Vitamin C (Ascorbic Acid)
1. Identity and Chemical Nature
Vitamin C, also known as ascorbic acid, is a water-soluble nutrient found in some foods. Found in two main forms, namely ascorbic acid (AA) and dehydroascorbic acid (DHA), vitamin C is a strong antioxidant and a cofactor for many enzymes, being involved in many biological functions, such as normal immune system functioning, carnitine and catecholamine metabolism, dietary iron absorption, and collagen biosynthesis. The body cannot synthesize vitamin C due to mutations in the L-gulonolactone oxidase (GLO) gene, which is responsible for its synthesis from L-gulono-1,4-lactones. The biologically active form in humans is the L-enantiomer, L-ascorbic acid.
Intestinal absorption of ascorbic acid occurs through a sodium-dependent active transport process that is saturable and dose dependent. At low gastrointestinal ascorbate concentrations, active transport predominates, while simple diffusion occurs at high concentrations. Some 70 to 90 percent of usual dietary intakes of ascorbic acid (30 to 180 mg/day) are absorbed; however, absorption falls to about 50 percent or less with increasing doses above 1 g/day. Dehydroascorbic acid (DHA) is the form of the vitamin that primarily crosses the membranes of blood and intestinal cells, after which it is reduced intracellularly to ascorbic acid.
Common Names and Chemical Synonyms
- IUPAC name: (R)-3,4-dihydroxy-5-((S)-1,2-dihydroxyethyl)furan-2(5H)-one
- Common name: Vitamin C; ascorbic acid; L-ascorbic acid
- Oxidized form: Dehydroascorbic acid (DHA)
- Supplement salt forms: Sodium ascorbate, calcium ascorbate, other mineral ascorbates
Natural Food Sources
The best sources of vitamin C are fruits and vegetables, especially citrus fruits, red and green peppers, kiwifruit, broccoli, strawberries, and Brussels sprouts. Orange juice, grapefruit juice, and tomato juice also contain large amounts of vitamin C, and vitamin C is added to some breakfast cereals. Vitamin C is not found in significant amounts in animal-based foods.
Vitamin C is water soluble and susceptible to heat, so cooking can reduce the vitamin C content of food. Because vitamin C is water-soluble, it leaches away from foods considerably during cooking, freezing, thawing, and canning. Up to 50 percent of vitamin C can be boiled away. Therefore, to maximize vitamin C intake from foods, one should eat fruits and vegetables raw or lightly steamed.
Supplement Forms and Preparations
The vitamin C in dietary supplements is usually in the form of ascorbic acid, but some supplements have other forms, such as sodium ascorbate, calcium ascorbate, other mineral ascorbates, and ascorbic acid with bioflavonoids. Research has not shown that any form of vitamin C is better than the other forms. Beyond oral solid and liquid formulations, vitamin C is also administered intravenously (IV) in clinical research and medical settings, particularly at high doses that cannot be achieved orally.
2. Historical and Traditional Use
Ancient and Pre-Modern Recognition of Scurvy
Observations on scurvy first appear in Egyptian medical scrolls 3,500 years ago, and continue through to the discovery of vitamin C and the modern research on the physiological role of ascorbic acid. The Ebers Papyrus of about 1550 BC gives an account of a disease likely to be scurvy. The suggested treatment of this disease is to eat onions, which we now know contain small amounts of vitamin C. Hippocrates of Cos, an ancient Greek physician considered to be the "father" of Western medicine, wrote extensively on medical matters and described the symptoms associated with scurvy.
The observations of great navigators during the 15th and 16th centuries, when scurvy plagued ships' crews, played an important role in clarifying scurvy's etiology. In winter, the frozen St Lawrence River in Canada stranded French explorer Jacques Cartier's ship. With limited food, scurvy broke out amongst his men. The native Indians suggested a remedy — a drink made by soaking the bark of a local tree. The remedy worked. This represents one of the earliest documented instances of indigenous peoples transmitting plant-based knowledge of vitamin C-rich preparations to European explorers.
James Lind and the First Clinical Trial (1747)
In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy.
