Curcumin (Curcuma, Turmeric) and Cancer (PDQ®): Integrative, alternative, and complementary therapies - Health Professional Information [NCI]

Overview

This cancer information summary provides an overview of the use of curcumin as a treatment for people with cancer.

This summary contains the following key information:

• Curcumin (diarylheptanoid) is one member of a group of natural compounds called curcuminoids, derived from the rhizome of Curcuma longa, an East Indian plant, contained in an extract commonly called turmeric.
• Turmeric has a long history of therapeutic application in traditional Asian medicine.
• Extensive research over the past two decades suggests that curcuminoids, the active ingredient in turmeric (C. longa), interfere with multiple cell signaling pathways, providing support for the potential role of curcumin in modulating cancer development and progression.
• With varying formulations and doses tested in phase I clinical trials, there is evidence of bioavailability of curcumin and curcumin conjugates in plasma, urine, and tissue.
• Results from early-phase trials of curcumin-containing products in the chemoprevention of colon, oral, and hepatic carcinoma appear promising. However, the findings from these early trials have to be confirmed in well-powered trials evaluating safety and effectiveness as indicated by modulation of clinical outcomes.
• Data from early-phase trials of the safety and effectiveness of curcumin-containing products in cancer treatment are at most from pilot trials that targeted various stages of cancer and cancer patient populations, and utilized different formulations and doses of curcumin and durations of intervention. Thus, the evidence is currently inadequate to recommend curcumin-containing products for the treatment of cancer.
• Data from early-phase trials of the safety and effectiveness of curcumin-containing products as adjuncts to traditional cancer therapies are from pilot trials that had small sample sizes, targeted various stages of cancer and cancer patient populations, and utilized different formulations and doses of curcumin and durations of intervention. Thus, the evidence is currently inadequate to recommend curcumin-containing products to be used as adjuncts for the treatment of cancer.
• Data from early-phase trials on the use of curcumin formulations to ameliorate cancer treatment–related effects have demonstrated (a) improved oxidative status in patients who received chemotherapy and radiation therapy, (b) delayed onset and severity of mucositis, (c) reduced severity of radiation dermatitis and (d) improved quality of life, without adverse effects with curcumin-containing products at these doses. However, these studies were short in duration and used varying doses and formulations of curcumin. Thus, these results should be interpreted with caution. The findings from these early trials have to be confirmed in well-powered trials evaluating safety or effectiveness.

General Information and History

Curcumin is a member of the diarylheptanoid class of natural products (curcuminoids) derived from the rhizome of Curcuma longa L., an East Indian plant, commonly called turmeric. The other major curcuminoids present in turmeric are demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin; together, they are termed the curcuminoid complex. The turmeric plant and preparations derived from it have a long history of therapeutic application in traditional Asian medicine. The crude and often dried plant material is widely consumed as a food additive, as part of curry spices, which typically contain numerous other ingredients. Turmeric and its preparations also have a long history of use as herbal medicines and dietary supplements, primarily to treat various inflammatory disorders.

Significant confusion exists in the scientific biomedical literature, as well as the popular literature, about the meaning of curcumin. Consequently, one group has developed a classification scheme that is described below.[1]

Several companies distribute curcumin as a dietary supplement. In the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. The quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements. The FDA can remove dietary supplements from the market that are deemed unsafe. Because dietary supplements are not formally reviewed for manufacturing consistency every year, ingredients may vary considerably from lot to lot. In addition, there is no guarantee that ingredients claimed on product labels are present at all or are present in the specified amounts. The FDA has not approved the use of curcumin as a treatment for cancer or any other medical condition.

Categories of Curcumin-type Products

The materials that have received the moniker curcumin may be divided into five categories:

1. Turmeric (T): Raw C. longa rhizomes.
2. Turmeric extract (TE): A solvent extract of dried or fresh C. longa rhizomes.
3. Curcuminoids-enriched turmeric extract (CTE): Typically the deep-yellow precipitate collected from the solvent extract upon concentration under reduced temperature.
4. Curcuminoids-enriched material (CEM): Obtained by additional, often large-scale, chromatographic purification of CTE.
5. Curcumin (CUR): A single-chemical entity, in a purity that is commensurate with that of a validated and/or metrological reference material.

It is important to note that materials often referred to as curcumin are not identical to the pure, single-chemical entity. Because of the deficiency in the adequate chemical characterization of the immense diversity of crude turmeric (T), extracts (CE), enriched materials (CTE, CEM), and even materials considered pure, augmented by the fact that the materials often share the same name (curcumin), the usefulness of the biological data acquired from the plethora of these preparations is questionable.[1] Furthermore, attributing biological activity of a complex mixture solely to the major component, however prominent, is problematic.[2]

This summary refers to all turmeric-derived intervention materials by using the collective term, curcumin-containing products. Tables at the end of each section specify the exact intervention material used in each cited study.

References:

1. Nelson KM, Dahlin JL, Bisson J, et al.: The Essential Medicinal Chemistry of Curcumin. J Med Chem 60 (5): 1620-1637, 2017.
2. Pauli GF, Chen SN, Friesen JB, et al.: Analysis and purification of bioactive natural products: the AnaPurNa study. J Nat Prod 75 (6): 1243-55, 2012.

Laboratory / Preclinical Studies

Extensive research over the past two decades suggests that curcuminoids belonging to the diferuloylmethane class of natural products, the major constituents in turmeric (Curcuma longa), interfere with multiple cell signaling pathways, which provides support for the potential role of curcumin in modulating carcinogenesis. These pathways include the following:[1,2,3,4,5,6,7,8,9,10,11,12]

• Cell cycle (cyclin D1 and cyclin E).
• Apoptosis (activation of caspases and down-regulation of antiapoptotic gene products).
• Proliferation (human epidermal growth factor receptor-2 [HER-2], epidermal growth factor receptor [EGFR], and activating protein-1 [AP-1]).
• Survival (phosphoinositide 3-kinase [PI3K]/protein kinase B [AKT]) invasion (matrix metallopeptidase-9 [MMP-9] and adhesion molecules).
• Angiogenesis (vascular endothelial growth factor [VEGF]).
• Metastasis (CXC-chemokine receptor-4 [CXCR-4]).
• Inflammation (nuclear factor-kappa B [NF-kappa B], tumor necrosis factor [TNF], interleukin- 1 [IL-1], interleukin-8 [IL-8], interleukin-12 [IL-12], cyclooxygenase-2 [COX-2], and 5-lipoxygenase [5-LOX]).

While these reports can possibly provide support for the potential role of curcumin-containing products in modulating carcinogenesis, definitive conclusions cannot be made, especially in light of the widespread confusion and/or misconception regarding the chemical nature of curcumin-containing products outlined above.

Because of the abundance of in vitro and preclinical studies in the past two decades, there has been a significant increase in the number of clinical trials investigating the therapeutic potential of curcumin-containing products. These clinical trials have used varying formulations and doses of curcuminoids for the prevention and treatment of cancer and to ameliorate symptoms of cancer treatment. This summary will focus on the bioavailability, safety, and effectiveness of curcumin-containing products reported in clinical trials that targeted individuals at high risk of cancer and cancer patients for the prevention and treatment of cancer and ameliorating the symptoms of cancer treatment.

