Curcumin

Known as the ‘golden spice of India’, turmeric has been used for centuries in traditional Ayurvedic and Chinese medicine. Curcumin is one of three phytochemical curcuminoids that are extracted from turmeric and sold collectively as ‘curcumin’. People use curcumin in a variety of conditions and diseases.

Gastrointestinal

Curcumin is proven to travel to the colonic mucosa, one of the layers in the lining of the bowel.[1] Curcumin has been shown to be anti-inflammatory in the bowel,[2] helping to reduce tumour formation where the colon is inflamed.[3] Curcumin has reduced pre-cancerous tumours in patients with familial adenomatous polyposis (FAP), where polyps decreased by around 60% in number and 50% in size.[4]

The way curcumin works has been well studied.[5] Despite interfering with the development of cancer, curcumin has been found to be relatively safe at very high doses.[6] In colorectal cancer, curcumin may enhance sensitivity to 5-FU chemotherapy [7] and slow down cell invasion.[8] An ongoing clinical trial of curcumin and FOLFOX chemotherapy called CUFOX will determine the success of adding 2g curcumin to advanced colorectal cancer treatment.[9]

Curcumin’s therapeutic benefits have been effective in a variety of other gastrointestinal conditions, as it has antioxidant activity[10-12] and is able to reduce inflammation.[13] Patients with irritable bowel syndrome (IBS) commonly report symptoms involving abdominal pain, bloating and altered bowel habits.[14] It is thought that low-grade inflammation of the intestinal lining is responsible for some symptoms that patients experience.[15]

In an eight-week study of IBS patients, turmeric extract was given to 207 people. After four weeks, members of the group reported up to a 60% reduction in IBS prevalence. In post-study analysis, abdominal pain and discomfort reduced by up to 25%.[16]

Two other studies found that levels of a form of the neurotransmitter serotonin are different in IBS.[17,18] When curcumin was added to the diets of rats with IBS, the amount of serotonin in the body changed, with the curcumin acting on the bowel through neurotransmitters to reduce the daily number of stools.[19]

Gastritis is caused by the production of an array of inflammatory cytokines induced by Helicobacter pylori infection in the stomach. A study conducted among H. pylori‐infected gastritis patients evaluated the effect of curcumin on the production of IL‐8, IL‐1β, TNF‐α and COX‐2 in gastric mucosa. However, curcumin was ineffective at decreasing the production of these cytokines, which indicates it has a limited effect on H. pylori‐induced inflammatory cytokine production. Nevertheless, other studies have reported that the symptoms of these patients with gastritis were ameliorated by the curcumin treatment.[20]

Curcumin has also been studied in relation to the inflammatory bowel diseases Ulcerative Colitis (UC) and Crohn’s Disease (CD).

Patients in one trial were tested for tolerance, with doses being increased over several weeks. All patients tolerated curcumin well, apart from two who complained of gassiness.[21] Researchers then conducted a small study of five patients with proctitis and five with Crohn’s Disease. A significant reduction in symptoms was reported after taking increasing doses of curcumin over several months. All proctitis patients improved and four were able to reduce their medication. Four of the five CD patients had lowered disease activity scores.[22] In an individual case study of a 60-year-old woman suffering from UC, curcumin was trialled after all other therapies were ineffective. After a year of treatment she had no ulcerations and the UC was inactive.[23] Another study concluded that curcumin, when combined with standard drug therapy, led to a reduced risk of relapse in UC patients.[20]

Results of a study published in 2010 revealed that curcumin appeared to have suppressed unwanted immune responses and enhanced more beneficial responses in IBD patients.[25]

The most exciting research was published in 2015. It showed that the addition of 3g curcumin to mesalamine therapy was more effective than the mesalamine combined with a placebo in bringing about remission in UC patients. The study also concluded there were no apparent adverse effects.[26]

Lung Disease

Curcumin has a range of activities in the body but is best known for it’s anti-inflammatory action[27]. Animal models have demonstrated that curcumin is a potent anti-inflammatory agent in the lungs[28] and that it may also protect against pulmonary fibrosis.[29] A number of studies have suggested that curcumin may have some protective role against the DNA damage caused by arsenic.[30,31] In a pre-clinical renal cancer study, addition of curcumin to cancer cells exhibited a strong potential for protection against diesel exhaust and cisplatin-induced cytotoxicity[32]. Preclinical trials have also shown that curcumin inhibited POP associated cellular and DNA damage[33,34]. It has also reversed nicotine induced liver toxicity in an animal study.[35]

Pre-clinical studies have shown that curcumin can prevent cadmium-induced IL-6 and IL-8 inflammatory secretion by human airway epithelial cells. Cadmium (Cd) is a toxic metal present in the environment and its inhalation can lead to pulmonary disease including lung cancer and COPD. Curcumin could therefore potentially be used to prevent airway inflammation due to cadmium inhalation.[36] An animal model investigated the effect of Cadmium (CdCl2)-polluted drinking water (40 mg CdCl2/L) on the level of tumour necrosis factor- alpha (TNF-α) and IL-6 and found a preventative action of curcumin against Cd toxicity.[37]

Specifically in COPD, curcumin has been shown in animal models to have a beneficial effect in smooth muscle cells and improve the mean pulmonary artery pressure and right ventricular myocardial infarction (RVMI) through stimulating the suppressor of cytokine signalling (SOCS) -3/JAK2/STAT signalling pathways.[38] In another model, curcumin was shown to suppress chemokines and affect corticosteroid sensitivity in COPD through modulating Histone deacetylase 2 (HDAC2) expression and its effect on histone modification.[39] Another animal model showed that curcumin attenuates alveolar epithelial injury in COPD, which may be partially due to the down-regulation of Protein 66 homologous- collagen homologue (p66Shc).[40] In a randomised, double blinded, parallel group study in patients with mild COPD and raised LDL cholesterol, 90mg curcumin was found to reduce the α1-antitrypsin–low-density lipoprotein (AT-LDL) complex, thus reducing risk of future cardiovascular events.[41]

