Vitamin C For Collagen

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Preclinical research demonstrated that vitamin C has the potential to speed up bone therapeutic after a fracture, enhance kind I collagen synthesis, and cut back oxidative stress parameters. No opposed results had been reported with vitamin C supplementation in both animal fashions or human individuals; thus, oral vitamin C seems to be a secure complement however lacks scientific proof in contrast with controls. Due to the restricted variety of human research, additional scientific investigations are wanted earlier than the implementation of vitamin C as a postinjury complement.

The preliminary search yielded 286 articles. After making use of the inclusion and exclusion standards, 10 articles had been included within the ultimate evaluation. Of the preclinical research evaluating fracture therapeutic, 2 research reported considerably accelerated bone therapeutic within the vitamin C supplementation group in contrast with management teams. The two preclinical research evaluating tendon therapeutic reported vital will increase in kind I collagen fibers and scar tissue formation with vitamin C in contrast with management teams. The 1 preclinical research after anterior cruciate ligament (ACL) reconstruction reported vital short-term (1-6 weeks) enhancements in ACL graft incorporation within the vitamin C group in contrast with management teams; nevertheless, there was no long-term (42 weeks) distinction. Of the scientific research evaluating fracture therapeutic, 1 research reported no vital variations within the charge of fracture therapeutic at 50 days or purposeful outcomes at 1 12 months. Vitamin C supplementation was proven to lower oxidative stress parameters by neutralizing reactive oxygen species via redox modulation in animal fashions. No animal or human research reported any opposed results of vitamin C supplementation.

To (1) summarize vitamin C therapy protocols; (2) report on the efficacy of vitamin C in accelerating therapeutic after bone, tendon, and ligament accidents in vivo and in vitro; and (3) report on the efficacy of vitamin C as an antioxidant defending in opposition to fibrosis and selling collagen synthesis.

Though laboratory research have reported that vitamin C is important for the formation of collagen fibers and cell differentiation, there may be controversy surrounding the efficacy of vitamin C as a complement for scientific therapy. Due to this fact, the needs of this systematic evaluate had been to (1) summarize vitamin C therapy protocols; (2) report on the efficacy of vitamin C in accelerating therapeutic after bone, tendon, and ligament accidents in vivo and in vitro; and (3) report on the efficacy of vitamin C as an antioxidant defending in opposition to fibrosis and selling collagen synthesis. It was hypothesized that vitamin C supplementation would end in decreased oxidative stress and accelerated tissue therapeutic compared with management teams.

Vitamin C has a necessary position in connective tissue therapeutic, being a cofactor for prolyl hydroxylase and lysyl hydroxylase. 22 , 28 These enzymes catalyze the hydroxylation of proline and lysine residues of procollagen, selling the right folding of the steady collagen triple-helix conformation. 9 , 22 Along with its position in collagen synthesis, vitamin C acts as a robust antioxidant by neutralizing deleterious reactive oxygen species (ROS) answerable for cell apoptosis through the inflammatory part. 1 , 14 , 16 Cell tradition research have additionally reported that vitamin C can induce tendon-derived stem cell mobilization, osteoblast development and differentiation, and fibroblast stimulation. 8 , 11 , 18 , 21 , 26 Due to this fact, vitamin C has been more and more studied for its contributions to the therapy of musculoskeletal accidents in each scientific and in vitro trials.

The therapeutic of musculoskeletal tissues, similar to bone, tendons, and ligaments, depends on the capability of collagen synthesis and cross-linking. 7 , 20 , 34 Poorly developed extracellular matrices derived from collagen can result in insufficient tissue constructions and biomechanical power, which can lead to unsatisfactory outcomes and an elevated danger for reinjuries. Fundamental science investigations on the biochemical pathways after a musculoskeletal damage have steered that vitamin C, also referred to as ascorbic acid, might improve collagen synthesis and mushy tissue therapeutic. 22 , 24 , 28 , 31

Each animal and human research had been collected. These findings included experimental focus, abnormality, animal mannequin kind, collagen kind (ie, bone, ligament, tendon), therapies, postoperative restrictions, route of vitamin C administration, and vitamin C dosage (together with frequency and length). The extent of proof of all accessible scientific research was assigned in line with the classification as specified by Wright et al. 38 Affected person demographics, supplementation dosage, therapy particulars, follow-up, and subjective and goal affected person outcomes had been recorded for all scientific research. For steady variables (age, end result scores, and so forth), the imply and vary had been obtained if reported.

