Scientific Name(s): Curcuma longa L.
Common Name(s): Curcuma, Curcumin, Haldi, Indian saffron, Turmeric
Medically reviewed by Drugs.com. Last updated on Jan 7, 2022.
Use of curcumin (turmeric) as a pharmacologic agent is limited due to its low systemic bioavailability following oral dosing. Curcumin is used as a spice in curry powders and mustard. It is marketed with claims of potent antioxidant activity, improving bone and joint health, and reducing inflammation, but clinical trials are limited. Its efficacy in treating numerous cancers has been investigated. Curcumin has been shown to provide antidepressant and anxiolytic effects in people with major depressive disorder; however, clinical trials are limited.
Curcumin is primarily available in capsule form from commercial manufacturers. The most common regimen is one to three 500 mg capsules daily with or without food. In one study, patients took one 500 mg capsule twice daily with or without food for 8 weeks for treatment of major depressive disorder. Powdered turmeric root has traditionally been used as a stimulant and carminative at dosages of 0.5 to 3 g/day. Dosages of 3 to 6 g/day have been investigated for protective effects against ulcers. Analgesic effects have been reported with doses of 1.5 to 2 g/day. Daily oral doses of 3,600 mg have been typically used in clinical trials, but dosages of up to 8 g/day have also been used. Higher doses are associated with adverse GI effects.
Avoid use if hypersensitive to any of the components of curcumin. Avoid use during pregnancy and lactation due to emmenagogue and uterine stimulant effects. The herb should not be used in patients with gall stones or bile duct or passage obstruction.
Avoid use. Documented emmenagogue and abortifacient effects.
C. longa may potentially interact with CYP2D6 and CYP3A substrates.
Clinical trials report few adverse reactions (eg, dyspepsia, pruritus). Rare cases of contact dermatitis and anaphylaxis have been reported.
Limited clinical data are available. The oral median lethal dose (LD50) of curcumin in rats and mice was higher than 2,000 mg/kg body weight.
The genus Curcuma L. may contain more than 100 species, with Curcuma longa L. probably the best known. Synonymous with Curcuma domestica Val, turmeric is a perennial plant found throughout Southeast Asia, as well as China, Australia, and the South Pacific. India and Thailand have the highest diversity with at least 40 species in each country. The plant grows to a height of 0.9 to 1.5 m and produces large, oblong leaves and funnel-shaped, dull-yellow flowers. The thick rhizome is yellowish in color externally and deep orange to reddish-brown internally. The lateral rhizomes contain more yellow coloring than the bulb. The dried primary bulb and secondary lateral rhizomes are collected, cleaned, boiled, and dried for use in medicinal and food preparations.1, 2, 3, 4, 5
Traditionally, turmeric has been used as a food, cosmetic, and medicine. Turmeric is a spice with a warm and bitter taste used primarily as a component of curry powders and some mustards. Its distinctive yellow color has commercial applications as a coloring agent in cheese, butter, and other foods.2, 3, 5
Turmeric and its natural curcuminoids have been used medicinally over the centuries in different parts of the world. In the traditional Ayurvedic medical system, turmeric is a well-recognized treatment for numerous respiratory conditions (eg, asthma, bronchial hyperactivity, allergies), liver disorders, anorexia, rheumatism, diabetic wounds, cough, and sinusitis.5, 6 In the Indian subcontinent, turmeric is medicinally valued for its wound healing properties. In traditional Chinese medicine, turmeric is used to treat conditions that cause abdominal pain. Turmeric has anti-inflammatory activity and was used to treat sprains and swelling in ancient Hindu medicine.5, 6
The rhizome contains up to 7% of an orange-yellow, volatile oil. Tumerone and artumerone together comprise about 60% of the oil, and zingiberene comprises about 25%. Cineole, d-phellandrene, d-sabinene, and borneol are present in low concentrations. The major yellow pigment has been identified as curcumin (diferuloylmethane), a phenolic antioxidant. Unlike most natural antioxidants that contain beta-diketone or polyphenolic functional groups, curcumin possesses both active moieties. Its superior antioxidant activity has been attributed to this structural combination. Curcumin modulates the Nrf2-keap1 pathway in the cell and binds to antioxidant responsive elements in DNA that reduce the reactive oxygen species. Other curcuminoids structurally related to curcumin are also found in the extract and include demethoxy-curcumin and bis-demothoxy-curcumin. Additionally, the turmeric rhizome contains protein, fat, minerals, and carbohydrates.2, 3, 4, 5, 6, 7, 8, 9, 123
Uses and Pharmacology
Most clinical trials focus on the active principle curcumin individually rather than on turmeric. The medicinal use of curcumin is limited due to its low systemic bioavailability following oral dosing limits. Curcumin is hydrophobic and cannot be given intravenously; it also disappears rapidly from tissues after intraperitoneal administration. An encapsulated liposomal form has been examined in animals2, 10, 11 and numerous approaches continue to be investigated to improve its bioavailability, including concomitant use of black pepper (Piper nigrum) or one of its active constituents piperine.12, 13, 123
