UC-II (Undenatured Collagen)

Collagen supplements have gained significant market popularity, with numerous products claiming to improve knee osteoarthritis symptoms. Previous clinical studies have primarily evaluated individual collagen formulations, with most being industry-sponsored, which raises potential bias concerns. This study aimed to evaluate the efficacy of combined undenatured type II collagen (UC-II) and hydrolysed collagen supplementation in patients with knee osteoarthritis. In this randomised, double-blind, placebo-controlled trial, 68 patients with knee osteoarthritis were divided into two groups: one receiving collagen supplements (tablets containing hydrolysed collagen and UC-II) and the other receiving a placebo. Clinical outcomes, including pain intensity (Verbal Numerical Rating Scale), functional outcomes (Knee Injury and Osteoarthritis Outcome Score [KOOS]), rescue medication consumption, and patient satisfaction, were assessed at baseline, 2, 6, and 12 weeks. Baseline demographic characteristics were comparable between the collagen and placebo groups. Both groups showed significant improvements in pain intensity (p < 0.001) and KOOS scores over time. However, no significant differences were observed between the groups in terms of pain intensity, functional outcomes, rescue medication consumption, or patient satisfaction (p > 0.05). No adverse effects were reported in either group. Combined UC-II and hydrolysed collagen supplementation over 12 weeks did not demonstrate superior efficacy compared with that of the placebo in managing knee osteoarthritis symptoms. Further research is required to explore the potential long-term benefits of combined collagen supplementation.Clinical Trial Registration: ClinicalTrials.gov (NCT06229951): registered on January 16, 2024. © 2025. The Author(s).

Objective: Joint-related stress models have been used in the past to induce a standardized load on physical structures, allowing researchers to observe changes in perceived stress on joints as accurately as possible in healthy individuals. Previous studies support the efficacy of UC-II® undenatured type II collagen ("undenatured collagen") supplementation in maintaining joint health. The purpose of this study was to assess the effect of undenatured collagen on knee flexibility in healthy subjects who experience activity-related joint discomfort (ArJD). Methods: This randomized, double-blind, placebo (PLA)-controlled study was conducted in healthy subjects with ArJD who had no history of osteoarthritis, or joint diseases. Ninety-six (n = 96, 20-55 years old) subjects who reported joint discomfort while performing a standardized single-leg-step-down test were randomized to receive either PLA (n = 48) or 40 mg of undenatured collagen (n = 48) supplementation daily for 24 weeks. Range of motion (ROM) flexion and extension were measured using a digital goniometer. Results: At the end of the study, a statistically significant increase in knee ROM flexion was observed in the undenatured collagen group versus the PLA group (3.23° vs. 0.21°; p = 0.025). In addition, an increase in knee ROM extension by 2.21° was observed over time in the undenatured collagen group (p = 0.0061), while the PLA group showed a nonsignificant increase by 1.27° (p > 0.05). Subgroup analysis by age showed a significant increase in knee ROM flexion in subjects >35 years old in the undenatured collagen supplemented group compared with PLA (6.79° vs. 0.30°; p = 0.0092). Conclusion: Overall, these results suggest that daily supplementation of 40 mg of undenatured collagen improved knee joint ROM flexibility and extensibility in healthy subjects with ArJD.

INTRODUCTION: Knee osteoarthritis (OA) is a serious public health problem since it is linked to loss of muscular function and independence, especially in older adults. In this study, the researchers have proposed a randomised controlled trial with a three-arm study strategy to explore the effectiveness of an oral nutritional supplementation containing hydroxymethylbutyrate and undenatured type-II collagen combined with exercise training (ET) on the OA-related symptoms and biomarkers among adults with knee OA. METHODS AND ANALYSIS: Adults with knee OA aged between 50 years and 75 years will be invited to participate in the study and thereafter will be randomly assigned to either one of three groups: oral nutrition supplementation+ET, ET or usual care. The primary outcomes include changes in OA-related symptoms and biomarkers. The secondary outcomes include changes in body composition, blood profiles, physical fitness, quality of life, dietary intake, disability, psychology status and morphological changes of the knee. ETHICS AND DISSEMINATION: Ethics approval was granted by the Medical Research Ethics Committee of the National University of Malaysia (reference number JEP-2024-264). Findings of this study will be disseminated via peer-reviewed presentations at scientific conferences as well as open access publications. TRIAL REGISTRATION NUMBER: ISRCTN14284561. © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

BACKGROUND: Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC). METHODS: One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method. RESULTS: At day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups. CONCLUSION: UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement's actions are warranted. TRIAL REGISTRATION: CTRI/2013/05/003663 ; CTRI/2013/02/003348 .

