Vitamin C, L-ASCORBIC ACID

What Is Vitamin C?

Vitamin C, chemically known as L-ascorbic acid, is a water-soluble essential nutrient that humans cannot synthesize internally. Unlike most mammals that produce vitamin C endogenously through the enzyme L-gulonolactone oxidase, humans lack functional expression of this enzyme due to evolutionary gene mutations ¹. This genetic loss occurred in primates, flying mammals, guinea pigs, and certain bird and fish species, creating absolute dietary dependence on external vitamin C sources.

The human body compensates for this biosynthetic inability through enhanced absorption efficiency, cellular recycling mechanisms, and renal reabsorption systems that exceed those found in vitamin C-synthesizing species ². These adaptations allow humans to maintain adequate vitamin C status despite relatively modest dietary intakes compared to the endogenous production rates observed in other mammals.

Molecular Structure and Chemistry

Vitamin C exists as L-ascorbic acid (the biologically active form) with the molecular formula C₆H₈O₆. The compound functions as an α-ketolactone with two enolic hydrogen atoms that provide electrons for its reducing capacity and antioxidant properties ³.

Ascorbic acid undergoes reversible oxidation to dehydroascorbic acid (DHA), the two-electron oxidation product. An intermediate one-electron oxidation produces the ascorbyl radical, which readily dismutates back to ascorbic acid and DHA. While both reduced and oxidized forms participate in biological processes, DHA can irreversibly degrade to 2,3-diketogulonic acid, permanently removing it from the vitamin C pool.

The D-form (isoascorbic or erythorbic acid) provides antioxidant activity but demonstrates little to no anti-scorbutic (scurvy-preventing) activity, highlighting the stereospecific requirements for vitamin C’s biological functions.

Chemical Forms and Bioavailability

Vitamin C supplements contain various chemical forms, each with distinct absorption characteristics, tolerability profiles, and cost considerations. Understanding these differences enables informed selection based on individual needs and physiological status.

Ascorbic Acid (Standard Form)

Plain ascorbic acid represents the most common and cost-effective supplemental form. Research demonstrates that synthetic ascorbic acid exhibits bioavailability equivalent to naturally occurring ascorbic acid from food sources ⁴.

Studies comparing ascorbic acid absorption from oranges, orange juice, cooked broccoli, and synthetic tablets found no appreciable differences in bioavailability when administered at physiologically relevant doses. This equivalence undermines marketing claims that “natural” vitamin C sources provide superior absorption compared to synthetic forms.

Mineral Ascorbates

Mineral ascorbates combine ascorbic acid with mineral salts, creating buffered forms with neutral pH that reduce gastrointestinal irritation in sensitive individuals:

Sodium Ascorbate

pH neutral formulation
111 mg sodium per 1,000 mg vitamin C
Consider sodium content for individuals on sodium-restricted diets

Calcium Ascorbate

Buffered, non-acidic form
90-110 mg calcium per 1,000 mg vitamin C
Provides supplemental calcium benefit
May reduce gastric distress compared to ascorbic acid

Ester-C (Calcium Ascorbate with Metabolites)

Ester-C represents a patented formulation containing calcium ascorbate combined with small amounts of vitamin C metabolites including dehydroascorbic acid, calcium threonate, xylonate, and lyxonate. Manufacturers claim enhanced bioavailability based on the presence of these metabolites.

Research findings present a mixed picture. One small study in eight women and one man found no differences between Ester-C and standard ascorbic acid tablets regarding absorption and urinary excretion ⁵. However, another investigation reported that Ester-C produced significantly higher leukocyte vitamin C concentrations 24 hours post-ingestion compared to plain ascorbic acid, despite similar plasma levels ⁶.

The limited published research and lack of independent verification of proprietary claims make definitive conclusions difficult. Given the substantially higher cost of Ester-C compared to ascorbic acid, the marginal potential benefits may not justify the premium for most consumers.

Liposomal Vitamin C

Liposomal formulations encapsulate ascorbic acid within phospholipid bilayers, theoretically enhancing cellular uptake and retention. Proponents claim superior bioavailability, particularly at higher doses where standard vitamin C absorption becomes saturated.

Limited published research examines liposomal vitamin C bioavailability in humans. One study comparing liposomal-encapsulated vitamin C to standard ascorbic acid found that the liposomal form produced higher plasma concentrations and appeared to provide protection against ischemia-reperfusion injury ⁷.

However, the clinical significance of these findings remains unclear, and the substantially higher cost of liposomal preparations may not provide proportional benefits for individuals with normal absorption capacity.

Ascorbyl Palmitate

Ascorbyl palmitate represents a fat-soluble vitamin C ester formed by combining ascorbic acid with palmitic acid. This form primarily serves as a food preservative to prevent oxidation in vegetable oils and processed foods rather than as a dietary supplement.

Ascorbyl palmitate demonstrates poor conversion to free ascorbic acid in the body and should not be confused with Ester-C despite both being marketed as “vitamin C esters.”

Bioavailability Comparison Summary

A 2025 systematic review evaluating enhanced vitamin C delivery forms concluded that calcium ascorbate combined with metabolites (Ester-C) demonstrated better tolerability and fewer gastrointestinal adverse events compared to standard ascorbic acid ⁸. Several studies reported more favorable plasma and leukocyte vitamin C concentrations with alternative forms, though the clinical significance of these differences remains uncertain.

For most healthy individuals, standard ascorbic acid provides effective and economical vitamin C supplementation. Alternative forms may benefit those experiencing gastrointestinal intolerance or seeking marginally enhanced leukocyte uptake, though the additional cost should be weighed against the modest potential advantages.

