Pain and inflammation.
Turmeric is used for many disorders involving pain and inflammation including osteoarthritis, rheumatoid arthritis (RA), acute injuries to the muscles and joints, headaches, and fibromyalgia.
See Curcuma monograph 2 for jaundice, hepatitis, and other liver and gallbladder conditions.
Mechanism of Action
Curcumin, a bright yellow flavonoid in turmeric, is a powerful antioxidant credited with anticancer effects. It has been the subject of more than 5000 scientific and clinical studies over the past decade.1,2 The group of compounds related to curcumin in turmeric are referred to as curcuminoids, and it include demethoxycurcumin and bisdemethoxycurcumin, both of which are less abundant and less potent antioxidants than curcumin itself. Curcumin’s major metabolite, tetrahydro-curcumin, is a less potent antioxidant than curcumin itself in many arenas, but it may be superior to curcumin in promoting liver glutathione and heptoprotection.1
Research has also investigated bisabolane-type sesquiterpenes and saikosaponins in turmeric that are reported to have antifibrotic effects on the liver. Additional active molecules in turmeric include the essential oils, a group of aromatic sesquiterpenes compounds including elemene, turmerin, turmerone, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone.1 Elemene is an approved anticancer agent in China and has been shown to retard cell cycle arrest, induce of apoptosis, and inhibit metastasis and tissue invasion.3,4
Turmeric has numerous anti-inflammatory mechanisms of action including the modulation of signal transduction cascades and effects on gene expression, especially antioxidant and immune-modulating proteins. Curcumin modulates numerous molecular targets by altering their gene expression and signaling pathways, or through direct interaction.
- Inflammatory cytokines (tumor necrosis factor, Interleukin-1, -6, -8, and 12)
- Growth factors (epidermal growth factors VEGF, EGF, FGF)
- Growth factor receptors (EGFR, HER-2, AR)
- Immune- and inflammation-modulating enzyme systems (cyclooxygenase [COX], lipoxygenase, metalloproteinase, mitogen-activated protein kinase, mTOR, Akt, nitric-oxide synthase, catalase, glutathione S-transferase, glutathione reductase, and glutathione peroxidase; levels of reduced glutathione, aldo-keto reductase family, serine/threonine-protein kinase, protein kinase C, polymerase, heme-oxygenase as well as superoxide dismutase)
- Adhesion molecules (ELAM-1, ICAM-1, VCAM-1)
- Apoptosis-related proteins (Bcl-2, caspases, DR, Fas)
- Cell-cycle proteins (cyclin D1)
- Transcription factors (NF-κB, AP-1, STAT) and their signaling pathways
- AMPK, PPAR-γ
- Inhibits prostaglandin E2
Turmeric has been extensively researched for systemic immune and antioxidant effects,25 giving it potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative diseases, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. Despite centuries of use, there have not yet been a large number of quality clinical trials on turmeric.19
Curcumin is hydrophobic and has poor bioavailability because of its rapid metabolism in the liver and intestinal wall and because it is quickly cleared from the plasma, further limiting its therapeutic utility. Many researchers are investigating nanospheres and molecular combinations to enhance curcumin’s solubility and absorption.26,27,28,29,30 Piperine, an alkaloid from black pepper (Piper nigrum), inhibits hepatic and intestinal glucuronidation and enhances the assimilation of many important nutrients. At a dose of 20 mg, piperine may increase the absorption of curcumin as much as 2000 times. Taking curcumin with fat, phospholipids, or in lipid-processed nutraceutical forms may also enhance its bioavailability.
