Vitamin C - Drug Monograph

Introduction

Vitamin C (ascorbic acid) is a water-soluble essential nutrient that serves as a critical cofactor for numerous enzymatic reactions in the human body. As humans lack the enzyme L-gulonolactone oxidase required for endogenous synthesis, vitamin C must be obtained through dietary sources or supplementation. Beyond its historical role in preventing scurvy, vitamin C has gained attention for its antioxidant properties and potential therapeutic applications.

Mechanism of Action

Vitamin C functions primarily as:

• Cofactor for enzymatic reactions: Essential for collagen synthesis (hydroxylation of proline and lysine residues), catecholamine biosynthesis (dopamine β-hydroxylase), and carnitine synthesis
• Antioxidant activity: Scavenges reactive oxygen and nitrogen species, regenerates other antioxidants (including vitamin E)
• Immune function support: Promotes neutrophil function, chemotaxis, and phagocytosis
• Iron absorption enhancement: Reduces dietary ferric iron (Fe³⁺) to ferrous iron (Fe²⁺) in the gastrointestinal tract

Indications

• Treatment and prevention of vitamin C deficiency (scurvy)
• Urinary acidification

• Antioxidant supplementation
• Common cold prophylaxis and symptom reduction
• Wound healing support
• Iron absorption enhancement in iron deficiency anemia
• Some evidence supports use in certain cancer protocols (typically intravenous administration)

Dosage and Administration

• Adults: 65-90 mg daily for maintenance; 100-200 mg daily for therapeutic purposes
• Scurvy treatment: 100-500 mg daily for 1-2 weeks, followed by adequate dietary intake
• Upper limit: 2,000 mg daily for adults

• Pregnancy: 85 mg daily
• Lactation: 120 mg daily
• Smokers: Additional 35 mg daily recommended

• Reserved for specific medical situations under physician supervision
• Dosing varies based on indication (typically 1-1.5 g daily for deficiency states)

Pharmacokinetics

• Absorption: Active transport in small intestine; dose-dependent bioavailability (approximately 70-90% at doses ≤180 mg daily, decreasing to ≤50% at 1 g doses)
• Distribution: Widely distributed to all body tissues; highest concentrations in pituitary gland, adrenal gland, and leukocytes
• Metabolism: Hepatic oxidation to dehydroascorbic acid
• Elimination: Renal excretion; half-life approximately 10-20 days in adequate states, shortened in deficiency states
• Steady-state: Plasma concentration typically 0.8-1.5 mg/dL in adequately nourished individuals

Contraindications

• History of hypersensitivity to ascorbic acid or any product component
• Hereditary iron overload disorders (hemochromatosis, thalassemia, sideroblastic anemia) due to enhanced iron absorption

Warnings and Precautions

• Nephrolithiasis risk: High doses may increase oxalate production and urinary excretion
• G6PD deficiency: High doses may cause hemolysis in susceptible individuals
• Diabetes mellitus: May interfere with certain blood glucose monitoring systems
• Renal impairment: Use with caution in patients with history of renal stones or renal failure
• Pregnancy category C: Use during pregnancy only if potential benefit justifies potential risk

Drug Interactions

• Aspirin: May decrease vitamin C concentrations
• Oral contraceptives/estrogen: May increase vitamin C requirements
• Warfarin: High doses may theoretically decrease anticoagulant effect
• Iron supplements: Enhances iron absorption (therapeutic advantage in iron deficiency, but caution in iron overload disorders)
• Aluminum-containing antacids: May increase aluminum absorption
• Chemotherapeutic agents: Theoretical concern that antioxidants may reduce effectiveness of some agents

Adverse Effects

• Gastrointestinal disturbances (nausea, abdominal cramps, diarrhea)
• Headache
• Flushing

• Nephrolithiasis (calcium oxalate stones)
• Hemolysis in G6PD-deficient individuals
• Iron overload in susceptible patients
• Rebound scurvy with abrupt discontinuation after prolonged high-dose supplementation
• Dental erosion with chewable formulations

Monitoring Parameters

• Clinical signs of deficiency (gingivitis, petechiae, impaired wound healing)
• Urinary oxalate levels in patients on high-dose therapy
• Iron status in patients with risk factors for iron overload
• Renal function in patients with history of renal impairment
• Plasma vitamin C levels when indicated (target >0.2 mg/dL)

Patient Education

• Take with food to minimize gastrointestinal upset
• Do not abruptly discontinue high-dose therapy after prolonged use
• Inform healthcare providers about all supplements being taken
• Dietary sources include citrus fruits, berries, tomatoes, potatoes, and leafy green vegetables
• Smoking and alcohol consumption may increase vitamin C requirements
• Store in a cool, dry place away from light (degrades with heat and light exposure)
• Chewable tablets may contribute to dental erosion; rinse mouth after use

References

1. National Institutes of Health. Vitamin C Fact Sheet for Health Professionals. 2021. 2. Levine M, et al. Vitamin C pharmacokinetics in healthy volunteers. Ann Intern Med. 1996;125(6):353-357. 3. Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9(11):1211. 4. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013;(1):CD000980. 5. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press; 2000. 6. FDA. Code of Federal Regulations Title 21. Sec. 182.8013 Ascorbic acid. 7. Michels AJ, Frei B. Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. Nutrients. 2013;5(12):5161-5192.