Adults with osteoarthritis of the knee experienced a significant reduction in severity of pain and function when administered 500 mg twice daily of C. longa rhizome extract (12.6% w/w polysaccharides) in a randomized, single-blind, placebo-controlled, comparative study (n = 120). A decrease in use of rescue analgesic (acetaminophen) was also significant in the treated group. Study medication acceptability was highest for the C. longa group who also exhibited the fewest adverse effects.87 A systematic review and meta-analysis of 8 randomized clinical trials (N = 734) published before December 2014 found an overall moderate to large effect of Zingiberaceae extracts (including turmeric, ginger, and galangal) on chronic pain compared with placebo; however, substantial heterogeneity was found. Significantly lower subjective pain was reported with the intervention (P = 0.004). A strong dose-response relationship was also demonstrated. Patient groups included 3 studies in patients with osteoarthritis of the knee or hip, and 1 study each in patients with gonarthritis, irritable bowel syndrome, muscle soreness following exercise, postoperative pain, and primary dysmenorrhea. The 2 trials that used curcumin or curcuminoids (n = 90) used 1,500 mg/day (combined with 15 mg/day of black pepper extract to enhance bioavailability) for 6 weeks in osteoarthritis patients and 2,000 mg/day for 3 weeks in patients recovering from surgery.105 A noninferiority test found curcumin extract (1,500 mg/day; 500 mg 3 times daily) to be as effective as ibuprofen (1,200 mg/day; 400 mg 3 times daily) for improving pain and function in osteoarthritis patients in a 4-week double-blind, randomized, controlled comparator study that enrolled 367 adults with primary knee osteoarthritis. Curcumin improved overall osteoarthritis index scores (P=0.01), pain (P=0.018), and function (P=0.01). The mean age of participants was 60 years consisting of approximately 90% women. The incidence of adverse events was similar between groups; however, significantly more patients in the ibuprofen group experienced abdominal pain and distension.109 A 2016 systematic review and meta-analysis that evaluated 8 randomized controlled trials reported significantly reduced pain scores for curcumin compared to placebo in arthritis patients (eg, osteoarthritis, rheumatoid arthritis). Doses were similar across the studies with about 1 g/day given in the absence of other analgesics and about 500 mg/day given concomitantly with pain killers. Duration of treatments ranged from 4 weeks to 4 months. No significant difference was observed for pooled results between curcumin and analgesic medications (ie, ibuprofen, diclofenac, glucosamine) suggesting about 1 g/day of curcumin may have similar effects to these analgesic agents.113
Curcumin has been shown to interfere with the eicosanoid pathway, involving cyclooxygenase and lipoxygenase enzymes, reflecting the traditional use of turmeric in Ayurvedic and Chinese medical systems for inflammation.64 Older clinical trials have been conducted comparing curcumin with phenylbutazone.2 The therapeutic effect of curcumin was comparable to that of hydrocortisone in treating experimental pulmonary fibrosis.65
A total of 100 hemodialysis patients who also experienced treatment-resistant uremic pruritus for at least 6 weeks were randomized in a double-blind trial to receive 1,500 mg of turmeric daily or placebo for 8 weeks. Both groups experienced significantly reduced total pruritus scores after treatment (P = 0.0001 for each). The authors reported that the mean reduction in the turmeric group (13.6) was significantly better than the mean reduction in the placebo group (7.2) (P = 0.001). Additionally, the mean decrease in C-reactive protein was significantly greater with turmeric than placebo (−0.8 mg/L vs 0.4 mg/L, respectively; P = 0.012).100
Management of acute inflammation pain subsequent to removal of impacted molars was explored in a randomized, controlled (n=90) trial. Both the active control (mefenamic acid) and curcumin (400 mg 3 times daily × 24 hours) were effective in reducing postoperative inflammatory pain with patients in the curcumin group reporting significantly higher reductions in pain at each time point (P=0.0001 each). Additionally, more patients in the curcumin group reported higher pain score reductions of either 6 or 7 than the control group (57% vs 24%, respectively, for treatment vs control), whereas score reductions in the control group were mostly 4 or 5 (55.6%).124
In a randomized, single-blind, placebo-controlled, comparative study (n = 120), adults with osteoarthritis of the knee experienced a significant reduction in severity of pain and function when administered 500 mg twice daily of C. longa rhizome extract (12.6% w/w polysaccharides). A decrease in use of rescue analgesic (acetaminophen) was also significant in the treated group. The C. longa group also exhibited the fewest adverse effects.87 A noninferiority test found curcumin extract (1,500 mg/day; 500 mg 3 times daily) to be as effective as ibuprofen (1,200 mg/day; 400 mg 3 times daily) for improving pain and function in osteoarthritis patients in a 4-week double-blind, randomized, controlled comparator study that enrolled 367 adults with primary knee osteoarthritis. Curcumin improved overall osteoarthritis index scores (P=0.01), pain (P=0.018), and function (P=0.01).109 A 2016 systematic review and meta-analysis that evaluated 8 randomized controlled trials reported significantly reduced pain scores for curcumin compared to placebo in arthritis patients (eg, osteoarthritis, rheumatoid arthritis). Doses were similar across the studies with about 1 g/day given in the absence of other analgesics and about 500 mg/day given concomitantly with pain killers. Duration of treatments ranged from 4 weeks to 4 months. No significant difference was observed for pooled results between curcumin and analgesic medications (ie, ibuprofen, diclofenac, glucosamine), suggesting approximately 1 g/day of curcumin may have similar effects to these analgesic agents. Functional outcomes, including morning stiffness and movements, also improved with curcumin, however fundamental improvement in arthritis symptoms were not seen. At doses up to 1,200 mg/day given for up to 4 months, turmeric preparations and curcumin were considered safe.113
A randomized, single-blind pilot study was conducted in 45 adults with rheumatoid arthritis who were randomly assigned to curcumin 500 mg, diclofenac 50 mg, or the combination of the 2 agents twice daily for 8 weeks. All 3 groups experienced significant improvements from baseline in disease activity scores (DAS) and American College of Rheumatology (ACR) joint scores. The curcumin group’s improvements in DAS and ACR scores were significantly better than the diclofenac group’s scores.91
