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The comparison of curcuminoid formulations or its combination with conventional therapies versus conventional therapies alone for knee osteoarthritis

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Abstract

Background

Presently, curcuminoid formulations or its combination with conventional therapies has been used for the treatment of knee osteoarthritis (KOA). Nevertheless, evidence is limited due to small-sized clinical trials. This study aims to evaluate the efficacy of curcuminoid formulations or its combination with conventional therapies for KOA.

Methods

Randomized controlled trials comparing curcuminoid formulations or its combination with conventional therapies versus conventional therapies, such as non-steroidal antiinflammatory drugs (NSAIDs) and chondroitin sulfate/glucosamine, were searched from databases.

Results

In total, 14 studies involving 1533 patients were included. Curcuminoid formulations were comparative to NSAIDs in reducing Visual Analogue Scale (VAS), total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and WOMAC score for pain/stiffness/physical function. No significant difference was seen between the two groups in terms of patients’ satisfaction index, patients’ global assessment, reduction of several inflammatory factor, rate of drug compliance, and rescue medication. Notably, curcuminoid formulations combined with NSAIDs significantly reduced VAS and WOMAC/Knee injury and OA Outcome Score (KOOS) pain score more than NSAIDs did. In addition, the curcuminoid formulations were superior to chondroitin sulfate/glucosamine in reducing VAS, total WOMAC score, and WOMAC score for stiffness/difficulty in physical function, while no significant difference was seen in reducing WOMAC pain score and Karnofsky Performance Scale score.

Conclusions

Curcuminoid formulations may be considered a promising alternative for treating KOA.

Key points

• Curcuminoid formulations are comparative to NSAIDs for KOA.

• Curcuminoid formulations are superior to chondroitin sulfate/glucosamine for KOA.

• Curcuminoid formulations could provide additional benefits in alleviating pain and some adverse events caused by NSAIDs.

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Data availability

All the data generated and analyzed during this study are included in this published article.

References

  1. Dieppe PA, Lohmander LS (2005) Pathogenesis and management of pain in osteoarthritis. Lancet 365(9463):965–973

    Article  CAS  PubMed  Google Scholar 

  2. Geyer M, Schönfeld C (2018) Novel insights into the pathogenesis of osteoarthritis. Curr Rheumatol Rev 14(2):98–107

    Article  CAS  PubMed  Google Scholar 

  3. Englund M, Guermazi A, Lohmander SL (2009) The role of the meniscus in knee osteoarthritis: a cause or consequence? Radiol Clin North Am 47(4):703–712. https://doi.org/10.1016/j.rcl.2009.03.003

    Article  PubMed  Google Scholar 

  4. Mohammad NS, Nazli R, Zafar H, Fatima S (2022) Effects of lipid based multiple micronutrients supplement on the birth outcome of underweight pre-eclamptic women: a randomized clinical trial. Pak J Med Sci 38(1):219–226

    PubMed  PubMed Central  Google Scholar 

  5. Favero M, El-Hadi H, Belluzzi E, Granzotto M, Porzionato A, Sarasin G, Rambaldo A, Iacobellis C, Cigolotti A, Fontanella CG, Natali A, Ramonda R, Ruggieri P, De Caro R, Vettor R, Rossato M, Macchi V (2017) Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study. Rheumatology (Oxford) 56(10):1784–1793

    Article  CAS  Google Scholar 

  6. Belluzzi E, Macchi V, Fontanella CG, Carniel EL, Olivotto E, Filardo G, Sarasin G, Porzionato A, Granzotto M, Pozzuoli A, Berizzi A, Scioni M, De Caro R, Ruggieri P, Vettor R, Ramonda R, Rossato M, Favero M (2020) Infrapatellar fat pad gene expression and protein production in patients with and without osteoarthritis. Int J Mol Sci 21(17):6016

    Article  CAS  PubMed Central  Google Scholar 

  7. Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ (2015) Osteoarthritis. Lancet 386(9991):376–387

    Article  CAS  PubMed  Google Scholar 

  8. Abramoff B, Caldera FE (2020) Osteoarthritis: pathology, diagnosis, and treatment options. Med Clin North Am 104(2):293–311

    Article  PubMed  Google Scholar 

  9. Lambova SN, Müller-Ladner U (2018) Osteoarthritis - current insights in pathogenesis, diagnosis and treatment. Curr Rheumatol Rev 14(2):91–97

    Article  PubMed  Google Scholar 

  10. Hunter DJ, Bierma-Zeinstra S (2019) Osteoarthritis. Lancet 393(10182):1745–1759

    Article  CAS  PubMed  Google Scholar 

  11. Onakpoya IJ, Spencer EA, Perera R, Heneghan CJ (2017) Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized clinical trials. Int J Rheum Dis 20(4):420–433