Absorption Mechanisms and Transport

Vitamin C absorption and distribution involve complex, dose-dependent mechanisms that tightly regulate tissue and plasma concentrations through specialized transport proteins and renal regulation systems.

Intestinal Absorption

Vitamin C absorption occurs through both active transport and passive diffusion mechanisms, with the relative contribution of each pathway depending on dose magnitude ⁹.

Active Transport (Low to Moderate Doses)

At dietary intake levels between 30-180 mg per dose, sodium-dependent vitamin C transporters (SVCTs) facilitate 70-90% absorption efficiency. Two SVCT isoforms mediate this process:

SVCT1: Primarily expressed in intestinal epithelial cells, kidney proximal tubules, and epithelial barriers. Functions in bulk vitamin C absorption and renal reabsorption.
SVCT2: Widely distributed in metabolically active tissues including brain, eyes, adrenal glands, and leukocytes. Facilitates cellular vitamin C accumulation in specialized tissues.

These sodium-dependent transporters become saturated at higher concentrations, limiting absorption efficiency as dosage increases ¹⁰.

Passive Diffusion (High Doses)

At supplemental doses exceeding 1,000 mg, SVCT saturation reduces active transport efficiency to approximately 50% or less. Passive diffusion across concentration gradients provides the remaining absorption, though this mechanism demonstrates significantly lower efficiency than active transport.

The dose-dependent absorption curve creates a ceiling effect where increasing oral vitamin C beyond certain thresholds produces diminishing returns in plasma concentration. At single doses of 1,000 mg or higher, the fraction absorbed continues to decline, with most excess vitamin C appearing in feces or urine.

Dehydroascorbic Acid Transport

The oxidized form of vitamin C (DHA) crosses cell membranes through glucose transporters (GLUT1, GLUT3, GLUT4) rather than through SVCTs ¹¹. Once inside cells, DHA undergoes rapid reduction back to ascorbic acid through NADH-dependent and glutathione-dependent mechanisms.

This cellular recycling system allows efficient vitamin C recovery from oxidative environments and may explain why ascorbic acid and DHA demonstrate similar bioavailability when consumed orally. The presence of glucose can competitively inhibit DHA uptake through glucose transporters, potentially reducing vitamin C absorption when consumed with high-carbohydrate meals.

Cellular Uptake and Distribution

Once absorbed into the bloodstream, vitamin C distributes throughout tissues with dramatic concentration gradients:

High-Concentration Tissues (>1.0 mM)

Pituitary and adrenal glands (highest concentrations)
Leukocytes and immune cells
Eye lens and aqueous humor
Brain and nervous tissue

Moderate-Concentration Tissues (0.2-1.0 mM)

Liver and kidneys
Pancreas
Skeletal muscle

Low-Concentration Compartments (<0.2 mM)

Plasma (maintained at 50-80 µM at saturation)
Saliva and other secretions

These tissue-specific concentrations reflect differential SVCT2 expression and the metabolic demands of various organs. Tissues with high oxidative stress or specialized biosynthetic functions (collagen synthesis, neurotransmitter production) accumulate higher vitamin C concentrations.

Renal Regulation and Excretion

The kidneys play a critical role in vitamin C homeostasis through filtration and reabsorption mechanisms. Ascorbic acid undergoes glomerular filtration, then SVCT1-mediated reabsorption in proximal tubules reclaims filtered vitamin C to maintain plasma concentrations.

At plasma concentrations below the renal threshold (approximately 80 µM), reabsorption efficiency approaches 100%, conserving vitamin C during low intake periods. When plasma levels exceed this threshold, renal reabsorption becomes saturated, and excess vitamin C appears in urine ¹².

This renal regulation creates the dose-response plateau observed in pharmacokinetic studies: oral doses beyond 200-400 mg per administration produce minimal additional plasma concentration increases because excess vitamin C undergoes rapid urinary excretion.

Bioavailability Saturation Point

Research indicates that plasma and cellular vitamin C concentrations plateau at oral doses of 200-400 mg per administration ¹³. Doses exceeding this range produce increasingly inefficient absorption and greater urinary elimination.

For individuals seeking to maximize vitamin C status, dividing large doses into multiple smaller administrations (e.g., 200 mg three times daily rather than 600 mg once daily) optimizes absorption and tissue saturation while minimizing waste through urinary excretion.

Recommended Daily Intake and Dosing

Vitamin C intake recommendations vary substantially across international health authorities, reflecting different philosophical approaches to defining optimal nutrient status—from minimal amounts preventing deficiency to higher intakes targeting health optimization.

Official Dietary Recommendations

The United States Institute of Medicine established current Recommended Dietary Allowances (RDAs) based on vitamin C intake necessary to maintain near-maximal neutrophil concentrations with minimal urinary excretion ¹⁴:

Adult RDAs

Men: 90 mg/day
Women: 75 mg/day
Pregnancy: 85 mg/day
Lactation: 120 mg/day
Smokers: Add 35 mg/day to baseline recommendation

Pediatric RDAs

Infants 0-6 months: 40 mg/day (AI)
Infants 7-12 months: 50 mg/day (AI)
Children 1-3 years: 15 mg/day
Children 4-8 years: 25 mg/day
Children 9-13 years: 45 mg/day
Adolescents 14-18 years: 65-75 mg/day (gender-specific)

These recommendations target antioxidant protection and physiological function rather than simply preventing scurvy, which requires only 10 mg daily for clinical manifestation prevention.

