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Vitamin C

Vitamin C

Common Names

  • Ascorbate
  • Sodium ascorbate

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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 a known antioxidant that protects the body against oxidative stress. This means that it reacts with and neutralizes free radicals in the body that can cause cellular and DNA damage. It is also important for the production of many essential molecules in the body, including proteins. Vitamin C plays an important role in the formation of collagen, which is the main structural protein in the skin. Therefore, vitamin C helps promote wound healing. Since the body cannot synthesize vitamin C, it must be gained from outside sources. In addition, scientists think that vitamin C might help reduce inflammation. However, vitamin C can make many chemotherapy drugs less effective. Patients should speak with their doctor before using vitamin C.

Purported Uses
  • To prevent and treat the common cold and upper respiratory infections
    Numerous clinical trials have shown that high-dose vitamin C (around 3 grams per day) does not prevent the common cold and other upper respiratory infections, but that it can slightly reduce the duration and severity of symptoms.
  • To prevent cancer
    Some studies suggest vitamin C from dietary sources can reduce risk of certain cancers. However, most large-scale trials did not find vitamin C and other antioxidants useful in preventing cancers.
  • To treat cancer
    High doses of oral and injectable vitamin C have been used as alternative cancer treatment. Clinical studies concluded oral vitamin C is not effective, probably due to limited absorption. High-dose of intravenous vitamin C is 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
    Long-term clinical trials show that antioxidant intake has no effect on development of cataracts or age-related visual loss.
  • To improve wound healing
    Clinical trials indicate that intravenous vitamin C benefits severely burned patients. Other clinical trials show conflicting results regarding the use of vitamin C for pressure sores or other wounds. Deficiencies in vitamin C are known to impair wound healing.

Do Not Take If
  • You suffer from recurrent kidney stones: Increased kidney stone formation can occur and lead to acute kidney failure damage.
  • You have kidney impairment or are on chronic hemodialysis.
  • 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 at high doses of Vitamin C.
  • You are a cancer patient undergoing radiation therapy or chemotherapy: These therapies use free radicals to kill cancer cells. Vitamin C or other antioxidants may neutralize these free radicals and lessen their effect.
  • You are taking bortezomib: Vitamin C may reduce the effect of this drug.

Side Effects
  • Nausea
  • Diarrhea
  • Stomach cramps
  • Low blood sugar and low blood pressure are possible with doses greater than 1 gram.
  • Excessive use of chewable tablets may break down tooth enamel, increasing the risk of tooth erosion and decay.

Special Point

Recent 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 undergoing radiation or chemotherapy.

It is controversial whether antioxidants like vitamin C can lessen or negate the effects of chemotherapy and radiation therapy. Because these therapies work by creating free radicals that kill cancer cells, some physicians have suggested that high levels of antioxidants can neutralize these free radicals and thereby protect cancer cells from these therapies. 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 more than the RDA of any antioxidant should consult with their doctor.

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For Healthcare Professionals

Scientific Name
Ascorbic Acid, C6H8O6

Clinical Summary

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin that is found in many fresh fruits and vegetables. It is essential for a variety of physiologic functions that include formation of collagen, 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 cold and flu, for wound healing, cardiovascular health, and cancer prevention. High-dose of intravenous vitamin C has also been used as an alternative cancer treatment.

The purported effects of vitamin C have been examined in many clinical and epidemiologic studies. Regular intake of vitamin C supplements may reduce the duration and severity of common cold. However, the effect is minimal except in people exposed to acute severe physical stress (2). Vitamin C is believed to promote cardiovascular health but findings are inconsistent. Previous studies suggest that intake of dietary vitamin C, not supplements, may reduce the risk of coronary heart diseases (3). However, two large scale randomized trials did not find any benefits (4) (5). Furthermore, supplementation with vitamins C and E increased risk of mortality and nonfatal myocardial infarction in patients with coronary artery disease (6). Data on vitamin C’s effect in reducing blood pressure are also conflicting (7) (8).

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 the 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 standard medication regimen (14). However, antioxidants including vitamin C do not prevent or slow the progression of age-related cataract (15) or macular degeneration (16).Vitamin C may also reduce endurance training efficiency (17).