Curcumin and its analogs exhibit growth suppressive activity against a broad range of tumors including skin, forestomach, duodenal, gall bladder, and colon at multiple stages of development, including initiation, promotion, and metastasis.2, 3, 14, 15, 16, 17, 88 Several mechanisms of action are proposed for curcumin’s anticancer activity, including inhibiting expression of growth and metastases-promoting genes; regulation of molecular targets that control cell adhesion, apoptosis, and invasion; and regulation of enzymes that control tumor growth.14, 15, 16, 17, 18, 88 Studies have also indicated that curcumin has a radiosensitizing effect on cancer cell cultures.19, 20
Numerous studies in animal models support curcumin’s possible suppression of tumorigenic activity of a wide variety of carcinogens involved in leukemia and colon, duodenum, esophagus, forestomach, stomach, liver, breast, oral cavity, and prostate cancers.5, 14, 17 However, not all experiments have shown positive results. A study in rats failed to demonstrate any effects in the prevention of prostate carcinoma.21
Phase 1, 2, and 3 clinical trials of curcumin are being conducted by the National Cancer Institute.22 A phase 1 study is measuring the levels of curcumin and its metabolites in normal colorectal tissue in patients undergoing colorectal endoscopy or colorectal cancer surgery following a 14-day course of curcumin. An open-label study is examining the short-term effects of supplementation with a turmeric extract on patients with newly diagnosed head and neck squamous cell carcinoma. A phase 2 trial is assessing whether curcumin can cause regression of colorectal and duodenal adenomatous polyps in patients with familial adenomatous polyposis. Another phase 1 trial is investigating the use of plant exosomes in delivering and improving the bioavailability of curcumin for treating colon tumors and normal colon tissue. Additional studies include assessment of the efficacy of curcumin and ashwagandha extract in treating high-grade relapsed or metastatic osteosarcoma, and examination of curcumin’s anti-inflammatory and anti-oxidative properties as a therapeutic option in pancreatic cancer patients.22 Results of a double-blind, randomized, placebo-controlled trial (n=44) in adults with familial adenomatous polyposis documented no significant difference in polyp burden (size or number) in patients treated for 12 months with curcumin (100% pure, 3 g/day) compared to placebo. Treatment was well tolerated with 1 report of pruritus likely related to curcumin.120
The efficacy of curcumin in preventing colorectal cancer has been investigated by the National Cancer Institute.14, 22 In smokers, turmeric 1.5 g/day for 30 days reduced the urinary excretion of mutagens compared with controls.23 Trials have been conducted in patients with colorectal cancer refractory to standard therapy, primarily to explore tolerance and safety.24, 25
A limited number of patients demonstrated stable radiological conditions for up to 4 months after curcumin treatment. Administration of curcumin to 12 patients with colorectal cancer showed pharmacologically active levels of the agent in the target tissue.26 Reduction in the biological marker M1G after curcumin use was attributed to an antioxidant action of curcumin in the tumor. Clinical outcomes were not reported. Investigators concluded that pharmacologically active levels of curcumin could not be achieved in patients with hepatic metastases because of poor oral bioavailability.2 An open-label clinical trial in 41 smokers found no reduction in procarcinogenic eicosanoids, prostaglandin E2 or 5-hydroxyeicosatetraebiuc acid, in aberrant crypt foci or normal flat mucosa during treatment with oral curcumin 2 or 4 g/day for 30 days. However, treatment with oral curcumin 4 g/day for 30 days reduced aberrant crypt foci formation.27 In a randomized, placebo-controlled clinical trial, a combination of soy isoflavones (40 mg) and curcumin (100 mg) decreased serum prostate specific antigen (PSA) in patients whose baseline PSA was more than 10 ng/mL.28
A phase 2 trial of curcumin in patients with pancreatic cancer was conducted with oral curcumin. Twenty-one patients received oral curcumin 8 g/day without treatment-related toxicity for up to 18 months. Changes in cytokine levels (elevated at baseline) were recorded, a nonsignificant reduction in nuclear factor kappa B was shown in most patients, and radiological stability was demonstrated in 2 patients.10 The efficacy of combined treatment of curcumin and gemcitabine in patients with advanced pancreatic cancer has been evaluated.29, 30
A phase 1 trial with combined treatment of curcumin and docetaxel in patients with advanced and metastatic breast cancer administered curcumin 6,000 mg/day for 7 consecutive days every 3 weeks in combination with docetaxel. The treatment dose did not lead to dose-limiting toxicity; rather, the pill burden from the number of curcumin capsules per day limited dosing.31
Studies in animals have demonstrated anti-platelet effects, as well as positive effects on lipid profiles, including a decreased susceptibility of low-density lipoprotein (LDL) to oxidation.32, 33, 34 In experimental atherosclerosis in rabbits, animals receiving the extract had less damage from fatty streaks in the thoracic and abdominal aortas at 30 days than did those in the control groups. Markers of oxidative stress were also improved in the trial group.8
Additional clinical trial data are needed to evaluate efficacy. Among healthy volunteers, curcumin 500 mg/day for 7 days decreased serum cholesterol and lipid peroxide levels and increased high-density lipoprotein (HDL).2 A 500 mg daily curcumin supplement was more effective than 6 g/day in reducing serum cholesterol and triglyceride levels.35 Another study documented similar results in patients with acute coronary syndrome.36 No effect on lipid profile was observed in a trial evaluating the effect of turmeric 1.5 g/day on urinary excretion of mutagens.23