References:

1. Alexandrow MG, Song LJ, Altiok S, et al.: Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev 21 (5): 407-12, 2012.
2. Panahi Y, Darvishi B, Ghanei M, et al.: Molecular mechanisms of curcumins suppressing effects on tumorigenesis, angiogenesis and metastasis, focusing on NF-κB pathway. Cytokine Growth Factor Rev 28: 21-9, 2016.
3. Cho JW, Lee KS, Kim CW: Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. Int J Mol Med 19 (3): 469-74, 2007.
4. Pal S, Bhattacharyya S, Choudhuri T, et al.: Amelioration of immune cell number depletion and potentiation of depressed detoxification system of tumor-bearing mice by curcumin. Cancer Detect Prev 29 (5): 470-8, 2005.
5. Sehgal A, Kumar M, Jain M, et al.: Synergistic effects of piperine and curcumin in modulating benzo(a)pyrene induced redox imbalance in mice lungs. Toxicol Mech Methods 22 (1): 74-80, 2012.
6. Dance-Barnes ST, Kock ND, Moore JE, et al.: Lung tumor promotion by curcumin. Carcinogenesis 30 (6): 1016-23, 2009.
7. Moghaddam SJ, Barta P, Mirabolfathinejad SG, et al.: Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice. Carcinogenesis 30 (11): 1949-56, 2009.
8. Lee JC, Kinniry PA, Arguiri E, et al.: Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. Radiat Res 173 (5): 590-601, 2010.
9. Sharma RA, Euden SA, Platton SL, et al.: Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10 (20): 6847-54, 2004.
10. Cheng AL, Hsu CH, Lin JK, et al.: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21 (4B): 2895-900, 2001 Jul-Aug.
11. Carroll RE, Benya RV, Turgeon DK, et al.: Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 4 (3): 354-64, 2011.
12. Aggarwal BB, Kumar A, Bharti AC: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23 (1A): 363-98, 2003 Jan-Feb.

Human / Clinical Studies

Bioavailability of Curcumin-Containing Products (Phase I Clinical Trials)

At least six phase I clinical trials of curcumin -containing products have investigated the pharmacokinetics and pharmacodynamics of pure curcumin (CUR) alone in humans. These studies have shown that systemic exposure to curcumin-containing products at doses of up to 8,000 mg /day was safe and tolerable and did not cause serious adverse events. In these studies, the peak serum concentrations ranged from 47 ng/mL (at a dose of 200 mg of oral curcumin daily) to 1,380 ng/mL (at a dose of 8,000 mg of oral curcumin daily).[1,2,3,4,5,6]

These concentrations refer to total curcumin, meaning that studies do not differentiate between free (unconjugated) curcumin and curcumin conjugated with glucuronic acid or sulfate. Conjugated curcumin is the more abundant metabolite in circulation. While studies indicate that conjugated curcumin is less bioactive than free curcumin, there are also indications for the enzymatic release of free curcumin from the conjugated forms at sites of inflammation.[7,8]

The assessment of curcuminoid bioavailability, including that of CUR, is confounded by the pronounced metabolic and (photo)chemical instability of these compounds. Because of the varying preparations, formulations, and doses of intervention materials tested in the phase I clinical trials, it is unclear which curcumin-containing products and doses of CUR and/or other constituents of Curcuma longa are required to produce a clinically significant modulation of biomarkers or even clinical outcomes. The general consensus that the plasma levels of CUR required to achieve any biological effects in patients are much higher than what has been observed clinically to date. Studies have directly compared the bioavailability of unformulated curcumin-containing preparations with CUR that is formulated for enhanced bioavailability. These studies have consistently shown an increase in plasma levels using formulated CUR; however, these levels are still relatively low and do not exceed therapeutically insufficient concentrations.[9,10]

Table 1. Curcumin-Containing Products in Phase I Clinical Trials

Source	Description of Curcuminoid-Containing Product	Supplier	Type of Producta
CEM = further processed curcuminoid-enriched materials; CUR = curcumin as a single-chemical entity; TE =turmeric extract.
a For a more detailed definition of these terms, see theGeneral Information and History section.
[1,3,5]	Standardized turmeric extract formulated incapsules(curcumin C3 complex); each capsule contained 450 mg of curcumin, 30 mg of demethoxycurcumin, and 20 mg of bisdemethoxycurcumin	Sabinsa Corp. (Piscataway, NJ, USA and East Windsor, NJ, USA)	TE
[2]	Theracurmin (200 mg, then escalated to 400 mg)	Theravalues Corp. (Tokyo)	CEM
[4]	P54FP formulated in soft gelatin capsules. Each capsule contained 20 mg of curcuminoids (18 mg of curcumin and 2 mg of demethoxycurcumin) suspended in 200 mg of essential oils derived fromCurcumaspp. Typical constituents ofCurcumaessential oils are tumerone, atlantone, and zingiberene.	Phytopharm plc. (Godmanchester, United Kingdom)	CEM
[6]	Diferuloylmethane (99.3% pure; 500 mg per tablet)	Yung-Shin Pharmaceutical Co. (Taiwan)	CUR

Cancer Prevention and Treatment of Precancerous Lesions

Investigations into products that may aid in the prevention of cancer and the treatment of precancerous lesions are important for the development of early intervention strategies and treatments. A few studies have investigated the potential clinical benefit of curcumin -containing products, and other studies are under way. See ClinicalTrials.gov.

Colorectal cancer

Researchers have explored curcumin's potential in curcumin-containing products for the prevention of colon cancer through its effects on precancerous lesions.

Published results (curcumin-containing product for prevention of colon cancer):

1. One small study (N = 5) assessed patients with familial adenomatous polyposis (FAP). The patients, all of whom had previous colectomies (four patients with retained rectums and one patient with an ileal anal pouch), received 480 mg of curcumin and 20 mg of quercetin 3 times per day orally for 6 months.[11]
   • At 3 months, four of five patients had a decrease in polyp number and size from baseline.
   • At 6 months, this decrease continued for four of the patients, one patient was lost to follow-up after 3 months of treatment.
2. This same group conducted a controlled trial of 100% pure CUR (1,500 mg orally, 2 times/day) in a similar population of individuals with FAP (N = 44; placebo = 23; curcumin = 21).[12]
   • Results of this study contradicted previous findings. No significant difference was found between the two treatment arms in this study.
3. A third study that investigated oral curcumin used 2 doses (2,000 mg and 4,000 mg) of curcuminoid-containing powder (98%) given orally once daily for 30 days.[13] The study investigated the potential efficacy of curcumin-containing products in reducing the concentrations of prostaglandin E2 (PGE2) and 5-hydroxyeicosatetraenoic acid (5-HETE) (procarcinogenic factors) within aberrant crypt foci (ACF) (primary endpoint) and associated normal mucosa. The secondary endpoints included total ACF number (visible on endoscopy) and an estimate of proliferation in normal mucosa using the proliferation marker Ki-67. Forty patients were evaluable, with 20 participants in each dose group.[13]
   • There was no significant decrease in primary or secondary endpoints in either group of patients, except for a 40% decrease in the number of ACF in the group of patients who received 4,000 mg doses.
   • The ACF reduction in the 4,000 mg group was associated with a significant, five-fold increase in posttreatment plasma curcumin and conjugate levels.