By the mid-18th century, scurvy had debilitated hundreds of thousands of British sailors and others whose diet was heavily dependent on meat and starch and devoid of fresh vegetables and citrus fruits. The first step in eradicating this disease came in 1757, when James Lind, a Scottish physician, wrote an essay recommending mandatory consumption of citrus fruits and lemon juice by sailors in the British Navy. The results in favor of vitamin C were so dramatic that in 1795, the Admiralty made lemon juice a required part of the standard diet of British seamen and scurvy disappeared.
Isolation, Identification, and Synthesis
While working at the University of Cambridge (1927, 1929) and at the Mayo Foundation, Rochester, Minnesota, Albert Szent-Györgyi found and isolated an organic reducing agent, which he called hexuronic acid (now known as ascorbic acid), from plant juices and adrenal gland extracts. He discovered that paprika (Capsicum annuum) was an extraordinarily rich source of the same substance and obtained more than three kilograms from it.
At the University of Szeged in Hungary, Szent-Györgyi and his research fellow Joseph Svirbely found that "hexuronic acid" was actually the long-sought antiscorbutic factor, also known as vitamin C. After Walter Norman Haworth had determined its structure, the antiscorbutic was given the formal chemical name of L-ascorbic acid. It was synthesized by Haworth, and independently by Tadeus Reichstein in 1933. In 1933, ascorbic acid was synthesized and since 1937 it has been in commercial production.
In 1937, Szent-Györgyi received the Nobel Prize in Physiology or Medicine for his discoveries concerning biological combustion, including the role of vitamin C in the process. Walter Norman Haworth's determination of the structure of vitamin C contributed to his receiving the 1937 Nobel Prize in Chemistry.
In the 1970s, Nobel Laureate Linus Pauling popularized the idea of high-dose vitamin C supplementation for the common cold and cancer prevention, sparking decades of clinical investigation. Since vitamin C was isolated in the 1930s it has been proposed for respiratory infections, and became particularly popular in the 1970s for the common cold when Nobel Prize winner Linus Pauling drew conclusions from earlier placebo-controlled trials of large dose vitamin C on the incidence of colds.
3. Key Constituents and Active Compounds
Vitamin C is itself the primary bioactive molecule. Its biological activity derives principally from its chemical structure as a lactone with two enolic hydroxyl groups that allow it to act as a potent reducing agent. The following describes its principal biochemical roles.
Antioxidant Activity
Vitamin C functions physiologically as a water-soluble antioxidant by virtue of its high reducing power. It is a cofactor for enzymes involved in the biosynthesis of collagen, carnitine, and neurotransmitters in vitro, and it can quench a variety of reactive oxygen species and reactive nitrogen species in aqueous environments. Evidence for in vivo antioxidant functions of ascorbate includes the scavenging of reactive oxidants in activated leukocytes, lung, and gastric mucosa, and diminished lipid peroxidation as measured by urinary isoprostane excretion.
Vitamin C has antioxidant properties, capable of regenerating other antioxidants such as vitamin E. In this way, it is possibly helpful in preventing oxidative stress-related diseases, which include certain cancers and cardiovascular diseases.
Enzymatic Cofactor Roles
Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Acting as a cofactor of Fe²⁺/αKG dioxygenases, vitamin C regulates epigenetic signatures, the redox status, and the extracellular matrix composition, depending on the enzymes' subcellular localization. Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum, vitamin C regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts and chondrocytes.
Other biochemical functions of vitamin C include carnitine synthesis, redox-reactions, production of adrenal steroids and catecholamines, metabolism of amino acids and cholesterol, and iron absorption.
Collagen Biosynthesis
L-Ascorbic acid (vitamin C) was extensively studied over the last century because it plays an essential role for proper folding and deposition of collagen proteins, which are the most abundant proteins in the human body and have a strong impact on the composition, structure, and biomechanical features of the extracellular matrix (ECM). The body also needs vitamin C to make collagen, a protein required to help wounds heal. Without adequate vitamin C, prolyl and lysyl hydroxylase enzymes — which require ascorbate as a cofactor — cannot properly hydroxylate collagen precursors, leading to structurally defective collagen. This failure of collagen synthesis is the biochemical basis of scurvy's hallmark connective tissue breakdown.
