- Curcumin is a constituent of turmeric (rhizomes of Curcuma longa), known as an Indian spice and food colouring agent.
- Currently there is insufficient evidence to support the effectiveness and efficacy of curcumin in the prevention or treatment of cancer.
- Based on the traditional use of turmeric and dose escalation studies, curcumin can be regarded as safe.
Curcumin or diferuloylmethane is the major constituent and the active component in the spice turmeric (rhizomes of Curcuma longa), a herb belonging to the ginger family (Zingiberaceae). Curcumin is claimed to have anticancer properties and to be chemopreventive. It has been suggested to have beneficial effects both as monotherapy and in combination with existing therapies.
There are currently insufficient data available to support the effectiveness and efficacy of curcumin for cancer due to lack of double-blind, randomized clinical trials. Mostly preliminary findings from small and uncontrolled studies are available.
Turmeric, containing curcumin, is generally regarded as safe by the US Food and Drug Administration (FDA). As for curcumin itself, epidemiological evidence and several clinical trials confirm the safety of curcumin up to 12 g per day over a period of several months. The most frequently reported adverse effects in clinical trials are peripheral neuropathies.
Summary fully revised and updated in April 2014 by Klara Rombauts.
Summary first published in May 2012 authored by Klara Rombauts and Liene Dhooghe.
Klara Rombauts, Liene Dhooghe, CAM-Cancer Consortium. Curcumin [online document]. May 7, 2014.
Scientific name(s), brand name(s), common name(s)
Curcumin or diferuloylmethane is the major constituent and active component in the Indian spice turmeric (rhizomes of Curcuma longa). Turmeric belongs to the ginger family or Zingiberaceae1. It is also known as Indian saffron, jiang huang, haridra, haldi, as the major ingredient of curry powder2 and as a bright yellow-orange food colouring agent (E100).
Numerous commercial products containing Curcuma longa extract are available. The activity of these preparations mainly depends on the content of curcumin.
Curcumin or diferuloylmethane [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the main constituent of Curcuma longa. Other constituents are the curcuminoids demethoxycurcumin and bisdemethoxycurcumin, in addition to volatile oils, sugars, proteins, and resins3.
Application and dosage
Although oral administration is the most common way of taking this spice, poor water solubility, short biological half-life (rapid metabolisation and elimination) and low bioavailability of curcumin limits its potential effect4-5. Doses ranging from 0.5 g up to 12 g per day have been used in clinical studies or trials. Even at high doses (up to 12 g per day) only minimal toxicity was observed6-7. For these reasons, different approaches have been investigated: development of curcumin analogues8; the use of adjuvants such as piperine to improve the bioavailability9; the development of liposomes10 and phospholipid complexes11 in order to improve oral bioavailability, and even nanoparticles in order to allow parental administration12. A report refers to the topical application of a curcumin ointment in patients with breast cancer13.
Besides the use of turmeric in Indian cooking, it has been used for centuries in Indian traditional medicine (Ayurveda) in the treatment of a variety of illnesses, such as infections of the bile duct, gall bladder, liver and inflammatory diseases14. Curcumin was first isolated in 1815 and its chemical structure was determined in 1910. In 1937 the use of curcumin in biliary diseases was documented and in 1949 antibacterial properties were reported. In 1972 the use of curcumin for the treatment of diabetes was demonstrated1. Since then, the number of reports on pharmacological effects of curcumin increased rapidly15. Although the Indian traditional medicine describes turmeric as a cancer remedy, the first scientific trials were not carried out until 198516.
Claims of efficacy / Mechanism(s) of action / Alleged indication(s)
Curcumin has been claimed to have therapeutic properties in the treatment of a broad variety of cancers, including leukemia, lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers and sarcoma13.