Curcuma for Autoimmune Modulation: Multiple sclerosis, RA, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythematosus, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. RA is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. Curcuma can promote appropriate apoptosis and protect against hyperplasia of the synovial fibroblasts in RA.14 Curcumin may induce apoptosis via activation of caspase-3 and -9 and the concomitant degradation of polymerase proteins.31 Tissue culture studies also show curcumin to inhibit the breakdown of the extracellular matrix in cartilage cells when stimulated by interleukin-β and helps protect arthritic joints from destruction,32 preventing osteoclast formation,33 and inhibiting interleukin β–induced degradation of the extracellular matrix and release of glycosaminoglycan.34 These mechanisms may also reduce adhesion after abdominal surgery35 and limit the replacement of functioning connective tissue with fibrotic tissue in autoimmune diseases. Curcumin also benefits autoimmune diseases by inhibiting the binding of autoantibodies to tissues in Sjögren’s syndrome and systemic lupus erythematosus.36 It suppresses chondrogenesis, inhibits reorganization of the actin cytoskeleton, down-regulates integrin β-1, and inhibits focal adhesion kinase phosphorylation.37
Curcuma for Joint Pain and Arthritis: Turmeric may help reduce connective tissue inflammation, provide pain relief, and reduce disease progression in osteoarthritis and autoimmune diseases. A common research model for inducing a rheumatoid-like arthritis involves injecting collagen type II subdermally or in connective tissues, which provokes autoimmune reactivity in susceptible animals. The administration of turmeric extract arrests the degenerative changes in the bone and joints of collagen-induced arthritic rats.38,39 Curcumin has been shown to attenuate acute inflammation in animal models of arthritis greater than that of prednisone in the first several hours, but less powerfully than the steroid after 48 h.40 When curcuminoids are dosed at the start of induced rheumatoid arthritis, the compounds lessen the severity of the inflammatory response and slow further disease progression.31 Curcuminoids increase the production of anti-inflammatory cytokines while decreasing the production of proinflammatory cytokines. One investigation reported greater efficacy than indomethacin at a dose of 200 mg/kg body weight.7
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medication for treatment of knee and other osteoarthritic pain, accomplished through inhibition of prostaglandin synthesis via COX-1 and COX-2 isoenzymes. However, the long-term use of NSAIDs has serious side effects on the kidneys, liver, and gastrointestinal (GI) system. One randomized controlled trial (RCT) study compared the effects of curcuminoids (30 mg 3 times per day) to the NSAID diclofenac (25 mg
3 times per day) on COX activity in the synovial fluid of patients with osteoarthritis. They found no significant differences between the groups.41 Another similar study compared diclofenac with curcumin (75 mg/100 mg) to diclofenac with placebo 75 mg/0) on osteoarthritic knee pain. After 3 months’ time the curcumin with diclofenac group showed a trend toward reduced pain and better function in daily living compared with the diclofenac only group.42 Several “noninferiority” RCTs have compared the efficacy of Curcuma domestica 1500 mg/day to ibuprofen 1200 mg/day on knee pain as a result of osteoarthritis in human subjects. After 4 weeks, the Western Ontario and McMaster Universities Osteoarthritis Index scores showed no significant difference in pain, stiffness, or function scores between the two group and adverse side effects of digestive upset and abdominal pain only in the ibuprofen group.43,44
Curcumin as an All-Purpose Anti-inflammatory: Based on cell culture and animal research, turmeric’s anti-inflammatory and immune-modulating effects can also offer therapeutic benefits for inflammatory bowel and gastric cancer.45 Curcumin reduces Helicobacter pylori–induced gastric inflammation by decreasing inflammatory cytokines and chemokines.46 Curcumin also reduces inflammatory processes in cardiovascular disease, pulmonary disease,47 allergies, pancreatitis, psoriasis, atherosclerosis, and chronic anterior uveitis as well as certain types of cancer.6,7 Curcumin may also reduce inflammation in the neurons and is being explored as preventative against the progression of Parkinson’s and Alzheimer’s diseases.48 Curcumin also promotes wound healing in burns by promoting re-epithelialization.49
Safety in Pregnancy and Breastfeeding
There are no published studies specifically investigating turmeric in pregnancy or lactation. However, curry blends containing turmeric have been consumed during pregnancy for thousands of years without reports of adverse effects. Some nursing women report that eating garlic, onions, curry, and other spices can be passed through the breast milk and give nursing infants gas or colic symptoms. The most common foods causing infant colic are garlic and onion, coffee and tea (caffeine), chocolate, and foods in the Brassicaceae and Fabaceae families.
