The use of dietary supplements by cancer patients has risen significantly over the past 2 decades despite insufficient evidence of safety and effectiveness. Finding reliable sources of information about dietary supplements can be daunting. Patients typically rely on family, friends, and the Internet, often receiving misleading information.
The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on complementary therapies commonly used by patients with cancer. We chose turmeric for this issue because of the growing interest in its anticancer potential.
Integrative Oncology is compiled by Barrie R. Cassileth, PhD, Chief of the Integrative Medicine Service and Laurance S. Rockefeller Chair in Integrative Medicine, and Jyothi Gubili, MS, Editor of About Herbs, Memorial Sloan-Kettering Cancer Center. The free About Herbs website and the free About Herbs application are managed by K. Simon Yeung, PharmD, MBA, Lac, Memorial Sloan-Kettering Cancer Center.
Turmeric
Scientific Name: Curcuma longa
Common Names: Indian saffron, curcumin, jiang huang.
Overview
Believed to have originated in India, turmeric is a perennial herb cultivated extensively in Southeast Asia and in many warm regions of the world, with a medicinal history that dates back 5,000 years. It is used in traditional medicine for wound healing, to treat stomach ailments, and to “purify” blood. The rhizome is used as a spice in regional cuisines, and as a coloring agent in food and cosmetics.
In addition to its role as a culinary agent and as a component in Ayurvedic formulations and traditional Chinese medicine, turmeric is under investigation for its therapeutic potential. Following discovery of a wide spectrum of biological effects, turmeric’s potential value in the treatment of several diseases, including cancer, has been widely studied.
Turmeric was the center of a controversy in 1995, when the U.S. Patent and Trademark Office granted a patent to the University of Mississippi Medical Center for use of turmeric as a wound-healing agent.1 The patent, however, was revoked after the Council for Agricultural Research in India disputed the novelty of the work and provided evidence of turmeric’s medicinal use in India since ancient times.
Extracts of turmeric are marketed as dietary supplements to improve memory, for arthritis, and for cancer prevention. Turmeric is also available in the form of ointments and creams for topical use.
It is generally considered safe to consume turmeric. However, data on its interactions with chemotherapy agents are conflicting. Cancer patients should discuss use of turmeric supplements with their physicians.
The Science
Several bioactive compounds from turmeric extracts have been studied in the past few decades. Much of the current investigation centers on curcumin, a water-soluble bioactive constituent.
In vitro studies suggest that curcumin acts as a weak phytoestrogen2 and exhibits neuroprotective,3 anti-inflammatory,4 immunomodulatory,5 and chemopreventive effects.6 Curcumin, its analogs, and liposomal formulations also produce chemo- and radiosensitizing effects.7,8
Epidemiologic data suggest improved cognitive performance in elderly Asians who consume turmeric in the form of curry powder.9 However, curcumin supplementation did not confer the same benefit in patients with Alzheimer’s disease.10
Turmeric may help alleviate the symptoms of irritable bowel syndrome11 and quiescent ulcerative colitis.12 It is safe and equally effective to a nonsteroidal anti-inflammatory drug for the treatment of osteoarthritis of the knee.13
In patients with colorectal cancer, oral curcumin administered during the presurgery waiting period improved cachexia and general health of patients.14 In a phase II trial of oral curcumin in patients with advanced pancreatic cancer, there were no treatment-related toxic effects, and clinically relevant biological activity was seen in two patients despite limited absorption.15 In other early-phase studies, combined administration of curcumin with docetaxel16 and gemcitabine17 was shown to be safe.
Curcumin has estrogenic activity,2 but its effects on breast cancer patients remain unclear. Overall, the use of turmeric for clinical purposes requires further investigation due to its inherent poor absorption, rapid metabolism, complex mechanistic profile, and the current availability of only preliminary, preclinical data.
Adverse Effects
Allergic dermatitis,18 contact urticaria,19 and transient atrioventricular block20 have been reported following intake of curcumin.
Herb-Drug Interactions
Anticoagulants/antiplatelets: Turmeric may increase the risk of bleeding due to its antiplatelet properties.21
Drugs metabolized by cytochrome P450 enzymes: Curcumin inhibits CYP3A4 and CYP1A2 but enhances CYP2A6 enzymes,22,23 altering the metabolism of some prescription drugs.