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The inclusion standards consisted of English-language research and each animal and human research on vitamin C supplementation after musculoskeletal accidents particular to collagen cross-linking, collagen synthesis, and biologic therapeutic of the bone, ligament, and tendon. Exclusion standards had been vitamin C supplementation particular to nonmusculoskeletal-related accidents or surgical procedure, wholesome/noninjured populations, scurvy, vitamin C deficiency, impact of vitamin C on mesenchymal stem cells, genetic research, mobile research, epidemiological research, dietary consumption with out vitamin C supplementation, editorial articles, evaluate articles, case reviews (degree 5 proof), and surveys. Two investigators (N.N.D., Z.S.A.) independently reviewed the abstracts from all recognized articles. If essential, full-text articles had been obtained for a evaluate to permit for additional utility of inclusion and exclusion standards. Moreover, reference lists from the included research had been reviewed and reconciled to confirm that every one eligible articles had been thought of.

A scientific evaluate of articles, utilizing the PRISMA (Most well-liked Reporting Objects for Systematic Meta-Analyses) pointers, on the efficacy of vitamin C in selling collagen synthesis, lowering irritation, and bettering bone/ligament/tendon therapeutic after musculoskeletal accidents was carried out utilizing the Cochrane Database of Systematic Opinions, the Cochrane Central Register of Managed Trials, PubMed (1980-2017), MEDLINE (1980-2017), and Embase (1980-2017); the queries had been carried out in November 2017. Registration of this systematic evaluate was carried out in January 2018 utilizing the PROSPERO worldwide potential register of systematic evaluations (CRD42018086378). The search phrases utilized had been “vitamin C” OR “ascorbic acid” AND “musculoskeletal injury”; “vitamin C” OR “ascorbic acid” AND “collagen cross-linking”; “vitamin C” OR “ascorbic acid” AND “orthopaedics”; “vitamin C” OR “ascorbic acid” AND “bone healing”; “vitamin C” OR “ascorbic acid” AND “ligament healing”; “vitamin C” OR “ascorbic acid” AND “tendon healing”; and “vitamin C” OR “ascorbic acid” AND “postoperative recovery.”