International Recommendation Disparities

Global vitamin C recommendations range from 45 mg/day (some European countries targeting scurvy prevention) to 200 mg/day (authorities emphasizing health optimization) ¹⁵. This five-fold variation reflects fundamental disagreements about appropriate criteria for establishing nutrient requirements:

Prevention-Focused Approach (45-60 mg/day)

Prevents clinical scurvy with safety margin
Based on minimal tissue saturation
Adopted by several European nations

Function-Optimization Approach (90-110 mg/day)

Maintains near-maximal immune cell concentrations
Provides antioxidant protection
Current U.S., Canadian, and Australian standard

Health-Maximization Approach (200+ mg/day)

Saturates plasma and tissues
Maximizes potential disease prevention benefits
Advocated by some researchers based on pharmacokinetic data

Smokers and Secondhand Smoke Exposure

Cigarette smoking substantially increases vitamin C requirements through multiple mechanisms:

Enhanced oxidative stress depleting vitamin C reserves
Increased metabolic turnover and degradation
Lower plasma and leukocyte vitamin C concentrations

Studies consistently demonstrate that smokers maintain 10-40% lower plasma vitamin C levels compared to nonsmokers despite similar dietary intakes ¹⁶. The additional 35 mg/day recommendation for smokers attempts to compensate for these increased losses and restore plasma concentrations to non-smoker levels.

Individuals exposed to secondhand smoke demonstrate intermediate vitamin C status between active smokers and unexposed nonsmokers, suggesting they may also benefit from modestly increased intake, though specific recommendations for this population remain undefined.

Tolerable Upper Intake Levels

The Institute of Medicine established a Tolerable Upper Intake Level (UL) of 2,000 mg/day for adults based on gastrointestinal disturbances observed at higher doses ¹⁷. This UL represents the maximum daily intake unlikely to cause adverse effects in the general population.

Age-Specific Upper Limits

Children 1-3 years: 400 mg/day
Children 4-8 years: 650 mg/day
Children 9-13 years: 1,200 mg/day
Adolescents 14-18 years: 1,800 mg/day
Adults 19+ years: 2,000 mg/day

Vitamin C demonstrates remarkably low toxicity, and the UL primarily targets gastrointestinal symptoms (osmotic diarrhea, nausea, abdominal cramping) rather than serious adverse effects. Most individuals tolerate doses below 2,000 mg daily without difficulty, though individual tolerance varies.

Optimal Dosing for Health Maintenance

Pharmacokinetic research suggests that plasma and cellular vitamin C saturation occurs at daily intakes of 200-400 mg divided into multiple doses ¹⁸. Beyond this threshold, additional vitamin C undergoes increasingly efficient renal excretion with minimal further increases in tissue concentrations.

For individuals seeking to maximize vitamin C status while avoiding waste:

Evidence-Based Dosing Strategy

Target total daily intake: 200-500 mg
Divide into 2-3 doses throughout the day
Consume with or without food (absorption not significantly affected)
Combine dietary sources with supplements as needed

This approach achieves near-maximal tissue saturation while remaining well below upper safety limits and optimizing absorption efficiency.

Collagen Synthesis and Wound Healing

Vitamin C serves as an essential cofactor for enzymes involved in collagen biosynthesis, making it indispensable for wound healing, tissue repair, and maintenance of structural integrity throughout the body.

Molecular Role in Collagen Formation

Collagen synthesis requires vitamin C as a cofactor for two critical hydroxylase enzymes ¹⁹:

Prolyl Hydroxylase

Catalyzes hydroxylation of proline residues to hydroxyproline
Hydroxyproline stabilizes collagen triple helix structure through additional hydrogen bonding
Without adequate vitamin C, prolyl hydroxylase activity decreases
Non-hydroxylated collagen demonstrates poor structural stability and rapid degradation

Lysyl Hydroxylase

Catalyzes hydroxylation of lysine residues to hydroxylysine
Hydroxylysine enables cross-linking between collagen molecules
Cross-linking provides tensile strength to collagen fibers
Inadequate hydroxylation produces weak, friable connective tissue

These enzymatic reactions require vitamin C in its reduced (ascorbic acid) form to maintain the iron cofactor in these enzymes in its active ferrous (Fe²⁺) state. Vitamin C deficiency leads to accumulation of non-functional ferric (Fe³⁺) iron, effectively inactivating the hydroxylases and halting collagen maturation.

Wound Healing Mechanisms

Vitamin C participates in all phases of the wound healing process—inflammatory, proliferative, and remodeling—through multiple distinct mechanisms ²⁰.

Inflammatory Phase

Promotes neutrophil apoptosis and clearance, facilitating transition to healing
Reduces excessive inflammatory mediator production
Protects cells from reactive oxygen species generated during inflammatory response
Supports immune cell function at the wound site

Proliferative Phase

Stimulates fibroblast proliferation and migration to wound area
Enhances collagen synthesis by activated fibroblasts
Promotes angiogenesis (new blood vessel formation) to supply oxygen and nutrients
Supports keratinocyte differentiation and epidermal barrier reformation

Remodeling Phase

Facilitates collagen fiber organization and cross-linking
Supports scar tissue maturation and strength development
Assists in degradation and replacement of provisional wound matrix

Vitamin C concentrations decline rapidly at wound sites, with tissue levels dropping 60-70% below normal and remaining depressed for at least 14 days post-injury ²¹. This depletion reflects both increased local consumption for collagen synthesis and loss of vitamin C to oxidative stress from inflammatory free radicals.

