Vitamin C
Vitamin C, also known as ascorbic acid, is a water-soluble vitamin commonly used in supplements to support immune function, skin health, and overall wellness. It acts as a potent antioxidant, neutralizing free radicals and reducing oxidative stress, which may protect against cellular damage linked to aging and chronic diseases. Vitamin C is essential for collagen synthesis, promoting skin elasticity, wound healing, and connective tissue health. It enhances immune function by supporting white blood cell activity and increasing interferon production, potentially reducing the severity or duration of colds. Additionally, it improves iron absorption in the gut, aiding anemia prevention. Supplements typically provide 500–1000 mg/day, but high doses (>2000 mg/day) may cause diarrhea, nausea, or kidney stone risk in susceptible individuals. Consult a healthcare provider for appropriate dosing, especially if on medications or with conditions like kidney disease.
Benefits
Immune System Support
Vitamin C enhances immune function by supporting white blood cell activity and acting as an antioxidant to protect immune cells from oxidative stress. May reduce the duration and severity of common colds by about 8% in adults and 14% in children, though it doesn’t prevent colds outright (Hemilä & Chalker, 2013).
Antioxidant Protection
Neutralizes free radicals, reducing oxidative stress linked to chronic diseases like heart disease and cancer. May help protect against age-related conditions, such as macular degeneration (Evans & Lawrenson, 2017).
Collagen Formation
Essential for collagen synthesis, supporting skin, cartilage, bones, and wound healing. May improve skin health and reduce signs of aging by promoting elasticity (Pullar et al., 2017).
Improved Iron Absorption
Enhances non-heme (plant-based) iron absorption, which can help prevent or manage iron-deficiency anemia, especially in vegetarians (Hallberg et al., 1989).
Cardiovascular Health
May lower blood pressure and improve endothelial function, potentially reducing heart disease risk (Ashor et al., 2017). Some studies link higher vitamin C intake to reduced risk of stroke (Chen et al., 2013).
Potential Anti-Inflammatory Effects
High doses may reduce inflammation markers like C-reactive protein, which could benefit conditions like arthritis or metabolic syndrome (Juraschek et al., 2012).
Mechanism of Action
Antioxidant Activity
Vitamin C is a potent water-soluble antioxidant that donates electrons to neutralize free radicals (reactive oxygen species, ROS) and reduce oxidative stress. It regenerates other antioxidants, like vitamin E, by reducing their oxidized forms (Carr & Frei, 1999).
Protects cells, DNA, proteins, and lipids from oxidative damage, which is linked to aging, cancer, and cardiovascular diseases. This is particularly relevant in high-oxidative-stress conditions (e.g., smoking, intense exercise).
Collagen Synthesis:
Acts as a cofactor for prolyl and lysyl hydroxylases, enzymes critical for stabilizing collagen’s triple-helix structure. It donates electrons to maintain these enzymes’ iron in the reduced (Fe²⁺) state (Peterkofsky, 1991). Supports connective tissue formation, aiding skin, cartilage, bone health, and wound healing.
Neurotransmitter and Hormone Synthesis:
Serves as a cofactor for dopamine β-hydroxylase, which converts dopamine to norepinephrine, and for enzymes involved in peptide hormone maturation (e.g., oxytocin, vasopressin) (Englard & Seifter, 1986). Influences nervous system function and stress responses.
Enhancement of Iron Absorption
Reduces dietary ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), which is more bioavailable, and forms chelates that keep iron soluble in the intestine (Hallberg et al., 1989). Increases non-heme iron absorption, helping prevent or treat iron-deficiency anemia, especially in plant-based diets.
Immune System Modulation
Enhances chemotaxis, phagocytosis, and oxidative burst in neutrophils, improving pathogen clearance. Protects immune cells from ROS damage during inflammation. Supports lymphocyte proliferation and function (Hemilä & Chalker, 2013). May reduce the duration and severity of infections like the common cold and support overall immune health.
Anti-Inflammatory and Cardiovascular Effects
Reduces pro-inflammatory markers (e.g., C-reactive protein) by scavenging ROS and modulating signaling pathways like NF-κB (Juraschek et al., 2012). Improves endothelial function by increasing nitric oxide bioavailability, which promotes vasodilation (Ashor et al., 2017). May lower blood pressure, improve vascular health, and reduce risk factors for heart disease and stroke.
