
Indian saffron, curcumin, jiang huang
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 coloring agent in food and cosmetics for its yellow-orange color. It is also used in traditional medicine for circulation and digestion. The extract is marketed as a dietary supplement 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. Data from an epidemiological study suggest improved cognitive performance in elderly Asians who consume turmeric in the form of curry powder (14); however, no benefits from curcumin supplementation were detected in patients with Alzheimer’s disease (15). Turmeric may help alleviate symptoms of irritable bowel syndrome (16) as well as quiescent ulcerative colitis (17). 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 may increase cholesterol levels is unclear, as study results are mixed (19) (20).
In patients with colorectal cancer, oral curcumin administered 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). 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).
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.
Curcumin’s hepatoprotective effects 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). In vitro and animal lung models point to anti-proliferative and modulatory mechanisms such as Stat3 (32), matrix metalloproteinase, and vascular endothelial growth factor (33) inhibition; caspase- and mitochondria-dependent apoptosis (34) (35); and cyclin-dependent kinase downregulation (35). Curcumin appears to synergize with isoflavones, suppressing PSA production in prostate cells through anti-androgen effects (36). Curcumin induced apoptosis via AKT-mTOR inhibition in uterine leiomyosarcoma cells (37). In pancreatic cancer patients, downregulation of NF-kappa B and cyclooxygenase-2 were observed (22). Another possible chemopreventive mechanism of curcumin may be via vitamin D receptor (VDR) binding and activation, thereby protecting tissues of the small intestine and colon where VDRs are expressed and vitamin D is known to serve anticancer functions (38). Curcumin-induced apoptosis may be p21-dependent in colon cancer (39). Upregulation of p53 modulation of Bax and Bcl- 2 was also observed in colorectal cancer patient tissues (21). Curcumin may inhibit chemotherapy-induced apoptosis via JNK pathway inhibition and reactive oxygen species generation (28).
Oral curcumin is poorly absorbed and rapidly metabolized (40) (41). However, bioavailability of curcumin can be increased when coadministered with piperine (42). Nanoparticle (43) or liposomal formulations (44) can also increase absorption. Metabolism is primarily via glucuronidation to glucuronide and glucuronide/sulfate metabolites (45). Excretion of the parent compound is primarily in the feces with metabolites present in the urine (46).
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).
Anticoagulants / Antiplatelets: Turmeric may increase risk of bleeding, as it also has antiplatelet properties (54) (55).
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).
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 CYP3A4 enzyme: Curcumin inhibits cytochrome 3A4 enzyme, altering the metabolism of some prescription drugs (26).
Drugs metabolized by CYP1A2 enzyme: Curcumin inhibits cytochrome 1A2 enzyme, affecting the metabolism of certain prescription medicines (27).
Drugs metabolized by CYP2A6 enzyme: Curcumin enhances cytochrome 2A6 enzyme, and can affect the metabolism of certain prescription drugs (27).
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: Pre-treatment 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).
He ZY, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011 Mar;29(3):208-13.
This study examined oral curcumin supplementation in newly diagnosed patients with colorectal cancer (CRC). Using the waiting period before surgery as the supplement therapy period, 126 patients were randomized to receive curcumin 360 mg three times daily (n=63) or vehicle capsule (placebo; n=63) prior to primary surgery for a period of 10 to 30 days. Postsurgical treatment included radiotherapy (n=31), chemotherapy (n=84), or both (n=9), but 20 patients received no additional chemotherapy. Treatment with curcumin led to body weight gain, with observed increases in p53 expression, DNA fragmentation, and Bax and Bcl-2 modulation. No significant differences between groups were noted for calorie intake or diarrhea events, and there were no cases of CRC-caused obstruction to affect interpretation of results. Investigators concluded that a supplemental remedy of presurgical curcumin could improve the general health of patients with CRC and provide a novel method to improve cachexia.
Kuptniratsaikul V, et al. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med. 2009 Aug;15(8):891-7.
This study included 107 patients with primary knee osteoarthritis with pain score of > or =5. Participants were randomized to receive 800 mg/day ibuprofen or 2g/day C. domestica extracts for 6 weeks. Improvement in pain on level walking, pain on stairs, and functions of the knee assessed by time spent during a 100-m walk and going up and down a flight of stairs were the primary outcome measures. The authors reported significant improvement at 0, 2, 4 and 6 weeks compared with baseline values in both groups, with the exception of pain on stairs (p = 0.016). Adverse events also did not differ much between the groups (33.3% vs 44.2%, p = 0.36 with C. domestica extracts and ibuprofen). C. domestica extracts demonstrated efficacy and were safe compared with ibuprofen in the treatment of knee osteoarthritis, but the small sample size of this study warrants further research.
Baum L, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol. 2008 Feb;28(1):110-3.
Twenty-seven patients with progressive decline in memory and cognitive function for 6 months were randomized to receive 4 g, 1 g (with 3 g color-matched placebo powder) or 4 g of placebo once daily for 6 months. Patients were also given one capsule containing 120 mg standardized ginkgo leaf extract as it showed moderate benefit in previous studies. A Mini-Mental State Examination was administered at baseline and at 6 months. Plasma and serum were monitored at 0, 1, and 6 months for levels of antioxidants, amyloid-beta, and liver and kidney function. Researchers reported lack of cognitive decline in patients in the placebo group precluding any conclusions about the beneficial effects of curcumin. However, serum amyloid-beta levels were higher in the curcumin group regardless of dose, compared with placebo. This suggests that curcumin may play a role in disaggregating amyloid-beta deposits in the brain releasing them into circulation. No adverse effects were observed with curcumin intake. Long-term, larger studies are needed to further evaluate curcumin’s role in preventing Alzheimer’s disease.
