D-limonene: Safety and clinical applications

Alternative Medicine Review

Volumn 12, Issue 3, 2007, Pages 259-264

  Sun, Jidong ^a,b  

^a UNIVERSITY OF NEBRASKA LINCOLN   (United States)

^b Thorne Research Incorporated   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM OXIDE; CITRUS OIL; FLAVORING AGENT; LIMONENE; PLACEBO; TERPENE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; BEVERAGE; BREAST CANCER; CANCER; CANCER RISK; CARCINOGEN TESTING; CLINICAL EFFECTIVENESS; COLORECTAL CANCER; DIARRHEA; DRUG ABSORPTION; DRUG CAPSULE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG RESPONSE; DRUG SAFETY; DRUG STRUCTURE; FRUIT JUICE; GALLSTONE DISSOLUTION; GASTROESOPHAGEAL REFLUX; GRAPEFRUIT; HEARTBURN; HUMAN; ICE CREAM; IMMUNOMODULATION; LEMON; LETHARGY; MANDARIN; MUTAGEN TESTING; NAUSEA; NEPHROTOXICITY; NONHUMAN; ORANGE (FRUIT); REPEATED DRUG DOSE; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; TREATMENT RESPONSE; VOMITING; WEIGHT REDUCTION;

ANIMALS; ANTICARCINOGENIC AGENTS; CYCLOHEXENES; FEMALE; GALLSTONES; GASTROESOPHAGEAL REFLUX; HUMANS; LETHAL DOSE 50; MALE; MICE; RATS; SOLVENTS; SWINE; TERPENES;

EID: 35348929897     PISSN: 10895159     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (34)