Epigenetic Regulation
Acts as a cofactor for TET (ten-eleven translocation) enzymes, which demethylate DNA, and Jumonji-domain histone demethylases, influencing gene expression (Young et al., 2015). Potentially affects cellular differentiation and disease processes, though clinical implications are still under research.
Clinical Trials
Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients with Sepsis and Severe Acute Respiratory Failure (CITRIS-ALI)
Study: A randomized, double-blind, placebo-controlled trial (USA, 2019) involving 167 patients with sepsis-related acute respiratory distress syndrome (ARDS). Patients received ~15 g/day of intravenous vitamin C (IVC) for 4 days or placebo. The primary outcome was change in Sequential Organ Failure Assessment (SOFA) scores; secondary outcomes included mortality and biomarkers of inflammation and vascular injury.
Findings: IVC did not significantly improve SOFA scores or biomarkers of inflammation and vascular injury. However, a trend toward reduced 28-day mortality was observed in the vitamin C group (30% vs. 46% in placebo, p=0.06). No significant adverse effects were reported.
Link: https://jamanetwork.com/journals/jama/fullarticle/2752063
Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected Pneumonia
Study: A randomized, placebo-controlled trial (China, 2020–2021, NCT04264533) conducted in Hubei with 56 critically ill COVID-19 patients in the ICU. Patients received 24 g/day IVC (12 g every 12 hours) for 7 days or placebo. Primary outcome was invasive mechanical ventilation-free days in 28 days (IMVFD28); secondary outcomes included 28-day mortality, organ failure (SOFA score), and interleukin-6 levels.
Findings: No significant improvement in IMVFD28 was observed. However, oxygenation (PaO2/FiO2) improved, especially in patients with higher baseline SOFA scores. No significant differences in mortality or interleukin-6 levels were noted. IVC was well-tolerated with no major side effects.
Link: https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00792-3
High-Dose Intravenous Vitamin C as an Adjunct to Chemotherapy in Stage IV Pancreatic Cancer
Study: A randomized, phase II trial (USA, University of Iowa, 2024) in 34 patients with metastatic pancreatic cancer. Patients received 75 g IVC three times weekly alongside gemcitabine and nab-paclitaxel chemotherapy, compared to chemotherapy alone. Outcomes included overall survival (OS) and progression-free survival (PFS).
Findings: IVC doubled OS (16 months vs. 8 months) and extended PFS (6.2 months vs. 3.9 months). Patients tolerated chemotherapy better with fewer side effects and improved quality of life. No significant toxicity was reported with IVC.
High-Dose Intravenous Vitamin C in Glioblastoma
Study: A phase II randomized trial (USA, University of Iowa, 2024) in patients with glioblastoma. Patients received high-dose IVC (dose not specified, typically 75 g three times weekly) with standard chemotherapy and radiation, compared to standard treatment alone. Outcomes focused on survival and quality of life.
Findings: IVC significantly increased survival compared to controls (specific data not provided in source). Patients reported improved tolerance to standard treatments. No significant adverse effects were noted.
Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit (LOVIT Trial)
Study: An international, randomized, placebo-controlled trial (2022) involving 385 ICU patients with sepsis receiving vasopressor therapy. Patients received IVC (dose not specified) or placebo. The primary outcome was a composite of death or persistent organ dysfunction at 28 days; secondary outcomes included 6-month mortality and biomarkers.
Findings: IVC unexpectedly increased the composite outcome (death or organ dysfunction) compared to placebo. No clear mechanism for harm was identified. Rare side effects included stage 3 acute kidney injury and hypoglycemia. Results contrasted with earlier meta-analyses suggesting mortality benefits.
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2112396
Vitamin C Supplementation in Community-Acquired Pneumonia (CAP)
Study: A systematic review and meta-analysis (2024) of six RCTs (up to November 2023) evaluating vitamin C supplementation (oral or IV, varying doses) in adults with CAP. Outcomes included mortality, hospital/ICU length of stay (LOS), and mechanical ventilation duration.
Findings: A non-significant trend toward reduced mortality was observed (relative risk: 0.51, p=0.052). No consistent effects on LOS or ventilation duration were found. Study quality was generally poor, limiting conclusions. Concerns included potential metabolic acidosis with ascorbic acid (vs. sodium ascorbate) and rebound oxidative stress upon abrupt cessation.