Iron Absorption Enhancement
Vitamin C improves the absorption of iron from plant-based foods and helps the immune system work properly to protect the body from disease. Specifically, vitamin C reduces ferric iron (Fe³⁺) to ferrous iron (Fe²⁺) in the gastrointestinal lumen, a form that is more readily absorbed by intestinal mucosal cells.
Immune Cell Support
Vitamin C plays an important role in both innate and adaptive immunity, probably because of its antioxidant effects, antimicrobial and antiviral actions, and effects on immune system modulators. Vitamin C helps maintain epithelial integrity, enhance the differentiation and proliferation of B cells and T cells, enhance phagocytosis, normalize cytokine production, and decrease histamine levels.
Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress.
4. Scientific Evidence by Area of Use
4.1 Scurvy Prevention and Treatment
The relationship between vitamin C and scurvy is among the most firmly established in nutritional science — representing the vitamin's definitional function. Overt deficiency symptoms occur only if vitamin C intake falls below approximately 10 mg/day for many weeks. Scurvy causes fatigue, inflammation of the gums, small red or purple spots on the skin, joint pain, poor wound healing, and corkscrew hairs. Additional signs of scurvy include depression as well as swollen, bleeding gums and loosening or loss of teeth. People with scurvy can also develop anemia. Scurvy is fatal if it is not treated.
Scurvy is caused by a prolonged dietary deficiency of vitamin C (ascorbic acid). Ascorbic acid levels less than 0.2 mg/dL (10 μmol/L) are consistent with severe deficiency. Today, scurvy is extremely rare because of improved food supplies, vitamin-fortified foods, and vitamin supplements, but it can occur in populations with poor diets.
Evidence strength: Conclusive. The causal link between vitamin C deficiency and scurvy, and the therapeutic efficacy of vitamin C repletion, is supported by centuries of clinical observation, multiple controlled trials beginning with James Lind's 1747 experiment, and a thorough mechanistic understanding at the biochemical level.
4.2 Common Cold
The role of vitamin C in the common cold has been among the most studied — and debated — topics in nutritional science. The most comprehensive synthesis of evidence comes from the Cochrane Collaboration.
A review restricted to placebo-controlled trials testing at least 0.2 g per day of vitamin C — thirty trials involving 11,350 participants — suggests that regular ingestion of vitamin C has no effect on common cold incidence in the ordinary population. Trials of high doses of vitamin C administered therapeutically (starting after the onset of symptoms) showed no consistent effect on either duration or severity of symptoms.
However, the same body of evidence found more nuanced results regarding duration and severity: The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds, but this was not replicated in the few therapeutic trials that have been carried out.
Research shows that for most people, vitamin C supplements or vitamin C-rich foods do not reduce the risk of getting the common cold. However, people who take vitamin C supplements regularly might have slightly shorter colds or somewhat milder symptoms. Taking a vitamin C supplement after a cold starts does not appear to be helpful.
Evidence strength: Moderate-to-strong for no effect on cold incidence in the general population; weak-to-moderate for a modest reduction in cold duration with regular supplementation; insufficient for therapeutic (post-onset) dosing. The magnitude of the duration effect, even where statistically significant, is generally considered too small to be clinically meaningful for most individuals. Evidence is stronger for populations under high physical stress (e.g., marathon runners, military personnel).
4.3 Cardiovascular Disease
Beyond its antioxidant activity, vitamin C is pivotal in regulating lipid metabolism, promoting angiogenesis, enhancing collagen synthesis, modulating remodeling, and stabilizing the extracellular matrix. While preclinical studies have shown promising results, clinical trials have yielded inconsistent findings, due to suboptimal study design, results misinterpretation, and misleading conclusions.
Much research has focused on whether vitamin C supplements protect against heart disease. Taking supplements doesn't seem to affect heart disease risk. Epidemiological studies suggest that populations with higher dietary vitamin C intakes from food have lower rates of cardiovascular events, but these associations cannot be separated from the broader effects of fruit and vegetable consumption.
The role of vitamin C in mitigating ROS-induced damage to endothelial and myocardial cells in ischemia/reperfusion or sepsis has been examined. By limiting endothelial dysfunction, vitamin C might improve tissue perfusion and reduce tissue hypoxia and subsequent organ dysfunction. However, translating these mechanistic findings into proven clinical benefit has been challenging.
