Abstract
Background
Menisci, one of the most important anatomical structures of the knee joint, plays a role in load transfer, stability, shock absorption, prevention of articular cartilage degeneration, and proprioception. Type I collagen, the main component of the meniscus, and type II collagen fibers play an important role in the stability of the knee joint. This study aimed to evaluate the effects of Naturagen® 4 Joint product containing type I, II, and III collagen on pain, quality of life, and physical functions in patients with meniscopathy.
Methods
This randomized, double-blind, placebo-controlled clinical study included 32 patients (collagen = 17 and placebo = 15) with meniscopathy. Patients completed the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthrtis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Oxford Knee Score (OKS), Tampa Scale for Kinesiophobia (TSK), Short Form Health Survey (SF-12), Lower Extremity Functional Scale (LEFS), Foot Function Index (FFI), proprioceptive sensation, Timed Up and Go (TUG), 6-Minute Walking Test (6MWT), The Five Repetition Sit to Stand Test (5STS), Stair Climbing Test (SCT), Berg Balance Scale (BBS) and back and leg strength tests and scales were applied. All tests were repeated before and after eight weeks of collagen supplementation.
Results
The study showed that eight weeks of supplementation with various collagen types had statistically significant effects on pain, quality of life, kinesiophobia, and foot function scale scores in patients with meniscopathy (p < 0.05). Similarly, eight weeks of supplementation showed a statistically significant difference in leg strength (p = 0.057), but no significant difference was found in back strength, proprioception, balance, and various functional test results (p > 0.05).
Conclusions
The results of the study showed that the eight-week collagen-based supplement had a positive effect on pain and quality of life levels and some functional test results in patients with meniscopathy. Longer-term studies and diversification of subject groups will help to understand better the effects of the product on meniscal tears and symptoms.
Trial registration
The study was retrospectively registered in the Iranian Clinical Trials Registry on 14/05/2024 with the number IRCT20240411061470N2.
Keywords: Meniscal tear, Collagen supplement, Pain, Physical function, Quality of life
Introduction
Menisci, one of the most important anatomical structures of the knee joint, are fibrocartilaginous tissues that act through interactions between the femur, tibia and patella [1]. Ligaments provide knee stability, articular cartilage reduces friction, and menisci play a role in load distribution, shock absorption, prevention of articular cartilage degeneration and proprioception [2]. The capacity to resist the forces applied to the knee is related to the biomechanical properties of the meniscus tissue and prevents overstretching and possible injury of the knee, especially in movements requiring high effort such as running, jumping and carrying heavy loads [2, 3]. However, the knee joint performs its movement in more than one plane and is therefore susceptible to injuries [2]. Meniscal tears may occur as a result of these injuries. These tears, which are characterized by slow healing, occur mostly in the avascular region [4]. Meniscal tears usually occur as a result of trauma in young people but may also occur without trauma in the elderly due to meniscal degeneration and decreased elasticity [5].
After a meniscal tear, the menisci cannot perform their normal functions, and the biomechanics of the knee joint deteriorate. In addition, the functional performance of the individual decreases with symptoms such as locking, effusion, and recurrent pain in the knee; daily life is restricted, and quality of life is significantly affected [6]. When conservative methods used to treat meniscal tears (nonoperative rehabilitation, non-steroidal anti-inflammatory drugs, and intra-articular injections) become insufficient to relieve these symptoms, surgical methods such as meniscal repair, meniscectomy, meniscal allograft transplantation and the use of meniscal scaffolds are used [3, 7]. According to the three-grade staging system currently used in meniscal injuries, most of the grade 1 and 2 injuries are treated conservatively, whereas arthroscopic surgery or excision is preferred in grade 3 injuries [8, 9]. Meniscectomy, which is based on the procedure of removing the damaged tissue, is one of the traditional and common methods in the treatment of meniscal tears [10, 11]. However, both partial and total meniscectomy are known to lead to degeneration and osteoarthritis in the knee joint due to increased cartilage contact stress [10, 12]. As a result of such limitations after intervention, orthopedists have turned to various treatment methods to preserve meniscal function in the process [7, 13–15]. Studies have shown that strengthening exercises may be as effective as arthroscopic surgery in relieving knee pain, improving knee function, and increasing patient satisfaction in degenerative horizontal tears of the meniscus [16–18]. In addition, the importance of considering non-surgical approaches, including rehabilitation and physical exercise, as the first line of treatment in asymptomatic meniscal injuries has been emphasized [18, 19].