Clinical Evidence for Supplementation in Wound Healing

Research on vitamin C supplementation and wound healing presents a nuanced picture dependent on baseline vitamin C status:

Deficient or Marginally Deficient Individuals

Vitamin C supplementation demonstrates clear benefits for wound closure time
Restoration of normal vitamin C status reverses impaired healing
Studies in populations with low baseline status (smokers, elderly, malnourished) show significant improvements ²²

Vitamin C-Sufficient Individuals

Supplementation beyond adequate status shows minimal effect on wound closure time
Surgical wound healing in well-nourished patients does not improve with high-dose vitamin C
Some measures of collagen synthesis may improve, but clinical outcomes remain unchanged

A systematic review of vitamin C supplementation for musculoskeletal healing found that while preclinical studies demonstrated accelerated bone healing and increased collagen synthesis, human clinical evidence remains limited ²³. The available human studies suggest potential benefits but lack sufficient power and methodological rigor for definitive conclusions.

Practical Implications for Wound Healing

For individuals undergoing surgery or managing wounds:

Evidence-Based Recommendations

Ensure adequate vitamin C status before elective surgery (≥90 mg/day dietary intake)
At-risk populations (smokers, elderly, restricted diets) may benefit from supplementation to 200-500 mg/day
Individuals with confirmed vitamin C deficiency require repletion before optimal healing occurs
Well-nourished individuals likely gain minimal benefit from megadose supplementation

The dramatic improvements in wound healing observed with vitamin C repletion in deficient individuals underscore its critical importance, while the absence of benefit in sufficient individuals highlights that more is not necessarily better beyond achieving adequate status.

Immune Function and Respiratory Infections {#immune-function}

Vitamin C supports multiple aspects of immune system function, though its effectiveness for preventing and treating infectious diseases varies considerably depending on population characteristics and clinical context.

Mechanisms of Immune Support

Vitamin C accumulates in immune cells at concentrations 50-100 times higher than plasma levels, suggesting functional importance for immune processes ²⁴. The vitamin contributes to immune defense through several pathways:

Innate Immunity Enhancement

Supports neutrophil chemotaxis and phagocytosis
Enhances natural killer cell activity
Protects immune cells from oxidative self-damage during respiratory burst
Promotes neutrophil apoptosis and clearance, preventing excessive inflammation

Adaptive Immunity Support

Stimulates lymphocyte proliferation
Enhances T-cell and B-cell differentiation
Supports antibody production
Modulates cytokine production to balance inflammatory responses

Epithelial Barrier Function

Maintains skin barrier integrity
Supports mucosal immune function
Enhances epithelial cell differentiation

Vitamin C concentrations in plasma and leukocytes decline rapidly during infections and physiological stress, potentially impairing immune function if not adequately replenished ²⁵.

Common Cold: Prevention and Treatment

Decades of research have established vitamin C’s limited but measurable effects on common cold incidence and duration in specific populations.

Incidence (Prevention)

Regular vitamin C supplementation does not reduce common cold incidence in the general population. A meta-analysis of eight randomized controlled trials involving 8,472 subjects demonstrated “very strong evidence” that vitamin C intake above 80 mg/day does not prevent colds in healthy adults and children ²⁶.

However, specific populations demonstrate different outcomes:

Populations with Reduced Incidence

Individuals under extreme physical stress (marathon runners, soldiers, skiers)
Studies in these groups show approximately 50% reduction in cold incidence with prophylactic vitamin C ²⁷
Benefit likely reflects compensation for stress-induced vitamin C depletion

Duration and Severity (Treatment)

When administered prophylactically (before cold onset), vitamin C produces modest but consistent reductions in cold duration and severity:

Children: 18% reduction in duration
Adults: 8% reduction in duration
Overall severity reduction: 15% across studies ²⁸

Therapeutic administration (starting after symptom onset) demonstrates limited effectiveness in most studies, though some trials using very high initial doses (hourly administration for the first 6 hours, then three times daily) reported greater symptom reduction ²⁹.

COVID-19 and Acute Respiratory Infections

The COVID-19 pandemic renewed interest in vitamin C’s potential therapeutic role in severe respiratory infections. Research findings present a complex picture:

Observational and Mixed-Quality Studies

An early meta-analysis of 19 trials (including both randomized and non-randomized studies) found vitamin C supplementation associated with reduced in-hospital mortality in COVID-19 patients (24.1% vs. 33.9%, OR = 0.59) ³⁰.

However, this analysis faced significant limitations:

High heterogeneity among included studies
Mixed quality of evidence
Inclusion of non-randomized trials
Varied vitamin C doses and administration routes

High-Quality Randomized Controlled Trials

More recent analyses restricted to randomized controlled trials failed to replicate these benefits. A 2024 systematic review of RCTs found that vitamin C supplementation did not significantly reduce in-hospital mortality or ICU stay duration in COVID-19 patients ³¹.

The discrepancy between early observational studies and rigorous RCTs likely reflects:

Selection bias in observational cohorts
Placebo effects and confounding variables
Publication bias favoring positive results in early pandemic research

Pneumonia and Severe Infections

Evidence for vitamin C in pneumonia prevention and treatment remains insufficient despite decades of investigation. A meta-analysis of seven clinical studies (2,774 participants) concluded that current evidence cannot support vitamin C supplementation for preventing or treating pneumonia due to limited trial numbers and very low study quality ³².

Studies conducted in specific populations (military personnel, individuals in developing countries) showed some benefits, but these findings may not generalize to well-nourished civilian populations in developed nations.

Practical Implications for Immune Health

Current evidence supports the following evidence-based approach to vitamin C for immune function:

General Population

Maintain adequate dietary intake (90-120 mg/day) through fruits and vegetables
No evidence supports prophylactic supplementation for healthy, well-nourished individuals
Regular supplementation provides no protection against common cold incidence

At-Risk Populations

Athletes and individuals under extreme physical stress: 200-500 mg/day may reduce respiratory infection incidence
Smokers: Ensure intake meets elevated requirements (125-110 mg/day)
Elderly and institutionalized individuals: Supplementation to 100-200 mg/day if dietary intake inadequate

During Infection

Vitamin C requirements increase during acute illness
Modest supplementation (200-500 mg/day) may slightly reduce cold duration if started before symptoms
Very high-dose therapy lacks evidence in general outpatient populations
Severely ill hospitalized patients: Intravenous administration under medical supervision may warrant investigation

The immune-supporting effects of vitamin C appear most pronounced in individuals with suboptimal baseline status or under extraordinary physiological stress, rather than providing benefit to already-sufficient individuals.

