Turmeric

• How It Works

  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.

  Patients with gastrointestinal disorders and those predisposed to kidney stone formation should consult their physicians before using turmeric supplements.

• Purported Uses
  • 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, animal and clinical studies suggest that turmeric reduces inflammation.
  • To treat kidney stones
    Evidence is lacking to support this claim.
  • To relieve stomach and intestinal gas
    Evidence is lacking to support this claim.
• Do Not Take If
  • 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. Clinical relevance is not known.
  • You are taking tacrolimus, an immunosuppressant: Curcumin supplements increase plasma levels of tacrolimus and may increase side effects. Clinical relevance is not known.
  • You are taking drugs metabolized by the CYP3A4 enzyme: Curcumin inhibits cytochrome 3A4 enzyme, altering the metabolism of certain prescription drugs. Clinical relevance is not known.
  • You are taking drugs metabolized by the CYP1A2 enzyme: Curcumin inhibits cytochrome 1A2 enzyme, altering the metabolism of certain prescription drugs. Clinical relevance is not known.
  • You are taking drugs metabolized by the CYP2A6 enzyme: Curcumin enhances cytochrome 2A6 enzyme, altering the metabolism of certain prescription drugs. Clinical relevance is not known.
  • You are taking drugs metabolized by the CYP2D6 enzyme: Curcumin inhibits cytochrome 2D6 activity and has the potential to interact with CYP2D6 substrates. Clinical relevance is not known.
  • 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. Clinical relevance is not known.
• Side Effects

  Possible gastrointestinal discomfort

  Case Reports

  • Allergic dermatitis: Associated with the use of curcumin.
  • Contact urticaria: Two cases, one of which was an occupational exposure, associated with use of curcumin powder.
  • 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. 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.
• Special Point
  • Patients with gastrointestinal problems or at higher risk of kidney stones should consult their physicians before using turmeric supplements.
• Scientific Name

  Curcuma longa, Curcuma domestica

• Clinical Summary

  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, among which curcumin has been the focus of research. In vitro studies suggest that curcumin 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⁾. Findings of a systematic review suggest that turmeric or curcumin supplementation may benefit patients with non alcoholic fatty liver disease by positively affecting serum concentrations of liver enzymes ⁽⁷⁵⁾.

  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⁾; and of topical application of turmeric or curcumin for controlling signs and symptoms of oral mucositis ⁽⁷⁶⁾.

  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.

• Food Sources

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

• Purported Uses
  • Cancer prevention
  • Infections
  • Inflammation
  • Kidney stones
  • Stomach and intestinal gas
• Mechanism of Action

  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⁾.

• Contraindications

  Patients with gastrointestinal disorders and those predisposed to kidney stone formation ⁽⁵⁰⁾ should consult their physicians before using turmeric supplements.

• Adverse Reactions

  Possible gastrointestinal discomfort  ⁽¹⁸⁾

  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.
• Herb-Drug Interactions

  Anticoagulants / Antiplatelets: Preclinical studies ^(54) (55) and a case report ⁽⁶⁶⁾ suggest that turmeric can increase risk of bleeding^.
  Camptothecin: Turmeric inhibits camptothecin-induced apoptosis of breast cancer cell lines in vitro ⁽²⁸⁾. Clinical relevance is not known.
  Mechlorethamine: Turmeric inhibits mechlorethamine-induced apoptosis of breast cancer cell lines in vitro ⁽²⁸⁾. Clinical relevance is not known.
  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⁾. Clinical relevance is not known.
  Cyclophosphamide: Dietary turmeric inhibits cyclophosphamide-induced tumor regression in animal studies ⁽²⁸⁾. Clinical relevance is not known.
  Norfloxacin: Pretreatment with curcumin resulted in increased plasma elimination half-life, thereby reducing the dosage of norfloxacin in animal model ⁽⁵⁶⁾. Clinical relevance is not known.
  Amphotericin B: Curcumin enhanced the effect, and decreased the toxicity of amphotericin B, in vitro ⁽⁵⁷⁾. Clinical relevance is not known.
  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 did not result in a clinically relevant interaction in healthy volunteers ⁽⁶⁷⁾.
  Drugs metabolized by the CYP1A2 enzyme: Curcumin inhibits cytochrome 1A2 enzyme, affecting the metabolism of certain prescription medicines, in vitro. Clinical relevance is not known ⁽²⁷⁾.
  Drugs metabolized by the CYP2A6 enzyme: Curcumin enhances cytochrome 2A6 enzyme, and can affect the metabolism of certain prescription drugs ⁽²⁷⁾. Clinical relevance is not known.
  Drugs metabolized by the CYP2D6 enzyme: Curcumin inhibits cytochrome 2D6 activity and has the potential to interact with CYP2D6 substrates ⁽⁷⁴⁾. Clinical relevance is not known.
  Celiprolol and Midazolam: Curcumin was shown to downregulate intestinal P-gp levels, thereby increasing the concentrations of celiprolol and midazolam in a murine model ⁽⁴⁸⁾. Clinical relevance is not known.
  Verapamil: Curcumin inhibited intestinal P-gp expression and function, thereby increasing concentrations of verapamil, in vitro ⁽⁴⁷⁾. Clinical relevance is not known.
  Tacrolimus: Pretreatment with turmeric increases the plasma levels of tacrolimus in a murine model ⁽⁵⁹⁾. Clinical relevance is not known.
  Acetaminophen: The cytotoxic effects of curcumin increased significantly in the presence of acetaminophen in vitro ⁽⁶⁰⁾. Clinical relevance is not known.
  Ibuprofen: The cytotoxic effects of curcumin increased significantly in the presence of ibuprofen ⁽⁶⁰⁾. Clinical relevance is not known.
  Aspirin: The cytotoxic effects of curcumin increased significantly in the presence of aspirin ⁽⁶⁰⁾. Clinical relevance is not known.

• Herb Lab Interactions

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

• References

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