Mechanism of Action

Vitamin C functions through multiple biochemical pathways:

Primary Antioxidant Activity:

• Directly scavenges reactive oxygen species (ROS) including superoxide, hydroxyl radicals, and singlet oxygen
• Regenerates other antioxidants (vitamin E, glutathione) from their oxidized forms
• Protects lipids, proteins, and DNA from oxidative damage
• Maintains cellular redox balance in aqueous environments

Collagen Synthesis:

• Essential cofactor for prolyl 4-hydroxylase and lysyl hydroxylase enzymes
• Hydroxylates proline and lysine residues in procollagen chains
• Stabilizes collagen triple helix structure
• Critical for wound healing, blood vessel integrity, and connective tissue formation

Immune System Modulation:

• Enhances neutrophil chemotaxis and phagocytosis
• Supports natural killer (NK) cell activity
• Required for T-lymphocyte proliferation and antibody production
• Concentrates in immune cells at levels 50-100x higher than plasma

Iron Metabolism:

• Reduces ferric iron (Fe³⁺) to ferrous iron (Fe²⁺) for enhanced absorption
• Facilitates iron release from ferritin stores
• Protects against iron-induced oxidative damage
• Essential for optimal hemoglobin synthesis

Neurotransmitter Synthesis:

• Cofactor for dopamine β-hydroxylase (dopamine → norepinephrine conversion)
• Supports serotonin and GABA synthesis pathways
• Maintains neurotransmitter balance affecting mood and cognition

Potential Side Effects

Vitamin C is generally well-tolerated but can cause issues at high doses:

Gastrointestinal Effects (dose-dependent, >1000mg):

• Diarrhea, nausea, abdominal cramps
• Gastric irritation and acid reflux
• Bloating and flatulence
• "Bowel tolerance" varies individually (500mg-10g+)

Systemic Effects (rare, usually >2000mg daily):

• Kidney stone formation (oxalate stones) in predisposed individuals
• Iron overload in individuals with hemochromatosis
• Rebound scurvy upon sudden discontinuation after megadoses

Individual Sensitivity:

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis
• Individuals with kidney disease may accumulate oxalate
• Diabetics may experience blood glucose test interference

Contraindications & Warnings

Absolute Contraindications:

• Hemochromatosis or iron overload disorders
• Severe G6PD deficiency
• History of oxalate kidney stones (use caution with doses >1000mg)

Relative Contraindications:

• Chronic kidney disease (monitor oxalate levels)
• Sickle cell disease (may precipitate crisis in rare cases)
• Thalassemia (avoid with iron supplements)

Drug Interactions:

• Iron supplements: Enhances absorption (beneficial interaction)
• Warfarin: May reduce anticoagulant effect at very high doses
• Chemotherapy: May reduce effectiveness of some agents (theoretical concern)
• Acetaminophen: May reduce hepatotoxicity (protective effect)
• Aspirin: Increases vitamin C excretion, may require higher doses

Laboratory Interference:

• May cause false-negative glucose tests
• Can interfere with stool occult blood tests
• May affect some cholesterol measurements

Stacking Recommendations

Antioxidant Synergy:

• Vitamin E: 400-800 IU daily (vitamin C regenerates oxidized vitamin E)
• Glutathione: 250-500mg daily (mutual regeneration cycle)
• Alpha-lipoic acid: 100-300mg daily (universal antioxidant support)
• Selenium: 200mcg daily (supports glutathione peroxidase)

Immune Support Stack:

• Zinc: 15-30mg daily (synergistic immune effects)
• Vitamin D3: 2000-4000 IU daily (complementary immune modulation)
• Elderberry: 300-600mg daily during illness
• Probiotics: Multi-strain formula for gut-immune axis support

Iron Absorption Enhancement:

• Take vitamin C with iron-rich meals or iron supplements
• Combine with heme iron sources (red meat) for maximum effect
• Avoid with calcium or tea/coffee which inhibit iron absorption
• Consider for vegetarians/vegans with plant-based iron sources

Collagen Support:

• Collagen peptides: 10-20g daily with vitamin C
• Silica: 5-10mg daily for connective tissue
• Copper: 1-2mg daily (lysyl oxidase cofactor)
• Vitamin K2: 100mcg daily for bone matrix proteins

Timing Optimization:

• Divide doses throughout day (every 4-6 hours) due to short half-life
• Take with meals to reduce gastric irritation
• Higher doses in morning for energy/immune support
• Lower evening doses to avoid potential sleep disruption

Additional Content

Bioavailability Optimization: Vitamin C absorption follows a dose-dependent curve. At 200mg doses, ~90% is absorbed, dropping to ~70% at 500mg and ~50% at 1000mg+ doses. Time-release formulations may improve utilization.

Form Considerations:

• Ascorbic acid: Most cost-effective, may cause gastric irritation
• Sodium ascorbate: Better tolerated, suitable for sensitive stomachs
• Calcium/magnesium ascorbate: Buffered forms, provide additional minerals
• Liposomal vitamin C: Enhanced absorption and cellular uptake

Stress Response: Vitamin C requirements increase dramatically during physical or psychological stress, illness, smoking, and exposure to pollutants. Stress can deplete vitamin C stores rapidly, making supplementation beneficial during challenging periods.

The "Pauling Controversy": While Linus Pauling's megadose recommendations (10-18g daily) for disease prevention lack strong evidence, moderate supplementation (500-2000mg daily) shows consistent benefits for immune function and antioxidant protection.

Evolutionary Perspective: Humans lost the ability to synthesize vitamin C millions of years ago, making us dependent on dietary sources. Most mammals produce 1-20g daily endogenously, suggesting human requirements may be higher than current RDA recommendations (90mg for men, 75mg for women).

Quality Markers: Look for USP-verified products, third-party testing for purity, and appropriate packaging to protect from light and moisture. Vitamin C degrades rapidly when exposed to heat, light, and alkaline conditions.

Deficiency vs. Optimization: While scurvy (severe deficiency) is rare in developed countries, subclinical deficiency affecting immune function and collagen synthesis may be more common than recognized, particularly in smokers, elderly individuals, and those with limited fruit/vegetable intake.