Antioxidant Properties

Vitamin C functions as the primary water-soluble, non-enzymatic antioxidant in plasma and tissues, protecting against oxidative damage through direct free radical scavenging and supporting other antioxidant systems.

Free Radical Scavenging

As a potent reducing agent, vitamin C readily donates electrons to neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS) in aqueous environments ³³:

Reactive Species Neutralized

Superoxide radical (O₂•⁻)
Hydroxyl radical (•OH)
Peroxyl radicals (ROO•)
Singlet oxygen (¹O₂)
Hypochlorous acid (HOCl)
Peroxynitrite (ONOO⁻)

During this scavenging process, ascorbic acid oxidizes to the ascorbyl radical, a relatively stable intermediate that can be regenerated back to ascorbic acid through enzymatic and non-enzymatic mechanisms. This regeneration capacity allows a single vitamin C molecule to participate in multiple antioxidant reactions before ultimate degradation.

Protection of Biomolecules

Vitamin C protects critical cellular components from oxidative damage:

Lipid Protection

Prevents lipid peroxidation in membranes
Reduces oxidized LDL cholesterol formation
Protects polyunsaturated fatty acids from free radical attack
Regenerates membrane-bound vitamin E from its oxidized form

Protein Protection

Prevents oxidative modification of amino acid residues
Maintains enzyme function by preventing oxidative inactivation
Protects structural proteins from cross-linking damage

DNA Protection

Scavenges reactive species before DNA damage occurs
Reduces oxidative base modifications
Supports DNA repair enzyme function

Studies measuring urinary F₂-isoprostanes (markers of in vivo lipid peroxidation) demonstrate that vitamin C supplementation can reduce oxidative stress markers in populations with elevated oxidative burden ³⁴.

Interaction with Other Antioxidants

Vitamin C participates in antioxidant networks that regenerate other oxidized antioxidant molecules:

Vitamin E Regeneration

Vitamin E (α-tocopherol) neutralizes lipid peroxyl radicals in membranes
This oxidizes vitamin E to the tocopheroxyl radical
Vitamin C reduces tocopheroxyl radical back to active vitamin E
This sparing effect extends vitamin E’s antioxidant capacity

Glutathione System Support

Vitamin C can reduce oxidized glutathione (GSSG) back to reduced glutathione (GSH)
Supports cellular glutathione pools during oxidative stress
Enhances overall cellular antioxidant capacity

Transition Metal Chelation

Binds free iron and copper ions
Prevents metal-catalyzed free radical formation (Fenton reaction)
Reduces hydroxyl radical generation from hydrogen peroxide

Pro-Oxidant Potential

Under specific conditions, vitamin C can exhibit pro-oxidant activity, generating rather than quenching free radicals:

Metal-Catalyzed Reactions

In the presence of free iron or copper, vitamin C can reduce these metals
Reduced metals catalyze hydrogen peroxide conversion to hydroxyl radicals
This pro-oxidant effect primarily occurs in vitro or in pathological conditions with metal overload

Clinical Relevance

Individuals with hemochromatosis or iron overload should exercise caution with high-dose vitamin C
In healthy individuals, cellular metal-binding proteins sequester transition metals, preventing pro-oxidant reactions
The pro-oxidant potential represents a theoretical concern rather than a common clinical problem in normal physiology

Antioxidant Limitations

Despite vitamin C’s antioxidant properties, supplementation beyond adequate status does not necessarily reduce disease risk in well-nourished populations:

Large-scale trials of antioxidant supplementation (including vitamin C) have not consistently demonstrated cardiovascular disease or cancer risk reduction
Baseline oxidative stress status determines whether additional antioxidant capacity provides benefit
Individuals with low dietary intake or increased oxidative burden likely benefit more than sufficient individuals
Very high plasma concentrations achieved through supplementation may not translate to proportional tissue-level antioxidant protection

The antioxidant benefits of vitamin C appear most significant in preventing deficiency-related oxidative damage and supporting individuals under conditions of elevated oxidative stress, rather than providing additional protection to already-sufficient, healthy individuals.

Interactions and Contraindications

Vitamin C interacts with numerous medications and nutrients, requiring consideration for individuals with specific health conditions or taking certain drugs.

Enhanced Iron Absorption

Vitamin C substantially increases non-heme iron absorption from plant-based foods through multiple mechanisms ³⁵:

Mechanisms

Reduces ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), the more readily absorbed form
Chelates iron, maintaining solubility in the alkaline small intestine
Prevents formation of insoluble iron complexes with phytates and tannins
Enhances iron uptake through enterocyte transporters

Clinical Implications

This interaction provides therapeutic benefit for individuals with iron deficiency anemia, particularly those consuming primarily plant-based diets. Consuming vitamin C-rich foods or supplements with iron-containing meals significantly improves iron status.

However, individuals with hemochromatosis or other iron overload conditions should avoid high-dose vitamin C supplementation, as enhanced iron absorption may exacerbate tissue iron accumulation and oxidative damage ³⁶.