In other patients, a population based study of 2478 people found that people taking dietary curcumin through eating curry had better pulmonary function. The mean adjusted FEV1associated with curry intake was 9.2% higher among current smokers, 10.3% higher among past smokers, and 1.5% higher among non-smokers.[42] In 89 patients who had poor pulmonary function due to sulphur mustard, curcumin (1500 mg/day) + piperine (15 mg/day) or a placebo were given for 4 weeks. The active supplement reduced systemic oxidative stress and clinical symptoms, and also improved health related quality of life.[43]

The anti-cancer effects of curcumin against lung cancer have been investigated in vitro and in vivo xenograft mouse models. The key pathways appear to be downregulation of NF-ĸB, modulation of miRNA pathways with inhibition of caspase-3 as well as inhibition of PI3K/AKT pathways. In addition curcumin can act both as a chemo- and radio-sensitizing agent in lung cancer.[44]

Cardiovascular diseases (CVD)

CVD includes acute coronary syndrome, acute myocardial infarction and dyslipidaemia. There are many drugs approved for the treatment of these problems but they are not without side effects. Therefore, the effect of curcumin has been studied in patients to see if it can help.

Acute coronary syndrome (ACS) is used to define any group of clinical symptoms compatible with acute myocardial ischaemia.[45] In a randomized controlled trial with 75 ACS patients, curcumin was evaluated for its effects on lipid levels. Curcumin was administered to the patients at increasing doses three times a day (low dose 15 mg, moderate dose 30 mg and high dose 60 mg). The findings revealed that curcumin effectively reduced the total cholesterol and low‐density lipoprotein cholesterol levels in the patients at low doses when compared with the higher doses.[46]

Curcumin was found to reduce the myocardial infarction associated with coronary artery bypass grafting (CABG) significantly. Researchers evaluated the effects of the curcuminoids on the frequency of acute myocardial infarction after CABG. A total of 121 patients were enrolled for this trial. The curcuminoid group exhibited lower levels of post‐operative C‐reactive protein (CRP), malondialdehyde and N‐terminal pro‐B‐type natriuretic peptide levels. These antioxidant and anti‐inflammatory effects might contribute to the cardioprotective effects of the curcuminoids.[47]

Dyslipidaemia is a well‐established modifiable disease risk factor. Treatment of this disease is usual for the prevention of cardiovascular diseases.[48] The hypolipidaemic activity of curcumin was examined in a randomized, double‐blind, placebo‐controlled, crossover trial. Supplementation of curcuminoids resulted in a decrease in the concentrations of serum triglycerides without causing any marked impact on the lipid profile, body mass index and body fat.[49]

Although some dietary supplements have extensive health benefits, Soare and colleagues observed that a combination of common dietary supplements of varying doses had no cardiovascular or metabolic effects in non‐obese relatively healthy individuals. In their study, 24 weeks of dietary supplementation did not influence arterial stiffness or endothelial function, or alter body fat measurements, blood pressure, plasma lipids, glucose, insulin, insulin‐like growth factor‐1 (IGF1) and markers of inflammation and oxidative stress in non‐obese individuals.[50] In contrast, it has been found that the consumption of curry spices rich in antioxidative compounds like curcumin and eugenol, improves postprandial endothelial function in healthy male subjects. The participants who ate curry had an increased flow‐mediated vasodilatation response. The presence of spices in the curry did not significantly change the systemic and forearm haemodynamics, or any biochemical parameters.[51]

Regular consumption of curcumin is probably an alternative way of modifying cholesterol‐related parameters, as evidenced by a study that measured the effect of curcumin extract on weight, glucose and lipid profiles in patients with metabolic syndrome. At 12 weeks after intake of the curcumin extract, there was an elevation in the high‐density lipoprotein cholesterol level, whereas the level of low‐density lipoprotein cholesterol was decreased significantly.[52] In another study conducted with 32 participants, curcumin was shown to increase the vascular endothelial function in postmenopausal women, which in turn decreases the risk of cardiovascular.[53]

The latest study was a well-designed randomised controlled trial of 33 patients with coronary artery disease. Patients were randomly assigned to receive curcumin or placebo, 500 mg capsules, four times daily for 8 weeks 2 g of curcumin a day significantly decreased serum levels of triglycerides, LDL-cholesterol, and VLDL-cholesterol compared to baseline, without significant changes in total cholesterol, HDL-cholesterol, blood glucose and hs-CRP levels.[54]

Biliary diseases

The first clinical trial of curcumin in human diseases was done by Oppenheimer in 1937 to examine the effects of ‘curcumen’ or ‘curcunat’ (contains 0.1 to 0.25 g sodium curcumin and 0.1 g calcium cholate) on human biliary diseases. Healthy people were given an i.v. injection of 5% sodium curcumin solution, which resulted in rapid emptying of the gallbladder. Notably, one patient showed a complete cure throughout a long period of observation.[55] In another study, Cholagogum F Nattermann (dried extracts from Schöllkraut and Curcuma) treatment caused an effective reduction in biliary dyskinesia.[56]

Chronic anterior uveitis

Uveitis is a major cause of vision loss worldwide. Chronic anterior uveitis (CAU) includes a heterogeneous group of diseases, of which some are idiopathic in origin. As curcumin has shown to be effective as a treatment of diverse inflammatory conditions, a couple of clinical trials were attempted to evaluate its efficacy against CAU of different aetiologies. The oral administration of curcumin to CAU patients improved their health and a follow‐up after 3 years indicated a 55% recurrence rate.[57] Another group investigated the efficacy of oral phospholipidic curcumin on recurrent CAU of different aetiologies. The findings claimed that phospholipidic curcumin reduced the symptoms and signs of eye discomfort efficiently after a few weeks of treatment in the majority of the patients.[58]

Chronic cutaneous complications

Chronic cutaneous complications are one of the major and frequent complaints of patients in countries where people are exposed to sulphur mustard (SM). A clinical trial investigated the effect of curcumin on serum inflammatory biomarkers such as IL‐8 and hs‐CRP and their association with the severity of a chronic cutaneous complication called pruritus. The results suggest that curcumin is highly effective at lessening the inflammation in patients with chronic SM‐induced cutaneous complications.[59]

