What is the mechanism of action of vitamin C (ascorbic acid) on viral illnesses?

Mechanism of Action of Vitamin C on Viral Illness

Primary Mechanisms

Vitamin C functions through multiple interconnected mechanisms during viral infections, primarily acting as a potent water-soluble antioxidant that directly scavenges free radicals, serves as a cofactor for critical biosynthetic pathways, and modulates both innate and adaptive immune responses. 1, 2

Antioxidant and Cytoprotective Effects

• Direct radical scavenging: Vitamin C donates electrons to neutralize reactive oxygen species (ROS) that accumulate during viral infections, preventing cellular and tissue damage 1, 3
• Recycling of other antioxidants: It regenerates other antioxidant molecules, amplifying the body's overall antioxidant capacity 1
• Mitigation of oxidative stress: Viral infections, including coronaviruses and influenza, dramatically increase oxidative stress; vitamin C counteracts this pathophysiologic response 3
• Endothelial protection: Promotes collagen synthesis and maintains endothelial vasodilation and barrier function, which is critical during severe viral infections 1

Immunomodulatory Functions

• Enhancement of innate immunity: Multiple cellular processes of both innate and adaptive immunity are supported by vitamin C, strengthening overall immune system function 2
• Leukocyte function: During acute infection, vitamin C levels in serum and leukocytes become depleted due to increased metabolic demands; supplementation helps normalize these levels and restore immune cell function 4
• Host defense enhancement: Improves antibacterial and antiviral defenses through enhanced immune cell activity 5
• Anti-inflammatory effects: Limits excessive inflammatory responses that can lead to tissue damage during severe viral infections 5, 4

Biosynthetic Cofactor Role

• Neurotransmitter synthesis: Serves as cofactor for production of noradrenaline and serotonin 1
• Hormone production: Required for synthesis of cortisol, vasopressin, and peptide hormones 1
• Collagen synthesis: Essential cofactor for collagen production, supporting tissue integrity and wound healing during infection 1, 4

Vascular and Microcirculatory Effects

• Prevention of microcirculatory deterioration: Maintains blood flow to tissues during sepsis and severe viral illness 5
• Inhibition of platelet aggregation: Reduces risk of thrombotic complications 5
• Restoration of vascular responsiveness: Helps preserve normal response to vasoconstrictors during shock states 5
• Anticoagulant properties: May reduce coagulation abnormalities associated with severe viral infections 2

Epigenetic and Gene Regulation

• HIF-1 degradation: Suppresses hypoxia-inducible factor-1 (HIF-1) controlled genes through enhanced degradation, thereby mitigating chronic inflammation and tissue hypoxia 1
• Gene expression modulation: Influences expression of genes involved in immune response and inflammation 6

Clinical Context and Limitations

Depletion During Illness

• Rapid consumption: Plasma vitamin C concentrations decline rapidly with progressive inflammation, particularly when C-reactive protein (CRP) exceeds 10 mg/L 7, 8
• Severity correlation: Low plasma vitamin C levels are associated with severity of oxidative stress, organ failure, and mortality in critically ill patients 1
• Metabolic demands: Increased utilization during acute infection leads to functional deficiency even with normal baseline stores 4

Important Caveats

• Mechanism vs. clinical efficacy: While these mechanisms are well-established, recent high-quality trials (such as C-EASIE 2025) have not demonstrated significant clinical benefits in sepsis despite these theoretical mechanisms 5
• Enteral absorption limitations: Oral vitamin C absorption is saturable due to limited intestinal transporter capacity; IV administration is necessary during critical illness for adequate tissue levels 1, 7
• Vitamin C transporter dysregulation: Expression of vitamin C transporters may be altered during severe illness, potentially affecting cellular uptake even when plasma levels are corrected 6

Practical Implications

• Not a substitute for standard care: These mechanisms do not justify delaying evidence-based treatments (antibiotics, source control, fluid resuscitation, vasopressors) for viral infections or sepsis 5
• Deficiency correction vs. pharmacologic dosing: Correcting documented deficiency (restoring normal physiologic function) differs from using supraphysiologic doses as pharmacotherapy 1
• Context-dependent benefit: The clinical relevance of these mechanisms appears most significant when correcting documented deficiency states rather than as routine pharmacologic intervention 1, 5