Medication Interactions

Chemotherapy and Radiation Therapy

High-dose vitamin C may theoretically interfere with cancer treatments that rely on oxidative stress to kill tumor cells. However, research presents conflicting evidence:

Some studies suggest vitamin C protects tumor cells from oxidative damage
Other research indicates vitamin C selectively protects normal tissues while enhancing treatment effects on cancer cells
The interaction likely depends on vitamin C dose, administration route (oral vs. intravenous), cancer type, and specific treatment regimen

Cancer patients should consult their oncologist before taking high-dose vitamin C supplements during active treatment ³⁷.

Statins (HMG-CoA Reductase Inhibitors)

Limited evidence suggests vitamin C might interact with certain statin medications:

Combination of simvastatin-niacin with antioxidants (vitamin C, vitamin E, selenium, beta-carotene) blunted HDL increases in one study
Clinical significance remains uncertain
Most cardiologists do not restrict reasonable vitamin C intake in statin-treated patients

Warfarin (Anticoagulant)

Very high doses of vitamin C (>1,000 mg/day) may decrease warfarin effectiveness in some individuals, though evidence is limited and inconsistent. Patients taking warfarin should maintain consistent vitamin C intake and monitor INR if changing supplementation substantially.

Aluminum-Containing Antacids

Vitamin C increases aluminum absorption from antacids. Individuals with kidney disease, who are at risk for aluminum accumulation, should separate vitamin C supplementation from aluminum-containing antacid use by several hours.

Kidney Stone Risk

Vitamin C undergoes partial metabolism to oxalate, raising theoretical concerns about increased kidney stone formation. Research findings provide reassurance for most individuals:

Evidence Assessment

Population studies find no consistent association between vitamin C intake and kidney stone risk in individuals without predisposing conditions
One large prospective study found modestly increased risk only at very high intakes (≥1,000 mg/day) in men with history of kidney stones
Women in the same study showed no increased risk at any vitamin C intake level ³⁸

Risk Factors for Stone Formation

Personal or family history of calcium oxalate kidney stones
Conditions causing increased urinary oxalate excretion
Dehydration and low fluid intake
High dietary oxalate consumption

Practical Recommendations

Individuals with no kidney stone history: No special precautions needed at doses <2,000 mg/day
Those with stone history: Consider limiting supplemental vitamin C to <500 mg/day
All individuals: Maintain adequate hydration to dilute urinary oxalate

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Individuals with G6PD deficiency face increased hemolysis risk from high-dose vitamin C. Case reports document severe hemolytic anemia following intravenous vitamin C administration in G6PD-deficient patients ³⁹.

Oral vitamin C at physiological doses appears safe for most G6PD-deficient individuals, but high-dose supplementation (>1,000 mg/day) requires caution. Intravenous administration should be avoided unless G6PD deficiency has been ruled out.

Rebound Scurvy

Prolonged very high-dose vitamin C supplementation (>1,000 mg/day for months) may cause “rebound scurvy” upon sudden discontinuation. This phenomenon occurs because:

Chronic high vitamin C intake upregulates degradation enzymes
Cellular transport systems may downregulate
Abrupt cessation leaves these adaptive mechanisms in place
Relative deficiency develops despite adequate dietary intake

Individuals discontinuing long-term high-dose supplementation should taper gradually over several weeks rather than stopping abruptly.

Special Population Considerations

Pregnancy and Lactation

Vitamin C crosses the placenta and appears in breast milk
Recommended intakes increase modestly (85 mg pregnancy, 120 mg lactation)
Very high doses (>400 mg/day) during pregnancy may cause vitamin C dependency in newborns
Stick to moderate supplementation if dietary intake inadequate

Chronic Kidney Disease

Impaired vitamin C excretion may increase oxalate accumulation risk
Reduced doses (60-100 mg/day) typically recommended
Monitor for oxalate nephropathy with high-dose supplementation

Sickle Cell Disease

Limited evidence suggests high-dose vitamin C may worsen sickling in some patients
More research needed to clarify this potential interaction

Deficiency and Scurvy

Vitamin C deficiency manifests along a spectrum from subclinical inadequacy to frank scurvy, the potentially fatal endpoint of severe, prolonged deficiency.

Biochemical Thresholds

Vitamin C status correlates with plasma ascorbic acid concentrations:

Status Categories

Adequate: >50 µM (>11 mg/L)
Marginal deficiency: 11-28 µM (2-6 mg/L)
Depletion: <11 µM (<2 mg/L)
Scurvy risk: <11 µM with clinical manifestations

Plasma concentrations below 11 µM indicate depleted body pools and increased scurvy risk, though clinical symptoms may not appear until concentrations fall below 6 µM ⁴⁰.

Clinical Manifestations of Scurvy

Scurvy develops after 1-3 months of vitamin C intake below 10 mg/day, though individual susceptibility varies. The disease primarily affects connective tissue, blood vessels, and immune function due to impaired collagen synthesis.

Early Symptoms (appear at 1-3 months of deficiency)

Fatigue and weakness
Irritability and depression
Myalgia (muscle pain)
Joint pain and swelling

Dermatologic Signs

Perifollicular hemorrhage (bleeding around hair follicles)
Perifollicular hyperkeratosis (rough, bumpy skin)
Corkscrew hairs and fragile, coiled hair shafts
Purpura and ecchymoses (bruising)
Poor wound healing

Gingival Changes

Swollen, bleeding gums (gingivitis)
Loosening of teeth
Tooth loss in severe cases
Occurs only in dentate individuals (those with teeth)

Advanced Manifestations

Extensive subcutaneous and intramuscular hemorrhages
Hemarthrosis (bleeding into joints)
Subperiosteal hemorrhages in children
Anemia (from impaired iron absorption and bleeding)
Edema in dependent areas
Delayed wound healing and wound dehiscence

Life-Threatening Complications

Severe anemia from chronic blood loss
Dyspnea and heart failure
Increased infection susceptibility
Death from bleeding or infection if untreated

Vulnerable Populations

Scurvy remains rare in developed countries but occurs in specific at-risk groups:

High-Risk Populations

Elderly individuals on very restricted diets
Individuals with alcohol use disorder
People with severe mental illness and dietary neglect
Patients with malabsorption syndromes
Individuals following extreme elimination diets
Infants fed improperly prepared formula or boiled milk
Low-income individuals with limited access to fresh produce

Case reports document scurvy in developed nations among individuals consuming diets devoid of fruits and vegetables for extended periods, highlighting that deficiency remains a clinical reality even in resource-rich settings ⁴¹.