Clinical trials have reported excellent tolerability without significant adverse events.7,42,50,51 One clinical trial dosing 3 g/day of fermented turmeric powder reported no adverse events over the 12-week trial and no adverse effects on blood glucose, total protein, albumin, blood urea nitrogen, or creatinine levels.52 A pilot phase I clinical trial reported curcumin to be safe even when consumed at a daily dose
of 12 g/day for 3 months.46
A standard battery of in vitro genotoxicity tests, bacterial reverse mutation test, chromosome aberration, and micronucleus tests revealed no concerns. In an acute oral toxicity study, turmeric was found to be safe up to 5 g/kg body weight in Wistar rats.53
Turmeric affects cytochrome p450 enzymes including 3A4; however, cell line studies often do not match human results and drug interactions have not been reported.54 Animal studies have shown turmeric to magnify the inhibitory effects of paclitaxel and cisplatin on some cytochrome pathways, an effect that is mentioned as a concern for drug-herb interactions55 but that may also allow for a reduced dose of these chemotherapeutic drugs. At supraphysiologic doses, Curcuma longa treatment was shown to cause reversible suppression of spermatogenesis and fertility in male mice; however, no such studies have been undertaken in humans nor have anecdotal findings been reported in clinical trials on turmeric.56
Traditional dosing of crude turmeric powder was in the range of 1–3 g daily or prepared in various teas and curries and formulas of 10 g of fermented powder or several grams whole turmeric root. Has been standardized to curcuminoids, dihydrocurcumoids, or both.
Safe at high doses, with the highest dose in a trial of 18 g/day, and the most common side effect is GI upset.
There are several lipid extracts and nanoparticle products on the market that claim to be more bioavailable, but clinical trials are required to determine their actual clinical effectiveness and appropriate dosage.
Curcuma longa is a common culinary spice in East India, going by the name turmeric, and it is included in curry blends. Turmeric has been widely used in the traditional Chinese Pharmacopoeia57 as well as being traditionally used as a spice, natural food preservative, natural food coloring, textile dye, antiaging and facial cosmetic ingredient, and herbal medicine. Traditional medicinal indications include biliary disorders; anorexia; cough; rheumatism; cancer, sinusitis; liver and bladder disorders including gallstones, jaundice, hepatitis and liver cancer; hyperglycemia; obesity; diabetes and diabetes-related liver disorders; nerve pain and disease; kidney and vascular diseases; bacterial and fungal infections; skin inflammation and disease; digestive and pancreatic disorders; and mood disorders.
Turmeric is traditionally combined with Boswellia,58 ginger,59,60 or bromelain in traditional formulations for musculoskeletal pain and arthritis, all having some research showing efficacy for pain and inflammation.
Mol Nutr Food Res. 2013;57(9):1529–42. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Aggarwal BB, Yuan W, Li S, Gupta SC.
2 Arch Physiol Biochem. 2008;114(2):127–49. Role of curcumin in health and disease. Pari L, Tewas D, Eckel J.
3 J Ethnopharmacol. 2012;143(2):406–11. Anti-cancer properties of terpenoids isolated from Rhizoma Curcumae–a review. Lu JJ, Dang YY, Huang M, Xu WS, Chen XP, Wang YT.
4 Mol Med Rep. 2012;6(1):185–90. Potential role of β-elemene on histone H1 in the H22 ascites hepatoma cell line. Bao F, Qiu J, Zhang H.
