- Sodium ascorbate
- Ascorbic Acid
For Patients & Caregivers
Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.
What is it?
Vitamin C is a vitamin that keeps you healthy. Your body can’t make vitamin C on its own so you need to get it from food. Foods that are rich in vitamin C include citrus fruits like oranges, fresh vegetables, berries, and melons.
If you don’t get enough vitamin C from food, your healthcare provider may recommend you take vitamin C supplements or take a multivitamin that has vitamin C.
What is it used for?
Vitamin C is used to:
- Prevent and treat the common cold
- Treat upper respiratory infections (infections that affect your breathing)
- Improve heart health
- Heal wounds
- Prevent and treat cancer
Vitamin C also has other uses that haven’t been studied by doctors to see if they work.
It’s generally safe to eat foods that are rich in vitamin C. However, talk with your healthcare provider before taking supplements or higher amounts of vitamin C.
Herbal supplements can interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.
What are the side effects?
What else do I need to know?
Foods that are rich in vitamin C are safe. The statements below refer to vitamin C supplements.
- Talk to your healthcare provider if you have kidney stones or kidney disease. Vitamin C can make these conditions worse.
- Talk to your healthcare provider if you’re on dialysis for kidney disease. Vitamin C can worsen your condition.
- Avoid vitamin C if you’re on bortezomib (Velcade®) as part of your cancer treatment. Vitamin C can affect the way this medication acts in your body.
- Avoid vitamin C if you’re on radiation therapy or chemotherapy. Vitamin C can interfere with these treatments and decrease their effects.
- Talk to your healthcare provider if you’re taking acetaminophen (paracetamol®). Vitamin C can increase the side effects of this medication.
- Talk to your healthcare provider if you have hemochromatosis (a condition where too much iron builds up in your body). Vitamin C can increase how much iron your body absorbs.
For Healthcare Professionals
Vitamin C, also known as ascorbic acid, exists as either ascorbic acid or ascorbate. It is a water-soluble vitamin found in many fresh fruits and vegetables, and is essential for a variety of physiologic functions including formation of collagen and catecholamines, and carnitine and peptide synthesis (1). It is not synthesized in the human body, and deficiency can cause scurvy.
Oral vitamin C is consumed as an antioxidant supplement for immune protection against colds and flu, wound healing, cardiovascular health, and cancer prevention. Although supplemental intake may reduce duration and severity of the common cold, the effect is minimal except in those exposed to acute physical stress (2). High-dose vitamin C supplementation alone or in combination with high-dose zinc did not decrease symptom duration in ambulatory patients infected with SARS-CoV-2 (90).
In large-scale randomized trials, supplemental vitamin C did not reduce risk of coronary heart disease (4) (5). Further, supplementation with vitamins C and E increased risk of mortality and nonfatal myocardial infarction in patients with coronary artery disease (6). Data on effects for reducing blood pressure are mixed (7) (8), and studies do not support prophylactic vitamin C to lower postoperative atrial fibrillation incidence among cardiac surgery patients (69) (70), but other data suggest reductions in length of hospital stay, duration of mechanical ventilation, and atrial fibrillation incidence (80).
The role of vitamin C in cancer prevention is not definitive. High plasma levels of vitamin C were associated with lower gastrointestinal cancer incidence probably due to protective effects against dietary carcinogenic nitroso compounds (19). Intake of vitamins A, C, or E reduced cervical cancer risk (20), but did not prevent gastrointestinal (21), prostate (22), lung (23) cancers or affect mortality (24) (73). Supplemental but not dietary vitamin C was associated with an increased risk of liver cancer (25).
There are also conflicting theories against the use of vitamin C supplements during chemotherapy. Preclinical studies found that cancer cells preferentially uptake vitamin C (37) and render some chemotherapy drugs less effective (38). Also, a major concern surrounding the use of antioxidants such as vitamin C is that they can interfere with the actions of chemotherapy and radiation therapy that rely on the production of reactive oxygen species for their cytotoxic activities (39). However, a clinical study showed that ascorbic acid does not reduce the therapeutic effects of paclitaxel and carboplatin (40). Another study found an increase in chemotherapy-associated adverse effects with inadequate intake of vitamin C in children with acute lymphoblastic leukemia (41). In other preliminary studies, short-term vitamin C plus E supplementation during radiotherapy had a protective effect against xerostomia in patients with head and neck cancer (75); a combination of vitamins C, E, and selenium lowered radioiodine-induced oxidative stress in thyroid cancer patients (76); and supplementation may enhance effects of DNA methyl transferase inhibitors in patients with myeloid cancers (89). Still, older trials in advanced cancer patients using 10 g per day of oral vitamin C did not demonstrate significant benefits (29) (30). This lack of effect is explained by the finding of a pharmacokinetic study that ascorbic acid can only reach a limited plasma concentration through oral administration (31).
Intravenous high-dose vitamin C has been long been used as an alternative cancer treatment (26) based on the hypothesis that formation of new collagen resists malignant infiltration (27). In preclinical studies, higher pharmacologic concentrations could be achieved via intravenous injection and had selective cytotoxic effects on cancer cell lines (32) (33), and early reports using parenteral plus oral ascorbic acid showed promising results (28). Ascorbic acid is postulated to act as a carrier of hydrogen peroxide to the extracelluar fluid (32) where it generates free radicals against tumor cells (33). High-dose IV ascorbic acid up to 1.5 g/kg/day (34), or used with chemotherapy (74) appears to be well-tolerated. It may improve the quality of life of terminal cancer patients (35), and reduce chemotherapy-associated toxicity (67). This led to a renewed interest in studying high-dose IV vitamin C as an anticancer treatment (34) (36). However, it should be regarded as an investigational drug and used only in a clinical trial setting, as studies of IV vitamin C therapies in patients with sepsis have not found benefit (84) (85) (91) (92) and adverse events (93) (94) (95) and interference with glucometer readings (96) (97) have been reported.
