The safety and efficacy of the use of vitamin C and other antioxidants during cancer treatment is controversial [ 53, 91, 92]. Some data indicate that antioxidants might protect tumor cells from the action of radiation therapy and chemotherapeutic agents, such as cyclophosphamide, chlorambucil, carmustine, busulfan, thiotepa, and doxorubicin [ 54, 91, 93, 94]. At least some of these data have been criticized because of poor study design [ 52]. Other data suggest that antioxidants might protect normal tissues from chemotherapy- and radiation-induced damage [ 91, 93] and/or enhance the effectiveness of conventional cancer treatment [ 95]. However, due to the physiologically tight control of vitamin C, it is unclear whether oral vitamin C supplements could alter vitamin C concentrations enough to produce the suggested effects. Individuals undergoing chemotherapy or radiation should consult with their oncologist prior to taking vitamin C or other antioxidant supplements, especially in high doses [ 54]. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)

Deicher R, Hörl WH. Vitamin C in chronic kidney disease and hemodialysis patients. Kidney Blood Press Res 2003;26:100-6. [ PubMed abstract] Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Intake of vitamins B6 and C and the risk of kidney stones in women. J Am Soc Nephrol 1999;10:840-5. [ PubMed abstract] Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 2006;(2):CD000254. [ PubMed abstract]

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Seifried HE, Anderson DE, Sorkin BC, Costello RB. Free radicals: the pros and cons of antioxidants. Executive summary report. J Nutr 2004;134:3143S-63S. [ PubMed abstract] Osganian SK, Stampfer MJ, Rimm E, Spiegelman D, Hu FB, Manson JE, et al. Vitamin C and risk of coronary heart disease in women. J Am Coll Cardiol 2003;42:246-52. [ PubMed abstract] Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. [ PubMed abstract] The intestinal absorption of vitamin C is regulated by at least one specific dose-dependent, active transporter [ 4]. Cells accumulate vitamin C via a second specific transport protein. In vitro studies have found that oxidized vitamin C, or dehydroascorbic acid, enters cells via some facilitated glucose transporters and is then reduced internally to ascorbic acid. The physiologic importance of dehydroascorbic acid uptake and its contribution to overall vitamin C economy are unknown. Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care 2002;5:66-74. [ PubMed abstract]

Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH. Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis. BMJ 2007;335:755. [ PubMed abstract] Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, et al. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst 1999;91:547-56. [ PubMed abstract] Cook NR, Albert CM, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, 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 2007;167:1610-8. [ PubMed abstract] At this time, the evidence is inconsistent on whether dietary vitamin C intake affects cancer risk. Results from most clinical trials suggest that modest vitamin C supplementation alone or with other nutrients offers no benefit in the prevention of cancer.Most case-control studies have found an inverse association between dietary vitamin C intake and cancers of the lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and esophagus [ 2, 4]. Plasma concentrations of vitamin C are also lower in people with cancer than controls [ 2]. According to the 2001–2002 National Health and Nutrition Examination Survey (NHANES), mean intakes of vitamin C are 105.2 mg/day for adult males and 83.6 mg/day for adult females, meeting the currently established RDA for most nonsmoking adults [ 19]. Mean intakes for children and adolescents age 1–18 years range from 75.6 mg/day to 100 mg/day, also meeting the RDA for these age groups [ 19]. Although the 2001–2002 NHANES analysis did not include data for breastfed infants and toddlers, breastmilk is considered an adequate source of vitamin C [ 8, 14]. Use of vitamin C-containing supplements is also relatively common, adding to the total vitamin C intake from food and beverages. NHANES data from 1999–2000 indicate that approximately 35% of adults take multivitamin supplements (which typically contain vitamin C) and 12% take a separate vitamin C supplement [ 20]. According to 1999–2002 NHANES data, approximately 29% of children take some form of dietary supplement that contains vitamin C [ 21]. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 2008;19:1969-74. [ PubMed abstract] Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119:1417-36. [ PubMed abstract] Levine M, Wang Y, Padayatty SJ, Morrow J. A new recommended dietary allowance of vitamin C for healthy young women. Proc Natl Acad Sci U S A 2001;98:9842-6. [ PubMed abstract]