The role of vitamin C in cancer prevention is unclear. Studies indicate that vitamin C reduces oxidative stress (18). High plasma level of vitamin C is 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 risk of cervical cancer (20), but they do not prevent gastrointestinal (21), prostate (22), lung cancers (23) and other cancer incidence or affect cancer mortality (24). Further, vitamin C supplementation is associated with increased risk of liver cancer, although this effect is 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 10g per day of oral vitamin C did not demonstrate any significant benefits (29) (30). This lack of effect is explained by the finding of 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 1.5g /kg/day appears to be well-tolerated (34), may improve the quality of life of terminal cancer patients (35), and reduce chemotherapy-associated toxicity in patients with ovarian cancer (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.

Interestingly, there is contradicting evidence against the use of vitamin C supplements during chemotherapy. In vitro and animal studies found that cancer cells preferentially uptake vitamin C (37) and render some chemotherapy drugs less effective (38). Also, a major concern surrounding 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 chemo-associated adverse effects with inadequate intake of vitamin C in children with acute lymphoblastic leukemia (41).

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 history of oxalate kidney stones, renal insufficiency, hematochromatosis, or those undergoing chemotherapy should consult their physicians before taking vitamin C supplements.

Food Sources

Citrus fruits, fresh vegetables, berries, melons

Purported Uses
  • Bronchitis
  • Cancer prevention
  • Cancer treatment
  • Cardiovascular disease
  • Cataracts
  • Common cold
  • Glaucoma
  • Hypertension
  • Immunostimulation
  • Infections
  • Parkinson’s disease
  • Strength and stamina
  • Wound healing

Mechanism of Action

Ascorbic acid 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 is 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 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 ovarian cancer cells (67).

Ascorbate decreases colon cancer cell proliferation by downregulating specificity proteins (Sp) (48). It 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).

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
  • Large doses of vitamin C may induce copper deficiency

Adverse Reactions

Common: Nausea, diarrhea and stomach cramps
Reported (oral): In patients with a history of kidney stones, increased oxalate kidney stone formation occurs with possible nephrolithiasis, acute renal failure, or renal insufficiency (42) (58) (59).
Reported (oral): In patients with G6PDH deficiency, hemolytic anemia may occur at high doses (43) (44).
Reported (oral): Severe cyanide poisoning following ingestion of 3 grams of amygdalin with concurrent use of 4800 mg of vitamin C per day (60).
Reported (oral): Excessive use of chewable tablets may break down tooth enamel, increasing the risk of dental caries (61).

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 can reduce the effectiveness of many 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).

Herb Lab Interactions

High dose ascorbic acid supplementation may alter results of urine glucose testing strips, and may cause a false negative guaiac (occult blood) test (66).

Dosage (OneMSK Only)

References

  1. Sauberlich HE. Pharmacology of vitamin C. Annual review of nutrition. 1994;14:371-391.

  2. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013;1:CD000980.

  3. Ye Z, Song H. Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. Eur J Cardiovasc Prev Rehabil. Feb 2008;15(1):26-34.

  4. Sesso HD, Buring JE, Christen WG, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA. Nov 12 2008;300(18):2123-2133.

  5. Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women’s Antioxidant Cardiovascular Study. Arch Intern Med. Aug 13-27 2007;167(15):1610-1618.

  6. Waters DD, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. Nov 20 2002;288(19):2432-2440.

  7. Kim MK, Sasaki S, Sasazuki S, et al. Lack of long-term effect of vitamin C supplementation on blood pressure. Hypertension. Dec 2002;40(6):797-803.

  8. Mullan BA, Young IS, Fee H, et al. Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension. Dec 2002;40(6):804-809.

  9. Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. Nov 2007;126(5):471-474.

  10. Ochoa-Brust GJ, Fernandez AR, Villanueva-Ruiz GJ, et al. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86(7):783-787.

  11. Nathens AB, Neff MJ, Jurkovich GJ, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg. Dec 2002;236(6):814-822.

  12. Foley DJ, White LR. Dietary intake of antioxidants and risk of Alzheimer disease: food for thought. JAMA. Jun 26 2002;287(24):3261-3263.