The meniscal content is highly hydrated (72% water) [3, 20]. The remaining content consists of extracellular matrix and cells. The organic matter consists mainly of collagen (75%), glycosaminoglycans (17%), DNA (2%), adhesion glycoproteins (< 1%), and elastin (< 1%) [3, 20]. Along with type I collagen, which is the main component of the meniscus, type II collagen fibers play an important role in the stability of the knee joint by showing the ability to withstand the stresses exposed [10, 21, 22]. It is said that a collagen matrix must be formed for the deposition of glycosaminoglycans that contribute to the compression properties of the meniscus [23]. Collagen plays a vital role in joint health and cartilage formation and is highly effective in preventing joint pain and progressive cartilage damage over time [24, 25]. In addition, it is thought that collagen supplementation may help the treatment of knee injuries with its positive effects on healing and symptom reduction [26]. Many studies have shown that collagen supplementation is effective in treating degenerative joint disorders and reduces pain symptoms [27–30].
There are many studies on knee joint injuries in the literature. Although meniscal tears are one of the most common orthopedic injuries of the knee, there are limited studies on the effect of collagen supplementation on meniscal tears and symptoms. In this context, our study aims to examine the effects of type I and type III collagen peptide and type II hydrolyzed collagen component supplementation on pain, quality of life, and physical functions associated with meniscal tears.
Material and method
Investigational products
The study product was provided by Naturagen® 4 Joint Naturagen İlaç Kozmetik AŞ, Turkey, registered with the US Food and Drug Administration (Registration No: 12537420128). The product contained 15 stick sachets of 5.75 g in a box. Naturagen® 4 Joint contained varying amounts of PROFIN® bovine collagen peptides (type I and type III), glucosamine sulfate, chondroitin sulfate, methylsulfonylmethane, malic acid, lemon flavoring, calcium l-ascorbate, hyaluronic acid, maltodextrin, olibanum gum resin extract, chicken hydrolyzed collagen (type II), silicon dioxide, steviol glycosides and vitamin C. The ingredient profile of the product is shown in Table 1. The placebo product contained 5.2 g maltodextrin. Both products contained sweeteners with the same flavor. All products had the same appearance, taste, and texture.
Table 1.
Product ingredients and daily doses
| Ingredients | Daily intake dose per sachet |
|---|---|
| Collagen peptides (Type I, III) | 2000 mg |
| Glucosamine sulfate | 1500 mg |
| Chondroitin sulfate | 750 mg |
| Methylsulfonylmethane | 500 mg |
| Hyaluronic acid | 100 mg |
| Olibanum Gumresin Extract | 50 mg |
| Hydrolyzed Collagen (Type II) | 40 mg |
| Vitamin C | 100 mg |
Study design
This randomized, double-blind, placebo-controlled clinical trial evaluated the effects of eight weeks of use of Naturagen® 4 Joint product with a combination of type I and type III collagen peptide and type II hydrolyzed collagen, glucosamine sulfate, chondroitin sulfate, hyaluronic acid, and vitamin C on various pain and quality of life scales, balance and various functional test results in meniscopathy patients. The study included 32 patients who completed written informed consent forms (Fig. 1). In addition to descriptive information and limb lengths, Western Ontario and McMaster Universities Osteoarthrtis Index (WOMAC), Visual Analog Scale (VAS), Oxford Knee Score (OKS), Foot Function Index (FFI) and Berg Balance Scale (BBS) scales, 6-Minute Walking Test (6MWT), The Five Repetition Sit to Stand Test (5STS) and proprioception measurements were taken at their first visit. On the day following the first visit, Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Tampa Scale for Kinesiophobia (TSK), Short Form Health Survey (SF-12), and Lower Extremity Functional Scale (LEFS) scales, Timed Up and Go (TUG), Stair-Climbing Test (SCT), back and leg strength tests were performed. After completion of the pre-tests, participants were randomized to one of the two treatment groups using computer-certified software (www.random.org) and divided into collagen (n = 17) and placebo (n = 15) groups. Blinding of the products was done using blinding codes in sealed envelopes. Participants and the investigators responsible for data collection were blinded to treatment allocation. Participants were instructed to consume the products according to the manufacturer's recommendation, one sachet per day, dissolved in one glass (200 ml) of water, for eight weeks. For a better follow-up process, participants were assigned diary cards, and their product use was recorded in this way. Participants continued their usual rehabilitation programme throughout the study. They were also asked to keep their general daily physical activity level and not to participate in any additional physical activity programme other than their ongoing rehabilitation during the study period. Participants returned after eight weeks of product use, and the post-tests were completed on two consecutive days in the same order as the pre-tests. All measurements in the study were performed at the same time of the day (13.00–15.00). The primary endpoint of the study was the successful completion of the final tests after eight weeks of product use, and the secondary endpoints were the patient's unwillingness to continue the study for various reasons, discontinuation of product use earlier than eight weeks, any additional trauma to the index joint, and the development of hypersensitivity to the product used in the study.
Fig. 1.
