Table 1.
The characteristics of included papers.
| NO | Citation | Country | Scope | Study year | Total sample size | Intervention sample Size | Control sample Size | Intervention group sex rate | Control group sex rate | Mean age of intervention group | Mean age of control group | Type of intervention | Duration of intervention | Out comes measure | Main conclusion |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Bolognesi et al. (26) | China | Single-center | 2018 | 120 | 60 | 60 | 0.417 | 0.383 | 60.4 | 61.3 | Celecoxib + glucosamine sulfate / Celecoxib | 8 weeks | VAS, WOMAC | The combination of celecoxib with glucosamine sulfate effectively reduces immune inflammatory response, and joint pain associated with KOA |
| 2 | Srivastavs et al. (27) | India | Single-center | - | 160 | 78 | 82 | 0.679 | 0.610 | 50.23 | 50.27 | CL extract/ Placebo | 120 days | VAS, WOMAC | Clinically, the VAS and WOMAC scores became Better |
| 3 | Vishal et al. (28) | India | Single-center | 2011 | 60 | 30 | 29 | 0.633 | 0.621 | 53.2 | 55.3 | Aflapin/ Placebo | NM | VAS, WOMAC | The changes were not significant |
| 4 | Kanzaki al. (29) | Japan | Single-center | 2008 | 40 | 20 | 20 | 0.800 | 0.850 | 55.1 | 58.3 | glucosamine hydrochloride, chondroitin/ placebo | 16 weeks | VAS | GCQ supplement was more effective than placebo in decreasing the KOA-associated clinical symptoms |
| 5 | Velangi et al. (30) | India | Single-center | - | 100 | 50 | 50 | 0.500 | 0.500 | - | - | Vitamin D3 + Virgin Coconut Oil/ Vitamin D3 | 12 weeks | VAS, WOMAC | The mean difference of effect in all parameters was higher in intervention group than control group |
| 6 | Kuptniratsaikul et al. (31) | Thailand | Multi-center | - | 367 | 171 | 160 | 0.918 | 0.869 | 60.3 | 60.9 | C. domestica extracts / Ibuprofen | 4 weeks | WOMAC | C. domestica extracts are as effective as ibuprofen for the treatment of KOA |
| 7 | Pavelka et al. (32) | CZ, SK, HU, PL, RO | Multi-center | - | 366 | 142 | 121 | 62.3 | 62.2 | Piascledine® 300 mg/ chondroitin sulfate | 180 days | WOMAC | The first direct comparison between avocado soybean unsaponifiable 300 mg once daily and chondroitin sulfate three times daily revealed no difference in efficacy or safety aspects | ||
| 8 | Debbi et al. (33) | Israel | Single-center | 2006 | 59 | 25 | 25 | 0.840 | 0.480 | 67 | 71 | Methylsulfonylmethane/ placebo | 12 weeks | VAS, WOMAC | Patients in intervention group showed small clinical improvement in pain and physical function |
| 9 | Kanzak, et al. (34) | Japan | Single-center | 2012 | 100 | 50 | 50 | 0.560 | 0.560 | 51.9 | 51.6 | gCQID, glucosamine hydrochloride, chondroitin sulfate, type II collagen peptides, quercetin glycosides, imidazole peptides, and vitamin D/ placebo | 16weeks | VAS | GCQID supplementation was safe and effective in improving knee-joint functions and locomotor functions in subjects with knee pain |
| 10 | Notarnicol et al. (35) | Italy | Single-center | - | 120 | 54 | 58 | 0.704 | 0.724 | 58.7 | 59.5 | MEBAGA (Methylsulfonylmethane and Boswellic Acids versus Glucosamine sulfate in the treatment of knee Arthritis)/ Glucosamine sulfate | 3 months | VAS | This new combination of integration (MSM and BS) has good results in comparison with GS, until now the cornerstone of the treatment of arthritis in according to guidelines |
| 11 | McAlindon et al. (36) | Italy | Na (registry based) | - | 54 | 28 | 26 | 0.357 | 0.385 | 52.3 | 53.1 | Movardol®, Leonardo Medica, Vinci, Florence, Italy (N-acetyl-D-glucosamine, Ginger, Boswellia, boswellic acids) / standard management | 6 months | WOMAC | Oral supplementation with a combination of products of natural origin can be effectively used to target multiple OA signs and symptoms |
| 12 | Farid et al. (37) | Iran | Single-center | - | 40 | 17 | 16 | 0.706 | 0.813 | 55 | 49.71 | Pycnogenol pills/ placebo | 3 months | WOMAC | The efficacy of Pycnogenol detected in alleviating osteoarthritis symptoms and reducing the need for NSAIDs |