  13. Engelhart MJ, Geerlings MI, Ruitenberg A, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. Jun 26 2002;287(24):3223-3229.

  14. Zojaji H, Talaie R, Mirsattari D, et al. The efficacy of Helicobacter pylori eradication regimen with and without vitamin C supplementation. Dig Liver Dis. Sep 2009;41(9):644-647.

  15. Mathew MC, Ervin AM, Tao J, et al. Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract. Cochrane Database Syst Rev. 2012;6:CD004567.

  16. Chong EW, Wong TY, Kreis AJ, et al. Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis. BMJ. Oct 13 2007;335(7623):755.

  17. Gomez-Cabrera MC, Domenech E, Romagnoli M, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. Jan 2008;87(1):142-149.

  18. Muralikrishnan G, Amanullah S, Basha MI, et al. Effect of vitamin C on lipidperoxidation and antioxidant status in tamoxifen-treated breast cancer patients. Chemotherapy. 2010;56(4):298-302.

  19. Loh YH, Jakszyn P, Luben RN, et al. N-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study. Am J Clin Nutr. May 2011;93(5):1053-1061.

  20. Kim J, Kim MK, Lee JK, et al. Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea. Nutr Cancer. 2010;62(2):181-189.

  21. Bjelakovic G, Nikolova D, Simonetti RG, et al. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. Oct 2-8 2004;364(9441):1219-1228.

  22. Kirsh VA, Hayes RB, Mayne ST, et al. Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst. Feb 15 2006;98(4):245-254.

  23. Cortes-Jofre M, Rueda JR, Corsini-Munoz G, et al. Drugs for preventing lung cancer in healthy people. Cochrane Database Syst Rev. 2012;10:CD002141.

  24. Lin J, Cook NR, Albert C, et al. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J Natl Cancer Inst. Jan 7 2009;101(1):14-23.

  25. Zhang W, Shu XO, Li H, et al. Vitamin intake and liver cancer risk: a report from two cohort studies in China. J Natl Cancer Inst. Aug 8 2012;104(15):1173-1181.

  26. Padayatty SJ, Sun AY, Chen Q, et al. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PloS one. 2010;5(7):e11414.

  27. Cameron E, Pauling L, Leibovitz B. Ascorbic acid and cancer: a review. Cancer Res. Mar 1979;39(3):663-681.

  28. Cameron E, Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact. Oct 1974;9(4):285-315.

  29. Creagan ET, Moertel CG, O’Fallon JR, et al. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. New Engl J Med. Sep 27 1979;301(13):687-690.

  30. Moertel CG, Fleming TR, Creagan ET, et al. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. New Engl J Med. Jan 17 1985;312(3):137-141.

  31. Padayatty SJ, Sun H, Wang Y, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Int Med. Apr 6 2004;140(7):533-537.

  32. Chen Q, Espey MG, Krishna MC, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A. Sep 20 2005;102(38):13604-13609.

  33. Chen Q, Espey MG, Sun AY, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A. Aug 12 2008;105(32):11105-11109.

  34. Hoffer LJ, Levine M, Assouline S, et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. Nov 2008;19(11):1969-1974.

  35. Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci. Feb 2007;22(1):7-11.

  36. Padayatty SJ, Riordan HD, Hewitt SM, et al. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ. Mar 28 2006;174(7):937-942.

  37. Agus DB, Vera JC, Golde DW. Stromal cell oxidation: a mechanism by which tumors obtain vitamin C. Cancer Res. Sep 15 1999;59(18):4555-4558.

  38. Heaney ML, Gardner JR, Karasavvas N, et al. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res. Oct 1 2008;68(19):8031-8038.

  39. Lawenda BD, Kelly KM, Ladas EJ, et al. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. Jun 4 2008;100(11):773-783.

  40. Pathak AK, Bhutani M, Guleria R, et al. Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer. J Am Coll Nutr. Feb 2005;24(1):16-21.

  41. Kennedy DD, Tucker KL, Ladas ED, et al. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. Am J Clin Nutr. Jun 2004;79(6):1029-1036.

  42. Thomas LD, Elinder CG, Tiselius HG, et al. Ascorbic acid supplements and kidney stone incidence among men: a prospective study. JAMA Int Med. Mar 11 2013;173(5):386-388.

