Absorption, transport, and disposition of ascorbic acid in humans

Journal of Nutritional Biochemistry

Volumn 9, Issue 3, 1998, Pages 116-130

  Rumsey, Steven C ^a   Levine, Mark ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Ascorbate recycling; Ascorbic acid; Dehydroascorbic acid; Pharmacokinetics; Transport; Vitamin C

Indexed keywords

ASCORBIC ACID;

BIOAVAILABILITY; BLOOD LEVEL; DRUG ABSORPTION; DRUG TRANSPORT; ENERGY; HUMAN; INTESTINE ABSORPTION; RECYCLING; REVIEW; TISSUE DISTRIBUTION; TISSUE SPECIFICITY; TRANSPORT KINETICS; URINARY EXCRETION;

EID: 0032031568     PISSN: 09552863     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-2863(98)00002-3     Document Type: Review

References (209)

1. Burns J.J., Peyser P., Moltz A. Missing step in guinea pigs required for the biosynthesis of L-ascorbic acid. Science. 124:1956;1148-1149.
2. Chatterjee M.L., De M.S. Adrenal ascorbic acid content of rats after different rauwolfia alkaloids. Bull. Calcutta. Sch. Trop. Med. 17:1969;15-16.
3. Chatterjee I.B., Majumder A.K., Nandi B.K., Subramanian N. Synthesis and some major functions of vitamin C in animals. Ann. N.Y. Acad. Sci. 258:1975;24-47.
4. Nishikimi M., Fukuyama R., Minoshima S., Shimizu N., Yagi K. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 269:1994;13685-13688.
5. Lind, J. (1753). A Treatise on the Scurvy. A. Millar, London, UK.
6. Hodges J.R., Sadow J. Hypothalamo-pituitary-adrenal function in the rat after prolonged treatment with cortisol. Br. J. Pharmacol. 36:1969;489-495.
7. Irwin M.I., Hutchins B.K. A conspectus of research on vitamin C requirements of man. J. Nutr. 106:1976;821-879.
8. Hodges R.E. Scurvy. World Health Organ. Monogr. Ser. 1976;120-125.
9. Mussini E., Hutton J.J. Jr, Udenfriend S. Collagen proline hydroxylase in wound healing, granuloma formation, scurvy, and growth. Science. 157:1967;927-929.
10. Levine M. New concepts in the biology and biochemistry of ascorbic acid. N. Engl. J. Med. 314:1986;892-902.
11. Levine M., Hartzell W. Ascorbic acid The concept of optimum requirements . Ann. N.Y. Acad. Sci. 498:1987;424-444.
12. Levine M., Dhariwal K.R., Washko P.W., Butler J.D., Welch R.W., Wang Y.H., Bergsten P. Ascorbic acid and in situ kinetics A new approach to vitamin requirements . Am. J. Clin. Nutr. 54:1991;1157S-1162S.
13. Levine, M., Dhariwal, K.R., Washko, P., Welch, R., Wang, Y.H., Cantilena, C.C., and Yu, R. (1992). Ascorbic acid and reaction kinetics in situ: A new approach to vitamin requirements, J. Nutr. Sci. Vitaminol. (Tokyo) (Spec Issue) 169-172.
14. How should the recommended dietary allowances be revised? 1994;National Academy Press, Washington, DC.
15. Levine M., Conry-Cantilena C., Wang Y., Welch R.W., Washko P.W., Dhariwal K.R., Park J.B., Lazarev A., Graumlich J., King J., Cantilena L.R. Vitamin C pharmacokinetics in healthy volunteers Evidence for a Recommended Dietary Allowance . Proc. Natl. Acad. Sci. U.S.A. 93:1996;3704-3709.
16. Tolbert B.M., Ward J.B. Dehydroascorbic acid. Seib P.A., Tolbert B.M. Ascorbic Acid Chemistry, Metabolism, and Uses . 1982;101-123 American Chemical Society, Washington, DC.
17. Lewin S. Vitamin C Its Molecular Biology and Medical Potential . 1976;Academic Press, London.
18. Penney J.R., Zilva S.S. Chemical behavior of dehydro-l-ascorbic acid in vitro and in vivo. Biochem. J. 37:1943;403-417.
