What is the current research on vitamin C (ascorbic acid) intravenous (IV) infusions?

Current Research on Vitamin C IV Infusions

The current research on vitamin C (ascorbic acid) intravenous infusions shows potential benefits in specific clinical scenarios, but high-dose IV vitamin C should only be administered in critical illness settings at doses of 2-3 g per day during acute inflammation phases.

Established Functions and Mechanisms of Vitamin C

Vitamin C serves multiple important physiological functions:

• Most potent water-soluble antioxidant that scavenges radicals and mitigates oxygen radical production 1
• Essential cofactor/cosubstrate for biosynthesis of:
  • Neurotransmitters (noradrenaline, serotonin)
  • Cortisol
  • Peptide hormones (vasopressin)
  • Collagen 1
• Protects endothelium by promoting collagen synthesis and maintaining endothelial vasodilation and barrier function 1
• Limits inflammatory response and ischemia-reperfusion injury 1
• Improves host defense and wound healing 1
• Has epigenetic roles by suppressing response element-controlled genes through enhanced HIF-1 degradation 1

Clinical Applications of IV Vitamin C

Critical Illness and Sepsis

IV vitamin C administration is particularly relevant in critical illness for several reasons:

• During critical illness, IV administration is crucial as enteral uptake is unpredictable due to limited absorption and impaired gut function 1
• High vitamin C doses (2-3 g/day) are required to restore plasma concentrations to normal levels during critical illness 1
• Very high doses (100-200 mg/kg/day) are needed to achieve supranormal plasma concentrations 1

Current evidence suggests:

• A recent meta-analysis shows IV vitamin C might improve short-term mortality (RR, 0.82; 95% CI, 0.65-1.02) and overall mortality (RR, 0.86; 95% CI, 0.74-1.01) in patients with sepsis 2
• SOFA scores of sepsis patients improved significantly after treatment with vitamin C for over 72 hours 2

Recommended Dosing in Critical Illness

For critical illness, the ESPEN micronutrient guideline recommends:

• During critical illness, a higher vitamin C repletion dose of 2-3 g per day should be given IV during the acute phase of inflammation 1
• For patients with chronic oxidative stress (diabetes mellitus, smoking, heart failure, alcoholism, severe COPD, and chronic dialysis) or malabsorption, a dose of 200-500 mg/day may be provided 1

Exercise-Induced Bronchoconstriction

The American Thoracic Society provides a weak recommendation for dietary supplementation with ascorbic acid for patients with exercise-induced bronchoconstriction (EIB) based on moderate-quality evidence 1. In clinical trials, patients with EIB who received ascorbic acid supplementation had approximately half the maximum percent fall in FEV1 after exercise compared to those who did not receive supplementation 1.

Safety Profile and Considerations

High-dose IV vitamin C appears to be relatively safe with proper patient selection:

• A survey of Complementary and Alternative Medicine practitioners found that of 9,328 patients treated with IV vitamin C (average dose 28 grams every 4 days), only 101 had side effects, mostly minor 3
• Common minor side effects included lethargy/fatigue (59 patients), change in mental status (21 patients), and vein irritation/phlebitis (6 patients) 3
• Serious adverse events have been documented in patients with known risk factors for IV vitamin C 3

Important contraindications and precautions:

• Patients with renal impairment or glucose-6-phosphate dehydrogenase deficiency should not receive high-dose IV vitamin C 3
• For IV administration, vitamin C should be diluted with normal saline or glucose to minimize adverse reactions 1

Practical Aspects of IV Vitamin C Administration

Stability and Preparation

• Vitamin C solutions of 1.5 g per 50 mL of 0.9% saline and 2.5 g per 50 mL of dextrose 5% remain stable for up to 96 hours 4
• These solutions do not need to be protected from light 4
• The high susceptibility of vitamin C to degradation requires specific pre-analytical precautions when measuring plasma levels 1

Monitoring Considerations

• Assessment of vitamin C status can be determined from its concentration in either plasma or leukocytes 1
• Plasma vitamin C analysis is the preferred option for status assessment; serum determination should be avoided 1
• Vitamin C plasma levels decline rapidly with progressive inflammation, making interpretation difficult 1
• Blood levels decrease as soon as CRP >10 mg/L; normal values are not detected if CRP >40 mg/L 1

Research Gaps

Despite significant advances in understanding IV vitamin C, several knowledge gaps remain:

• Optimal dosing, frequency, and duration of IV vitamin C therapy for different conditions 5
• Whether correcting plasma concentration during severe inflammation improves outcomes 1
• Full understanding of vitamin C's pro-oxidant mechanisms at high concentrations 6
• Whether vitamin C-induced reactive oxygen species occur in vivo and translate to clinical benefit 6

Conclusion

While IV vitamin C shows promise in critical illness settings, particularly sepsis, its use should be guided by clinical guidelines and administered at appropriate doses (2-3 g/day) during acute inflammation phases. For other applications, such as cancer therapy, the evidence remains inconclusive, and use outside clinical trials is not recommended 6.