Head and neck cancer

Treatment of patients with oral leukoplakia using a curcumin-containing product was investigated in a randomized trial.[14]

Published results (curcumin-containing product to treat oral leukoplakia):

1. In one trial, 223 patients with oral leukoplakia were randomly assigned to receive either 3,600 mg of an oral curcumin-containing product (N = 111) or a placebo (N = 112) twice daily after food for 6 months.[14] The intervention material contained a curcuminoid-enriched material (CEM) reconstituted with turmeric oil and dispensed in capsules (BCM95–Biocurcumax). Clinical response (primary endpoint) was determined by measurement of leukoplakia at baseline and at 6 months. At 6 months, 213 patients were evaluable (curcumin, N = 105; placebo, N = 108).
   • Of these patients, complete or partial responses were observed in 75 patients from the curcumin-containing product group and in 62 patients from the placebo group (a statistically significant difference).
   • One hundred three patients with a clinical response at 6 months continued the curcumin-containing product or placebo treatment to evaluate long-term treatment effects.
   • There was no statistically significant difference between treatment arms at 12 months, suggesting no additional benefits with treatment longer than 6 months.
   • Histological response (complete reversal of dysplasia/hyperplasia vs. partial reversal vs. no response vs. increased severity; secondary endpoint) between the groups was not significant, but combined histological and clinical response showed a significantly better response to the curcumin-containing product.

Multiple myeloma

The effect of a curcumin-containing product was investigated in patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma ( SMM).

Published results (effectiveness of curcumin-containing product on MGUS and SMM):

1. A double-blind, placebo-controlled, crossover study followed by an open-label extension study explored the effectiveness of a curcumin-containing product in patients with MGUS or SMM. Thirty-six patients (19 with MGUS and 17 with SMM) were randomly assigned to receive either 4,000 mg of the curcumin-containing product (curcumin stick-pack contained 3,600 mg of curcumin, 320 mg of demethoxycurcumin, and 80 mg of bisdemethoxycurcumin; one-half in the morning and one-half in the evening as a divided dose) or 4,000 mg of placebo, crossing over at 3 months. At completion of the first study, patients were given the option to begin the open-label 8,000 mg dose-extension study. Twenty-five patients (9 with SMM and 16 with MGUS) completed the crossover study and 18 patients (7 with SMM and 11 with MGUS) completed the extension study.[15]
   • Serum analysis revealed decreases in free light-chain ratio (rFLC); a difference between clonal and nonclonal light-chain (dFLC) and involved free light-chain (iFLC) was observed but not statistically significant in the group of patients who received the curcumin-containing product in the crossover study.
   • In the group of patients who received the placebo and then crossed over to receive the curcumin-containing product, no significant changes occurred after crossover. Urinary deoxypyridinoline (uDPYD), a marker of bone resorption, decreased in the curcumin-containing product arm and increased in the placebo arm.
   • Significant decrease in rFLC and uDPYD occurred in the open-label study.

Hepatoma (liver cancer)

The efficacy and safety of curcumin-containing products have been studied in patients with nonalcoholic fatty liver disease (NAFLD).

Published results (effectiveness of curcumin-containing product on NAFLD):

1. A study evaluated the efficacy and safety of supplementation with a phytosomal curcumin-containing product in patients with NAFLD (grades 1–3 according to liver ultrasonography) These patients were randomly assigned to receive either the curcumin-containing product (phytosomal form; 1,000 mg/day in 2 divided doses; N = 50) or the placebo (N = 52) for a period of 8 weeks.[16]
   • Results indicated that supplementation with the curcumin-containing product was associated with a reduction in body mass index (-0.99 ± 1.25 in the curcumin-containing product group vs. -0.15 ± 1.31 in the placebo group; P = .003) and waist circumference (1.74 ± 2.58 in the curcumin-containing product group vs. -0.23 ± 3.49 in the placebo group; P = .024).
   • Ultrasonographic findings were improved in 75.0% of patients in the curcumin-containing product group, while the rate of improvement in the control group was 4.7% (P < .001).
   • Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were reduced by the end of the trial in the patients in the curcumin-containing product group (P < .001) but elevated in the patients in the control group (P < .001).
   • The curcumin-containing product was safe and well-tolerated during the trial.
2. A 2019 meta-analysis analyzed four randomized controlled trials that included 228 patients.[17]
   • Results indicated a trend toward significant reduction of ALT blood concentrations in a subgroup of patients who received ≥1,000 mg/day curcumin-containing product supplementation (-11.36 IU/L; 95% confidence interval [CI], -22.75–0.02; I²: 51%).
   • The meta-analysis showed a significant reduction of AST levels in patients who received curcumin-containing products in studies with 8 weeks of administration (-9.22 IU/L; 95% CI, -12.77 to -5.67; I²: 49%).

   Based on these findings, the authors suggested that curcumin-containing products, at higher dosages, might have a favorable effect on patients with NAFLD.[17]

Table 2. Curcumin-Containing Products in Cancer Prevention and Treatment of Precancerous Lesions Trials

Source	Description of Curcuminoid-Containing Product	Supplier	Type of Producta
CEM = further processed curcuminoid-enriched materials; CUR = curcumin as a single-chemical entity; HPLC = high-performance liquidchromatography; TE = turmericextract.
a For a more detailed definition of these terms, see theGeneral Information and History section.
[11]	Curcumin-containing product (480 mg) and quercetin (20 mg) using Oxy-Q tablets	Farr Laboratories (Santa Clarita, CA, USA)	CEM
[12]	100% pure curcumin (CUR)	No source given	CUR
[13]	Pure curcumin (CUR) powder; 98.0% by HPLC	Sabinsa Corp. (East Windsor, NJ, USA)	TE
[14]	Curcumin-containing product, reconstituted with turmeric oil and dispensed in capsules (BCM95–Biocurcumax)	Arjuna Natural Extracts Ltd. (Kerela, India)	CEM
[15]	C3 curcuminoid granule stick-packs (Allepey finger turmeric); each curcumin-containing product stick-pack contained 4,000 mg of curcuminoids (3,600 mg of curcumin [CUR], 320 mg of demethoxycurcumin, and 80 mg of bisdemethoxycurcumin)	Sabinsa Corp. (Piscataway, NJ, USA)	TE
[16]	A phytosomal formulation that contained a complex of curcuminoids andsoyphosphatidylcholine in a 1:2 weight ratio, and 2 parts of microcrystallinecellulose, with an overall content of curcumin in the final product of around 20%	Meriva; Indena S.p.A, (Milan, Italy)	CEM

Cancer Treatment

Biomarker studies

Biomarkers have long been used to identify and understand the etiology of various diseases. In cancer research, there are different types of cancer biomarkers. Prognostic biomarkers determine the likely outcome of the disease and if further treatment is warranted and predictive biomarkers ascertain the likelihood the disease will respond to treatment.[18]

Five clinical studies have been performed to evaluate the effects of supplementation with curcumin -containing products on predictive biomarkers in patients with different types of cancer. Various biomarkers from these studies were evaluated as potential efficacy measures to ascertain the usefulness of curcumin-containing products alone and as an adjunctive therapy. Different curcumin-containing products were used. Curcuminoid doses used in these studies ranged from 20 mg/day to 3,000 mg/day. One of the studies did not identify the amount of curcuminoids administered, but used 5 g of turmeric powder dissolved in 150 mL of milk 3 times/day.[19]

