Jialin Xiong, Yuxuan Yang, Qiang Zhang, Kongyan Wu, Yuhuan Gong, Jie Luo
Perioperative vitamin C may be associated with reduced acute pain and opioid consumption, with a favorable safety profile, although these findings were limited by substantial heterogeneity and publication bias. Vitamin C showed a potential protective effect against postoperative CRPS-1 in high-risk orthopedic populations. Current evidence is insufficient to support routine clinical recommendation of vitamin C for acute pain management, and more standardized high-quality RCTs are needed to better confirm its benefits.
OBJECTIVE: To evaluate the effects of perioperative vitamin C on postoperative pain, opioid consumption, and other clinically relevant outcomes.
METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, Embase, and ClinicalTrials.gov from inception to December 2025, and included randomized controlled trials (RCTs) that assessed perioperative vitamin C administration in patients undergoing surgery.
RESULTS: 27 RCTs with 3041 patients were included. Perioperative vitamin C reduced postoperative pain at 24 h (SMD = -0.69, 95% CI: -0.98 to -0.40) and decreased 24-h morphine consumption (MD = -4.25 mg, 95% CI: -6.14 to -2.35), with a greater opioid-sparing effect at 48 h (MD = -11.70 mg, 95% CI: -14.18 to -9.21). It reduced the need for rescue analgesia (RR = 0.63, 95% CI: 0.47 to 0.84) and lowered the incidence of postoperative nausea and vomiting at 1 h (RR = 0.48, 95% CI: 0.29 to 0.79). Furthermore, the risk of postoperative complex regional pain syndrome-1 (CRPS-1) was reduced (RR = 0.36, 95% CI: 0.23 to 0.58), whereas the reduction in chronic pain at 3 months did not reach statistical significance. No significant effects were observed on hospital stay or intraoperative blood loss, and no serious adverse events related to vitamin C were reported.
CONCLUSIONS: Perioperative vitamin C may be associated with reduced acute pain and opioid consumption, with a favorable safety profile, although these findings were limited by substantial heterogeneity and publication bias. Vitamin C showed a potential protective effect against postoperative CRPS-1 in high-risk orthopedic populations. Current evidence is insufficient to support routine clinical recommendation of vitamin C for acute pain management, and more standardized high-quality RCTs are needed to better confirm its benefits.
KEY MESSAGE: This meta-analysis suggests that perioperative vitamin C may reduce acute postoperative pain and opioid consumption, but evidence is limited by heterogeneity and publication bias.