Evidence strength: Weak-to-insufficient for supplemental vitamin C reducing cardiovascular disease risk in the general population. Mechanistic (in vitro and animal) evidence is substantial, but large randomized controlled trials have not demonstrated a protective effect of oral vitamin C supplementation on cardiovascular endpoints.
4.4 Cancer
People with high intakes of vitamin C from fruits and vegetables might have a lower risk of getting many types of cancer, such as lung, breast, and colon cancer. However, taking vitamin C supplements, with or without other antioxidants, doesn't seem to protect people from getting cancer.
High-dose intravenous (IV) vitamin C has attracted particular research interest as a potential adjunct in cancer treatment. One of the proposed mechanisms of intravenous vitamin C (IVC) is to target cancer cells via an indirect pro-oxidant mechanism relying on transition metal ion-dependent generation of hydrogen peroxide; vitamin C must be injected intravenously in order to achieve sufficiently high plasma vitamin C concentrations to facilitate this mechanism. Intravenous administration may also be required to enhance diffusion of vitamin C into solid tumours with subsequent modulation of important cell signaling pathways.
Vitamin C is involved in various molecular mechanisms that underlie its anticarcinogenic effect. Vitamin C leads to the inhibition of cell proliferation and growth by generating ROS and altering the expression of genes involved in angiogenesis, glycolysis, and metastasis by regulating the transcriptional activity of hypoxia. Vitamin C also allowed for T lymphocyte infiltration and induced cytokine production, resulting in an anti-tumor immune response.
The U.S. Food and Drug Administration (FDA) has not approved the use of IV vitamin C as a treatment for cancer.
Evidence strength: Weak-to-preliminary for IV vitamin C as an adjunctive cancer treatment. The mechanistic rationale is scientifically credible but clinical evidence from adequately powered RCTs is lacking. Dietary vitamin C from food sources is epidemiologically associated with lower cancer risk, but this association may reflect broader dietary patterns rather than vitamin C specifically. Supplemental oral vitamin C has not been shown to reduce cancer risk.
4.5 Age-Related Macular Degeneration (AMD)
The most robust clinical evidence for vitamin C's role in eye disease comes from the Age-Related Eye Disease Study (AREDS). The original AREDS study, launched in 1996, showed that a dietary supplement formulation (500 mg vitamin C, 400 international units vitamin E, 2 mg copper, and 80 mg zinc) reduced the progression to advanced AMD. The AREDS and AREDS2 studies demonstrated that supplements including vitamins C and E, beta-carotene, and zinc may reduce the progression to advanced AMD, in some patients, by 25% in five years. This is one of the few nutritional supplements known to have beneficial effects in any eye disease.
Taking oral vitamin C supplements with other vitamins and minerals seems to keep age-related macular degeneration (AMD) from getting worse. AMD is a leading cause of vision loss among older adults. Some studies also suggest that people who have higher levels of vitamin C in their diets have a lower risk of getting cataracts.
An important caveat: the AREDS formulation contains multiple nutrients (vitamin C, vitamin E, zinc, copper, and in AREDS2, lutein/zeaxanthin), making it impossible to attribute the observed benefit specifically to vitamin C alone.
Evidence strength: Moderate-to-strong for the combination AREDS/AREDS2 formulation in slowing AMD progression in patients with intermediate or advanced AMD in one eye. Evidence is insufficient to attribute this effect to vitamin C independently of the other formula components. Evidence on vitamin C's role in cataract prevention from observational data is preliminary.
4.6 Immune Function and Infection
More than half a century of research has shown vitamin C to be a crucial player in various aspects of the immune system, particularly immune cell function. Vitamin C's association with immune strengthening is derived from its ability to enhance the function of the immune system, including antimicrobial and natural killer cell activities, macrophages, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity.
Several studies revealed that vitamin C possesses antimicrobial properties, thus reducing the risk of infections, and has immunomodulatory functions, particularly in high concentrations.
