BioFactorsVolume 15, Issue 2-4 p. 71-74 Article Ideal vitamin C intake Mark Levine, Corresponding Author Mark Levine Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USABuilding 10 Room 4D52 MSC 1372, National Institutes of Health, Bethesda MD 20892-1372, USA. Tel.: +1 301 402 5588; Fax: +1 301 402 6436; E-mail: [email protected]Search for more papers by this authorYaohui Wang, Yaohui Wang Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorArie Katz, Arie Katz Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorPeter Eck, Peter Eck Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorOran Kwon, Oran Kwon Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorShenglin Chen, Shenglin Chen Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorJe-Hyuk Lee, Je-Hyuk Lee Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorSebastian J. Padayatty, Sebastian J. Padayatty Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this author Mark Levine, Corresponding Author Mark Levine Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USABuilding 10 Room 4D52 MSC 1372, National Institutes of Health, Bethesda MD 20892-1372, USA. Tel.: +1 301 402 5588; Fax: +1 301 402 6436; E-mail: [email protected]Search for more papers by this authorYaohui Wang, Yaohui Wang Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorArie Katz, Arie Katz Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorPeter Eck, Peter Eck Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorOran Kwon, Oran Kwon Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorShenglin Chen, Shenglin Chen Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorJe-Hyuk Lee, Je-Hyuk Lee Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this authorSebastian J. Padayatty, Sebastian J. Padayatty Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Building 10 Room 4D52, MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USASearch for more papers by this author First published: 16 December 2008 https://doi.org/10.1002/biof.5520150203Citations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 M. Levine, S. C. Rumsey, R. C. Daruwala, J. B. Park and Y. Wang, Criteria and recommendations for vitamin C intake, J.A.M.A. 281 (1999), 1415–1423. 2 M. Levine, C. Conry-Cantilena and Y. Wang et al., Vitamin C pharmacokinetics in healthy volunteers: evidence for a Recommended Dietary Allowance, Proc. Natl. Acad. Sci. USA 93 (1996), 3704–3709. 3 J. King, Y. Wang, R. W. Welch, K. R. Dhariwal, C. Conry-Cantilena and M. Levine, Use of a new vitamin C-deficient diet in a depletion/repletion clinical trial, Am. J. Clin. Nutr. 65 (1997), 1434–1440. 4 J. F. Graumlich, T. M. Ludden, C. Conry-Cantilena, L. R. Jr. Cantilena L. R., Y. Wang and M. Levine, Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion, Pharmaceutical Research 14 (1997), 1133–1139. 5 M. Levine, New concepts in the biology and biochemistry of ascorbic acid, N. Engl. J. Med. 314 (1986), 892–902. Citing Literature Volume15, Issue2-42001Pages 71-74 ReferencesRelatedInformation

The recently released Recommended Dietary Allowance of vitamin C for women, 75 mg daily, was based on data for men. We now report results of a depletion–repletion study with healthy young women hospitalized for 186 +/− 28 days, using vitamin C doses of 30–2,500 mg daily. The relationship between dose and steady-state plasma concentration was sigmoidal. Only doses above 100 mg were beyond the linear portion of the curve. Plasma and circulating cells saturated at 400 mg daily, with urinary elimination of higher doses. Biomarkers of endogenous oxidant stress, plasma and urine F2-isoprostanes, and urine levels of a major metabolite of F2-isoprostanes were unchanged by vitamin C at all doses, suggesting this vitamin does not alter endogenous lipid peroxidation in healthy young women. By using Food and Nutrition Board guidelines, the data indicate that the Recommended Dietary Allowance for young women should be increased to 90 mg daily.

To conduct an inpatient study on the recommended dietary allowance (RDA) for vitamin C, we developed a unique vitamin C-deficient diet using a nutrient database and selective menus. Fourteen different menus were developed offering > 300 items with 0-2.4 mg vitamin C per serving. During the 4-6 mo volunteers were hospitalized, daily dietary vitamin C was restricted to < or = 5.0 mg. The mean daily dietary vitamin C intake was < 3.9 mg for the seven study subjects. With concurrent supplementation, the diet provided > or = 85% of the RDA for 17 essential nutrients. Within 3 wk of admission the diet induced vitamin C deficiency as indicated by plasma concentrations, which decreased from 23 +/- 6.9 to 6.9 +/- 2.0 mumol/L. Daily intake of vitamin C and five other nutrients was determined by nutrient database analyses. Mean energy, protein, the iron were 105-185% of the RDA and total and saturated fat were 32% and 10% of energy, respectively. Weight and nutritionally relevant indexes remained normal. Dietary adherence, calculated by the number of days with < or = 5.0 mg vitamin C per total study days, was 88-98% per repletion dose. Computer analyses of menu selections permitted individual preferences to be met while restricting vitamin C intake to < or = 5.0 mg/d. There were no complications from the diet during the depletion and repletion phase. With this diet, ascorbic acid pharmacokinetics for escalating doses could be determined in healthy volunteers.

Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30- and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value.