Teeth and gums

Curcumin, being a well‐known anti‐inflammatory agent, can be used to develop an effective preventive and treatment approach for chronic periodontitis. A comparative study was conducted to measure the therapeutic efficacy of chlorhexidine (CHX) chips and curcumin‐based collagen as adjuncts to scaling and root planing in the management of chronic periodontitis. At the end of a 6 month study period, a decrease in plaque and gingival index scores and improved microbiological parameters, probing pocket depth and clinical attachment levels were observed in both CHX chips and curcumin‐based collagen‐treated patients.[60] Another study carried out by the same group of investigators indicated that 1% curcumin irrigation when used as an adjunct to scaling and root planing had a mild to moderate beneficiary effect.[61] In addition, 1% curcumin solution was found to resolve inflammatory symptoms, in cases of chronic periodontitis[62] and a local drug‐delivery system comprising 2% whole turmeric gel, can be used as an adjunct to scaling and root planing in the treatment of periodontal pockets.[20]

Gingivitis is one of the most common inflammatory periodontal diseases. Curcumin therapy holds high potential as a treatment of gingivitis. As an anti‐inflammatory, curcumin mouthwash was found to be almost as good as CHX and hence it may act as an efficacious adjunct to mechanical periodontal therapy.[64] Similarly, the anti‐inflammatory potential of topical curcumin was found to be comparable with that of CHX‐MTZ and higher than CHX in affecting the levels of IL‐1β and CCL28.[65] Besides curcumin, in another clinical study whole turmeric mouthwash was found to be useful as an adjunct to mechanical plaque control methods in the prevention of plaque and gingivitis.[66]

Mouth problems

Oral mucositis is a commonly occurring problem in some cancer therapies. Several in vivo studies have shown that curcumin can avert oral mucositis. In a clinical settings, a pilot study was undertaken to measure the tolerability and efficacy of a curcumin mouthwash against oral mucositis in paediatric patients receiving doxorubicin‐based chemotherapy. Curcumin mouthwash decreased inflammations as shown by decreased inflammatory scores, and the study documented no adverse reactions in the children.[67]

Oral lichen planus (OLP) is a chronic immunological disease where white sore patches occur inside the mouth. Curcuminoids were assessed for their efficacy against OLP and found to be well tolerated.[68] A later study performed by the same group suggested curcuminoids at doses of 6000 mg·day-1 divided up as 3 doses was well tolerated and might be of use in regulating the signs and symptoms of OLP.[69] In another controlled trial conducted with 53 patients, administration of 6000 mg·day-1 curcuminoids reduced the symptoms of OLP in 60% of the patients.[70]

Chronic kidney disease

Chronic kidney disease (CKD) is characterized by reduced kidney function, enhanced inflammation and decreased vitamin levels. To evaluate the effect of curcumin in CKD in humans, a study was conducted with 16 patients. A herbal supplement composed of Curcumin and Boswellia serrata or placebo was given to non‐dialysis CKD patients and plasma levels of IL‐6, TNF‐α, glutathione peroxidase and serum CRP were measured. Curcumin was found to be safe and well tolerated and helped to reduce the levels of the inflammatory cytokine IL‐6.[71] A later randomized double-blind placebo-controlled clinical trial in patients with nondiabetic or diabetic proteinuric CKD used 320mg /d. It did not improve proteinuria, estimated glomerular filtration rate, or lipid profile. However, in plasma, CUR attenuated lipid peroxidation in individuals with nondiabetic proteinuric CKD and enhanced the antioxidant capacity in subjects with diabetic proteinuric CKD. No effect was observed on the antioxidant enzymes activities or Nrf2 activation.[72]

Bones and Joints

The rationale for trialing curcumin in osteoarthritis comes from several in vitro studies. Curcumin inhibited the matrix degradation of articular explants and chondrocytes.[73] It decreased the production of MMP-3, −9 and −13 via c-Jun-N-terminal kinases, nuclear factor kappa-beta (NFκβ), and the JAK/STAT pathways. It also restored type II collagen and glycosaminoglycan synthesis. A random double blind study on knee OA patients compared the ability of curcuminoids and the NSAID diclofenac to inhibit cyclo-oxygenase 2.[74] Both the groups significantly reduced cyclo-oxygenase 2 secretions by similar efficacies.

One randomised double blind study compared the effects of ibuprofen (2 × 400 mg/day) with those of curcumin (4 × 500 mg/day) in patients who were over 50 years of age, had severe knee pain and their radiography showed the presence of osteophytes.[75] Both the groups showed improvements in all assessments but the curcumin group was statistically better in patient satisfaction, timed walk or stair climbing and pain during walking or stair climbing. A similar study with a larger number of patients compared the effects of Curcuma. domestica extracts (1500 mg/day, n = 171) with ibuprofen (1200 mg/day n = 160) for 4 weeks.[76] After 4 weeks, all measures of WOMAC and the 6 min walk test improved significantly (p <0.001) in both groups with no differences between the groups. The safety profile was found to be somewhat better in the curcumin group. Another study compared the effects of the NSAID diclofenac (75 mg) combined with placebo (n = 36) or with Curcuma longa extracts (1000 mg) (n = 37) on pain and function. The combination was no more effective than diclofenac alone indicating that the effects of the two treatments are not additive.[77]

A pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events.[78] A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo.[79]

Haematology

The inhibition of the transcription nuclear factor, NF-κB, is a primary mode of action of curcumin, which act to mediate various anti-inflammatory effects for various diseases [80]. NF-κB has been widely implicated in both tumorigenesis and radioresistance,[80] hence results of pre-radiotherapy curcumin intake leading to radiosensitization in murine cancer models are not surprising in light of suppressing NF-κB.[81] There is also data to support the NF-κB suppression theory as means for radiosensitization in lymphomas, which are important in light of resistance to biologic therapies for some types of lymphomas for example supporting radiosensitization in Burkitt’s lymphoma,[82,83] similarly benefit of radiosensitization in NHL (which constitute large proportions of lymphomas treated with RT) has also been demonstrated.[84] The study found that cell cycle arrest in the G2-M checkpoint was augmented with curcumin administration. Another study looked at the antitumor effect of curcumin on cutaneous T-cell lymphoma (CTCL) cell lines and peripheral blood mononuclear cells (PBMCs) from patients with CTCL compared with healthy donors’ controls. Curcumin selectively induced apoptosis in association with the downregulation of STAT-3 and NF-kappaB signaling pathways in CTCL cells.[85]

