The paper examines the effects of grapefruit consumption in relation to drugs, obesity and cardiovascular risk factors. The review includes the most updated studies found in Pub-Med. The grapefruit effect refers to the ability of grapefruit juice and supplements to interact with a wide variety of pharmaceuticals, either enhancing or limiting their systemic availability. Due to altering the active dosage of the pharmaceutical, Grapefruit juice is commonly not allowed to be used alongside with many drugs. Naringin is the most important one, which can inhibit absorption of some drugs but more commonly 6 ’ 7 ’ -dihydroxybergamottin, which inhibits CYP3A4. Lately, grapefruit has been found both in rats and adults to reduce body weight, blood pressure, improve lipid and hepatic profile and decrease platelet aggregation. These promising results must be followed by additional studies in order to add to the importance of the role and effects of grapefruit as part of our diet.
D. G. Bailey, J. Malcolm, O. Arnold and J. D. Spence, “Grapefruit Juice-Drug Interactions,” British Journal of Clinical Pharmacology, Vol. 58, No. 7, 2004, pp. S831S840. http://dx.doi.org/10.1111/j.1365-2125.2004.02305.x
W. V. De Castro, S. Mertens-Talcott, A. Rubner, V. Butterweck and H. Derendorf, “Variation of Flavonoids and Furanocoumarins in Grapefruit Juices: A Potential Source of Variability in Grapefruit Juice-Drug Interaction Studies,” Journal of Agricultural and Food Chemistry, Vol. 54, No. 1, 2006, pp. 249-255. http://dx.doi.org/10.1021/jf0516944
G. Gattuso, D. Barreca, C. Gargiulli, U. Leuzzi and C. Caristi, “Flavonoid Composition of Citrus Juices,” Molecules, Vol. 12, No. 8, 2007, pp. 1641-1673. http://dx.doi.org/10.3390/12081641
D. J. Edwards, M. E. Fitzsimmons, E. G. Schuetz, K. Yasuda, M. P. Ducharme, L. H. Warbasse, P. M. Woster, J. D. Schuetz and P. Watkins, “6’,7’-Dihydroxybergamottin in Grapefruit Juice and Seville Orange Juice: Effects on Cyclosporine Disposition, Enterocyte CYP3A4, and P-Glycoprotein,” Clinical Pharmacology & Therapeutics, Vol. 65, No. 3, 1999, pp. 237-244. http://dx.doi.org/10.1016/S0009-9236(99)70102-5
L. Q. Guo, K. Fukuda, T. Ohta and Y. Yamazoe, “Role of Furanocoumarin Derivatives on Grapefruit Juice-Mediated Inhibition of Human CYP3A Activity,” Drug Metabolism and Disposition, Vol. 28, 2000, pp. 766-771.
G. K. Dresser, D. G. Bailey, B. F. Leake, U. I. Schwarz, P. A. Dawson, D. J. Freeman and R. B. Kim, “Fruit Juices Inhibit Organic Anion Transporting Polypeptidemediated Drug Uptake to Decrease the Oral Availability of Fexofenadine,” Clinical Pharmacology & Therapeutics, Vol. 71, No. 1, 2002, pp. 11-20. http://dx.doi.org/10.1067/mcp.2002.121152
R. L. Rouseff, S. F. Martin and C. O. Youtsey, “Quantitative Survey of Narirutin, Naringin, Hesperidin, and Neohesperidin in Citrus,” Journal of Agricultural and Food Chemistry, Vol. 35, No. 6, 1987, pp. 1027-1030. http://dx.doi.org/10.1021/jf00078a040
P. C. Ho, D. J. Saville, P. F. Coville and S. Wanwimolruk, “Content of CYP3A4 Inhibitors, Naringin, Naringenin and Bergapten in Grapefruit and Grapefruit Juice Products,” Pharmaceutica Acta Helvetiae, Vol. 74, No. 4, 2000, pp. 379-385. http://dx.doi.org/10.1016/S0031-6865(99)00062-X
D. G. Bailey, J. D. Spence, B. Edgar, C. D. Bayliff and J. M. Arnold, “Ethanol Enhances the Hemodynamic Effects of Felodipine,” Clinical & Investigative Medicine, Vol. 12, No. 6, 1989, pp. 357-362.
