Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis

Seth, Ishith; Bulloch, Gabriella; Seth, Nimish; Siu, Adrian Hang Yue; Clayton, Stephanie; Lower, Kirk; Roshan, S.; Nara, Naveen

doi:10.1053/j.jfas.2021.11.008

Cited by 10 publications

(4 citation statements)

References 34 publications

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“…This finds support in a meta-analysis for the setting of surgery: only parenteral administration, not oral administration, is associated with pain reduction and a decreased need for analgesics [ 28 ]. For other pain conditions, oral administration is shown to be effective [ 29 , 30 ].…”

Section: Resultsmentioning

confidence: 99%

The Use of High-Dose Intravenous l-Ascorbate in Pain Therapy: Current Evidence from the Literature

Likar,

Poglitsch,

Bejvančický

et al. 2024

Pain Ther

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Introduction Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l -ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice. Methods The current literature on the therapeutic effect of l -ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l -ascorbate. Results A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l -ascorbate in pain treatment. Discussion Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l -ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions. Conclusions l -ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

The Use of High-Dose Intravenous l-Ascorbate in Pain Therapy: Current Evidence from the Literature

Likar,

Poglitsch,

Bejvančický

et al. 2024

Pain Ther

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“…Because these meta‐analyses suggest efficacy, the GRADE was upgraded one level to “moderately confident.” The study from 1999 concluded that daily supplementation with 500 mg of vitamin C daily after wrist fracture decreased the 1‐year risk of CRPS 75 . When expanding to more injury types, a larger analysis assessing outcomes after distal radius, wrist, foot, and ankle surgeries concluded that vitamin C is associated with a decreased rate of CRPS I, although no difference in functional outcomes or pain scores compared to placebo 79 . As such, we recommend the use of vitamin C in the prevention of CRPS, with the caveat that there may be a more robust response depending on the type of injury.…”

Section: Discussionmentioning

confidence: 99%

“…75 When expanding to more injury types, a larger analysis assessing outcomes after distal radius, wrist, foot, and ankle surgeries concluded that vitamin C is associated with a decreased rate of CRPS I, although no difference in functional outcomes or pain scores compared to placebo. 79 As such, we recommend the use of vitamin C in the prevention of CRPS, with the caveat that there may be a more robust response depending on the type of injury.…”

Section: Crpsmentioning

confidence: 99%

The role of diet and non‐pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review

Frediani,

Lal,

Kim

et al. 2023

Pain Practice

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Background/ImportanceDietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases.ObjectiveThis systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults.Evidence ReviewThe review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non‐pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence.FindingsForty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy‐induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS‐I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N‐acetyl‐cysteine (2), acetyl‐l‐carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha‐lipoic acid (1), l‐carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha‐lipoic acid (5 studies), vitamin B12 (3), acetyl‐l‐carnitine (3), vitamin E (1), vitamin D (2), and a low‐fat plant‐based diet (1). Vitamin C was studied to treat CRPS‐I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.ConclusionsBased on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N‐acetyl‐cysteine, l‐carnosine, crocin, and magnesium is warranted. Acetyl‐l‐carnitine was found to be likely ineffective or harmful. Alpha‐lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha‐lipoic acid, acetyl‐l‐carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS‐I also seems promising. Further research is warranted to confirm these findings.

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“…Using a daily regimen of at least 500 mg of oral vitamin C initiated immediately after extremity surgery or injury and continued for 45 to 50 days, all studies showed a significant decrease of CRPS incidence up to 90 days after the event. Two other meta-analyses showed that daily supplementation with 500 mg of vitamin C for 50 days decreased the 1-year risk of CRPS after wrist fracture or limb extremity fractures 32 33. Taking 1 g per day of vitamin C for 40 days after a total knee arthroplasty also reduces CRPS risk 34.…”

Section: Introductionmentioning

confidence: 99%

Impact of vitamin C on the reduction of opioid consumption after an emergency department visit for acute musculoskeletal pain: a double-blind randomised control trial protocol

et al. 2023

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IntroductionRecent evidence has shown that vitamin C has some analgesic properties in addition to its antioxidant effect and can, therefore, reduce opioid use during recovery time. Vitamin C analgesic effect has been explored mostly during short-term postoperative context or in disease-specific chronic pain prevention, but never after acute musculoskeletal injuries, which are often seen in the emergency department (ED). The protocol’s primary aim is to compare the total morphine 5 mg pills consumed during a 2-week follow-up between patients receiving vitamin C or a placebo after ED discharge for an acute musculoskeletal pain complaint.Methods and analysisWe will conduct a two-centre double-blind randomised placebo-controlled trial with 464 participants distributed in two arms, one group receiving 1000 mg of vitamin C two times 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 pills consumed during the 2-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 used. Three months after the injury, participants will also be contacted to evaluate chronic pain development. We hypothesised that vitamin C, compared with a placebo, will reduce opioid consumption during a 14-day follow-up for ED discharged patients treated for acute musculoskeletal pain.Ethics and disseminationThis study has received approval from the Ethics Review Committee from the ‘Comité d'éthique de la recherche du CIUSSS du Nord-de-l'Île-de-Montréal (No 2023–2442)’. Findings will be disseminated through scientific conferences and peer-reviewed journal publication. The data sets generated during the study will be available from the corresponding author on reasonable request.Trial registration numberNCT05555576ClinicalTrials.Gov PRS.

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Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis

Cited by 10 publications

References 34 publications

The Use of High-Dose Intravenous l-Ascorbate in Pain Therapy: Current Evidence from the Literature

The Use of High-Dose Intravenous l-Ascorbate in Pain Therapy: Current Evidence from the Literature

The role of diet and non‐pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review

Impact of vitamin C on the reduction of opioid consumption after an emergency department visit for acute musculoskeletal pain: a double-blind randomised control trial protocol

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