A problem with taking curcumin orally can be bioavailability. Quercetin-decorated liposomes of curcumin (QCunp) enhancing curcumin absorption was more effective in increasing the life span and body weight of lymphoma inflicted mice compared to “standard” curcumin.[86] Interleukin-1 (IL-1α and IL-1β) is a proinflammatory cytokine affecting nearly all cell types. Expression of IL-1 is up regulated in different tumour phenotypes and is implicated as an important factor in tumour progression via expression of metastatic, angiogenic genes and growth factors. Therefore, down regulation of expression of IL-1 may be able to inhibit cancer progression. One study focused on the long term effect of curcumin on expression of IL-1α and IL-1β in the liver of mice with lymphoma. Elevated expression and protein level of IL-1α and IL-1β were found in these mice, and they were significantly down regulated by curcumin treatment. The addition of curcumin down regulated activation of IL-1α and IL-1β via AP-1 and NF-IL-6 respectively.[87] Another study found that curcumin led to the prevention of lymphoma growth by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like isoform nitric oxide synthases (iNOS) and cyclooxygenase-2 (COX2) in the liver of mice with lymphoma.[88] Curcumin has also been shown to reduce incidence of thymic lymphoma by 55% in mice exposed to whole body irradiation.[89]

Curcumin has been studied in an animal model of B-cell CLL/lymphoma 2 (Bcl-2). Curcumin treated animals had reduced gene expression of Bcl-2.[90] An Australian clinical trial used 6g of Curcumin C3 complex and 2g of rice bran during early CLL and other early stage malignancies. The supplements were given to 10 CLL patients and 2 of 9 (22%) of patients showed a >20% decrease in absolute lymphocyte count at 6 months. The percentage of CD4 and CD8 T-cells also increased in 2 of 9 (22%) patients in the stage 0/1 CLL group.[92]

Studies with liposomal curcumin have shown that curcumin distribution into peripheral blood mononuclear cells in patients with CLL was higher compared to peripheral blood mononuclear cells from healthy individuals. The potential greater distribution of curcumin into PBMC from CLL patients could form part of curcumin’s therapeutic benefit.[92]

Breast

While breast cancer is the most common cancer among women worldwide,[93] breast cancer in India is among the lowest in the world – over three times lower than in the UK.[94] The reasons for this are complex, but it is interesting to note that India also has the highest worldwide consumption of turmeric, a primary source of dietary curcumin. Curcumin appears to be useful in preventing human breast cancer development after the carcinogen triclocarban (from household cleaning products) is added to breast cells to stimulate cancer.[95]

There are several other in vitro studies showing curcumin’s effect on breast cancer cells.[96-98]

Pancreas

Studies have found that populations with the highest curcumin consumption have a lower incidence and risk of various types of cancers, including pancreatic cancer.[99-101] Curcumin can halt the growth of pancreatic cancer cells in vitro.[102]

Three published human clinical trials have used 8g curcumin a day: A trial of curcumin in 25 patients with advanced pancreatic cancer, demonstrated biological activity in two patients. One had ongoing stable disease for >18 months; one additional patient had brief, but marked, tumour regression (73%) accompanied by significant increases in serum cytokine levels.[103]

Curcumin has also been used in combination with gemcitabine in locally advanced pancreatic cancer which could not be surgically removed.[104] However the trial used patients of poor nutritional status and had high drop-out rates from gastrointestinal symptoms.[105]

A phase I clinical trial used 19 patients with pancreatic cancer who were resistant to gemcitabine-based chemotherapy. Four patients continued for >6 months. The average survival time was 161 days and there was a one-year survival rate of 19%,[106] much higher than the average.

A human randomised controlled trial using 500mg curcumin per day and 5mg piperine per day (a compound in black pepper) may reverse lipid peroxidation, a sign of stress on the pancreas, in patients with tropical pancreatitis.[107] Curcumin has also been shown to prevent[108] and help treat[109,110] acute pancreatitis in animal models.

Diabetes

Curcumin has been shown to protect human pancreatic islets cells from oxidative stress.[111] A randomised placebo controlled trial was undertaken on 240 glucose-intolerant patients for nine months. Patients took 6 x 250mg curcumin capsules a day. Curcumin treatment lowered HbA1c and slowed the deterioration to T2DM.[112] In diabetic animals, curcumin improves high blood sugar and high blood lipids.[113-115]

Liver

Curcumin has been shown to prevent hepatocellular carcinoma (HCC) through apoptosis[116,117] and, during an HCC in vitro study, 5-Fu chemotherapy and curcumin resulted in significant additional anti-cancer effects.[118]

Similarly, combination therapy using curcumin has resulted in a reduction in tumour cell production and an increase in cell death of tumour cells in-vitro.[119]

An in vitro study showed that curcumin decreases the hepatitis C gene expression [120]. It may therefore be potentially useful as an anti-hepatitis C agent in humans.[120] Another study found that curcumin inhibits hepatitis C liver cell entry, independently of the person’s genotype, by affecting membrane fluidity, impairing the virus binding and fusion.[121]

Hepatitis B also infects the liver and uses its cell host for gene expression and propagation. One in vitro study showed that the combination of Lamivudine and curcumin treatments suppresses hepatitis B expression by up to 75% when compared to non-treated cells. Curcumin also inhibits hepatitis B gene expression and replication.[122,123]

These early study results suggest that curcumin may work together with current hepatitis B treatments, and that this combination may result in a better suppression of the virus, reducing progression to cirrhosis and HCC.