The main biomarkers used in these studies were serum levels of the following:

• Total antioxidant capacity (TAC).[20]
• Superoxide dismutase (SOD).[20]
• Glutathione peroxidase (GPx).[20]
• Tumor necrosis factor-alpha (TNF-alpha).[21,22]
• Transforming growth factor-beta (TGF-beta).[22]
• Interleukin-6 (IL-6).[22]
• Cyclooxygenase-2 (COX-2).[23]
• Prostaglandin E2 (PGE2).[23]
• Nitric oxide.[19]
• Histological expression of p53 on cancer cells. [21]

Results from four of the studies indicated an association between a positive change in a biomarker and patient outcome as follows:

• TAC increased and SOD decreased.[20]
• p53 expression increased and TNF-alpha decreased.[21,22]
• TGF-beta and IL-6 decreased.[22]
• Reduction in nitric oxide.[19]

However, another study found no statistically significant difference between comparison groups when accounting for the observed biomarker, PGE2.[23] Additionally, a different study found no significant change in GPx.[20]

Another study conducted using a proprietary lecithin delivery system of a curcumin-containing product (500 mg tablet) given 3 times/day found that curcumin-containing product supplementation consistently improved oxidative status in patients who received chemotherapy and radiation therapy.[24]

Curcumin-containing products alone

Two studies have been published that suggest a possible antitumor effect of curcumin-containing products.

Published results (possible antitumor effect of curcumin-containing product):

1. One report described a patient with treatment-resistant myeloma who began a daily oral regime of a curcumin-containing product. A single 8,000 mg dose of the curcumin-containing product (containing curcuminoids complexed with bioperine to aid with absorption) was taken on an empty stomach each evening. The patient also underwent hyperbaric oxygen treatment.[25]
   • Over the course of 60 months, the patient's cancer remained stable with minor fluctuations in paraprotein levels.
2. An open-label phase II trial investigated the efficacy and toxicity of curcumin-containing products alone in patients with advanced pancreatic cancer.[26] The study enrolled 25 patients who received 8,000 mg (orally) of a curcuminoid-containing product daily until disease progression; each 1 g capsule contained 900 mg of curcumin, 80 mg of demethoxycurcumin, and 20 mg of bisdemethoxycurcumin. Of the 25 patients, 21 were evaluable for response and 24 for toxicity.
   • No treatment-related toxicity was reported.
   • One patient had stable disease for more than18 months and another patient had a brief tumor regression.

Imatinib and curcumin-containing products

Imatinib and curcumin-containing products have been studied in patients with metastatic adenoid cystic carcinoma (ACC).

Published results (treatment of c-kit –positive metastatic ACC with imatinib and a curcumin-containing product):

1. A published case report described the successful treatment of a patient with a c-kit–positive metastatic ACC using imatinib and a curcumin-containing product. Imatinib was administered orally at 400 mg/day along with 225 mg/m² of a curcumin-containing product in 1,000 mL of normal saline intravenously (IV) over 2 to 3 hours, twice a week. An oral curcumin-containing product was also administered, two capsules twice daily (42 mg curcumin per capsule). This regimen was continued for 6 months.[27]
   • Stable disease was observed after 2 months of treatment, and a significant reduction in tumor mass (80% decrease in tumor volume in lungs) was observed at 6 months.
   • After cessation of IV treatment at 6 months, but with steady use of an oral curcumin-containing product and imatinib, the patient showed continuous clinical and radiographic improvements.

   Given the known activity of imatinib against c-kit–positive tumors, the contribution of curcumin-containing products to the efficacy of this patient's treatment regimen is unclear.

Docetaxel and curcumin-containing products

Two studies have explored the efficacy, tolerability, and feasibility of docetaxel plus curcumin-containing products in the treatment of cancer.[28,29]

Published results (efficacy of docetaxel and a curcumin-containing product):

1. The first study, published in 2010 and conducted in France, examined docetaxel plus curcumin-containing products in patients with advanced and metastatic breast cancer.[28] Six dose levels of oral curcumin-containing products were studied. Doses varied from 500 mg to 8,000 mg daily along with docetaxel (100 mg/m²) administered as a 1-hour IV infusion on day 1 of each 3-week cycle for six cycles. Fourteen patients were enrolled in the study, and ten patients completed the treatments of docetaxel plus a curcumin-containing product. Diarrhea and headaches were the main dose-limiting toxicities, and three patients considered the amount of the curcumin-containing product (16 capsules a day) as unacceptable. A curcumin-containing product dose of 6,000 mg/day for 7 consecutive days every 3 weeks was determined to be the recommended dose for further investigation in combination with a standard dose of docetaxel.[28]
   • Among the evaluable patients enrolled on the study, no disease progression was observed with the combination treatment.
   • One patient had evaluable bone lesions that were stable after six cycles of treatment.
   • Five patients had partial responses, and three patients had stable disease.
   • A biological response was documented with a decrease of tumor markers in seven patients.
2. A randomized phase II study compared docetaxel and curcumin with docetaxel and placebo in patients with metastatic castration -resistant prostate cancer.[29] Patients received 75 mg/m² of docetaxel on day 1 every 3 weeks for six cycles and 5 mg of prednisone or prednisolone twice a day. Patients also received either 6 g of curcumin or placebo daily (4 capsules, 500 mg each, 3 times per day: morning, lunchtime, and evening) for 7 consecutive days every 3 weeks.
   • There were no differences in progression-free survival (PFS), prostate-specific antigen response rate, overall survival (OS), or quality of life between the groups.

A multicenter, phase II, randomized, double-blind study was initiated at the same institution in France and compared docetaxel plus a curcumin-containing product with docetaxel plus placebo in the first-line treatment of patients with metastatic castration-resistant prostate cancer. The study was terminated for futility in view of results from the interim analysis (NCT02095717).

Gemcitabine and curcumin-containing products

Three studies investigated the efficacy and safety of variable formulations and doses of curcumin-containing products in combination with gemcitabine. All studies administered gemcitabine 1,000 mg/m² IV weekly for 3 of 4 weeks, but differed in rate of gemcitabine administration.

Two research studies of first-line treatment in patients with advanced and metastatic pancreatic cancer (PC) showed differing results in tolerability and toxicity profiles.

Published results (gemcitabine and a curcumin-containing product):

1. A research group from Israel enrolled 17 patients in an open-label, phase II trial.[30] Patients received 8,000 mg of a curcumin-containing product by mouth daily concurrently with chemotherapy.
   • Five patients discontinued the curcumin component of the combined treatment mostly because of gastrointestinal toxicity, and 11 evaluable patients received the planned concurrent treatment of the two drugs until progression of disease (median, 2.5 months); one patient died at home from causes unrelated to the study.
   • Seven patients reported gastrointestinal toxicity, mostly diarrhea.
   • Of the 11 evaluable patients, 1 had a partial response, 4 had stable disease, and 6 had tumor progression.
   • Median overall survival was 5 months.

   The authors concluded that this combination of curcumin-containing products and gemcitabine is not feasible in this population of patients.