19. Lewin S. Hydrolytic rupture of ascorbate by adenosine 3′:5′-cyclic monophosphate phosphodiesterase. Biochem. Soc. Trans. 4:1976;71-73.
20. Washko P.W., Wang Y., Levine M. Ascorbic acid recycling in human neutrophils. J. Biol. Chem. 268:1993;15531-15535.
21. Buettner G.R. The pecking order of free radicals and antioxidants Lipid peroxidation, alpha-tocopherol, and ascorbate . Arch. Biochem. Biophys. 300:1993;535-543.
22. Welch R.W., Wang Y., Crossman A. Jr, Park J.B., Kirk K.L., Levine M. Accumulation of vitamin C (ascorbate) and its oxidized metabolite dehydroascorbic acid occurs by separate mechanisms. J. Biol. Chem. 270:1995;12584-12592.
23. Park J.B., Levine M. Purification, cloning, and expression of dehydroascorbic acid reduction activity from human neutrophils Identification as glutaredoxin . Biochem. J. 315:1996;931-938.
24. Stevenson N.R. Active transport of L-ascorbic acid in the human ileum. Gastroenterology. 67:1974;952-956.
25. Thorn N.A., Nielsen F.S., Jeppesen C.K. Characteristics of ascorbic acid uptake by isolated ox neurohypophyseal nerve terminals and the influence of glucocorticoid and tri-iodothyronine on uptake. Acta Physiol. Scand. 141:1991;97-106.
26. Wright J.R., Castranova V., Colby H.D., Miles P.R. Ascorbate uptake by isolated rat lung cells. J. Appl. Physiol. 51:1981;1477-1483.
27. Bianchi J., Wilson F.A., Rose R.C. Dehydroascorbic acid and ascorbic acid transport systems in the guinea pig ileum. Am. J. Physiol. 250:1986;G461-G468.
28. Socci R.R., Delamere N.A. Characteristics of ascorbate transport in the rabbit iris-ciliary body. Exp. Eye Res. 46:1988;853-861.
29. Chu T.C., Candia O.A. Active transport of ascorbate across the isolated rabbit ciliary epithelium. Invest. Ophthalmol. Vis. Sci. 29:1988;594-599.
30. Delamere N.A., Coca-Prados M., Aggarwal S. Studies on regulation of the ascorbic acid transporter in a cell line derived from rabbit non-pigmented ciliary epithelium. Biochim. Biophys. Acta. 1149:1993;102-108.
31. Franceschi R.T., Wilson J.X., Dixon S.J. Requirement for Na(+)-dependent ascorbic acid transport in osteoblast function. Am. J. Physiol. 268:1995;C1430-C1439.
32. Washko P.W., Rotrosen D., Levine M. Ascorbic acid transport and accumulation in human neutrophils. J. Biol. Chem. 264:1989;18996-19002.
33. Dixon S.J., Wilson J.X. Adaptive regulation of ascorbate transport in osteoblastic cells. J. Bone Miner. Res. 7:1992;675-681.
34. Washko P., Levine M. Inhibition of ascorbic acid transport in human neutrophils by glucose. J. Biol. Chem. 267:1992;23568-23574.
35. Lam K.W., Yu H.S., Glickman R.D., Lin T. Sodium-dependent ascorbic and dehydroascorbic acid uptake by SV-40-transformed retinal pigment epithelial cells. Ophthalmic Res. 25:1993;100-107.
36. Welch R.W., Bergsten P., Butler J.D., Levine M. Ascorbic acid accumulation and transport in human fibroblasts. Biochem. J. 294:1993;505-510.
37. Bergsten P., Yu R., Kehrl J., Levine M. Ascorbic acid transport and distribution in human B lymphocytes. Arch. Biochem. Biophys. 317:1995;208-214.
38. Castranova V., Wright J.R., Colby H.D., Miles P.R. Ascorbate uptake by isolated rat alveolar macrophages and type II cells. J. Appl. Physiol. 54:1983;208-214.
39. Siliprandi L., Vanni P., Kessler M., Semenza G. Na+-dependent, electroneutral L-ascorbate transport across brush border membrane vesicles from guinea pig small intestine. Biochim. Biophys. Acta. 552:1979;129-142.
