Abstract
- Background
Vitamin C (ascorbic acid) is an essential metabolite in humans due to evolutionary genetic mutations. Requirements for vitamin C increase significantly during severe infections, cancer, and other major illnesses. Recent research highlights the potential for intravenous vitamin C administration to improve outcomes in sepsis, severe respiratory illness, and malignancy, alongside emerging insights into its epigenetic and immunomodulatory functions. This Special Issue, inspired by the 2nd Vitamin C Symposium (2019), presents translational "bench to bedside" research spanning pharmacokinetics, immune function, epidemiology, oncology, surgical outcomes, and severe infections.
- Methods
This Special Issue compiled 15 original research papers and comprehensive reviews. Studies evaluated oral vs. intravenous pharmacokinetic profiles, erythrocyte ascorbate kinetics, neutrophil functions (chemotaxis, phagocytosis, oxidative burst, apoptosis, and NET formation), epidemiological risk factors using the EPIC-Norfolk cohort, tumor cell/xenograft metastasis models, surgical outcomes (reperfusion injury during PCI and postoperative analgesia), and clinical trials in pneumonia, sepsis, septic shock subphenotypes, and COVID-19/ARDS.
- Results
Key findings include:
Pharmacokinetics & Epidemiology: Intravenous administration achieves distinct high-plasma kinetics compared to oral dosing. Erythrocyte ascorbate levels were identified as a stable status biomarker. Vitamin C deficiency was independently linked to older age, male sex, smoking, lower physical activity, lower educational attainment, and reduced physical/vitality scores.
Oncology: Vitamin C suppressed triple-negative breast cancer metastasis by modulating SYNPO2 and YAP1 expression. Depleted vitamin C status was frequently observed during chemotherapy with stem cell transplantation and was strongly correlated with patient and tumor characteristics.
Surgical Outcomes: Pre-PCI intravenous vitamin C offered cardioprotection against reperfusion injury. Perioperative intravenous (but not oral) vitamin C significantly reduced postoperative pain scores and morphine consumption.
Infections, Sepsis & COVID-19: Severe pneumonia and sepsis were characterized by marked ascorbate depletion and elevated oxidative stress/inflammatory cytokines. Subphenotype analysis demonstrated that septic shock patients with hyperinflammatory profiles benefited most from combination therapy. Intravenous vitamin C reduced mortality in sepsis-induced acute lung injury (CITRIS-ALI trial) and displayed potential therapeutic relevance in severe SARS-CoV-2/COVID-19 management.
- Conclusions
Vitamin C plays crucial, pleiotropic roles across a broad spectrum of human diseases. Addressing knowledge gaps requires well-designed observational and interventional trials that strictly account for baseline nutritional status and unique pharmacological kinetics. Continued mechanistic research will be essential to translate leading-edge laboratory discoveries into effective clinical practice.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8066298/