    Article  CAS  PubMed  Google Scholar 

  12. Martinez-Arroyo G, Ramos-Gomez S, Rojero-Gil EK, Rojas-Gongora JA, Barajas-Ochoa A, Bustamante-Montes LP, Yañez J, Ramos-Remus C (2019) Potential uses of an infodemiology approach for health-care services for rheumatology. Clin Rheumatol 38(3):869–876

    Article  PubMed  Google Scholar 

  13. Ahsan R, Arshad M, Khushtar M, Ahmad MA, Muazzam M, Akhter MS, Gupta G, Muzahid M (2020) A comprehensive review on physiological effects of curcumin. Drug Res 70(10):441–447

    Article  CAS  Google Scholar 

  14. Chin KY (2016) The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis. Drug Des Dev Ther 10:3029–3042

    Article  CAS  Google Scholar 

  15. Zhang Y, Zeng Y (2019) Curcumin reduces inflammation in knee osteoarthritis rats through blocking TLR4 /MyD88/NF-κB signal pathway. Drug Dev Res 80(3):353–359

    Article  CAS  PubMed  Google Scholar 

  16. Sun Y, Liu W, Zhang H, Li H, Liu J, Zhang F, Jiang T, Jiang S (2017) Curcumin prevents osteoarthritis by inhibiting the activation of inflammasome NLRP3. J Interferon Cytokine Res 37(10):449–455

    Article  CAS  PubMed  Google Scholar 

  17. Hashemzadeh K, Davoudian N, Jaafari MR, Mirfeizi Z (2020) The effect of nanocurcumin in improvement of knee osteoarthritis: a randomized clinical trial. Curr Rheumatol Rev 16(2):158–164

    Article  CAS  PubMed  Google Scholar 

  18. Haroyan A, Mukuchyan V, Mkrtchyan N, Minasyan N, Gasparyan S, Sargsyan A, Narimanyan M, Hovhannisyan A (2018) Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med 18(1):7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Henrotin Y, Malaise M, Wittoek R, de Vlam K, Brasseur JP, Luyten FP, Jiangang Q, Van den Berghe M, Uhoda R, Bentin J, De Vroey T, Erpicum L, Donneau AF, Dierckxsens Y (2019) Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study. Arthritis Res Ther 21(1):179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, McKenzie JE (2021) PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 372:n160

    Article  PubMed  PubMed Central  Google Scholar 

  21. van Tulder M, Furlan A, Bombardier C, Bouter L (2003) Editorial Board of the Cochrane Collaboration Back Review Group. Updated method guidelines for systematic reviews in the Cochrane collaboration back review group. Spine (Phila Pa 1976) 28(12):1290–1299

    Google Scholar 

  22. Singhal S, Hasan N, Nirmal K, Chawla R, Chawla S, Kalra BS, Dhal A (2021) Bioavailable turmeric extract for knee osteoarthritis: a randomized, non-inferiority trial versus paracetamol. Trials 22(1):105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Heidari-Beni M, Moravejolahkami AR, Gorgian P, Askari G, Tarrahi MJ, Bahreini-Esfahani N (2020) Herbal formulation “turmeric extract, black pepper, and ginger” versus naproxen for chronic knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Phytother Res 34(8):2067–2073

    Article  CAS  PubMed  Google Scholar 

  24. Gupte PA, Giramkar SA, Harke SM, Kulkarni SK, Deshmukh AP, Hingorani LL, Mahajan MP, Bhalerao SS (2019) Evaluation of the efficacy and safety of Capsule Longvida® optimized curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study. J Inflamm Res 12:145–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Shep D, Khanwelkar C, Gade P, Karad S (2019) Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Trials 20(1):214

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, Buntragulpoontawee M, Lukkanapichonchut P, Chootip C, Saengsuwan J, Tantayakom K, Laongpech S (2014) Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging 9:451–458

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kertia N, Asdie AH, Rochmah W, Marsetyawan (2013) Anti-inflammatory activities and the safety of curcuminoid from curcuma domestica val. Rhyzome extract compared to diclofenac sodium for the treatment of osteoarthritis. Altern Integ Med 2(10):252. https://doi.org/10.4172/2327-5162.S1.004

    Article  Google Scholar 

  28. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V (2009) Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med 15(8):891–897

    Article  PubMed  Google Scholar 

  29. Shep D, Khanwelkar C, Gade P, Karad S (2020) Efficacy and safety of combination of curcuminoid complex and diclofenac versus diclofenac in knee osteoarthritis: a randomized trial. Medicine (Baltimore) 99(16):e19723

    Article  Google Scholar 

  30. Atabaki M, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M (2020) Significant immunomodulatory properties of curcumin in patients with osteoarthritis; a successful clinical trial in Iran. Int Immunopharmacol 85:106607