| 13 | Jacquet et al. (13) | France | Single-center | - | 81 | 41 | 40 | 0.659 | 0.700 | 56.8 | 57.5 | fish oils rich in omega-3 and omega-6 fatty acids, Urtica dioica (the common nettle)/ zinc and vitamin E; or an identical placebo |
3 months | WOMAC | Use of three capsules a day over three months of this nutraceutical com-pound might decrease disease scores in patients KOA |
| 14 | Farid et al. (38) | Iran | Single-center | - | 40 | 19 | 18 | 0.947 | 0.944 | 47.5 | 48.9 | Pycnogenol pills/ placebo | 3 months | WOMAC | Alleviating KOA symptoms and reducing the need for NSAIDs or COX-2 inhibitors Administration detected |
| 15 | Panda et al. (39) | India | Single-center | 2017 | 50 | 25 | 25 | - | - | 55.2 | 53.12 | Curene/ placebo | 60 days | VAS, WOMAC | This study validates a potential application of Curene as a useful alternative treatment option for the symptoms of KOA |
| 16 | Henrotin et al. (40) | India | Single-center | 2006 | 120 | 29 | 24 | 0.552 | 0.792 | 56.63 | 56.8 | NR-INF-02/ glucosamine sulfate (GS) | 42 days | VAS, WOMAC | This study effectively demonstrated acceptable efficacy and tolerability profile of NR-INF-02 in a small group of subjects indicating its utility as one of the treatment options in symptomatic management of pain among patients with uncomplicated knee OA |
| 17 | Henrotin et al. (40) | India | Single-center | 2006 | 120 | 29 | 28 | 0.552 | 0.786 | 56.63 | 58.17 | NR-INF-02/ NR-INF-02 and GS | 42 days | VAS, WOMAC | |
| 18 | Henrotin et al. (40) | India | Single-center | 2006 | 120 | 29 | 29 | 0.552 | 0.552 | 56.63 | 56.77 | NR-INF-02/ placebo | 42 days | VAS, WOMAC | |
| 19 | Atabaki et al. (8) | Iran | Single-center | - | 30 | 15 | 15 | - | - | 49.13 | 48.26 | Curcumin / placebo | 3 months | VAS | The curcumin can significantly reduce inflammation and pain in patients with O |
| 20 | Maheu et al. (41) | France | Multi-center | 1994 | 164 | 85 | 79 | 0.741 | 0.696 | 63.3 | 65.1 | ASU (avocadoisoybean unsaponifiables) / placebo | 6 months | VAS | Significant symptomatic efficacy over placebo in the treatment of OA, acting from month 2 and showing a persistent effect after the end of treatment |
| 21 | Madhu et al. (42) | US | Single-center | 2009 | 146 | 73 | 73 | 0.671 | 0.548 | 61.8 | 63 | Vitamin D Supplementation / placebo | 24 months | WOMAC | Vitamin D compared with placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic KOA |
| 22 | Panahi et al. (43) | Iran | Single-center | 2012 | 53 | 27 | 26 | 0.667 | 0.846 | 57.32 | 57.57 | Curcuminoids / placebo | 6 months | WOMAC | Curcuminoids represent an effective and safe alternative treatment for KOA |
| 23 | Altman et al. (44) | US | Multi-center | - | 261 | 124 | 123 | 59.700 | 63.400 | 64.06 | 66.36 | Ginger Extract /placebo | 6 weeks | WOMAC | A highly purified and standardized ginger extract had a statistically significant effect on reducing symptoms of KOA. This effect was moderate |
| 24 | Appelbo et al. (45) | Belgium | Multi-center | - | 260 | 86 | 86 | 0.651 | - | 63.4 | 65.2 | ASU 300/ ASU 600 | 3 moths | VAS | The efficacy of ASU at a dosage of 300mg/day and 600mg/day was consistently superior to that of placebo at all endpoints, with no differences observed between the two doses |
| 25 | Appelbo et al. (45) | Belgium | Multi-center | - | 260 | 86 | 88 | 0.849 | - | 63.4 | 66.3 | ASU 300/ Placebo | 3 moths | VAS | |
| 26 | Kimmatkar et al. (46) | India | Single-center | - | 62 | 31 | 31 | - | - | - | - | RA- 11 | 32 weeks | VAS, WOMAC | This controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32 weeks of therapy |
| 27 | Pavelka et al. (32) | India | Single-center | 2013 | 91 | 29 | 30 | 0.517 | 0.500 | 43.7 | 45.1 | NXT15906F6 (TamaFlexTM) 250 mg/ NXT15906F6 (TamaFlexTM) 400mg | 90 days | WOMAC | NXT15906F6 provided substantial relief from knee pain after physical activity and improved joint function in non-arthritic adults |
