The impact of perioperative vitamin C on postoperative pain: A systematic review and meta-analysis.

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.