What is the therapeutic dose of intravenous (IV) vitamin C?

Therapeutic Dose of Intravenous Vitamin C

The therapeutic dose of IV vitamin C depends on the clinical indication: for critically ill patients during acute inflammation, use 2-3 g/day IV; for sepsis protocols (though not routinely recommended), the most studied regimen is 1.5 g IV every 6 hours for 4 days (total 6 g/day); and for documented vitamin C deficiency with malabsorption, doses may range from 1-3 g/day IV until repletion is achieved. 1, 2

Context-Specific Dosing Recommendations

Critical Illness and Acute Inflammation

• Administer 2-3 g/day IV during the acute phase of inflammation (Grade B recommendation, 84% consensus) 1, 2
• This higher repletion dose addresses the rapid depletion of vitamin C that occurs when inflammation is present 1
• Plasma vitamin C levels decline precipitously when CRP >10 mg/L, and normal values are typically undetectable if CRP >40 mg/L 1, 2

Continuous Renal Replacement Therapy (CRRT)

• Use 2-3 g/day IV for patients on CRRT to compensate for losses through dialysis 1, 2

Perioperative Cardiac Surgery

• Administer 1-2 g/day IV for 5-7 days in the perioperative period 1, 2

Sepsis (Off-Guideline Use)

• The most extensively studied protocol is 1.5 g IV every 6 hours for 4 days (total 6 g/day), often combined with thiamine and hydrocortisone 1
• However, current guidelines recommend AGAINST routine use of vitamin C for sepsis treatment 1
• The Surviving Sepsis Campaign pediatric guidelines (2020) provide a weak recommendation against ascorbic acid use in septic shock (very low quality evidence) 1
• The C-EASIE 2025 trial using this dosing regimen showed no significant reduction in SOFA scores (ratio 0.91,95% CI 0.77-1.08, P=0.30) 1

Documented Vitamin C Deficiency (Scurvy)

• For symptomatic deficiency with malabsorption, use 1-3 g/day IV until symptoms resolve and levels normalize 3
• IV administration is necessary when oral supplementation fails to maintain adequate levels despite high-dose oral therapy (up to 2000 mg daily) 3
• Treatment of established infections requires significantly higher (gram) doses to compensate for increased inflammatory response and metabolic demand 4

Administration Guidelines

Route and Preparation

• Dilute IV vitamin C with normal saline or glucose to minimize adverse reactions 2
• IV administration is crucial in critically ill patients because enteral uptake is unpredictable due to limited intestinal transporter capacity and impaired gut function 2
• Oral absorption is limited at higher doses due to saturation of intestinal transporters 5

Duration of Therapy

• Sustained therapy is needed to prevent recurrence of hypovitaminosis 2
• Most protocols for acute conditions use 4-7 days of IV therapy 1, 2
• For chronic deficiency with malabsorption, routine home IV supplementation may be necessary 3

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Screen for and avoid vitamin C in patients with:
  • Hemochromatosis 1, 2
  • G6PD deficiency 1, 2
  • Severe renal dysfunction 1, 2
  • History of oxalate kidney stones 1, 2

Monitoring Considerations

• Do NOT measure plasma vitamin C levels during acute sepsis or critical illness - inflammation makes interpretation unreliable 1, 5
• Plasma vitamin C measurement is only recommended for suspected scurvy or chronic low intake in stable patients 5, 2
• Monitor for edema if using doses above 1 g daily 1

Common Pitfalls to Avoid

Clinical Decision-Making Errors

• Never delay standard sepsis care (antibiotics, source control, fluid resuscitation, vasopressors) to administer vitamin C 1
• Do not use vitamin C as monotherapy antioxidant in high doses without proven deficiency (Grade B recommendation, 96% consensus) 1
• Avoid dosages exceeding 10 times the dietary reference intake in clinical settings without severe proven deficiency 1

Inappropriate Use in Sepsis

• Consider vitamin C in sepsis ONLY in these specific contexts: 1
  • Documented severe vitamin C deficiency with clinical suspicion of scurvy
  • Research protocol participation with appropriate informed consent
  • Refractory septic shock after exhausting all guideline-recommended therapies (understanding this is not evidence-based)

Hemodialysis-Specific Dosing (Anemia Context)

For the specific indication of anemia in hemodialysis patients, studied doses have ranged from 100-500 mg three times weekly, though results have been mixed 6:

• 300 mg three times weekly showed statistically significant improvement in hemoglobin (10.5 vs 9.6 g/dL) in patients with ESA resistance 6
• However, safety concerns regarding pro-oxidant effects and oxalosis with prolonged administration have not been fully established in CKD patients 6