Evidence strength: Mechanistic evidence for vitamin C's role in immune cell function is well-established and supported by in vitro and animal data. Human clinical evidence demonstrating that supplementation above adequate intake levels meaningfully improves immunity in non-deficient individuals is limited. The benefit is clearest in individuals who are vitamin C-deficient.
4.7 Wound Healing and Musculoskeletal Injury
Basic science investigations on the biochemical pathways after a musculoskeletal injury have suggested that vitamin C may enhance collagen synthesis and soft tissue healing. Preclinical studies demonstrated that vitamin C has the potential to accelerate bone healing after a fracture, increase type I collagen synthesis, and reduce oxidative stress parameters.
Animal studies using the vitamin C-dependent Gulo knockout mouse indicated that deficiency did not affect the formation of collagen in the skin of unchallenged mice; however, following full thickness excisional wounding there was significantly decreased collagen formation in vitamin C-deficient mice. This finding is in agreement with an earlier study carried out with scorbutic guinea pigs. Thus, vitamin C appears to be particularly essential during wound healing, also decreasing the expression of pro-inflammatory mediators and enhancing the expression of various wound healing mediators.
No adverse effects were reported with vitamin C supplementation in either animal models or human participants; thus, oral vitamin C appears to be a safe supplement but lacks clinical evidence compared with controls. Because of the limited number of human studies, further clinical investigations are needed before the implementation of vitamin C as a postinjury supplement.
Evidence strength: Preclinical evidence is strong; human clinical trial evidence is limited and insufficient to make a firm recommendation for supplemental vitamin C specifically for wound healing in non-deficient individuals. Adequate vitamin C status is necessary for normal wound healing.
4.8 Critical Illness and Sepsis
Vitamin C has attracted growing research interest as a potential adjunctive therapy in critically ill patients. The use of vitamin C in critical illness has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients.
Evidence strength: Preliminary and mixed. Multiple randomized controlled trials have investigated IV vitamin C in sepsis and critical illness, with some showing benefits in secondary endpoints (organ dysfunction scores, vasopressor requirements) but results on mortality and primary outcomes have been inconsistent. The evidence is not yet sufficient to establish a standard-of-care role for IV vitamin C in sepsis.
5. Body Systems and Health Areas
Vitamin C is associated with the following body systems and health areas, based on established mechanistic roles and clinical evidence:
- Connective tissue and musculoskeletal system: Vitamin C plays an essential role for proper folding and deposition of collagen proteins, which are the most abundant proteins in the human body. This underlies its role in skin integrity, bone strength, cartilage health, tendon function, and wound repair.
- Immune system: Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. It supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin.
- Cardiovascular system: Vitamin C is pivotal in regulating lipid metabolism, promoting angiogenesis, enhancing collagen synthesis, modulating remodeling, and stabilizing the extracellular matrix. Collagen is a critical structural component of blood vessel walls.
- Nervous system and adrenal function: Vitamin C is involved in production of adrenal steroids and catecholamines, and in the metabolism of amino acids. Ascorbate is present in high concentrations in the adrenal glands and brain, where it participates in neurotransmitter synthesis (including norepinephrine).
- Hematologic system (iron metabolism): Vitamin C improves the absorption of iron from plant-based foods. This is clinically relevant in the management of non-heme iron deficiency anemia.
- Ocular system: As demonstrated by the AREDS trials, vitamin C (as part of a combination formula) has documented benefit in reducing progression of intermediate and advanced AMD.
- Gastrointestinal system: Vitamin C acts as an antioxidant in the gastric mucosa and prevents oxidative damage by scavenging reactive oxygen species.
- Integumentary system (skin): Vitamin C has been shown to have an extremely good antioxidant effect, protecting against oxidative stress, facilitating collagen synthesis, and supporting skin health.
6. Dosage: RDA, Supplemental Doses, and Clinical Trial Doses
Recommended Dietary Allowances (RDA)
To provide antioxidant protection, a Recommended Dietary Allowance (RDA) of 90 mg/day for adult men and 75 mg/day for adult women is set based on the vitamin C intake to maintain near-maximal neutrophil concentration with minimal urinary excretion of ascorbate.