References

1. Irving GRB, 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). 2013;6(2):119–128. [PUBMED]
2. Su CC, Chen GW, Lin JG, et al. Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res 2006;26:1281-8. [PUBMED]
3. Murakami A, Furukawa I, Miyamoto S et al. Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis. Biofactors 2013;39(2):221-32. [PUBMED]
4. Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol 2006;4:1035-8. [PUBMED]
5. Aggarwal BB, Sundaram C, Malani N, et al. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1–75. [PUBMED]
6. Lao CD, Ruffin MTt, Normolle D et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10. [PUBMED]
7. Shakibaei M, Buhrmann C, Kraehe P et al. Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures. PLoS One. 2014;3:9(1):e85397. [PUBMED]
8. Chen A, Xu J, Johnson AC. Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 2006;25:278-87. [PUBMED]
9. Irving GR, Steward WP. A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Ca.
10. Sharma OP. Antioxidant activity of curcumin and related compounds. Biochem Pharmacol 1976;25(15):1811–1812.
11. Ruby AJ, Kuttan G, Babu, KD et al. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 1995;94(1):79–83. [PUBMED]
12. Sugiyama Y, Kawakishi S, Osawa T. Involvement of the-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem Pharmacol 1996;52(4):519–25. [PUBMED]
13. Srimal RC, Dhawan BN. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 1973;25(6):447–52.
14. Camilleri M. Dyspepsia, irritable bowel syndrome, and constipation: review and what’s new. Rev Gastroenterol Disord 2001;1:2-17. [PUBMED]
15. Barbara G, De Giorgio R, Stanghellini V, et al. A role for inflammation in irritable bowel syndrome? Gut 2002;51:i41-i44.
16. Bundy R, Walker AF, Middleton RW et al. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. J Altern Complement Med 2004;10:1015-1018. [PUBMED]
17. Dunlop SP, Coleman NS, Blackshaw E et al. Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol 2005; 3: 349–357. [PUBMED]
18. Wheatcroft J, Wakelin D, Smith A et al. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of post-infectious bowel dysfunction. Neurogastroenterol Motil 2005; 17 863–870. [PUBMED]
19. Yu Y, Wu S, Li J et al. The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signalling. Metab Brain Dis; 2015; 30(1):47-55 [PUBMED]
20. Koosirirat C, Linpisarn S, Changsom D, Chawansuntati K, Wipasa J (2010). Investigation of the anti‐inflammatory effect of Curcuma longa in Helicobacter pylori‐infected patients. Int Immunopharmacol 10: 815–818. [PubMed].
21. Suskind, DL, Wahbeh, G, Burpee, T et al. Tolerability of curcumin in pediatric inflammatory bowel disease: A forced-dose titration study. J. Pediatr. Gastronenterol. Nutr. 2013, 56, 277–279. [PUBMED]
22. Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci. 2005;50(11):2191-3. [PUBMED]
23. Lahiff, C.; Moss, A.C.M. Curcumin for clinical and endoscopic remission in ulcerative colitis. Inflamm. Bowel Dis. 2011, 17, E66. [PUBMED]
24. Hanai, H, Iida, T, Takeuchi, K et al. Curcumin maintenance therapy for ulcerative colitis: Randomized, multicenter, double-blind, placebo-controlled trial. Clin. Gastroenterol. Hepatol. 2006, 4, 1502–1506. [PUBMED]
25. Epstein J, Docena G, MacDonald TT et al. Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr. 2010;103(6):824–32. [PUBMED]
26. Lang A, Salomon N, Wu JC et al. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2015;24 pii: S1542-3565(15)00158-5.[PUBMED]
27. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin the Indian solid gold. Adv Exp Med Biol. 2007;595:1–75. [PubMed]
28. Yang X, Lv JN, Li H, Jiao B, Zhang QH, Zhang Y, et al. Curcumin reduces lung inflammation via Wnt/β-catenin signaling in mouse model of asthma. J Asthma. 2017;54:335–340. [PubMed]
29. Chauhan PS, Dash D, Singh R. Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma. Inflammation. 2017;40:248–258. [PubMed]
30. Khan S, Vala JA, Nabi SU, Gupta G, Kumar D. Telang et al. Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytes in vitro. J Immunotoxicol. 2012;9:148–159. [PubMed]
31. 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;29:513–524. [PubMed]
32. Waly MI, Ali BH, Nemmar A. Acute effects of diesel exhaust particles and cisplatin on oxidative stress in cultured human kidney (HEK 293) cells, and the influence of curcumin thereon. Toxicol In Vitro. 2013;27:2299–2304. [PubMed]
33. Çelik A, Eke D, Ekinci SY, Yıldırım S. The protective role of curcumin on perfluorooctane sulfonate-induced genotoxicity: single cell gel electrophoresis and micronucleus test. Food Chem Toxicol. 2013;53:249–255. [PubMed]
34. Eke D, Çelik A. Curcumin prevents perfluorooctane sulfonate-induced genotoxicity and oxidative DNA damage in rat peripheral blood. Drug Chem Toxicol. 2016;39:97–103.[PubMed]
35. Salahshoor M, Mohamadian S, Kakabaraei S, Roshankhah S, Jalili C. Curcumin improves liver damage in male mice exposed to nicotine. J Tradit Complement Med. 2016;6:176–183.[PMC free article] [PubMed]
36. Rennolds J, Malireddy S, Hassan F, Tridandapani S, Parinandi N, Boyaka PN, et al. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium. Biochem Biophys Res Commun. 2012;417:256–261. [PMC free article] [PubMed]
37. Alghasham A, Salem TA, Meki AR. Effect of cadmium-polluted water on plasma levels of tumor necrosis factor-α, interleukin-6 and oxidative status biomarkers in rats: protective effect of curcumin. Food Chem Toxicol. 2013;59:160–164. [PubMed]