A dose of curcumin 300 mg orally twice daily over 8 weeks reduced inflammatory cytokines and markers of oxidative stress on endothelial dysfunction comparable with that of atorvastatin in patients with type 2 diabetes.37 Another double-blind randomized clinical trial in Thai patients with type 2 diabetes (n = 240), observed significant improvement in atherogenic risk during 6 months of supplementation with curcuminoid 750 mg/day (250 mg 3 times daily) that followed a 3-month lead-in of diet and lifestyle education. Antiatherogenic activity, measured by pulse wave velocity, adiponectin, leptin, insulin resistance, triglycerides, uric acid, and total body fat were all significantly improved at 6 months (P < 0.001) as was visceral fat (P < 0.05). The majority of these parameters were also significantly improved at the 3-month visit. Compliance was comparable between the treatment and placebo group with no serious side effects reported.97
A meta-analysis of 7 treatments across 6 studies that included 172 subjects found a significant reduction in the systemic inflammation biomarker, C-reactive protein, with standardized curcuminoid preparations that were taken for at least 4 weeks. Doses ranged from 200 to 6,000 mg/day with variable bioavailability. Over half of the studies (4/6) were rated high-quality, while the other 2 were low-quality; overall heterogeneity was high.96 Another meta-analysis of 7 randomized, controlled trials (N=649) in patients with cardiovascular risk factors (eg, type 2 diabetes, metabolic syndrome) identified an overall significant positive effect for turmeric and/or curcumin products on LDL cholesterol (P<0.0001) and triglycerides (P=0.007) with no significant heterogeneity. Subgroup analysis revealed significant improvement in patients with metabolic syndrome (N=136; P<0.0001) but not in those with hyperglycemia. No serious adverse reactions were reported.119
In vitro and in vivo studies have examined curcumin’s complex mechanism of action.2, 38, 39, 40, 41 Curcumin may target several pathophysiological pathways involved in Alzheimer disease including the beta-amyloid cascade, tau phosphorylation, neuroinflammation, or oxidative stress. Its poor bioavailability and insolubility in water creates therapeutic limitations; however, curcumin analogues may warrant further investigation for Alzheimer treatment.40, 42
There are limited clinical trial data on the use of curcumin in treating Alzheimer disease. In a randomized clinical trial, the low bioavailability of curcumin 1 to 4 g/day for 6 months may have contributed to no improvement in cognitive performance in patients with mild to moderate Alzheimer disease. No beneficial effect was documented on proinflammatory biomarkers such as serum amyloid-beta peptide and isoprostanes.43 Another study found that vitamin D3 may interact with curcuminoids to stimulate beta-amyloid clearance by activating type I macrophages in patients with Alzheimer disease.44, 45 In 46 middle-aged and elderly (age 50 to 90 years) non-demented volunteers with clinical histories consistent with normal aging or mild neurocognitive disorder, administration of a highly bioavailable colloidal curcumin (180 mg/day Theracurmin) for 18 months improved verbal memory performance as seen with significantly better differences in long-term recall scores compared to placebo (effect size d=0.68, P=0.05). Additionally, differences in the measure of attention was also found to be significantly better in the curcumin group compared to controls (d=0.55). No significant change between groups was seen for visual memory assessments. Deposition of amyloid plaques and tau tangles was found to be significantly improved with curcumin compared to placebo in the hypothalamus and were correlated significantly with the changes in Beck Depression Inventory scores (P=0.02). Findings from this double-blind, randomized, placebo-controlled trial were adjusted for age and education; apolipoprotein E4 status or family history of dementia was not found to significantly affect the results.118 Improvements in sustained attention, working memory, and prevention of cognition loss in older healthy adults has also been documented.123
A randomized controlled trial compared safety and efficacy of curcumin with that of fluoxetine in 60 patients with major depressive disorder (without suicidal ideation). After 6 weeks, curcumin 1,000 mg/day was found to be equivalent to fluoxetine 20 mg/day in proportion of responders based on Hamilton depression scale scores; however, patients on combination therapy showed a better response than either of the monotherapy regimens. None of the responses were statistically significant. Fewer patients on curcumin achieved remission. Curcumin was well tolerated with only mild gastritis and nausea reported.95 Both placebo and curcumin (1,000 mg/day) provided significant improvements from baseline to week 4 in self-reported depressive and anxiety scores in subjects with major depressive disorder participating in an 8-week, randomized, double-blind, placebo-controlled trial (N = 56). However, beneficial effects continued from week 4 to 8 only in the curcumin group. Additionally, curcumin administration resulted in a significant and greater benefit than placebo in a subgroup of participants with atypical depression.101 A small double-blind trial randomized 48 elderly prediabetes patients (median age, 71 to 75 years) to receive a single dose of turmeric (1 g), cinnamon (2 g), both (1 and 2 g, respectively), or placebo prior to a white-bread breakfast to determine acute effects on working memory. Of a total score of 3, postprandial working memory increased over the 6-hour observation period from 2.6 to 2.9 (P = 0.05) with turmeric users compared with non-turmeric users. These changes were not noted with cinnamon users and were independent of body fat, glycemia, insulin, or Alzheimer disease biomarkers.99
