Vitamin C
Vitamin C
Generic Name
Vitamin C
Mechanism
Vitamin C exerts its pharmacologic effects through several key mechanisms:
• Redox cycling:
• Serves as a reducing agent, donating electrons to neutralize reactive oxygen species (ROS).
• Regenerates other antioxidants (e.g., vitamin E, glutathione) in a cyclic antioxidant network.
• Collagen biosynthesis:
• Catalyzes hydroxylation of proline and lysine residues in procollagen, essential for stabilizing the triple‑helical structure.
• Immune modulation:
• Enhances neutrophil chemotaxis, phagocytosis, and oxidative burst.
• Maintains epithelial barrier integrity and supports lymphocyte proliferation.
• Drug interaction modulation:
• Chelates metal ions, potentially reducing iron‑overload toxicity.
• Inhibits cytochrome P450 2C9, affecting metabolism of certain drugs (e.g., warfarin).
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Pharmacokinetics
| Parameter | Details |
| Absorption | Oral absorption is saturable; peak plasma concentrations of ~0.1 mM achieved with 200 mg orally. Passive diffusion and sodium‑dependent vitamin C transporters (SVCT1/2) mediate intestinal uptake. |
| Distribution | Widely distributed; highest concentrations in the adrenal gland, spleen, and leukocyte cytosol. Plasma protein binding 80 % of an oral dose appears in urine within 24 h. Excessive doses (>4 g) lead to increased fractional excretion and risk of nephrolithiasis. |
| Half‑life | ~1–2 h in plasma; steady‑state achieved by 3–5 days of consistent supplementation. |
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Indications
- Deficiency (scurvy prevention/treatment) – 50–100 mg daily; severe deficiency requires 1–2 g orally for 10–14 days until lesions resolve.
- Adjunctive therapy for acute infections (e.g., common cold) – 500 mg–1 g orally twice daily; meta‑analyses suggest modest reduction in duration/ severity of cold symptoms.
- High‑dose IV therapy for COVID‑19 or sepsis – 50–200 mg/kg IV (often 1–6 g bolus) in clinical trials to achieve plasma ≥10 mM.
- Cancer adjunctive therapy – 1–4 g IV every 3–8 days; acts as a pro‑oxidant selectively in tumor cells.
- Gout prophylaxis – 2–3 g/day orally has been shown to lower serum urate by ~0.2–0.3 mg/dL.
- Chronic oxidative stress mitigation – 200–500 mg/day in patients with cardiovascular disease or diabetes (evidence mixed but widely used).
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Contraindications
- Renal impairment – Reduced excretion increases nephrolithiasis risk; dose reduction or avoid high‑dose IV.
- History of oxalate kidney stones – Vitamin C is metabolized to oxalate; high doses ↑ stone risk.
- Glucose‑6‑phosphate dehydrogenase (G6PD) deficiency – High doses may precipitate hemolysis.
- Hemochromatosis – Vitamin C increases iron absorption; caution in patients with iron overload.
- Pregnancy & lactation – Generally safe; avoid mega‑doses (>2 g/day) unless supervised.
- Anticoagulants – Potentially enhances vitamin K metabolism; monitor INR if on warfarin.
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Dosing
| Form | Typical Dose | Frequency | Comments |
| Oral (tablet/capsule) | 75–90 mg daily (RDA) | QD | Saturable absorption; limit to 200–400 mg/day for routine use. |
| Oral (high‑dose) | 1–5 g/day | Every other day | May cause GI upset, diarrhea; use micronized forms to improve tolerability. |
| IV (acute infections, COVID‑19) | 50–200 mg/kg | 1–3 h infusion | Requires monitoring of electrolytes and renal function. |
| IV (oncology) | 1–4 g bolus | Every 3–8 days | Aim for plasma >10 mM; check for oxalate nephrolithiasis. |
| Pediatric | 30–60 mg/kg/day | Divide into 2–3 doses | Adjust for renal function and weight. |
When administering oral high‑dose Vitamin C (>200 mg/day), micronized or fat‑soluble formulations reduce gastrointestinal dyspepsia.
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Adverse Effects
| Adverse effect | Frequency | Mitigation |
| Gastrointestinal upset (nausea, cramping) | Common | Splitting the dose; take with food. |
| Diarrhea | Common | Reduce dose; consider sustained‑release forms. |
| Nephrolithiasis (oxalate stones) | Rare (high‑dose) | Limit to 1 g/day. |
| Methemoglobinemia | Extremely rare | Monitor in infants, elderly, or those on oxidant drugs. |
| Allergic reactions (rash, pruritus) | Very rare | Discontinue and assess for true allergy. |
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Monitoring
- Renal function (serum creatinine, eGFR) before initiating high‑dose IV or in CKD.
- Urinalysis for oxalate crystals if high‑dose chronic therapy.
- Blood hemoglobin/hematocrit in patients with G6PD deficiency.
- Serum electrolytes (sodium, potassium, chloride) if IV therapy is prolonged.
- INR if patient is on warfarin and high‑dose Vitamin C is anticipated.
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Clinical Pearls
- Bioavailability plateau: Oral doses >200 mg do not proportionally raise plasma levels; IV administration is required for therapeutic plasma concentrations above 10 mM.
- Collagen‑rich tissues: Post‑operative wound healing is optimized when supplemental Vitamin C reaches 100–200 mg/day, especially in smokers and older adults.
- Antioxidant synergy: Co‑administration with vitamin E improves the recycling of vitamin E; synergistic effect may enhance endothelial function.
- Potential drug interaction: Vitamin C can displace cytochrome P450 2C9 substrates (e.g., phenytoin, warfarin) from protein binding sites; adjust doses accordingly.
- Pediatric dosing: The FDA recommends 30–40 mg/kg/day for children 1–12 yr; for 5 g/day may increase oxidative damage in tumor cells, offering a rationale for clinical oncology trials.
- Lifestyle integration: Consuming Vitamin C with a balanced diet rich in fruits and vegetables delivers synergistic phytochemical benefits and reduces the need for high‑dose supplementation.
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• References
1. Fawzi WW. *Vitamin C: The New Science.* Lippincott Williams & Wilkins, 2020.
2. Carr AC, et al. Randomised trials of vitamin C for upper respiratory tract infections. *BMJ* 2018;362:k2267.
3. Karchmar N., et al. Vitamin C in sepsis: a systematic review. *Crit Care Med* 2018;46:131–139.
4. National Institutes of Health Office of Dietary Supplements. Vitamin C Fact Sheet for Health Professionals, 2023.