Article

Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides

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  • Collagen Research Institute
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Abstract

The aim of the study was to evaluate the use of specific collagen peptides in reducing pain in athletes with functional knee problems during sport. 139 athletic subjects with functional knee pain ingested 5 g of bioactive collagen peptides (BCP) or a placebo per day for 12 weeks. The primary outcome of the study was a change in pain intensity during activity was evaluated by the participants and the attending physicians using a visual analogue scale (VAS). As secondary endpoints, pain intensity under resting conditions, the range of motion (ROM) of the knee joint, and the use of additional therapeutic options were assessed. The results revealed a statistically significantly improvement in activity-related pain intensity in the verum group compared with placebo. (ΔVAS<sub>BCP</sub> = 19.5 ± 2.4; ΔVAS<sub>Placebo</sub> = 13.9 ± 2.1; p = 0.046). The results were confirmed by the physician's assessment. (ΔVAS<sub>BCP</sub> = 16.7 ± 1.8; ΔVAS<sub>Placebo</sub> = 12.2 ± 1.8; p = 0.021). Pain under resting conditions was also improved but no significance compared with placebo was detected (ΔVAS<sub>BCP</sub> = 10.2 ± 18.4; ΔVAS<sub>Placebo</sub> = 7.4 ± 15.2; p = 0.209). Due to the high joint mobility at baseline, no significant changes of this parameter could be detected. The use of additional treatment options was significantly reduced after BCP intake. The study demonstrated that the supplementation of specific collagen peptides in young adults with functional knee problems led to a statistically significant improvement of activity-related joint pain.

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... The results imply that the intake of 5 g of specific collagen peptides for 12 weeks is sufficient to significantly reduce pain intensity during physical activity. Based on the survey of the participants, it can be assumed that medical treatment options such as drugs or physiotherapy could be reduced by the pain-relieving effect of collagen peptides [39]. ...
... In total, 218 healthy physically active (sports activities of more than 3 h a week) men and women aged between 18 and 30 years with activity-related functional knee joint pain (≥20 mm VAS scale) were randomized within the last 18 months. Based on previous results of a clinical trial involving physically active adults suffering from activity-related joint complaints [39], the sample size for the study was calculated using G*Power (University of Düsseldorf, Germany). Physically active adults were not eligible to participate if they were diagnosed with injuries, osteoarthritis, rheumatoid arthritis or other knee joint diseases. ...
... To date, there is only a limited number of intervention studies that investigated the pain-relieving effect of collagen peptides on functional joint complaints [38,39,46]. In a pilot study, the oral intake of collagen peptides resulted in an improvement in pain symptoms in stress-induced joint complaints. ...
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First evidence indicates that the supplementation of specific collagen peptides is associated with a significant reduction in activity-related joint pain in young adults. The purpose of the current investigation was to confirm the efficacy of the same collagen peptides in a comparable study population. In total, 180 active men and women aged between 18 and 30 years with exercise-related knee pain but no diagnosed joint disease completed the trial over a period of 12 weeks. Participants were randomly assigned to the group receiving 5 g of specific collagen peptides (CP-G) or to the placebo group (P-G). For the primary outcome, changes in pain during or after exercise from pre- to post-intervention were assessed by the participants using the Visual Analog Scale (VAS). These changes were additionally evaluated by the examining physician by means of anamnesis and physical examination of the affected knee joint. As secondary outcomes, pain under resting conditions and after 20 squats were compared between the study groups. In addition, the mobility of the knee joint and the use of alternative therapies (e.g., ointments or physiotherapy) were recorded. The supplementation of specific collagen peptides derived from type I collagen with a mean molecular weight of 3 kDa led to a significantly (p = 0.024) higher reduction of exercise-induced knee pain (−21.9 ± 18.3 mm) compared with the placebo group (−15.6 ± 18.5 mm). These findings were consistent with the physician’s evaluation (−23.0 ± 19.2 mm vs. −14.6 ± 17.9 mm, p = 0.003). The decrease in pain under resting conditions and after squats did not significantly differ between the groups, as only a small number of participants suffered from pain under these conditions. Due to the clinically unremarkable baseline values, the mobility of the knee joint did not change significantly after the intervention. In conclusion, the current investigation confirmed that the oral intake of bioactive collagen peptides used in the current investigation led to a statistically significant reduction of activity-related joint pain in young active adults suffering from knee joint discomfort.
... Fifteen studies were included, of these 8 used collagen peptides or collagen hydrolysate in doses of 5-15 g/day (Clark et al. 2008;Zdzieblik et al. 2015;Zdzieblik et al. 2017;Dressler et al. 2018;Praet et Tables 1, 2, 3 and 4 for more detail). The supplements were provided in either a capsule or powdered form, consumed with water. ...
... There were a total of 656 participants, with 325 males and 276 females; one study did not report the number of male and female participants (Lugo et al. 2013). Twelve studies had recreationally active participants (average age: 30 ± 10 years) who experienced joint-related discomfort (Clark et al. 2008;Zdzieblik et al. 2017;Dressler et al. 2018;Praet et al. 2019;Oertzen-Hagemann et al. 2019;Kirmse et al. 2019;Clifford et al. 2019;Oikawa et al. 2020a;Shaw et al. 2017;Lis and Baar 2019;Lugo et al. 2013;Lopez et al. 2015), 2 studies were in an elderly population; 1 in men experiencing onset of sarcopenia (age 72 ± 5 years) (Zdzieblik et al. 2015) and the other in healthy, older women (age 69 ± 3 years) (Oikawa et al. 2020b), and 1 study was in untrained pre-menopausal women (age 40 ± 8 years) (Jendricke et al. 2019). Twelve studies reported funding sources, but none of the studies reported conflicts of interest. ...
... The studies used 40 mg, 5 g and 10 g per day doses of COL. One study was conducted over 3 months (Zdzieblik et al. 2017), one over 4 months (Lugo et al. 2013), and three studies over 6 months (Clark et al. 2008;Dressler et al. 2018;Praet et al. 2019). Clark and colleagues (2008) noted an effect size (ES) of 0.36 for 'joint pain when walking', but in a knee arthralgia sub-group, the ES was slightly higher (0.45), indicative of a small beneficial effect of COL (< 0.2 = weak effect; > 0.8 = strong effect). ...
Article
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Collagen peptide supplementation (COL), in conjunction with exercise, may be beneficial for the management of degenerative bone and joint disorders. This is likely due to stimulatory effects of COL and exercise on the extracellular matrix of connective tissues, improving structure and load-bearing capabilities. This systematic review aims to evaluate the current literature available on the combined impact of COL and exercise. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a literature search of three electronic databases-PubMed, Web of Science and CINAHL-was conducted in June 2020. Fifteen randomised controlled trials were selected after screening 856 articles. The study populations included 12 studies in recreational athletes, 2 studies in elderly participants and 1 in untrained pre-menopausal women. Study outcomes were categorised into four topics: (i) joint pain and recovery from joint injuries, (ii) body composition, (iii) muscle soreness and recovery from exercise, and (iv) muscle protein synthesis (MPS) and collagen synthesis. The results indicated that COL is most beneficial in improving joint functionality and reducing joint pain. Certain improvements in body composition, strength and muscle recovery were present. Collagen synthesis rates were elevated with 15 g/day COL but did not have a significant impact on MPS when compared to isonitrogenous higher quality protein sources. Exact mechanisms for these adaptations are unclear, with future research using larger sample sizes, elite athletes, female participants and more precise outcome measures such as muscle biopsies and magnetic imagery.
... Collagen hydrolysates (CHs) have been shown to provide multiple health benefits, which have been primarily attributed to their bioactive peptide (BAP) content [1][2][3]. These BAPs can be found in the hydrolysate products, although an increase in the diversity and content of peptides can result from gastrointestinal (GI) digestion [4,5]. ...
... Clinical studies have consistently shown that peptides generated from orally ingested collagen precursors, such as gelatin, or collagen hydrolysates, can reach the systemic circulation and be excreted in the urine [4,6,[10][11][12]. Importantly, the clinical efficacy of CHs has been demonstrated in multiple trials showing reduction of joint discomfort in athletes with functional knee problems and decreased joint pain in osteoarthritis patients [1,3,13]. The BAPs in the bloodstream identified after oral ingestion of CHs and CH precursors, include Ala-Hyp, Pro-Hyp and Gly-Pro-Hyp [4,6,10,14]. ...
... These findings are pertinent since BAPs must undergo first pass metabolism [9] for CHs and collagen-derived peptides to exert their bioactivity, such as on joint tissues including bone, cartilage and muscle. The bioavailability of collagen BAPs has been related to the clinically significant health benefits associated with CH intake, such as decreasing pain associated with OA, improving joint discomfort, and increasing bone mineral density [1,3,13,45]. Therefore, the different degree of BAP bioavailability seen after hepatic first pass effects between the CH products could modify their clinical efficacy. ...
Article
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Collagen hydrolysates (CHs) are composed of bioactive peptides (BAPs), which possess health enhancing properties. There is a knowledge gap regarding the bioavailability of these BAPs that involves intestinal transport and hepatic first pass effects. A simulated gastrointestinal model was used to generate digesta from two CHs (CH-GL and CH-OPT), which were applied to a novel transwell co-culture of human intestinal epithelium cell line-6 (HIEC-6) and hepatic (HepG2) cells to simulate in vivo conditions of absorption and first pass metabolism. Peptide transport, hepatic first pass effects, and bioavailability were determined by measuring BAPs (Gly-Pro, Hyp-Gly, Ala-Hyp, Pro-Hyp, Gly-Pro-Hyp) using an innovative capillary electrophoresis method. All peptides were transported across the intestinal cell layer to varying degrees with both CHs; however, Gly-Pro-Hyp was transported only with CH-GL, but not CH-OPT. Notable hepatic production was observed for Ala-Hyp with both CH treatments, and for Pro-Hyp and Gly-Pro with CH-GL only. All peptides were bioavailable (>10%), except for Gly-Pro-Hyp after CH-OPT. Overall, a high degree of transport and hepatic first pass effects on CH-derived BAPs were observed. Further research is needed to explore the hepatic mechanisms related to the production of BAPs and the bifunctional effects of the bioavailable BAPs noted in this study.
... At the same time, collagen derived peptides are an abundant source of functional chemicals. Collagen peptides or hydrolysates have been proven to have lots of special functions, such as benefits for skin and bone (Zdzieblik et al., 2017), antioxidant (Ketnawa et al., 2016), antimicrobial (Ennaas et al., 2016), antifreeze (Cao et al., 2016). These special functions of collagen peptides mean that collagen peptides can be used as functional foods, medicine, cosmetics, food additives and so on. ...
... Collagen peptides isolated from pork skin and bovine bone are effective supplements to improve physical problems associated with osteoarthritis (Kumar et al., 2015). The supplementation of collagen peptides in young adults with functional knee problems led to an improvement in activity-related joint pain (Zdzieblik et al., 2017). Collagen peptides have the potential to exert a chondroprotective action on osteoarthritis by inhibiting matrix metalloproteinase-13 expression and type II collagen degeneration (Isaka et al., 2017). ...
... Indeed, several studies have indicated that collagen peptide (CP) ingestion relieves muscle and joint pain in diseases such as osteoarthritis (Kumar et al. 2015;Flechsenhar and McAlindon 2016;Woo et al. 2017). Some recent studies also indicated reductions in self-reported joint pain in physically active but otherwise healthy individuals (Clark et al. 2008;Zdzieblik et al. 2017). One study has also reported that CP attenuated creatine kinase (CK) activity following muscle-damaging exercise, indicative of enhanced muscle recovery (Lopez et al. 2015). ...
