Grapefruit (C. paradisi) is a large, dimpled, round citrus fruit measuring 7.6 to 15.2 cm in diameter. It descends from a cross between a pomelo (pummelo) or shaddock (Citrus grandis), a large Malaysian citrus, and a sweet orange, and may have originated as a mutation of another type of citrus tree. The fruit grows in clusters similar to grapes, a possible origin of its name. Noteworthy cultivars of grapefruit include Duncan ("white," seeded), Marsh (seedless), Foster (pink, seeded), Thompson (pink, seedless), and redblush (red, seedless).Carper 1988, Davidson 1991, Ensminger 1993, USDA 2018
The Greek philosopher Theophrastus (371 to 287 BC), regarded as the founder of botany, wrote that "citron" could sweeten the breath and was thought to be an antidote to poison. Later, the Roman naturalist Pliny (AD 23 to 79) used the word "citrus" for the first time and labeled the fruit as a medicine. The grapefruit, known at the time as “small shaddock,” was first mentioned by Griffith Hughes (1707 to 1758) as the "forbidden fruit" of Barbados. The name "grapefruit," referring to the clusters of fruit on the trees, was said to have first been used in Jamaica in 1814. In 1823, the grapefruit was introduced in Florida by the French count Odette Phillippe, but it did not gain popularity until the end of the nineteenth century. In the 1930s, the Hollywood Diet, which recommended a limited calorie intake of approximately 800 calories per day and included grapefruit consumption at each meal, became popular. Worldwide production of grapefruit was projected in 2010 at approximately 5.5 million metric tons, and the juice of the fruit, including concentrate, accounts for approximately 42% of all US-processed grapefruit products.Carper 1988, Davidson 1991, Ensminger 1993, USDA 2018
The chemistry of grapefruit is well studied. Grapefruit is high in polyphenols, with its flavonoid naringin responsible for imparting the bitter taste. Other constituents include sugars, polysaccharides, organic acids, nitrogenous compounds, lipids, carotenoids such as beta-carotene and lycopene (that contribute to pink and red color), vitamins, minerals, flavonoids, and volatile components that contribute to aroma. Grapefruit is high in water and fiber, and contains a small amount of protein. The whole fruit is also a good source of potassium, vitamin C, inositol, bioflavonoids, and pectin; however, the juice alone is not high in pectin. Other vitamins and minerals present in grapefruit are vitamin A, thiamine, folate, vitamin B6, niacin, magnesium, calcium, and iron. The amount of vitamin A can be almost 1,000 times higher in the pink/red variations. In addition, grapefruit has minimal fat and is low in calories and sodium. The peel contains citral (an aldehyde that antagonizes the effects of vitamin A) and other terpenes (including limonene), which are of interest because of their chemoprotective and cholesterol-solvent properties.Carper 1988, Ensminger 1993, Giamperi 2004, Onakpoya 2017, Rampersaud 2017, Sun 2007
Constituents in grapefruit that affect cytochrome P450 (CYP-450) enzymes include the furanocoumarins bergamottin and 6′,7′-dihydroxybergamottin (DHB). DHB has been identified as a principal inhibitory furanocoumarin, with constituents of varying CYP3A inhibitory potencies; this effect is absent with consumption of low-furanocoumarin grapefruit juice.Kawaguchi-Suzuki 2017 Naringin and naringenin also exhibit inhibitory effects on the CYP-450 system but may inhibit CYP enzymes primarily in the intestine and less so in the liver. Concentrations of these inhibitory constituents have been shown to vary among commercially available juices; an approximately 200-fold difference in DHB has been observed among batches of grapefruit juice.Giamperi 2004, Hu 2016, van Erp 2011 Naringenin is a potent inhibitor of organic anion transporting polypeptide (OATP), and grapefruit also interferes with P-glycoprotein (P-gp) and adenosine triphosphate (ATP)–binding cassette drug transporters.Romaszko 2017, van Erp 2011
In vitro screening of a grapefruit seed extract found bactericidal activity against gram-negative and gram-positive bacteria at dilutions up to 1:512.Heggers 2002
In a series of case reports, chewing and swallowing 5 to 6 grapefruit seeds every 8 hours was effective against Klebsiella, Staphylococcus aureus, and Escherichia coli urinary tract infections, but not against Pseudomonas aeruginosa–resistant strains.Oyelam 2005