Link: https://www.nature.com/articles/s41598-024-61409-8
Vitamin C for Preventing Atrial Fibrillation in High-Risk Patients
Study: A systematic review and meta-analysis (2017) of RCTs evaluating vitamin C supplementation (doses not specified) in high-risk patients for atrial fibrillation (e.g., post-cardiac surgery). Outcomes focused on incidence of atrial fibrillation and related complications.
Findings: No significant reduction in atrial fibrillation incidence was observed. Vitamin C was safe, with no notable side effects reported.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC5295104/
Effect of Vitamin C, Vitamin E, and α-Lipoic Acid in Mild-to-Moderate Alzheimer’s Disease
Study: A double-blind, randomized controlled trial (year not specified, cited 2022) in 78 patients with mild-to-moderate Alzheimer’s disease. Patients received 500 mg/day vitamin C, 800 IU/day vitamin E, and 900 mg/day α-lipoic acid for 16 weeks, compared to placebo. Outcomes included CSF biomarkers and clinical progression.
Findings: The combination increased antioxidant levels and reduced CSF lipoprotein oxidation but had no effect on clinical progression of Alzheimer’s disease. No significant side effects were reported.
Link: https://lpi.oregonstate.edu/mic/vitamins/vitamin-C
Vitamin C Supplementation for Gout Prevention
Study: A 2011 meta-analysis of 13 RCTs in healthy individuals with elevated serum uric acid, testing vitamin C supplementation (median 500 mg/day for 30 days) vs. placebo. The primary outcome was reduction in serum uric acid levels.
Findings: Vitamin C modestly reduced serum uric acid by 0.35 mg/dL, but this was not clinically significant. No notable side effects were reported.
Link: https://lpi.oregonstate.edu/mic/vitamins/vitamin-C
Vitamin C Supplementation for Cancer Prevention
Study: A meta-analysis (2014) of seven RCTs involving 62,619 participants, comparing vitamin C supplementation (doses not specified) to placebo or control for cancer prevention. The primary outcome was cancer incidence.
Findings: No significant association was found between vitamin C supplementation and cancer risk (relative risk: 1.00, 95% CI: 0.95–1.05). No significant side effects were reported.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC4646942/
Oral Vitamin C in Critically Ill COVID-19 Patients
Study: A double-blind RCT (Iran, 2021) in 31 critically ill COVID-19 patients, administering 500 mg/day oral vitamin C for 14 days vs. placebo. Outcomes included survival duration, biochemical markers, and clinical outcomes.
Findings: Oral vitamin C increased survival duration (8 vs. 4 days) and lowered serum potassium levels but had no effect on blood glucose, arterial blood gas, or other markers. No significant side effects were reported.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC9010351
Intravenous Ascorbic Acid as an Adjunct to Pazopanib in Metastatic Sarcoma
Study: A phase I/II trial (USA, Mayo Clinic, registered 2021, ongoing) evaluating IVC as an adjunct to pazopanib in patients with metastatic sarcoma in first-line or post-immunotherapy settings. Specific dosing and outcomes not fully reported in the source.
Findings: Results not yet available (trial ongoing). No interim side effect data provided.
Link: https://www.mayo.edu/research/clinical-trials/cls-20516241
High-Dose Intravenous Vitamin C in Non-Small Cell Lung Cancer
Study: A phase II trial (USA, University of Iowa, ongoing as of 2024) evaluating high-dose IVC (likely 75 g three times weekly) with standard chemotherapy in non-small cell lung cancer. Outcomes focus on survival and treatment tolerance.
Findings: Results not yet published (expected within 2025). Preliminary data from related trials suggest improved treatment tolerance and potential survival benefits.
Potential Side Effects
Gastrointestinal Issues
Diarrhea, nausea, abdominal cramps, or bloating. High doses overwhelm intestinal absorption, leading to osmotic effects and irritation. Common at doses exceeding the tolerable upper limit (2,000 mg/day).
Kidney Stones
Increased risk of oxalate kidney stones in susceptible individuals (e.g., those with a history of kidney stones or renal issues). Vitamin C is metabolized to oxalate, which can bind with calcium to form stones, especially at doses >1,000 mg/day (Curhan et al., 1999).
Urinary Issues
Increased urinary oxalate or uric acid, potentially causing discomfort or crystalluria. Excess vitamin C excretion in urine alters pH and increases oxalate levels (Levine et al., 1996).