40. Diliberto E.J. Jr, Heckman G.D., Daniels A.J. Characterization of ascorbic acid transport by adrenomedullary chromaffin cells. Evidence for Na+-dependent co-transport. J. Biol. Chem. 258:1983;12886-12894.
41. Padh H., Aleo J.J. Characterization of the ascorbic acid transport by 3T6 fibroblasts. Biochim. Biophys. Acta. 901:1987;283-290.
42. Helbig H., Korbmacher C., Wohlfarth J., Berweck S., Kuhner D., Wiederholt M. Electrogenic Na+-ascorbate cotransport in cultured bovine pigmented ciliary epithelial cells. Am. J. Physiol. 256:1989;C44-C49.
43. Wilson J.X., Jaworski E.M., Dixon S.J. Evidence for electrogenic sodium-dependent ascorbate transport in rat astroglia. Neurochem. Res. 16:1991;73-78.
44. Maffia M., Ahearn G.A., Vilella S., Zonno V., Storelli C. Ascorbic acid transport by intestinal brush-border membrane vesicles of the teleost Anguilla anguilla. Am. J. Physiol. 264:1993;R1248-R1253.
45. Bianchi J., Rose R.C. Na+-independent dehydro-L-ascorbic acid uptake in renal brush-border membrane vesicles. Biochim. Biophys. Acta. 819:1985;75-82.
46. Dreyer R., Rose R.C. Lacrimal gland uptake and metabolism of ascorbic acid. Proc. Soc. Exp. Biol. Med. 202:1993;212-216.
47. Dixon S.J., Wilson J.X. Transforming growth factor-beta stimulates ascorbate transport activity in osteoblastic cells. Endocrinology. 130:1992;484-489.
48. Heath H., Fiddick R. The active transport of ascorbic acid by the rat retina. Exp. Eye Res. 5:1966;156-163.
49. Kern H.L., Zolot S.L. Transport of vitamin C in the lens. Curr. Eye Res. 6:1987;885-896.
50. Ingermann R.L., Stankova L., Bigley R.H. Role of monosaccharide transporter in vitamin C uptake by placental membrane vesicles. Am. J. Physiol. 250:1986;C637-C641.
51. Hughes R.E., Maton S.C. The passage of vitamin C across the erythrocyte membrane. Br. J. Haematol. 14:1968;247-253.
52. 14C)- dehydroascorbic acid by platelets of guinea pigs. Clin. Chim. Acta. 33:1971;187-196.
53. Patterson J.W. The diabetogenic effect of dehydroascorbic and dehydroisoascorbic acids. J. Biol. Chem. 183:1950;81-88.
54. Bigley R., Wirth M., Layman D., Riddle M., Stankova L. Interaction between glucose and dehydroascorbate transport in human neutrophils and fibroblasts. Diabetes. 32:1983;545-548.
55. Stahl R.L., Farber C.M., Liebes L.F., Silber R. Relationship of dehydroascorbic acid transport to cell lineage in lymphocytes from normal subjects and patients with chronic lymphocytic leukemia. Cancer Res. 45:1985;6507-6512.
56. Vera J.C., Rivas C.I., Zhang R.H., Farber C.M., Golde D.W. Human HL-60 myeloid leukemia cells transport dehydroascorbic acid via the glucose transporters and accumulate reduced ascorbic acid. Blood. 84:1994;1628-1634.
57. Mann G.V., Newton P. The membrane transport of ascorbic acid. Ann. N.Y. Acad. Sci. 258:1975;243-252.
58. Ingermann R.L., Stankova L., Bigley R.H., Bissonnette J.M. Effect of monosaccharide on dehydroascorbic acid uptake by placental membrane vesicles. J. Clin. Endocrinol. Metab. 67:1988;389-394.
59. Mooradian A.D. Effect of ascorbate and dehydroascorbate on tissue uptake of glucose. Diabetes. 36:1987;1001-1004.
60. Keller K., Mueckler M. Different mammalian facilitative glucose transporters expressed in Xenopus oocytes. Biomed. Biochim. Acta. 49:1990;1201-1203.
61. Hediger M.A., Coady M.J., Ikeda T.S., Wright E.M. Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. Nature. 330:1987;379-381.