Adverse effects from vitamin C supplements are generally rare, but there are reports of gastrointestinal upset, kidney stone formation (42), and hemolytic anemia in patients with G6PDH deficiency (43) (44). Patients with a history of oxalate kidney stones, renal insufficiency, hematochromatosis, or those undergoing chemotherapy should consult their physicians before taking vitamin C supplements.
Mechanism of Action
Vitamin C is essential for the formation and polymerization of collagen; therefore deficiency results in scurvy and poor wound healing (1). Vitamin C also inhibits hyaluronidase leading to the hypothesis that it can prevent cancer metastasis by strengthening the buildup and preventing the breakdown of collagen (45).
Ascorbic acid acts as an antioxidant to protect against oxidative damage from free radicals (46). It inactivates nitric oxide and improves endothelium-dependent vasodilation (47), and acts via different mechanisms depending on its plasma concentration. Plasma concentrations <0.1mM are achieved through oral intake of dietary or supplemental forms. At pharmacologic plasma concentrations of 0.3 - 20mM via intravenous injection, ascorbic acid is oxidized to an ascorbate radical which acts as a prodrug for hydrogen peroxide formation within interstitial fluids (33). This induces DNA damage and adenosine triphosphate (ATP) depletion, and triggers ataxia telangiectasia mutated (ATM)/adenosine monophosphate–activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) in cancer cells (67).
Other preclinical studies suggest that ascorbate can regulate hematopoietic stem cell function and leukemogenesis (77). In leukemic cells, vitamin C compensated for Tet2 mutations to restore normal function (78). In non-small-cell lung cancer and glioblastoma cells, pharmacological ascorbate selectively sensitized these cells (79). Ascorbate decreases colon cancer cell proliferation by downregulating specificity proteins (48). It also depletes ATP and induces autophagy and cell death in prostate cancer cells (49). Preferential oxidative cytotoxic effects on cancer cells may be due to the presence of intracellular iron (50), copper (51), an increase in p53 activity (52), and overexpression of sodium-dependent vitamin C transporter 2 (53). Further, high-dose vitamin C was reported to inhibit metastasis of breast cancer cells by inhibiting epithelial-mesenchymal transition (82).
Dehydroascorbic acid, the oxidized form of vitamin C, may have cytoprotective effects by preserving mitochondrial membrane potential (38).
Common: Nausea, diarrhea and stomach cramps.
Case reports: Oral
Increased oxalate kidney stone formation, nephrolithiasis, acute renal failure, or renal insufficiency: In patients with history of kidney stones (42) (58) (59).
Hemolytic anemia: May occur at high doses in patients with G6PDH deficiency (43) (44).
Severe cyanide poisoning: With concurrent use of amygdalin 3 grams + vitamin C 4800 mg per day (60).
Eroded tooth enamel or dental caries: With excessive use of chewable tablets (61).
Case reports: Intravenous
During infusion (74)
Common: Thirst and increased urinary flow.
Isolated incidences: nausea/vomiting, rumbling or unpleasant fluttering in abdomen, chills, and/or headache.
Isolated incidences: Mental haze, increased leg edema lasting for a few days.
Oxalate nephropathy: In critically ill patients who received intravenous vitamin C as supportive sepsis therapy (93) (94) (95).
Factitious hyperglycemia: In a peritoneal dialysis patient receiving high-dose vitamin-C that persisted for 6 days after therapy discontinuation (96).
Intratubular oxalate deposits: Attributed to high-dose vitamin C used as an immune booster in a kidney transplant patient who also had COVID-19 (98).
Methemoglobinemia and hemolytic anemia: In a 75-year-old woman with previously unrecognized G6PD deficiency, who had jaundice, dark urine, and shortness of breath after receiving 30 g of vitamin C infusion as an unconventional therapy for hemifacial spasm (99).
Iron: Ascorbic acid increases iron absorption and modulates transport and storage in the body. Significant in patients with hematochromatosis (61).
Chemotherapy drugs: Vitamin C may reduce the effectiveness of some antineoplastic agents including vincristine, doxorubicin, methotrexate, cisplatin, and imatinib (38).
Bortezomib: Ascorbic acid intake reduces the activity of bortezomib (62). In a clinical trial using these agents together, the interaction is minimized by administrating bortezomib in the morning and ascorbic acid in the evening (63).
Glutathione: Glutathione as an antioxidant reduces the pro-oxidant cytotoxic effects of ascorbic acid (64).
Beta-blockers: Ascorbic acid can enhance the cardioprotective effects of beta-blockers in post-bypass patients (65).
Paracetamol: When taken simultaneously, vitamin C increased the extent of absorption of paracetamol in healthy volunteers, and may increase the risk of side effects (83).
Herb Lab Interactions
Ascorbic acid supplementation may cause a false negative guaiac (occult blood) test (66).
Erroneous interpretation of point-of-care blood glucometer readings were attributed to interference from high-dose IV vitamin C, resulting in a patient death and highlighting the potential for incorrect diagnosis of pseudohyperglycemia or pseudohypoglycemia (97). In a peritoneal dialysis patient receiving high-dose IV vitamin C, factitious hyperglycemia persisted for 6 days after therapy discontinuation (96).