Dhillon N, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008 Jul 15;14(14):4491-9.
Twenty-five patients with advanced pancreatic cancer were given 8 g curcumin daily, orally, until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. Researchers observed downregulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients, many of whom had high baseline values compared with healthy volunteers. Clinically relevant biological activity was seen in two patients. Curcumin should be evaluated in larger, randomized trials. Increasing its bioavailability may render it more effective.
Baum L, et al. Curcumin effects on blood lipid profile in a 6-month human study. Pharmacol Res. 2007 Dec;56(6):509-14.
The effects of curcumin on blood lipid profiles were assessed in this randomized, double-blind study of 36 elderly participants. Subjects were separated into a control or curcumin-treated groups (1 or 4 g/day), and serum lipid profiles were measured at baseline, 1 month, and 6 months. The side effects were similar between the groups. No significant differences in serum lipid profiles were detected upon curcumin administration; however, levels of absorbed curcumin were modestly associated with increased cholesterol concentration. Larger studies are required to determine if curcumin supplementation may increase cholesterol levels.
Eighty-nine patients with quiescent ulcerative colitis were randomized to receive curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, or placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at baseline, every 2 months (CAI), at the end of the trial, and at the 6-month follow-up. The recurrence rates showed significant difference between curcumin and placebo groups (p = 0.049). Curcumin also improved both CAI (p = 0.038) and EI (p = 0.0001) thereby reducing the morbidity associated with ulcerative colitis. Two patients on curcumin relapsed during the study period compared with 8 in the placebo group. A 6-month follow-up showed that an additional 8 patients in the curcumin group and 6 in the placebo group relapsed. Further studies are needed to evaluate curcumin's potential as a maintenance therapy for ulcerative colitis.
Bottom Line: Turmeric demonstrated anti-inflammatory and anticancer activities in lab studies. Recent clinical trial suggests curcumin has biological activity in some cancer patients but more studies are needed to verify its benefits.
Turmeric is a spice that has been used in cooking for centuries. Scientists have determined that turmeric has many biological activities, although they do not fully understand exactly how it exerts these effects. From laboratory experiments, it has been deduced that substances in turmeric (called curcuminoids) prevent inflammation by inhibiting the molecules that mediate inflammatory reactions. Curcuminoids may protect the body in a few ways: they enhance the activity of an important detoxifying enzyme and they also act as antioxidants by neutralizing free radicals (which can cause DNA damage). In rats, turmeric prevented the development of kidney damage from toxins. Turmeric also stimulates the flow of bile in the gastrointestinal tract.
In rats exposed to cancer-causing substances, those that were treated with turmeric were protected from colon, stomach, and skin cancers. Turmeric also stops the replication of tumor cells when applied directly to them in the laboratory, 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 have suggested that turmeric might interfere with the activity of some chemotherapy drugs in breast cancer, 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.
Osteoarthritis
This study randomized 107 patients with primary knee osteoarthritis with pain score of > or =5 to receive 800 mg/day ibuprofen or 2 g/day C. domestica extracts for 6 weeks. The authors report significant improvement at 0, 2, 4 and 6 weeks compared to baseline values in both the groups, with the exception of pain on stairs. Side effects also did not differ much between the groups. C. domestica extracts were as effective and safe as ibuprofen in the treatment of knee osteoarthritis.
Alzheimer's Disease
Twenty-seven patients with progressive decline in memory and cognitive function for 6 months were randomized to receive 4 g, 1 g (with 3 g color-matched placebo powder) or 4 g of placebo once daily for 6 months. Patients were also given one capsule containing 120 mg standardized ginkgo leaf extract as it showed moderate benefit in previous studies. Researchers reported lack of cognitive decline in patients in the placebo group so it is not clear if curcumin can benefit patients with Alzheimer's disease. More studies are needed.
Cancer Treatment
Twenty-five patients with advanced pancreatic cancer were given 8 g curcumin daily, orally, until disease progression, with restaging every 2 months. Researchers reported biological activity (lowered expression of some immune system markers) of curcumin in some patients, with brief remission in one patient. Larger, randomized studies are needed.
High Cholesterol
The effects of curcumin on blood lipid profiles were studied in this randomized, double-blind trial of 36 elderly participants. Subjects received curcumin (1 or 4 g/day) or placebo and their serum lipid profiles were measured at baseline, 1 month, and 6 months. The side effects were similar between the groups. The authors observed a slight increase in cholesterol levels in the curcumin group. Larger studies are required to determine if curcumin supplementation may increase cholesterol levels.
Ulcerative colitis
Eighty-nine patients with inactive ulcerative colitis were randomized to receive curcumin, 1 g after breakfast and 1 g after the evening meal, plus sulfasalazine (SZ) or mesalamine, or placebo plus SZ or mesalamine for 6 months. The recurrence rates showed significant difference between curcumin and placebo groups, with those in curcumin group faring better; curcumin reduced the morbidity associated with ulcerative colitis.