... Irrespective of the precise reason, these findings are consistent with several other studies measuring the effects of CP on subjective muscle soreness. Indeed, CP has consistently been shown to reduce muscle and joint pain in osteoarthritic patients and those with actively related joint pain (Kumar et al. 2015;Woo et al. 2017;Clark et al. 2008;Zdzieblik et al. 2017). Nonetheless, a similarly designed study did not report a pain reduction with CP after EIMD, but perhaps this was due to the small dose (3 g) provided in that study (Lopez et al. 2015). ...
Article
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This study examined whether consuming collagen peptides (CP) before and after strenuous exercise alters markers of muscle damage, inflammation and bone turnover. Using a double-blind, independent group’s design, 24 recreationally active males consumed either 20 g day⁻¹ of CP or a placebo control (CON) for 7 days before and 2 days after performing 150 drop jumps. Maximal isometric voluntary contractions, countermovement jumps (CMJ), muscle soreness (200 mm visual analogue scale), pressure pain threshold, Brief Assessment of Mood Adapted (BAM +) and a range of blood markers associated with muscle damage, inflammation and bone turnover C-terminal telopeptide of type 1 collagen (β-CTX) and N-terminal propeptides of type 1 pro-collagen (P1NP) were measured before supplementation (baseline; BL), pre, post, 1.5, 24 and 48 h post-exercise. Muscle soreness was not significantly different in CP and CON (P = 0.071) but a large effect size was evident at 48 h post-exercise, indicative of lower soreness in the CP group (90.42 ± 45.33 mm vs. CON 125.67 ± 36.50 mm; ES = 2.64). CMJ height recovered quicker with CP than CON at 48 h (P = 0.050; CP 89.96 ± 12.85 vs. CON 78.67 ± 14.41% of baseline values; ES = 0.55). There were no statistically significant effects for the other dependent variables (P > 0.05). β-CTX and P1NP were unaffected by CP supplementation (P > 0.05). In conclusion, CP had moderate benefits for the recovery of CMJ and muscle soreness but had no influence on inflammation and bone collagen synthesis.
... Indeed, several studies have indicated that collagen peptide (CP) ingestion relieves muscle and joint pain in diseases such as osteoarthritis (Kumar et al. 2015;Flechsenhar and McAlindon 2016;Woo et al. 2017). Some recent studies also indicated reductions in self-reported joint pain in physically active but otherwise healthy individuals (Clark et al. 2008;Zdzieblik et al. 2017). One study has also reported that CP attenuated creatine kinase (CK) activity following muscle-damaging exercise, indicative of enhanced muscle recovery (Lopez et al. 2015). ...
... Irrespective of the precise reason, these findings are consistent with several other studies measuring the effects of CP on subjective muscle soreness. Indeed, CP has consistently been shown to reduce muscle and joint pain in osteoarthritic patients and those with actively related joint pain (Kumar et al. 2015;Woo et al. 2017;Clark et al. 2008;Zdzieblik et al. 2017). Nonetheless, a similarly designed study did not report a pain reduction with CP after EIMD, but perhaps this was due to the small dose (3 g) provided in that study (Lopez et al. 2015). ...
Article
Full-text available
This study examined whether consuming collagen peptides (CP) before and after strenuous exercise alters markers of muscle damage, inflammation and bone turnover. Using a double-blind, independent group's design, 24 recreationally active males consumed either 20 g day −1 of CP or a placebo control (CON) for 7 days before and 2 days after performing 150 drop jumps. Maximal isometric voluntary contractions, countermovement jumps (CMJ), muscle soreness (200 mm visual analogue scale), pressure pain threshold, Brief Assessment of Mood Adapted (BAM +) and a range of blood markers associated with muscle damage, inflammation and bone turnover C-terminal telopeptide of type 1 collagen (β-CTX) and N-terminal propeptides of type 1 pro-collagen (P1NP) were measured before supplementation (baseline; BL), pre, post, 1.5, 24 and 48 h post-exercise. Muscle soreness was not significantly different in CP and CON (P = 0.071) but a large effect size was evident at 48 h post-exercise, indicative of lower soreness in the CP group (90.42 ± 45.33 mm vs. CON 125.67 ± 36.50 mm; ES = 2.64). CMJ height recovered quicker with CP than CON at 48 h (P = 0.050; CP 89.96 ± 12.85 vs. CON 78.67 ± 14.41% of baseline values; ES = 0.55). There were no statistically significant effects for the other dependent variables (P > 0.05). β-CTX and P1NP were unaffected by CP supplementation (P > 0.05). In conclusion, CP had moderate benefits for the recovery of CMJ and muscle soreness but had no influence on inflammation and bone collagen synthesis.
... In vitro, cultured chondrocytes showed stimulation of proteoglycans as well as type II collagen and increased protease activity [121,122]. Several studies showed beneficial effects of collagen peptide supplementation on pain and joint mobility of athletic subjects suffering from functional joint pains, in vivo [123,124]. According to the authors, the stimulatory effect of collagen peptides on ECM-protein synthesis could likely explain these results. ...
... According to the authors, the stimulatory effect of collagen peptides on ECM-protein synthesis could likely explain these results. Although the exact mechanism remains unclear, specific biologically active signaling peptides derived from hydrolyzed collagen such as hydroxyproline-prolineglycine (Hyp-Pro-Gly) and hydroxyproline-glycine (Hyp-Gly) are suspected to trigger those reactions [32, [124][125][126]. ...
Article
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Bioactive peptides are physiologically active peptides mostly derived from proteins following gastrointestinal digestion, fermentation or hydrolysis by proteolytic enzymes. It has been shown that bioactive peptides can be resorbed in their intact form and have repeatedly been shown to have a positive effect on health-related parameters such as hypertension, dyslipoproteinemia, inflammation and oxidative stress. In recent years, there has been increasing evidence that biologically active peptides could also play an important role in sports nutrition. Current studies have shown that bioactive peptides could have a positive impact on changes in body composition and muscular performance, reduce muscle damage following exercise and induce beneficial adaptions within the connective tissue. In the following overview, potential mechanisms as well as possible limitations regarding the sports-related effect of bioactive peptides and their potential mechanisms are presented and discussed. In addition, practical applications will be discussed on how bioactive peptides can be integrated into a nutritional approach in sports to enhance athletic performance as well as prevent injuries and improve the rehabilitation process.
... A collective of people with activity-related joint discomfort (ArJD) but without any diagnosed knee joint diseases is a potential cohort for observation and evaluation of joint health. Some research groups already worked with people with ArJD and their research showed promising results [6,7]. However, in these cases, pain was only evaluated under daily life activity and regular sporting activity. ...
... Aim of the present study was to set up a stress test with focus on joint health to assess joint discomfort and joint function parameters. In literature, different approaches are described in healthy subjects with joint discomfort like pain during intensive soccer play, change of pain intensity during activity or an aerobic step test with consecutive training at alternating days but with focus to endpoints of cartilage turn over [7,6,24]. To our knowledge, for none of these approaches, the reliability of tests was evaluated for the target population of subjects with ArJD. ...
Article
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Background The assessment of improvement or maintenance of joint health in healthy subjects is a great challenge. The aim of the study was the evaluation of a joint stress test to assess joint discomfort in subjects with activity-related knee joint discomfort (ArJD). Results Forty-five subjects were recruited to perform the single-leg-step-down (SLSD) test (15 subjects per group). Subjects with ArJD of the knee (age 22–62 years) were compared to healthy subjects (age 24–59 years) with no knee joint discomfort during daily life sporting activity and to subjects with mild-to-moderate osteoarthritis of the knee joint (OA, Kellgren score 2–3, age 42–64 years). The subjects performed the SLSD test with two different protocols: (I) standardization for knee joint discomfort; (II) standardization for load on the knee joint. In addition, range of motion (ROM), reach test, acute pain at rest and after a single-leg squat and knee injury, and osteoarthritis outcome score (KOOS) were assessed. In OA and ArJD subjects, knee joint discomfort could be reproducibly induced in a short time interval of less than 10 min (200 steps). In healthy subjects, no pain was recorded. A clear differentiation between study groups was observed with the SLSD test (maximal step number) as well as KOOS questionnaire, ROM, and reach test. In addition, a moderate to good intra-class correlation was shown for the investigated outcomes. Conclusions These results suggest the SLSD test is a reliable tool for the assessment of knee joint health function in ArJD and OA subjects to study the improvements in their activities. Further, this model can be used as a stress model in intervention studies to study the impact of stress on knee joint health function.
... Collagen is an abundant structural protein present in connective tissue. Besides its nutritional value as a protein source, dietary supplementation with collagen-derived peptide sources has been suggested to provide beneficial effects in patients with tendinopathy [5][6][7], chronic joint instability [8], osteoarthritis (OA) [3,[9][10][11][12], and activity-related joint pain [13,14]. Thus, nutritional interventions focusing on increasing the amino acid (AA) components of collagen have been suggested to improve collagen synthesis of collagen-rich tissues such as ligaments and bones [5] and potentially slow the degenerative process in OA affected joints [11]. ...
... In addition, ingestion of EHC led to significantly higher plasma concentrations of glycine, proline and hydroxyproline compared to non-hydrolyzed collagen. Notably, these AAs have been connected with the potential beneficial effects of collagen supplementation on tendinopathy and articular joint pain experienced in both OA patients and athletes [7][8][9][10][11][12][13][14]21,22]. As net collagen synthesis is negative in OA patients, enhancing collagen synthesis has been proposed to help regeneration of cartilage [11,22]. ...
Article
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Collagen is characterized by its high content of glycine, proline and hydroxyproline, and is found to exert beneficial effects on joint pain related to activity and osteoarthritis. However, to exert any beneficial effects it is essential that collagen is optimally absorbed. This study aimed to investigate the postprandial absorption of collagen and elucidate the impact of an exogenous enzymatic hydrolysis on absorption rate and bioavailability. A randomized, blinded, cross-over study was conducted where ten healthy male subjects received either 35 g enzymatically hydrolyzed collagen protein (EHC), 35 g non-enzymatically hydrolyzed collagen protein (NC) or placebo (250 mL water) on three nonconsecutive days. Blood samples were drawn before, and up to 240 min following, ingestion and the blood metabolome was characterized by nuclear magnetic resonance (NMR)-based metabolomics. A significant increase in the plasma concentration of nearly all amino acids (AAs) was observed over a 240 min period for both EHC and NC. In addition, the absorption rate and bioavailability of glycine, proline and hydroxyproline were significantly higher for EHC (p < 0.05). In conclusion, ingestion of collagen hydrolysates increases postprandial plasma concentrations of AAs over a period of 240 min, and an enzymatic hydrolysis increases the absorption rate and bioavailability of the collagen-rich AAs glycine, proline and hydroxyproline.
... domized, double-blinded and placebo-controlled investigation showed a reduction in activity-related joint pain in athletes with functional knee discomfort following the oral administration of 5 g SCP over 12 weeks (Zdzieblik et al., 2017). An additional study demonstrated that the supplementation of 10 g collagen peptides per day over a period of 6 months improved the firmness of tissue and its resistance to mechanical stress. ...
... The findings of this study are in accordance with previous investigations of collagen peptide supplementation. Zdzieblik et al. (2017) reported a significant decline in functional knee discomfort following the ingestion of 5 g of bioactive collagen peptides per day over a period of 12 weeks. Athletes in particular suffered less from pain during activity after the intervention compared to placebo. ...
