- Sodium ascorbate
- Ascorbic Acid
For Patients & Caregivers
How It Works
Vitamin C is important for maintaining general health, but vitamin C supplementation may not help lower the risk of cancer.
Vitamin C is an essential nutrient that must be gained from sources outside the human body. It is an antioxidant used for colds and for cancer prevention because it is thought to protect cells from free radical damage. It is also important for the production of proteins and formation of collagen in the skin. Therefore, vitamin C helps promote wound healing and a deficiency can cause scurvy. In addition, scientists think that vitamin C might help reduce inflammation.
Oral vitamin C supplements are not an effective cancer treatment. Clinical studies using high doses of injectable vitamin C do show promising results, but more studies are needed. Vitamin C may also make some chemotherapy drugs less effective. Patients should speak with their doctor before using vitamin C, especially during cancer treatment.
To prevent and treat the common cold and upper respiratory infections
Vitamin C does not prevent the common cold or other upper respiratory infections, but it may slightly reduce symptoms.
To prevent cancer
Some studies suggest vitamin C from food can reduce risk of certain cancers. However, most large-scale trials did not find vitamin C supplements useful in preventing cancers.
To treat cancer
Clinical studies concluded oral vitamin C is not effective, probably due to limited absorption. High-doses of injectable vitamin C are currently under investigation as a cancer treatment.
To treat heart disease
High dietary intake and blood levels of vitamin C have been associated with lower risk of heart disease, but a long-term study did not find benefit when taking vitamin C supplements.
To treat cataracts
Vitamin C intake has no effect on development of cataracts or age-related visual loss.
To improve wound healing
Intravenous vitamin C benefits severely burned patients. Other clinical trials show conflicting results for pressure sores or other wounds. Deficiencies in vitamin C can slow wound healing.
Do Not Take If
- You suffer from recurrent kidney stones: Increased kidney stone formation can occur and lead to kidney failure.
- You have kidney problems or are on dialysis.
- You have hemochromatosis: Vitamin C increases iron absorption, transport, and storage in the body.
- You have known G6PDH (glucose-6-dehydrogenase) deficiency: Rupture of red blood cells may occur with high doses of Vitamin C.
- You are a cancer patient undergoing radiation therapy or chemotherapy: Vitamin C may interfere with these treatments and lessen their effect.
- You are taking bortezomib: Vitamin C may reduce the effect of this drug.
- You are taking paracetamol: Vitamin C can increase the risk of side effects of paracetamol.
Laboratory experiments and animals studies suggest that cancer cells preferentially uptake vitamin C. This raises the possibility that high-dose vitamin C may be detrimental to cancer patients.
Some practitioners recommend using vitamin C supplements to reduce the side effects of chemotherapy and radiation therapy. However, it is controversial whether antioxidants like vitamin C can also lessen the effects of these treatments, which work by creating free radicals to kill cancer cells. So what protects healthy cells may protect cancer cells as well. This question is still not fully understood and patients who are interested in taking antioxidant supplements should consult with their doctor.
For Healthcare Professionals
Vitamin C, also known as ascorbic acid, exists as either ascorbic acid or ascorbate. It is a water-soluble vitamin that is 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 the flu, wound healing, cardiovascular health, and cancer prevention. High-dose intravenous (IV) vitamin C is being studied as a cancer treatment.
Vitamin C has been investigated in many clinical and epidemiologic studies. Regular intake of vitamin C supplements may reduce duration and severity of the common cold. However, the effect is minimal except in people exposed to acute severe physical stress (2). In adults undergoing oral surgery, vitamin C reduced postoperative pain without increased side-effects (72). It is also believed to promote cardiovascular health but findings are inconsistent. Previous studies suggest that dietary vitamin C, but not supplements, may reduce the risk of coronary heart diseases (3). However, two large-scale randomized trials did not find any benefits (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 of vitamin C’s effects in reducing blood pressure are conflicting as well (7) (8). Additional studies do not support prophylactic vitamin C to lower postoperative atrial fibrillation incidence among cardiac surgery patients (69) (70), but conflicting data show a reduction in other post-surgical side effects (71), and a systematic review reported reductions in the length of hospital stay, duration of mechanical ventilation, and decreased incidence of atrial fibrillation (80).
In a study of patients with sepsis and ARDS, intravenous vitamin C had no significant effect on organ dysfunction or inflammatory markers (84).
Vitamin C supplementation may reduce blood glucose and lipids in type 2 diabetes patients (9). It also decreases urinary infection rates in pregnant women (10); lowers incidence of organ failure and shortens ICU stay after surgery (11); and protects against Alzheimer’s disease (12) (13). Vitamin C can help eradicate H. pylori infection when added to a standard medication regimen (14) and supplementation may potentiate treatment efficacy in some patients with thalassemia (68). However, antioxidants including vitamin C do not prevent or slow the progression of age-related cataracts (15) or macular degeneration (16). Vitamin C may also reduce endurance training efficiency (17).
The role of vitamin C in cancer prevention is not definitive. Conclusions of a systematic review suggest its safety (81) and another study showed its ability to reduce oxidative stress (18). Further, high plasma levels of vitamin C were associated with lower gastrointestinal cancer incidence probably due to its protective effects against dietary carcinogenic nitroso compounds (19). Intake of vitamins A, C, or E reduced the risk of cervical cancer (20), but they did not prevent gastrointestinal (21), prostate (22), lung cancers (23) , or other cancer incidences, or affect cancer mortality (24) (73). In addition, vitamin C supplementation was associated with increased risk of liver cancer, although this effect was not observed with vitamin C from dietary sources (25).
High-dose vitamin C has been long been used as an alternative cancer treatment (26) based on the hypothesis that the formation of new collagen resists malignant infiltration (27). Early reports using parenteral plus oral ascorbic acid showed promising results (28), but subsequent randomized placebo-controlled 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). A higher pharmacologic concentration, achieved only via intravenous injection, had selective cytotoxic effects on cancer cell lines (32) (33). 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.
There are 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). Preliminary findings indicate that short-term vitamin C plus E supplementation during radiotherapy had a protective effect against xerostomia in patients with head and neck cancer (75); and a combination of vitamins C, E, and selenium lowered radioiodine-induced oxidative stress in thyroid cancer patients (76).
Adverse effects from vitamin C are 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 (NSCLC) and glioblastoma (GBM) cells, pharmacological ascorbate selectively sensitized these cells (79). Ascorbate decreases colon cancer cell proliferation by downregulating specificity proteins (Sp) (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 (SVCT-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.
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 prooxidant 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).