Treatment and Recovery

Scurvy responds rapidly to vitamin C repletion:

Treatment Protocol

Immediate: 100-300 mg vitamin C daily (oral or parenteral)
Clinical improvement begins within 24-48 hours
Hemorrhages resolve within days to weeks
Fatigue and weakness improve within 24 hours
Gingival changes resolve over 1-2 weeks
Complete recovery: 1-3 months depending on severity

Even individuals with advanced scurvy demonstrate remarkable recovery with appropriate vitamin C administration. The dramatic response to treatment serves as both diagnostic confirmation and therapeutic intervention.

Subclinical Deficiency

Marginal vitamin C deficiency (plasma levels 11-28 µM) produces subtle impairments before frank scurvy develops:

Reduced immune function and increased infection susceptibility
Impaired wound healing
Easy bruising
Fatigue and reduced exercise tolerance
Mood changes and reduced wellbeing

These non-specific symptoms overlap with numerous other conditions, making diagnosis challenging without laboratory assessment. Populations at risk for marginal deficiency (smokers, elderly, individuals with poor dietary variety) may benefit from dietary assessment and supplementation to ensure adequate status.

Quality Considerations and Testing

Vitamin C supplement quality varies substantially across manufacturers, with factors including chemical form, stability, contaminant screening, and manufacturing standards affecting both safety and efficacy.

Manufacturing Quality Standards

Reputable vitamin C supplements should demonstrate compliance with Good Manufacturing Practices (GMP) and ideally carry third-party certification:

Key Quality Certifications

USP Verified: Confirms ingredient identity, potency, purity, and dissolution; includes facility audits
NSF Certified: Verifies label accuracy, contaminant testing, and manufacturing quality
Informed Choice: Banned substance testing for athletes
ConsumerLab Approved: Independent retail product testing for quality and label accuracy

These certifications provide assurance that products contain stated amounts of vitamin C, meet purity standards, and undergo regular testing. For more details on supplement testing standards, see our comprehensive supplement certifications comparison.

Stability and Degradation

Vitamin C demonstrates notable instability, degrading upon exposure to oxygen, light, heat, and alkaline pH. Supplement stability depends on formulation and storage:

Factors Affecting Stability

Moisture content in tablets (low moisture essential)
Packaging type (opaque, moisture-resistant preferred)
Storage temperature (cool, dry conditions extend shelf life)
Tablet coating and excipients
Chemical form (mineral ascorbates generally more stable than ascorbic acid)

Quality manufacturers employ stability testing to establish appropriate expiration dates and formulate products to maintain potency throughout shelf life. Expired vitamin C supplements demonstrate reduced potency but generally pose no safety hazard.

Contaminant Screening

High-quality vitamin C supplements undergo testing for potential contaminants:

Tested Contaminants

Heavy metals (lead, mercury, cadmium, arsenic)
Microbiological contamination (bacteria, yeast, mold)
Pesticide residues (for plant-derived sources)
Residual solvents from manufacturing

Third-party certified products provide greatest assurance of contaminant testing, as certification bodies verify analytical results rather than relying solely on manufacturer claims. For more information on independent testing versus in-house claims, see our guide to independent laboratory testing.

Bioavailability Testing

While most vitamin C forms demonstrate similar bioavailability at physiological doses, enhanced formulations claim superior absorption. High-quality manufacturers should provide:

Human pharmacokinetic studies (not just animal or in vitro data)
Peer-reviewed publication of bioavailability claims
Comparison to standard ascorbic acid under controlled conditions
Disclosure of study funding sources and potential conflicts

Marketing claims about “superior absorption” frequently lack rigorous human evidence. Consumers should seek products with published bioavailability data to substantiate premium pricing for specialty formulations.

Synthetic vs. Natural Source

Synthetic L-ascorbic acid demonstrates chemical and biological equivalence to naturally-derived vitamin C. The molecular structure is identical, and absorption, distribution, and function show no meaningful differences ⁴².

Marketing emphasizing “natural” or “food-based” vitamin C sources often commands premium pricing without providing additional benefits for most consumers. Some individuals prefer whole-food sources for philosophical reasons or to obtain accompanying phytonutrients, but the vitamin C itself functions identically regardless of origin.

Selecting Quality Vitamin C Supplements

For consumers seeking high-quality vitamin C supplements:

Evidence-Based Selection Criteria

Third-party certification (USP, NSF, ConsumerLab, or Informed Choice)
Transparent manufacturing information and batch testing
Appropriate packaging (opaque, moisture-resistant containers)
Published bioavailability data for specialty formulations
Reasonable pricing relative to vitamin C content
No unsubstantiated claims about superiority over standard forms

Standard ascorbic acid from a reputable, certified manufacturer provides effective, economical vitamin C supplementation for most individuals. Specialty forms may benefit those experiencing gastrointestinal intolerance or specific absorption challenges, but should demonstrate evidence supporting claimed advantages.

Frequently Asked Questions

What is the best form of vitamin C to take?