Curcumin is a potent scavenger of reactive oxygen species (ROS), protecting lipids, hemoglobin and DNA against oxidative degradation. In addition, it inhibits ROS-generating enzyme cyclooxygenase and lipoxygenase. Curcumin has shown to inhibit chemical carcinogenesis in different tissues, and it induces apoptosis in several tumor cell lines. The underlying mechanisms of the cancer chemopreventive properties of curcumin are: suppression of c-jun and c-fos expression; inhibition of protein kinase C (PKC) and epidermal growth factor receptor (EGFR) tyrosine kinase; suppression of colonic aberrant crypt foci through inhibiting inducible nitric oxide synthase (iNOS); inhibition of cyclo oxygenase-2 (COX-2) in bile acid and cells treated with phorbol-12-myristate-13-acetate (PMA); inhibition of xanthine oxidase; modulation of Ca+2 and cellular p53 protein; reduction of estrogen receptor positive and progesterone receptor positive mammary tumor; induction of phase-2 detoxification enzymes; suppression of hepatocellular carcinoma invasion by inhibiting matrix metallopeptidase 9 (MMP-9)17.
Also enhancement of the apoptotic process (e.g. by inducing mitochondrial damage18 and anti-angiogenic properties (by inhibiting the vascular endothelial growth factor (VEGF)19 are reported. The potent anti-proliferative activity potentiates other anti-tumor drugs such as gemcitabine20. Curcumin works as a chemosensitizer and radiosensitizer by downregulating various growth regulatory pathways and specific genetic targets, including genes for nuclear factor of B cells (NF-B), signal transducer and activator of transcription 3 (STAT-3), cyclooxygenase 2, protein kinase Akt, antiapoptotic proteins, growth factor receptors, and multidrug-resistance proteins2.
The epigenetic property of curcumin is based on its interaction with histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and microRNAs21.
Several articles are available on the potential anticancer properties of curcumin. They include chemoprevention, treatment of cancer as monotherapy and in combination with existing anticancer medicines.
Prevalence of use
There is no information available on the prevalence of use of curcumin as an anticancer agent.
Curcumin is sold all over the world in supermarkets as an ingredient of turmeric.
Cost(s) and expenditures
It is possible to purchase curcumin products containing 95% curcumin over the internet, at about US$12 to US$36, depending on the dose (between 400 and 600 mg) and the amount of capsules (ranging from 60 to 180).
Several clinical trials explore the use of curcumin as a preventive or therapeutic agent, mostly with promising results. Most trials are, however, rather small and early phase, and very few controlled trials are available42.
Until now the most trials have been performed using curcumin as a chemopreventive agent, especially for the prevention of gastrointestinal cancers. As a therapeutic agent, most trials are performed using curcumin in combination with chemotherapy. It seems that curcumin is the most promising when used in combination with conventional therapy although this is a very preliminary conclusion which needs to be confirmed.
Clinical trials performed with curcumin as monotherapy are the least successful, probably due to the low bioavailability of curcumin itself. Several efforts to improve this low availability are currently ongoing.
For a description of included controlled clinical trials please see table 1.
Two randomized clinical trials are available. One including 82 patients with ulcerative colitis showed significantly lower relapse rates for patients receiving standard treatment with 2g of curcumin compared to standard treatment with placebo22. Reduced DNA damage and antioxidant activitiy were observed in 286 healthy volunteers chronically exposed to arsenic who received 1 g curcumin daily compared to placebo27.
Epidemiological data show that the incidence of several types of cancer is low in populations consuming curcumin at levels of about 100-200 mg per day over long periods of time15. Uncontrolled trials suggest a decrease of the number of aberrant crypt foci in 41 smokers receiving 4g but not 2g or curcumin daily25, a biological effect of curcumin in 25 patients with high-risk or pre-malignant lesions in different organs 7 and an arrest or regression of cervical low-grade squamous intraepithelial neoplasia and a reduction in circulating IL-6 levels by a curcumin extract (NBFR-3) in 21 women47.
Four controlled clinical trials are available43,29,44,46, two thereof are randomized43,29, These trials are mostly small with short term follow up, use different curcumin preparations with different bioavailability and include different types of cancer. All of these are major limitations so no firm conclusions can be made about the efficacy of curcumin in the treatment of cancer at this point.