Flowchart
This study was conducted in compliance with the ethical principles stated in the Declaration of Helsinki and ICH Good Clinical Practice guidelines. Ethics committee approval was obtained from Sinop University Human Research Ethics Committee (protocol no: 2023/182) and registered in the Iranian Clinical Trials Registry on 14/05/2024 with the number IRCT20240411061470N2.
Participants
Thirty-two male and female subjects aged 35–65 years with grade 1 and 2 meniscal tears according to the three-grade staging system developed by Fischer et al. [9] participated in the study. G*Power 3.1 software was used to determine the number of subjects to participate in the study, and the results showed that it would be appropriate to conduct the study with 15 subjects in both groups (effect size r: 0.93, lower and upper critical p: 0.51, true power: 0.85). The inclusion and exclusion criteria for the subjects in the study are presented in Table 2.
Table 2.
Inclusion and exclusion criteria for the study
| Inclusion criteria |
| Diagnosis of unilateral or bilateral grade 1 or 2 meniscal tear |
| No history of any serious acute trauma to the knee |
| No X-ray or MRI evidence of osteoarthritis |
| ACL and other ligament structures are healthy according to MRI and Lachman test |
| Non-vegetarian |
| Willingness to participate in all visits and tests foreseen for the study |
| Exclusion criteria |
| Any history of trauma, fracture, or surgery on the index joint |
| Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, or neurologic diseases or malignancies within the last five years |
| Active viral or bacterial infection according to clinical examination |
| Knee surgery within the last 12 months or planned surgery within the working period |
| Intra-articular injections (cortisol, hyaluronic acid, etc.) within the last six months |
| Taking supplements such as hydrolyzed collagen, glucosamine, or chondroitin in the last six months |
| Intolerance to protein-based foods or supplements, pregnant or breastfeeding, and alcohol dependence |
Evaluation tools
Pain and quality of life scales
Visual Analogue Scale (VAS): It is used for knee pain assessment and the patient self-assesses [31]. It is a 100 mm scale. The patient marks the point on the line between ‘no pain’ and ‘excruciating pain’ according to their own pain level during free walking movement. A higher score means more pain.
Western Ontario and McMaster Universities Osteoarthrtis Index (WOMAC): A 5-point Likert-type scale (none, mild, moderate, severe, extreme) consisting of 24 items and three subscales: pain, stiffness, and physical function. The scale is scored from 0 to 100, with a higher score indicating increased pain, stiffness, and functional limitations [32].
Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS): The KOOS-PS scale assesses activities of daily living and physical function after knee injuries [33]. The scale is scored on a 5-point Likert scale (none, mild, moderate, severe, extreme) and is evaluated between 0 and 100 points. A score of 0 indicates the absence of a problem, and a score of 100 indicates the severity of the knee problem.
Oxford Knee Score (OKS): The OKS assesses the patient's pain and functional status over the last four weeks and consists of 12 questions [34]. On a scale of 0 to 48, lower scores indicate worse pain and functional status.
Tampa Scale for Kinesiophobia (TSK): The scale, which covers fear of falling and fear of movement, has 17 questions scored between 1–4. Questions 4, 8, 12, and 16 are reversed. The highest score is 68. Higher scores indicate more fear of falling and movement in the patient [35].
Short Form Health Survey (SF-12): It is scored in two sub-dimensions: Physical Component Score (PCS) and Mental Component Score (MCS). Both subscales are scored between 0 and 100, with higher scores indicating better physical and mental health [36].
Lower Extremity Functional Scale (LEFS): The LEFS consists of 20 items assessing lower limb function and activity limitation [37]. Each item is scored between 0 and 4 on a scale of 'extremely difficult' to 'no difficulty,' with a maximum score of 80. High scores indicate a high functional level.
Foot Function Index (FFI): There are a total of 23 items on the scale, which is evaluated in the sub-dimensions of pain, disability, and activity limitation [38]. A higher score indicates more pain, disability, and activity limitation. All answers are summed and divided by the maximum score that can be obtained, and the total score is calculated by multiplying the number obtained by 100.
Functional tests
Back and leg force
For back strength measurement, feet were placed on the dynamometer stand. Knees and arms were stretched, the back was straight, and the trunk was slightly tilted forward; the dynamometer bar grasped with both hands was pulled vertically as best as possible with the back muscles active. For leg strength, they were asked to pull the bar in a vertical direction using only the leg until the knee was in extension with arms stretched, back straight, and trunk slightly tilted forward.