D. G. Bailey, J. Malcolm, O. Arnold and J. D. Spence, “Grapefruit Juice-Drug Interactions,” British Journal of Clinical Pharmacology, Vol. 46, No. 2, 1998, pp. 101110. http://dx.doi.org/10.1046/j.1365-2125.1998.00764.x
M. F. Paine and N. H. Oberlies, “Clinical Relevance of the Small Intestine as an Organ of Drug Elimination: Drug-Fruit Juice Interactions,” Expert Opinion on Drug Metabolism & Toxicology, Vol. 3, No. 1, 2007, pp. 67-80. http://dx.doi.org/10.1517/17425255.3.1.67
D. G. Bailey and G. K. Dresser, “Interactions between Grapefruit Juice and Cardiovascular Drugs,” American Journal of Cardiovascular Drugs, Vol. 4, No. 5, 2004, pp. 281-297. http://dx.doi.org/10.2165/00129784-200404050-00002
C. D. Harapu, A. Miron, M. Cuciureanu and R. Cuciureanu, “Flavonoids—Bioactive Compounds in Fruits Juice,” Revista Medico-Chirurgicala a Societatii de Medici si Naturalisti din Iasi, Vol. 114, No. 4, 2010, pp. 1209-1214.
M. Murray, “Encyclopedia of Nutritional Supplements,” Prima Publishing, 1996.
Y. Sun, L. Qiao, Y. Shen, P. Jiang, J. Chen and X. Ye, “Phytochemical Profile and Antioxidant Activity of Physiological Drop of Citrus Fruits,” Journal of Food Science, Vol. 78, No. 1, 2013, pp. C37-C42. http://dx.doi.org/10.1111/j.1750-3841.2012.03002.x
A. Dahan and H. Altman, “Food-Drug Interaction: Grapefruit Juice Augments Drug Bioavailability—Mechanism, Extent and Relevance,” European Journal of Clinical Nutrition, Vol. 58, No. 1, 2004, pp. 1-9. http://dx.doi.org/10.1038/sj.ejcn.1601736
H. Takanaga, A. Ohnishi, H. Murakami, H. Matsuo, S. Higuchi and A. Urae, “Relationship between Time after Intake of Grapefruit Juice and the Effect on Pharmacokinetics and Pharmacodynamics of Nisoldipine in Healthy Subjects,” Clinical Pharmacology & Therapeutics, Vol. 67, No. 3, 2000, pp. 201-214. http://dx.doi.org/10.1067/mcp.2000.104215
J. Lundahl, C. G. Regardh, B. Edgar and G. Johnsson, “Relationship between Time of Intake of Grapefruit Juice and Its Effect on Pharmacokinetics and Pharmacodynamics of Felodipine in Healthy Subjects,” European Journal of Clinical Pharmacology, Vol. 49, No. 1-2, 1995, pp. 6167. http://dx.doi.org/10.1007/BF00192360
G. K. Dresser and D. G. Bailey, “The Effects of Fruit Juices on Drug Disposition: A New Model for Drug Interactions,” European Journal of Clinical Investigation, Vol. 33, No. 1, 2003, pp. 10-6. http://dx.doi.org/10.1046/j.1365-2362.33.s2.2.x
D. I. Min, Y. M. Ku, D. R. Geraets and H. Lee, “Effect of Grapefruit Juice on the Pharmacokinetics and Pharmacodynamics of Quinidine in Healthy Volunteers,” Journal of Clinical Pharmacology, Vol. 36, No. 5, 1996, pp. 469476. http://dx.doi.org/10.1002/j.1552-4604.1996.tb05034.x
C. C. Libersa, S. A. Brique, K. B. Motte, J. F. Caron, L. M. Guedon-Moreau, L. Humbert, et al., “Dramatic Inhibition of Amiodarone Metabolism Induced by Grapefruit Juice,” British Journal of Clinical Pharmacology, Vol. 49, No. 4, 2000, pp. 373-378. http://dx.doi.org/10.1046/j.1365-2125.2000.00163.x
I. Fukazawa, N. Uchida, E. Uchida and H. Yasuhara, “Effects of Grapefruit Juice on Pharmacokinetics of Atorvastatin and Pravastatin in JAPANESE,” British Journal of Clinical Pharmacology, Vol. 57, No. 4, 2004, pp. 448455. http://dx.doi.org/10.1046/j.1365-2125.2003.02030.x
