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Orthop J Sports Med. 2018 Oct 25;6(10):2325967118804544. doi: 10.1177/2325967118804544. eCollection 2018 Oct.

Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review.

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The Steadman Clinic, Vail, Colorado, USA.
Steadman Philippon Research Institute, Vail, Colorado, USA.
Oslo University Hospital, Oslo, Norway.
OSTRC, Norwegian School of Sports Science, Oslo, Norway.



Recent investigations on the biochemical pathways after a musculoskeletal injury have suggested that vitamin C (ascorbic acid) may be a viable supplement to enhance collagen synthesis and soft tissue healing.


To (1) summarize vitamin C treatment protocols; (2) report on the efficacy of vitamin C in accelerating healing after bone, tendon, and ligament injuries in vivo and in vitro; and (3) report on the efficacy of vitamin C as an antioxidant protecting against fibrosis and promoting collagen synthesis.

Study Design:

Systematic review; Level of evidence, 2.


A systematic review was performed, with the inclusion criteria of animal and human studies on vitamin C supplementation after a musculoskeletal injury specific to collagen cross-linking, collagen synthesis, and biologic healing of the bone, ligament, and tendon.


The initial search yielded 286 articles. After applying the inclusion and exclusion criteria, 10 articles were included in the final analysis. Of the preclinical studies evaluating fracture healing, 2 studies reported significantly accelerated bone healing in the vitamin C supplementation group compared with control groups. The 2 preclinical studies evaluating tendon healing reported significant increases in type I collagen fibers and scar tissue formation with vitamin C compared with control groups. The 1 preclinical study after anterior cruciate ligament (ACL) reconstruction reported significant short-term (1-6 weeks) improvements in ACL graft incorporation in the vitamin C group compared with control groups; however, there was no long-term (42 weeks) difference. Of the clinical studies evaluating fracture healing, 1 study reported no significant differences in the rate of fracture healing at 50 days or functional outcomes at 1 year. Vitamin C supplementation was shown to decrease oxidative stress parameters by neutralizing reactive oxygen species through redox modulation in animal models. No animal or human studies reported any adverse effects of vitamin C supplementation.


Preclinical studies demonstrated that vitamin C has the potential to accelerate bone healing after a fracture, increase type I collagen synthesis, and reduce oxidative stress parameters. No adverse effects were reported with vitamin C supplementation in either animal models or human participants; thus, oral vitamin C appears to be a safe supplement but lacks clinical evidence compared with controls. Because of the limited number of human studies, further clinical investigations are needed before the implementation of vitamin C as a postinjury supplement.


ACL reconstruction; ascorbic acid; collagen cross-linking; collagen synthesis; fracture healing; oxidative stress

Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: R.F.L. is a consultant for and receives royalties from Arthrex, Ossur, and Smith & Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

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