For most individuals, standard ascorbic acid provides effective and economical supplementation with bioavailability equivalent to naturally-occurring vitamin C in foods. Buffered forms (sodium ascorbate, calcium ascorbate) may reduce gastrointestinal irritation in sensitive individuals. Specialty formulations like Ester-C and liposomal vitamin C lack compelling evidence of clinically meaningful advantages to justify substantially higher costs for general health maintenance.

How much vitamin C should I take daily?

The Recommended Dietary Allowance provides baseline guidance: 90 mg/day for men, 75 mg/day for women, with an additional 35 mg/day for smokers. Research suggests that total daily intake (diet plus supplements) of 200-500 mg divided into 2-3 doses optimizes plasma and tissue saturation while remaining well below the 2,000 mg upper safety limit. Higher doses produce minimal additional benefit due to absorption saturation and renal excretion.

Can I take too much vitamin C?

Vitamin C demonstrates low toxicity, with the primary adverse effects being gastrointestinal disturbances (diarrhea, nausea, cramping) at doses exceeding 2,000 mg/day. These symptoms reflect osmotic effects of unabsorbed vitamin C in the intestine. Individuals with hemochromatosis, G6PD deficiency, or history of kidney stones should exercise caution with high-dose supplementation. For most healthy adults, doses below 2,000 mg/day pose minimal risk.

Does vitamin C prevent colds?

Regular vitamin C supplementation does not reduce common cold incidence in the general population. However, prophylactic supplementation modestly reduces cold duration (8% in adults, 18% in children) and severity (15% overall reduction). Populations under extreme physical stress (athletes, soldiers) demonstrate approximately 50% reduction in cold incidence with vitamin C supplementation, likely reflecting compensation for stress-induced depletion.

Should I take vitamin C with or without food?

Vitamin C absorption occurs efficiently regardless of food intake, so individuals may take supplements with or without meals based on personal preference. Taking vitamin C with food may reduce gastrointestinal irritation in sensitive individuals. Consuming vitamin C with iron-rich meals enhances non-heme iron absorption, providing benefit for individuals with iron deficiency or those consuming plant-based diets.

What’s the difference between vitamin C and ascorbic acid?

Vitamin C and ascorbic acid are synonymous terms for the same compound. “Vitamin C” serves as the common name, while “ascorbic acid” represents the chemical designation. The biologically active form is L-ascorbic acid. Supplements may contain various forms (ascorbic acid, mineral ascorbates, Ester-C) that ultimately provide the same active compound after absorption.

Can vitamin C cause kidney stones?

Research finds no consistent association between moderate vitamin C intake and kidney stone risk in individuals without predisposing conditions. One study found modestly increased risk only at very high intakes (≥1,000 mg/day) in men with history of kidney stones, while women showed no increased risk. Individuals with personal or family history of calcium oxalate stones may consider limiting supplemental vitamin C to 500 mg/day or less.

Does cooking destroy vitamin C?

Yes, vitamin C degrades upon exposure to heat, light, oxygen, and prolonged storage. Boiling vegetables can reduce vitamin C content by 50-80% depending on cooking time and method. To preserve vitamin C in foods: consume raw when possible, use minimal cooking water, employ brief cooking times, steam rather than boil, and consume shortly after preparation. Frozen fruits and vegetables often retain more vitamin C than fresh produce stored for extended periods.

Is vitamin C safe during pregnancy?

Vitamin C is safe and essential during pregnancy at recommended intakes (85 mg/day). Requirements increase modestly to support fetal development and maternal tissue expansion. Very high doses (>400 mg/day) may cause vitamin C dependency in newborns, potentially leading to rebound scurvy after birth when the infant’s intake suddenly drops. Pregnant individuals should maintain moderate supplementation if dietary intake proves inadequate.

How long does it take to correct vitamin C deficiency?

Clinical improvement from scurvy begins within 24-48 hours of vitamin C repletion at doses of 100-300 mg/day. Acute symptoms (fatigue, hemorrhages) resolve within days to weeks, while complete tissue repair requires 1-3 months depending on deficiency severity. Even advanced scurvy demonstrates remarkable recovery with appropriate treatment. Subclinical deficiency correction occurs more gradually over several weeks of adequate intake.

Conclusion: Evidence-Based Vitamin C Use

Vitamin C serves essential biological functions in collagen synthesis, immune support, antioxidant protection, and numerous enzymatic reactions. While the vitamin demonstrates remarkable effects in correcting deficiency states, evidence for supplementation benefits beyond achieving adequate status remains limited for generally healthy, well-nourished individuals.

Key Takeaways:

Adequate intake (90-120 mg/day) prevents deficiency and supports normal physiological function
Absorption saturates at 200-400 mg per dose, with diminishing returns at higher amounts
Immune benefits appear most pronounced in deficient individuals and those under extreme physical stress
Collagen synthesis requires vitamin C as an essential cofactor, making adequate status critical for wound healing
Form selection matters less than ensuring third-party testing and quality manufacturing
Safety profile remains excellent at recommended doses, with minimal risk below 2,000 mg/day
Specialty formulations rarely justify premium pricing given lack of robust bioavailability advantages

For individuals seeking to optimize vitamin C status: prioritize dietary sources from fruits and vegetables, supplement modestly (200-500 mg/day divided doses) if dietary intake proves inadequate, select quality-tested products from reputable manufacturers, and avoid megadose supplementation lacking evidence for additional benefit in sufficient individuals.

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About This Article: This comprehensive guide represents current evidence on vitamin C, including peer-reviewed research on absorption mechanisms, clinical applications, and supplementation strategies. All recommendations align with established safety guidelines from authoritative health organizations. For personalized supplement recommendations based on your specific health goals and needs, explore our Smart Stacks tool.

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Abstract / Summary