The recommended daily allowance (RDA) for vitamin C, which has been established by the US federal government, is 90 mg for adult males and 75 mg for adult females. However, pregnant and lactating women are recommended to increase their vitamin C intake to 85 and 120 mg per day, respectively, while smokers are recommended to increase their consumption of vitamin C by 35 mg per day, regardless of sex.
The RDA for vitamin C is 15 to 115 mg for infants and children, depending on age, and 75 to 120 mg for nonsmoking adults, including women who are pregnant or lactating.
Deficiency Threshold
A plasma level of 50 µmol/L (~0.9 mg/dL) is now widely considered the threshold for adequacy, indicating a level sufficient to meet metabolic demands and prevent chronic disease. Hypovitaminosis C, or vitamin C deficiency, is clinically defined by a plasma ascorbic acid level below 23 µmol/L (approximately 0.4 mg/dL).
Tolerable Upper Intake Level (UL)
High doses of vitamin C have been reported to cause numerous problems, but the only consistently shown side effects are gastrointestinal upset and diarrhea. To prevent these discomforts, the Institute of Medicine has set a UL for adults at 2,000 milligrams per day (greater than twenty times the RDA).
Doses Used in Clinical Studies
- Common cold (regular supplementation, Cochrane review): Placebo-controlled trials testing at least 0.2 g per day of vitamin C.
- Age-related macular degeneration (AREDS): The AREDS formulation included 500 mg vitamin C in combination with other antioxidants and zinc.
- AREDS dosing (reproduced in clinical trial context): Participants were randomly assigned to antioxidants (500 mg vitamin C, 4,000 IU vitamin E, 15 mg beta-carotene), zinc (80 mg zinc oxide, 2 mg cupric oxide), antioxidants plus zinc, or placebo.
- Gastritis study (oxidative stress biomarkers): Vitamin C supplementation at 2,000 mg/day for 4 to 12 months in 41 patients with non-atrophic gastritis decreased gastric mucosal nitrotyrosine.
- High-dose intravenous (critical illness): High doses of intravenous vitamin C have been evaluated, with doses up to 100 g/day used to manage critically ill patients. In one specific trial, vitamin C was used at 200 mg/kg per day for 4 days (CITRIS-ALI).
- High-dose IV vitamin C (COVID-19 safety study): One hundred four patients underwent high-dose intravenous administration of vitamin C, precisely 10 g in 250 cc of saline solution in slow infusion for three consecutive days.
Typical Intake from Food
According to the 2001–2002 National Health and Nutrition Examination Survey (NHANES), mean intakes of vitamin C from food and beverages are 105.2 mg/day for adult males and 83.6 mg/day for adult females, meeting the currently established RDA for most nonsmoking adults. Mean intakes for children and adolescents age 1 to 18 years range from 75.6 mg/day to 100 mg/day, also meeting the RDA for these age groups.
7. Safety Considerations and Interactions
Gastrointestinal Effects
When taken at suggested doses by mouth, vitamin C supplements are mostly safe. Taking too much vitamin C can cause side effects, including upset stomach, vomiting and loose stools, and stomach cramps or bloating. Serious side effects from too much vitamin C are very rare, because the body cannot store the vitamin. However, amounts greater than 2,000 mg/day are not recommended. Doses this high can lead to stomach upset and diarrhea, and, although rarely, kidney stones.
Kidney Stones
Oxalate is a metabolite of vitamin C. At high concentrations, it can deposit in the kidneys leading to oxalate nephropathy. There is some evidence that taking vitamin C supplements at high doses increases the likelihood of developing kidney stones; however, this effect is most often observed in people who already have multiple risk factors for kidney stones. A minor product of vitamin C metabolism is oxalate, and elevated urinary oxalate excretion has been reported after oral vitamin C intakes of 2 g/day, raising concerns associating vitamin C with increased risk of renal stones, which can potentially result in oxalate nephropathy.
G6PD Deficiency
Case reports have shown that people with an inherited disorder called G6PD deficiency should not be given high doses of vitamin C because it may cause hemolysis. A systematic review identified that about 71.4% of reported cases of vitamin C-induced hemolysis were diagnosed to have glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Hemochromatosis
Because vitamin C may make iron more easily absorbed and used by the body, high doses of vitamin C are not recommended for people with hemochromatosis (a condition in which the body takes up and stores more iron than it needs).
