Turmeric

Turmeric

Common Names

  • Indian saffron
  • Curcumin
  • Jiang huang

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For Patients & Caregivers

Turmeric demonstrated anti-inflammatory and anticancer activities in the lab. A few studies suggest that curcumin has biological activity in some cancer patients, but more data are needed to verify its benefits.

Turmeric is a spice that has been used in cooking for centuries. It has many biological activities, although how these effects occur is not fully understood. Lab experiments show that substances in turmeric, called curcuminoids, prevent inflammation by inhibiting the molecules that cause it. Curcuminoids may protect the body by enhancing the activity of an important detoxifying enzyme, and by neutralizing molecules that cause DNA damage, such as free radicals. In rats, turmeric prevented the development of kidney damage from toxins. Turmeric also stimulates the flow of bile in the gastrointestinal tract.

Animal studies have also shown that turmeric may have protective effects against colon, stomach, and skin cancers. Turmeric also stopped replication of tumor cells when applied directly to them in the lab, but it is unknown if this effect occurs in the human body. Curcumin, a curcuminoid, has shown biological activity in pancreatic cancer patients and there are ongoing studies to test its effect as an addition to current cancer treatment. However, recent experiments suggest turmeric may interfere with the activity of some chemotherapy drugs, so the question remains whether this spice is helpful or harmful during chemotherapy. Curcumin also showed weak phytoestrogenic activity in a laboratory study. Human data are needed to determine the clinical relevance.

 

  • To prevent cancer
    Several animal studies suggest that turmeric prevents colon, stomach, and skin cancers in rats exposed to carcinogens. However, in a double-blind randomized trial of patients with familial adenomatous polyposis (FAP), a rare genetic predisposition to precancerous colorectal polyps, there was no reduction in lower intestinal tract adenomas with long-term use of curcumin compared with placebo. A trial is currently underway to evaluate safety and effectiveness of turmeric in patients with metastatic disease undergoing active chemotherapy.
  • To treat infections
    One clinical trial showed that turmeric does not help lower viral load in HIV positive patients.
  • To reduce inflammation
    Laboratory and animal studies suggest that turmeric reduces inflammation. There are ongoing clinical trials on this effect in humans.
  • To treat kidney stones
    No scientific evidence supports this use. In addition, it is generally recommended to avoid turmeric for those with a predisposition to kidney stones, or gastrointestinal disorders such as stomach ulcers and hyperacidity disorders.
  • To relieve stomach and intestinal gas
    No clinical trials have evaluated this use.
  • Recent laboratory findings indicate that dietary turmeric may inhibit the antitumor action of chemotherapeutic drugs such as cyclophosphamide and doxorubicin in treating breast cancer. There was also a case report of a lung cancer patient who suffered liver toxicity while undergoing active treatment with paclitaxel. Although he was taking multiple supplements, turmeric was thought to be among the likely causes. Therefore, more research is necessary, and patients undergoing chemotherapy should ask their doctor if they should limit their intake of turmeric and turmeric-containing foods.
  • You have bile duct obstruction, gallstones, predisposition to kidney stones, or gastrointestinal disorders such as stomach ulcers and hyperacidity disorders.
  • You have hypersensitivity to spices: Turmeric is a spice and may therefore also cause similar effects.
  • You are taking reserpine, a blood pressure drug: Turmeric may lessen its effects.
  • You are taking indomethacin, a nonsteroidal anti-inflammatory drug (NSAID): Turmeric may lessen its effects.
  • You are taking warfarin or other blood thinners: Turmeric may increase your risk of bleeding.
  • You are taking chemotherapy drugs such as camptothecin, mechlorethamine, doxorubicin, or cyclophosphamide: Turmeric inhibits the action of these drugs against breast cancer cells in lab experiments.
  • You are taking tacrolimus, an immunosuppressant: Curcumin supplements increase plasma levels of tacrolimus and may increase side effects.
  • You are taking norfloxacin, a fluoroquinolone antibiotic: Curcumin makes this stay in the blood for a longer time, thereby reducing the need for taking higher amounts of the drug.
  • You are taking drugs metabolized by the CYP3A4 enzyme: Curcumin inhibits cytochrome 3A4 enzyme, altering the metabolism of certain prescription drugs.
  • You are taking drugs metabolized by the CYP1A2 enzyme: Curcumin inhibits cytochrome 1A2 enzyme, altering the metabolism of certain prescription drugs.
  • You are taking drugs metabolized by the CYP2A6 enzyme: Curcumin enhances cytochrome 2A6 enzyme, altering the metabolism of certain prescription drugs.
  • You are taking drugs metabolized by the CYP2D6 enzyme: Curcumin inhibits cytochrome 2D6 activity and has the potential to interact with CYP2D6 substrates.
  • You are taking drugs transported by P-Glycoprotein: Curcumin affects intestinal P-glycoprotein levels and function, thereby increasing the concentrations of prescription drugs such as celiprolol, midazolam and verapamil.
  • You are undergoing certain laboratory tests that use dyes: Curcumin may interfere with some lab tests due to its strong absorptive and fluorescent properties.
  • Allergic skin inflammation, hives
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For Healthcare Professionals

