What is the appropriate dosage and administration of intravenous (IV) ascorbic acid (vitamin C) in patients with deficiency or increased demand?

Intravenous Ascorbic Acid Dosing and Administration

For vitamin C deficiency or scurvy, administer 100 mg three times daily orally (or 250 mg twice daily) for at least one month, with IV administration reserved for malabsorption or critical illness requiring 2-3 g/day during acute inflammation. 1, 2

Standard Treatment for Vitamin C Deficiency

Begin treatment immediately when clinical symptoms suggest deficiency (bleeding gums, petechiae, ecchymoses, poor wound healing, perifollicular hemorrhages) without waiting for laboratory confirmation. 2

Oral Repletion Protocol (First-Line)

• 100 mg three times daily (300 mg/day total) for at least 1 month 1, 2
• Alternative regimen: 250 mg twice daily for 3 weeks for clinical scurvy 1, 2
• Alternative single-dose regimen: 500 mg once daily for 1 month 1
• Continue until clinical symptoms resolve and adequate dietary intake is established 2

Maintenance After Repletion

• Healthy adults: 75-90 mg/day (achievable with one medium-sized orange) 2
• High-risk populations: 200-500 mg/day indefinitely (post-bariatric surgery, chronic oxidative stress, alcoholism, severe psychiatric illness, poor dietary habits) 1, 2

Intravenous Administration

Indications for IV Route

• Malabsorption suspected (use IM, IV, or subcutaneous routes) 2
• Critical illness during acute inflammation 1, 2
• Continuous renal replacement therapy 1, 2
• Perioperative cardiac surgery 1, 2

IV Dosing Protocols by Clinical Scenario

Critical illness/acute inflammation:

• 2-3 g/day IV during acute phase (typically 4-7 days) 1, 2
• Grade B recommendation with 84% consensus 1

Continuous renal replacement therapy:

• 2-3 g/day IV 1, 2

Cardiac surgery (perioperative):

• 1-2 g/day IV for 5-7 days 1, 2

Burn resuscitation:

• Maximum approximately 4-5 g/day (based on 66 mg/kg/hour for 24 hours for average adult) 1

Maximum Safe Dosing

• Absolute maximum: 2-3 g/day IV for most clinical scenarios 1
• The Tolerable Upper Level is 2 g based on gastrointestinal upset; doses above this may cause severe diarrhea and increase oxalate absorption/renal risk 1

Adjunctive Use in Specific Conditions

Methemoglobinemia

• Ascorbic acid can be added as adjunctive therapy to methylene blue (first-line treatment) 3
• Can be given orally, intramuscularly, or IV 3
• Ineffective as monotherapy in hemoglobin disorders (HbM, unstable Hb) 3

Anemia in Hemodialysis Patients

• 100-500 mg three times weekly IV has been studied 3
• Evidence shows mixed results: one study (300 mg three times weekly) showed statistically significant Hb improvement (10.5 vs 9.6), while others showed no difference between arms 3
• May enhance iron absorption when given with oral iron (250-500 mg twice daily), though effectiveness data for IDA treatment are lacking 3

Absolute Contraindications

Do not administer high-dose vitamin C (>1 g/day) in patients with: 1, 2

• Hemochromatosis
• G6PD deficiency
• Active oxalate kidney stones
• Severe renal dysfunction

Screen for these contraindications before administration. 4

Critical Monitoring Considerations

Laboratory Testing

• Do NOT measure plasma vitamin C levels during acute inflammation or critical illness - results will be falsely low and misleading 1, 2
• Levels decline when CRP >10 mg/L; normal values typically not detected if CRP >40 mg/L 1, 2
• Testing only recommended for suspected scurvy or chronic low intake in stable patients 1, 2

Administration Precautions

• Resuscitation facilities must be available when giving IV ascorbic acid due to anaphylaxis risk 3
• Monitor for edema if using doses above 1 g daily 4
• IV administration is necessary in critical illness as enteral uptake is unpredictable 1

Common Pitfalls to Avoid

• Oral absorption is limited at higher doses due to saturation of intestinal transporters - this is why IV is required for critical illness 1
• Do not use vitamin C as routine pharmacotherapy for sepsis - current evidence does not support this practice 2, 4
• The Surviving Sepsis Campaign recommends against ascorbic acid use in pediatric septic shock (weak recommendation, very low quality evidence) 4
• Do not delay standard care (antibiotics, source control, fluid resuscitation, vasopressors) to administer vitamin C in sepsis 4
• Vitamin C samples require special handling for accurate measurement 1

Pediatric Dosing

• Preterm and term infants up to 12 months: 15-25 mg/kg/day 2
• Older children: 80 mg/day 2