Gershoff SN. Vitamin C (ascorbic acid): new roles, new requirements? Nutr Rev 1993;51:313-26. [ PubMed abstract] Until the end of the 18 th century, many sailors who ventured on long ocean voyages, with little or no vitamin C intake, contracted or died from scurvy. During the mid-1700s, Sir James Lind, a British Navy surgeon, conducted experiments and determined that eating citrus fruits or juices could cure scurvy, although scientists did not prove that ascorbic acid was the active component until 1932 [ 24-26]. Moyad MA, Combs MA, Vrablic AS, Velasquez J, Turner B, Bernal S. Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations. Adv Ther 2008;25:995-1009. [ PubMed abstract] Emerging research suggests that the route of vitamin C administration (intravenous [IV] vs. oral) could explain the conflicting findings [ 1, 46, 47]. Most intervention trials, including the one conducted by Moertel and colleagues, used only oral administration, whereas Cameron and colleagues used a combination of oral and IV administration. Oral administration of vitamin C, even of very large doses, can raise plasma vitamin C concentrations to a maximum of only 220 micromol/L, whereas IV administration can produce plasma concentrations as high as 26,000 micromol/L [ 47, 48]. Concentrations of this magnitude are selectively cytotoxic to tumor cells in vitro [ 1, 67]. Research in mice suggests that pharmacologic doses of IV vitamin C might show promise in treating otherwise difficult-to-treat tumors [ 49]. A high concentration of vitamin C may act as a pro-oxidant and generate hydrogen peroxide that has selective toxicity toward cancer cells [ 49-51]. Based on these findings and a few case reports of patients with advanced cancers who had remarkably long survival times following administration of high-dose IV vitamin C, some researchers support reassessment of the use of high-dose IV vitamin C as a drug to treat cancer [ 3, 47, 49, 52]. Today, vitamin C deficiency and scurvy are rare in developed countries [ 8]. Overt deficiency symptoms occur only if vitamin C intake falls below approximately 10 mg/day for many weeks [ 5-8, 22, 23]. Vitamin C deficiency is uncommon in developed countries but can still occur in people with limited food variety. Groups at Risk of Vitamin C InadequacyEpidemiologic evidence suggests that higher consumption of fruits and vegetables is associated with lower risk of most types of cancer, perhaps, in part, due to their high vitamin C content [ 1, 2]. Vitamin C can limit the formation of carcinogens, such as nitrosamines [ 2, 29], in vivo; modulate immune response [ 2, 4]; and, through its antioxidant function, possibly attenuate oxidative damage that can lead to cancer [ 1]. Due to the enhancement of nonheme iron absorption by vitamin C, a theoretical concern is that high vitamin C intakes might cause excess iron absorption. In healthy individuals, this does not appear to be a concern [ 8]. However, in individuals with hereditary hemochromatosis, chronic consumption of high doses of vitamin C could exacerbate iron overload and result in tissue damage [ 4, 8]. Bruno EJ Jr, Ziegenfuss TN, Landis J. Vitamin C: research update. Curr Sports Med Rep 2006;5:177-81. [ PubMed abstract] Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products.

Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. J Urol 1996;155:1847-51. [ PubMed abstract] Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties. Nature 1998;392:559. [ PubMed abstract] Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals Honarbakhsh S, Schachter M. Vitamins and cardiovascular disease. Br J Nutr 2008:1-19. [ PubMed abstract] Francescone MA, Levitt J. Scurvy masquerading as leukocytoclastic vasculitis: a case report and review of the literature. Cutis 2005;76:261-6. [ PubMed abstract]Hecht SS. Approaches to cancer prevention based on an understanding of N-nitrosamine carcinogenesis. Proc Soc Exp Biol Med 1997;216:181-91. [ PubMed abstract] High dietary intakes of vitamin C and higher plasma ascorbate concentrations have been associated with a lower risk of cataract formation in some studies [ 2, 4]. In a 5-year prospective cohort study conducted in Japan, higher dietary vitamin C intake was associated with a reduced risk of developing cataracts in a cohort of more than 30,000 adults age 45–64 years [ 74]. Results from two case-control studies indicate that vitamin C intakes greater than 300 mg/day reduce the risk of cataract formation by 70%–75% [ 2, 4]. Use of vitamin C supplements, on the other hand, was associated with a 25% higher risk of age-related cataract extraction among a cohort of 24,593 Swedish women age 49–83 years [ 75]. These findings applied to study participants who took relatively high-dose vitamin C supplements (approximately 1,000 mg/day) and not to those who took multivitamins containing substantially less vitamin C (approximately 60 mg/day). Most Popular Products: Butter Bronzer , Eye Booster Ultra-Fine Liquid Eyeliner, Organic Wear Natural Origin, Mascara and the new Diamond Plumper Lip Gloss and All-Star Face Palette, Other clinical trials have generally examined the effects on cardiovascular disease of supplements combining vitamin C with other antioxidants, such as vitamin E and beta-carotene, making it more difficult to isolate the potential contribution of vitamin C. The SU.VI.MAX study examined the effects of a combination of vitamin C (120 mg/day), vitamin E (30 mg/day), beta-carotene (6 mg/day), selenium (100 mcg/day), and zinc (20 mg/day) in 13,017 French adults from the general population [ 33]. After a median follow-up time of 7.5 years, the combined supplements had no effect on ischemic cardiovascular disease in either men or women. In the Women's Angiographic Vitamin and Estrogen study, involving 423 postmenopausal women with at least one coronary stenosis of 15%–75%, supplements of 500 mg vitamin C plus 400 IU vitamin E twice per day not only provided no cardiovascular benefit, but significantly increased all-cause mortality compared with placebo [ 65]. Taylor PR, Li B, Dawsey SM, Li JY, Yang CS, Guo W, et al. Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. Cancer Res 1994;54(7 Suppl):2029s-31s. [ PubMed abstract]