Written by Klara Rombauts, Liene Dhooghe and the CAM-Cancer Consortium.
Updated May 7, 2014

Curcumin

Abstract and key points

  • 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.

This summary is currently (April 2016) being updated. The version published here was last updated in April 2014.

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.

Read about the regulation, supervision and reimbursement of herbal medicine at NAFKAMs website CAM Regulation.

What is it?

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 Zingiberaceae 1. It is also known as Indian saffron, jiang huang, haridra, haldi, as the major ingredient of curry powder 2 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.

Ingredient(s)

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 resins 3.

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 effect 4-5. 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 observed 6-7. For these reasons, different approaches have been investigated: development of curcumin analogues 8; the use of adjuvants such as piperine to improve the bioavailability 9; the development of liposomes 10 and phospholipid complexes 11 in order to improve oral bioavailability, and even nanoparticles in order to allow parental administration 12. A report refers to the topical application of a curcumin ointment in patients with breast cancer 13.

History/provider(s)

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 diseases 14. 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 demonstrated 1. Since then, the number of reports on pharmacological effects of curcumin increased rapidly 15. Although the Indian traditional medicine describes turmeric as a cancer remedy, the first scientific trials were not carried out until 1985 16.

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 sarcoma 13.

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 damage 18 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 gemcitabine 20. 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 proteins 2.

The epigenetic property of curcumin is based on its interaction with histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and microRNAs 21.

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.

Legal issues

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).

Does it work?

This summary is currently (April 2016) being updated. The version published here was assessed as up to date in April 2014.

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 available. 42

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. 

Prevention 

Controlled trials

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 placebo.22 Reduced DNA damage and antioxidant activitiy were observed in 286 healthy volunteers chronically exposed to arsenic who received 1 g curcumin daily compared to placebo.27 

Uncontrolled trials 

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 time 15. Uncontrolled trials suggest a decrease of the number of aberrant crypt foci in 41 smokers receiving 4g but not 2g or curcumin daily 25, 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 women.47 

Treatment 

Controlled trials 

Four controlled clinical trials are available, 43,29,44,46 two thereof are randomized.43, 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 placebo.43 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 placebo.29 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 placebo.44 Nitric oxide levels were significantly decreased in 50 patients with chronic myeloid leukaemia receiving 15g imatinib and turmeric powder daily compared to imatinib alone.46  

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.

Is it safe?

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 8g 7,33, 34, 35, taken for a period of up to 18 months 26, and in high doses of up to 12g for 3 months 3,6.

 

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 effects. 48

 

Possible adverse effects include gastro-intestinal side effects 35 and a potential for allergic dermatitis related to topical administration 36.

 

Contraindications

 

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 drugs 36.

 

Interactions

 

Curcumin has been suggested to improve the oral bioavailability and therapeutic efficacy of paclitaxel (administered in nanoemulsions) in ovarian adenocarcinoma in mice 37, of etoposide after oral but not intravenous administration in rats 38 and docetaxel in combination with a curcumin self-emulsifying drug delivery system in rats 39. These interactions are explained by inhibition of P-glycoprotein and intestinal CYP3A enzyme 38, 39, although this effect was not found in vitro in an intestinal cell culture model 41.

 

Curcumin has been reported to inhibit CYP1A2 function but enhance CYP2A6 activity in healthy, male Chinese volunteers 40. Since many drugs are metabolized by CYP-enzymes, it is very important to acknowledge that curcumin could alter the efficacy of regular drugs.

Citation

Klara Rombauts, Liene Dhooghe, CAM-Cancer Consortium. Curcumin [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Curcumin. May 7, 2014.

Document history

Summary fully revised and updated in April 2014 by Klara Rombauts.

Summary first published in May 2012 authored by Klara Rombauts and Liene Dhooghe.

References

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