Reduced radiation dermatitis was reported in an RCT of 30 breast cancer patients receiving 6g oral curcumin daily compared with placebo43. Body weight gain, reduced serum levels of TNF-α and an increase in cancer cell apoptosis were reported in an RCT of 126 colorectal cancer patients receiving 360mg oral curcumin or placebo29. Adverse effects of chemotherapy and radiotherapy in 160 cancer patients were improved in those receiving a curcumin-phospholipid complex with improved bioavailability (1.5g Meriva) compared to those receiving placebo44. Nitric oxide levels were significantly decreased in 50 patients with chronic myeloid leukaemia receiving 15g imatinib and turmeric powder daily compared to imatinib alone46.
Uncontrolled clinical trials
One uncontrolled clinical trial is available evaluating the topical application of a curcumin ointment in 62 patients with locally recurrent ulcerating tumors. Positive responses were reduction of smell, relief of itching, drying of the exudates, relief of pain, or reduction in the lesion size (10%)30.
Adverse effects / toxicity
Turmeric, containing curcumin, is generally regarded as safe (GRAS) by the FDA. Several phase I/II trials report curcumin to be safe in doses of 8g7,33,34,35, taken for a period of up to 18 months26, and in high doses of up to 12g for 3 months3,6.
The safety and pharmacokinetics of Theracurmin, a curcumin formulation with improved bioavailability, was investigated in ten cancer patients. Adding Theracurmin to gemcitabine did not increase the incidence of adverse effects48.
Existing data do not show any risk concerning contraindications. There is, however, a potential risk during pregnancy. It was noted that curcumin can exhibit some blood-thinning properties such as suppression of platelet aggregation, although it remains to be established whether it interacts in any way with blood-thinning drugs36.
Curcumin has been suggested to improve the oral bioavailability and therapeutic efficacy of paclitaxel (administered in nanoemulsions) in ovarian adenocarcinoma in mice37, of etoposide after oral but not intravenous administration in rats38 and docetaxel in combination with a curcumin self-emulsifying drug delivery system in rats39. These interactions are explained by inhibition of P-glycoprotein and intestinal CYP3A enzyme38,39, although this effect was not found in vitro in an intestinal cell culture model41.
Curcumin has been reported to inhibit CYP1A2 function but enhance CYP2A6 activity in healthy, male Chinese volunteers40. Since many drugs are metabolized by CYP-enzymes, it is very important to acknowledge that curcumin could alter the efficacy of regular drugs.
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- Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer 2010;62(7):919-30.
- Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 2009 Jun;14(2):141-53.
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- Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 2006;6:10.
- Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001 Jul;21(4B):2895-900.
- Liang G, Shao L, Wang Y, Zhao C, Chu Y, Xiao J, et al. Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. Bioorg Med Chem 2009 Mar 15;17(6):2623-31.
- Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998 May;64(4):353-6.
- Takahashi M, Uechi S, Takara K, Asikin Y, Wada K. Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. J Agric Food Chem 2009 Oct 14;57(19):9141-6.
- Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin-phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm 2007 Feb 7;330(1-2):155-63.
- Gao Y, Li Z, Sun M, Li H, Guo C, Cui J, et al. Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as stabilizer. Drug Dev Ind Pharm 2010 Oct;36(10):1225-34.
- Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett 2008 Aug 18;267(1):133-64.
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- Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009 Jan;41(1):40-59.
- Kuttan R, Bhanumathy P, Nirmala K, George MC. Potential anticancer activity of turmeric (Curcuma longa). Cancer Lett 1985 Nov;29(2):197-202.
- Lin JK, Lin-Shiau SY. Mechanisms of cancer chemoprevention by curcumin. Proc Natl Sci Counc Repub China B 2001 Apr;25(2):59-66.
- Li ZX, Ouyang KQ, Jiang X, Wang D, Hu Y. Curcumin induces apoptosis and inhibits growth of human Burkitt's lymphoma in xenograft mouse model. Mol Cells 2009 Mar 31;27(3):283-9.
- Lu B, Yu L, Xu L, Chen H, Zhang L, Zeng Y. The effects of radix curcumae extract on expressions of VEGF, COX-2 and PCNA in gastric mucosa of rats fed with MNNG. Curr Pharm Biotechnol 2010 Apr;11(3):313-7.
- Bar-Sela G, Epelbaum R, Schaffer M. Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem 2010;17(3):190-7.