2. Conversely, an Italian study (N = 44) reported good tolerability using 2,000 mg daily of a curcumin-containing product.[31]
   • A partial response was observed in 27.3% of patients and stable disease was observed in 34.1% of patients; the overall disease control rate was 61.4%.
   • The median OS was 10.2 months and median time to progression was 8.4 months, which is reported to be higher than the historically observed OS rates of 5.7 to 6.7 months for gemcitabine as a single agent.
   • The researchers also noted that patients using this combination of a curcumin-containing product and gemcitabine reported lower-than-expected hematological toxicity. Grade 3 to grade 4 diarrhea occurred in only one patient.
3. A clinical trial of patients with gemcitabine-resistant PC also found this combination to be safe and effective (N = 21). In addition to gemcitabine, this study administered 60 mg/m² of S-1 orally for 14 consecutive days every 3 weeks.[32] Patients received a mixture of curcuminoids (8,000 mg/day) that they took at their own convenience, while on a standard chemotherapy treatment schedule; the compliance rate was 90%.
   • No patients experienced a partial or complete response.
   • Five patients demonstrated stable disease.
   • The most common adverse events of fatigue, anorexia, and diarrhea were attributed to chemotherapy or disease progression.

FOLFOX and curcumin-containing products

A group from the United Kingdom conducted a combined phase I dose-escalation study and a phase IIA study of oral daily curcumin-containing products with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) (CUFOX) in patients with metastatic colorectal cancer to assess safety, tolerability, and a suitable dose of curcumin.[33,34] Both studies used the same curcumin-containing product.

Published results (FOLFOX and a curcumin-containing product):

1. In the phase I dose-escalation trial, oral doses of 500 mg, 1,000 mg, or 2,000 mg of curcumin-containing products were given daily with a loading period of 1 week before initiation of FOLFOX chemotherapy.[33]
   • The curcumin-containing product was determined to be a safe and well-tolerated adjuvant therapy to FOLFOX at doses up to 2,000 mg/day.
   • Of the 12 patients, 11 patients demonstrated stable disease or partial responses to the treatment after six cycles and 8 patients maintained these responses.
   • Median PFS was 34 weeks.
   • The adverse events (AEs) reported were primarily gastrointestinal, mainly diarrhea, which is consistent with those described with FOLFOX alone and in some curcumin-containing product trials.
2. In the phase IIA study, 28 patients were accrued, 18 of whom received CUFOX with or without bevacizumab, while 9 patients were randomly assigned to the control arm and received FOLFOX with or without bevacizumab. One patient was deemed ineligible and was excluded from analyses.[34]
   • Grade 1 or grade 2 fatigue, peripheral neuropathy, and diarrhea were the most reported AEs in both arms.
   • Three patients who received CUFOX reported grade 3 or grade 4 thromboembolic events.
   • No complete response was observed; however, 22% of patients who received FOLFOX exhibited stable disease and 44% of patients who received FOLFOX exhibited partial responses; 28% of patients who received CUFOX exhibited stable disease and 56% of patients who received CUFOX exhibited partial responses.
   • The median PFS was 171 days for patients who received FOLFOX and 320 days for patients who received CUFOX.
   • The median OS was 200 days for patients who received FOLFOX and 596 days for patients who received CUFOX.
   • The difference in median OS rates between the two arms in this study was statistically significant. However, the small sample size and an imbalance between the two groups regarding the percentage of patients with two or more metastatic sites makes this result difficult to interpret.

Table 3. Clinical Trials of Curcumin-Containing Products for Cancer Treatment

Reference	Trial Design	Conditionor Cancer Type	Type of Chemotherapy	Treatment Groups	Results	Level of Evidence Scorea
CRLM = colorectal livermetastases;FOLFOX = folinic acid, fluorouracil, and oxaliplatin; PSA = prostate-specific antigen.
a For information aboutlevels of evidenceanalysis and scores, seeLevels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
[26]	Phase II, open-label trial	Advanced pancreatic cancer	N/A	N = 25 patients enrolled; 24 were evaluable for toxicity and 21 were evaluable for response	No treatment-related toxicities were observed; one patient remained stable for >18 months and another patient had a dramatic but brief tumor response	2Dii
[28]	Phase I, dose-escalation trial	Advanced and metastatic breast cancer	Docetaxel	N = 14	3 dose-limiting toxicities were observed and 2 of 3 patients at these dose levels refused to continue treatment	2C
[29]	Randomized, phase II	Castration-resistant prostate cancer	Docetaxel	N = 50; 24 patients received placebo and docetaxel and 26 patients received docetaxel and curcumin	No difference between groups was reported	1iDii
[30]	Phase II, open-label trial	Locally advancedand metastatic pancreatic cancer	Gemcitabine	N = 17; 4 locally advanced and 11 metastatic	Median time to tumor progression was 2.5 mo	2Diii
[31]	Phase II trial	Locally advanced and metastatic pancreatic cancer	Gemcitabine	N = 44; 13 locally advanced and 34 metastatic	Partial response in 27.3% of patients and stable disease in 34.1% of patients	2Diii
[32]	Phase I/II trial	Gemcitabine-resistant pancreatic cancer	Gemcitabine	N = 21; 19 patients receivedcombination therapyand 2 patients received gemcitabinemonotherapy	Phase I study outcome showed safety of oral curcumin-containing product. Additionally, no patients withdrew from this study because of curcumin-containing product intolerability, thus meeting the primary endpoint of the phase II study	2C
[33]	Phase I, dose-escalation trial	CRLM	FOLFOX	N = 12	This study revealed curcumin-containing products to be safe and tolerable adjuncts to FOLFOX chemotherapy in patients with CRLM at doses up to 2 g/d	2C
[34]	Phase IIA trial	Colorectal cancer withinoperableliver metastases	FOLFOX	N = 28; 9 received FOLFOX alone and 18 received FOLFOX + a curcumin-containing product	Daily oral curcumin-containing product combined with FOLFOX chemotherapy was safe and tolerable	2C