62. Kanai Y., Lee W.S., You G., Brown D., Hediger M.A. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J. Clin. Invest. 93:1994;397-404.
63. Vera J.C., Rivas C.I., Fischbarg J., Golde D.W. Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature. 364:1993;79-82.
64. Rumsey S.C., Kwon O., Xu G.W., Burant C.F., Simpson I., Levine M. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J. Biol. Chem. 272:1997;18982-18989.
65. Padh H., Aleo J.J. Ascorbic acid transport by 3T6 fibroblasts. Regulation by and purification of human serum complement factor. J. Biol. Chem. 264:1989;6065-6069.
66. Hendry J.M., Easson L.H., Owen J.A. The uptake and reduction of dehydroascorbic acid by human leukocytes. Clin. Chim. Acta. 9:1964;498-499.
67. Bigley R.H., Stankova L. Uptake and reduction of oxidized and reduced ascorbate by human leukocytes. J. Exp. Med. 139:1974;1084-1092.
68. Dyer D.L., Kanai Y., Hediger M.A., Rubin S.A., Said H.M. Expression of a rabbit renal ascorbic acid transporter in Xenopus laevis oocytes. Am. J. Physiol. 267:1994;C301-C306.
69. Hornig D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann. N.Y. Acad. Sci. 258:1975;103-118.
70. Dhariwal K.R., Hartzell W.O., Levine M. Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum. Am. J. Clin. Nutr. 54:1991;712-716.
71. Okamura M. An improved method for determination of L-ascorbic acid and L-dehydroascorbic acid in blood plasma. Clin. Chim. Acta. 103:1980;259-268.
72. Borsook H., Davenport H.W., Jeffreys C.E.P., Warner R.C. The oxidation of ascorbic acid and its reduction in vitro and in vivo. J. Biol. Chem. 117:1936;237-279.
73. Schultze M.O., Stotz E., King C.G. Studies on the reduction of dehydroascorbic acid by guinea pig tissues. J. Biol. Chem. 122:1937;395-406.
74. Bigley R., Stankova L., Roos D., Loos J. Glutathione-dependent dehydroascorbate reduction A determinant of dehydroascorbate uptake by human polymorphonuclear leukocytes . Enzyme. 25:1980;200-204.
75. Rose R.C. Transport of ascorbic acid and other water-soluble vitamins. Biochim. Biophys. Acta. 947:1988;335-366.
76. Winkler B.S., Orselli S.M., Rex T.S. The redox couple between glutathione and ascorbic acid A chemical and physiological perspective . Free Radic. Biol. Med. 17:1994;333-349.
77. Wells W.W., Xu D.P. Dehydroascorbate reduction. J. Bioenerg. Biomembr. 26:1994;369-377.
78. Levine M., Rumsey S.C., Wang Y., Park J.B., Xu G.W., Amano N. Vitamin C. Filer L.J., Ziegler E.E. Present Knowledge in Nutrition. 1996;146-159 International Life Sciences Institute, Washington, DC.
79. Melhorn R.J. Ascorbate- and dehydroascorbic acid-mediated reduction of free radicals in the human erythrocyte. J. Biol. Chem. 266:1991;2724-2731.
80. Coassin M., Tomasi A., Vannini V., Ursini F. Enzymatic recycling of oxidized ascorbate in pig heart One-electron vs two-electron pathway . Arch. Biochem. Biophys. 290:1991;458-462.
81. Winkler B.S. Unequivocal evidence in support of the nonenzymatic redox coupling between glutathione/glutathione disulfide and ascorbic acid/dehydroascorbic acid. Biochim. Biophys. Acta. 1117:1992;287-290.
82. Xu D.P., Wells W.W. Alpha-Lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria. J. Bioenerg. Biomembr. 28:1996;77-85.
83. Wells W.W., Xu D.P., Yang Y., Rocque P.A. Mammalian thioltransferase (Glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. J. Biol. Chem. 265:1990;15361-15364.
84. Del Bello B., Maellaro E., Sugherini L., Santucci A., Comporti M., Casini A.F. Purification of NADPH-dependent dehydroascorbate reductase from rat liver and its identification with 3 alpha-hydroxysteroid dehydrogenase. Biochem. J. 304:1994;385-390.