This study was designed as a randomized, placebo-controlled, double-blinded, cross-over trial performed to investigate the effects of a dietary supplement containing undenatured type II collagen (UCII®) and Boswellia Serrata on mobility, pain and joint metabolism in mild moderate osteoarthritis (OA) in dogs. A total of 60 dogs with mobility problems were evaluated and enrolled in the study. Seventeen of these dogs with mild/moderate OA were randomized to receive the product A (UCII® + Boswellia Serrata supplement-UCII®-BW) or product B (Placebo -PL), 1 chew per day for 8 weeks by oral route, and repeated in a crossover design after 4 weeks of washout period. All the subjects had veterinary evaluations during the trial and owners were requested to fill out a questionnaire on mobility impairment using the Liverpool Osteoarthritis in dogs scale (L.O.A.D.) at each time of the study. Objective tools were used to assess mobility, activity, and pain. Metabolomic analysis was performed on synovial fluid of most affected joint at the beginning and the end of the study. The results proved that UCII®+Boswellia serrata supplemented group over a period of eight weeks results in an improvement of mobility impairment, already at 4 weeks of administration, according to the owner´s evaluation. In contrast, its absence increased the risk of OA crisis and decreased the pain threshold on the most affected joint. Furthermore, the synovial fluid metabolic profile showed moderate differences between the beginning and the end of the supplementation period, with a particular influence associated to the time of UCII®-BW administration. Copyright: © 2024 Stabile et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Comment in Addiction. 2024 Aug;119(8):1364-1365. doi: 10.1111/add.16580. BACKGROUND AND AIMS: Offering financial incentives is effective for smoking cessation during pregnancy. We tested the effectiveness of financial incentives for maintaining postpartum cessation, comparing 12-month and 3-month incentives with each other and with usual care (UC). DESIGN, SETTING AND PARTICIPANTS: This study was a pragmatic, multi-centre, three-arm randomized controlled trial involving four English, National Health Service, stop smoking services. A total of 462 postpartum women (aged ≥ 16 years) took part, who stopped smoking during pregnancy with financial incentives, validated as abstinent from smoking at end of pregnancy or early postpartum. INTERVENTIONS: Interventions comprised (i) UC; (ii) UC plus up to £60 of financial voucher incentives offered to participants and £60 offered to an optional significant-other supporter, over 3 months postpartum, contingent upon validated abstinence ('3-month incentives'); or (iii) UC plus '3-month incentives' plus £180 of vouchers offered to participants over 9 months postpartum, contingent upon abstinence ('12-month incentives'). MEASUREMENTS: Primary outcome: biochemically validated abstinence at 1 year postpartum. To adjust for testing all comparisons between groups with equal precision, P < 0.017 was necessary for significance. SECONDARY OUTCOMES: self-reported and validated abstinence at 3 months postpartum; self-reported abstinence at 1 year postpartum. FINDINGS: Primary outcome ascertainment: abstinence was 39.6% (63/159) 12 months incentives, 21.4% (33/154) 3 months incentives and 28.2% (42/149) UC. Adjusted odds ratios [95% confidence interval (CI)] = 12-month versus 3-month incentives OR = 2.41 (95% CI = 1.46-3.96), P = 0.001; 12 months versus UC 1.67 (1.04-2.70), P = 0.035; 3 months versus UC 0.69 (0.41-1.17), P = 0.174. Bayes factors indicated that for 12-month versus 3-month incentives and 12 months versus UC there was good evidence for the alternative hypothesis, and for 3 months versus UC there was good evidence for the null hypothesis. CONCLUSIONS: This randomized controlled trial provides weak evidence that up to £300 o

The aim of the study was to compare the metabolomic synovial fluid (SF) profile of dogs affected by spontaneous osteoarthritis (OA) and supplemented with undenatured type II collagen (UC-II), with that of healthy control dogs. Client-owned dogs were enrolled in the study and randomized in two different groups, based on the presence/absence of OA (OA group and OA-free group). All dogs were clinically evaluated and underwent SF sampling for 1H-Nuclear Magnetic Resonance spectroscopy (1H-NMR) analysis at time of presentation. All dogs included in OA group were supplemented with UC-II orally administered for 30 days. After this period, they were reassessed (OA-T30). The differences in the 1H-NMR metabolic SFs profiles between groups (OA-free, OA-T0 and OA-T30) were studied. The multivariate statistical analysis performed on SFs under different conditions (OA-T0 vs OA-T30 SFs; OA-T0 vs OA-free SFs and OA-T30 vs OA-free SFs) gave models with excellent goodness of fit and predictive parameters, revealed by a marked separation between groups. β-Hydroxybutyrate was identified as a characteristic compound of osteoarthritic joints, showing the important role of fat metabolism during OA. The absence of β-hydroxybutyrate after UC-II supplementation suggests the supplement's effectiveness in rebalancing the metabolism inside the joint. The unexpectedly high level of lactate in the OA-free group suggests that lactate could not be considered a good marker for OA. These results prove that 1H-NMR-based metabolomic analysis is a valid tool to study and monitor OA and that UC-II improves clinical symptoms and the SF metabolic profile in OA dogs. © 2022. The Author(s).