Table 4. Curcumin-Containing Products in Cancer Treatment Trials

Source	Description of Curcuminoid-Containing Product	Supplier	Type of Producta
CEM = further processed curcuminoid-enriched materials; CTE = curcuminoid-enriched turmeric extract; CUR = curcumin as a single-chemical entity; T = Turmeric; TE = a hybrid of a CEM and Turmericessential oil.
a For a more detailed definition of these terms, see theGeneral Information and History section.
[19]	Turmeric powder dissolved in 150 mL of milk	No source given	T
[20]	Curcumin-containing product capsules (BCM-95 CURCUGREEN)	Arjuna Natural Extracts Ltd. (Kerela, India)	TE
[21]	Curcumin-containing product (not further described)	Sigma Aldrich (Shanghai, China)	CUR
[22,31]	Phytosomal preparation of curcuminoids	Meriva; Indena S.p.A (Milan, Italy)	CEM
[23]	P54FP, an extract of Curcuma spp.; a liquid in 220 mg capsules (9% curcumin [CUR] and 1% demethoxycurcumin with the remainder constituted by essential oils derived fromCurcuma domestica andCurcuma xanthorrhiza)	Sigma Chemical Co. (Poole, United Kingdom); Phytopharm plc (Godmanchester, United Kingdom)	CEM
[24]	Meriva (ratio of curcumin: demethoxycurcumin: bis-demethoxycurcumin, 33:8:1), 200 mg soy lecithin, and 200 mg microcrystalline cellulose	Meriva; Indena S.p.A (Milan, Italy)	CEM
[25]	Curcumin-containing product complexed with bioperine	Patient administered, notprescribedby aphysician; no source given	CEM
[35]	Curcumin-containing product (not specified)	No source given	CUR
[26]	A preparation containing CUR (87.2%); demethoxycurcumin (10.5%); and bisdemethoxycurcumin (2.3%)	Sabinsa Corp. (Piscataway, NJ, USA)	TE
[27]	A proprietary formulation containing 42 mg of CUR in a form that enhances the solubility of CUR in water	Arantal	CTE
[28]	Curcuma extract(not specified)	No source given	TE
[29]	Each capsule contained 500 mg of CUR	No source given	CUR
[30]	Each capsule contained 500 mg of curcuminoids (curcumin [CUR] 450 mg, demethoxycurcumin 40 mg, and bisdemethoxycurcumin 10 mg)	Sabinsa Corp. (Piscataway, NJ, USA)	TE
[32,33,34]	Curcumin-containing product in microbead form, containing a mixture of curcuminoids (Curcumin C3 Complex) that contains curcumin (CUR; 73%), demethoxycurcumin (22%), and bisdemethoxycurcumin (4%)	Sabinsa Corp. (Piscataway, NJ, USA)	TE

Quality-of-Life Studies

One study examined the potential effect of curcumin on the quality of life (QOL) of cancer patients (N = 80) with solid tumors, predominantly gastric, colorectal, and breast cancer.[22] All patients received standard treatment for their respective cancers while enrolled in the study. Patients were randomly assigned to receive either curcuminoids (180 mg /day) or matched placebo for 8 weeks. Curcuminoids were prepared with phosphatidylcholine to boost bioavailability. Meriva contains 20% curcuminoids; therefore, each patient was asked to take three 300 mg capsules per day (one capsule tid).

This study reported an overall increase in self-reported QOL in both groups, with greater improvement in the curcuminoid group. However, because of the higher baseline QOL values in the placebo group when compared with the curcuminoid group, it is difficult to interpret these results.

Table 5. Curcumin-Containing Products in Quality-of-Life Studies

Source	Description of Curcuminoid-Containing Product	Supplier	Type of Producta
CEM = further processed curcuminoid-enriched materials.
a For a more detailed definition of these terms, see theGeneral Information and History section.
[22]	Phytosomal preparation of curcuminoids	Meriva; Indena S.p.A, (Milan, Italy)	CEM

Cancer Therapy Side Effects

Dermatitis

The effects of curcumin -containing products on radiation-induced dermatitis were investigated in three studies.[36,37,38] Two of the studies evaluated oral curcumin-containing products while one study assessed topical application of a curcumin-containing cream.

Published results (curcumin-containing products in the treatment of radiation-induced dermatitis):

1. In a randomized, double-blind, placebo-controlled study, 30 adult women with breast cancer who received radiation therapy alone were randomly assigned to receive either experimental treatment (oral curcumin-containing product; 2,000 mg) or control treatment (placebo) 3 times a day.[36]
   • Self-reported pain measures showed no significant differences between the treatment arms. However, the severity of radiation dermatitis at the treatment site was reduced in patients who received the oral curcumin-containing product.
2. A multi-site, randomized, double-blind, placebo-controlled study assessed the efficacy of an oral curcumin-containing product to reduce radiation dermatitis severity. Breast cancer patients (N = 686) were randomly assigned to received an oral curcumin-containing product (2,000 mg) or placebo 3 times a day.[37]
   • While curcumin did not reduce radiation dermatitis severity, fewer curcumin-treated patients with a Radiation Dermatitis Severity scale score of >3.0 suggested a trend towards reduced severity; the outcome lacked statistical significance.
3. In a prospective, investigator -blinded study, 40 adult breast cancer patients underwent radiation therapy and received either a turmeric -containing cream or baby oil (placebo) for 5 weeks. The skin was treated with 5 g of turmeric-containing cream or baby oil 5 times daily, before and after radiation therapy.[38]
   • Results showed that curcumin was effective in reducing the severity of dermatitis at 2, 3, and 4 weeks, compared with placebo.

Mucositis

Several studies evaluated the tolerability and efficacy of a curcuminoid-containing product by oral application (mouthwash) in the treatment of oral mucositis.[39,40] The studies used several objective outcome measures, including the World Health Organization's mucositis scale and Oral Mucositis Assessment Scale.

Published results (curcuminoid-containing products in the treatment of oral mucositis):

1. A study of adult patients who received chemotherapy and radiation therapy aimed to assess the efficacy of turmeric powder with honey on treating oral mucositis. The experimental group of patients (n = 30) were given a mixture of turmeric powder and honey to apply 5 minutes before treatment, maintain during treatment, and then reapplied 5 minutes after treatment. The control group of patients received no supplementation (n = 30).[40]
   • Good tolerability and a reduction in oral mucositis were noted in patients using the turmeric and honey treatment.
   • No adverse effects were observed.
2. In an investigator-blinded, randomized, controlled trial, 80 patients with head and neck cancer underwent combined carboplatin /radiation therapy and received turmeric (6 times a day) or povidone-iodine (twice a day) mouthwash every other day. Oral mucositis was assessed using the Radiation Therapy Oncology Group (RTOG) grading system.[41]
   • Turmeric mouthwash delayed and reduced the levels of radiation-induced oral mucositis at all time points.
   • Patients who used the turmeric mouthwash had decreased intolerable mucositis, fewer treatment breaks during the first 4 weeks of treatment, and reduced weight loss.
3. In a double-blind randomized study, 32 adult patients with head and neck cancer received radiation therapy and either an oral nano-encapsulated curcumin-containing product (80 mg a day) or a placebo. Fifteen patients received the nano-encapsulated curcumin-containing product (study group), and 14 patients received the placebo (control group). Oral mucositis was assessed by the National Cancer Institute Common Toxicity Criteria.[42]
   • In the study group of patients, onset of oral mucositis was delayed.
   • Severity of mucositis increased in all patients, but the grade was significantly lower in patients receiving curcumin.
   • While 50% of patients in the control group (7 of 14) developed grade 4 mucositis, no patients developed grade 4 mucositis in the study group.
   • The study group had reduced weight loss, and no side effects were detectable in this group.
4. In a randomized single-blind study, 61 adult patients with head and neck cancer who underwent radiation therapy received either an oral curcumin-containing product (500 mg capsule; total dose of 1.5 g a day) or a placebo 3 times a day. Patients were assessed weekly during radiation therapy and 2 months after treatment.[43]
   • Beginning with week 3 of treatment, patients who received curcumin had decreased incidence and severity of oral mucositis. Two months after treatment, these patients experienced less severe oral mucositis.
   • Results from the subjective assessment of patients were comparable to those obtained using the objective scale.
   • No systemic toxicity was observed.