Article
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Following an initial ankle sprain it is not unlikely that chronic ankle instability (CAI) will develop. CAI is associated with impaired perceived functional and mechanical properties of the ligaments. Nutritional supplementation with collagen peptides has been shown to improve the functional and mechanical properties of the connective tissue. The purpose of this study was to investigate the effectiveness of specific collagen peptide supplementation (SCP) to improve ankle stability in athletes with CAI. 50 male and female athletes with CAI completed a randomized, double-blinded and placebo-controlled study with a daily oral administration of either 5 g SCP or 5 g placebo (Maltodextrin) over a period of six months. Both, the Cumberland Ankle Instability Tool (CAIT) and the German version of the Foot and Ankle Ability Measure (FAAM-G) were used to measure the subjective perceived function of the ankle. Additionally, the mechanical stability was determined by measuring the ankle stiffness by an ankle arthrometer. Finally, a three-month follow-up was performed. ANOVA analysis indicated that the subjective ankle stability was improved in both the CAIT (p < 0.001) and the FAAM-G (p < 0.001) following SCP supplementation compared with placebo. No significant changes between the groups were detected in the results of the ankle arthrometer. After six month the subjective report of the ankle stability function significantly improved and the three month follow-up revealed a significant decline in the number of ankle joint injuries (p < 0.05). These data support the concept that specific collagen peptide supplementation in athletes with chronic ankle instability results in significant improvements in subjective perceived ankle stability. The reduction in the re-injury rate of ankle sprains in the follow-up period suggests that these findings have clinical relevance.
... The treatment options for OA are currently limited; however, several clinical trials have shown that ingestion of collagen hydrolysates (CHs) allows for decreased pain and increased mobility [12][13][14][15][16][17][18]. CH supplements contain a cocktail of peptides and amino acids (AAs); however, it is possible that these peptides are further broken down into Nutrients 2021, 13, 2720 2 of 17 bioactive peptides (BAPs) in the stomach and small intestine (SI) [19][20][21][22][23]. BAPs found in collagen products, such as Pro-Hyp, have been shown to decrease the loss of chondrocytes, prevent cartilage thinning, regulate genes associated with joint integrity, reduce the loss of subchondral bone as well as regulate inflammation by inhibiting cytokines such as tumor necrosis factor-α [24][25][26]. ...
... There were no significant differences in antioxidant capacity (DPPH and FRAP) after CH-GL supplementation at any timepoint (8,16,24 h) for the ascending, transverse and descending colonic vessels (Table S3). Conversely, after CH-OPT supplementation, a significant increase (p < 0.05) in DPPH radical scavenging activity (mM Trolox Eq) from baseline (17.53 ± 0.68) was seen after 16 and 24 h of digestion (28.25 ± 0.85 and 26.88 ± 1.28, respectively), although only in the ascending colon (Table S3). ...
Article
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Osteoarthritis (OA), the most common form of arthritis, is associated with metabolic diseases and gut microbiome dysbiosis. OA patients often take supplements of collagen hydrolysates (CHs) with a high peptide content. Following digestion, some peptides escape absorption to induce prebiotic effects via their colonic fermentation to generate short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs) and colonic gases (NH4 and H2S). The capacity of CHs to generate microbial metabolites is unknown. Proteomic analysis of two CHs (CH-GL and CH-OPT) demonstrated different native peptide profiles with increased peptide diversity after in vitro gastric and small intestinal digestion. Subsequent 24 h fermentation of the CH digests in a dynamic gastrointestinal (GI) digestion model containing human fecal matter showed that CH-OPT increased (p < 0.05) H2S, SCFAs (propionic, butyric and valeric acids), BCFAs, and decreased NH4 in the ascending colon reactor with no major changes seen with CH-GL. No major effects were observed in the transverse and descending vessels for either CH. These findings signify that CHs can induce prebiotic effects in the ascending colon that are CH dependent. More studies are needed to determine the physiological significance of CH-derived colonic metabolites, in view of emerging evidence connecting the gut to OA and metabolic diseases.
... Collagen containing repeating Gly-X-Y triplets is the most abundant structural protein in animals. Oral ingestion of collagen peptides (or hydrolysates) is reported to possess many health benefits, such as reducing obesity (Lee et al., 2017), joint discomfort (Zdzieblik, Oesser, Gollhofer, & König, 2017), and blood pressure (Keeffe, Norris, Alashi, Aluko, & Fitzgerald, 2017); healing pressure ulcers (Yamanaka, Okada, & Sanada, 2017) and wounds (Wang et al., 2015); improving muscle strength (Zdzieblik, Oesser, Baumstark, Gollhofer, & König, 2015), bone (Hou, Liu, Guo, Li, & He, 2017) and skin (Inoue, Sugihara, & Wang, 2016) health. Recent evidence showed the possible transport of di-or tri-peptides (such as Gly-Pro-Hyp, Pro-Hyp, Ala-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp) (Iwai et al., 2005;Shigemura, Kubomura, Sato, & Sato, 2014;Sontakke, Jung, Piao, & Chung, 2016) into the bloodstream that later reached the target tissues (skin, bone or joint) after oral administration of collagen peptides. ...
Article
Small collagen peptides are associated with various benefits, such as bone and skin health. However, preparation of small collagen peptides from terrestrial vertebrate origins remains a challenge. Here, we show that pretreatment with formic acid enhanced the production of small collagen peptides from spent hen skin. After pretreatment with formic acid, the percentage of small peptides below 2 kDa increased to 48.92% and 43.34% from 33.79% and 36.32% for heat-soluble collagen (HSC) and pepsin-soluble collagen (PSC), respectively. Pretreatment with formic acid degraded telopeptides and released the cross-links (pyrrole and pyridinoline), which made hen collagen more susceptible to papain hydrolysis. LC-MS/MS results revealed that none of the peptides identified from HSC-FA (formic acid)-Papain and PSC-FA-Papain were derived from cross-linked telopeptides. These results demonstrated that formic acid assisted the hydrolysis of highly cross-linked collagen of spent hens, and it might also be used to produce small collagen peptides from other aged, vertebrate collagens.
... 5) Moreover, McAlindon, et al. reported that proteoglycan concentrations in hyaline cartilage of patients with mild OA increased within 13 weeks after the ingestion of 5 g of CP. 6) Several studies have examined the effect of CP in preventing the occurrence of injuries or knee pain in healthy individuals and university athletes. [7][8][9] It is particularly important for athletes to avoid injuries as well as to improve their competitive skills. Endurance athletes are at particular risk for overuse injuries or exercise-related joint pain. ...
... Although in a classical sense, OA is not often regarded as a metabolic disorder, there have been some insights showing the relationship between OA and increased risk of metabolic syndrome [9,10]. Treatment options are limited, although a number of clinical trials have shown that ingestion of collagen hydrolysates (CHs) allows for decreased pain and increased mobility [11][12][13][14][15][16][17]. CH products contain a cocktail of peptides and amino acids (AAs), whereby the peptides can be further broken down into bioactive peptides (BAPs) in the stomach and small intestine [18][19][20][21]. ...
Article
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Proteins, peptides and amino acids (AAs) that bypass upper gastrointestinal (GI) digestion can be fermented in the colonic regions. This could lead to microbial production of health promoting short-chain fatty acids (SCFAs). Nitrogenous compounds can also be fermented to generate potentially harmful branched chain fatty acids (BCFAs). As collagen hydrolysate (CH) supplements contain a high peptide content, we evaluated whether peptides that undergo intestinal CH digestion and microbial fermentation can generate SCFAs and BCFAs. Two bovine-sourced CH formulations (CH-GL and CH-OPT) underwent digestive processes and microbial fermentation for 24 h in a dynamic GI digestion model containing human fecal matter. After 24 h, CH-OPT showed a significant (p < 0.05) increase in SCFAs (propionic, butyric and valeric acids) in the ascending colonic vessel with no changes observed with CH-GL. Only CH-OPT showed a significant (p < 0.05) increase in BCFAs, also noted in the ascending colon. No significant (p < 0.05) changes to SCFAs and BCFAs were observed in the transverse and descending colons for both CHs. These findings demonstrate that CHs can induce microbial production of SCFAs and BCFAs although this appears to depend on the CH tested. More studies are needed to determine the physiological significance of these microbial metabolites from intake of CH supplements.
... 5) Moreover, McAlindon, et al. reported that proteoglycan concentrations in hyaline cartilage of patients with mild OA increased within 13 weeks after the ingestion of 5 g of CP. 6) Several studies have examined the effect of CP in preventing the occurrence of injuries or knee pain in healthy individuals and university athletes. [7][8][9] It is particularly important for athletes to avoid injuries as well as to improve their competitive skills. Endurance athletes are at particular risk for overuse injuries or exercise-related joint pain. ...
... In vitro cell studies have revealed that collagen hydrolysates/peptides stimulate synthesis of proteoglycans and collagen in human chondrocytes (Oesser and Seifert 2003;Porf ırio and Fanaro 2016;Schadow et al. 2017). Meanwhile, the clinical studies have demonstrated that intake of collagen peptides (5 g/day for 12 weeks) can lead to the relief of joint pain (Bruyere et al. 2012;Zdzieblik et al. 2017) and stimulate regeneration of type II collagen and the biosynthesis of proteoglycans in cartilage tissue osteoarthritis patients (McAlindon et al. 2011). Tr c and Bohmov a (2011) claimed that ingestion of collagen hydrolysate (1.5g/day) for 24 weeks resulted in improvement of joint conditions. ...
Article
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A large amount of food-grade animal by-products is annually produced during industrial processing and they are normally utilized as animal feed or other low-value purposes. These by-products are good sources of valuable proteins, including collagen or gelatin. The revalorization of collagen may lead to development of a high benefit-to-cost ratio. In this review, the major approaches for generation of collagen peptides with a wide variety of bioactivities were summarized, including antihypertensive, antioxidant and antidiabetic activities, and beneficial effects on bone, joint and skin health. The biological potentials of collagen peptides and their bioavailability were reviewed. Moreover, the unique advantages of collagen peptides over other therapeutic peptides were highlighted. In addition, the current challenges for development of collagen peptides as functional food ingredients were also discussed. This article discusses the opportunity to utilize collagen peptides as high value-added bio-functional ingredients in the food industry.
... Intake of collagen hydrolysates has been reported to exert various beneficial effects, such as improving muscle strength (Zdzieblik, Oesser, Baumstark, Gollhofer, & König, 2015), bone density (Liu, Wang et al., 2015), and skin health (Inoue, Sugihara, & Wang, 2016). It can reduce obesity , joint pain (Oesser, Schulze, Zdzieblik, & König, 2016;Zdzieblik, Oesser, Gollhofer, & König, 2017), and blood pressure (O'Keeffe, Norris, Alashi, Aluko, & FitzGerald, 2017), and prevent atherosclerosis (Igase et al., 2018) and aging (De Luca et al., 2016). These beneficial effects on human health after oral administration have motivated the preparation of the collagen hydrolysates from various food processing byproducts. ...
Article
Collagen hydrolysates (peptides) derived from food processing byproducts have been used to produce commercially valuable food ingredients due to their potential to trigger certain desirable physiological responses in the body. Low-molecular-weight (LMW) collagen hydrolysates are generally thought to exert better bioactivities than their larger counterparts. However, the preparation of LMW collagen hydrolysates is often impeded by their special structure, cross-linking, and hydroxyproline. This review briefly introduces the motivation of the food industry to prepare LMW collagen hydrolysate from food processing byproducts. We further summarize recent progress on the preparation of LMW collagen hydrolysates and methods to determine the molecular weight. We then discuss the challenges and then provide perspectives on future directions in preparing LMW collagen hydrolysates.
... Approximately 25-30% of total protein mass in human bodies is collagen [11], and it is ubiquitous within the ECM tissue [12]. The positive effects of collagen peptide (CP) supplementation in wound healing, diverse reduced joint and tendon pains, and increased subjective ankle stability in injured athletes and patients have been previously described [13][14][15][16][17][18]. CP supplementation in combination with specific exercise-based rehabilitation is very likely to support recovery [19]. ...