Curcuma longa, Curcuma domestica

Turmeric is a plant that is native to South Asia but is cultivated in tropical areas around the world. The rhizome is used as a spice in regional cuisines, and as a coloring agent in food and cosmetics for its yellow-orange color. It is also used in traditional medicine for improving circulation and digestion. Turmeric extracts are marketed as dietary supplements to improve memory, for arthritis, and for cancer prevention.

The active constituents are turmerone oil and water-soluble curcuminoids, mainly curcumin which is the focus of most research. In vitro studies suggest that curcumin, the principal bioactive ingredient of turmeric, acts as a weak phytoestrogen (1), and exhibits neuroprotective (2), choleretic (3), anti-inflammatory (4), immunomodulatory (5), anti-proliferative (3), and chemopreventive effects (6) (7) (8). Curcumin, its analogs, and liposomal formulations have also produced chemosensitizing (9) (10) (11) and radiosensitizing effects (12) (13).

Turmeric and its active constituents have been investigated for their therapeutic activities in humans. A clinical trial suggests it may be effective against major depressive disorder  (62). Data from an epidemiological study suggest improved cognitive performance in elderly Asians who consume turmeric in the form of curry powder (14); however, there were no benefits from curcumin supplementation in patients with Alzheimer’s disease (15). Turmeric may help alleviate symptoms of irritable bowel syndrome  (16) or quiescent ulcerative colitis (17), but in a double-blind randomized trial of patients with familial adenomatous polyposis, there was no reduction in lower intestinal tract adenomas with long-term use of curcumin versus placebo  (70).

Turmeric extract was found to be safe and equally effective as a non-steroidal anti-inflammatory drug for the treatment of osteoarthritis of the knee (18). Whether curcumin supplementation increases cholesterol levels is unclear, as study results are mixed (19) (20). In a study of postmenopausal women, consumption of curcumin along with aerobic exercise training were shown to improve vascular endothelial function (61).

Turmeric has also been studied in cancer patients. Oral curcumin administered to colorectal cancer patients during the pre-surgery waiting period improved cachexia and the general health of patients (21). In a phase II trial of oral curcumin in patients with advanced pancreatic cancer, no treatment-related toxic effects were observed, and clinically relevant biological activity was seen in two patients despite limited absorption (22). Other preliminary results suggest turmeric during capecitabine treatment may reduce rates of hand-foot syndrome  (71). In another study, supplementation with a blend of green tea, pomegranate, broccoli and curcumin resulted in a reduction in the rate of prostate-specific antigen (PSA) increase among men with prostate cancer following a PSA relapse post-radical treatment (65).

In early phase studies, a combination of curcumin and docetaxel was shown to be safe (23). Curcumin with gemcitabine was also found to be safe and feasible for further study (24) (25), but a high dose of curcumin must be used to achieve systemic effect (23) (25). A dose-finding trial of a curcumin extract to determine safety and efficacy for patients with metastatic disease undergoing standard FOLFOX chemotherapy is currently underway (72). 

Preliminary data suggest effectiveness of a topical turmeric-based cream for reduction of radiotherapy-induced dermatitis in patients with head and neck cancer (64).

Curcumin is known to interfere with cytochrome P450 enzymes (26) (27) and may interact with chemotherapy drugs like cyclophosphamide and doxorubicin (28). Overall, the development of turmeric for clinical use needs further investigation due to its inherent poor absorption, rapid metabolism, complex mechanistic profile, and largely preclinical data.

Turmeric is a major ingredient in curry powder, a spice commonly found in South Asian food.