38. Lin X, Chen Y, Effect LZ. its molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2016;45:469–476. [PubMed]
39. Gan L, Li C, Wang J, Guo X. Curcumin modulates the effect of histone modification on the expression of chemokines by type II alveolar epithelial cells in a rat COPD model. Int J Chron Obstruct Pulmon Dis. 2016;11:2765–2773. [PMC free article] [PubMed]
40. Zhang M, Xie Y, Yan R, Shan H, Tang J, Cai Y, et al. Curcumin ameliorates alveolar epithelial injury in a rat model of chronic obstructive pulmonary disease. Life Sci. 2016;164:1–8. [PubMed]
41. Funamoto M, Sunagawa Y, Katanasaka Y, Miyazaki Y, Imaizumi A, Kakeya H, et al. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2029–2034.[PMC free article] [PubMed]
42. Ng TP, Niti M, Yap KB, Tan WC. Curcumins-Rich Curry Diet and Pulmonary Function in Asian Older Adults. Shi W, ed. PLoS One. 2012;7:e51753. [PMC free article] [PubMed]
43. Panahi Y, Ghanei M, Hajhashemi A, Sahebkar A. Effects of Curcuminoids-Piperine Combination on Systemic Oxidative Stress, Clinical Symptoms and Quality of Life in Subjects with Chronic Pulmonary Complications Due to Sulfur Mustard: A Randomized Controlled Trial. J Diet Suppl. 2016;13:93–105. [PubMed]
44. Lelli D, Sahebkar A, Johnston TP, Pedone C. Curcumin use in pulmonary diseases: State of the art and future. Pharm Res. 2017;115:133–148. [PubMed]
45. Kumar A, Cannon CP (2009). Acute coronary syndromes: diagnosis and management, part I. Mayo Clin Proc 84: 917–938. [PubMed]
46. Alwi I, Santoso T, Suyono S, Sutrisna B, Suyatna FD, Kresno SB et al. (2008). The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta Med Indones 40: 201–210. [PubMed]
47. Wongcharoen W, Jai‐Aue S, Phrommintikul A, Nawarawong W, Woragidpoonpol S, Tepsuwan T et al. (2012). Effects of curcuminoids on frequency of acute myocardial infarction after coronary artery bypass grafting. Am J Cardiol 110: 40–44. [PubMed]
48. Cicero AF, Colletti A (2015). Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: the available clinical data. Phytomedicine 23: 1113–1118. [PubMed]
49. Mohammadi A, Sahebkar A, Iranshahi M, Amini M, Khojasteh R, Ghayour‐Mobarhan M et al. (2013). Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Phytother Res 27: 374–379. [PubMed]
50. Soare A, Weiss EP, Holloszy JO, Fontana L (2014). Multiple dietary supplements do not affect metabolic and cardio‐vascular health. Aging (Albany NY) 6: 149–157. [PubMed]
51. Nakayama H, Tsuge N, Sawada H, Masamura N, Yamada S, Satomi S et al. (2014). A single consumption of curry improved postprandial endothelial function in healthy male subjects: a randomized, controlled crossover trial. Nutr J 13: 67. [PubMed]
52. Yang YS, Su YF, Yang HW, Lee YH, Chou JI, Ueng KC (2014). Lipid‐lowering effects of curcumin in patients with metabolic syndrome: a randomized, double‐blind, placebo‐controlled trial. Phytother Res 28: 1770–1777. [PubMed]
53. Akazawa N, Choi Y, Miyaki A, Tanabe Y, Sugawara J, Ajisaka R et al. (2012). Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women. Nutr Res 32: 795–799. [PubMed]
54. Mirzabeigi P, Mohammadpour AH, Salarifar M et al. The Effect of Curcumin on some of Traditional and Non-traditional Cardiovascular Risk Factors: A Pilot Randomized, Double-blind, Placebo-controlled Trial. Iran J Pharm Res. 2015;14(2):479-86. [PUBMED]
55. Oppenheimer A (1937). Turmeric (curcumin) in biliary diseases. Lancet 229: 619–621.
56. Niederau C, Gopfert E (1999). The effect of chelidonium‐ and turmeric root extract on upper abdominal pain due to functional disorders of the biliary system. Results from a placebo‐controlled double‐blind study. Med Klin (Munich) 94: 425–430. [PubMed]
57. Lal B, Kapoor AK, Asthana OP, Agrawal PK, Prasad R, Kumar P et al. (1999). Efficacy of curcumin in the management of chronic anterior uveitis. Phytother Res 13: 318–322. [PubMed]
58. Allegri P, Mastromarino A, Neri P (2010). Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long‐term follow‐up. Clin Ophthalmol 4: 1201–1206. [PubMed]
59. Panahi Y, Sahebkar A, Parvin S, Saadat A (2012b). A randomized controlled trial on the anti‐inflammatory effects of curcumin in patients with chronic sulphur mustard‐induced cutaneous complications. Ann Clin Biochem 49: 580–588. [PubMed]
60. Gottumukkala SN, Sudarshan S, Mantena SR (2014). Comparative evaluation of the efficacy of two controlled release devices: chlorhexidine chips and indigenous curcumin based collagen as local drug delivery systems. Contemp Clin Dent 5: 175–181. [PubMed]
61. Gottumukkala SN, Koneru S, Mannem S, Mandalapu N (2013). Effectiveness of sub gingival irrigation of an indigenous 1% curcumin solution on clinical and microbiological parameters in chronic periodontitis patients: a pilot randomized clinical trial. Contemp Clin Dent 4: 186–191. [PubMed]
62. Suhag A, Dixit J, Dhan P (2007). Role of curcumin as a subgingival irrigant: a pilot study. PERIO: Periodontal Pract Today 2: 115–121.
63. Behal R, Mali AM, Gilda SS, Paradkar AR (2011). Evaluation of local drug‐delivery system containing 2% whole turmeric gel used as an adjunct to scaling and root planing in chronic periodontitis: a clinical and microbiological study. J Indian Soc Periodontol 15: 35–38. [PubMed]
64. Muglikar S, Patil KC, Shivswami S, Hegde R (2013). Efficacy of curcumin in the treatment of chronic gingivitis: a pilot study. Oral Health Prev Dent 11: 81–86. [PubMed]
65. Pulikkotil SJ, Nath S (2015). Effects of curcumin on crevicular levels of IL‐1beta and CCL28 in experimental gingivitis. Aust Dent J 60: 317–327. [PubMed]