Multiple effects

A proprietary lecithin delivery system of a curcuminoid-containing product given 3 times/day (500 mg tablet) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of chemotherapy and radiation therapy in patients undergoing these treatments 1 month after surgery for their cancer (N = 160; 80 patients each in the chemotherapy group and the radiation therapy group). These groups were further divided into experimental and control groups, with 40 patients in each subgroup receiving Meriva or a comparable placebo tablet. In both the chemotherapy and radiation therapy groups, frequency and severity of reported symptoms were significantly lower in the Meriva group and no significant changes were reported in the control group.[24]

Table 6. Clinical Trials of Curcumin-Containing Products for Cancer Therapy Side Effects

Reference	Trial Design	Conditionor Cancer Type	Treatment Groups (Enrolled; Treated; Placebo or No Treatment Control)	Results	Level of EvidenceScorea
RCT = randomized controlled trial.
a For information about levels of evidence analysis and scores, seeLevels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
[36]	RCT	Radiation dermatitis in breast cancer patients	35; 17; 18	Reduced severity of radiation dermatitis	1iC
[37]	RCT	Radiation dermatitis in breast cancer patients	695; 344; 342	No difference in severity between the groups	1iC
[38]	RCT	Radiation dermatitis in breast cancer patients	40; 20; 20	Reduced radiation dermatitis	1iC
[40]	Nonrandomized trial	Oral mucositis	60; 30; 30	Reduced oral mucositis	2C
[41]	RCT	Oral mucositis	80; 40; 40	Reduced oral mucositis	1iiC
[42]	RCT	Oral mucositis	32; 15; 14	Reduced oral mucositis	1iC
[43]	RCT	Oral mucositis	64; 30; 31	Reduced oral mucositis	1iiC

Table 7. Curcumin-Containing Products in Symptom Management Trials

Source	Description of Curcuminoid-Containing Product	Supplier	Type of Producta
CEM = further processed curcuminoid-enriched materials; T = Turmeric; TE = turmericextract; w/w = weight per weight.
a For a more detailed definition of these terms, see theGeneral Information and History section.
[36,37]	Curcumin C3 complex, 500 mg/capsule	Sabinsa Corp. (UT, USA)	TE
[39]	Curcumall, a liquid formula mouthwash containing a tincture of curcumin (C3 complex), turmeric, andgingerdissolved in glycerin and 0.4% of alcohol	Tumron health products (Jerusalem, Israel); Sabinsa Corp. (UT, USA)	CEM
[40]	Mixture of turmeric powder and honey	Made by researchers	T
[24]	Meriva (ratio of curcumin: demethoxycurcumin: bis-demethoxycurcumin 33:8:1), 200 mgsoylecithin and 200 mg microcrystallinecellulose	Meriva; Indena S.p.A (Milan, Italy)	CEM
[38]	Turmeric extract (16% w/w) and sandalwood oil (0.5% w/w) in a non-greasybase	Vicco Laboratories, (Maharashtra, India)	TE
[41]	Turmeric powder, 400 mg suspended in 80 mL water (use of 10 mL for mouthwash)	Himalaya Drug Company (Bangalore, India)	T
[42]	SinaCurcumin (nanocurcumin)	Nanotechnology Research Center of Mashhad University of Medical Science (Iran)	Undefined
[43]	Turmeric extract capsules (BCM-95/Curcugreen) containing essential oils of turmeric	Arjuna Natural, Aluva (India)	TE

Pediatric Population and Curcumin-Containing Products

Anticancer effects

A case report has been published that suggests a possible antitumor effect of a curcumin-containing product. The case report described a 6 month-old infant with infantile hemangioendothelioma. The curcuminoid-containing product was given at a dose of 400 mg/day over the course of 9 months.[35]

• Radiographic improvement was seen within 3 months.
• There was a notable decrease in liver size at 6 months, and an ultrasound showed no residual lesions within 1 year.
• The patient was well and thriving with no evidence of disease at the age of 6 years.

Given that this disease is known to frequently undergo spontaneous involution, the therapeutic activity of the curcumin-containing product in this case should be questioned. However, the authors indicated that this patient's tumor had some signs of an adverse prognosis.

Mucositis

One pediatric study evaluated the tolerability and efficacy of a curcuminoid-containing product by oral application (mouthwash) in the treatment of oral mucositis.[39] The study used several objective outcome measures, including the WHO's mucositis scale and Oral Mucositis Assessment Scale. Seven patients (four evaluable) used 10 drops of Curcumall in 50 mL of water along with standard oral care (0.2% chlorohexidine mouthwash for 30 seconds) 2 times a day during doxorubicin-containing chemotherapy treatment. Curcumall is a liquid formula mouthwash containing a tincture of curcumin C3 complex, turmeric, and ginger dissolved in glycerin and 0.4% of alcohol to create a serving dose. Compliance was inconsistent as follows:[39]

• Good tolerability and a reduction in oral mucositis were noted in patients using the curcumin/turmeric mouthwash.
• Except for one patient with gastrointestinal upset, no adverse effects were observed.

Table 8. Clinical Studies of Curcumin-Containing Products for Pediatric Population

Reference	Trial Design	Condition or Cancer Type	Treatment Groups (Enrolled; Treated; Placebo or No Treatment Control)	Results	Level of Evidence Scorea
N/A = not applicable.
a For information about levels of evidence analysis and scores, seeLevels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
[35]	Case report	Infantile hemangioendothelioma	1; none; none	A decrease in liver size at 6 months, and an ultrasound showed no residual lesions within 1 year	N/A
[39]	Case series	Oral mucositis in pediatric patients	7; 4; none	Reduced oral mucositis	3iC

References:

