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 patients with septic shock, vitamin C combined with corticosteroids and thiamine did not protect against organ injury ⁽⁸⁵⁾. But 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 acute respiratory distress syndrome (ARDS), intravenous vitamin C had no significant effect on organ dysfunction or inflammatory markers ⁽⁸⁴⁾, but it may help prevent postoperative pulmonary complications in low-risk cardiac surgery patients ⁽⁸⁶⁾; improve ventricular function in patients undergoing coronary artery bypass grafting along with decreasing the length of ICU stay ⁽⁸⁷⁾; as well as minimize oxidative imbalance and vascular remodeling caused by mental stress ⁽⁸⁸⁾.

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⁾; a combination of vitamins C, E, and selenium lowered radioiodine-induced oxidative stress in thyroid cancer patients ⁽⁷⁶⁾; and supplementation may enhance the biological effects of DNA methyl transferase inhibitors in patients with myeloid cancer ⁽⁸⁹⁾.

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.