66. Waghmare PF, Chaudhari AU, Karhadkar VM, Jamkhande AS (2011). Comparative evaluation of turmeric and chlorhexidine gluconate mouthwash in prevention of plaque formation and gingivitis: a clinical and microbiological study. J Contemp Dent Pract 12: 221–224. [PubMed]
67. Elad S, Meidan I, Sellam G, Simaan S, Zeevi I, Waldman E, Weintraub M, Revel-Vilk S. Topical curcumin for the prevention of oral mucositis in pediatric patients: case series. Altern Ther Health Med. 2013;19(3):21-4. [PUBMED]
68. Chainani‐Wu N, Silverman S Jr, Reingold A, Bostrom A, Mc Culloch C, Lozada‐Nur F et al. (2007). A randomized, placebo‐controlled, double‐blind clinical trial of curcuminoids in oral lichen planus. Phytomedicine 14: 437–446. [PubMed]
69. Chainani‐Wu N, Madden E, Lozada‐Nur F, Silverman S Jr (2012b). High‐dose curcuminoids are efficacious in the reduction in symptoms and signs of oral lichen planus. J Am Acad Dermatol 66: 752–760. [PubMed].
70. Wu N, Collins K, Silverman S Jr (2012a). Use of curcuminoids in a cohort of patients with oral lichen planus, an autoimmune disease. Phytomedicine 19: 418–423. [PubMed]
71. Moreillon JJ, Bowden RG, Deike E, Griggs J, Wilson R, Shelmadine B et al. (2013). The use of an anti‐inflammatory supplement in patients with chronic kidney disease. J Complement Integr Med 10. pii: /j/jcim.2013.10.issue‐1/jcim‐2012‐0011/jcim‐2012‐0011.xml. [PubMed]
72. Jiménez-Osorio AS, García-Niño WR, González-Reyes S, Álvarez-Mejía AE, Guerra-León S, Salazar-Segovia J, Falcón I, Montes de Oca-Solano H, Madero M, Pedraza-Chaverri J. The Effect of Dietary Supplementation With Curcumin on Redox Status and Nrf2 Activation in Patients With Nondiabetic or Diabetic Proteinuric Chronic Kidney Disease: A Pilot Study. J Ren Nutr. 2016 Jul;26(4):237-44.
73. Shen CL, Smith BJ, Lo DF, Chyu MC, Dunn DM, Chen CH, et al. Dietary polyphenols and mechanisms of osteoarthritis. J Nutr Biochem. 2012;23:1367–1377. doi: 10.1016/j.jnutbio.2012.04.001. [PubMed] [Cross Ref]
74. Kertia N, Asdie AH, Rochmah W, Marsetyawan Ability of curcuminoid compared to diclofenac sodium in reducing the secretion of cycloxygenase-2 enzyme by synovial fluid’s monocytes of patients with osteoarthritis. Acta Med Indones. 2012;44:105–113. [PubMed]
75. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med. 2009;15:891–897. doi: 10.1089/acm.2008.0186. [PubMed] [Cross Ref]
76. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, Buntragulpoontawee M, Lukkanapichonchut P, Chootip C, et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014;9:451–458. doi: 10.2147/CIA.S58535. [PMC free article] [PubMed] [Cross Ref]
77. Pinsornsak P, Niempoog S. The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial. J Med Assoc Thai. 2012;95(Suppl 1):S51–S58. [PubMed]
78. Chandran B., Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res Phytother Res. 2012;26(11):1719–1725. [PubMed]
79. Amalraj A, Varma K, Jacob J, Divya C, Kunnumakkara AB, Stohs SJ, Gopi S. A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study. J Med Food. 2017;20(10):1022-1030 [PUBMED]
80. Aggarwal BB: Nuclear factor-kappaB: the enemy within. Cancer Cell 6, 203-208, 2004. doi: 10.1016/j.ccr.2004.09.003 [PUBMED]
81. Orr WS, Denbo JW, Saab KR, Ng CY, Wu J et al.: Curcumin potentiates rhabdomyosarcoma radiosensitivity by suppressing NF-κB activity. PLoS One 8, e51309, 2013. doi: 10.1371/journal.pone.0051309. [PUBMED]
82. Zhao Z, Verma V, Zhang M: Anaplastic lymphoma kinase: Role in cancer and therapy perspective. Cancer Biol Ther 16, 1691-1701, 2015.  doi: 10.1080/15384047.2015.1095407. [PUBMED]
83. Qiao Q, Jiang Y, Li G:  Inhibition of the PI3K/AKT-NF-κB pathway with curcumin enhanced radiation-induced apoptosis in human Burkitt’s lymphoma. J Pharmacol Sci 121, 247-256, 2013. doi: 10.1254/jphs.12149FP  [DOI] [PUBMED]
84. Qiao Q, Jiang Y, Li G: Curcumin enhances the response of non-Hodgkin’s lymphoma cells to ionizing radiation through further induction of cell cycle arrest at the G2/M phase and inhibition of mTOR phosphorylation. Oncol Rep 29, 380-386, 2013. doi: 10.3892/or.2012.2091. [PUBMED]
85. Zhang C, Li B, Zhang X, Hazarika P, Aggarwal BB et al.: Curcumin selectively induces apoptosis in cutaneous T-cell lymphoma cell lines and patients’ PBMCs: potential role for STAT-3 and NF-kappaB signaling. J Invest Dermatol 130, 2110-2119, 2010. doi: 10.1038/jid.2010.86 [PUBMED]
86. Ravichandiran V, Masilamani K, Senthilnathan B, Maheshwaran A, Wui WT, et al.: Quercetin-decorated curcumin liposome design for cancer therapy: In-vitro and in-vivo studies. Curr Drug Deliv 14, 1053-1059, 2017. doi: 10.2174/1567201813666160829100453. [PUBMED]
87. Das L, Vinayak M: Curcumin attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1α and IL-1β) via modulation of AP-1 and NF-IL6 in lymphoma bearing mice. Int Immunopharmacol 20, 141-147, 2014. doi: 10.1016/j.intimp.2014.02.024. [PUBMED]
88. Das L, Vinayak M: Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer. PLoS ONE 10, e0124000, 2015. doi: 10.1371/journal.pone.0124000. [PUBMED]
89. Dange P, Sarma H, Pandey BN, Mishra KP: Radiation-induced incidence of thymic lymphoma in mice and its prevention by antioxidants. J Environ Pathol Toxicol Oncol 26, 273-9, 2007. doi: 10.1615/JEnvironPatholToxicolOncol.v26.i4.40 [PUBMED]
90. El-Bahr SM: Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats. BMC Complement and Altern Med 13, 368, 2013. doi: 10.1186/1472-6882-13-368. [PUBMED]