Animal studies in diabetic mice and rats have shown hypoglycemic effects for curcumin.3, 46, 47, 48 A review documented curcumin’s beneficial effects in reducing the complications of type 2 diabetes including hepatic fibrosis, retinopathy, neuropathy, and nephropathy.49 Curcumin may suppress advanced glycation end products, therefore reducing oxidative stress, inflammation, and hepatic stellate cell activation.49 Curcumin supplementation in rats over 7 weeks improved muscle insulin resistance by increasing oxidation of fatty acid and glucose.50 In an experimental type 1 diabetes animal model, curcumin improved left ventricular function and reduced fibrosis and hypertrophy in rats.51
Limited clinical trial data are available. In healthy volunteers, oral turmeric 2.8 g/day for 4 weeks had no effect on fasting blood glucose levels.52 A 4-week pilot study examined the effects on diabetic microangiopathy using a lecithin formulation of curcumin at a dose of 1 g orally per day in 25 diabetic patients. Curcumin improved microcirculation and decreased edema when compared with controls.53A 500 mg curcumin regimen administered 3 times daily to type 2 diabetic nephropathy patients in a 2-month randomized, double-blind, and placebo-controlled study improved urinary protein excretion and expression of transforming growth factor and interleukin (IL)-8.54
Curcumin extract was evaluated for prevention of type 2 diabetes in 240 adult patients with prediabetes in a randomized, double-blind, placebo-controlled trial. After a 3-month run-in with instructions on diet and exercise, patients were randomized to receive 3 oral capsules containing curcuminoid 250 mg per capsule or matching placebo twice daily for 9 months. A diagnosis of type 2 diabetes was seen in 16.4% of placebo patients, compared with 0% in the curcumin group. As compared with placebo, the curcumin group had significantly lower results for hemoglobin A1c, fasting plasma glucose, and 2-hour oral glucose tolerance test glucose level. The curcumin group also had significant changes in 9-month values for reductions in body mass index and waist circumference, improved beta-cell function, and increased adiponectin. Body mass and waist circumference were numerically but not statistically lower at 3 months and 6 months with curcumin.89
Another small double-blind trial randomized 48 elderly prediabetes patients (median age, 71 to 75 years) to receive a single dose of turmeric (1 g), cinnamon (2 g), both (1 and 2 g, respectively), or placebo prior to a white-bread breakfast to determine acute effects on working memory. Of a total score of 3, postprandial working memory increased over the 6-hour observation period from 2.6 to 2.9 (P = 0.05) with turmeric users compared with non-turmeric users. These changes were not noted with cinnamon users and were independent of body fat, glycemia, insulin, or Alzheimer disease biomarkers.99 The TAK-MetS trial, a double-blind, randomized controlled trial comparing the efficacy of powdered black seeds (kalongi) and turmeric as mono- and combination therapy in Pakistani males with metabolic syndrome reported significant improvements in cholesterol, LDL-cholesterol, and C-reactive protein after 8 weeks of turmeric monotherapy (2.4 g/day) compared to placebo. Combination therapy (900 mg/day black seeds + 1.5 g/day turmeric) resulted in significant improvements in percent body fat, all lipid parameters, fasting blood glucose, and C-reactive protein compared to placebo. Compared to baseline, the placebo group exhibited significant improvements in body mass index and percent body fat by the end of the study. Mild adverse effects (ie, dyspepsia, pruritus) were reported at 4 weeks in 4 patients receiving turmeric with only the additional report of weakness and weight reduction in the combination therapy group leading to withdrawal of one patient at 6 weeks.103 Similarly, in a phase 3 double-blind, randomized controlled trial in Iran, supplementation with a proprietary combination (curcuminoid 500 mg/piperine 5 mg twice daily) for 8 weeks in 100 men and women diagnosed with metabolic syndrome who had not previously taken lipid-lowering medication resulted in a significant improvement in oxidative and inflammatory markers, including hs-C-reactive protein, superoxide dismutase, malondialdehyde, and fasting blood glucose (P < 0.001 each). The authors also conducted a meta-analysis of 8 randomized controlled trials (N = 562) and determined the effect of curcuminoids on C-reactive protein to be robust with potential publication bias noted.107
In a randomized, double-blind study involving 12 patients, a curcumin 20 mg dose induced 30% contractions in the gall bladder.5, 66 A similar study administering curcumin 40 and 80 mg produced 50% and 70% contraction of the gall bladder volume, respectively.5, 67 Another clinical study documented reduced pain and postoperative fatigue after laparoscopic cholecystectomy in patients treated with 500 mg of oral curcumin every 6 hours.68
Turmeric and curcumin have been found to cause species changes in the gut microbiota of healthy adults with curcumin primarily responsible for the changes. In contrast to placebo, responses of the gut microbiota to turmeric and curcumin were highly personalized and non-uniform, but not random. Responders exhibited uniform increases in Clostridium species, Bacteroides species, Citrobacter species, Cronobacter species, Enterobacter species, Enterococcus species, Klebsiella species, Parabacteroides species, and Pseudomonas species as well as decreases in Blautia and Ruminococcus species.122, 122
Pretreatment of rats with curcumin for 5 days before induction of colitis resulted in a reduction in colonic inflammation, histologic damage, and inflammatory markers. Curcumin recipients also demonstrated reduced weight loss compared with controls.55 Another animal study showed that treatment of mice with curcumin reduced the incidence of diarrhea and the disruption of colonic architecture.56 Curcumin reduced key inflammatory signaling through p38 MAPK activation, enhanced IL-10, and reduced IL-1–beta in colonic mucosal biopsies and colonic myofibroblasts isolated from children and adults with active irritable bowel disease.57 Curcumin’s protective effects may be IL-10–dependent as shown by its limited effectiveness on Th-1–mediated colitis in IL-10–deficient mice.58
