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Efficacy of Vitamin C in Acute Musculoskeletal Pain Management: A Double-Blind Randomized Controlled Pilot Study

Daoust, R.; Williamson, D.; Arbour, C.; Perry, J. J.; Berthelot, S.; Huard, V.; Archambault, P.; Emond, M.; Rouleau, D.; Morris, J.; Lessard, J.; Kochoedo, M.; Cournoyer, A.

2026-02-27 emergency medicine
10.64898/2026.02.25.26347033 medRxiv
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IntroductionRecent evidence has shown that vitamin C has analgesic properties in immediate postoperative context. However, while a clinical trial is currently underway to evaluate vitamin C for reducing opioid consumption in acute musculoskeletal (MSK) injuries emergency department (ED) patients, its direct analgesic effect in this population has not yet been established. This pilot study evaluated the feasibility of conducting a randomized placebo-controlled trial to determine the analgesic effect of vitamin C alone compared with placebo in acute MSK injured ED patients. MethodsWe conducted a double-blind, randomized controlled pilot trial stratified by fracture status in a tertiary care center. Adults ([≥]18 years) presenting to the ED with MSK injuries of [≤] 48 hours duration and pain intensity >3/10 were randomized to receive vitamin C 900 mg twice daily for three days or placebo. Participants completed a six-day diary (electronic or paper) and were contacted on day six to document analgesic use, treatment adherence, and pain intensity. ResultsOverall, 147 patients were screened; 63 (42.9%) were excluded, 24 (16.4%) refused, leaving 60 (41.1%) participants, with a consent rate of 13.0/month. Mean age (SD) was 41.8 years (14.23) and 50% were female. Lost to follow-up rate differed between participants with electronic diary (n=7; 16.7%) and participants with paper diary (n=10; 55.6%). Patients compliance with treatment was 97.6%. The least-squares mean difference between group A and group B in the time-weighted sum of pain intensity differences over 72 hours (SPID72) was 348.7 (95% confidence interval [CI]:-698.9 to 1396.4) for the intention-to-treat analysis and 357.6 (95%CI:-709.67 to 1424.82) for the per-protocol analysis. ConclusionThis pilot study supports the feasibility of a larger randomized controlled trial on the analgesic properties of vitamin C for acute MSK injured ED patients. Strategies to reduce the missed patients and lost to follow-up rates are proposed. Trial registration numberNCT06306183, ClinicalTrials.gov

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