The scientific trial evaluating muscle restoration after ACLR reported no vital variations between the vitamin C and management teams. 2 Nonetheless, baseline vitamin C standing was related to vital enhancements in power, suggesting that long-term dietary habits could also be simpler than short-term dietary supplements. 2 The outcomes of the two scientific trials evaluating bone therapeutic after fractures had been conflicting. Sandukji et al 32 reported vital will increase in osteocalcin ranges and the exercise of alkaline phosphatase within the blood plasma of sufferers who obtained antioxidants for two weeks (P < .05), each of that are bone markers beforehand reported to be positively correlated with bone mineral density (BMD). 13 , 35 Nonetheless, these authors didn't report on the long-term outcomes of fracture therapeutic. In distinction, Ekrol et al 6 famous no vital distinction within the time to fracture therapeutic in sufferers with lengthy bone fractures who had been supplemented with vitamin C in contrast with controls. Moreover, there have been no vital variations between the two therapy teams at 1-year follow-up. 6 No opposed results had been reported in any scientific research (n = 3) relating to the usage of vitamin C, and 1 research reported a dropout charge of 26% and a compliance charge of 84%. 6 Regardless of this excessive dropout charge, the authors nonetheless managed to incorporate a big pattern dimension (n = 162) of their ultimate evaluation. 6 Additional outcomes are detailed in . The affected person demographics, research design, and experimental focus of all scientific research are reported in . Of the three scientific research, 2 research evaluated a mixed complement of vitamin C and different antioxidants, 2 , 32 whereas 1 research evaluated completely the consequences of vitamin C. 6 The dosage of orally supplemented vitamin C ranged from 60 mg twice every day to 500 mg twice every day for no less than 7 days and most of three months. The two research evaluating bone fracture therapeutic started vitamin C supplementation on day 1 after the fracture. 6 , 32 The research evaluating oxidative stress and muscle restoration started vitamin C supplementation 2 weeks earlier than the deliberate ACLR. 2 Three preclinical research 5 , 10 , 19 evaluated oxidative stress after vitamin C supplementation. All 3 preclinical research reported that vitamin C was efficient in lowering oxidative stress after accidents by reducing endogenous or exogenous ROS, signified by an improved tissue composition in ligaments, tendons, and bone. Nonetheless, only one of the three research reported vitamin C as an antagonist for oxidative stress after 2 weeks. 19 Moreover, 1 scientific research evaluated oxidative stress and muscle restoration after vitamin C and E supplementation after ACLR. 2 The authors reported that vitamin C and E supplementation had no vital results on oxidative stress parameters in contrast with controls after ACLR. 2 Total, the preclinical research supported the usage of vitamin C for tendon, bone, and ligament graft therapeutic. Three of the 4 research evaluating the consequences of vitamin C on fracture therapeutic reported a rise or acceleration in collagen synthesis compared with management teams. 5 , 33 , 41 One research reported that there have been no vital histological or histomorphological rating variations between the vitamin C and management teams for fracture therapeutic. 15 Each research evaluating tendon therapeutic after ruptures reported improved structural high quality with vitamin C supplementation. 19 , 25 Omeroglu et al 25 reported that there was a major enhance in kind I collagen formation and the next charge in lively fibroblasts in low-dose vitamin C teams. Hung et al 19 reported comparable structural integrity in tendons, as vitamin C considerably decreased the fibrotic dimension and peritendinous adhesion. Nonetheless, the authors didn't report on tendinous collagen composition. 19 Fu et al 10 reported that low-dose vitamin C restored anteroposterior knee stability and considerably decreased graft deterioration after ACLR in contrast with the management group after 6 weeks; nevertheless, there have been no vital variations in long-term outcomes (42 weeks) or ACL graft incorporation between teams. All the research evaluating the position of vitamin C as an antioxidant and collagen synthesizer (n = 3) steered that vitamin C positively influences bone, tendon, and graft therapeutic by antagonizing oxidative stress. 5 , 10 , 19 No opposed results had been reported in any preclinical research (n = 7).

