Systematic review and meta-analysis on vitamin C in musculoskeletal disorders

Table 1 Summary of included studies on vitamin C in musculoskeletal disorders

Ref.	Country	Type	Sample size	Condition/population	Dose/route	Duration	Key outcomes
Zollinger et al[32], 1999	Netherlands	RCT	123 adults (127 fractures)	Conservatively treated wrist fractures	500 mg oral daily	50 days	↓RSD incidence (7% vs 22%)
Zollinger et al[33], 2007	Netherlands	RCT	416	Distal radius fractures	200 mg/500 mg/1500 mg oral	50 days	↓CRPS incidence
Besse et al[34], 2009	France	Prospective trial	329	Foot & ankle surgery	1 g oral	40 days	↓CRPS-I incidence
Shibuya et al[35], 2013	United States	Systematic review	Pooled	Extremity trauma/surgery	High-dose oral/intravenous injection	Variable	Supportive evidence
Evaniew et al[36], 2015	Canada	Meta-analysis	Pooled	Distal radius fractures	500 mg oral (pooled)	45-50 days	Mixed results
Aïm et al[37], 2017	France	Systematic review	Multiple	Wrist fractures	500 mg oral	45-50 days	↓CRPS risk
DePhillipo et al[38], 2018	United States	Systematic review	Multiple	Tendon/bone healing	Vitamin C	Variable	Collagen synthesis support
Giustra et al[39], 2021	Italy	Systematic review	Multiple	Orthopedic CRPS prevention	500-1000 mg oral	40-50 days	Possible CRPS benefit
Jacques et al[40], 2021	France	Prospective RCT	292 (153 intervention/139 control)	Patients undergoing TKA	1 g/day PO vitamin C	Approximately 40 days post-operative	↓CRPS-I risk: 3.9% vs 12.2%, OR approximately of 0.27; significant prevention effect
Hung et al[26], 2021	Taiwan (multi-center data pooled)	Meta-analysis of RCTs	Pooled (several hundred across included RCTs)	Orthopedic patients after trauma/surgery (fractures, arthroplasty, etc.)	Oral vitamin C, 500-1000 mg/day (varied by trial)	Up to 1 year (follow-up in included RCTs)	↓CRPS incidence, improved functional outcomes, some benefit on pain control; overall evidence supportive but heterogeneous
Barrios-Garay et al[41], 2022	Mexico	Systematic review	Multiple	Bone healing	Oral vitamin C	Weeks-months	Mixed healing evidence
Çelik et al[42], 2021	Turkey	Experimental	Animal	Tendon repair	Vitamin C + fibrin clot	Experimental period	Improved tendon healing
Noriega-González et al[43], 2022	Spain	Scoping review	Multiple	Tendinopathy	Vitamin C	Variable	Potential benefit
Qamar et al[44], 2024	United States	Narrative review		Orthopedics	Vitamin C (oral/intravenous injection)	Variable	Proposed uses
Zhang et al[45], 2024	China/United States	Cohort	NHANES dataset	OA/BMD	Dietary vitamin C	Cross-sectional	Associations with OA risk
Chaganti et al[46], 2014	United States	Cohort	Large cohort	Knee OA	Plasma vitamin C	Years	↑Vitamin C slowed OA progression
Seth et al[27], 2022	Multiple countries	Systematic review and meta-analysis	8 studies included	Distal radius, wrist, foot, and ankle fractures	500 mg or 1000 mg oral	42-50 days post-injury/surgery	↓CRPS-I incidence (OR = 0.33, 95%CI: 0.17-0.63)
Hosseini-Monfared et al[47], 2025	Iran	Clinical study	Small	Post-TKA	IV vitamin C	Perioperative	↓Inflammation, ↓blood loss
Azevedo Filho et al[48], 2025	Brazil	RCT	122	Distal radius fractures	1 g oral	60 days	↓Incidence of CRPS at 12 weeks and 24 weeks compared to placebo (P = 0.014 and P = 0.007)
Bechara et al[49], 2022	Australia	Systematic review	Multiple	Various tissue injuries including musculoskeletal tissues	Vitamin C (oral/supplementation)	Variable	↑Collagen synthesis, ↓oxidative stress, supports tissue repair and regeneration
Santos de Lima et al[8], 2023	Brazil	Meta-analysis	400 pooled	Exercise-induced damage	Vitamin C + vitamin E	4-8 weeks	↓Inflammation, ↓soreness
Ramón et al[11], 2023	Spain	RCT	80-110	Post TKA	IV vitamin C	Immediate postop	↓Inflammation
Han et al[50], 2024	China	Prospective trial	107	Total hip arthroplasty patients	IV vitamin C	Perioperative/postoperative	↑Pain relief, ↑functional recovery, ↓opioid consumption
Ueda et al[51], 2025	Japan	Experimental	In vitro	Tendon cells exposed to oxidative stress	High-dose vitamin C	Variable	↑Type I collagen gene expression; ↓oxidative stress; maintained cytoskeletal
Marzagalli et al[52], 2024	Italy	Experimental	In vitro	Tenocytes exposed to inflammatory stimuli	Vitamin C + collagen + resveratrol + astaxanthin	Variable	↓Pro-inflammatory markers; ↑antioxidant capacity; ↓fibrotic response
Lassig et al[53], 2023	United States	RCT	60	Mandibular fracture patients	500 mg oral daily	6 weeks	↓Post-operative complications; ↑bone healing biomarkers; ↓wound infection rates
Beytemur et al[18], 2024	Turkey	Experimental	30	Steroid-induced ON	Vitamin C + vitamin E	8 weeks	↓ON risk
Ranjbari and Alimohammadi[19], 2024	China	Clinical study	110	Post-op spinal pain	1000 mg/day	4 weeks	↓Pain
Daoust et al[1], 2024	Canada	Pilot RCT	160	Acute MSK injuries (ED)	1000 mg oral	14 days	↓Opioid use, ↓pain
He et al[54], 2024	China	Observational study	99 postmenopausal women	Postmenopausal osteoporosis	Not applicable (observational study)	Cross-sectional analysis	Combined vitamin C and vitamin D deficiency significantly associated with lower lumbar BMD and higher risk of osteoporosis

RCT: Randomized controlled trial; NHANES: National Health and Nutrition Examination Survey; OA: Osteoarthritis; CRPS: Complex regional pain syndrome; TKA: Total knee arthroplasty; ON: Osteonecrosis; MSK: Musculoskeletal; ED: Emergency department; BMD: Bone mineral density; PO: Per os; RSD: Reflex sympathetic dystrophy; OR: Odds ratio; CI: Confidence interval.