Vitamin C for Musculoskeletal Pain

Overseen By Martin Marquis, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hopital du Sacre-Coeur de Montreal

Must not be taking: Cyclosporin, Coumadin

Disqualifiers: Opioid use, Cancer, Chronic pain, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

464 Participants Needed

Trial Summary

What is the purpose of this trial?

Recent evidence has shown that vitamin C has some analgesic properties and can therefore reduce opioids used during healing. Vitamin C analgesic effect has been explored mostly during the short-term postoperative context or in disease specific chronic pain prevention but not after acute musculoskeletal injuries, which are often seen in the emergency department (ED). The study's primary aim is to compare the total morphine 5 mg equivalent pills consumed during a two-week follow-up between patients receiving vitamin C or a placebo after ED discharge for an acute musculoskeletal pain complaint. The investigators will conduct a double-blind randomized placebo-controlled trial with 464 participants distributed in two arms, one group receiving 1 000 mg of vitamin C twice a day for 14 days and another one receiving a placebo. Participants will be ≥18 years of age, treated in ED for acute musculoskeletal pain present for less than 2 weeks, and discharged with an opioid prescription for home pain management. Total morphine 5 mg equivalent pills consumed during the two-week follow-up will be assessed via an electronic (or paper) diary. In addition, patients will report their daily pain intensity, pain relief, side effects, and other types of pain medication or other non-pharmacological approach (ice, heat, immobilization, etc.) used. Three months after the injury, participants will also be contacted to evaluate chronic pain development. The investigators hypothesized that vitamin C, compared to a placebo, will reduce opioid consumption during a 14-day follow-up for ED discharged patients treated for acute pain.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are treated with cyclosporin or coumadin, or if you are already taking vitamin C supplements.

What data supports the effectiveness of the treatment Vitamin C for musculoskeletal pain?

Research suggests that vitamin C (ascorbic acid) may help improve collagen production and tissue healing, which are important for musculoskeletal health. Some studies have found that low levels of vitamin C are linked to increased back pain and arthritis, indicating that vitamin C might be beneficial in managing these conditions. ^{1 2 3 4 5}

Is Vitamin C safe for humans?

Vitamin C (ascorbic acid) is generally considered safe for humans, with studies showing its potential benefits in bone health and tissue repair. However, excessive intake should be avoided, especially in children, as it may have harmful effects. ^{2 3 4 6 7}

How does the treatment Vitamin C differ from other treatments for musculoskeletal pain?

Vitamin C is unique in treating musculoskeletal pain because it enhances collagen synthesis, which is crucial for soft tissue healing, and reduces oxidative stress, which can contribute to pain. Unlike other treatments, it also acts as a cofactor for the production of opioid peptides, potentially reducing the need for traditional pain medications. ^{2 3 5 8 9}

Research Team

Raoul Daoust, MD MSc

Principal Investigator

Université de Montréal

Eligibility Criteria

This trial is for adults over 18 who visited the emergency department (ED) with musculoskeletal pain that's been there for less than two weeks. They must have left the ED with a prescription for opioids and be able to speak French or English.

Inclusion Criteria

I speak French or English.

I was prescribed opioids when I was discharged.

I was treated in the emergency department for recent muscle or bone pain.

Exclusion Criteria

Opioid use 1 month prior to the ED visit

My cancer is currently active.

I am receiving treatment for chronic pain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive 1,000 mg of vitamin C or placebo twice a day for 14 days

2 weeks

Initial visit for randomization and dispensing of medication

Follow-up

Participants are monitored for opioid consumption and pain relief via electronic or paper diary

2 weeks

Remote monitoring through diary entries

Long-term Follow-up

Participants are contacted to evaluate chronic pain development and opioid use

3 months

1 contact (remote)

Treatment Details

Interventions

• Placebo
• Vitamin C

Trial Overview The study tests if taking vitamin C reduces opioid use after an ED visit for acute musculoskeletal pain. Participants will either receive 1000 mg of vitamin C twice daily or a placebo, over two weeks, and track their opioid intake and pain levels.

Participant Groups

Group I: Vitamin C Experimental Treatment 1 Intervention

1 000 mg vitamin C taken orally twice a day

Group II: Placebo Placebo Group 1 Intervention

Matching placebo

Vitamin C is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in European Union as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in Canada as Vitamin C for:

• Scurvy
• Dietary supplement

Who Is Running the Clinical Trial?

Hopital du Sacre-Coeur de Montreal

Lead Sponsor

Trials

52

Recruited

12,100+

Hopital de l'Enfant-Jesus

Collaborator

Trials

17

Recruited

5,800+

Findings from Research

In a study of 58 patients with chronic widespread musculoskeletal pain and vitamin D deficiency, treatment with 50,000 IU/week of vitamin D3 for 3 months significantly increased vitamin D levels and improved pain, fatigue, and quality of life measures.