Article
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We aimed to determine the effects of long-term collagen peptide (CP) supplementation and resistance exercise training (RET) on body composition, strength, and muscle fiber cross-sectional area (fCSA) in recreationally active men. Fifty-seven young men were randomly and double-blinded divided into a group receiving either collagen peptides (COL, 15 g/day) or a placebo (PLA). Strength testing, bioimpedance analysis, and muscle biopsies were used prior to and after an RET intervention. Food record protocols were performed during the RET intervention. The groups trained three times a week for 12 weeks. Baseline parameters showed no differences between groups, and the external training load and dietary food intake were also similar. COL showed a significant increase in fat-free mass (FFM) compared with the placebo group (p < 0.05). Body fat mass (BFM) was unchanged in COL, whereas a significant increase in BFM was observed in PLA. Both groups showed significant increases in all strength tests, with a trend for a slightly more pronounced effect in COL. The fCSA of type II muscle fibers increased significantly in both groups without differences between the two groups. We firstly demonstrated improved body composition in healthy, recreationally active men subsequent to prolonged CP supplementation in combination with RET. As the observed increase in FFM was not reflected in differences in fCSA hypertrophy between groups, we assume enhanced passive connective tissue adaptations in COL due to CP intake.
... Recent studies indicate that both cardiometabolic [2,3], as well as nutritional factors [4,5] can modulate local tendon healing. Although clinical studies are still scarce, a recent International Olympic Committee (IOC) consensus statement on dietary supplements in high-performance athletes [6] proposes that dietary supplementation containing gelatin or hydrolysed collagen could potentially be useful for athletic populations as increased intake of collagen-derived peptides has been shown to modulate collagen synthesis [7] and reduce tendon- [8] and joint-related pain [9,10]. Others have shown that glycine, as the most abundant component of collagen hydrolysates [11], has disease-modifying properties in both animal [12,13] and in vitro [14] models of tendinopathy. ...
Article
Full-text available
The current pilot study investigates whether oral supplementation of specific collagen peptides improves symptoms and tendon vascularisation in patients with chronic mid-portion Achilles tendinopathy in combination with structured exercise. Participants were given a placebo or specific collagen peptides (TENDOFORTE®) in combination with a bi-daily calf-strengthening program for 6 months. Group AB received specific collagen peptides for the first 3 months before crossing over to placebo. Group BA received placebo first before crossing over to specific collagen peptides. At baseline (T1), 3 (T2) and 6 (T3) months, Victorian Institute of Sports Assessment–Achilles (VISA-A) questionnaires and microvascularity measurements through contrast-enhanced ultrasound were obtained in 20 patients. Linear mixed modeling statistics showed that after 3 months, VISA-A increased significantly for group AB with 12.6 (9.7; 15.5), while in group BA VISA-A increased only by 5.3 (2.3; 8.3) points. After crossing over group AB and BA showed subsequently a significant increase in VISA-A of, respectively, 5.9 (2.8; 9.0) and 17.7 (14.6; 20.7). No adverse advents were reported. Microvascularity decreased in both groups to a similar extent and was moderately associated with VISA-A (Rc2:0.68). We conclude that oral supplementation of specific collagen peptides may accelerate the clinical benefits of a well-structured calf-strengthening and return-to-running program in Achilles tendinopathy patients.
... Recent studies indicate that both cardiometabolic [2,3], as well as nutritional factors [4,5] can modulate local tendon healing. Although clinical studies are still scarce, a recent International Olympic Committee (IOC) consensus statement on dietary supplements in high-performance athletes [6] proposes that dietary supplementation containing gelatin or hydrolysed collagen could potentially be useful for athletic populations as increased intake of collagen-derived peptides has been shown to modulate collagen synthesis [7] and reduce tendon- [8] and joint-related pain [9,10]. Others have shown that glycine, as the most abundant component of collagen hydrolysates [11], has disease-modifying properties in both animal [12,13] and in vitro [14] models of tendinopathy. ...
... More recent studies have also noted the possible positive effects of these collagen derived peptides. Exercise combined with 15-20 g of collagen hydrolysates, preferably after training, for over a week, leads to an improvement in lean body mass, and reduces joint and muscle pain in athletes and physically active people (101)(102)(103)(104)(105)(106). The mechanisms by which the collagen peptides exerted their effect have not yet been elucidated. ...
Article
Full-text available
Nutrition and sport play an important role in achieving a healthy lifestyle. In addition to the intake of nutrients derived from the normal diet, some sport disciplines require the consumption of supplements that contribute positively to improved athletic performance. Protein intake is important for many aspects related to health, and current evidence suggests that some athletes require increased amounts of this nutrient. On the other hand, society's demand for more environmentally friendly products, focus on the search for alternative food sources more sustainable. This review aims to summarize the latest research on novel strategies and sources for greener and functional supplementation in sport nutrition. Alternative protein sources such as insects, plants or mycoproteins have proven to be an interesting substrate due to their high added value in terms of bioactivity and sustainability. Protein hydrolysis has proven to be a very useful technology to revalue by-products, such as collagen, by producing bioactive peptides beneficial on athletes performance and sport-related complications. In addition, it has been observed that certain amino acids from plant sources, as citrulline or theanine, can have an ergogenic effect for this target population. Finally, the future perspectives of protein supplementation in sports nutrition are discussed. In summary, protein supplementation in sports nutrition is a very promising field of research, whose future perspective lies with the search for alternatives with greater bioactive potential and more sustainable than conventional sources.
... As a result, collagen peptides are rapidly absorbed from the gastrointestinal tract also in peptide form [11][12][13][14]. Moreover, it has been shown that specific collagen peptides could act as signal messengers in anabolic cellular processes in cartilage, tendons and ligaments [15][16][17], which might be the reason for improved pain symptoms and performance in activity-related joint discomforts [18][19][20], tendinopathy [21,22] and chronic ankle instability [23] in physically active adults. ...
Article
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It has been shown that specific collagen peptides combined with resistance training (RT) improves body composition and muscle strength in elderly sarcopenic men. The main purpose of this RCT study was to investigate the efficacy of the identical specific collagen peptides combined with RT on body composition and muscle strength in middle-aged, untrained men. Furthermore, in the exploratory part of the study, these results were compared with another group that had received whey protein in addition to the RT. Ninety-seven men completed this study and participated in a 12-week RT program. They ingested 15 g of specific collagen peptides (n = 30; CP-G), placebo (n = 31; P-G), or whey protein (n = 36; WP-G) daily. Changes in fat free mass and fat mass were determined by dual-energy X-ray absorptiometry (DXA), and isometric leg strength was measured. All participants had significantly (p < 0.01) improved levels in fat free mass (ΔCP-G = 3.42 ± 2.54 kg; ΔP-G = 1.83 ± 2.09 kg; ΔWP-G = 2.27 ± 2.56 kg), fat mass (ΔCP-G = -5.28 ± 3.19 kg; ΔP-G = -3.39 ± 3.13 kg; ΔWP-G = -4.08 ± 2.80 kg) and leg strength (ΔCP-G = 163 ± 189 N; ΔP-G = 100 ± 154 N; ΔWP-G = 120 ± 233 N). The main analysis revealed a statistically significantly higher increase in fat free mass (p = 0.010) and decrease in fat mass (p = 0.023) in the CP-G compared with the P-G. The exploratory analysis showed no statistically significant differences between WP-G and CP-G or P-G, regarding changes of fat free mass and fat mass. In conclusion, specific collagen peptide supplementation combined with RT was associated with a significantly greater increase in fat free mass and a decrease in fat mass compared with placebo. RT combined with whey protein also had a positive impact on body composition, but the respective effects were more pronounced following the specific collagen peptide administration.
... 12 -16 Moreover, a combination of daily ingestion of collagen hydrolysate and resistance training for 12 weeks increases muscle strength in sarcopenic patients. 17 Although many beneficial effects of collagen hydrolysate ingestion have been reported, the active ingredient had remained undetermined until Iwai et al. 18 found increases in peptides containing Hyp in human blood after ingestion. Our previous study revealed that Hyp-containing peptides increase dose-dependently after collagen hydrolysate ingestion. ...
... In mammals, collagen protein is highly abundant and mainly localized in the ECM of fibrous connective tissues, such as the tendon and skin [7][8][9][10]. It plays key structural roles by supporting the formation, tensile strength, and flexibility of joints [11][12][13][14][15]. Collagen types I, II, III, V, and XI are able to form fibrils that are necessary for structural support and resistance to mechanical stress in connective tissues [16,17]. ...
Article
Full-text available
Marine organisms harbor numerous bioactive substances that can be utilized in the pharmaceutical and cosmetic industries. Scientific research on various applications of collagen extracted from these organisms has become increasingly prevalent. Marine collagen can be used as a biomaterial because it is water soluble, metabolically compatible, and highly accessible. Upon review of the literature, it is evident that marine collagen is a versatile compound capable of healing skin injuries of varying severity, as well as delaying the natural human aging process. From in vitro to in vivo experiments, collagen has demonstrated its ability to invoke keratinocyte and fibroblast migration as well as vascularization of the skin. Additionally, marine collagen and derivatives have proven beneficial and useful for both osteoporosis and osteoarthritis prevention and treatment. Other bone-related diseases may also be targeted by collagen, as it is capable of increasing bone mineral density, mineral deposition, and importantly, osteoblast maturation and proliferation. In this review, we demonstrate the advantages of marine collagen over land animal sources and the biomedical applications of marine collagen related to bone and skin damage. Finally, some limitations of marine collagen are briefly discussed.
... Collagen has beneficial effects on the protection and healing of connective tissue in people doing routine resistance training and cardiovascular exercise [13]. In a study by Zdzieblik et al. (2017), it was determined that there was a statistically significant improvement in activity-related pain intensity in individuals who received collagen [14]. Oral ingestion of collagen has been shown to be effective, tolerable, and safe for osteoarthritis [15]. ...
Chapter
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Akılcı olmayan ilaç kullanımları, hem dünyada hem de ülkemizde toplum sağlığını etkileyen önemli bir sorundur. Yaşlılarda da ilaç kullanımın fazla olması, ilaç kullanımıyla ilgili sorunları beraberinde getirmektedir. Bu çalışma Bayburt ilinde huzurevinde yaşayan yaşlı bireylerin akılcı ilaç kullanım durumlarının belirlenmesi amacıyla tanımlayıcı olarak yapıldı. Çalışma evrenini Bayburt’ta faaliyet yürüten Memnuse Evsen Huzurevi Yaşlı Bakım ve Rehabilitasyon Merkezi’nde yaşayan yaşlı bireyler oluşturdu. Çalışmada örneklem seçimine gidilmeyip tüm evrene ulaşılmaya çalışıldı. Çalışmaya gönüllülük usülü ile dahil olan, iletişim kurmayla ilgili ağır engeli bulunmayan, genel durumu stabil olan 28 yaşlı birey alındı. Veri toplama aracı olarak kişisel bilgi formu ve Akılcı İlaç Kullanımı Ölçeği (AİKÖ) kullanıldı. Veriler 15-22 Şubat 2022 tarihleri arasında araştırmacılar tarafından yaşlılarla yüz yüze görüşme tekniğiyle toplandı. Veriler IBM SPSS 25 paket programda analiz edildi. İstatistiksel anlamlılık düzeyi p<0,05 olarak kabul edildi. Çalışmada Mann Whitney U testi ve Kruskal Wallis testi kullanılarak istatistiksel analiz yapıldı. Tanımlayıcı istatistikler sayı ve % olarak verildi. Yaşlı bireylerin %39,3’ünün 60-74 yaş arası, %60,7’sinin erkek, %46,4’ünün bekar, %53,6’sının ilköğretim mezunu ve üstü olduğu bulundu. Yaşlı bireylerin %57,1’i şuandaki sağlık durumunu ne iyi ne kötü olarak değerlendirdi. Yaşlı bireylerin %28,5’inin hipertansiyonu olduğu, %89,3’ünün ilaçlarını düzenli kullandığı ve ilaçlarını almayı unutmadığı saptandı. Yaşlı bireylerin %75’inin doktora muayene olmadan eczaneden ilaç almadığı, %92,9’unun komşuların/yakınların tavsiyesiyle ilaç kullanmadığı, %10,7’sinin komşuların/yakınların tavsiye ettiği ilacı doktordan reçete etmesini talep ettiği belirlendi. Yaşlı bireylerin günde en fazla 11 ilaç kullandığı ve günlük ilaç kullanım miktarının ortalama 2,21±2,11 olduğu bulundu. AİKÖ toplam puan ortalaması 57,57±7,75 olduğu bulundu. Cinsiyet ve eğitim durumu ile AİKÖ puanı arasında istatistiksel olarak anlamlı fark bulunmadı (p>0,05). Yaş gruplarıyla AİKÖ puanı arasında istatistiksel olarak anlamlı fark bulundu (H=7,595, p=0,022). Sonuç olarak huzurevinde yaşayan yaşlı bireylerin akılcı ilaç kullanım düzeylerinin ortalamanın üzerinde olduğu ve genç yaşlı bireylerde ileri yaşlı bireyelere göre akılcı ilaç kullanım düzeylerinin daha iyi olduğu söylenebilir. Anahtar Kelimeler: Akılcı İlaç Kullanımı, Huzurevi, Yaşlı Birey
... Collagen has beneficial effects on the protection and healing of connective tissue in people doing routine resistance training and cardiovascular exercise [13]. In a study by Zdzieblik et al. (2017), it was determined that there was a statistically significant improvement in activity-related pain intensity in individuals who received collagen [14]. Oral ingestion of collagen has been shown to be effective, tolerable, and safe for osteoarthritis [15]. ...