The grapefruit constituents pectin, lycopene, and d-limonene have been evaluated for potential chemotherapeutic roles via antioxidant and apoptosis-inducing activity. Clinical trials have produced mixed results.Giamperi 2004, Sun 2007, van Breemen 2008
Limited clinical trials have been conducted, possibly due to the potential for drug interactions. Two trials in post–coronary bypass patients with atherosclerosis demonstrated improved lipid profiles following whole grapefruit and grapefruit juice consumption.Gorinstein 2004, Gorinstein 2006 Antioxidant-carrying capacity also improved. Systolic and diastolic blood pressure were unchanged throughout the 30-day study.Reshef 2005 A systematic review of randomized controlled trials reporting the effects of grapefruit on body weight and cardiovascular risk factors identified 3 studies that met inclusion criteria (N=250). All participants were overweight or obese, with a mean body mass index (BMI) ranging from 31.4 to 36.8 kg/m2. Fresh grapefruit, grapefruit juice, or grapefruit capsules, with naringin doses of the grapefruit formulations ranging from 81 to 142 mg/day, was given for either 6 or 12 weeks. A reduction in systolic blood pressure (SBP), but not diastolic blood pressure, was reported compared to controls in a meta-analysis of all 3 trials (mean difference, −2.43 mm Hg; no P value reported) but significance was lost in the sensitivity analysis; no heterogeneity was evident in either analysis. Improvement in HDL cholesterol was reported by both the overall and sensitivity analyses as being important (mean difference, +3.21 and +4.6 mg/dL, respectively); heterogeneity was moderate to high. In contrast, no difference in fasting blood glucose, total cholesterol, or low-density lipoprotein (LDL) was found. Subgroup analysis reported fresh grapefruit provides a statistically significant improvement in SBP compared with grapefruit juice (mean difference, −2.48 mm Hg; no P value provided), with low heterogeneity. HDL cholesterol was also reported as statistically significantly improved (+3.56 mg/dL); however, this was incongruent with the P value provided (P=0.06). Constipation and diarrhea were reported as adverse events in 1 trial. Overall, the quality of evidence for the studies was rated as moderate, except for the LDL and HDL results, which were considered low quality.Onakpoya 2017
In a randomized, double-blind, controlled, crossover trial in healthy postmenopausal women (N=48), consumption of grapefruit juice for 6 months (340 mL/day; 201 mg/day of naringenin glycosides) significantly reduced central aortic stiffness compared with placebo (P=0.019).Habauzit 2015 Prolongation of the QTc interval has also been demonstrated in healthy volunteers, as well as in patients with cardiomyopathy, possibly due to the naringenin glycoside content.Piccirillo 2008, Zitron 2005
Initial animal and in vitro studies showed the capacity of d-limonene to dissolve gallstones.Sun 2007
Associations between fruit consumption and the risk of type 2 diabetes were assessed using data from 3 prospective longitudinal cohort studies (66,105 women in the Nurses' Health Study [1984-2008], 85,104 women in the Nurses' Health Study II [1991-2009], and 36,173 men from the Health Professionals Follow-up Study [1986-2008]). At baseline, patients did not have diabetes, cardiovascular disease, or cancer. A total of 12,198 participants developed type 2 diabetes during the 3,464,641 person-years of follow-up. The pooled hazard ratio (HR) for risk of type 2 diabetes was 0.95 (95% CI, 0.91 to 0.99) for grapefruit, with the lowest risk observed for blueberries (HR, 0.74; 95% CI, 0.66 to 0.83) and an inverse correlation observed for cantaloupe (HR, 1.1; 95% CI, 1.02 to 1.18). Associations with risk of type 2 diabetes differed significantly among individual fruits. In contrast, greater fruit juice consumption was associated with an increased risk, while substitution of whole fruits for fruit juice lowered this risk (except for strawberries and cantaloupe). Replacing 3 servings per week of grapefruit juice with whole grapefruit lowered the risk of diabetes by 12% (8% to 17%) after multifactorial adjustments, whereas the pooled analysis showed a 7% lower risk for whole fruits (1 serving of grapefruit was equal to one-half of a grapefruit); the highest reduction in diabetes risk occurred with blueberries (33%). No significant associations between risk of type 2 diabetes and total whole fruit consumption, glycemic index/glycemic load of fruits, or flavonoid subtypes were observed. The mechanism of action for grapefruit leads to improved glucose tolerance that appears to result from an increase in glucagonlike peptide 1 due to inhibition of dipeptidyl peptidase 4 by naringin, which is found in high amounts in grapefruit.Muraki 2013
