Vitamin C Dosing for ESRD Patients with Restless Leg Syndrome
The American Academy of Sleep Medicine recommends 200 mg of vitamin C daily for ESRD patients with restless legs syndrome, based on evidence showing clinically significant improvement in disease severity with a moderate effect size. 1
Evidence-Based Dosing Recommendation
The 2025 AASM guidelines provide a conditional recommendation for vitamin C use in this specific population (low certainty of evidence), making it one of the few evidence-supported treatments for uremic RLS. 1 The recommendation is based on a randomized controlled trial that demonstrated:
- Dose: 200 mg daily 2
- Duration: 8 weeks minimum (the trial duration that showed efficacy) 2
- Route: Oral administration 2
The mean reduction in International Restless Legs Scale (IRLS) score was 10.0 ± 3.5 points with vitamin C 200 mg daily compared to 3.1 ± 3.0 points with placebo (P < 0.001). 2 This improvement is clinically meaningful and comparable to 0.18 mg of pramipexole. 3
Treatment Algorithm for ESRD-RLS
First-line approach:
- Check iron parameters (ferritin and transferrin saturation) 1
- If ferritin < 200 ng/mL AND transferrin saturation < 20%, administer IV iron sucrose (conditional recommendation, moderate certainty of evidence) 1
- Simultaneously initiate vitamin C 200 mg daily (conditional recommendation, low certainty of evidence) 1
Second-line if inadequate response:
- Add gabapentin at renally-adjusted doses (conditional recommendation, very low certainty of evidence) 1
- Start with 100 mg post-dialysis or at bedtime, maximum 200-300 mg daily 4
Key Advantages of Vitamin C in ESRD
The AASM task force noted several favorable characteristics: 1
- Negligible cost
- Trivial undesirable effects (no adverse events leading to study withdrawal reported)
- Does not affect health equity
- Feasible to implement
- No risk of augmentation (unlike dopaminergic agents)
Combination Therapy Considerations
Vitamin E (400 mg daily) showed equivalent efficacy to vitamin C alone, and the combination of vitamin C + E provided no additional benefit over either vitamin alone. 2 Therefore, adding vitamin E is not necessary if using vitamin C 200 mg daily. 1
Critical Pitfalls to Avoid
- Do not use higher doses without evidence: The trial specifically used 200 mg, and higher doses have not been studied in this population 2
- Do not use vitamin C as monotherapy without checking iron status: Iron deficiency is highly prevalent in ESRD-RLS and should be corrected first 1
- Avoid dopaminergic agents (levodopa, ropinirole, pramipexole, rotigotine) as standard treatment: These carry substantial risk of augmentation in ESRD patients 1
- Monitor for renal stone formation: Although the trial excluded patients with history of renal stones, this remains a theoretical concern with vitamin C supplementation in ESRD 2
Monitoring and Duration
Continue vitamin C indefinitely as long as symptoms persist and the patient tolerates it well, given the excellent safety profile and negligible cost. 1 Reassess RLS severity using the IRLS scale at 8 weeks to determine treatment response. 2