5 Biofactors. 2013;39(1):37–55. Molecular mechanisms of curcumin action: gene expression. Shishodia S.
6 Altern Med Rev. 2009;14(2):141–53. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Jurenka JS.
7 Curr Drug Targets. 2011;12(3):332–47. The targets of curcumin. Zhou H, Beevers CS, Huang S.
8 Oncol Lett. 2014;7(1):17–22. Analysis of the anticancer activity of curcuminoids, thiotryptophan and 4-phenoxyphenol derivatives. Parsai S, Keck R, Skrzypczak-Jankun E, Jankun J.
9 Cell Mol Life Sci. 2008;65(11):1631–52. Curcumin: from ancient medicine to current clinical trials. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV.
10 Otol Neurotol. 2014;35(5):e169–77. Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction. Fetoni AR, Eramo SL, Paciello F, Rolesi R, Podda MV, Troiani D, Paludetti G.
11 Chin Med. 2008;3:11. Recent advances in the investigation of curcuminoids. Itokawa H, Shi Q, Akiyama T, Morris-Natschke SL, Lee KH.
12 Phytother Res. 2015;29(1):134–40. Effect of curcumin on hepatic antioxidant enzymes activities and gene expressions in rats intoxicated with aflatoxin b1. El-Bahr SM.
13 Molecules. 2014;19(6):8289–302. A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Jiménez-Flores LM, López-Briones S, Macías-Cervantes MH, Ramírez-Emiliano J, Pérez-Vázquez V.
14 Int J Mol Med. 2007;20(3):365–72. Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis. Park C, Moon DO, Choi IW, Choi BT, Nam TJ, Rhu CH, Kwon TK, Lee WH, Kim GY, Choi YH.
15 Adv Exp Med Biol. 2007;595:425–51. Curcumin and autoimmune disease. Bright JJ.
16 Adv Exp Med Biol. 2007;595:1–75. Curcumin: the Indian solid gold. Aggarwal BB, Sundaram C, Malani N, Ichikawa H.
17 J Immunol. 2007;178(1):111–21. Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth. Gururajan M, Dasu T, Shahidain S, Jennings CD, Robertson DA, Rangnekar VM, Bondada S.
18 Evid Based Complement Alternat Med. 2006;3(2):255–60. Comparison of anti-inflammatory activities of six Curcuma rhizomes: a possible curcuminoid-independent pathway mediated by Curcuma phaeocaulis extract. Tohda C, Nakayama N, Hatanaka F, Komatsu K.
19 Ann N Y Acad Sci. 2005;1056:206–17. Curcumin: getting back to the roots. Shishodia S, Sethi G, Aggarwal BB.
20 Clin Exp Pharmacol Physiol. 2015;42(5):520–9. Curcumin ameliorates asthmatic airway inflammation by activating Nrf2/HO-1 signaling pathway. Liu L, Shang Y, Li M, Han X, Wang J, Wang J.
21 Int Immunopharmacol. 2015;25(2):235–41. Curcumin relieves TPA-induced Th1 inflammation in K14-VEGF transgenic mice. Sun J, Zhao Y, Jin H, Hu J.
22 Molecules. 2015;20(1):863–78. Inhibition of the NF-κB signaling pathway by a novel heterocyclic curcumin analogue. Katsori AM, Palagani A, Bougarne N, Hadjipavlou-Litina D, Haegeman G, Vanden Berghe W.
23 Pathologe. 2014;35 Suppl 2:249–53. Inflammation as molecular target in chondrosarcoma. Kalinski T.
24 PLoS One. 2014;9(11):e111559. Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration. Young NA, Bruss MS, Gardner M, Willis WL,
Mo X, Valiente GR, Cao Y, Liu Z, Jarjour WN, Wu.
25 J Ethnopharmacol. 2010;128(2):549–53. Curcumin alleviates ethanol-induced hepatocytes oxidative damage involving heme oxygenase-1 induction. Bao W, Li K, Rong S, Yao P, Hao L, Ying C, Zhang X, Nussler A, Liu L.