T. Kantola, K. T. Kivisto and P. J. Neuvonen, “Grapefruit Juice Greatly Increases Serum Concentrations of Lovastatin and Lovastatin Acid,” Clinical Pharmacology & Therapeutics, Vol. 63, No. 4, 1998, pp. 397-402. http://dx.doi.org/10.1016/S0009-9236(98)90034-0
J. J. Lilja, K. T. Kivisto and P. J. Neuvonen, “Grapefruit Juice-Simvastatin Interaction: Effect on Serum Concentrations of Simvastatin, Simvastatin Acid, and HMG-CoA Reductase Inhibitors,” Clinical Pharmacology & Therapeutics, Vol. 64, No. 5, 1998, pp. 477-483. http://dx.doi.org/10.1016/S0009-9236(98)90130-8
J. J. Lilja, M. Neuvonen and P. J. Neuvonen, “Effects of Regular Consumption of Grapefruit Juice on the Pharmacokinetics of Simvastatin,” British Journal of Clinical Pharmacology, Vol. 58, No. 1, 2004, pp. 56-60. http://dx.doi.org/10.1111/j.1365-2125.2004.02095.x
G. C. Yee, D. L. Stanley, L. J. Pessa, T. Dalla Costa, S. E. Beltz, J. Ruiz and D. T. Lowenthal, “Effect of Grapefruit Juice on Blood Cyclosporine Concentration,” Lancet, Vol. 345, No. 8955, 1995, pp. 955-956. http://dx.doi.org/10.1016/S0140-6736(95)90700-9
C. Bistrup, F. T. Nielsen, U. E. Jeppesen and H. Dieperink, “Effect of Grapefruit Juice on Sandimmune Neoral Absorption among Stable Renal Allograft Recipients,” Nephrology Dialysis Transplantation, Vol. 16, No. 2, 2001, pp. 373-377. http://dx.doi.org/10.1093/ndt/16.2.373
G. C. Kane and J. J. Lipsky, “Drug-Grapefruit Juice Interactions,” Mayo Clinic Proceedings, Vol. 75, No. 9, 2000, pp. 933-942. http://dx.doi.org/10.4065/75.9.933
V. A. Eagling, L. Profit and D. J. Back, “Inhibition of the CYP3A4-Mediated Metabolism and P-Glycoprotein-Mediated Transport of the HIV-1 Protease Inhibitor Saquinavir by Grapefruit Juice Components,” British Journal of Clinical Pharmacology, Vol. 48, No. 4, 1999, pp. 543552. http://dx.doi.org/10.1046/j.1365-2125.1999.00052.x
C. A. Dow, S. B. Going, H. H. Chow, B. S. Patil and C. A. Thomson, “The Effects of Daily Consumption of Grapefruit on Body Weight, Lipids, and Blood Pressure in Healthy, Overweight Adults,” Metabolism, Vol. 61, No. 7, 2012, pp. 1026-1035. http://dx.doi.org/10.1016/j.metabol.2011.12.004
K. Fujioka, F. Greenway, J. Sheard and Y. Ying, “The Effects of Grapefruit on Weight and Insulin Resistance: Relationship to the Metabolic Syndrome,” Journal of Medicinal Food, Vol. 9, No. 1, 2006, pp. 49-54. http://dx.doi.org/10.1089/jmf.2006.9.49
C. Dallas, A. Gerbi, G. Tenca, F. Juchaux and F. X. Bernard, “Lipolytic Effect of a Polyphenolic Citrus Dry Extract of Red Orange, Grapefruit, Orange (SINETROL) in Human Body Fat Adipocytes. Mechanism of Action by Inhibition of cAMP-Phosphodiesterase (PDE),” Phytomedicine, Vol. 15, No. 10, 2008, pp. 783-792. http://dx.doi.org/10.1016/j.phymed.2008.05.006
P. J. Mink, C. G. Scrafford, L. M. Barraj, L. Harnack, C. P. Hong, J. A. Nettleton, et al., “Flavonoid Intake and Cardiovascular Disease Mortality: A Prospective Study in Postmenopausal Women,” American Journal of Clinical Nutrition, Vol. 85, No. 3, 2007, pp. 895-909.
