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.