Proprioceptive sensory evaluation
Knee joint proprioceptive sensation was measured with a digital goniometer (2176–300 Insize Digital Angle Meter) with one degree of sensitivity. The goniometer was fixed to the patient's knee joint with EMG bandages. Then, 15°, 30°, 45°, and 60° angles were set as targets for evaluation. The goniometer was zeroed in the prone and supine positions with eyes closed, the patient's hips in a neutral position, both knees in full extension position, and the knee set to the target angle was verbally communicated to the patient. The patient then focused on the target angle for five seconds. Then, the patient positioned the knee to the target angle without external intervention. The mean angular errors of the measurements repeated three times for each angle were evaluated.
Timed up and go (TUG)
While seated in a standard chair, the patient was instructed first to stand up, walk three meters, and then turn around and sit back in the chair. The patient was able to use assistive devices such as a cane when necessary. The time until sitting again was recorded in seconds.
Six-minute walking test (6MWT)
A 30 m corridor was allocated for the Test. The patient was asked to walk in this corridor for six minutes. He was allowed to stop and rest when needed and to use assistive devices such as canes. When the time was over, the distance covered was recorded in meters.
The five repetition sit to stand test (5STS)
On a standard chair, the patient was asked to sit and stand once with his/her hands crossed over his/her chest. The Test was then initiated, and the patient was instructed to sit and stand on the chair five times as fast as possible. The time taken for five repetitions was recorded in seconds.
Stair-climbing test (SCT)
They were asked to ascend and descend a five-step ladder at a standard height for SCT as fast as possible. When necessary, they were allowed to hold on to the bars on the sides of the stairs, and the elapsed time was recorded in seconds.
Berg balance scale (BBS)
The scale consists of 14 questions that evaluate fall risk and loss of balance. Each item is scored between 0 and 4. The scores are evaluated as high fall risk (0–20), moderate fall risk (21–40), and low fall risk (41–56). A standard chair, a standard step, a 15-m corridor, and a stopwatch were used for the Test.
Statistical analysis
Data analyses were conducted using IBM SPSS Statistics version 22.0 (IBM Inc., Chicago, IL, USA). We represented our data using means and standard deviations. To check whether the data was normally distributed, we looked at histograms and conducted the Shapiro–Wilk test. Differences among groups were assessed using the One-Way ANOVA test. To compare groups over time, we employed a mixed repeated-measures analysis of variance (RM ANOVA), incorporating a Bonferroni correction for post hoc analyses. The study considered 'time' (pre- and post-measurements) and 'group' (placebo and collagen) as within-subject and between-subject factors, respectively. We tested for sphericity using Mauchly’s Test. If this assumption was not met (indicated by p < 0.05), we adjusted our approach using the Greenhouse–Geisser method. Another important aspect of our analysis was to examine the interaction between 'time' and 'group.' This interaction check helps understand if the effect of time varies across different groups. An interaction may suggest that time changes between groups may not be equivalent; however, no substantial violations were detected. All our statistical tests were two-tailed, and we set our threshold for statistical significance at p < 0.05.
Results
In Table 3, the descriptive data of the groups are presented as mean ± standard deviation. There was no statistical difference between the placebo and collagen groups, and all parameters were similar (p > 0.05).
Table 3.
Descriptive data
| Placebo (n = 15) | Collagen (n = 17) | |
|---|---|---|
| Mean ± SD | Mean ± SD | |
| Characteristic | ||
| Age (year) | 43.1 ± 13.7 | 41.7 ± 8.2 |
| Height (cm) | 170.1 ± 6.8 | 165.1 ± 9.4 |
| Weight (kg) | 83.5 ± 16.2 | 76.9 ± 11 |
| BMI (kg/m2) | 28.7 ± 4.2 | 28.3 ± 3.6 |
| Gender | ||
| Male | 6 (40%) | 6 (35%) |
| Female | 9 (60%) | 11 (65%) |
| Meniscopaty side | ||
| Right | 3 (20%) | 6 (35%) |
| Left | 12 (80%) | 11 (65%) |
| Dominant side | ||
| Right | 14 (93%) | 15 (88%) |
| Left | 1 (7%) | 2 (12%) |
SD standard deviation, BMI body mass index
Table 4 shows the pre and post-comparisons of pain, kinesiophobia, and quality of life scales in placebo and control groups. In the collagen group, VAS (p = 0.052) and WOMAC Stiffness (p = 0.237) parameters were not significant, while KOOS (p = 0.004), OXFORD (p = 0.002), TSK (p = 0.002), SF-12 PCS (p < 0.001), SF-12 MCS (p = 0.001), LEFS (p < 0. 001) WOMAC Pain (p < 0.001), WOMAC Physical function (p < 0.001) and WOMAC TOTAL (p < 0.001) scores showed a statistically significant difference and a positive result was observed. In the placebo group, no significant difference was found in any parameter (p > 0.05).
Table 4.