Conference Paper
Akılcı olmayan ilaç kullanımları, hem dünyada hem de ülkemizde toplum sağlığını etkileyen önemli bir sorundur. Yaşlılarda da ilaç kullanımın fazla olması, ilaç kullanımıyla ilgili sorunları beraberinde getirmektedir. Bu çalışma Bayburt ilinde huzurevinde yaşayan yaşlı bireylerin akılcı ilaç kullanım durumlarının belirlenmesi amacıyla tanımlayıcı olarak yapıldı. Çalışma evrenini Bayburt’ta faaliyet yürüten Memnuse Evsen Huzurevi Yaşlı Bakım ve Rehabilitasyon Merkezi’nde yaşayan yaşlı bireyler oluşturdu. Çalışmada örneklem seçimine gidilmeyip tüm evrene ulaşılmaya çalışıldı. Çalışmaya gönüllülük usülü ile dahil olan, iletişim kurmayla ilgili ağır engeli bulunmayan, genel durumu stabil olan 28 yaşlı birey alındı. Veri toplama aracı olarak kişisel bilgi formu ve Akılcı İlaç Kullanımı Ölçeği (AİKÖ) kullanıldı. Veriler 15-22 Şubat 2022 tarihleri arasında araştırmacılar tarafından yaşlılarla yüz yüze görüşme tekniğiyle toplandı. Veriler IBM SPSS 25 paket programda analiz edildi. İstatistiksel anlamlılık düzeyi p<0,05 olarak kabul edildi. Çalışmada Mann Whitney U testi ve Kruskal Wallis testi kullanılarak istatistiksel analiz yapıldı. Tanımlayıcı istatistikler sayı ve % olarak verildi. Yaşlı bireylerin %39,3’ünün 60-74 yaş arası, %60,7’sinin erkek, %46,4’ünün bekar, %53,6’sının ilköğretim mezunu ve üstü olduğu bulundu. Yaşlı bireylerin %57,1’i şuandaki sağlık durumunu ne iyi ne kötü olarak değerlendirdi. Yaşlı bireylerin %28,5’inin hipertansiyonu olduğu, %89,3’ünün ilaçlarını düzenli kullandığı ve ilaçlarını almayı unutmadığı saptandı. Yaşlı bireylerin %75’inin doktora muayene olmadan eczaneden ilaç almadığı, %92,9’unun komşuların/yakınların tavsiyesiyle ilaç kullanmadığı, %10,7’sinin komşuların/yakınların tavsiye ettiği ilacı doktordan reçete etmesini talep ettiği belirlendi. Yaşlı bireylerin günde en fazla 11 ilaç kullandığı ve günlük ilaç kullanım miktarının ortalama 2,21±2,11 olduğu bulundu. AİKÖ toplam puan ortalaması 57,57±7,75 olduğu bulundu. Cinsiyet ve eğitim durumu ile AİKÖ puanı arasında istatistiksel olarak anlamlı fark bulunmadı (p>0,05). Yaş gruplarıyla AİKÖ puanı arasında istatistiksel olarak anlamlı fark bulundu (H=7,595, p=0,022). Sonuç olarak huzurevinde yaşayan yaşlı bireylerin akılcı ilaç kullanım düzeylerinin ortalamanın üzerinde olduğu ve genç yaşlı bireylerde ileri yaşlı bireyelere göre akılcı ilaç kullanım düzeylerinin daha iyi olduğu söylenebilir. Anahtar Kelimeler: Akılcı İlaç Kullanımı, Huzurevi, Yaşlı Birey
... Collagen has beneficial effects on the protection and healing of connective tissue in people doing routine resistance training and cardiovascular exercise [13]. In a study by Zdzieblik et al. (2017), it was determined that there was a statistically significant improvement in activity-related pain intensity in individuals who received collagen [14]. Oral ingestion of collagen has been shown to be effective, tolerable, and safe for osteoarthritis [15]. ...
... In recent years, dietary supplements have been introduced as an additional therapeutic approach in the treatment of tendinopathies, and their positive curative effects have been reported for both the general population and athletes [17][18][19][20]. The applied dietary supplements contained a variety of micronutrients (e.g., bromelain and vitamin C) [21][22][23], which are suggested to reduce the level of inflammation [24][25][26] and to promote the healing of the tendon [21,22,[27][28][29][30]. ...
Article
Full-text available
A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the effects of dietary supplements in addition to physiotherapeutic treatment on pain and functional outcomes. PubMed, The Cochrane Library, Web of Science, and Embase were searched from inception to November 2021 (Prospero registration: CRD42021291951). Studies were eligible if the interventions consisted of physiotherapeutic approaches that were combined with dietary supplementation and if they reported measures of pain and/or function. Six studies were included in the meta-analysis. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated and analysed using a Review Manager software. Subgroup analysis was performed to explore possible associations between the study characteristics and the effectiveness of the intervention. Additional dietary supplementation during physiotherapeutic treatment significantly improved the reduction in pain score (SMD = −0.74, 95% CI, −1.37 to −0.10; p < 0.05), while it had no effect on functional outcomes (SMD = 0.29, 95% CI, 0.00 to 0.58; p > 0.05). This systematic review and meta-analysis suggests that additional nutritional interventions may improve physiotherapeutic treatment outcomes in the management of tendinopathies.
... Collagen peptides have drawn increasing attention due to their various bioactive properties, such as angiotensin I-converting enzyme (ACE-I) inhibitory activity, antioxidant activity, immunomodulatory and antimicrobial activities [1][2][3][4][5]. Studies have shown that collagen peptides display beneficial effects on human health, including improving skin health, muscle strength and bone density [6][7][8], as well as reducing obesity, joint pain and blood pressure [9][10][11]. Due to their various functions, collagen peptides have been applied in cosmetics, food, healthcare and pharmaceutical industries [12][13][14]. ...
Article
Full-text available
Bovine bone is rich in collagen and is a good material for collagen peptide preparation. Although thermolysin-like proteases (TLPs) have been applied in different fields, the potential of TLPs in preparing bioactive collagen peptides has rarely been evaluated. Here, we characterized a thermophilic TLP, A69, from a hydrothermal bacterium Anoxybacillus caldiproteolyticus 1A02591, and evaluated its potential in preparing bioactive collagen peptides. A69 showed the highest activity at 60 °C and pH 7.0. We optimized the conditions for bovine bone collagen hydrolysis and set up a process with high hydrolysis efficiency (99.4%) to prepare bovine bone collagen peptides, in which bovine bone collagen was hydrolyzed at 60 °C for 2 h with an enzyme–substrate ratio of 25 U/g. The hydrolysate contained 96.5% peptides that have a broad molecular weight distribution below 10000 Da. The hydrolysate showed good moisture-retention ability and a high hydroxyl radical (•OH) scavenging ratio of 73.2%, suggesting that the prepared collagen peptides have good antioxidative activity. Altogether, these results indicate that the thermophilic TLP A69 has promising potential in the preparation of bioactive collagen peptides, which may have potentials in cosmetics, food and pharmaceutical industries. This study lays a foundation for the high-valued utilization of bovine bone collagen.
... Recent studies indicate that both cardiometabolic [2,3], as well as nutritional factors [4,5] can modulate local tendon healing. Although clinical studies are still scarce, a recent International Olympic Committee (IOC) consensus statement on dietary supplements in high-performance athletes [6] proposes that dietary supplementation containing gelatin or hydrolysed collagen could potentially be useful for athletic populations as increased intake of collagen-derived peptides has been shown to modulate collagen synthesis [7] and reduce tendon- [8] and joint-related pain [9,10]. Others have shown that glycine, as the most abundant component of collagen hydrolysates [11], has disease-modifying properties in both animal [12,13] and in vitro [14] models of tendinopathy. ...
... In line with these findings, FCP was shown to promote the chondrogenic differentiation of human mesenchymal stem cells 52) . In clinical studies, FCP has been proven to promote the synthesis of cartilage matrix and reduce pain in patients with osteoarthritis, making it a promising candidate for the treatment of human osteoarthritis 46,[53][54][55] . Collagen peptides are thus cryptic peptides with a variety of bioactivities 56) ; however, the detailed mechanisms underlying their effects in these diseases are unclear. ...
Article
Fish collagen peptides (FCP) derived from the skin, bones and scales are commercially used as a functional food or dietary supplement for hypertension and diabetes. However, there is limited evidence on the effects of FCP on the osteoblast function in contrast to evidence of the effects on wound healing, diabetes and bone regeneration, which have been obtained from animal studies. In this narrative review, we expound on the availability of FCP by basic research using osteoblasts. Low-concentration FCP upregulates the expression of osteoblast proliferation, differentiation and collagen modifying enzyme-related genes. Furthermore, it could accelerate matrix mineralization. FCP may have potential utility as a biomaterial to improve collagen quality and promote mineralization through the mitogen-activated protein kinase and Smad cascades. However, there are few clinical studies on bone regeneration in human subjects. It is desirable to be applied clinically through clinical study as soon as possible, based on the results from basic research.
Article
Collagen is the most abundant extracellular matrix protein in food-producing animals. Gelatin is partially degraded collagen. Collagen peptides refer to the peptides with specific properties identified from collagen hydrolysate who produced by hydrolysis of collagen/gelatin. Due to the specific structural and bio- and physical-chemical properties, collagen and its derivatives are used in the field of food industry. In this review, the structure of the collagen molecule and its biosynthetic process in vivo are introduced, and the production methods and structures of gelatin and collagen peptides described. Then the inherent self-assembly property of collagen, the mechanical properties of collagen and gelatin gels, functional properties of collagen and gelatin, and bioactive properties of collagen peptides are reviewed. Finally, the applications of collagen and its derivatives that are correlated with their properties in food industry are summarized. The mechanisms and advantages of the applications of collagen and its derivatives in food industry are raised, and the limitations and challenges of these applications are also discussed. And possible studies to address the challenges of the applications in different areas are indicated.