    Article  CAS  PubMed  Google Scholar 

  31. Srivastava S, Saksena AK, Khattri S, Kumar S, Dagur RS (2016) Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: a four-month, double-blind, randomized, placebo-controlled trial. Inflammopharmacology 24(6):377–388

    Article  PubMed  Google Scholar 

  32. Pinsornsak P, Niempoog S (2012) The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial. J Med Assoc Thai 95(Suppl 1):S51-8

    PubMed  Google Scholar 

  33. Thomas JV, Smina TP, Khanna A, Kunnumakkara AB, Maliakel B, Mohanan R, Krishnakumar IM (2021) Influence of a low-dose supplementation of curcumagalactomannoside complex (CurQfen) in knee osteoarthritis: a randomized, open-labeled, active-controlled clinical trial. Phytother Res 35(3):1443–1455

    Article  CAS  PubMed  Google Scholar 

  34. Khanna A, Das SS, Smina TP, Thomas JV, Kunnumakkara AB, Maliakel B, Krishnakumar IM, Mohanan R (2020) Curcumagalactomannoside/glucosamine combination improved joint health among osteoarthritic subjects as compared to chondroitin sulfate/glucosamine: double-blinded, randomized controlled study. J Altern Complement Med 26(10):945–955

    Article  PubMed  Google Scholar 

  35. Madhu K, Chanda K, Saji MJ (2013) Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo-controlled trial. Inflammopharmacology 21(2):129–136

    Article  CAS  PubMed  Google Scholar 

  36. Memarzia A, Khazdair MR, Behrouz S, Gholamnezhad Z, Jafarnezhad M, Saadat S, Boskabady MH (2021) Experimental and clinical reports on anti-inflammatory, antioxidant, and immunomodulatory effects of Curcuma longa and curcumin, an updated and comprehensive review. BioFactors 47(3):311–350

    Article  CAS  PubMed  Google Scholar 

  37. Razavi BM, Ghasemzadeh Rahbardar M, Hosseinzadeh H (2021) A review of therapeutic potentials of turmeric (Curcuma longa) and its active constituent, curcumin, on inflammatory disorders, pain, and their related patents. Phytother Res 35(12):6489–6513

    Article  CAS  PubMed  Google Scholar 

  38. Chainoglou E, Hadjipavlou-Litina D (2019) Curcumin analogues and derivatives with anti-proliferative and anti-inflammatory activity: structural characteristics and molecular targets. Expert Opin Drug Discov 14(8):821–842

    Article  CAS  PubMed  Google Scholar 

  39. Mantzorou M, Pavlidou E, Vasios G, Tsagalioti E, Giaginis C (2018) Effects of curcumin consumption on human chronic diseases: a narrative review of the most recent clinical data. Phytother Res 32(6):957–975

    Article  CAS  PubMed  Google Scholar 

  40. Morshedi K, Borran S, Ebrahimi MS, Masoud Khooy MJ, Seyedi ZS, Amiri A, Abbasi-Kolli M, Fallah M, Khan H, Sahebkar A, Mirzaei H (2021) Therapeutic effect of curcumin in gastrointestinal cancers: a comprehensive review. Phytother Res 35(9):4834–4897

    Article  CAS  PubMed  Google Scholar 

  41. Adibian M, Hodaei H, Nikpayam O, Sohrab G, Hekmatdoost A, Hedayati M (2019) The effects of curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Phytother Res 33(5):1374–1383

    Article  CAS  PubMed  Google Scholar 

  42. Nouri-Vaskeh M, Malek Mahdavi A, Afshan H, Alizadeh L, Zarei M (2020) Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: a randomized controlled trial. Phytother Res 34(6):1446–1454

    Article  CAS  PubMed  Google Scholar 

  43. Ghazimoradi M, Saberi-Karimian M, Mohammadi F, Sahebkar A, Tavallaie S, Safarian H, Ferns GA, Ghayour-Mobarhan M, Moohebati M, Esmaeili H, Ahmadinejad M (2017) The effects of curcumin and curcumin-phospholipid complex on the serum pro-oxidant-antioxidant balance in subjects with metabolic syndrome. Phytother Res 31(11):1715–1721

    Article  CAS  PubMed  Google Scholar 

  44. Dai W, Yan W, Leng X, Chen J, Hu X, Ao Y (2021) Effectiveness of Curcuma longa extract versus placebo for the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Phytother Res 35(11):5921–5935

    Article  PubMed  Google Scholar 

  45. Sadeghi N, Mansoori A, Shayesteh A, Hashemi SJ (2020) The effect of curcumin supplementation on clinical outcomes and inflammatory markers in patients with ulcerative colitis. Phytother Res 34(5):1123–1133

    Article  CAS  PubMed  Google Scholar 

  46. Velusami CC, Richard EJ, Bethapudi B (2018) Polar extract of Curcuma longa protects cartilage homeostasis: possible mechanism of action. Inflammopharmacology 26(5):1233–1243

