, grapefruit juice may increase concentrations of digitalis (foxglove) and vitamin C levels, although clinical significance is unknown.
- Theoretically, grapefruit may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
- Preliminary evidence suggests that grapefruit juice may interfere with the way the body processes certain herbs or supplements using the liver’s “cytochrome P450” enzyme system. As a result, the levels of other herbs or supplements may become too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
- Grapefruit may interfere with the body’s conversion of cortisol to cortisone. If both licorice and grapefruit are taken together, the risk of high blood pressure and other side effects may be increased.
- Grapefruit juice has a weak interaction with theophylline-containing drugs. In theory, grapefruit may interact with xanthine-containing herbs and caution is advised.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
- This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration ().
- Bailey DG, Spence JD, Munoz C, et al. Interaction of citrus juices with felodipine and nifedipine. Lancet 2-2-1991;337(8736):268-269.
- Chaobal HN, Kharasch ED. Single-point sampling for assessment of constitutive, induced, and inhibited cytochrome P450 3A activity with alfentanil or midazolam. Clin Pharmacol Ther 2005;78(5):529-539.
- Dresser GK, Kim RB, Bailey DG. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 2005;77(3):170-177.
- Fujioka K, Greenway F, Sheard J, et al. The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome. J Med Food 2006 Spring;9(1):49-54.
- Goosen TC, Cillie D, Bailey DG, et al. Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans. Clin Pharmacol Ther 2004;76(6):607-617.
- Gorinstein S, Caspi A, Libman I, et al. Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. J Agric Food Chem 2006 Mar 8;54(5):1887-92.
- Lilja JJ, Laitinen K, Neuvonen PJ. Effects of grapefruit juice on the absorption of levothyroxine. Br J Clin Pharmacol 2005;60(3):337-341.
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- Paine MF, Criss AB, Watkins PB. Two major grapefruit juice components differ in time to onset of intestinal CYP3A4 inhibition. J Pharmacol Exp Ther 2005;312(3):1151-1160.
- Shi J, Montay G, Leroy B, et al. Effects of itraconazole or grapefruit juice on the pharmacokinetics of telithromycin. Pharmacotherapy 2005;25(1):42-51.
- Staudte H, Sigusch BW, Glockmann E. Grapefruit consumption improves vitamin C status in periodontitis patients. Br Dent J 8-27-2005;199(4):213-7, discussion.
- Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun.Mass Spectrom 2004;18(19):2273-2281.
- Yee GC, Stanley DL, Pessa LJ, et al. Effect of grapefruit juice on blood cyclosporin concentration. Lancet 4-15-1995;345(8955):955-956.
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to . Selected references are listed below.