Intragroup and intergroup evaluation of pain, kinesiophobia, and quality of life scale results
| Placebo | Collagen | Interaction | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre | Post | Pre | Post | Pre vs. Pre | Post vs. Post | Group | Time | Group x Time | |||
| Mean ± SD | Mean ± SD | p | Mean ± SD | Mean ± SD | p | p | p | p | p | p | |
| VAS | 6.4 ± 2.3 | 5.6 ± 2.1 | 0.229 | 5.3 ± 3.3 | 4 ± 2.8 | 0.052 | 0.285 | 0.053 | 0.063 | 0.022* | 0.780 |
| KOOS-PS | 11.7 ± 6.4 | 12.1 ± 4.4 | 0.829 | 11.8 ± 7.8 | 5.8 ± 6.3 | 0.004* | 0.804 | 0.028* | 0.204 | 0.013* | 0.093 |
| OKS | 15.5 ± 6.6 | 13.3 ± 7.5 | 0.410 | 13.7 ± 8.1 | 5.8 ± 7.2 | 0.002* | 0.659 | 0.018* | 0.045* | 0.001* | 0.266 |
| TSK | 45.3 ± 6.3 | 41.7 ± 6.1 | 0.218 | 42.1 ± 7.8 | 33.2 ± 9.7 | 0.002* | 0.051 | 0.014* | 0.004* | 0.007* | 0.135 |
| SF-12 PCS | 37.9 ± 9.3 | 37.3 ± 7.7 | 0.835 | 38.3 ± 6.9 | 52.4 ± 7.8 | < 0.001* | 0.934 | < 0.001* | 0.011* | 0.001* | 0.001* |
| SF-12 MCS | 44.3 ± 13 | 43.8 ± 12.4 | 0.862 | 41.4 ± 11.7 | 52.3 ± 7.8 | 0.001* | 0.057 | 0.051 | 0.212 | 0.208 | 0.005* |
| LEFS | 44.3 ± 13.7 | 44.4 ± 12.4 | 0.980 | 45.6 ± 18.3 | 68.5 ± 14.7 | < 0.001* | 0.954 | 0.001* | 0.020* | 0.001* | 0.008* |
| WOMAC Pain | 5.8 ± 3.9 | 6.5 ± 2.8 | 0.542 | 7.6 ± 4.3 | 2.2 ± 3.4 | < 0.001* | 0.274 | 0.004* | 0.414 | 0.005* | 0.002* |
| WOMAC Stiffness | 2.7 ± 2.7 | 2.5 ± 2.6 | 0.786 | 2.2 ± 1.7 | 1.4 ± 1.8 | 0.237 | 0.425 | 0.190 | 0.113 | 0.257 | 0.816 |
| WOMAC Physical function | 22.1 ± 10.3 | 22.5 ± 7.8 | 0.900 | 24.6 ± 13.9 | 8.3 ± 12.5 | < 0.001* | 0.760 | 0.003* | 0.224 | 0.003* | 0.005* |
| WOMAC TOTAL | 31.5 ± 15.8 | 33.2 ± 11.7 | 0.749 | 35.3 ± 19.2 | 12.4 ± 18.2 | < 0.001* | 0.680 | 0.003* | 0.193 | 0.003* | 0.005* |
SD standard deviation, VAS visual analog scale, KOOS-PS knee injury and osteoarthritis outcome score physical function short form, OKS Oxford knee score, TSK Tampa scale for kinesiophobia, SF-12 short-form health survey, PCS physical, MCS mental, LEFS lower extremity functional scale, WOMAC Western Ontario and McMaster Universities Osteoarthritis index
* p < 0.05
In Table 5, knee proprioceptive sensation was evaluated pre- and post-in meniscopathy and contralateral sides in placebo and collagen groups. In the collagen group, statistically significant positive results were obtained on the contralateral side at 15 (p = 0.024) and 30 degrees prone (p = 0.044) and 15 (p = 0.007) and 30 degrees supine (p < 0.001). In the placebo group, significance was seen at 30 degrees supine on the contralateral side (p < 0.001). In both groups, pre and post-evaluations of the meniscopathy side showed similar results (p > 0.05).
Table 5.
