High-Dose Vitamin C (1000 mg TID) Indications
High-dose vitamin C at 1000 mg three times daily is primarily prescribed for patients with critical illness, severe inflammation, or chronic oxidative stress conditions to improve clinical outcomes by addressing vitamin C deficiency and providing antioxidant support.
Clinical Scenarios Requiring High-Dose Vitamin C
- Critical illness: During critical illness, a higher vitamin C repletion dose of 2-3 g per day should be given intravenously during the acute phase of inflammation 1
- Chronic oxidative stress conditions: Patients with diabetes mellitus, heart failure, smoking, alcoholism, severe COPD, and chronic dialysis may require 200-500 mg/day of vitamin C 1
- Sepsis and acute respiratory failure: Some protocols have used 200 mg/kg/day of vitamin C for 4 days 1
- Malabsorption: Patients with chronic malabsorption may require 2-3 g/day intravenously 1
- Continuous renal replacement therapy: Patients on CRRT may require 2-3 g/day IV 2
Mechanisms of Action Supporting High-Dose Therapy
- Vitamin C primarily acts on the endothelium and microcirculation, preventing microcirculatory flow impairment 1
- It prevents thrombin-induced platelet aggregation and platelet surface P-selectin expression, thus preventing micro thrombi formation 1
- Vitamin C restores vascular responsiveness to vasoconstrictors and preserves the endothelial barrier 1
- As a powerful antioxidant, it counteracts oxidative stress present in critical illness 3
- Vitamin C augments antibacterial defenses, potentially reducing infectious complications 1
Physiological Considerations
- Critically ill patients exhibit low circulating ascorbic acid concentrations, associated with inflammation, severity of organ failure, and mortality 1
- Plasma vitamin C levels decline rapidly with inflammation, with normal values rarely detected when CRP exceeds 40 mg/L 1
- Vitamin C plasma concentrations in patients on RRT are comparable to critically ill patients not receiving RRT 4
- Oral vitamin C absorption is limited at higher doses due to saturation of intestinal transporters, making IV administration necessary in critical illness 2
Monitoring and Safety Considerations
- Measurement of plasma vitamin C is not recommended in critical illness or severe inflammation due to difficulty in interpretation of results 1, 2
- High-dose vitamin C may cause oxalate nephropathy in patients with renal impairment 5
- Patients with glucose-6-phosphate dehydrogenase deficiency are at risk of severe hemolysis with high-dose vitamin C 5
- Vitamin C may interfere with laboratory tests based on oxidation-reduction reactions, including blood and urine glucose testing 5
Dosing Recommendations
- For critical illness: 2-3 g per day IV during acute inflammation 1, 2
- For chronic oxidative stress: 200-500 mg/day 1
- For sepsis and ARDS: 1.5-2 g every 6 hours IV during acute inflammation 3
- For treatment of established infections: gram doses are required to compensate for increased inflammatory response and metabolic demand 6
- For prevention of infection: dietary vitamin C intakes of 100-200 mg/day 6
Common Pitfalls and Caveats
- Oral vitamin C absorption is limited at higher doses, making IV administration necessary in critical illness 2
- Sustained therapy is needed to prevent recurrence of hypovitaminosis 2
- Safe doses of vitamin C are less than 1000 mg daily for long-term use, and vitamin C daily doses above 400 mg have no evident value in healthy individuals 7
- Vitamin C samples require special handling for accurate measurement 8
- Ascorbic acid may decrease the activities of certain antibiotics including erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin 5