  • Cancer prevention
  • Infections
  • Inflammation
  • Kidney stones
  • Stomach and intestinal gas

The hepatoprotective effects of curcumin, the most researched active constituent in turmeric, may occur via MMP-13 induction and TGF-alpha inhibition (30), as well as anti-apoptotic/anti-necrotic mechanisms (31). However, it has also been shown to inhibit cell-cycle progression during normal liver regeneration (3).

A meta-analysis of randomized clinical trials revealed that curcumin is effective in decreasing the concentration of tumor necrosis factor-alpha, a key mediator in many inflammatory diseases (68). In vitro and animal studies of lung models point to antiproliferative and modulatory mechanisms involving inhibition of the signal transducer and activator of transcription 3 Stat3 pathway (32), matrix metalloproteinase, and vascular endothelial growth factor (33); caspase- and mitochondria-dependent apoptosis (34) (35); and cyclin-dependent kinase downregulation (35). Curcumin also appears to have synergistic effects with isoflavones, suppressing the prostate-specific antigen (PSA) production in prostate cells through anti-androgen effects (36).

Studies done on breast cancer show that curcumin may inhibit chemotherapy-induced apoptosis via inhibition of the c-Jun NH2-terminal kinase (JNK) pathway and generation of reactive oxygen species (ROS) (28). Data also suggest that curcumin induces apoptosis in human colon cancer cells independent of p21 expression (39). Curcumin’s antitumor actions appear to be due to its interactions with arachidonate metabolism and its in vivo antiangiogenic properties (14). Another possible chemopreventive mechanism may be via binding and activating the vitamin D receptor (VDR), thereby protecting the small intestine and colon where VDRs are expressed and vitamin D is known to serve an anticancer function (38). Curcumin also inhibited growth of uterine leiomyosarcoma cells by targeting the AKT-mTOR (RAC-alpha serine-threonine-protein kinase; mTOR (mammalian target of rapamycin) pathway (37). Curcumin may inhibit bladder cancer progression by downregulating the expression of beta-catenin, high levels of which are associated with several cancers (69).

Another study found that CRM1, an important nuclear exportin, is a cellular target of curcumin; and that the inhibition of nuclear traffic by curcumin may be responsible for its many biological effects (63).

  • Laboratory findings indicate that dietary turmeric may inhibit the anti-tumor action of chemotherapeutic agents such as cyclophosphamide (28).
  • Curcumin may also interact with drugs that are substrates of P-glycoprotein (P-gp) (47) (48) or cytochrome P450 enzymes (48) (49).
  • Patients with gastrointestinal disorders or predisposed to kidney stone formation (50) should also use this supplement with caution.

Patients with bile duct obstruction, gallstones, and GI disorders including stomach ulcers and hyperacidity disorders should not take this supplement (51).

Case Reports

  • Allergic dermatitis: Associated with the use of curcumin (52).
  • Contact urticaria: Two cases, one of which was an occupational exposure, associated with use of curcumin powder (53).
  • Paclitaxel toxicity/Acute toxic hepatitis: In a 67-year-old lung cancer patient, related to a possible interaction with turmeric and contaminated chlorella which were taken during active cancer treatment  (73). Although other supplements were also being taken, increased paclitaxel plasma concentrations were attributed to potential CYP 2C9 and 3A4 inhibition of turmeric as among the causes.