Intragroup and intergroup evaluation of prone and supine proprioception scores
| Meniscopathy | Contralateral | Interaction | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre | Post | Pre | Post | Pre vs. Pre | Post vs. Post | Group | Time | Group x Time | |||||
| Mean ± SD | Mean ± SD | P | Mean ± SD | Mean ± SD | P | P | P | P | P | P | |||
| Collagen | Face down | 15° | 4.7 ± 2.6 | 4 ± 3 | 0.555 | 5.8 ± 3.7 | 3 ± 4.9 | 0.024* | 0.337 | 0.468 | 0.976 | 0.044* | 0.218 |
| 30° | 4.8 ± 3.7 | 5.7 ± 4.9 | 0.410 | 7.2 ± 4.3 | 4.7 ± 3.5 | 0.044* | 0.090 | 0.505 | 0.544 | 0.380 | 0.046* | ||
| 45° | 5.4 ± 4.1 | 7.2 ± 7.1 | 0.139 | 6.2 ± 4.2 | 4.5 ± 3.4 | 0.184 | 0.540 | 0.170 | 0.536 | 0.911 | 0.051 | ||
| 60° | 6.8 ± 4.5 | 6.4 ± 5 | 0.792 | 5.5 ± 3.8 | 4 ± 2.4 | 0.270 | 0.355 | 0.079 | 0.073 | 0.334 | 0.549 | ||
| Supine Position | 15° | 5.4 ± 3.6 | 4.8 ± 3.9 | 0.539 | 3.3 ± 2.5 | 6.3 ± 4 | 0.007* | 0.049* | 0.258 | 0.742 | 0.124 | 0.020* | |
| 30° | 3.9 ± 3.7 | 2.3 ± 2 | 0.246 | 11.8 ± 4.9 | 4.5 ± 4.1 | < 0.001* | < 0.001* | 0.049* | < 0.001* | < 0.001* | 0.008* | ||
| 45° | 4 ± 3.2 | 3.4 ± 2.3 | 0.586 | 5.7 ± 3.4 | 4.6 ± 3.3 | 0.361 | 0.148 | 0.208 | 0.040* | 0.304 | 0.791 | ||
| 60° | 4.9 ± 4.2 | 3.2 ± 2.2 | 0.173 | 5.9 ± 3.8 | 6.6 ± 3.7 | 0.611 | 0.463 | 0.003* | 0.016* | 0.538 | 0.187 | ||
| Placebo | Face down | 15° | 4.5 ± 2.9 | 4.9 ± 3.8 | 0.823 | 4.7 ± 4.4 | 6.7 ± 4.4 | 0.244 | 0.872 | 0.227 | 0.206 | 0.325 | 0.500 |
| 30° | 4.7 ± 3.4 | 6.3 ± 6.3 | 0.306 | 3.7 ± 2.8 | 3.3 ± 3.1 | 0.791 | 0.356 | 0.109 | 0.072 | 0.588 | 0.362 | ||
| 45° | 4.5 ± 2.7 | 4.8 ± 3.2 | 0.714 | 5.4 ± 2.3 | 5.6 ± 3.8 | 0.845 | 0.331 | 0.574 | 0.346 | 0.691 | 0.903 | ||
| 60° | 4.7 ± 4.1 | 5.6 ± 4.3 | 0.619 | 4.8 ± 2.7 | 7.6 ± 5.5 | 0.101 | 0.960 | 0.264 | 0.307 | 0.131 | 0.406 | ||
| Supine Position | 15° | 4.5 ± 2.9 | 3 ± 3.6 | 0.166 | 3.7 ± 3.4 | 4.9 ± 2.4 | 0.285 | 0.472 | 0.107 | 0.550 | 0.817 | 0.087 | |
| 30° | 3.5 ± 2.9 | 4.6 ± 2.5 | 0.339 | 13.6 ± 4.9 | 4 ± 3.7 | < 0.001* | < 0.001* | 0.608 | < 0.001* | < 0.001* | < 0.001* | ||
| 45° | 4 ± 4.1 | 3.5 ± 3.2 | 0.637 | 4.6 ± 2.4 | 3 ± 2.1 | 0.157 | 0.656 | 0.592 | 0.990 | 0.183 | 0.495 | ||
| 60° | 5.3 ± 3.5 | 5.3 ± 4.6 | 0.974 | 5.4 ± 3.8 | 3.3 ± 2.7 | 0.128 | 0.907 | 0.145 | 0.313 | 0.287 | 0.267 | ||
* p < 0.05
Figure 2 demonstrates that when the pain, activity limitation, and inability sub-dimensions of the Foot Function Index are evaluated pre- and post-intervention in the placebo and collagen groups, the collagen group showed statistically significant positive results. Specifically, there were significant improvements in the meniscopathy side AFI pain (p = 0.014) and activity inability (p = 0.034) sub-dimensions, as well as in the contralateral side AFI pain (p = 0.013) and activity inability (p = 0.034) sub-dimensions. The placebo group showed no statistically significant difference in AFI scores and similar results in meniscopathy and contralateral side pre and post-evaluations (p > 0.05).
Fig. 2.
Intragroup and intergroup evaluation of foot function index results. *p < 0.05; FFI foot function index
Figure 3 shows the pre- and post-comparisons of TUG, 6MWT, 5STS, SCT, and BBS and back and leg strength assessments in the placebo and collagen groups. Although there was a difference close to significance in leg strength in the collagen group, in general, pre and post-evaluations of all parameters in the collagen and placebo groups revealed similar results (p > 0.05).