A pilot study investigated the use of standardized turmeric root extract 1,800 or 3,600 mg/day in 207 patients with irritable bowel syndrome. Improvement in quality of life scores was reported by both groups. A trend favoring the higher dosage was observed in a post hoc analysis of abdominal pain and discomfort.46 A similar pilot study conducted in patients with Crohn disease found favorable results.59
A randomized, double-blind, placebo-controlled 6-month trial in 89 patients given curcumin as maintenance therapy for ulcerative colitis showed differences in relapse rate compared with placebo. The dose of curcumin used was 1 g twice daily in combination with standard maintenance therapy of mesalamine or sulfasalazine.60
Improvement in colitis has been attributed to the anti-inflammatory and antioxidant effects of curcumin.46, 55, 56 Results from animal studies61 and uncontrolled trials62, 63 suggest a role for turmeric in the treatment of duodenal or gastric ulcer. A 2016 double-blind, randomized, placebo-controlled trial investigated adjunctive use of curcumin in 68 Iranian adults with gastric pain, dyspepsia symptoms, and confirmed gastric or duodenal ulcers in the presence of H. pylori. In addition to standard H. pylori triple therapy, patients received curcumin 500 mg plus piperine 5 mg daily as adjunctive therapy. The same number of patients in both groups had documented infection eradication (73.3%) and significant improvement in all dyspepsia symptoms, except vomiting, with total severity scores also improved (P<0.001). However, adjunctive use of curcumin led to significantly greater improvements in belching (P=0.028), upper abdominal dull ache (P=0.002), stomach pain before meals (P=0.004), and total dyspeptic severity scores (P<0.001). More patients in the curcumin group reached a non-dyspeptic total score by the end of the study than those in the placebo group (27.6% vs 6.7%, respectively; P<0.001) and significantly more had resolution of dyspepsia with curcumin also (P=0.042). Treatment was well tolerated with no serious adverse events reported.111
A protective effect against chloroquine-induced hepatotoxicity was demonstrated by curcumin administered to rats.69 Curcumin given adjunctively with antituberculosis therapy reduced the incidence of hepatotoxicity in patients in a clinical trial.70
The benefit of turmeric in 48 adult patients with elevated serum ALT levels was investigated in a 12-week, randomized, placebo-controlled trial. Patients received 2 fermented turmeric powder 500 mg capsules or matching placebo 3 times daily. Significant reductions at week 12 compared with placebo were seen with fermented turmeric powder for ALT and AST. No significant difference between groups was seen for gamma glutamyl transferase, alkaline phosphatase, total bilirubin, or lipid levels.90
Administration of a single 6 g dose of curcuma containing mixed curcuminoids (120 mg curcumin) to healthy male volunteers resulted in significant decrease in hepcidin levels at 3 time points over 48 hours post ingestion. Serum ferritin levels were also significantly decreased compared to placebo (P=0.015); however, serum iron, transferrin, transferrin saturation, and glucose levels were not significantly affected. Transient GI symptoms occurred in 2 participants; no serious adverse events were reported. The results of this proof-of-concept double-blind, randomized, controlled cross-over study (n=18) confirmed earlier results demonstrated in vitro.116
Oral lichen planus is the mucosal counterpart to cutaneous lichen planus; both are T-cell mediated autoimmune diseases. The efficacy of curcumin in treatment of oral lichen planus (OLP) was explored in a double-blind, randomized, placebo-controlled trial that enrolled 20 patients with confirmed diagnosis of erosive-atrophic OLP. In addition to routine treatment with dexamethasone 0.5 mg mouthwash and Nystatin suspension, patients received oral curcumin 2,000 mg/day (1,000 mg twice daily) or placebo for 4 weeks. Both the treatment and placebo groups experienced significant reductions from baseline in severity of pain and burning as well as in the type and severity of lesions at 2 and 4 weeks; no statistically significant difference was observed between groups.110
Administration of turmeric with black pepper (400 mg + 100 mg; 2 capsules 3 times daily for 3 months) produced a significant improvement in mouth opening and burning sensation (P<0.01 each) in patients with oral submucous fibrosis in a double-blind, randomized, comparator trial (n=40). Serum superoxide dismutase levels were also significantly improved (P<0.05). No significant difference was found in patients treated with turmeric/black pepper and those treated with nigella sativa. Both interventions were well tolerated.117
Delayed onset of cataracts has been associated with the use of oral curcumin in rats. However, the effect was only observed at low dosages (0.002%), and a higher dosage of 0.01% showed no benefit.71 In a clinical trial among patients with chronic anterior uveitis, curcumin appeared to be comparable with standard corticosteroid therapy at 375 mg 3 times a day.2
In vitro studies and animal experiments suggest a role for curcumin in wound healing. An in vitro study demonstrated protective effects of curcumin against hydrogen peroxide in human keratinocytes and dermal fibroblasts.9 Oral pretreatment with curcumin 100 mg/kg hastened wound healing in mice exposed to postoperative gamma radiation.72 Enhancement of collagen synthesis and markers of wound healing were demonstrated. Histological assessment of wound biopsy specimens showed improved collagen deposition as well as increased fibroblast and vascular densities.