91. Golombick T, Diamond TH, Manoharan A, Ramakrishna R: Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia): A Preliminary Clinical Study. Integr Cancer Ther 15 183-189, 2016. doi: 10.1177/1534735416635742. [PUBMED]
92. Bolger GT, Licollari A, Tan A, Greil R, Pleyer L et al.: Distribution of Curcumin and THC in Peripheral Blood Mononuclear Cells Isolated from Healthy Individuals and Patients with Chronic Lymphocytic Leukemia. Anticancer Res 38, 121-130, 2018. doi: 10.21873/anticanres.1219 [PUBMED]
93. Centers for Disease Control and Prevention. 1999–2011 Incidence and Mortality Web-Based Report. Atlanta GA: Department of Health and Human Services, Center for Disease Control and Prevention, and National Cancer Institute; [Accessed 25 Nov 2014]. Available from: http://www.cdc.gov/uscs
94. World Health Organization, International Agency for Research on Cancer. GLOBOCAN. Lyon, France: 2012. [Accessed 25 Nov 2014]. Available from: http://globocan.iarc.fr.
95. Sood S, Choudhary S, Wang H-CR. Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin, Biochem Biophys Res Commun 2013; 438(4): 600–606. [PUBMED]
96. Lv Z-D, Liu X-P, Zhao W-J, et al. Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo. International Journal of Clinical and Experimental Pathology. 2014;7(6):2818-2824. [PUBMED]
97. Thulasiraman P, McAndrews DJ, Mohiudddin IQ. Curcumin restores sensitivity to retinoic acid in triple negative breast cancer cells. BMC Cancer. 2014;14:724. doi:10.1186/1471-2407-14-724. [PUBMED]
98. Chen B, Zhang Y, Wang Y et al. Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression. J Steroid Biochem Mol Biol. 2014;143:11-8. [PUBMED]
99. Aggarwal BB, Kumar A, Bharti AC et al. Anticancer potential of curcumin:Preclinical and clinical studies. Anticancer Research 2003;23(1A):363-398. [PUBMED]
100. Sinha R, Anderson DE, McDonald SS, Greenwald P. Cancer risk and diet in India. J Postgrad Med. 2003;49:222–8. [PUBMED]
101. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75:787–809. [PUBMED]
102. Stan SD, Singh SV, Brand RE. Chemoprevention strategies for pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2010;7:347–56. [PUBMED]
103. Youns M, Fathy G. Upregulation of extrinsic apoptotic pathway in curcumin-mediated antiproliferative effect on human pancreatic carcinogenesis. J Cell Biochem 2013;114(12):2654-65. [PUBMED]
104. Dhillon N, Aggarwal BB, Newman RA et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clinical Cancer Research 2008;14(14):4491-4499. [PUBMED]
105. Epelbaum R, Schaffer M, Vizel B et al. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010;62:1137–1141. [PUBMED]
106. 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 2011;68(1):157-164. [PUBMED]
107. Durgaprasad S, Pai CG, Vasanthkumar et al. A pilot study of the antioxidant effect of curcumin in tropical pancreatitis. Indian J Med Res. 2005;122(4):315–318. [PUBMED]
108. Yu WG, Xu G, Ren GJ et al. Preventive action of curcumin in experimental acute pancreatitis in mouse. Indian J Med Res. 2011;134(5):717-24. [PUBMED]
109. Zhong K. Curcumin Mediates a Protective Effect Via TLR-4/NF-κB Signaling Pathway in Rat Model of Severe Acute Pancreatitis. Cell Biochem Biophys. 2015; 73(1):175-80. [PUBMED]
110. Gulcubuk A, Haktanir D, Cakiris A et al. Effects of curcumin on proinflammatory cytokines and tissue injury in the early and late phases of experimental acute pancreatitis. Pancreatology. 2013;13(4):347-54. [PUBMED]
111. Balamurugan AN, Akhov L, Selvaraj G & Pugazhenthi S. Induction of antioxidant enzymes by curcumin and its analogues in human islets: implications in transplantation. Pancreas 2009; 159 85–93. [PUBMED]
112. Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R et al. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012;35 2121–2127. [PUBMED]
113. Hussain HE. Hypoglycemic, hypolipidemic, and antioxidant properties of combination of curcumin from Curcuma longa, Linn, and partially purified product from Abroma augusta, Linn. in streptozotocin induced diabetes. Indian Journal of Clinical Biochemistry 2002; 17 33–43. [PUBMED]
114. Arun N, Nalini N. Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant Foods for Human Nutrition 2002; 57 41–52. [PUBMED]
115. Pari L, Murugan P. Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats. Journal of Basic and Clinical Physiology and Pharmacology 2005;16 257–274. [PUBMED]
116. Chuang SE, Kuo ML, Hsu CH, et al. Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. Carcinogenesis 2000; 21:331–335. [PUBMED]
117. Darvesh AS, Aggarwal BB, Bishayee A. Curcumin and liver cancer: a review. Curr Pharm Biotechnol. 2012 Jan;13(1):218-28. [PUBMED]
118. Zhu R, Wu X Xiao Y et al. Synergetic Effect of SLN-Curcumin and LDH-5-Fu on SMMC-7721 Liver Cancer Cell Line. Cancer Biother Radiopharm 2013;28(8):579-87. [PUBMED]
119. Notarbartolo M, Poma P, Perri D et al. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett. 2005;224:53–65. [PUBMED]
120. Kim K, Kim KH, Kim HY et al. Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway. FEBS Letters. 2010;584(4):707–712. [PUBMED]
121. Anggakusuma, Colpitts CC, Schang LM et al. Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells. Gut. 2014;63(7):1137-49. [PUBMED]
122. Rechtman MM, Har-Noy O, Bar-Yishay I, et al. Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1α [FEBS Lett. 584, (2010), 2485-2490] FEBS Letters. 2010;584(11):2485–2490. [PUBMED]
123. Rechtman MM, Har-Noy O, Bar-Yishay I, et al. Erratum to Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1α [FEBS Lett. 584, (2010), 2485-2490] FEBS Letters. 2010;584(14):p. 3239.