Pregnancy
Large doses of vitamin C supplementation are not recommended during pregnancy. They can lead to shortage of vitamin C in the baby after delivery.
Oxidative Stress at Very High Doses with Iron
At very high doses in combination with iron, vitamin C has sometimes been found to increase oxidative stress, reaffirming that getting antioxidants from foods is better than from supplements, as that helps regulate intake levels.
Intravenous-Specific Risks
In general, vitamin C given by IV infusion has caused very few side effects in clinical trials. However, IV vitamin C may cause serious side effects in people with kidney disease, G6PD deficiency, or hemochromatosis. High-dose intravenous vitamin C may alter the measurements of some handheld blood glucose meters, which may measure false-high blood glucose levels. In a systematic review of 2,801 patients, five cases of oxalate nephropathy (0.18%), five cases of hypernatremia (0.18%), three cases of hemolysis in G6PD-deficient patients (0.11%), two cases of glucometer error (0.07%), and one case of kidney stones (0.04%) were reported.
Drug Interactions
Several clinically notable interactions have been identified:
- Chemotherapy: There is concern that use of vitamin C and other antioxidants during chemotherapy might keep chemotherapy medicines from working well.
- Statins and niacin: People with high cholesterol might take these medicines. Taking vitamin C with statins and niacin could keep the medicines from working as well as expected.
- Estrogen-containing medications: Taking vitamin C with birth control pills or hormone replacement therapy might raise estrogen levels.
- Protease inhibitors: Use of vitamin C might keep these antiviral medicines from working as well as they should.
- Iron supplements: Vitamin C makes the body absorb more iron. Getting more iron can be harmful for people who have a condition that causes too much iron in the body, called hemochromatosis.
References
- NIH Office of Dietary Supplements — Vitamin C: Fact Sheet for Health Professionals
- NIH Office of Dietary Supplements — Vitamin C: Fact Sheet for Consumers
- National Academies Press (NCBI Bookshelf) — Dietary Reference Intakes for Vitamin C: Vitamin C Chapter
- Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11):1211. PMC5707683
- Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews 2013, Issue 1. CD000980
- Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. PubMed PMID: 23440782
- PMC11820684 — Vitamin C: A Comprehensive Review of Its Role in Health, Disease Prevention, and Therapeutic Potential
- PMC6204628 — Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review
- PMC5415867 — Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and Epigenetics
- PMC12108419 — Vitamin C in Cardiovascular Disease: From Molecular Mechanisms to Clinical Evidence and Therapeutic Applications
- PMC9885715 — An update of the effects of vitamins D and C in critical illness
- PMC8857720 — Vitamin C-induced Hemolysis: Meta-summary and Review of Literature
- Dresen E et al. History of scurvy and use of vitamin C in critical illness: A narrative review. Nutrition in Clinical Practice. 2023;38:46–54
- Bhatt DL et al. Scurvy: past, present and future. European Journal of Internal Medicine. 2011. PubMed PMID: 21402244
- National Eye Institute — NIH study confirms benefit of AREDS2 supplements for slowing AMD
- Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for AMD: AREDS report no. 8. PubMed PMID: 11594942
- National Cancer Institute (NCI) — Intravenous Vitamin C (PDQ®): Patient Version
- NCI/NCBI Bookshelf — Intravenous Vitamin C (PDQ®): Health Professional Version
- MedlinePlus Medical Encyclopedia — Vitamin C (U.S. National Library of Medicine)
- Science History Institute — Albert Szent-Györgyi: Biography
- Nobel Prize Biographical — Albert Szent-Györgyi (1937 Nobel Prize in Physiology or Medicine)
- American Chemical Society — Albert Szent-Györgyi and the Discovery of Vitamin C (ACS National Historic Chemical Landmark)
- PMC4423646 — Vitamin C revisited (cardiovascular and critical illness review)
- PMC5244028 — Nutritional and Lifestyle Interventions for Age-Related Macular Degeneration: A Review
- NIH Office of Dietary Supplements — Dietary Supplements for Immune Function and Infectious Diseases: Health Professional Fact Sheet
- PMC7166744 — Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold
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