Anticoagulants / Antiplatelets: Turmeric may increase risk of bleeding, as it also has antiplatelet properties (54) (55) (66).
Camptothecin: Turmeric inhibits camptothecin-induced apoptosis of breast cancer cell lines in vitro (28).
Mechlorethamine: Turmeric inhibits mechlorethamine-induced apoptosis of breast cancer cell lines in vitro (28).
Paclitaxel: In a recent case report, a lung cancer patient suffered liver toxicity while undergoing active treatment with paclitaxel. Although he was taking multiple supplements, one of which was tainted, turmeric was thought to be among the likely causes (73).
Doxorubicin: Turmeric inhibits doxorubicin-induced apoptosis of breast cancer cell lines in vitro (28).
Cyclophosphamide: Dietary turmeric inhibits cyclophosphamide-induced tumor regression in animal studies (28).
Norfloxacin: Pretreatment with curcumin resulted in increased plasma elimination half-life, thereby reducing the dosage of norfloxacin (56).
Amphotericin B: Curcumin may enhance the effect and decrease the toxicity of amphotericin B (57).
Drugs metabolized by the CYP3A4 enzyme: Curcumin inhibits cytochrome 3A4 enzyme, altering the metabolism of some prescription drugs (26). But according to conflicting data, short-term use of curcumin may not result in a clinically relevant interaction (67).
Drugs metabolized by the CYP1A2 enzyme: Curcumin inhibits cytochrome 1A2 enzyme, affecting the metabolism of certain prescription medicines (27).
Drugs metabolized by the CYP2A6 enzyme: Curcumin enhances cytochrome 2A6 enzyme, and can affect the metabolism of certain prescription drugs (27).
Drugs metabolized by the CYP2D6 enzyme: Curcumin inhibits cytochrome 2D6 activity and has the potential to interact with CYP2D6 substrates (74).
Celiprolol and Midazolam: Curcumin was shown to downregulate intestinal P-gp levels, thereby increasing the concentrations of celiprolol and midazolam (48).
Verapamil: Curcumin inhibited intestinal P-gp expression and function, thereby increasing concentrations of verapamil (47).
Tacrolimus: Pretreatment with turmeric increases the plasma levels of tacrolimus (59).
Acetaminophen: The cytotoxic effects of curcumin increased significantly in the presence of acetaminophen (60).
Ibuprofen: The cytotoxic effects of curcumin increased significantly in the presence of ibuprofen (60).
Aspirin: The cytotoxic effects of curcumin increased significantly in the presence of aspirin (60).

Curcumin can interfere with thioflavin T assays due to its strong absorptive and fluorescent properties (58).

  1. Bachmeier BE, Mirisola V, Romeo F, et al. Reference profile correlation reveals estrogen-like trancriptional activity of Curcumin. Cell Physiol Biochem. 2010;26(3):471-482.

  2. Cemil B, Topuz K, Demircan MN, et al. Curcumin improves early functional results after experimental spinal cord injury. Acta Neurochir (Wien). Sep 2010;152(9):1583-1590; discussion 1590.

  3. Seehofer D, Schirmeier A, Bengmark S, et al. Inhibitory effect of curcumin on early liver regeneration following partial hepatectomy in rats. J Surg Res. Aug 2009;155(2):195-200.

  4. Yun JM, Jialal I, Devaraj S. Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. J Nutr Biochem. May 2011;22(5):450-458.

  5. Jantan I, Bukhari SN, Lajis NH, et al. Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes. J Pharm Pharmacol. Mar 2012;64(3):404-412.

  6. Chang KW, Hung PS, Lin IY, et al. Curcumin upregulates insulin-like growth factor binding protein-5 (IGFBP-5) and C/EBPalpha during oral cancer suppression. Int J Cancer. Jul 1 2010;127(1):9-20.

  7. Siwak DR, Shishodia S, Aggarwal BB, et al. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer. Aug 15 2005;104(4):879-890.

  8. Uddin S, Hussain AR, Manogaran PS, et al. Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma. Oncogene. Oct 27 2005;24(47):7022-7030.

  9. Kunnumakkara AB, Guha S, Krishnan S, et al. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. Apr 15 2007;67(8):3853-3861.

  10. Selvendiran K, Ahmed S, Dayton A, et al. HO-3867, a curcumin analog, sensitizes cisplatin-resistant ovarian carcinoma, leading to therapeutic synergy through STAT3 inhibition. Cancer Biol Ther. Nov 1 2011;12(9):837-845.

  11. Sreekanth CN, Bava SV, Sreekumar E, et al. Molecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer. Oncogene. Jul 14 2011;30(28):3139-3152.

  12. Qiao Q, Jiang Y, Li G. Curcumin improves the antitumor effect of X-ray irradiation by blocking the NF-kappaB pathway: an in-vitro study of lymphoma. Anticancer Drugs. Jan 23 2012.

  13. Kunnumakkara AB, Diagaradjane P, Guha S, et al. Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappaB-regulated gene products. Clin Cancer Res. Apr 1 2008;14(7):2128-2136.

  14. Ng TP, Chiam PC, Lee T, et al. Curry consumption and cognitive function in the elderly. Am J Epidemiol. Nov 1 2006;164(9):898-906.

  15. Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol. Feb 2008;28(1):110-113.

  16. Bundy R, Walker AF, Middleton RW, et al. Turmeric extract may improve irritable bowel syndrome symptomatology in otherwise healthy adults: a pilot study. J Altern Complement Med. Dec 2004;10(6):1015-1018.