Grapefruit has value as a dietary supplement, similar to other citrus fruits. Grapefruit juice is an excellent source of vitamin C, with the pink variation consistently ranking among the most nutrient dense. It is also a good source of potassium and provides folate, thiamine, magnesium, vitamin B6, iron, niacin, and calcium; pink and red varieties are high in vitamin A, primarily due to beta-carotene. An 8 oz serving of the juice also contains approximately 1.3 g of protein. Grapefruit juice is also rich in polyphenols, especially naringin. Caloric content is provided mostly by sugars (sucrose, fructose, glucose), with 22 g of carbohydrates delivered in an 8 oz serving of 100% juice.Rampersaud 2017 Consumption of the whole fruit has been shown in multiple analyses to provide improved health benefits compared with consuming the juice.Muraki 2013, Onakpoya 2017
Vitamin C status and bleeding scores were improved in a study of patients with periodontitis who consumed 2 grapefruits a day for 2 weeks.Staudte 2005
Weight loss has been observed in some, but not all, clinical studies; conflicting findings could be due to variability of dosage regimens.Fujioka 2006, Gorinstein 2006 A meta-analysis of randomized controlled trials reported the effects of grapefruit on body weight and cardiovascular risk factors in obese adults (mean BMI ranging from 31.4 to 36.8 kg/m2). A total of 3 studies were identified that met inclusion criteria (N=250) in the systematic review, all of which incorporated lifestyle modifications as part of a weight management regimen. Fresh grapefruit, grapefruit juice, or grapefruit capsules, with naringin doses of the grapefruit formulations ranging from 81 to 142 mg/day, was given for either 6 or 12 weeks. Sensitivity analyses revealed a nonsignificant reduction in body weight but found a statistically significant reduction in body fat (mean difference, −0.49%; P=0.002) and waist circumference (mean difference, −1.15 cm; P<0.0001) in favor of grapefruit over controls in overweight or obese participants. Quality of evidence for the studies was considered moderate.Onakpoya 2017 Another systematic review pointed to preliminary data from a National Health and Nutrition Examination Survey (NHANES) analysis report that demonstrated lower body weight, BMI, and waist circumference in women who consumed any amount of grapefruit (ie, fresh, juice, frozen) compared with nonconsumers.Rampersaud 2017
Quality clinical trials upon which to base therapeutic dosing recommendations are limited.
1 grapefruit daily for 30 days has been used in a clinical trial to improve lipid profiles.Gorinstein 2006 Fresh grapefruit, grapefruit juice, and grapefruit capsules for 6 or 12 weeks, with naringin doses of the formulations ranging from 81 to 142 mg/day, have been used in randomized controlled trials evaluating effects on cardiovascular risk factors in obese adults.Onakpoya 2017 In a trial of healthy postmenopausal women, 340 mL/day (providing 201 mg/day of naringenin) of grapefruit juice was administered for 6 months to evaluate effects on arterial stiffness.Habauzit 2015
Pooled results from 3 prospective longitudinal cohort studies (N=187,382; 3,464,641 person-years of follow-up) reported consumption of 2 to 4 servings per week of grapefruit to reduce the risk of type 2 diabetes. In one cohort of women, 2 to 4 servings per week or 5 or more servings per week of grapefruit (1 serving of grapefruit was one-half of a grapefruit) also reduced risk.Muraki 2013
2 grapefruits per day for 2 weeks were consumed in a trial evaluating effects on vitamin C status of patients with periodontitis.Staudte 2005
8 oz (237 mL) of grapefruit juice, or half of a fresh grapefruit, 3 times a day before each meal for 12 weeks was used in a clinical trial evaluating effects on body weight and metabolic syndrome.Fujioka 2006 In a meta-analysis evaluating effects on body weight, fresh grapefruit, grapefruit juice, or grapefruit capsules (with naringin dosages of the formulations ranging from 81 to 142 mg) were administered for 6 or 12 weeks in the included randomized controlled trials.Onakpoya 2017