Camptothecin: Turmeric inhibits camptothecin-induced apoptosis of breast cancer cell lines in vitro.24
Mechlorethamine: Turmeric inhibits mechlorethamine-induced apoptosis of breast cancer cell lines in vitro.24
Doxorubicin: Turmeric inhibits doxorubicin-induced apoptosis of breast cancer cell lines in vitro.24
Cyclophosphamide: Dietary turmeric inhibits cyclophosphamide-induced tumor regression in animal studies.24
Norfloxacin: Pretreatment with curcumin results in increased plasma elimination half-life, thereby reducing the dosage of norfloxacin.25
Amphotericin B: Curcumin may enhance the effect and decrease the toxicity of amphotericin B.26
Midazolam: Curcumin downregulates intestinal P-glycoprotein levels, thereby increasing the concentration of midazolam.27
Verapamil: Curcumin inhibits intestinal P-glycoprotein expression and function, thereby increasing the concentration of verapamil.28 ■
Disclosure: Drs. Cassileth and Yeung and Ms. Gubili reported no potential conflicts of interest.
References
1. Kumar S: India wins battle with USA over turmeric patent. Lancet 350:724, 1997.
2. Bachmeier BE, Mirisola V, Romeo F, et al: Reference profile correlation reveals estrogen-like trancriptional activity of Curcumin. Cell Physiol Biochem 26:471-482, 2010.
3. Cemil B, Topuz K, Demircan MN, et al: Curcumin improves early functional results after experimental spinal cord injury. Acta Neurochir (Wien) 152:1583-1590, 2010.
4. Yun JM, Jialal I, Devaraj S: Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. J Nutr Biochem 22:450-458, 2011.
5. Jantan I, Bukhari SN, Lajis NH, et al: Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes. J Pharm Pharmacol 64:404-412, 2012.
6. Chang KW, Hung PS, Lin IY, et al: Curcumin upregulates insulin-like growth factor binding protein-5 (IGFBP-5) and C/EBPalpha during oral cancer suppression. Int J Cancer 127:9-20, 2010.
7. Selvendiran K, Ahmed S, Dayton A, et al: HO-3867, a curcumin analog, sensitizes cisplatin-resistant ovarian carcinoma, leading to therapeutic synergy through STAT3 inhibition. Cancer Biol Ther 12:837-845, 2011.
8. Qiao Q, Jiang Y, Li G: Curcumin improves the antitumor effect of X-ray irradiation by blocking the NF-kappaB pathway: An in-vitro study of lymphoma. Anticancer Drugs 23:597-605, 2012.
9. Ng TP, Chiam PC, Lee T, et al: Curry consumption and cognitive function in the elderly. Am J Epidemiol 164:898-906, 2006.
10. Baum L, Lam CW, Cheung SK, et al: Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 28:110-113, 2008.
11. Bundy R, Walker AF, Middleton RW, et al: Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: A pilot study. J Altern Complement Med 10:1015-1018, 2004.
12. Hanai H, Iida T, Takeuchi K, et al: Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clinical Gastroenterol Hepatol 4:1502-1506, 2006.
13. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, et al: Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med 15:891-897, 2009.
14. He ZY, Shi CB, Wen H, et al: Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest 29:208-213, 2011.
15. Dhillon N, Aggarwal BB, Newman RA, et al: Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 14:4491-4499, 2008.
16. Bayet-Robert M, Kwiatkowski F, Leheurteur M, et al: Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther 9:8-14, 2010.
17. Epelbaum R, Schaffer M, Vizel B, et al: Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 62:1137-1141, 2010.
18. Lamb SR, Wilkinson SM: Contact allergy to tetrahydrocurcumin. Contact Dermatitis 48:227, 2003.
19. Liddle M, Hull C, Liu C, et al: Contact urticaria from curcumin. Dermatitis 17:196-197, 2006.
20. Lee SW, Nah SS, Byon JS, et al: Transient complete atrioventricular block associated with curcumin intake. Int J Cardiol 150(2):e50-2, 2011.
21. Prakash P, Misra A, Surin WR, et al: Anti-platelet effects of Curcuma oil in experimental models of myocardial ischemia-reperfusion and thrombosis. Thromb Res 127:111-118, 2011.
22. Zhang W, Lim LY: Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro. Drug Metab Dispos 36:1283-1290, 2008.
23. Chen Y, Liu WH, Chen BL, et al: Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers. Ann Pharmacother 44:1038-1045, 2010.
24. Somasundaram S, Edmund NA, Moore DT, et al: Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 62:3868-3875, 2002.
25. Pavithra BH, Prakash N, Jayakumar K: Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits. J Vet Sci 10:293-297, 2009.
26. Kudva AK, Manoj MN, Swamy, BM, et al: Complexation of amphotericin B and curcumin with serum albumins: Solubility and effect on erythrocyte membrane damage. J Exp Pharmacol 3:1-6, 2011.
27. Zhang W, Tan TM, Lim LY: Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos 35:110-115, 2007.
28. Hou XL, Takahashi K, Tanaka K, et al: Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. Int J Pharm 358(1-2):224-229, 2008.