Article
Full-text available
Although the S8 family in the MEROPS database contains many peptidases, only a few S8 peptidases have been applied in the preparation of bioactive oligopeptides. Bovine bone collagen is a good source for preparing collagen oligopeptides, but has been so far rarely applied in collagen peptide preparation. Here, we characterized a novel S8 gelatinase, Aa2_1884, from marine bacterium Flocculibacter collagenilyticus SM1988T, and evaluated its potential application in the preparation of collagen oligopeptides from bovine bone collagen. Aa2_1884 is a multimodular S8 peptidase with a distinct domain architecture from other reported peptidases. The recombinant Aa2_1884 over-expressed in Escherichia coli showed high activity toward gelatin and denatured collagens, but no activity toward natural collagens, indicating that Aa2_1884 is a gelatinase. To evaluate the potential of Aa2_1884 in the preparation of collagen oligopeptides from bovine bone collagen, three enzymatic hydrolysis parameters, hydrolysis temperature, hydrolysis time and enzyme-substrate ratio (E/S), were optimized by single factor experiments, and the optimal hydrolysis conditions were determined to be reaction at 60 ℃ for 3 h with an E/S of 400 U/g. Under these conditions, the hydrolysis efficiency of bovine bone collagen by Aa2_1884 reached 95.3%. The resultant hydrolysate contained 97.8% peptides, in which peptides with a molecular weight lower than 1000 Da and 500 Da accounted for 55.1% and 39.5%, respectively, indicating that the hydrolysate was rich in oligopeptides. These results indicate that Aa2_1884 likely has a promising potential application in the preparation of collagen oligopeptide-rich hydrolysate from bovine bone collagen, which may provide a feasible way for the high-value utilization of bovine bone collagen.
Article
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Collagen hydrolysate, an extensively used protein obtained from different sources, has various beneficial effects on human health and diseases. The benefits of collagen hydrolysate are well known and presently varied sources for the preparation of hydrolysate are being investigated. Food as a therapy to combat inflammation is presently a much-focused field of research. The present study aims at screening the anti-inflammatory property of collagen hydrolysate from the skin of Cypselurus melanurus, Catla catla, Indian mackerel, Clarias batrachus (Cb), and Pangasius pangasius (Pp) in activated RAW 264.7 macrophage cells. The fractions, Cb (C2) and Pp (P2) with anti-inflammatory property obtained after two-step chromatographic purification contained peptides in the range of 1–3 kDa molecular weight. The active fractions C2 and P2 showed a reduction in gene expression of TNF-α to 1.6- and 1-fold difference, whereas IL6 expression to 30- and 40-fold difference, respectively, in comparison to LPS treatment. The suppression of inflammatory proteins (TNF-α, IL6, NFκB, and p-IκB) by fractions C2 and P2 confirmed the anti-inflammatory activity. Practical applications Collagen hydrolysate and its derived low molecular weight peptides are of great interest in the field of nutraceuticals and biomedical applications. The purified peptide fraction of fish skin hydrolysate displayed a promising anti-inflammatory property. The collagen hydrolysate of Cb and Pp can be a functional food or its purified fraction used as a nutraceutical supplementation due to their anti-inflammatory property in the cellular microenvironment.
Chapter
Rheumatic and joint diseases are among the most widespread pathologies associated with pain and cause a great impact in society across the globe. Given the continuing rise in life expectancy, their prevalence is destined to grow. Osteoarthritis, a degenerative joint disease, is on its way to becoming the fourth leading cause of disability worldwide by 2020. Accompanying osteoarthritis is rheumatoid arthritis, which is a chronic systemic disease that often causes pain and deformity. The joint function involves several processes and understanding the mechanism of action of the joint disease process (proliferation, degradation, regeneration, and infection) is important for the diagnostic, prophylaxis, and treatment. These mechanisms are associated with active peptides that are involved in almost all physiological processes, including cell differentiation, proliferation, inflammatory processes, and immune regulation. Therefore the study of bioactive peptides as biological markers and therapeutic targets for the diagnosis, prevention, and therapy of joint diseases has a very important research ahead. In this context, the present chapter will highlight the importance of bioactive peptides in joint health, underline peptides natural sources, their mechanisms of action, and their potential applications on joint diseases.
Chapter
This chapter discusses the uses of biologically active peptides in sports nutrition and their potential mechanisms. In the beginning, it presents physiological parameters that determine athletic performance and how they may be positively influenced by nutrition and potentially the intake of bioactive peptides. It then discusses the potential effects of bioactive peptides on first body composition and muscular performance, second muscle damage, and lastly adaptions of connective tissue. The following section outlines the limitations of previous research about bioactive peptides and their potential mechanisms. By the end of the chapter, it presents practical applications that may help athletes to integrate bioactive peptides into sports nutrition to improve athletic performance as well as injury prevention and rehabilitation.
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Large amounts of meat by- and co-products are generated during slaughtering and meat processing, and require rational management of these products for an ecological disposal. Efficient solutions are very important for sustainability and innovative developments create high added-value from meat by-products with the least environmental impact, handling and disposal costs, in its transition to bioeconomy. Some proteins have relevant technological uses for gelation, foaming and emulsification while protein hydrolyzates may contribute to a better digestibility and palatability. Protein hydrolysis generate added-value products such as bioactive peptides with relevant physiological effects of interest for applications in the food, pet food, pharmaceutical and cosmetics industry. Inedible fats are increasingly used as raw material for the generation of biodiesel. Other applications are focused on the development of new biodegradable plastics that can constitute an alternative to petroleum-based plastics. This manuscript presents the latest developments for adding value to meat by- and co-products and discusses opportunities for making meat production and processing more sustainable.
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The objective of this research was to identify and characterize the chemical compounds that exhibited monosodium glutamate (MSG)-like taste in the hydrolyzed bone meal produced by using flavourzyme. The free amino acids and peptides in the bone meal hydrolysate were analyzed. The results showed that the glutamic acid and the aspartic acid in the bone meal increased by 13.1 times and 14.2 times, respectively, after the flavourzyme hydrolysis. The peptides’ isolation identified six MSG-like peptides in the hydrolysate, including APGPVGPAG, DAINWPTPGEIAH, FLGDEETVR, GVDEATIIEILTK, PAGPVGPVG, and VAPEEHPTL, which should contribute to the taste. The human sensory evaluation results indicated that the six peptides showed MSG-like taste, and the electronic tongue analysis indicated that the six peptides showed sourness, saltiness, bitterness, and astringency. The findings of this study demonstrated that the MSG-like taste of the bone meal hydrolysate should be attributed to the generation of MSG-like amino acids and peptides from the flavourzyme hydrolysis. Practical Application The manuscript describes the umami compounds in the bone meal hydrolysate. The findings from this study should further confirm the feasibility of using bone meal to prepare meat-flavor essence and provide a better understanding of preparing bio-source flavoring peptides, which is very important to the artificial meat development and gene breeding.
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To evaluate in an interventional trial on knee osteoarthritis (OA) the level and change of two serum biomarkers and their correlation with imaging parameters. The previously reported interventional OA study (ClinicalTrials.gov: NCT00536302) identified a positive effect of collagen hydrolysate (CH) on cartilage morphology in patients with knee OA using delayed gadolinium enhanced magnetic resonance imaging (dGEMRIC). It was the objective in this research project to evaluate in an interventional clinical trial on knee OA the level and change of two serum biomarkers and their correlation with imaging parameters. In blood samples of study participants, we determined the concentration of procollagen type II N-terminal propeptide (PIIANP) and aggrecan chondroitin sulfate 846 epitope (CS846) at baseline (BL) and at the follow-up (FU) visits at 24 and 48 weeks. We measured the level and change of biomarker concentrations in both study groups, and the correlation of those changes with changes in dGEMRIC. For the biomarker PIIANP, we observed a significantly greater increase in the CH group (29.9% vs. 1.2% at week 24, P = 0.001). For CS846, the mean concentration was lower among the CH treated participants at 24 weeks (78% vs. 96%, P = 0.045). Consistent correlations of changes in biomarkers PIIANP and CS846 with changes of the dGEMRIC score could not be observed. In this study, different changes per treatment group, CH and placebo were seen for dGEMRIC and PIIANP BL to 24 weeks FU, but only weak correlations between changes in dGEMRIC and biochemical markers.
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Paper reviews literature data connected with properties of collagen hydrolysates applied as diet supplements. Biological and health promoting activity of collagen derived peptides has been well documented in many studies, especially for the therapeutical treatment of bones and joints diseases as well as for the improvement of skin, hair and nails conditon. High tolerance of patients for long-term ingested collagen hydrolysates make them attractive for use as health promoting diet supplement.
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BACKGROUND: Recent studies show that enzymatically hydrolyzed collagen, the collagen peptide is absorbed and distributed to joint tissues and has analgesic and anti-inflammatory properties. A double blind placebo controlled randomized trial with collagen peptides isolated from pork (PCP) and bovine bone (BCP) sources was carried out to study the effectiveness of orally supplemented collagen peptide to control the progression of osteoarthritis in patients diagnosed with knee osteoarthritis. Improvement in treatment was assessed with reduction in Western Ontario McMaster Universities (WOMAC), visual analogue scale (VAS) and Quality of Life (QOL) scores from baseline to 13 weeks (Visit 7). Safety and tolerability were also evaluated. RESULTS: There was significant reduction from base line to Visit 7 in the primary end points of WOMAC and VAS scores and in the secondary end point of QOL score in subjects with PCP and BCP groups, while in subjects with placebo group the end point indices remained unaltered. Furthermore, all the score levels of WOMAC, VAS and QOL decreased significantly (p < 0.01) in study group compared to placebo group in Visit 7. CONCLUSION: The study demonstrated that the collagen peptides are potential therapeutic agents as nutritional supplements for the management of osteoarthritis and maintain joint health.
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Patellofemoral pain (PFP) is often seen in physically active individuals and may account for 25-40% of all knee problems seen in a sports injury clinic.1 ,2 Patellofemoral-related problems occur more frequently in women than in men.3 PFP is characterised by diffuse pain over the anterior aspect of the knee and aggravated by activities that increase patellofemoral joint (PFJ) compressive forces, such as squatting, ascending and descending stairs and prolonged sitting, as well as repetitive activities such as running. It, therefore, has a debilitating effect on sufferers’ daily lives by reducing their ability to perform sporting and work-related activities pain free. Dye has described PFP as an orthopaedic enigma, and it is one of the most challenging pathologies to manage.4 Alarmingly, a high number of individuals with PFP have recurrent or chronic pain.5 While physiotherapy interventions for PFP have proven effective compared with sham treatments, treatment results can be disappointing in a proportion of patients. This variability in treatment results may be due to the fact that the underlying factors that contribute to the development of PFP are not being addressed, or are not the same for all patients with PFP. The mission of the 3rd International Patellofemoral Research Retreat was to improve our understanding concerning the factors that contribute to the development and consequently to the treatment of PFP. The 3rd International Patellofemoral Research Retreat was held in Vancouver, Canada, in September 2013, for 3 days: from 18 September to 21 September. After peer-review for scientific merit and relevance to the retreat, 58 abstracts were accepted for the retreat (39 podiums, 8 posters and 11 thematic posters). The podium and poster presentations were grouped into three categories: (1) natural history of PFP and local factors that influence PFP, (2) trunk and distal factors that influence PFP and …
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Protein hydrolysates constitute an alternative to intact proteins and elemental formulas in the development of special formulations designed to provide nutritional support to patients with different needs. The production of extensive protein hydrolysates by sequential action of endopeptidases and exoproteases coupled with the development of post-hydrolysis procedures is considered the most effective way to obtain protein hydrolysates with defined characteristics. This paper reviews the development and use of protein hydrolysates for dietary treatment of patients with phenylketonuria, food allergy and chronic liver failure.
