†Steadman Philippon Analysis Institute, Vail, Colorado, USA.
†Steadman Philippon Analysis Institute, Vail, Colorado, USA.
†Steadman Philippon Analysis Institute, Vail, Colorado, USA.
†Steadman Philippon Analysis Institute, Vail, Colorado, USA.
§OSTRC, Norwegian Faculty of Sports activities Science, Oslo, Norway.
†Steadman Philippon Analysis Institute, Vail, Colorado, USA.
Summary
The therapeutic of musculoskeletal tissues, reminiscent of bone, tendons, and ligaments, relies 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 energy, which can lead to unsatisfactory outcomes and an elevated threat for reinjuries. Primary science investigations on the biochemical pathways after a musculoskeletal damage have steered that vitamin C, also called ascorbic acid, could improve collagen synthesis and tender tissue therapeutic.22,24,28,31
Vitamin C has a necessary function 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 function in collagen synthesis, vitamin C acts as a robust antioxidant by neutralizing deleterious reactive oxygen species (ROS) chargeable for cell apoptosis in the course of 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 Subsequently, vitamin C has been more and more studied for its contributions to the therapy of musculoskeletal accidents in each scientific and in vitro trials.
Though laboratory research have reported that vitamin C is crucial 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. Subsequently, the needs of this systematic evaluation 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 lead to diminished oxidative stress and accelerated tissue therapeutic compared with management teams.
Strategies
Outcomes
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 (Determine 1). There have been 7 research that evaluated the results 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) (Desk 1). Six of the animal research used a rat mannequin, and 1 research used a rooster mannequin. There have been 3 research that evaluated the results of vitamin C supplementation in human fashions: 1 after ACLR and a couple 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 – “vitamin c collagen synthesis”
A very powerful discovering of this systematic evaluation 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 Determine 2). Nonetheless, scientific proof doesn’t replicate the outcomes seen in animal fashions thus far. 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 big distinction of elevated bone biomarkers in contrast with controls. General, there are restricted information concerning 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 as a consequence of irritation. All 3 preclinical research evaluating oxidative stress reported that vitamin C was efficient in lowering oxidative stress after accidents by lowering endogenous or exogenous ROS, signified by an improved tissue composition in ligaments, tendons, and bone.5,10,19 Nonetheless, just one of the three research reported vitamin C as an antagonist for oxidative stress after 2 weeks,19 limiting preclinical help for the scientific implications as a postinjury complement.
4 of 5 research investigating the results 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 growth 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 as a consequence of vitamin C resulted from osteoblast proliferation, though mobile exercise was not quantified. General, 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.
Barker et al2 reported that vitamin C and E supplementation was ineffective in potentiating the development in power manufacturing of the injured limb after ACLR. Nonetheless, baseline vitamin C standing was related to helpful outcomes in energy, 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 important 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, incidence of continual regional ache syndrome, or fracture therapeutic with vitamin C therapy in sufferers with a distal radius fracture. You will need to notice that purposeful outcomes after a distal radius fracture are additionally influenced by the situation of sentimental 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; due to this fact, 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 larger than the utmost tolerated oral doses.27 This means that prime doses given via intravenous administration is probably not needed, 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, nearly all of preclinical research administering vitamin C parenterally noticed important advantages within the charge of therapeutic and diminished 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 important 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 issue administering intravenous drugs over lengthy durations and quite counsel that intravenous vitamin C administration instantly postoperatively could have helpful results on musculoskeletal therapeutic. We encourage future research that try and delineate the results of intravenous vitamin C throughout these restoration intervals earlier than intravenous doses might be advisable.
An entire understanding of the mechanism of motion of vitamin C stays unclear. A number of primary science and scientific research investigating tumor growth have reported that the overexpression of antioxidant enzymes and excessive doses of vitamin C (ie, ≥1000 mg/d) could impair wound therapeutic and angiogenesis.29,30,36,40 Though excessive concentrations of ROS might be deleterious to tissue therapeutic, low concentrations of ROS have been demonstrated to advertise angiogenesis and mesenchymal stem cell proliferation.3 Subsequently, it has been hypothesized that overscavenging of ROS by vitamin C could impair therapeutic in musculoskeletal damage settings.19 Sandukji et al32 reported elevated biomarkers of bone with 60 mg/d of vitamin C, which gives scientific proof for the usage of low doses of vitamin C as a postinjury complement. Subsequently, 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 through parental routes, and the synergistic actions of mixed antioxidant administration are inspired.
Conclusion
Preclinical research demonstrated that vitamin C has the potential to speed up bone therapeutic after fractures, 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 protected 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.
Footnotes