Effect of Vitamin C on Pain Reduction After an Emergency Department Visit

Background:

Acute musculoskeletal (MSK) injuries are a major cause of emergency department (ED) visits and frequently result in moderate to severe pain during the first days following presentation. First-line analgesics such as NSAIDs and acetaminophen have important contraindications and safety limitations, particularly in older adults and patients with comorbidities, underscoring the need for safe, accessible, opioid-sparing alternatives. Preclinical studies and postoperative trials suggest that vitamin C (ascorbic acid) may provide analgesic and anti-inflammatory effects through reduction of oxidative stress, protection of neural tissues, and enhanced collagen synthesis. Meta-analyses have reported reductions in postoperative opioid consumption, pain intensity, and inflammatory markers. However, no randomized controlled trial has evaluated vitamin C for acute traumatic MSK pain in the ED.

Objective:

The primary objective is to determine whether a single 900 mg oral dose of vitamin C reduces pain intensity one hour after administration compared with placebo in adults presenting with acute MSK injuries. The main secondary objective is to assess whether 900 mg of vitamin C taken twice daily for three days reduces the time-weighted sum of pain-intensity difference (SPID) over 72 hours.

Methods:

The VICAMED study is a multicentre, triple-blind, randomized, placebo-controlled trial conducted in three university-affiliated EDs in Canada. Eligible participants are adults aged ≥18 years with MSK pain ≤48 hours, triaged to ambulatory care, and reporting pain >3/10. Exclusion criteria include recent vitamin C use, active cancer, recent analgesic intake, chronic pain treatment, and contraindications such as oxalate nephropathy or interactions with cyclosporine or warfarin. Participants receive an initial 900 mg dose of vitamin C or placebo in the ED, followed by twice-daily dosing for three days. Pain intensity is measured using validated 0-100 visual analog scales through electronic or paper diaries. A structured day-six follow-up captures missing data, analgesic use, adverse events, and health-related quality of life (EQ-5D-5L). The primary analysis uses ANCOVA adjusting for site and fracture status. Secondary analyses evaluate SPID72, analgesic consumption, time to significant pain relief, time to pain-free, proportion of days with adequate relief, adverse events, and healthcare utilization.

Based on a minimal clinically important difference of 13 points on a 0-100 pain scale and prior variance estimates, 204 participants are required for the primary outcome. The sample size for SPID72 will be finalized using pilot study data currently being analyzed. The study is powered to detect clinically meaningful differences in both immediate and short-term pain trajectories.

Expected Results:

If vitamin C demonstrates analgesic efficacy in acute MSK injuries, it could represent a safe, inexpensive, widely accessible, and opioid-sparing therapeutic option for ED patients, including those unable to use NSAIDs or acetaminophen. Given its favourable safety profile and over-the-counter availability, vitamin C has strong potential for rapid clinical integration. The research team's established collaborations within national emergency medicine networks will support broad dissemination and facilitate implementation across Canadian EDs.

Inclusion criteria

• Age ≥ 18 years old
• Presenting to the ED with acute MSK pain of ≤ 48 hours duration at triage
• Verbal numerical rating scale pain intensity at triage of ≥ 4 on a 0-10 scale
• Triaged to the ambulatory section of the ED
• Able to communicate in French or English

Exclusion criteria

• Usage of Vit C supplements in the last week
• Active cancer
• Treated with opioids for any pain within 24 hours prior to recruitment
• Treatment for chronic pain
• Unable to fill out a pain intensity diary or unavailable for follow-up
• Allergy to milk (lactose in the placebo) or Vit C
• Treated with cyclosporine or warfarin
• Pre-existing oxalate nephropathy, liver cirrhosis or hemochromatosis
• Hospitalized after clinician evaluation