A small, randomized, placebo-controlled trial was conducted in 30 breast cancer patients undergoing radiation therapy to evaluate the benefit of oral curcumin 2 g 3 times daily beginning at the start of radiation. Patients were permitted to use topical agents (eg, hydrocortisone, silver sulfadiazine) that constitute usual care for radiation dermatitis. The curcumin group had significantly lower radiation dermatitis scores and incidence of moist desquamation compared with the placebo group.92
A randomized, double-blind study evaluated the benefit of curcumin 1 g/day in 96 war veterans with chronic cutaneous complications from sulphur-mustard exposure. Curcumin was statistically superior to placebo for improvements at 4 weeks for itching, dermatology life quality index scores, lab values including interleukin (IL) -8, calcitonin gene-related peptide, and high-sensitivity C-reactive protein. IL-6 change was not statistically better with curcumin versus placebo.93
A phase IV, double-blind, randomized, placebo-controlled, single-center, pilot study (n = 21) sought to demonstrate a local therapeutic response in patients with moderate to severe plaque psoriasis to oral Curcuma extract when activated by local visible light phototherapy in addition to whole-body ultraviolet (A) phototherapy (minus the local plaque area). Plaque lesions were larger than 4 cm2. Curcuma extract 72 mg/day (100 mg standardized C. longa with 12 mg curcumin per tablet) was taken 48 to 72 hours prior to starting the phototherapy regimen of twice a week × 2 months; groups were randomized to receive either real or simulated visible light treatment to the experimental plaque area. At follow up visit 9 of 18, 100% of the patients receiving real visible light therapy experienced improvement in lesions to at least "moderate" compared to 40% in the placebo (simulated) group. By visit 18 at the end of the study, evolution of lesion improvement to "slight" was exhibited by 81% and 30% of real versus simulated light therapy, suggesting a possible new and safer therapeutic method for these patients.106 A systematic review of alternative therapies for psoriasis found preliminary high-quality evidence to support a recommendation of oral phospholipid-based curcumin on a trial basis as adjunctive treatment for patients with psoriasis. Evidence for use of topical curcumin in these patients is limited.121
Vitamin E levels
A 6-week randomized controlled trial investigated the effect of curcumin on serum vitamin E levels in Iranian patients with metabolic syndrome (n=120). Curcumin-phospholipid complex (1 g/day; equivalent to 200 mg/day pure curcumin) supplementation resulted in a significant reduction in the mean vitamin E levels compared to baseline (−0.12 micromol/L; P=0.004). Additionally the mean reduction between the curcumin-phospholipid as well as the curcumin (1 g/day) groups and controls was significant (P=0.004 and P=0.005, respectively). The increase in ratios of vitamin E to total cholesterol, LDL, and triglycerides observed in the control group were mitigated with the curcumin treatments. This was also true for the increase observed with the vitamin E:HDL ratio in controls that was significantly lower in the intervention groups.114
Curcumin is primarily available in capsule form from commercial manufacturers. It is marketed with claims of potent antioxidant activity, improving bone and joint health, and reducing inflammation. One to three 500 mg capsules daily with or without food is the most common regimen recommended by manufacturers. In one study, patients took one 500 mg capsule twice daily with or without food for 8 weeks for treatment of major depressive disorder.101 Powdered turmeric root has traditionally been used as a stimulant and carminative at dosages of 0.5 to 3 g/day. Dosages of 3 to 6 g/day have been investigated for protective effects against ulcers.62, 63 Daily oral doses of curcumin 3,600 mg have been advocated for use in clinical trials25 but dosages of up to 8 g/day have been used in patients with advanced pancreatic cancer.10 A highly absorbable colloidal nanoparticle formulation has been used at 1,800 mg/day for memory improvement and reduction of amyloid deposition in non-demented adults.118 Higher doses are associated with adverse GI effects.2
Pregnancy / Lactation
Avoid use during pregnancy and lactation because potential emmenagogue and abortifacient effects have been documented.73, 74, 75 Estrogenic and antiandrogenic effects are documented in animal models.76 An extract of C. longa had a contraceptive effect in male rats. A reduction in sperm motility was observed in rats receiving turmeric 500 mg/kg/day as an aqueous or alcoholic extract.77
Agents with Antiplatelet Properties: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification.78, 79, 80, 81
Herbs (Anticoagulant/Antiplatelet Properties): May enhance the adverse/toxic effect of other Herbs (Anticoagulant/Antiplatelet Properties). Bleeding may occur. Consider therapy modification.78, 79, 80, 81
Nonsteroidal Anti-Inflammatory Agents: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Consider therapy modification.78, 79, 80, 81