Grapefruit and grapefruit juice is considered GRAS for use as food. Safety of amounts greater than those in foods are unproven.Ernst 2002 Naringenin concentration has been shown to increase in human breast milk after consumption of a single 250 mL dose of grapefruit juice, with mean concentrations increasing by approximately 35% from baseline within the first 4 hours. Additionally, a low-naringenin diet that limited citrus and tomato products reduced naringenin levels in breast milk.Romaszko 2017
Grapefruit seed extract is not the equivalent of grapefruit juice, and it is not known whether extracts of grapefruit seed also have potential to alter drug metabolism. Grapefruit may interact with medications via mechanisms including inhibition of CYP3A4, CYP1A2, CYP2A6, P-gp, ATP-binding cassette drug transporters, and uptake transporters such as OATPs.Seden 2010, van Erp 2011
CYP inhibition appears to occur predominantly via intestinal enzymes and less so via the hepatic system.Hu 2016, van Erp 2011 Studies have indicated an approximate 12-hour half-life of CYP enzyme inhibition, with a mean 62% inhibition still present 5 days after grapefruit consumption.Cohen 2012 The inhibitory effect of grapefruit juice on the CYP1A2 isozyme appears to be weak and uncertain as reflected by equivocal results in pharmacokinetic studies using the substrates caffeine and theophylline. Adding to the uncertainty is the wide variation in inhibitory flavonoids that occurs among grapefruit juice preparations.Hu 2016 Grapefruit juice with concentrations of bergamotten and DHB selected specifically to induce a clinically relevant effect on CYP3A4 with the substrate sunitinib were measured to be at least 23.5 and 2.7 mcmol/L, respectively.van Erp 2011
Albendazole: Grapefruit juice may increase serum concentrations of the active metabolite(s) of albendazole. Monitor therapy.Nagy 2002
Amiodarone: Grapefruit juice may decrease serum concentrations of the active metabolite(s) of amiodarone. Grapefruit juice may increase the serum concentration of amiodarone. Avoid combination.Cordarone December 2008, Libersa 2000
Antifungal agents (azole derivatives, systemic): Grapefruit juice may increase the serum concentration of antifungal agents (azole derivatives, systemic). This specifically applies to oral antifungal administration, and the interaction may be different depending on the specific dosage form being used. Monitor therapy.Gubbins 2004, Gubbins 2008, Kawakami 1998, Penzak 1999
Avanafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of avanafil. Consider therapy modification.Stendra April 2012
Benzodiazepines (metabolized by oxidation): Grapefruit juice may decrease the metabolism of benzodiazepines (metabolized by oxidation) and their metabolites. Consider therapy modification.Hukkinen 1995, Kawaguchi-Suzuki 2017, Kupferschmidt 1995
Bosutinib: CYP3A4 inhibitors (moderate) and P-gp/ABCB1 inhibitors may increase the serum concentration of bosutinib. Avoid combination.Abbas 2011, Bosulif September 2012
Budesonide (systemic, oral inhalation): Grapefruit juice may increase the serum concentration of budesonide (systemic, oral inhalation). Avoid combination.Entocort June 2009, Pulmicort July 2010, Seidegard 2009
Buspirone: Grapefruit juice may decrease the metabolism of buspirone. Consider therapy modification.Lilja 1998
Cabozantinib: Grapefruit juice may increase the serum concentration of cabozantinib. Avoid combination.Cometriq December 2012
Carbamazepine: Grapefruit juice may decrease the metabolism of carbamazepine. Monitor therapy.Bonin 2001, Garg 1998
Clomipramine: Grapefruit juice may increase the serum concentration of clomipramine. Monitor therapy.Oesterheld 1997
Clopidogrel: Grapefruit juice may decrease the effect of clopidogrel. Avoid combination.Holmberg 2014
Crizotinib: Grapefruit juice may increase the serum concentration of crizotinib. Avoid combination.Xalkori August 2011
CYP3A4 substrates: CYP3A4 inhibitors (moderate) may decrease the metabolism of CYP3A4 substrates. Monitor therapy.Bjornsson 2003, Kawaguchi-Suzuki 2017
Dabigatran etexilate: P-gp/ABCB1 inhibitors may increase serum concentrations of the active metabolite(s) of dabigatran etexilate. Consider therapy modification.Pradax January 2012, Pradaxa November 2011
Docetaxel (oral): Grapefruit juice may reduce the clearance and increase the serum concentration of docetaxel (oral). Monitor closely.Valenzuela 2011