1. No authors listed. Limonene monograph. Cri Rev Food Sci Nutr 1999;39:260-265.
2. The United States Code of the Federal Regulations, Title 21, Part 182.60.
3. Flavor and Extract Manufacturers' Association D-Limonene Monograph, 1-4, Flavor and Extract Manufacturers' Association; Washington, DC: 1991.
4. Hakim IA, Harris RB, Ritenbaugh C. Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin. Nutr Cancer 2000;37:161-168.
5. Igimi H, Nishimura M, Kodama R, Ide H. Studies on the metabolism of d-limonene (p-mentha-1,8-diene). I. The absorption, distribution and excretion of d-limonene in rats. Xenobiotica 1974;4:77-84.
6. Kodama R, Yano T, Furukawa K, et al. Studies on the metabolism of d-limonene (p-mentha-1,8-diene). IV. Isolation and characterization of new metabolites and species differences in metabolism. Xenobiotica 1976;6:377-389.
7. Crowell PL, Lin S, Vedejs E, Gould MN. Identification of metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth. Cancer Chemother Pharmacol 1992;31:205-212.
8. Vigushin DM, Poon GK, Boddy A, et al. Phase I and pharmacokinetic study of d-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. Cancer Chemother Pharmacol 1998;42:111-117.
9. Crowell PL, Elson CE, Bailey HH, et al. Human metabolism of the experimental cancer therapeutic agent d-limonene. Cancer Chemother Pharmacol 1994;35:31-37.
10. Poon GK, Vigushin D, Griggs LJ, et al. Identification and characterization of limonene metabolites in patients with advanced cancer by liquid chromatography/ mass spectrometry. Drug Metab Dispos 1996;24:565-571.
11. Chow HH, Salazar D, Hakim IA. Pharmacokinetics of perillic acid in humans after a single dose administration of a citrus preparation rich in d-limonene content. Cancer Epidemiol Biomarkers Prev 2002;11:1472-1476.
12. No authors listed. D-limonene. IARC Monogr Eval Carcinog Risk Chem Hum 1999;73:307-327.
13. Igimi H, Watanabe D, Yamamoto F, et al. A useful cholesterol solvent for medical dissolution of gallstones. Gastroenterol Jpn 1992;27:536-545.
14. Igimi H, Hisatsugu T, Nishimura M. The use of d-limonene preparation as a dissolving agent of gallstones. Am J Dig Dis 1976;21:926-939.
15. National Toxicology Program. Toxicology and Carcinogenesis Studies of d-Limonene (CAS No. 5989-27-5) in F344/N Rats and B6C3F1 Mice. http://ntp. niehs.nih.gov/index.cfm?objectid=07086449-9787-5414-556E052773467BE9. [Accessed July 11, 2007]
16. Whysner J, Williams GM. D-limonene mechanistic data and risk assessment: absolute species-specific cytotoxicity, enhanced cell proliferation, and tumor promotion. Pharmacol Ther 1996;71:127-136.
17. Turner SD, Tinwell H, Piegorsch W, et al. The male rat carcinogens limonene and sodium saccharin are not mutagenic to male big blue rats. Mutagenesis 2001;16:329-332.
18. Igimi H, Tamura R, Toraishi K, et al. Medical dissolution of gallstones. Clinical experience of d-limonene as a simple, safe, and effective solvent. Dig Dis Sci 1991;36:200-208.
19. Wilkins J Jr. Method for treating gastrointestinal disorder. U.S. Patent (642045). 2002.
20. Lis-Balchin M, Ochocka RJ, Deans SG, et al. Bioactivity of the enantiomers of limonene. Med Sci Res 1996;24:309-310.
21. Elegbede JA, Elson CE, Qureshi A, et al. Inhibition of DMBA-induced mammary cancer by the monoterpene d-limonene. Carcinogenesis 1984;5:661-664.
22. Elson CE, Maltzman TH, Boston JL, et al. Anti-carcinogenic activity of d-limonene during the initiation and promotion/ progression stages of DMBA-induced rat mammary carcinogenesis. Carcinogenesis 1988;9:331-332.
23. Maltzman TH, Hurt LM, Elson CE, et al. The prevention of nitrosomethylurea-induced mammary tumors by d-limonene and orange oil. Carcinogenesis 1989;10:781-783.
24. Wattenberg LW. Inhibition of neoplasia by minor dietary constituents. Cancer Res 1983;43:2448S-2453S.
25. Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999;129:775S-778S.
26. Uedo N, Tatsuta M, Iishi H, et al. Inhibition by d-limonene of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats. Cancer Lett 1999;137:131-136.
27. Yano H, Tatsuta M, Iishi H, et al. Attenuation by d-limonene of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N′-nitro-N- nitrosoguanidine in Wistar rats. Int J Cancer 1999;82:665-668.
28. Dietrich DR, Swenberg JA. The presence of alpha 2u-globulin is necessary for d-limonene promotion of male rat kidney tumors. Cancer Res 1991;51:3512-3521.
29. Wattenberg LW, Sparnins VL, Barany G. Inhibition of N-nitrosodiethylamine carcinogenesis in mice by naturally occurring organosulfur compounds and monoterpenes. Cancer Res 1989;49:2689-2692.
30. Wattenberg LW, Coccia JB. Inhibition of 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone carcinogenesis in mice by d-limonene and citrus fruit oils. Carcinogenesis 1991;12:115-117.
31. Van der Logt EM, Roelofs HM, van Lieshout EM, et al. Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases. Anticancer Res 2004;24:843-849.
32. Giri RK, Parija T, Das BR. D-limonene chemoprevention of hepatocarcinogenesis in AKR mice: inhibition of c-jun and c-myc. Oncol Rep 1999;6:1123-1127.
33. Kaji I, Tatsuta M, Iishi H, et al. Inhibition by d-limonene of experimental hepatocarcinogenesis in Sprague-Dawley rats does not involve p21(ras) plasma membrane association. Int J Cancer 2001;93:441-444.
34. Del Toro-Arreola S, Flores-Torales E, Torres-Lozano C, et al. Effect of d-limonene on immune response in BALB/c mice with lymphoma. Int Immunopharmacol 2005;5:829-838.