1. Garcea G, Berry DP, Jones DJ, 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 14 (1): 120-5, 2005.
2. 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 71 (6): 1521-30, 2013.
3. Irving GR, Howells LM, Sale S, et al.: Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration--a clinical pilot study including assessment of patient acceptability. Cancer Prev Res (Phila) 6 (2): 119-28, 2013.
4. Sharma RA, McLelland HR, Hill KA, et al.: Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 7 (7): 1894-900, 2001.
5. Sharma RA, Euden SA, Platton SL, et al.: Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10 (20): 6847-54, 2004.
6. Cheng AL, Hsu CH, Lin JK, et al.: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21 (4B): 2895-900, 2001 Jul-Aug.
7. Kunihiro AG, Brickey JA, Frye JB, et al.: Curcumin, but not curcumin-glucuronide, inhibits Smad signaling in TGFβ-dependent bone metastatic breast cancer cells and is enriched in bone compared to other tissues. J Nutr Biochem 63: 150-156, 2019.
8. Kunihiro AG, Luis PB, Brickey JA, et al.: Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone. J Nat Prod 82 (3): 500-509, 2019.
9. Schiborr C, Kocher A, Behnam D, et al.: The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res 58 (3): 516-27, 2014.
10. Stohs SJ, Ji J, Bucci LR, et al.: A Comparative Pharmacokinetic Assessment of a Novel Highly Bioavailable Curcumin Formulation with 95% Curcumin: A Randomized, Double-Blind, Crossover Study. J Am Coll Nutr 37 (1): 51-59, 2018.
11. Cruz-Correa M, Shoskes DA, Sanchez P, et al.: Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol 4 (8): 1035-8, 2006.
12. Cruz-Correa M, Hylind LM, Marrero JH, et al.: Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis. Gastroenterology 155 (3): 668-673, 2018.
13. Carroll RE, Benya RV, Turgeon DK, et al.: Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 4 (3): 354-64, 2011.
14. Kuriakose MA, Ramdas K, Dey B, et al.: A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia. Cancer Prev Res (Phila) 9 (8): 683-91, 2016.
15. Golombick T, Diamond TH, Manoharan A, et al.: 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 87 (5): 455-60, 2012.
16. Panahi Y, Kianpour P, Mohtashami R, et al.: Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Drug Res (Stuttg) 67 (4): 244-251, 2017.
17. Mansour-Ghanaei F, Pourmasoumi M, Hadi A, et al.: Efficacy of curcumin/turmeric on liver enzymes in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials. Integr Med Res 8 (1): 57-61, 2019.
18. La Thangue NB, Kerr DJ: Predictive biomarkers: a paradigm shift towards personalized cancer medicine. Nat Rev Clin Oncol 8 (10): 587-96, 2011.
19. Ghalaut VS, Sangwan L, Dahiya K, et al.: Effect of imatinib therapy with and without turmeric powder on nitric oxide levels in chronic myeloid leukemia. J Oncol Pharm Pract 18 (2): 186-90, 2012.
20. Hejazi J, Rastmanesh R, Taleban FA, et al.: Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study. Nutr Cancer 68 (1): 77-85, 2016.
21. He ZY, Shi CB, Wen H, et al.: Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest 29 (3): 208-13, 2011.
22. Panahi Y, Saadat A, Beiraghdar F, et al.: Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res 28 (10): 1461-7, 2014.
23. Plummer SM, Hill KA, Festing MF, et al.: Clinical development of leukocyte cyclooxygenase 2 activity as a systemic biomarker for cancer chemopreventive agents. Cancer Epidemiol Biomarkers Prev 10 (12): 1295-9, 2001.
24. 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. Phytother Res 28 (3): 444-50, 2014.
25. Zaidi A, Lai M, Cavenagh J: Long-term stabilisation of myeloma with curcumin. BMJ Case Rep 2017: , 2017.
26. Dhillon N, Aggarwal BB, Newman RA, et al.: Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 14 (14): 4491-9, 2008.
27. Demiray M, Sahinbas H, Atahan S, et al.: Successful treatment of c-kit-positive metastatic Adenoid Cystic Carcinoma (ACC) with a combination of curcumin plus imatinib: A case report. Complement Ther Med 27: 108-13, 2016.
28. 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 (1): 8-14, 2010.
29. Passildas-Jahanmohan J, Eymard JC, Pouget M, et al.: Multicenter randomized phase II study comparing docetaxel plus curcumin versus docetaxel plus placebo in first-line treatment of metastatic castration-resistant prostate cancer. Cancer Med 10 (7): 2332-2340, 2021.
30. Epelbaum R, Schaffer M, Vizel B, et al.: Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 62 (8): 1137-41, 2010.
31. Pastorelli D, Fabricio ASC, Giovanis P, et al.: Phytosome complex of curcumin as complementary therapy of advanced pancreatic cancer improves safety and efficacy of gemcitabine: Results of a prospective phase II trial. Pharmacol Res 132: 72-79, 2018.
32. Kanai M, Yoshimura K, Asada M, et al.: A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol 68 (1): 157-64, 2011.
33. James MI, Iwuji C, Irving G, et al.: Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett 364 (2): 135-41, 2015.
34. Howells LM, Iwuji COO, Irving GRB, et al.: Curcumin Combined with FOLFOX Chemotherapy Is Safe and Tolerable in Patients with Metastatic Colorectal Cancer in a Randomized Phase IIa Trial. J Nutr 149 (7): 1133-1139, 2019.
35. Hassell LA, Roanh le D: Potential response to curcumin in infantile hemangioendothelioma of the liver. Pediatr Blood Cancer 55 (2): 377-9, 2010.
36. Ryan JL, Heckler CE, Ling M, et al.: Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res 180 (1): 34-43, 2013.
37. Ryan Wolf J, Heckler CE, Guido JJ, et al.: Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients. Support Care Cancer 26 (5): 1543-1552, 2018.
38. Rao S, Hegde SK, Baliga-Rao MP, et al.: Sandalwood Oil and Turmeric-Based Cream Prevents Ionizing Radiation-Induced Dermatitis in Breast Cancer Patients: Clinical Study. Medicines (Basel) 4 (3): , 2017.
39. Elad S, Meidan I, Sellam G, et al.: Topical curcumin for the prevention of oral mucositis in pediatric patients: case series. Altern Ther Health Med 19 (3): 21-4, 2013 May-Jun.
40. Francis M, Williams S: Effectiveness of Indian Turmeric Powder with Honey as Complementary Therapy on Oral Mucositis : A Nursing Perspective among Cancer Patients in Mysore. Nurs J India 105 (6): 258-60, 2014 Nov-Dec.
41. Rao S, Dinkar C, Vaishnav LK, et al.: The Indian Spice Turmeric Delays and Mitigates Radiation-Induced Oral Mucositis in Patients Undergoing Treatment for Head and Neck Cancer: An Investigational Study. Integr Cancer Ther 13 (3): 201-10, 2014.
42. Delavarian Z, Pakfetrat A, Ghazi A, et al.: Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers. Spec Care Dentist 39 (2): 166-172, 2019.
43. Arun P, Sagayaraj A, Azeem Mohiyuddin SM, et al.: Role of turmeric extract in minimising mucositis in patients receiving radiotherapy for head and neck squamous cell cancer: a randomised, placebo-controlled trial. J Laryngol Otol : 1-6, 2020.

Adverse Effects

Most clinical studies of curcuma-containing products have demonstrated few, if any, associated adverse effects. In one small study (N = 17) of patients who received a curcumin -containing product along with gemcitabine chemotherapy, about 30% of patients (N = 5) who received 8,000 mg/day of the curcumin-containing product discontinued the product because of intractable abdominal fullness. Two other patients had a dose reduction to 4,000 mg, also because of abdominal complaints.[1] In this study, seven patients had grade 3 gastrointestinal toxicity and two patients had grade 2 gastrointestinal toxicity.

Table 9. Curcumin-Containing Products With Reported Adverse Effects

Source	Description of Curcuminoid-Containing Product	Supplier	Type of Producta
TE =turmeric extract.
a For a more detailed definition of these terms, see theGeneral Information and History section.
[1]	Eachcapsulecontained 500 mg of curcuminoids (curcumin 450 mg, demethoxycurcumin 40 mg, and bisdemethoxycurcumin 10 mg)	Sabinsa Corp. (Piscataway, NJ)	TE

References:

1. Epelbaum R, Schaffer M, Vizel B, et al.: Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 62 (8): 1137-41, 2010.

Summary of the Evidence for Curcumin (Curcuma, Turmeric)

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

• Be published in a peer-reviewed scientific journal.
• Report on therapeutic outcome or outcomes, such as tumor response, improvement in survival, or measured improvement in quality of life.
• Describe clinical findings in sufficient detail for a meaningful evaluation to be made.

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

Latest Updates to This Summary (10 / 31 / 2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of curcumin in the treatment of people with cancer.. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Integrative, Alternative, and Complementary Therapies Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

The preferred citation for this PDQ summary is:

PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Curcumin (Curcuma, Turmeric) and Cancer. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/curcumin-pdq. Accessed <MM/DD/YYYY>. [PMID: 33651529]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.

Last Revised: 2024-10-31