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4 research decided vitamin C dosage as a perform of animal weight, starting from 0.5 mg/kg to 500 mg/kg. 5 , 15 , 33 , 41 The remaining 3 research utilized customary doses between 0.005 mg and 150 mg. 10 , 19 , 25 The supply of vitamin C assorted, together with intraperitoneally (n = 4), 5 , 15 , 25 , 33 regionally (n = 1), 19 intramuscularly (n = 1), 41 or by intraoperative irrigation (n = 1). 10 The intervention was initiated on postinjury day 0 in all preclinical research (n = 7). The frequency of vitamin C dosage assorted between as soon as on the time of damage to as soon as per day till the tip of the trial. The length of particular person trials ranged from 3 days to six weeks. 4 research allowed free entry to straightforward weight loss plan and water, 5 , 25 , 33 , 41 1 research supplied a weight loss plan that didn't comprise vitamin C, 15 and a pair of research didn't report meals and water restrictions. 10 , 19 5 research allowed animals to maneuver freely with out immobilization after the process, 10 , 15 , 25 , 33 , 41 1 research immobilized the injured limb, 19 and 1 research didn't report on immobilization 5 ( ). The literature search recognized 286 research from the aforementioned databases. After duplicates had been eliminated, 264 articles had been screened, and 10 articles met the inclusion standards ( ). There have been 7 research that evaluated the consequences of vitamin C supplementation in animal fashions: 4 after bone fractures (nonoperative therapy), 2 after tendon ruptures (nonoperative and surgical therapy), and 1 after anterior cruciate ligament (ACL) reconstruction (ACLR) ( ). Six of the animal research used a rat mannequin, and 1 research used a rooster mannequin. There have been 3 research that evaluated the consequences of vitamin C supplementation in human fashions: 1 after ACLR and a pair of after bone fractures (nonoperative and surgical therapy). Two of the scientific research had been degree 1 proof, whereas 1 research was degree 2 proof. Dialogue A very powerful discovering of this systematic evaluate was that there's preclinical proof that vitamin C supplementation accelerates bone therapeutic after fractures, will increase kind I collagen synthesis, and reduces oxidative stress parameters (detailed in ). Nonetheless, scientific proof doesn't replicate the outcomes seen in animal fashions to this point. Moreover, excessive doses (ie, ≥1000 mg/d) of orally administered vitamin C had no direct profit in contrast with controls. Conversely, low doses (ie, 60 mg/d) of orally administered vitamin C had a major distinction of elevated bone biomarkers in contrast with controls. Total, there are restricted knowledge relating to the efficacy of vitamin C supplementation after musculoskeletal accidents. No opposed results had been reported with vitamin C supplementation in both animal fashions or human individuals. After a musculoskeletal damage, the activation of inflammatory cells has been noticed to overproduce ROS, inflicting deleterious oxidative stress. Oxidative stress has been described as an imbalance between ROS and antioxidants,19 leading to a hostile therapeutic atmosphere that negatively impacts the viability and proliferation of recruited collagen-producing cells and finally selling apoptosis.14,16,17,21 Vitamin C as an antioxidant is able to neutralizing ROS via redox reactions, relieving oxidative stress on account of irritation. All 3 preclinical research evaluating oxidative stress reported that vitamin C was efficient in lowering oxidative stress after accidents by reducing endogenous or exogenous ROS, signified by an improved tissue composition in ligaments, tendons, and bone.5,10,19 Nonetheless, only one of the three research reported vitamin C as an antagonist for oxidative stress after 2 weeks,19 limiting preclinical assist for the scientific implications as a postinjury complement. 4 of 5 research investigating the consequences of vitamin C on collagen manufacturing steered that vitamin C was efficient by stimulating biochemical pathways related to collagen synthesis. Omeroglu et al25 reported that vitamin C elevated the exercise for procollagen-secreting fibroblasts and general kind I collagen manufacturing. The stimulation of collagen-producing cells was additionally reported by Yilmaz et al,41 who noticed accelerated charges of chondrocyte improvement and hypertrophy. Sandukji et al32 reported elevations in alkaline phosphatase, a vitamin C–dependent enzyme concerned in osteoblastic differentiation and bone formation.8,11,18,26 Sarisozen et al33 additionally steered that the noticed enhance in callus formation on account of vitamin C resulted from osteoblast proliferation, though mobile exercise was not quantified. Total, these research present proof that vitamin C could also be efficient in selling collagen synthesis in vivo, though additional scientific research are wanted to strengthen the implications for postoperative vitamin C supplementation.