- Fu S, Kurzrock R. Development of curcumin as an epigenetic agent. Cancer 2010 Oct 15;116(20):4670-6.
- Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, Andoh A, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006 Dec;4(12):1502-6.
- Garcea G, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, et al. Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer 2004 Mar 8;90(5):1011-5.
- Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev 2005 Jan;14(1):120-5.
- Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011 Mar;4(3):354-64.
- Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci 2005 Nov;50(11):2191-3.
- Biswas J, Sinha D, Mukherjee S, Roy S, Siddiqi M, Roy M. Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal. Hum Exp Toxicol 2010 Jun;29(6):513-24.
- Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 2004 Oct 15;10(20):6847-54.
- He ZY, Shi CB, Wen H, Li FL, Wang BL, Wang J. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest 2011 Mar;29(3):208-13.
- Kuttan R, Sudheeran PC, Josph CD. Turmeric and curcumin as topical agents in cancer therapy. Tumori 1987 Feb 28;73(1):29-31.
- Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 2008 Jul 15;14(14):4491-9.
- Ide H, Tokiwa S, Sakamaki K, Nishio K, Isotani S, Muto S, et al. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate 2010 Jul 1;70(10):1127-33.
- Bayet-Robert M, Kwiatkowski F, Leheurteur M, Gachon F, Planchat E, Abrial C, et al. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther 2010 Jan;9(1):8-14.
- Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S, et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol 2011 Jul;68(1):157-64.
- Epelbaum R, Schaffer M, Vizel B, Badmaev V, Bar-Sela G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 2010;62(8):1137-41.
- Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol 2008 Feb 15;75(4):787-809.
- Ganta S, Devalapally H, Amiji M. Curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of Paclitaxel upon administration in nanoemulsion formulation. J Pharm Sci 2010;99(11): 4630-4641.
- Lee C, Ki S, Choi J. Effects of oral curcumin on the pharmacokinetics of intravenous and oral etoposide in rats: possible role of intestinal CYP3A and P-gp inhibition by curcumin. Biopharm Drug Dispos 2011;32:245-251.
- Yan Y, Marasini N, Choi Y, Kim J, Woo J et al. Effect of dose and dosage interval on the oral bioavailability of docetaxel in combination with a curcumin self-emulsifying drug delivery system (SEDDS). Eur J Drug Metab Pharmacokinet 2011 [Epub ahead of print].
- Chen Y, Liu W, Chen B, Fan L, Han Y et al. Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers. Ann Pharmacother 2010;44:1038-45.
- Graber-Maier A, Büter K, Aeschlimann J, Bittel C, Kreuter M, et al. Effects of curcuma extracts and curcuminoids on expression of P-glycoprotein and cytochrome P450 3A4 in the intestinal cell culture model LS180. Planta Med 2010;76:1864-1866.
- Schaffer M, Schaffer PM, Zidan J, Bar Sela G. Curcuma as a functional food in the control of cancer and inflammation. Curr Opin Clin Nutr Metab Care 2011; 14: 588-97.
- Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, Morrow GR. Curcumin for radiation dermatitis: A randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiation Research 2013;180:34-43
- Belcaro G, Hosoi M, Pellegrini L, et al. A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment. 2014 Mar; 28:444-50.
- Golombick T, Diamond T, Manoharan A, Ramakrishna R. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: A randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study. Am J Hematol 2012;87:455-60.
- Ghalaut VS, Sangwan L, Dahiya K, Ghalaut PS, Dhankhar R, Saharan R. Effect of imatinib therapy with and without turmeric powder on nitric oxide levels in chronic myeloid leukemia. J Oncol Pharm Pract 2012;18:186-90.
- Joshi JV, Paradkar PH, Jagtap SS, Agashe SV, Soman G, and Vaidya AB. Chemopreventive potential and safety profile of a curcuma longa extract in women with cervical low-grade squamous intraepithelial neoplasia. Asian Pacific J Cancer Prev 2011;12:3305-11.
- Kanai M, Otsuka Y, Otsuka K, et al. A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin®) in cancer patients. Cancer Chemother Pharmacol 2013;71:1521-30.