C. longa significantly inhibited the formation of the dextromethorphan metabolites, dextrorphan (DOR) and 3-methoxymorphinan (3-MM), in a dose-dependent and linear fashion. Urine metabolic ratio of dextromethorphan:DOR was significantly increased, while the dextromethorphan:3-MM ratio was insignificantly increased. C. longa has great potential to inhibit CYP2D6 enzyme activities.102
A case report noted a probable interaction between turmeric (2.5 g/day for 5 days) and the vitamin K antagonist fluindione that resulted in a sudden increase in a 56-year-old woman’s previously stabilized international normalized ratio (INR) from 2 or 3 up to 6.5. However, no clinical signs of bleeding were observed. No information was documented that identified this interaction as an INR lab interaction versus a pharmacological one.98
A case report of probable interaction between turmeric (at least 15 spoonsful/day) and tacrolimus was reported in a 56-year-old male liver transplant patient. All other possible causes of elevated tacrolimus and acute kidney injury were ruled out. The interaction was attributed to likely interference of tacrolimus metabolism by turmeric via the P450 3A system, which led to acute calcineurin inhibitor nephrotoxicity. Data from animal studies regarding the potential for turmeric to affect the P450 system supported the conclusion.112
Other interaction data
Some studies have reported insignificant pharmacokinetic drug interactions with natural products. Limited information as well as potentially high interpatient variability in clinical response warrants cautious interpretation and/or application of these data in practice.
A small pharmacokinetic interactions study in healthy volunteers who received curcuminoid 4 g 4 times daily for 2 days prior to oral administration of single doses of midazolam, flurbiprofen, and acetaminophen found no significant changes in pharmacokinetic parameters including Cmax, area under the curve, and terminal half-life. Investigators selected these agents to probe cytochrome (CYP) 3a (midazolam), 2C9 (flurbiprofen), sulfotransfer, and UDP-glucuronosyltransferase (acetaminophen).94
Trials have generally reported few adverse reactions associated with turmeric or curcumin ingestion, even at the high dosages used in cancer trials.10, 25 GI-related symptoms have been reported.2, 7, 25, 103 Allergic contact dermatitis was reported in 2 patients after using curcumin-containing chlorhexidine solutions,82 and patch tests were positive for curcumin in both cases. A case of anaphylaxis after turmeric ingestion has been documented.83 Over a 3-day period, the patient experienced recurrent urticaria and angioedema that was unresponsive to treatment with epinephrine, antihistamines, and corticosteroids. Allergy testing for turmeric was positive. A review identified 3 studies (n = 121) and 10 case reports confirming allergenic potential of curcumin via patch and skin prick testing.104 A 2017 FDA Safety Alert documented 2 acute serious hypersensitivity cases resulting from the IV injection of a curcumin emulsion compounded with polyethylene glycol (PEG) 40 castor oil. The latter is an ungraded product that is not suitable for human consumption and is known to cause hypersensitivity reactions. Both patients had a positive history of allergies; 1 case was fatal. The safety profile of curcumin administered by the IV route has not been established. The FDA recommendation was for the recall of all unexpired products containing the ungraded PEG 40 castor oil by the compounding agent, ImprimisRx.115
Turmeric contains relatively high concentrations of oxalate, and increased levels of urinary oxalate excretion have been demonstrated.52 Although the risk of kidney stone formation may be increased in susceptible individuals, reports of kidney problems are lacking. The addition of curcumin to the diets of mice induced iron-deficiency anemia, including a decline in serum iron, decreased hematocrit, decreased transferrin saturation, and appearance of hypochromic RBCs. Curcumin also decreased iron levels in the bone marrow and spleen.84
Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases was caused by herbals and dietary supplements whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, turmeric was among the 22% (116) of the single-ingredient products.108
Evaluation of mice treated with short- and long-term C. longa ethanolic extracts of 100 mg/kg/day for 90 days found no serious adverse reactions. Weight was not affected by long-term treatment; however, changes in heart and lung weight were reported, and white and red blood cell levels were reduced.85 The oral median lethal dose (LD50) of curcumin in rats and mice was higher than 2,000 mg/kg body weight.86 No clinical ophthalmic, body weight, feed consumption, or organ weight changes were documented in a 90-day toxicity study in rats. Furthermore, no adverse effects from the toxicity study were noted on hematology, serum chemistry, and urinalysis.
- Curcuma domestica Val
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