Dronedarone: Grapefruit juice may increase the serum concentration of dronedarone. Avoid combination.Multaq June 2009
Eplerenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of eplerenone. Consider therapy modification.Inspra June 2012, Inspra August 2012
Fluvoxamine: Grapefruit juice may increase the serum concentration of fluvoxamine. Monitor therapy.Hori 2003
Ifosfamide: CYP3A4 inhibitors (moderate) may decrease serum concentrations of the active metabolite(s) of ifosfamide. Monitor therapy.Ifex March 2012, Kerbusch 2001, McCune 2005
Ibrutinib (oral): Grapefruit juice may increase the absolute bioavailability and serum concentrations of ibrutinib. Monitor therapy.de Vries 2016
Ivabradine: Grapefruit juice may increase the serum concentration of ivabradine. Consider therapy modification.Procoralan August 2010
Ivacaftor: Grapefruit juice may increase the serum concentration of ivacaftor. Avoid combination.Kalydeco January 2012
Lapatinib: Grapefruit juice may increase the serum concentration of lapatinib. Avoid combination.Smith 2009, Tykerb August 2011
Lomitapide: CYP3A4 inhibitors (moderate) may increase the serum concentration of lomitapide. Avoid combination.Juxtapid December 2012
Lurasidone: CYP3A4 inhibitors (moderate) may increase the serum concentration of lurasidone. Consider therapy modification.Latuda June 2012, Latuda December 2012
Methadone (oral): Grapefruit juice may decrease the CYP3A4-induced metabolite of methadone (2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP]), with minimal effects on serum concentrations and clearance. Consider this when monitoring EDDP for compliance.Feng 2017
Montelukast: Grapefruit juice may increase the serum concentration of montelukast. Avoid combination.Cingi 2013
Nitrendipine: Grapefruit juice may increase the serum concentration of nitrendipine. Monitor therapy.Ohnishi 2006, Soons 1991, Uesawa 2008
Oxycodone (oral): Grapefruit juice may increase the serum concentration and half-life of oxycodone (oral). Monitor therapy.Feng 2017
P-gp/ABCB1 substrates: P-gp/ABCB1 inhibitors may increase the serum concentration of P-gp/ABCB1 substrates. P-gp inhibitors may also enhance the distribution of P-gp substrates to specific cells/tissues/organs where P-gp is present in large amounts (eg, brain, T-lymphocytes, testes). Monitor therapy.Albermann 2005, Callagan 2008, Gurley 2008, Ho 2005, Kim 2002, Kivisto 2004, Leslie 2005, Teng 2008, Wakasugi 1998
Pazopanib: Grapefruit juice may increase the serum concentration of pazopanib. Avoid combination.Votrient October 2009
Pirfenidone: CYP1A2 inhibitors may increase the serum concentration of pirfenidone. Avoid combination.Esbriet October 2017 Grapefruit juice may decrease serum concentrations of pirfenidone during a fasted state, as demonstrated in persons of Han Chinese descent.Hu 2016
Pomalidomide: P-gp/ABCB1 inhibitors may increase the serum concentration of pomalidomide. Avoid combination.Pomalyst February 2013
Ponatinib: Grapefruit juice may increase the serum concentration of ponatinib. Consider therapy modification.Iclusig December 2012
Prasugrel: Grapefruit juice may decrease the serum concentration of the active metabolite of prasugrel. Platelet inhibition may be affected. Monitor closely.Holmberg 2015
Propafenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of propafenone. Monitor therapy.Rythmol SR November 2011
Prucalopride: P-gp/ABCB1 inhibitors may increase the serum concentration of prucalopride. Monitor therapy.Resotran December 2011
Regorafenib: Grapefruit juice may increase the serum concentration of regorafenib. Avoid combination.Stivarga September 2012
Rivaroxaban: P-gp/ABCB1 inhibitors may increase the serum concentration of rivaroxaban. Monitor therapy.Kubitza 2008, Xarelto September 2008
Ruxolitinib: Grapefruit juice may increase the serum concentration of ruxolitinib. Consider therapy modification.Jakafi November 2011, Shi 2012
Salmeterol: CYP3A4 inhibitors (moderate) may increase the serum concentration of salmeterol. Monitor therapy.Manchee 1996, Serevent March 2008
Saxagliptin: CYP3A4 inhibitors (moderate) may increase the serum concentration of saxagliptin. Monitor therapy.Onglyza July 2009, Patel 2011
Sertraline: Grapefruit juice may increase the serum concentration of sertraline. Monitor therapy.Lee 1999, Ueda 2009
Silodosin: P-gp/ABCB1 inhibitors may increase the serum concentration of silodosin. Avoid combination.Rapaflo September 2008