Fig. 3.
Intragroup and intergroup evaluation of functional test and scale results. *p < 0.05; TUG timed up and go Test; 5STS the five repetitions sit to stand Test; SCT stair-climbing Test; 6MWT six-minute walking test BBS berg balance scale
Discussion
This randomized, placebo-controlled study evaluated the effects of a newly developed supplement with a combination of type I and type III collagen peptide and type II hydrolyzed collagen, glucosamine sulfate, chondroitin sulfate, hyaluronic acid, and vitamin C on various pain and quality of life scales, balance, various functional test results, and strength levels in patients diagnosed with grade 1 and 2 meniscopathy according to the three-grade staging system developed by Fischer et al. [9]. The main finding of the study showed that eight weeks of supplementation with various collagen types had statistically significant effects on pain, quality of life, kinesiophobia, and foot function scale scores in patients with meniscopathy. Similarly, eight weeks of supplementation showed a near statistically significant difference in leg strength (p = 0.057), but no significant difference was found in back strength, proprioception, balance, and various functional test results.
Meniscopathy is a common disease that significantly affects the functional and biomechanical structure of the knee [39]. The meniscus plays an important role in load transmission, joint lubrication, stability, shock absorption, and proprioception [40–42]. Therefore, various conservative and surgical treatment methods are utilized after meniscopathy, depending on the degree of tear [43–45]. However, researchers have recently focused on alternative treatment methods in order to preserve the meniscus function fully [7, 13–15]. As an alternative method, oral administration of type I collagen, which is the main component of the meniscus, is thought to be beneficial on the negative effects of meniscopathy [46].
The evaluation of various factors such as pain, kinesiophobia, and functional status that commonly occur after meniscopathy is very important in terms of understanding both the level of disease and the effects of the treatment method. In the WOMAC pain and VAS scores included in our study, eight weeks of collagen supplementation had a significant positive effect on the pain level. This result was similar to previous studies evaluating the effects of collagen supplementation on different knee injuries, especially osteoarthritis [30, 47–51]. Uncontrolled damage to mechanoreceptors occurs after meniscopathy [52]. This damage causes irregular afferent impulses in healthy mechanoreceptors, leading to decreased proprioceptive sensation [53]. When this decrease in proprioceptive sensation is combined with other biomechanical effects that occur after injury in the knee joint, it may have an effect on kinesiophobia, quality of life, functional capacity, and strength levels in addition to pain. Similar to the pain scale scores, eight-week collagen supplementation in our study also had positive effects on quality-of-life scores such as WOMAC, KOOS-PS, OKS, SF-12, LEFS, FFI, and kinesiophobia scores evaluated with TSK. Although studies evaluating collagen supplementation in patients with meniscopathy are very limited in the literature, researchers have reported similar positive effects in various studies evaluating the quality of life and kinesiophobia levels in different knee injuries [51, 54]. Collagen produces anti-inflammatory cytokines that stimulate chondrocytes and are responsible for the synthesis of cartilage matrix components by induction and migration of regulatory T cells to the site of inflammation and damage [55]. Therefore, the positive effects of collagen supplementation on pain, quality of life, and kinesiophobia levels in our study can be explained by the protective effect of collagen on cartilage.
Since various parts of the meniscus are innervated by mechanoreceptors that provide proprioceptive and sensory function, proprioceptive sensory loss may occur in the knee joint after meniscal injury [56]. In the proprioceptive sensory evaluation performed in our study, it was found that eight weeks of collagen supplementation contributed to significant improvements on the contralateral side, although it showed similar results on the side with meniscal injury. These variable effects of collagen supplementation may depend on the severity of the meniscal tear, the individual differences of the patients, and the level of functional differences with the healthy knee.
Mechanoreceptor injury due to meniscal tears may be associated with decreased proprioception as well as postural stability and balance [52]. Taşkın et al. (2022) [57] found that the use of collagen supplementation for 12 weeks positively affected balance performances in their study with male patients with meniscopathy. In our study, BBS was used to assess the level of balance and the results showed that there was no statistical difference after collagen supplementation. For the BBS, scores above 41 are considered a low fall risk [58]. The BBS scores in the study show that even before supplementation, both subject groups had a low fall risk (placebo = 54.7 ± 2.3 and collagen = 54.1 ± 3.9). Therefore, the low fall risk of the subjects before supplementation may have played an important role in the lack of significant differences between pre- and post-tests.