| 28 | Pavelka et al. (32) | India | Single-center | 2013 | 91 | 29 | 30 | 0.517 | 0.500 | 43.7 | 45.3 | NXT15906F6 (TamaFlexTM) 250 my/ placebo | 90 days | WOMAC | |
| 29 | Dehghan et al. (47) | Iran | Single-center | 2014 | 120 | 35 | 38 | 0.629 | 0.553 | 47.54 | 46.78 | oral diclofenac + oral vitamin E/ oral diclofenac + oral B vitamin | 21 days | VAS, WOMAC | The mean score of WOMAC and VASs of knee pain, total pain severity, knee joint stiffness, and function decreased significantly two groups |
| 30 | Dehghan et al. (47) | Iran | Single-center | 2014 | 120 | 35 | 37 | 0.629 | 0.541 | 47.54 | 46.4 | oral diclofenac + oral vitamin E/ oral diclofenac + placebo |
21 days | VAS, WOMAC | |
| 31 | Rao et al. (48) | India | Single-center | 2008 | 60 | 19 | 19 | 0.842 | 0.632 | 51.6 | 53.2 | 5-Loxin/ Aflapin | 90 days | VAS, WOMAC | Aflapin exhibited better efficacy compared to 5-Loxin®. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups |
| 32 | Rao et al. (48) | India | Single-center | 2008 | 60 | 19 | 19 | 0.842 | 0.526 | 51.6 | 52.4 | 5-Loxin/ Placebo | 90 days | VAS, WOMAC | |
| 33 | Lubis et al. (49) | Indonesia | Single-center | - | 147 | 49 | 50 | 65.300 | 78.000 | 60.9 | 58.3 | glucosamine-chondroitin sulfate/ glucosamine-chondroitin sulfate-methylsulfonylmethane | 3 months | VAS, WOMAC | There were significant differences between three treatment groups on the WOMAC and VAS scores |
| 34 | Lubis et al. (49) | Indonesia | Single-center | - | 147 | 49 | 48 | 65.300 | 41.700 | 60.9 | 62.8 | glucosamine-chondroitin sulfate/ placebo | 3 months | VAS, WOMAC, | |
| 35 | Sengupta et al. (7) | India | Single-center | - | 75 | 24 | 23 | 0.708 | 0.652 | 52.37 | 53.22 | 5-Loxin/ Aflapin | 90 days | WOMAC | Aflapin exhibited better efficacy compared to 5-Loxin® |
| 36 | Sengupta et al. (7) | India | Single-center | - | 75 | 24 | 23 | 0.708 | 0.783 | 52.37 | 52.43 | 5-Loxin/ placebo | 90 days | WOMAC | In comparison with placebo, the safety parameters were almost unchanged in the treatment groups |
| 37 | Haroyan et al. (50) | Armenia | Multi-center | 2016 | 210 | 66 | 67 | 0.909 | 0.925 | 54.65 | 57.91 | CuraMed® 500-mg capsules (333 mg curcuminoids)/ Curamin® 500-mg capsules (350 mg curcuminoids and 150 mg boswellic acid) |
12 weeks | WOMAC | Favorable effects of both preparations compared to placebo were observed after only 3 months of continuous treatment |
| 38 | Haroyan et al. (50) | Armenia | Multi-center | 2016 | 210 | 66 | 68 | 0.909 | 0.956 | 54.65 | 56.04 | CuraMed® 500-mg capsules (333 mg curcuminoids)/ placebo | 12 weeks | WOMAC | A significant effect of Curamin® compared to placebo was observed both in physical performance tests and the WOMAC joint pain index |
| 39 | Henrotin et al. (40) | Belgium | Multi-center | 2017 | 150 | 32 | 33 | 85.100 | 79.600 | 61.4 | 60.9 | bio-optimized Curcuma longa extracts (BCL) low dosage/ BCL high dosage | 3-month | VAS | daily intake of 186.6 mg/day of BCL in patients with symptomatic knee OA leads to a reduction in pain |
| 40 | Henrotin et al. (40) | Belgium | Multi-center | 2017 | 150 | 32 | 36 | 85.100 | 75.600 | 61.4 | 63.3 | bio-optimized Curcuma longa extracts (BCL) low dosage/ placebo | 3-month | VAS | BCL is superior to placebo with a good safety profile and a good compliance |
| 41 | Chopra et al. (51) | India | Single-center | 2007 | 440 | 75 | 86 | _ | _ | 55.55 | 55.28 | Ayurvedic formulations (SGCG)/ SGC | 24 weeks | VAS, WOMAC | Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function |
| 42 | Chopra et al. (51) | India | Single-center | 2007 | 440 | 75 | 75 | _ | _ | 55.55 | 55.51 | Ayurvedic formulations (SGCG)SGCG/ glucosamine sulfate | 24 weeks | VAS, WOMAC | Ayurvedic formulations (especially SGCG) were equivalent to glucosamine |
| 43 | Chopra et al. (51) | India | Single-center | 2007 | 440 | 75 | 78 | _ | _ | 55.55 | 56.6 | Ayurvedic formulation (SGCG)SGCG/ celecoxib | 24 weeks | VAS, WOMAC | Ayurvedic formulations (especially SGCG) were equivalent to celecoxib |