85. Maellaro E., Del Bello B., Sugherini L., Santucci A., Comporti M., Casini A.F. Purification and characterization of glutathione-dependent dehydroascorbate reductase from rat liver. Biochem. J. 301:1994;471-476.
86. Mieyal J.J., Starke D.W., Gravina S.A., Dothey C., Chung J.S. Thioltransferase in human red blood cells Purification and properties . Biochemistry. 30:1991;6088-6097.
87. Bergsten P., Amitai G., Kehrl J., Dhariwal K.R., Klein H.G., Levine M. Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. Depletion and reaccumulation. J. Biol. Chem. 265:1990;2584-2587.
88. Wang Y., Russo T.A., Kwon O., Chanock S., Rumsey S.C., Levine M. Ascorbate recycling in human neutrophils Induction by bacteria . Proc. Natl. Acad. Sci. USA. 94:1997;13816-13819.
89. Larsen P.R., Ingbar S.H. The thyroid gland. Wilson J.D., Foster D.W. Williams Textbook of Endocrinology. 1992;365-371 Saunders, Philadelphia, PA, USA.
90. DeChatelet L.R. Oxidative bactericidal mechanisms of polymorphonuclear leukocytes. J. Infect. Dis. 131:1975;295-303.
91. Halliwell B., Wasil M., Grootveld M. Biologically significant scavenging of the myeloperoxidase-derived oxidant hypochlorous acid by ascorbic acid. Implications for antioxidant protection in the inflamed rheumatoid joint. FEBS Lett. 213:1987;15-17.
92. Liles W.C., Kiener P.A., Ledbetter J.A., Aruffo A., Klebanoff S.J. Differential expression of FAS (CD95) and Fas ligand on normal human phagocytes Implications for the reulation of apoptosis in neutrophils . J. Exp. Med. 184:1996;429-440.
93. Segal A., Gelsow M., Garcia R., Harper A., Miller R. The respiratory burst of phagocytic cells is associated with a rise in vaculoar pH. Nature. 290:1981;406-408.
94. Whyte M.K.B., Meagher L.C., MacDermot J., Haslet C. Impairment of function in aging neutrophils is associated with apoptosis. J. Immunol. 150:1993;5124-5134.
95. Kasahara Y., Iwai K., Yachie A., Ohta K., Konno S., Seki H., Miyawaki T., Taniguchi N. Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1) mediated apoptosis of neutrophils. Blood. 89:1997;1748-1753.
96. Vanderslice J.T., Higgs D.J. Vitamin C content of foods sample variability . Am. J. Clin. Nutr. 54:1991;1323S-1327S.
97. Bilic N. Assay for both ascorbic and dehydroascorbic acid in dairy foods by high-performance liquid chromatography using precolumn derivatization with methoxy- and ethoxy-1,2-phenylenediamine. J. Chromatogr. 543:1991;367-374.
98. Mellors A.J., Nahrwold D.L., Rose R.C. Ascorbic acid flux across mucosal border of guinea pig and human ileum. Am. J. Physiol. 233:1977;E374-E379.
99. Stewart J.S., Booth C.C. Ascorbic acid absorption in malabsorption. Clin. Sci. 27:1964;15-22.
100. Nelson E.W., Lane H., Fabri P.J., Scott B. Demonstration of saturation kinetics in the intestinal absorption of vitamin C in man and the guinea pig. J. Clin. Pharmacol. 18:1978;325-335.
101. Kubler W., Gehler J. [Kinetics of intestinal absorption of ascorbic acid. Calculation of non-dosage-dependent absorption processes]. Int. A. Vitaminforsch. 40:1970;442-453.
102. Mayersohn M. Ascorbic acid absorption in man - pharmacokinetic implications. Eur. J. Pharmacol. 19:1972;140-142.
103. King G., Beins M., Larkin J., Summers B., Ordman A.B. Rate of excretion of vitamin C in human urine. Age. 17:1994;87-92.
104. Karasov W.H., Darken B.W., Bottum M.C. Dietary regulation of intestinal ascorbate uptake in guinea pigs. Am. J. Physiol. 260:1991;G108-G118.
105. Bianchi J., Rose R.C. Dehydroascorbic acid and cell membranes Possible disruptive effects . Toxicology. 40:1986;75-82.