After meniscopathy, patients are likely to experience a significant deficit in functional capacity due to negative effects on pain and proprioceptive sensation. After eight weeks of collagen supplementation, no difference was observed in TUG, 6MWT, 5STS, and SCT tests in which functional capacities were evaluated. Similarly, no difference was observed in the back strength assessment included in the study. However, collagen supplementation was significantly effective on leg strength, although not statistically significant (p = 0.057). Musculoskeletal pain perception and kinesiophobia limit the performance of repetitive activities, reduce range of motion, and lead to a decrease in physical capacity by reducing power production [5]. Collagen utilization promotes bone strength, density, and joint stability [57]. Although it was observed that collagen usage made positive contributions especially in terms of physiological characteristics such as pain [27–30, 47, 51], these effects were observed to be more limited in functional performance evaluations [57]. Therefore, improvements in pain and kinesiophobia levels due to collagen use and the effects of collagen on bone structure may have played a role in the increase in leg strength.
In addition to collagen, the supplement used in our study also contained ingredients such as hyaluronic acid, glucosamine sulfate, and chondroitin sulfate, which have proven to be effective in the treatment of pain related to knee joint injuries [59, 60]. Therefore, in addition to collagen, other effective ingredients in the product may have played a role in the positive effects of eight weeks of supplementation on pain and quality of life. However, a clearer understanding of this depends on comparing the ingredients in separate groups.
This study had several limitations, including the groups having the minimum number of subjects allowed by power analysis, the relatively wide age range of all participants, differences in the types and levels of meniscal injury, not differentiating between internal and external meniscus in injury evaluations, lack of gender-specific assessments, duration of supplement use, and evaluation of a single product with varying amounts of ingredients. Nevertheless, our study showed that eight weeks of collagen supplementation significantly improved pain, kinesiophobia, quality of life, and leg strength levels in patients with meniscopathy. However, similar results were seen in other functional tests. Although there are studies examining the effects of collagen supplementation in the treatment of various knee injuries [29, 30, 47, 49, 51, 54, 61], studies specifically evaluating the effects of collagen supplementation in meniscus injuries are very limited [27, 57]. Therefore, supportive studies similar to our study are needed to associate the effects of collagen supplementation with meniscal tissue directly. In addition, in future studies, separate evaluations of collagen supplementation in different groups in terms of age, gender, and meniscopathy levels may allow a clearer understanding of the treatment effects. Considering that another important factor is the duration of supplement use, longer supplement use and regular follow-up in future studies may contribute to revealing the effects of collagen in more detail.
Conclusions
Our study showed that eight weeks of collagen supplementation significantly improved pain, kinesiophobia, quality of life and leg strength levels in patients with meniscopathy. However, other functional tests showed similar results between groups. Although positive effects of collagen supplementation were observed in patients with meniscopathy, additional studies with different designs are needed to better understand the effects of this supplementation.
Acknowledgements
Not applicable.
Abbreviations
- 5STS
The Five Repetition Sit to Stand Test
- 6MWT
6-Minute Walking Test
- BBS
Berg Balance Scale
- BMI
Body Mass Index
- FFI
Foot Function Index
- KOOS-PS
Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form
- LEFS
Lower Extremity Functional Scale
- MCS
Mental Component Score
- OKS
Oxford Knee Score
- PCS
Physical Component Score
- RM ANOVA
Repeated-measures Analysis of Variance
- SCT
Stair-Climbing Test
- SD
Standard Deviation
- SF-12
Short Form Health Survey
- TSK
Tampa Scale for Kinesiophobia
- TUG
Timed Up and Go
- VAS
Visual Analog Scale
- WOMAC
Western Ontario and McMaster Universities Osteoarthrtis Index
Authors' contributions
The first draft of the manuscript and the revised manuscript were written by ASG, AKY, BA, EKS, EA, BG and AM, and HAY, NG and LK completed the data analysis and suggested revisions to the manuscript. HAY and LK participated in the design of the study and performed the statistical analysis, AKY and BG conceived of the study and participated in its design and coordination and helped to draft the manuscript. BA, EKS and EA completed the visualization. All authors read and approved the final manuscript.
Funding
This research received no external funding.
Data availability
Data supporting the findings of this study are available through the corresponding author, but restrictions apply to the availability of these data used for the current study and are therefore not publicly available. However, data are available from the corresponding author (akerim.yilmaz@omu.edu.tr) upon reasonable request.
Declarations
Ethics approval and consent to participate
This study was conducted in compliance with the ethical principles stated in the Declaration of Helsinki and ICH Good Clinical Practice guidelines. Ethics committee approval was obtained from Sinop University Human Research Ethics Committee (protocol no: 2023/182) and registered in the Iranian Clinical Trials Registry on 14/05/2024 with the number IRCT20240411061470N2. Participants were included in the study after written informed consent forms were collected.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data supporting the findings of this study are available through the corresponding author, but restrictions apply to the availability of these data used for the current study and are therefore not publicly available. However, data are available from the corresponding author (akerim.yilmaz@omu.edu.tr) upon reasonable request.