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Barker et al2 reported that vitamin C and E supplementation was ineffective in potentiating the development in drive manufacturing of the injured limb after ACLR. Nonetheless, baseline vitamin C standing was related to helpful outcomes in power, suggesting that long-term dietary habits could also be simpler than short-term dietary supplements. Ligamentous integrity at follow-up (3 months postoperatively) was not examined2; thus, collagen synthesis and ligament therapeutic with vitamin C supplementation haven't been investigated clinically within the present literature. Ekrol et al6 discovered no vital distinction in purposeful outcomes at 1 12 months between sufferers handled with vitamin C or a placebo after both a nondisplaced or displaced distal radius fracture. Though different research have steered a helpful impact of vitamin C on fracture therapeutic in animal fashions, Ekrol and colleagues6 discovered no distinction within the Disabilities of the Arm, Shoulder and Hand (DASH) rating, different purposeful outcomes, prevalence of persistent regional ache syndrome, or fracture therapeutic with vitamin C therapy in sufferers with a distal radius fracture. It is very important notice that purposeful outcomes after a distal radius fracture are additionally influenced by the situation of soppy tissues along with bone therapeutic. Sandukji et al32 discovered that osteocalcin ranges considerably elevated within the plasma of sufferers handled with vitamin C for two weeks in contrast with these of the non–antioxidant-treated group. An elevation of osteocalcin ranges may enhance BMD and consequently might speed up therapeutic of bone fractures as a result of excessive ranges of osteocalcin and alkaline phosphatase have been reported to be positively correlated with BMD.12,23,37,39 The authors concluded that the administration of the antioxidant nutritional vitamins A, E, and C, along with selenium, might speed up bone therapeutic after long-bone fixation surgical procedure; subsequently, antioxidants might be thought of in designing therapeutic protocols for postoperative bone fracture surgical procedure.32 Earlier analysis has demonstrated that the intravenous administration of vitamin C produces a plasma focus 30- to 70-fold increased than the utmost tolerated oral doses.27 This means that top doses given via intravenous administration might not be essential, if not deleterious to musculoskeletal therapeutic. Nonetheless, low doses of vitamin C administered intravenously permits for optimum bioavailability of the complement, which can present the means for musculoskeletal therapeutic.4,27 With regard to supplementation after musculoskeletal accidents, the vast majority of preclinical research administering vitamin C parenterally noticed vital advantages within the charge of therapeutic and decreased oxidative stress parameters in contrast with controls.5,10,19,25,33,41 Though there's a paucity of scientific research within the literature, 2 research administering vitamin C orally (500 mg/d2 and 1000 mg/d6) didn't observe vital advantages of vitamin C supplementation after musculoskeletal accidents in contrast with controls. Nonetheless, no present research have evaluated the efficacy of solely vitamin C administered intravenously after musculoskeletal accidents. We acknowledge that there's problem administering intravenous medicines over lengthy durations and relatively counsel that intravenous vitamin C administration instantly postoperatively might have helpful results on musculoskeletal therapeutic. We encourage future research that try and delineate the consequences of intravenous vitamin C throughout these restoration durations earlier than intravenous doses may be advisable. A whole understanding of the mechanism of motion of vitamin C stays unclear. A number of primary science and scientific research investigating tumor improvement have reported that the overexpression of antioxidant enzymes and excessive doses of vitamin C (ie, ≥1000 mg/d) might impair wound therapeutic and angiogenesis.29,30,36,40 Though excessive concentrations of ROS may be deleterious to tissue therapeutic, low concentrations of ROS have been demonstrated to advertise angiogenesis and mesenchymal stem cell proliferation.3 Due to this fact, it has been hypothesized that overscavenging of ROS by vitamin C might impair therapeutic in musculoskeletal damage settings.19 Sandukji et al32 reported elevated biomarkers of bone with 60 mg/d of vitamin C, which offers scientific proof for the usage of low doses of vitamin C as a postinjury complement. Due to this fact, we advocate that the low-dose oral administration (ie, 60 mg/d) of vitamin C could also be an efficient type of therapy after musculoskeletal accidents. Nonetheless, there are at present no definitive therapy protocols for the administration of vitamin C. Additional scientific research analyzing a broader vary of oral doses, the efficacy of vitamin C administration by way of parental routes, and the synergistic actions of mixed antioxidant administration are inspired.

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