26 Int J Nanomedicine. 2014;9:1139–52. Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals. Farazuddin M, Dua B, Zia Q, Khan AA, Joshi B, Owais M.
27 Evid Based Complement Alternat Med. 2013;2013:636053. Curcumin and diabetes: a systematic review. Zhang DW, Fu M, Gao SH, Liu JL.
28 J Nanobiotechnol. 2013;11:37. Characterization of CurcuEmulsomes: nanoformulation for enhanced solubility and delivery of curcumin. Ucisik MH, Küpcü S, Schuster B, Sleytr UB.
29 Biomaterials. 2014;35(10):3365–83. Curcumin nanoformulations: a review of pharmaceutical properties
and preclinical studies and clinical data related to cancer treatment. Naksuriya O, Okonogi S, Schiffelers RM, Hennink WE.
30 World J Gastroenterol. 2013;19(48):9256–70. Therapeutic potential of curcumin in digestive diseases. Dulbecco P, Savarino V.
31 Inflammation. 2011;34(4):291–301. Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis. Ramadan G, Al-Kahtani MA, El-Sayed WM.
32 J Agric Food Chem. 2010;58(2):842–9. Anti-arthritic effects and toxicity of the essential oils of turmeric (Curcuma longa L.). Funk JL, Frye JB, Oyarzo JN, Zhang H, Timmermann BN.
33 Arthritis Rheum. 2006;54(11):3452–64. Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis. Funk JL, Frye JB, Oyarzo JN, Kuscuoglu N, Wilson J, McCaffrey G, Stafford G, Chen G, Lantz RC, Jolad SD, Sólyom AM, Kiela PR, Timmermann BN.
34 Ann N Y Acad Sci. 2009;1171:428–35. Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation. Clutterbuck AL, Mobasheri A, Shakibaei M, Allaway D, Harris P.
35 Med Princ Pract. 2015;24(2):153–8. Effect of intraperitoneal curcumin instillation on postoperative peritoneal adhesions. Türkoğlu A, Gül M, Yuksel HK, Alabalik U, Ülger BV, Uslukaya O, Avci Y.
36 Mol Nutr Food Res. 2010;54(8):1202–9. Heat-solubilized curry spice curcumin inhibits antibody-antigen interaction in in vitro studies: a possible therapy to alleviate autoimmune disorders. Kurien BT, D’Souza A, Scofield RH.
37 Exp Mol Med. 2009;41(9):656–64. Curcumin inhibits cellular condensation and alters microfilament organization during chondrogenic differentiation of limb bud mesenchymal cells. Kim DK, Kim SJ, Kang SS, Jin EJ.
38 Clin Ter. 2011;162(3):201–7. Anti-inflammatory effect of Curcuma longa (turmeric) on collagen-induced arthritis: an anatomico-radiological study. Taty Anna K, Elvy Suhana MR, Das S, Faizah O, Hamzaini AH.
39 J Nat Prod. 2006;69(3):351–5. Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis. Funk JL, Oyarzo JN, Frye JB, Chen G, Lantz RC, Jolad SD, Sólyom AM, Timmermann BN.
40 Acta Cir Bras. 2014;29(11):727–34. Oral administration of curcumin (Curcuma longa) can attenuate the neutrophil inflammatory response in zymosan-induced arthritis in rats. Nonose N, Pereira JA, Machado PR, Rodrigues MR, Sato DT, Martinez CA.
41 Acta Med Indones. 2012;44(2):105–13. Ability of curcuminoid compared to diclofenac sodium in reducing the secretion of cycloxygenase-2 enzyme by synovial fluid’s monocytes of patients with osteoarthritis. Kertia N, Asdie AH, Rochmah W, Marsetyawan.
42 J Med Assoc Thai. 2012;95 Suppl 1:S51–8. The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial. Pinsornsak P, Niempoog S.
43 Clin Interv Aging. 2014;9:451–8. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, Buntragulpoontawee M, Lukkanapichonchut P, Chootip C, Saengsuwan J, Tantayakom K, Laongpech S.