  17. Hanai H, Iida T, Takeuchi K, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clinical Gastroenterol Hepatol. Dec 2006;4(12):1502-1506.

  18. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014 Mar 20;9:451-8.

  19. Pungcharoenkul K, Thongnopnua P. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects. Phytother Res. Nov 2011;25(11):1721-1726.

  20. Baum L, Cheung SK, Mok VC, et al. Curcumin effects on blood lipid profile in a 6-month human study. Pharmacol Res. Dec 2007;56(6):509-514.

  21. He ZY, Shi CB, Wen H, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. Mar 2011;29(3):208-213.

  22. Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. Jul 15 2008;14(14):4491-4499.

  23. 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. Jan 2010;9(1):8-14.

  24. 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. Jul 2011;68(1):157-164.

  25. Epelbaum R, Schaffer M, Vizel B, et al. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010;62(8):1137-1141.

  26. Zhang W, Lim LY. Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro. Drug Metab Dispos. Jul 2008;36(7):1283-1290.

  27. Chen Y, Liu WH, Chen BL, et al. Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers. Ann Pharmacother. Jun 2010;44(6):1038-1045.

  28. Somasundaram S, Edmund NA, Moore DT, et al. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. Jul 1 2002;62(13):3868-3875.

  29. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons; 1996.

  30. Morsy MA, Abdalla AM, Mahmoud AM, et al. Protective effects of curcumin, alpha-lipoic acid, and N-acetylcysteine against carbon tetrachloride-induced liver fibrosis in rats. J Physiol Biochem. Oct 11 2011.

  31. Bulku E, Stohs SJ, Cicero L, et al. Curcumin exposure modulates multiple pro-apoptotic and anti-apoptotic signaling pathways to antagonize acetaminophen-induced toxicity. Curr Neurovasc Res. Feb 1 2012;9(1):58-71.

  32. Alexandrow MG, Song LJ, Altiok S, et al. Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev. Dec 7 2011.

  33. Lin SS, Lai KC, Hsu SC, et al. Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and Vascular Endothelial Growth Factor (VEGF). Cancer Lett. Nov 28 2009;285(2):127-133.

  34. Chen QY, Lu GH, Wu YQ, et al. Curcumin induces mitochondria pathway mediated cell apoptosis in A549 lung adenocarcinoma cells. Oncol Rep. May 2010;23(5):1285-1292.

  35. Wu SH, Hang LW, Yang JS, et al. Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways. Anticancer Res. Jun 2010;30(6):2125-2133.

  36. Ide H, Tokiwa S, Sakamaki K, et al. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate. Jul 1 2010;70(10):1127-1133.

  37. Wong TF, Takeda T, Li B, et al. Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition. Gynecol Oncol. Jul 2011;122(1):141-148.

  38. Bartik L, Whitfield GK, Kaczmarska M, et al. Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. J Nutr Biochem. Dec 2010;21(12):1153-1161.

  39. Watson JL, Hill R, Lee PW, et al. Curcumin induces apoptosis in HCT-116 human colon cancer cells in a p21-independent manner. Exp Mol Pathol. Jun 2008;84(3):230-233.

  40. Yang KY, Lin LC, Tseng TY, et al. Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. Jun 15 2007;853(1-2):183-189.

  41. 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. Jan 2005;14(1):120-125.

  42. Bishnoi M, Chopra K, Rongzhu L, et al. Protective effect of curcumin and its combination with piperine (bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence. Neurotox Res. Oct 2011;20(3):215-225.

  43. Tsai YM, Chien CF, Lin LC, et al. Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int J Pharm. Sep 15 2011;416(1):331-338.

  44. Orr WS, Denbo JW, Saab KR, et al. Liposome-encapsulated curcumin suppresses neuroblastoma growth through nuclear factor-kappa B inhibition. Surgery. Jan 26 2012.

  45. Asai A, Miyazawa T. Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. Life Sci. Oct 27 2000;67(23):2785-2793.

  46. Ravindranath V, Chandrasekhara N. Absorption and tissue distribution of curcumin in rats. Toxicology. 1980;16(3):259-265.

  47. Hou XL, Takahashi K, Tanaka K, et al. Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. Int J Pharm. Jun 24 2008;358(1-2):224-229.

  48. Zhang W, Tan TM, Lim LY. Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos. Jan 2007;35(1):110-115.

  49. Appiah-Opong R, Commandeur JN, van Vugt-Lussenburg B, et al. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology. Jun 3 2007;235(1-2):83-91.