The treatment led to a reduction in the number of patients meeting the criteria for fibromyalgia from 52% to 34%, indicating that vitamin D replacement can effectively alleviate symptoms associated with chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vitamin D replacement therapy on patients with chronic nonspecific widespread musculoskeletal pain with vitamin D deficiency. Yilmaz, R., Salli, A., Cingoz, HT., et al.[2017]

A study of 4,742 adults from the U.S. National Health and Nutrition Examination Survey found that low serum vitamin C levels are associated with an increased prevalence of neck and low back pain, suggesting a potential link between vitamin C deficiency and spinal pain.

The findings indicate that suboptimal vitamin C concentrations may contribute to functional limitations and self-reported diagnoses of arthritis/rheumatism, highlighting the need for further research into vitamin C's role in back pain treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum vitamin C and spinal pain: a nationwide study. Dionne, CE., Laurin, D., Desrosiers, T., et al.[2021]

Preclinical studies suggest that vitamin C supplementation can accelerate bone healing and enhance collagen synthesis in tendon injuries, with no reported adverse effects, indicating it may be a safe option for recovery after musculoskeletal injuries.

However, clinical evidence is limited, as one study found no significant differences in fracture healing rates or functional outcomes after vitamin C supplementation, highlighting the need for more research before widespread use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. DePhillipo, NN., Aman, ZS., Kennedy, MI., et al.[2022]

Ascorbic acid (vitamin C) has shown potential benefits in improving bone density and reducing hip fracture risk based on observational studies, although its effects in human trials remain underexplored.

The American Academy of Orthopaedic Surgeons supports the use of ascorbic acid as an adjunct treatment to potentially reduce the incidence of complex regional pain syndrome after distal radius fractures, highlighting its safety and low cost for musculoskeletal injury management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic Acid and Its Clinical Role in Orthopaedic Surgery. Luo, TD., Marois, AJ., Smith, TL., et al.[2019]

Vitamin C supplementation significantly reduces oxidative stress markers, specifically lipid peroxidation, immediately and up to 2 hours after exercise, based on a meta-analysis of 18 randomized clinical trials involving 313 participants.

It also attenuates the inflammatory response, particularly interleukin-6 (IL-6) levels, after exercise, but does not appear to affect muscle soreness, strength, or other inflammatory markers like creatine kinase and C-reactive protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of vitamin C on oxidative stress, inflammation, muscle soreness, and strength following acute exercise: meta-analyses of randomized clinical trials. Righi, NC., Schuch, FB., De Nardi, AT., et al.[2022]

In a study of 49 young adolescent boys, daily supplementation of 70 mg of ascorbic acid (vitamin C) for two months significantly increased plasma vitamin C levels and improved physical working capacity, as indicated by a rise in VO2 max.

The study found that a plasma vitamin C level of around 0.86 mg/dl is associated with optimal physical performance, suggesting that a daily intake of about 80 mg of ascorbic acid may be beneficial for enhancing aerobic capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C status and physical working capacity in adolescents. Suboticanec-Buzina, K., Buzina, R., Brubacher, G., et al.[2015]

In a study of 67 children with myelomeningocele, both fracture and non-fracture groups had high ascorbic acid intake, exceeding recommended allowances from food and supplements, with no significant difference between the two groups.

The findings suggest that ascorbic acid supplementation does not prevent fractures in these patients, and caution is advised regarding excessive intake due to potential harmful effects in growing children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic acid and fractures in children with myelomeningocele. Repasky, D., Rickard, K., Lindseth, R.[2013]

Vitamin C treatment significantly reduced pain and other symptoms associated with complex regional pain syndrome (CRPS) in a rat model, showing reductions in allodynia by 64-78% and muscle hyperalgesia by 34-40%.

The study suggests that oxidative stress plays a role in CRPS development, as Vitamin C not only alleviated pain but also decreased oxidative stress markers and inflammatory mediators in the affected tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome. Guo, TZ., Wei, T., Huang, TT., et al.[2020]

Vitamin C administration has been shown to reduce pain in various conditions, including chronic regional pain syndrome and cancer-related pain, suggesting its potential as an effective adjunctive therapy for pain relief.

A proposed mechanism for vitamin C's analgesic properties is its role as a cofactor in the biosynthesis of amidated opioid peptides, which may help decrease the need for opioid analgesics in patients receiving high doses of vitamin C.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of vitamin C in the treatment of pain: new insights. Carr, AC., McCall, C.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of vitamin D replacement therapy on patients with chronic nonspecific widespread musculoskeletal pain with vitamin D deficiency. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Serum vitamin C and spinal pain: a nationwide study. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Ascorbic Acid and Its Clinical Role in Orthopaedic Surgery. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Effects of vitamin C on oxidative stress, inflammation, muscle soreness, and strength following acute exercise: meta-analyses of randomized clinical trials. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Vitamin C status and physical working capacity in adolescents. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Ascorbic acid and fractures in children with myelomeningocele. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome. [2020]

9. England pubmed.ncbi.nlm.nih.gov

The role of vitamin C in the treatment of pain: new insights. [2022]