J. Mursu, S. Voutilainen, T. Nurmi, T. P. Tuomainen, S. Kurl and J. T. Salonen, “Lavonoid Intake and the Risk of Ischaemic Stroke and CVD Mortality in Middle-Aged Finnish Men: The Kuopio Ischaemic Heart Disease Risk Factor Study,” British Journal of Nutrition, Vol. 100, No. 4, 2008, pp. 890-895. http://dx.doi.org/10.1017/S0007114508945694
O. Benavente-García and J. Castillo, “Update on Uses and Properties of Citrus Flavonoids: New Findings in Anticancer, Cardiovascular, and Anti-Inflammatory Activity,” Journal of Agricultural and Food Chemistry, Vol. 56, No. 15, 2008, pp. 6185-6205. http://dx.doi.org/10.1021/jf8006568
N. M. Borradaile, L. E. de Dreu and M. W. Huff, “Inhibition of Net HepG2 Cell Apolipoprotein B Secretion by the Citrus Flavonoid Naringenin Involves Activation of Phosphatidylinositol 3-Kinase, Independent of Insulin Receptor Substrate-1 Phosphorylation,” Diabetes, Vol. 52, No. 10, 2003, pp. 2554-2561. http://dx.doi.org/10.2337/diabetes.52.10.2554
M. T. Monforte, A. Trovato, S. Kirjavainen, A. M. Forestieri, E. M. Galati and R. B. Lo Curto, “Biological Effects of Hesperidin, a Citrus Flavonoid. (noteII): Hypolipidemic Activity on Experimental Hypercholesterolemia in Rat,” Farmaco, Vol. 50, No. 9, 1995, pp. 595-599.
M. A. Alam, K. Kauter and L. Brown, “Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats,” Nutrients, Vol. 27, No. 5, 2013, pp. 637-650. http://dx.doi.org/10.3390/nu5030637
J. G. Keevil, H. E. Osman, J. D. Reed and J. D. Folts, “Grape Juice, but Not Orange Juice or Grapefruit Juice, Inhibits Human Platelet Aggregation,” Journal of Nutrition, Vol. 130, No. 1, 2000, pp. 53-56.
S. M. Njoroge, H. Koaze, P. N. Karanja and M. Sawamura, “Volatile Constituents of Redblush Grapefruit (Citrus paradisi) and Pummelo (Citrus grandis) Peel Essential Oils from Kenya,” Journal of Agricultural and Food Chemistry, Vol. 53, No. 25, 2005, pp. 9790-9794. http://dx.doi.org/10.1021/jf051373s
K. Nakagawa and T. Goto, “Effects of Ingestion of Grapefruit Juice or Grapefruit on the Hypotensive Effect and Plasma Concentrations of Dihydropyridine Calcium Antagonists (Amlodipine and Nifedipine): A Case Study,” Clinical and Experimental Hypertension, Vol. 32, No. 2, 2010, pp. 71-75. http://dx.doi.org/10.3109/10641960902960540