Vitamin C

Purported Benefits, Side Effects & More
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Vitamin C

Purported Benefits, Side Effects & More
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Vitamin C

Common Names

  • Ascorbate
  • Sodium ascorbate
  • Ascorbic Acid

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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 are the potential uses and benefits?

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

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?

Vitamin C is generally safe. But supplements can sometimes cause side effects such as:

  • Nausea (feeling like you’re going to throw up)
  • Diarrhea (loose or watery bowel movements)
  • Stomach cramps
  • Low blood sugar
  • Low blood pressure
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.
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For Healthcare Professionals

Scientific Name
Ascorbic Acid, C6H8O6
Clinical Summary

Vitamin C is a water-soluble vitamin that exists as either ascorbic acid or ascorbate. It is found in many fresh fruits and vegetables and is essential for a variety of physiologic functions. It is not synthesized in the human body, and deficiency can cause scurvy.

Vitamin C is promoted as an antioxidant supplement to support immune health. Its effect on the common cold is generally minimal (2), and high-dose vitamin C alone or with high-dose zinc did not decrease SARS-CoV-2 symptoms (90). But supplementation in pregnant smokers improved respiratory health in the offspring (102).

In large randomized trials, supplemental vitamin C did not reduce coronary heart disease risk (4) (5). Further, it may increase risk of mortality and nonfatal myocardial infarction in patients with coronary artery disease (6).

The role of vitamin C in cancer prevention is mixed (19) (20) (21) (22) (23) (24) (25) (73).

Although increased chemotherapy-associated adverse effects have been observed with inadequate vitamin C intake (41), there are also theories against the use of vitamin C supplements during treatment. Preclinical studies suggest cancer cells preferentially uptake vitamin C (37) and render some chemotherapy drugs less effective (38). Also, a major concern with antioxidant use is potential interference with cancer treatments that rely on ROS production for their cytotoxic activities (39).

Oral supplement studies
A few small trials suggest vitamin C along with other supplements may reduce some cancer therapy-induced side effects (75) (76), but older trials in advanced cancer patients using 10 g per day of oral vitamin C did not yield significant benefit (29) (30). This lack of effect may be explained by limited plasma concentrations reached via oral route in a pharmacokinetic study (31).

Other small studies suggest supplementation does not reduce therapeutic effects of paclitaxel and carboplatin (40) and may enhance effects of DNA methyl transferase inhibitors (89), but more studies are needed.

Although adverse effects from vitamin C supplements are generally rare, there are reports of GI 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.

Intravenous high-dose studies
Intravenous high-dose vitamin C has been used as an alternative cancer treatment (26) based on the hypothesis that formation of new collagen resists malignant infiltration (27). Higher pharmacologic concentrations had selective cytotoxic effects in cancer cell lines (32) (33). Early reports of parenteral plus oral ascorbic acid showed promising results (31). High-dose IV ascorbic acid up to 1.5 g/kg/day (34) or used with chemotherapy (74) appears to be well-tolerated. Other preliminary data suggest various regimens may improve quality of life in terminal cancer patients (35) and reduce chemotherapy-associated toxicity (67).

However, high-dose IV vitamin C as an anticancer treatment (34) (36) should be considered an investigational drug used only in clinical trial settings, as it did not improve survival in patients with metastatic colorectal cancer (100), did not improve PSA response in patients with metastatic castration-resistant prostate cancer (107), sepsis studies have not found benefit (84) (85) (91) (92) (103) (108), and adverse events (93) (94) (95) (101), and interference with glucometer readings (96) (97) have been reported.

Food Sources

Citrus fruits, fresh vegetables, berries, melons

Purported Uses and Benefits
  • Bronchitis
  • Cardiovascular disease
  • Common cold
  • Immunostimulation
  • Infections
  • Wound healing
Mechanism of Action

Vitamin C is essential for the formation and polymerization of collagen, so its deficiency results in scurvy and poor wound healing (1). It also inhibits hyaluronidase leading to the hypothesis that it can prevent metastasis by strengthening collagen (45).

Ascorbic acid acts as an antioxidant to protect against oxidative damage from free radicals (46). It inactivates nitric oxide, improves endothelium-dependent vasodilation (47), and acts via different mechanisms depending on its plasma concentration.

Plasma concentrations <0.1 mM are achieved through oral intake of dietary or supplemental forms. At pharmacologic plasma concentrations of 0.3–20 mM via IV injection, ascorbic acid is oxidized to an ascorbate radical which acts as a prodrug for hydrogen peroxide formation within interstitial fluids (32) (33). This induces DNA damage and adenosine triphosphate (ATP) depletion, and triggers ataxia telangiectasia mutated/adenosine monophosphate–activated protein kinase and inhibition of mammalian target of rapamycin in cancer cells (67).

Other preclinical data suggest 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), increased p53 activity (52), and overexpression of sodium-dependent vitamin C transporter 2 (53). High-dose vitamin C also appeared to suppress 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).

Contraindications
  • Recurrent kidney stone formation
  • Renal impairment or on chronic hemodialysis
  • Hematochromatosis
  • Known G6PDH deficiency
Adverse Reactions

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).
Acute kidney injury: In a 55-year-old female following excessive intake of vitamin C necessitating hemodialysis (104).

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.
Post-infusion  (74)
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).
Acute oxalate nephropathy: In a 41-year-old female kidney transplant recepient following high dose intravenous vitamin C (105).
Sarcoidal granulomatous reaction: In a 54-year-old female following microneedling treatments on the neck with vitamin C serum (106).
Hemolysis: In two patients with colorectal cancer, with glucose-6-phosphate dehydrogenase deficiency, following high dose intravenous vitamin C treatment. Both patients imrpoved after blood replacement therapy (109).

Herb-Drug Interactions

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).

Dosage (OneMSK Only)
References
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