The aim of the study was to evaluate the clinical efficacy of 30 days treatment of undenatured type II collagen(UC-II®), compared to cimicoxib and to their combination, in osteoarthritic dogs. Client-owned dogs were enrolled in a clinical, randomized, controlled and prospective study. Posture, lameness, pain, range of motion and x-ray of affected joint(s) were evaluated and scored based on severity (CLINICAL score). The Liverpool Osteoarthritis in Dogs survey was used to score the owner evaluation of dog's mobility (LOAD score and MOBILITY score). Osteoarthritis (OA) stage was defined through the Canine Osteoarthritis Staging tool (COAST). After diagnosis (T0), all patients were randomly assigned to different treatment groups: C group = cimicoxib 2 mg/kg/day orally OS, F group = UC-II® 1 tablet per day OS; C + F group = cimicoxib-UC-II® at the same previous dosages; CTR group = dogs who didn't received any treatment. All treatments were administered for 30 days. Seventy-six dogs completed the study. LOAD score was recorded significant lower after treatment for each group, with a reduction in percentage of 29.5% for C, 31.4% for F, 21.1% for C + F. LOAD score was lower in C(P = 0.04), F(P = 0.001) and C + F(P = 0.009) group at T30 than CTR group. MOBILITY and CLINICAL scores were significantly lower in all groups at T30, when compared to T0. MOBILITY score was lower than CTR in C(P = 0.02) and F(P = 0.01); CLINICAL score was lower in C + F(P = 0.016). The present findings prove that the treatment with UC-II®, cimicoxib and their combination provide significant reduction in clinical signs associated with OA.

BACKGROUND: Knee osteoarthritis (OA) is characterized by a progressive degeneration of cartilage and menisci, leading to pain and locomotor disability. Here, we aimed to assess the effect of an exercise protocol and the oral use of non-hydrolyzed collagen (UC-II) on the functionality and quality of life of women with knee OA. MATERIAL AND METHODS: Individuals were divided into three groups (CG [control group]; MG [medication group]; EG [exercise group]). In the CG there was no intervention, while MG received an oral dose (1 capsule/day) of UC-II and the EG held 12 sessions of an exercise protocol. RESULTS: In the functionality tests (6-min walk test, 6MWT and timed up and go test [TUG]) the EG (p < 0.001/p = 0.020) and MG (p = 0.010/p = 0.010) revealed a significant improvement when compared to the CG. In the analysis of quality of life by WOMAC, a significant improvement was found only in the EG (p = 0.030) when compared to the CG; the same happened in the stiffness domain (EG, p = 0.010), despite in the pain domain, both the EG (p < 0.001) and the MG (p = 0.060) were better than the CG. CONCLUSION: Data obtained here reveal that an exercise protocol and UC-II have similar effects for functionality, despite exercise being superior in promoting the quality of life score. © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days. © 2011 Blackwell Verlag GmbH.

Previous studies have shown that undenatured type II collagen (UC-II) is effective in the treatment of rheumatoid arthritis, and preliminary human and animal trials have shown it to be effective in treating osteoarthritis (OA). The present clinical trial evaluated the safety and efficacy of UC-II as compared to a combination of glucosamine and chondroitin (G+C) in the treatment of OA of the knee. The results indicate that UC-II treatment was more efficacious resulting in a significant reduction in all assessments from the baseline at 90 days; whereas, this effect was not observed in G+C treatment group. Specifically, although both treatments reduced the Western Ontario McMaster Osteoarthritis Index (WOMAC) score, treatment with UC-II reduced the WOMAC score by 33% as compared to 14% in G+C treated group after 90 days. Similar results were obtained for visual analog scale (VAS) scores. Although both the treatments reduced the VAS score, UC-II treatment decreased VAS score by 40% after 90 days as compared to 15.4% in G+C treated group. The Lequesne's functional index was used to determine the effect of different treatments on pain during daily activities. Treatment with UC-II reduced Lequesne's functional index score by 20% as compared to 6% in G+C treated group at the end of 90-day treatment. Thus, UC-II treated subjects showed significant enhancement in daily activities suggesting an improvement in their quality of life.

129. J Vet Pharmacol Ther. 2007 Jun;30(3):275-8. doi: 10.1111/j.1365-2885.2007.00844.x. Therapeutic efficacy and safety of undenatured type-II collagen (UC-II) alone or in combination with (-)-hydroxycitric acid and chromemate in arthritic dogs. Peal A(1), D'Altilio M, Simms C, Alvey M, Gupta RC, Goad JT, Canerdy TD, Bagchi M, Bagchi D. Author information: (1)Toxicology Department, Murray State University, Hopkinsville/Murray, KY 42240, USA. DOI: 10.1111/j.1365-2885.2007.00844.x PMID: 17472662 [Indexed for MEDLINE]

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.