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The aim of the present systematic review was to evaluate the clinical effect of vitamin C on bone healing after bone fracture or bone reconstruction procedures. In October 2020, Cochrane Library, Scopus and PubMed-Medline databases were searched without restrictions to identify animal and human studies that fulfilled the eligibility criteria. Outcome measures were bone healing time, bone gain (mm), bone density and adverse events. The risk of bias assessment of the selected studies was evaluated by means of Cochrane Collaboration?s Tool for randomized clinical trials, while randomized clinical animal trials were assessed according to SYRCLE?s tool. Additionally, quality of reporting animal studies were assessed according to ARRIVE guidelines. Out of the 248 articles that yielded the initial search, 11 papers about the effect of ascorbic acid on bone healing were selected. In most of the animal studies, vitamin C seemed to accelerate bone formation owing to an enhanced osteoblastic proliferation and differentiation and its antioxidant function when pro-oxidant substances were added. It was not possible to observe this phenomenon in human studies. Although additional well-performed animal and human studies are required, vitamin C seems to accelerate bone regeneration without adverse events. However, it is not possible to recommend a specific dose or route of administration of vitamin C to improve the bone healing process in humans as there was great heterogeneity among the included studies.
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