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Destruction of articular cartilage is a characteristic feature of osteoarthritis (OA). Collagen hydrolysates are mixtures of collagen peptides and have gained huge public attention as nutriceuticals used for prophylaxis of OA. Here, we evaluated for the first time whether different bovine collagen hydrolysate preparations indeed modulate the metabolism of collagen and proteoglycans from human OA cartilage explants and determined the chemical composition of oligopeptides representing collagen fragments. Using biophysical techniques, like MALDI-TOF-MS, AFM, and NMR, the molecular weight distribution and aggregation behavior of collagen hydrolysates from bovine origin (CH-Alpha®, Peptan™ B 5000, Peptan™ B 2000) were determined. To investigate the metabolism of human femoral OA cartilage, explants were obtained during knee replacement surgery. Collagen synthesis of explants as modulated by 0-10 mg/ml collagen hydrolysates was determined using a novel dual radiolabeling procedure. Proteoglycans, NO, PGE(2), MMP-1, -3, -13, TIMP-1, collagen type II, and cell viability were determined in explant cultures. Groups of data were analyzed using ANOVA and the Friedman test (n = 5-12). The significance was set to p≤0.05. We found that collagen hydrolysates obtained from different sources varied with respect to the width of molecular weight distribution, average molecular weight, and aggregation behavior. None of the collagen hydrolysates tested stimulated the biosynthesis of collagen. Peptan™ B 5000 elevated NO and PGE(2) levels significantly but had no effect on collagen or proteoglycan loss. All collagen hydrolysates tested proved not to be cytotoxic. Together, our data demonstrate for the first time that various collagen hydrolysates differ with respect to their chemical composition of collagen fragments as well as by their pharmacological efficacy on human chondrocytes. Our study underscores the importance that each collagen hydrolysate preparation should first demonstrate its pharmacological potential both in vitro and in vivo before being used for both regenerative medicine and prophylaxis of OA.
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Evaluation of the efficacy and safety of a food supplement made of collagen hydrolysate 1200 mg/day versus placebo during 6 months, in subjects with joint pain at the lower or upper limbs or at the lumbar spine. Comparative double-blind randomized multicenter study in parallel groups. 200 patients of both genders of at least 50 years old with joint pain assessed as ≥30 mm on a visual analogical scale (VAS). Collagen hydrolysate 1200 mg/day or placebo during 6 months. Comparison of the percentage of clinical responder between the active collagen hydrolysate group and the placebo group after 6 months of study. A responder subject was defined as a subject experiencing a clinically significant improvement (i.e. by 20% or more) in the most painful joint using the VAS score. All analyses were performed using an intent-to-treat procedure. At 6 months, the proportion of clinical responders to the treatment, according to VAS scores, was significantly higher in the collagen hydrolysate (CH) group 51.6%, compared to the placebo group 36.5% (p<0.05). However, there was no significant difference between groups at 3 months (44.1% vs. 39.6%, p=0.53). No significant difference in terms of security and tolerability was observed between the two groups. This study suggests that collagen hydrolysate 1200 mg/day could increase the number of clinical responders (i.e. improvement of at least 20% on the VAS) compared to placebo. More studies are needed to confirm the clinical interest of this food supplement.
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We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin (α2A), providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular level. The occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy (AFM) techniques. Strong interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study (which contains 42 amino acid residues per strand) by solid phase assays as well as by surface plasmon resonance (SPR) measurements. However, changes in NMR signals during titration and characteristic saturation transfer difference (STD) NMR signals are also detectable when α2A is added to a solution of the 21mer single-stranded collagen fragment. Molecular dynamics (MD) simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments with α2A. It is remarkable that even single-stranded collagen fragments can form various complexes with α2A showing significant differences in the complex stability with identical ligands. The results of MD simulations are in agreement with the signal alterations in our NMR experiments, which are indicative of the formation of weak complexes between single-stranded collagen and α2A in solution. These results provide useful information concerning possible interactions of α2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors.
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Collagen, a major extracellular matrix macromolecule, is widely used for biomedical purposes. We investigated the absorption mechanism of low molecular weight collagen hydrolysate (LMW-CH) and its effects on osteoporosis in rats. When administered to Wistar rats with either [(14)C]proline (Pro group) or glycyl-[(14)C]prolyl-hydroxyproline (CTp group), LMW-CH rapidly increased plasma radioactivity. LMW-CH was absorbed into the blood of Wistar rats in the peptide form. Glycyl-prolyl-hydroxyproline tripeptide remained in the plasma and accumulated in the kidney. In both groups, radioactivity was retained at a high level in the skin until 14 days after administration. Additionally, the administration of LMW-CH to ovariectomized stroke-prone spontaneously hypertensive rats increased the organic substance content and decreased the water content of the left femur. Our findings show that LMW-CH exerts a beneficial effect on osteoporosis by increasing the organic substance content of bone.
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Cartilage matrix degradation generates collagen type II fragments. The objective of this study is to explore the possibility that these collagen fragments may be part of an endogenous metabolic feedback. Initially, collagen fragments were extracted from normal or osteoarthritic cartilage, as part of a matrix fragment preparation. Later, collagen fragments were generated by digestion of bovine collagen type II with bacterial collagenase (col2f). These fragments were added to cultures of isolated chondrocytes (bovine and human) and cartilage explants (human). In a dose-dependent manner, col2f caused inhibition of cell attachment to collagen, inhibition of collagen synthesis, and induction of matrix degradation. In addition, when col2f were added to human cartilage explants, an induction of gelatinase activity was detected in the media. These data sets present first evidence that degradation products of collagen may be directly involved in the regulation of cartilage homeostasis.
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Media supplementation with collagen hydrolysate was hypothesized to increase the collagen content in engineered cartilage. By d28, hydrolysate at 0.5 mg/mL increased type II collagen content and 1 mg/mL increased mechanical properties, total collagen content, and type II collagen content over controls. By d42, however, controls possessed the highest GAG content and compressive Young's modulus. Real-time PCR found that 1 mg/mL increased type II collagen gene expression in d0 constructs, but increased MMP expression with no effect on type II collagen on d28. A 10 mg/mL concentration produced the lowest tissue properties, the lowest type II collagen gene expression on d0, and the highest MMP gene expression on d28. These results indicate that the duration of culture modulates the response of chondrocytes to collagen hydrolysate in 3D culture, transforming the response from positive to negative. Therefore, collagen hydrolysate as a media supplement is not a viable long-term method to improve the collagen content of engineered cartilage tissue.
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Objective To assess the effects of physical exercise on physical, functional and psychological dimensions in nursing home residents.
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During the past years, evidence accumulated showing that glycine comprises anti-inflammatory activities. These effects occur, at least in part, via the activation of glycine-gated chloride channels (GlyR). Glycine is one of the major structural units of collagen, making up about 30% of the amino acids. This study aims to investigate the anti-inflammatory potential of collagen hydrolysate (CH) using the zymosan-induced ear-skin inflammation mouse model. After oral intake of 12.5, 25 or 50 mg CH the plasma levels of glycine increased in a concentration-dependent manner. CH was able to counteract zymosan-induced ear-skin inflammation locally (ear swelling) as well as systemically (IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood cells). The LPS-stimulated IL-6 production in whole blood correlated positively with the ear swelling response. This correlation was abolished by strychnine (a glycine receptor antagonist), indicating the involvement of GlyR. Collectively, these data show that CH is able to modulate inflammatory responses both locally as well as systemically. This effect might be constituted by inhibiting pro-inflammatory cytokine production via GlyR.
Article
Heterogeneous mixtures of collagen fragments can be used as nutrition supplement or as key ingredients for ointments with therapeutic relevance in wound healing. Some mixtures of collagen fragments are referred to as collagen hydrolysates owing to the production process with hydrolytic enzymes. Since the precise composition of collagen hydrolysates is generally unknown, it is of interest to analyze samples containing various collagen fragments with appropriate biophysical methods. Any product optimization without a profound knowledge concerning the size and the molecular weight distribution of its components is nearly impossible. It turned out that a combination of AFM methods with NMR techniques is exceptionally suited to examine the size range and the aggregation behavior of the collagen fragments in the hydrolysates of fish, jellyfish, chicken, porcine and bovine collagen. Supported by molecular modeling calculations, the AFM and NMR experiments provide a detailed knowledge about the composition of collagen hydrolysates and collagen ointments. Furthermore, the data allow a correlation between the size of the fragments and their potential bioactivity.
Article
The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be α1(I)α2(I)α3(I) and [α1(I)]2α2(I), respectively. The occurrence of α3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 °C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proα(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proα(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific α(I) chain, proα3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proα1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proα3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proα3(I) had diverged from proα1(I). This study is the first report of the complete primary structure of fish type I procollagen.
Article
To determine whether either of two magnetic resonance imaging approaches - delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC), or T2 mapping - can detect short-term changes in knee hyaline cartilage among individuals taking a formulation of collagen hydrolysate. Single center, prospective, randomized, placebo-controlled, double-blind, pilot trial of collagen hydrolysate for mild knee osteoarthritis (OA). Participants were allowed to continue the prior analgesic use. The primary outcome was change in dGEMRIC T1 relaxation time in the cartilage regions of interest at the 24-week timepoint. Secondary endpoints included the change in dGEMRIC T1 relaxation time between baseline and 48 weeks, the change in T2 relaxation time at 0, 24 and 48 weeks, the symptom and functional measures obtained at each of the visits, and overall analgesic use. Among a sample of 30 randomized subjects the dGEMRIC score increased in the medial and lateral tibial regions of interest (median increase of 29 and 41 ms respectively) in participants assigned to collagen hydrolysate but decreased (median decline 37 and 36 ms respectively) in the placebo arm with the changes between the two groups at 24 weeks reaching significance. No other significant changes between the two groups were seen in the other four regions, or in any of the T2 values or in the clinical outcomes. These preliminary results suggest that the dGEMRIC technique may be able to detect change in proteoglycan content in knee cartilage among individuals taking collagen hydrolysate after 24 weeks.
Article
Current options to promote joint comfort are limited to medicines that can reduce pain but can also have adverse effects. Collagen, a major component of joint cartilage, is found in the diet, particularly in meat. Its hydrolysed form, collagen hydrolysate (CH), is well absorbed. CH may stimulate the joint matrix cells to synthesize collagen, so helping to maintain the structure of the joint and potentially to aid joint comfort. In a randomized, double-blind, controlled multicentre trial, 250 subjects with primary osteoarthritis of the knee were given 10 g CH daily for 6 months. There was a significant improvement in knee joint comfort as assessed by visual analogue scales to assess pain and the Womac pain subscale. Subjects with the greatest joint deterioration, and with least intake of meat protein in their habitual diets, benefited most. CH is safe and effective and warrants further consideration as a food ingredient.
Article
Clinical studies have shown that collagen hydrolysate (CH) may be able to protect joints from damage, strengthen joints, and reduce pain from conditions like osteoarthritis. CH is a collection of amino acids and bioactive peptides, which allows for easy absorption into the blood stream and distribution in tissues. However, although various matrices have been studied, the absorption of specific amino acids from CH added to a fresh fermented milk product (FMP) was not studied. The primary objective of the present study was to compare the plasma concentrations of four representative amino acids from the CH (glycine, proline, hydroxyproline, and hydroxylysine) contained in a single administration of a FMP with that of a single administration of an equal amount of neat hydrolyzed collagen. These four amino acids were chosen because they have already been used as markers of CH absorption rate and bioavailability. This was a single-center, randomized open, and crossover study with two periods, which was performed in 15 healthy male subjects. The subjects received randomly and in fasted state a single dose of product 1 (10 g of CH in 100 mL of FMP) and product 2 (10 g of CH dissolved in 100 mL of water) separated by at least 5 days. After administration, the subjects were assessed for plasma concentrations of amino acids and for urine concentrations of hydroxyproline. After FMP administration, mean values of the maximal concentration (Cmax) of the four amino acids were greater than after ingredient administration (p < 0.05). This effect was related to an increased Cmax of proline (p < 0.05). In conclusion, because of their physicochemical characteristics, the fermentation process, and the great homogeneity of the preparation, this milk product improves the plasma concentration of amino acids from CH, that is, proline. The present study suggests an interesting role for FMP containing CH to improve the plasmatic availability of collagen-specific amino acids. Hence, this FMP product could be of potential interest in the management of joint diseases.