Sirolimus: Grapefruit juice may increase the serum concentration of sirolimus. Monitor closely when used strategically as adjunctive therapy.Cohen 2012
Sunitinib: Grapefruit juice may increase the serum concentration of sunitinib. Monitor closely.van Erp 2011
Ticagrelor: Grapefruit juice may increase the serum concentration of ticagrelor. Monitor therapy.Holmberg 2013
Tolvaptan: CYP3A4 inhibitors (moderate) may increase the serum concentration of tolvaptan. Avoid combination.Samsca May 2009
Toremifene: Grapefruit juice may increase the serum concentration of toremifene. Avoid combination.Fareston March 2011
Verapamil: Grapefruit juice may increase the serum concentration of verapamil. Monitor therapy.Fuhr 2002, Ho 2000, Zaidenstein 1998
Vilazodone: CYP3A4 inhibitors (moderate) may increase the serum concentration of vilazodone. Monitor therapy.Viibryd January 2011
Vincristine (liposomal): P-gp/ABCB1 inhibitors may increase the serum concentration of vincristine (liposomal). Avoid combination.Marqibo August 2012
Zuclopenthixol: CYP3A4 inhibitors (moderate) may increase the serum concentration of zuclopenthixol. Monitor therapy.Clopixol January 2011, Davies 2010
Grapefruit juice interacts with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, amiodarone, and warfarin; avoid use in patients with heart failure.Page 2016
Some studies have reported clinically unimportant pharmacokinetic drug interactions with natural products. Limited information as well as potentially high interpatient variability in clinical response warrants cautious interpretation and/or application of these data in practice.
Fentanyl (transmucosal): Grapefruit juice minimally affected maximum plasma concentration, time to maximum plasma concentration, area under the curve (AUC), and maximal pupil diameter change after administration of oral transmucosal fentanyl. The onset or magnitude of analgesia was deemed unlikely to be affected by CYP3A-related drug interactions when treating breakthrough pain, particularly if careful attention is paid to minimal swallowing and maximal mucosal absorption.Feng 2017
Midazolam: Compared with regular grapefruit juice, low-furanocoumarin grapefruit juice was demonstrated to have no clinically relevant interaction on midazolam metabolism.Kawaguchi-Suzuki 2017
Nadolol: Grapefruit juice had no effect on the elimination half-life of nadolol and a nonstatistically significant decrease on AUC in healthy volunteers.Misaka 2013
Reports of adverse reactions related to grapefruit consumption are limited. Grapefruit juice has been associated with hypotensionOnakpoya 2017, Reshef 2005 and deep vein thrombosis (presumed to be due to an interaction with ethinyl estradiol).Grande 2009 Prolongation of the QTc interval has been demonstrated in healthy volunteers and patients with cardiomyopathy.Piccirillo 2008, Zitron 2005 Case reports of allergy to pectin and pectin-induced asthma exist.Ferdman 2006 Constipation and diarrhea have also been reported in one trial.Onakpoya 2017
Data collected between 2004 and 2013 from 8 US centers in the Drug-Induced Liver Injury Network revealed 15.5% (n=130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (n=709) were related to medications. Of the 130 cases of liver injury related to supplements, 65% were from nonbodybuilding supplements and occurred most often in Hispanic/Latino populations compared with non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent in cases of toxicity from nonbodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher with supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, grapefruit was among the 22% (n=116) labeled as single-ingredient products.Navarro 2014
Toxicological studies on whole grapefruit are lacking. A meta-analysis of 3 landmark studies evaluating associations between grapefruit consumption and risk of breast cancer (European Prospective Investigation into Cancer and Nutrition [EPIC], the Nurses' Health Study, and the Multiethnic Cohort Study of Diet and Cancer) found no increased risk of breast cancer (HR, 1.06 [95% CI, 0.95 to 1.19]); however, the possibility of an association could not be ruled out.Kim 2008, Monroe 2007, Spencer 2009 The grapefruit constituent d-limonene has GRAS status.Sun 2007 Grapefruit seed extract has been shown to be toxic to human skin fibroblast cells up to concentrations of 1:128 but not 1:512 in antibacterial studies.Heggers 2002
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