    Article  CAS  PubMed  Google Scholar 

  47. Buhrmann C, Brockmueller A, Mueller AL, Shayan P, Shakibaei M (2021) Curcumin attenuates environment-derived osteoarthritis by Sox9/NF-kB signaling axis. Int J Mol Sci 22(14):7645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Han G, Zhang Y, Li H (2021) The combination treatment of curcumin and probucol protects chondrocytes from TNF-α induced inflammation by enhancing autophagy and reducing apoptosis via the PI3K-Akt-mTOR pathway. Oxid Med Cell Longev. 5558066:2021. https://doi.org/10.1155/2021/5558066

  49. Wang Z, Jones G, Winzenberg T, Cai G, Laslett LL, Aitken D, Hopper I, Singh A, Jones R, Fripp J, Ding C, Antony B (2020) Effectiveness of Curcuma longa extract for the treatment of symptoms and effusion-synovitis of knee osteoarthritis: a randomized trial. Ann Intern Med 173(11):861–869

    Article  PubMed  Google Scholar 

  50. Nakagawa Y, Mukai S, Yamada S, Matsuoka M, Tarumi E, Hashimoto T, Tamura C, Imaizumi A, Nishihira J, Nakamura T (2014) Short-term effects of highly-bioavailable curcumin for treating knee osteoarthritis: a randomized, double-blind, placebo-controlled prospective study. J Orthop Sci 19(6):933–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Panda SK, Nirvanashetty S, Parachur VA, Mohanty N, Swain T (2018) A randomized, double blind, placebo controlled, parallel-group study to evaluate the safety and efficacy of Curene® versus placebo in reducing symptoms of knee OA. Biomed Res Int. 5291945:2018. https://doi.org/10.1155/2018/5291945

  52. Wang Z, Singh A, Jones G, Winzenberg T, Ding C, Chopra A, Das S, Danda D, Laslett L, Antony B (2021) Efficacy and safety of turmeric extracts for the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomised controlled trials. Curr Rheumatol Rep 23(2):11

    Article  CAS  PubMed  Google Scholar 

  53. Atefi M, Darand M, Entezari MH, Jamialahmadi T, Bagherniya M, Sahebkar A (2021) A systematic review of the clinical use of curcumin for the management of gastrointestinal diseases. Adv Exp Med Biol 1291:295–326

    Article  PubMed  Google Scholar 

  54. Lubbad A, Oriowo M, Khan I (2009) Curcumin attenuates infammation through inhibition of TLR-4 receptor in experimental colitis. Mol Cell Biochem 322(1–2):127–135

    Article  CAS  PubMed  Google Scholar 

  55. Sahebkar A, Cicero AF, Simental-Mendía LE, Aggarwal BB, Gupta SC (2016) Curcumin downregulates human tumor necrosis factor-α levels: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 107:234–242

    Article  CAS  PubMed  Google Scholar 

  56. Judaki A, Rahmani A, Feizi J, Asadollahi K, Hafezi Ahmadi MR (2017) Curcumin in combination with triple therapy regimes ameliorates oxidative stress and histopathologic changes in chronic gastritis-associated helicobacter pylori infection. Arq Gastroenterol 54(3):177–182

    Article  PubMed  Google Scholar 

  57. Abbas SH, Abdulridha MK, Najeb AA (2017) Potential beneft of curcumin adjuvant therapy to the standard Helicobacter pylori eradication therapy in patients with peptic ulcer disease. Asian J Pharm Clin Res 10(5):313–317

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank professional editors of FREE SCIENCE for language editing. We would also like to thank Dr. Jianguo Chen for the useful guidance in the revision of manuscript.

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Authors and Affiliations

  1. Xiyuan Hospital, China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China

    Yingying Wan, Wenting Sun, Jiaxi Yang, Jianxun Ren & Qiuai Kou

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  1. Yingying Wan
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  2. Wenting Sun
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  3. Jiaxi Yang
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  4. Jianxun Ren
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  5. Qiuai Kou
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Contributions

Y. W., Q. K., and J. R. contributed to the conception and design. Y. W., W. S., and J. Y. contributed to the collection and assembly of the data. Y. W. and J. R. contributed to the analysis and interpretation of the data. Y. W. contributed to drafting and revision of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Jianxun Ren or Qiuai Kou.

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This study did not require ethical approval or informed consent because all the analyses were based on previously published data.

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Yingying Wan and Wenting Sun are co-first author

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Wan, Y., Sun, W., Yang, J. et al. The comparison of curcuminoid formulations or its combination with conventional therapies versus conventional therapies alone for knee osteoarthritis. Clin Rheumatol 41, 2153–2169 (2022). https://doi.org/10.1007/s10067-022-06105-2

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