44 J Altern Complement Med. 2009;15(8):891–7. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V.
45 World J Gastrointest Pathophysiol. 2011;2(1):1–14. Therapeutic potential of curcumin in gastrointestinal diseases. Rajasekaran SA.
46 Nutrients. 2015;7(1):306–20. Curcumin inhibits gastric inflammation induced by Helicobacter pylori infection in a mouse model. Santos AM, Lopes T, Oleastro M, Gato IV, Floch P, Benejat L, Chaves P, Pereira T, Seixas E, Machado J, Guerreiro AS.
47 Biochem Pharmacol. 2008;75(4):787–809. Curcumin as “Curecumin”: from kitchen to clinic. Goel A, Kunnumakkara AB, Aggarwal BB.
48 Molecules. 2014;19(12):20864–79. Relevance of the anti-inflammatory properties of curcumin in neurodegenerative diseases and depression. Tizabi Y, Hurley LL, Qualls Z, Akinfiresoye L.
49 World J Plast Surg. 2015;4(1):29–35. The healing effect of curcumin on burn wounds in rat. Mehrabani D, Farjam M, Geramizadeh B, Tanideh N, Amini M, Panjehshahin MR.
50 Springerplus. 2013;2(1):56. Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management. Henrotin Y, Priem F, Mobasheri A.
51 Phytother Res. 2014;28(4):579–85. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Sanmukhani J, Satodia V, Trivedi J, Patel T, Tiwari D, Panchal B, Goel A, Tripathi CB.
52 BMC Complement Altern Med. 2013;13:58. The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study. Kim SW, Ha KC, Choi EK, Jung SY, Kim MG, Kwon DY, Yang HJ, Kim MJ, Kang HJ, Back HI, Kim SY, Park SH, Baek HY, Kim YJ, Lee JY, Chae SW.
53 Biomed Res Int. 2013;2013:158348. Safety evaluation of turmeric polysaccharide extract: assessment of mutagenicity and acute oral toxicity. Velusami CC, Boddapati SR, Hongasandra Srinivasa S, Richard EJ, Joseph JA, Balasubramanian M, Agarwal A.
54 Eur J Drug Metab Pharmacokinet. 2015;40(1):61–6. Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects. Al-Jenoobi FI, Al-Thukair AA, Alam MA, Abbas FA, Al-Mohizea AM, Alkharfy KM, Al-Suwayeh SA.
55 Chem Biol Interact. 2014;220:25–32. Pretreatment with turmeric modulates the inhibitory influence of cisplatin and paclitaxel on CYP2E1 and CYP3A1/2 in isolated rat hepatic microsomes. Ahmed EM, EL-Maraghy SA, Teleb ZA, Shaheen AA.
56 Contraception. 2009;79(6):479–87. Reversible antifertility effect of aqueous rhizome extract of Curcuma longa L. in male laboratory mice. Mishra RK, Singh SK.
57 Nat Prod Commun. 2013;8(4):523–6. Chemical composition and antimicrobial activity of three essential oils from Curcuma wenyujin. Zhu J, Lower-Nedza AD, Hong M, Jie S, Wang Z, Yingmao D, Tschiggerl C, Bucar F, Brantner AH.
58 Mol Med Rep. 2013;8(5):1542–8. Clinical evaluation of a formulation containing Curcuma longa and Boswellia serrata extracts in the management of knee osteoarthritis. Kizhakkedath R.
59 Int J Rheum Dis. 2013;16(2):219–29. Protective effects of ginger-turmeric rhizomes mixture on joint inflammation, atherogenesis, kidney dysfunction and other complications in a rat model of human rheumatoid arthritis. Ramadan G, El-Menshawy O.
60 J Clin Rheumatol. 2004;10(5):236–45. A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an Ayurvedic drug, on osteoarthritis of the knees. Chopra A, Lavin P, Patwardhan B, Chitre D.