  50. Tang M, Larson-Meyer DE, Liebman M. Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects. Am J Clin Nutr. May 2008;87(5):1262-1267.

  51. Ulbricht CE, Basch, EM. Natual Standard Herb & Supplement Reference: Evidence-Based Clinical Reviews St. Louis, MO: Elsevier Mosby; 2005.

  52. Lamb SR, Wilkinson SM. Contact allergy to tetrahydrocurcumin. Contact Dermatitis. Apr 2003;48(4):227.

  53. Liddle M, Hull C, Liu C, et al. Contact urticaria from curcumin. Dermatitis. Dec 2006;17(4):196-197.

  54. Prakash P, Misra A, Surin WR, et al. Anti-platelet effects of Curcuma oil in experimental models of myocardial ischemia-reperfusion and thrombosis. Thromb Res. Feb 2011;127(2):111-118.

  55. Jantan I, Raweh SM, Sirat HM, et al. Inhibitory effect of compounds from Zingiberaceae species on human platelet aggregation. Phytomedicine. Apr 2008;15(4):306-309.

  56. Pavithra BH, Prakash N, Jayakumar K. Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits. J Vet Sci. Dec 2009;10(4):293-297.

  57. Kudva AK, Manoj, MN, Swamy, BM, et al. Complexation of amphotericin B and curcumin with serum albumins: solubility and effect on erythrocyte membrane damage. J Exp Pharmacol. 2011;2011(3):1-6.

  58. Hudson SA, Ecroyd H, Kee TW, et al. The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds. FEBS J. Oct 2009;276(20):5960-5972.

  59. Egashira K, Sasaki H, Higuchi S, Ieiri I. Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats. Drug Metab Pharmacokinet. 2012 Apr 25;27(2):242-7.

  60. Choi HA, Kim MR, Park KA, Hong J. Interaction of over-the-counter drugs with curcumin: influence on stability and bioactivities in intestinal cells. J Agric Food Chem. 2012 Oct 24;60(42):10578-84.

  61. Akazawa N, Choi Y, Miyaki A, et al. Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women. Nutr Res. 2012 Oct;32(10):795-9.

  62. Sanmukhani J, Satodia V, Trivedi J, et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014 Apr;28(4):579-85.

  63. Niu M, Wu S, Mao L, Yang Y. CRM1 is a cellular target of curcumin: new insights for the myriad of biological effects of an ancient spice. Traffic. 2013 Oct;14(10):1042-52.

  64. Palatty PL, Azmidah A, Rao S, et al. Topical application of a sandal wood oil and turmeric based cream prevents radiodermatitis in head and neck cancer patients undergoing external beam radiotherapy: a pilot study. Br J Radiol. 2014 Jun;87(1038):20130490.

  65. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P. A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the U.K. NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014 Jun;17(2):180-6.

  66. Daveluy A, Geniaux H, Thibaud L, et al. Probable interaction between an oral vitamin K antagonist and turmeric (Curcuma longa). Therapie. Nov-Dec 2014;69(6):519-520.

  67. Volak LP, Hanley MJ, Masse G, et al. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2013 Feb;75(2):450-62.

  68. Sahebkar A, Cicero AF, Simental-Mendía LE, Aggarwal BB, Gupta SC. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res. 2016 May;107:234-42.

  69. Shi J, Wang Y, Jia Z et al. Curcumin inhibits bladder cancer progression via regulation of β-catenin expression. Tumour Biol. 2017 Jul;39(7):1010428317702548.

  70. 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. Sep 2018;155(3):668-673.

  71. Scontre VA, Martins JC, de Melo Sette CV, et al. Curcuma longa (Turmeric) for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Pilot Study. J Diet Suppl. Sep 3 2018;15(5):606-612.

  72. Irving GR, Iwuji CO, Morgan B, et al. Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial. Trials. Mar 24 2015;16:110.

  73. Costa ML, Rodrigues JA, Azevedo J, et al. Hepatotoxicity induced by paclitaxel interaction with turmeric in association with a microcystin from a contaminated dietary supplement. Toxicon. Aug 2018;150:207-211.

  74. Al-Jenoobi FI, Al-Thukair AA, Alam MA, et al. Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects. Eur J Drug Metab Pharmacokinet. Mar 2015;40(1):61-66.

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