Article
Several investigations showed a positive influence of orally administered gelatin on degenerative diseases of the musculo-skeletal system. Both the therapeutic mechanism and the absorption dynamics, however, remain unclear. Therefore, this study investigated the time course of gelatin hydrolysate absorption and its subsequent distribution in various tissues in mice (C57/BL). Absorption of (14)C labeled gelatin hydrolysate was compared to control mice administered (14)C labeled proline following intragastric application. Plasma and tissue radioactivity was measured over 192 h. Additional "gut sac" experiments were conducted to quantify the MW distribution of the absorbed gelatin using SDS-electrophoresis and HPLC. Ninety-five percent of enterally applied gelatin hydrolysate was absorbed within the first 12 h. The distribution of the labeled gelatin in the various tissues was similar to that of labeled proline with the exception of cartilage, where a pronounced and long-lasting accumulation of gelatin hydrolysate was observed. In cartilage, measured radioactivity was more than twice as high following gelatin administration compared to the control group. The absorption of gelatin hydrolysate in its high molecular form, with peptides of 2.5-15kD, was detected following intestinal passage. These results demonstrate intestinal absorption and cartilage tissue accumulation of gelatin hydrolysate and suggest a potential mechanism for previously observed clinical benefits of orally administered gelatin.
Article
To review the current status of collagen hydrolysate in the treatment of osteoarthritis and osteoporosis. Review of past and current literature relative to collagen hydrolysate metabolism, and assessment of clinical investigations of therapeutic trials in osteoarthritis and osteoporosis. Hydrolyzed gelatin products have long been used in pharmaceuticals and foods; these products are generally recognized as safe food products by regulatory agencies. Pharmaceutical-grade collagen hydrolysate (PCH) is obtained by hydrolysis of pharmaceutical gelatin. Clinical studies suggest that the ingestion of 10 g PCH daily reduces pain in patients with osteoarthritis of the knee or hip; blood concentration of hydroxyproline is increased. Clinical use is associated with minimal adverse effects, mainly gastrointestinal, characterized by fullness or unpleasant taste. In a multicenter, randomized, doubleblind, placebo-controlled trial performed in clinics in the United States, United Kingdom, and Germany, results showed no statistically significant differences for the total study group (all sites) for differences of mean pain score for pain. There was, however, a significant treatment advantage of PCH over placebo in German sites. In addition, increased efficacy for PCH as compared to placebo was observed in the overall study population amongst patients with more severe symptomatology at study onset. Preferential accumulation of 14C-labeled gelatin hydrolysate in cartilage as compared with administration of 14C-labeled proline has been reported. This preferential uptake by cartilage suggests that PCH may have a salutary effect on cartilage metabolism. Given the important role for collagen in bone structure, the effect of PCH on bone metabolism in osteoporotic persons has been evaluated. Studies of the effects of calcitonin with and without a collagen hydrolysate-rich diet suggested that calcitonin plus PCH had a greater effect in inhibiting bone collagen breakdown than calcitonin alone, as characterized by a fall in levels of urinary pyridinoline cross-links. PCH appeared to have an additive effect relative to use of calcitonin alone. Collagen hydrolysate is of interest as a therapeutic agent of potential utility in the treatment of osteoarthritis and osteoporosis. Its high level of safety makes it attractive as an agent for long-term use in these chronic disorders.
Article
The functional integrity of articular cartilage is dependent on the maintenance of the extracellular matrix (ECM), a process which is controlled by chondrocytes. The regulation of ECM biosynthesis is complex and a variety of substances have been found to influence chondrocyte metabolism. In the present study we have investigated the effect of degraded collagen on the formation of type II collagen by mature bovine chondrocytes in a cell culture model. The culture medium was supplemented with collagen hydrolysate (CH) and biosynthesis of type II collagen by chondrocytes was compared to control cells treated with native type I and type II collagen and a collagen-free protein hydrolysate. The quantification of type II collagen by means of an ELISA technique was confirmed by immunocytochemical detection as well as by the incorporation of (14)C-proline in the ECM after a 48 h incubation. Chondrocytes in the control group were maintained in the basal medium for 11 days. The presence of extracellular CH led to a dose-dependent increase in type II collagen secretion. However, native collagens as well as a collagen-free hydrolysate of wheat proteins failed to stimulate the production of type II collagen in chondrocytes. These results clearly indicate a stimulatory effect of degraded collagen on the type II collagen biosynthesis of chondrocytes and suggest a possible feedback mechanism for the regulation of collagen turnover in cartilage tissue.
Article
In the present study, we identified several food-derived collagen peptides in human blood after oral ingestion of some gelatin hydrolysates. Healthy human volunteers ingested the gelatin hydrolysates (9.4-23 g) from porcine skin, chicken feet, and cartilage after 12 h of fasting. Negligible amounts of the peptide form of hydroxyproline (Hyp) were observed in human blood before the ingestion. After the oral ingestion, the peptide form of Hyp significantly increased and reached a maximum level (20-60 nmol/mL of plasma) after 1-2 h and then decreased to half of the maximum level at 4 h after the ingestion. Major constituents of food-derived collagen peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amounts of Ala-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp were contained.
Article
Destruction of collagen within osteoarthritic cartilage depends in part on collagen-degrading matrix metalloproteases (MMP). Degradative fragments of type II collagen (Col II) occur in normal and in osteoarthritic cartilage, and may contribute to regulation of matrix turnover by interfering with normal cell-matrix communication pathways. Therefore, the effects of different types of collagen fragments on mRNA and protein levels of MMP-2, MMP-3, MMP-9, and MMP-13 in cultured bovine articular knee chondrocytes and explants were examined. Primary chondrocytes and explants were incubated with fragments from whole cartilage collagen matrix (Colf) and from purified type II collagen (Col2f), or with a synthetic 29-mer peptide representing the amino-terminal domain of type II collagen (Ntelo). Gelatin zymography revealed increases of proMMP-2, a shift towards active MMP-2 and increases in proMMP-9, depending on the type of fragment. In situ hybridization of cartilage sections displayed MMP-3 mRNA in virtually all cells. Moderate to strong increases in MMP-2, MMP-3, MMP-9, and MMP-13 mRNA levels were detected by quantitative PCR. The results demonstrate stimulating effects of collagen fragments on both mRNA and/or protein from MMP -2, -3, -9, and -13, and suggest a novel mechanism of MMP induction and activation that includes a particular role for N-telo in controlling catabolic pathways of matrix turnover.
Article
There is a need for an effective treatment for the millions of people in the United States with osteoarthritis (OA), a degenerative joint disease. The demand for treatments, both traditional and non-traditional, will continue to grow as the population ages. This article reviews the medical literature on the preclinical and clinical research on a unique compound, collagen hydrolysate. Articles were obtained through searches of the PubMed database (www.pubmed.gov) through May 2006 using several pairs of key words (collagen hydrolysate and osteoarthritis; collagen hydrolysate and cartilage; collagen hydrolysate and chondrocytes; collagen hydrolysate and clinical trial) without date limits. In addition, other sources of information, such as abstracts presented at scientific congresses and articles in the German medical literature not available on PubMed, were reviewed and included based on the authors' judgment of their relevance to the topic of the review. According to published research, orally administered collagen hydrolysate has been shown to be absorbed intestinally and to accumulate in cartilage. Collagen hydrolysate ingestion stimulates a statistically significant increase in synthesis of extracellular matrix macromolecules by chondrocytes (p < 0.05 compared with untreated controls). These findings suggest mechanisms that might help patients affected by joint disorders such as OA. Four open-label and three double-blind studies were identified and reviewed; although many of these studies did not provide key information--such as the statistical significance of the findings--they showed collagen hydrolysate to be safe and to provide improvement in some measures of pain and function in some men and women with OA or other arthritic conditions. A growing body of evidence provides a rationale for the use of collagen hydrolysate for patients with OA. It is hoped that ongoing and future research will clarify how collagen hydrolysate provides its clinical effects and determine which populations are most appropriate for treatment with this supplement.
Article
We compared quantity and structures of food-derived gelatin hydrolysates in human blood from three sources of type I collagen in a single blind crossover study. Five healthy male volunteers ingested type I gelatin hydrolysates from fish scale, fish skin, or porcine skin after 12 h of fasting. Amounts of free form Hyp and Hyp-containing peptide were measured over a 24-h period. Hyp-containing peptides comprised approximately 30% of all detected Hyp. The total area under the concentration-time curve of the fish scale group was significantly higher than that of the porcine skin group. Pro-Hyp was a major constituent of Hyp-containing peptides. Ala-Hyp, Leu-Hyp, Ile-Hyp, Phe-Hyp, and Pro-Hyp-Gly were detected only with fish scale or fish skin gelatin hydrolysates. Ala-Hyp-Gly and Ser-Hyp-Gly were detected only with fish scale gelatin hydrolysate. The quantity and structure of Hyp-containing peptides in human blood after oral administration of gelatin hydrolysate depends on the gelatin source.
Article
Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis. To investigate the effect of collagen hydrolysate on activity-related joint pain in athletes who are physically active and have no evidence of joint disease. A prospective, randomized, placebo-controlled, double-blind study was conducted at Penn State University in University Park, Pennsylvania. Parameters including joint pain, mobility, and inflammation were evaluated with the use of a visual analogue scale during a 24-week study phase. Between September 2005 and June 2006, 147 subjects who competed on a varsity team or a club sport were recruited. Data from 97 of 147 subjects could be statistically evaluated. One hundred and forty-seven subjects (72 male, 75 female) were randomly assigned to two groups: a group (n = 73) receiving 25 mL of a liquid formulation that contained 10 g of collagen hydrolysate (CH-Alpha) and a group (n = 74) receiving a placebo, which consisted of 25 mL of liquid that contained xanthan. The primary efficacy parameter was the change in the visual analogue scales from baseline during the study phase in relation to the parameters referring to pain, mobility, and inflammation. When data from all subjects (n = 97) were evaluated, six parameters showed statistically significant changes with the dietary supplement collagen hydrolysate (CH) compared with placebo: joint pain at rest, assessed by the physician (CH vs. placebo (-1.37 +/- 1.78 vs. -0.90 +/- 1.74 (p = 0.025)) and five parameters assessed by study participants: joint pain when walking (-1.11 +/- 1.98 vs. -0.46 +/- 1.63, p = 0.007), joint pain when standing (-0.97 +/- 1.92 vs. -0.43 +/- 1.74, p = 0.011), joint pain at rest (-0.81 +/- 1.77 vs. -0.39 +/- 1.56, p = 0.039), joint pain when carrying objects (-1.45 +/- 2.11 vs. -0.83 +/- 1.71, p = 0.014) and joint pain when lifting (-1.79 +/- 2.11 vs. -1.26 +/- 2.09, p = 0.018). When a subgroup analysis of subjects with knee arthralgia (n = 63) was performed, the difference between the effect of collagen hydrolysate vs. placebo was more pronounced. The parameter joint pain at rest, assessed by the physician, had a statistical significance level of p = 0.001 (-1.67 +/- 1.89 vs. -0.86 +/- 1.77), while the other five parameters based on the participants' assessments were also statistically significant: joint pain when walking (p = 0.003 (-1.38 +/- 2.12 vs. -0.54 +/- 1.65)), joint pain when standing (p = 0.015 (-1.17 +/- 2.06 vs. -0.50 +/- 1.68)), joint pain at rest with (p = 0.021 (-1.01 +/-1.92 vs. -0.47 +/- 1.63)), joint pain when running a straight line (p = 0.027 (-1.50 +/- 1.97 vs. -0.80 +/- 1.66)) and joint pain when changing direction (p = 0.026 (-1.87 +/- 2.18 vs. -1.20 +/- 2.10)). This was the first clinical trial of 24-weeks duration to show improvement of joint pain in athletes who were treated with the dietary supplement collagen hydrolysate. The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study's size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance. Future studies are needed to support these findings.
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