What is the recommended vitamin C supplementation for patients with End-Stage Renal Disease (ESRD) undergoing Hemodialysis (HD)?

Vitamin C Supplementation in Hemodialysis Patients

Hemodialysis patients should receive 100 mg/day of vitamin C as the safe upper limit for routine supplementation, with monitoring and replacement guided by serum levels and dialysis losses. 1, 2

Rationale for Supplementation

Water-soluble vitamins including vitamin C must be monitored and supplemented in patients on kidney replacement therapy due to increased requirements and large effluent losses. 1

Documented Losses and Deficiency

• Hemodialysis patients lose approximately 68 mg of vitamin C daily in dialysate effluent during continuous renal replacement therapy 1, 2
• Plasma vitamin C concentrations drop to approximately 50% of baseline values during a single dialysis session, though levels nearly recover 44 hours later 3
• Actual dialysate losses in individual patients range from 92.5 to 333.6 mg per treatment session 3
• Low vitamin C levels are consistently documented in hemodialysis patients due to restricted fruit intake and dialysis losses 1

Recommended Dosing Algorithm

Standard Maintenance Dosing

For chronic hemodialysis patients: 100 mg/day (or 1000-1500 mg/week) as the safe upper limit 1, 2, 4

• This dose effectively replaces dialysis losses while avoiding oxalate accumulation 1, 2
• Historical studies suggested 150-200 mg/day (1000-1500 mg/week) was sufficient to normalize vitamin C levels 4
• The 2021 ESPEN guidelines specifically recommend 100 mg/day as optimal dosing to balance replacement needs against toxicity risk 1

Critical Illness with CRRT

For patients on continuous renal replacement therapy during critical illness: 2-3 g/day IV during the acute phase 2

• This higher dose accounts for the 68 mg daily effluent losses plus increased utilization during critical illness 1, 2
• Return to maintenance dosing (100 mg/day) once acute inflammation resolves 2

Pediatric Dosing

Lower supplemental doses are required in children 1, 2

• Infants on automated peritoneal dialysis receiving 140% of RDA from diet plus only 15 mg/day supplement achieved 180% of RDA 1, 2
• Children on APD showed negative mass transfer of 32 mg/day, which was adequately compensated by oral supplementation 1

Critical Safety Considerations

Oxalate Toxicity Risk

Never exceed 100 mg/day in chronic hemodialysis patients to prevent oxalate accumulation 1, 2

• Excessive vitamin C intake (500-1000 mg/day in adults) results in increased oxalate concentrations in plasma and soft tissues 1, 2
• Combined dietary and supplemental intake should not greatly exceed the DRI 1
• Patients on prolonged renal replacement therapy require close monitoring for signs of oxalate accumulation 2

Pro-Oxidant Effects

Vitamin C supplementation may paradoxically increase lipid peroxidation, especially in patients with elevated serum ferritin 5

• A study of 109 hemodialysis patients showed oral vitamin C at 360 and 1500 mg/week increased plasma malondialdehyde (a marker of lipid peroxidation) by 9% and 26% respectively 5
• Serum ferritin and vitamin C were strong independent predictors of lipid peroxidation in stepwise regression analysis 5
• This pro-oxidant effect in the presence of iron may outweigh benefits of restored vitamin C status 5
• Monitor ferritin levels and consider lower supplementation doses in patients with iron overload 5

Monitoring Requirements

Laboratory Assessment

Monitor serum vitamin C levels and adjust supplementation based on individual losses and clinical status 1

• Plasma ascorbic acid levels reflect dietary intake 1
• Leukocyte levels estimate total body pool 1
• Do not measure plasma vitamin C during critical illness or when CRP >10 mg/L due to difficulty in interpretation 2

Electrolyte Monitoring

Electrolyte abnormalities must be closely monitored in all patients receiving kidney replacement therapy 1, 2

• This is particularly important given the potential for oxalate-related complications 1

Practical Implementation

Route of Administration

• Oral supplementation is preferred for stable chronic hemodialysis patients 4
• Intravenous administration (200 mg three times weekly) can be used and has shown efficacy in reducing PTH levels, though effects may diminish over time 6
• IV vitamin C 750 mg every 2 months has been shown to significantly increase antioxidant capacity in hemodialysis patients 7

Timing Considerations

• Post-dialysis supplementation is recommended to replace acute losses 4
• Vitamin C levels nearly recover to baseline 44 hours after dialysis even without supplementation, suggesting the body has some compensatory mechanisms 3

Integration with Renal Multivitamins

Use renal-specific multivitamin formulations that provide vitamin C ≤100 mg along with other water-soluble B vitamins 8

• These formulations should avoid or limit vitamin A and E due to accumulation risk 8
• Vitamin D should be supplemented separately to correct deficiency 8