  43. Mehta JB, Singhal SB, Mehta BC. Ascorbic-acid-induced haemolysis in G-6-PD deficiency. Lancet. Oct 13 1990;336(8720):944.

  44. Rees DC, Kelsey H, Richards JD. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ. Mar 27 1993;306(6881):841-842.

  45. Cameron E. Vitamin C and cancer: an overview. Int J Vitam Nutr Res Suppl. 1982;23:115-127.

  46. Chen K, Suh J, Carr AC, et al. Vitamin C suppresses oxidative lipid damage in vivo, even in the presence of iron overload. Am J Physiol Endocrinol Metab. Dec 2000;279(6):E1406-1412.

  47. Taddei S, Virdis A, Ghiadoni L, et al. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation. Jun 9 1998;97(22):2222-2229.

  48. Pathi SS, Lei P, Sreevalsan S, et al. Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr Cancer. 2011;63(7):1133-1142.

  49. Chen P, Yu J, Chalmers B, et al. Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anti-Cancer Drugs. Apr 2012;23(4):437-444.

  50. Duarte TL, Almeida GM, Jones GD. Investigation of the role of extracellular H2O2 and transition metal ions in the genotoxic action of ascorbic acid in cell culture models. Toxicol Lett. Apr 5 2007;170(1):57-65.

  51. Ullah MF, Khan HY, Zubair H, et al. The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. Cancer Chemother Pharmacol. Jan 2011;67(1):103-110.

  52. Kim J, Lee SD, Chang B, et al. Enhanced antitumor activity of vitamin C via p53 in cancer cells. Free Radic Biol Med. Oct 15 2012;53(8):1607-1615.

  53. Hong SW, Lee SH, Moon JH, et al. SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment. Oncogene. Mar 21 2013;32(12):1508-1517.

  54. Corpe CP, Tu H, Eck P, et al. Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice. J Clin Invest. Apr 2010;120(4):1069-1083.

  55. Krajcovicova-Kudlackova M, Babinska K, Valachovicova M, et al. Vitamin C protective plasma value. Bratisl Lek Listy. 2007;108(6):265-268.

  56. Robitaille L, Mamer OA, Miller WH, Jr., et al. Oxalic acid excretion after intravenous ascorbic acid administration. Metabolism. Feb 2009;58(2):263-269.

  57. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC): National Academy Press; 2000.

  58. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. Dec 2004;15(12):3225-3232.

  59. McAllister CJ, Scowden EB, Dewberry FL, et al. Renal failure secondary to massive infusion of vitamin C. JAMA. Oct 5 1984;252(13):1684.

  60. Bromley J, Hughes BG, Leong DC, et al. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Ann Pharmacother. Sep 2005;39(9):1566-1569.

  61. Pronsky ZM. Food-Medication Interactions. 11th ed2000.

  62. Perrone G, Hideshima T, Ikeda H, et al. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. Sep 2009;23(9):1679-1686.

  63. Berenson JR, Yellin O, Woytowitz D, et al. Bortezomib, ascorbic acid and melphalan (BAM) therapy for patients with newly diagnosed multiple myeloma: an effective and well-tolerated frontline regimen. Eur J Hematol. Jun 2009;82(6):433-439.

  64. Chen P, Stone J, Sullivan G, et al. Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathione in preclinical cancer models. Free Radic Biol Med. Aug 1 2011;51(3):681-687.

  65. Eslami M, Badkoubeh RS, Mousavi M, et al. Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting. Tex Heart Inst J. 2007;34(3):268-274.

  66. Jaffe RM, Kasten B, Young DS, et al. False-negative stool occult blood tests caused by ingestion of ascorbic acid (vitamin C). Ann Int Med. Dec 1975;83(6):824-826.

  67. Ma Y, Chapman J, Levine M. High-Dose Parenteral Ascorbate Enhanced Chemosensitivity of Ovarian Cancer and Reduced Toxicity of Chemotherapy. Sci Transl Med. 5 February 2014. Vol. 6, Issue 222, p. 222ra18. DOI: 10.1126/scitranslmed.3007154.

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