Title: Efficacy of Vitamin C for Restless Legs Syndrome: A Systematic Review and Meta‑analysis of Randomized Controlled Trials
Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Jorge Patino, Andrew McGarry, Ian Walker
Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea
Objective
To evaluate the efficacy and safety of vitamin C (VITC) for treating restless legs syndrome (RLS) using evidence exclusively from randomized controlled trials (RCTs).
Background
VITC has been proposed as a potential therapy for RLS due to its antioxidant properties and possible modulation of dopaminergic pathways. Several RCTs have assessed its impact on symptom severity and related clinical outcomes, but findings have been inconsistent.
Design/Methods
A systematic review of PubMed and Google Scholar of RCTs comparing VITC to placebo or active comparators in adults with RLS was conducted. The primary outcome was change in International Restless Legs Scale (IRLS) scores. Secondary outcomes included itching, categorical RLS symptom severity, and sleep disturbance. Adverse events such as nausea and dyspepsia were also investigated. Random‑ and fixed‑effects models were applied. Heterogeneity was quantified using I².
Results
Four RCT arms from two studies contributed to the IRLS analysis (n=119). In subgroup analysis, VITC was significantly more effective than placebo (MD –8.12 points; 95% CI –11.52 to –4.71; p<0.001), while demonstrating no meaningful difference compared with vitamin E (MD 0.10; 95% CI –3.42 to 3.62) or pramipexole (MD 0.59; 95% CI –4.18 to 5.36) [Figure 1]. VITC also improved sleep outcomes (RD 0.36; 95% CI 0.17 to 0.54; p<0.001). However, effects on itching (RR 0.82; 95% CI 0.18–3.75) and global RLS severity (RR 0.80; 95% CI 0.20–3.31) varied substantially across subgroups, reflecting heterogeneity in clinical response. Nausea (RR 0.32; 95% CI 0.04–2.94) [Figure 2] and dyspepsia (RR 3.00; 95% CI 0.33–27.33) [Figure 3] remained infrequent adverse events and did not differ significantly between treatment groups.
Conclusions
VITC may reduce RLS severity compared with placebo, though benefits are inconsistent across comparators and limited by high heterogeneity. Evidence for secondary outcomes is mixed and largely derived from single‑study data. Larger, rigorously designed RCTs are needed to clarify VITC’s therapeutic role in RLS.
Citation
Caprara AL, Rissardo JP, Patino J, McGarry A, Walker I. Efficacy of Vitamin C for Restless Legs Syndrome: A Systematic Review and Meta‑analysis of Randomized Controlled Trials. Mov Disord 2026;41(Suppl_1):S448-S449.
Figure 1. Forest plot of pooled MD of IRLS.
Figure 2. Forest plot of pooled RR of nausea.

Figure 3. Forest plot of pooled RR of dispepsia.