106. Rose R.C., Choi J.L., Koch M.J. Intestinal transport and metabolism of oxidized ascorbic acid (dehydroascorbic acid). Am. J. Physiol. 254:1988;G824-G828.
107. Fox F.W., Levy L.F. Experiments confirming the antiscorbutic activity of dehydroascorbic acid and a study of its storage and that of ascorbic acid by the guinea pig at different levels of intake. Biochem. J. 30:1936;211-217.
108. Todhunter E.N., McMillan T., Ehmke A. Utilization of dehydroascorbic acid by human subjects. J. Nutr. 42:1950;297-308.
109. Linkswiler H. The effect of the ingestion of ascorbic acid and dehydroascorbic acid upon the blood levels of these two components in human subjects. J. Nutr. 63:1957;43-54.
110. Sabry J.H., Fisher K.H., Dodds M.L. Human Utilization of dehydroascorbic acid. J. Nutr. 68:1958;457-466.
111. Gibaldi M., Perrier D. Pharmacokinetics. 1982;Marcel Dekker, New York, USA.
112. Rowland M., Tozer T.M. Clinical Pharmacokinetics Concepts and Applications . 1989;Lea and Febiger, Philadelphia, USA.
113. Graumlich J.F., Ludden T.M., Conry-Cantilena C., Cantilena L.R. Jr, Wang Y., Levine M. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharmaceutical Research. 14:1997;1133-1139.
114. Yung S., Mayersohn M., Robinson J.B. Ascorbic acid absorption in man Influence of divided dose and food . Life Sci. 28:1981;2505-2511.
115. Piotrovskij V.K., Kallay Z., Gajdos M., Gerykova M., Trnovec T. The use of a nonlinear absorption model in the study of ascorbic acid bioavailability in man. Biopharm. Drug Dispos. 14:1993;429-442.
116. Zetler G., Seidel G., Siegers C.P., Ivens H. Pharmacokinetics of ascorbic acid in man. Eur. J. Clin. Pharmacol. 10:1976;273-282.
117. Bhagavan H.N., Wolkoff B.I. Correlation between the disintegration time and the bioavailability of vitamin C tablets. Pharm. Res. 10:1993;239-242.
118. Richards T.W., Cheraskin E., Ringsdorf W.M. Jr. Effect of sustained release versus regular multivitamin supplement upon vitamin C state. Int. Z. Vitaminforsch. 39:1969;407-415.
119. Yung S., Mayersohn M., Robinson J.B. Ascorbic acid absorption in humans a comparison among several dosage forms . J. Pharm. Sci. 71:1982;282-285.
120. Clayton M.M., Folsom M.T. A method for the study of the availability for human nutrition of the vitamin C in foods, with an application to the study of the potato. J. Home Econ. 32:1940;390-395.
121. Clayton M.M., Borden R.A. The availability for human nutrition of the vitamin C in raw cabbage and home-canned tomato juice. J. Nutr. 25:1943;349-369.
122. Hawley E.E., Stephens D.J., Anderson G. The excretion of vitamin C in normal individuals following a comparable quantitative administration in the form of orange juice, cevitamic acid by mouth and cevitamic acid intravenously. J. Nutr. 11:1936;135-145.
123. Todhunter E.N., Fatzer A.S. A comparison of the utilization by college women of equivalent amounts of ascorbic acid (vitamin C) in red raspberries and in crystalline form. J. Nutr. 19:1940;121-130.
124. Hartzler E.R. The availability of ascorbic acid in papayas and guavas. J. Nutr. 30:1945;355-365.
125. Mangels A.R., Block G., Frey C.M., Patterson B.H., Taylor P.R., Norkus E.P., Levander O.A. The bioavailability to humans of ascorbic acid from oranges, orange juice and cooked broccoli is similar to that of synthetic ascorbic acid. J. Nutr. 123:1993;1054-1061.
126. Vinson J.A., Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am. J. Clin. Nutr. 48:1988;601-604.
127. Vanderslice J.T., Higgs D.J., Beecher G.R., Higgs H.E., Bouma J. On the presence of dehydroascorbic acid in human plasma. Int. J. Vitam. Nutr. Res. 62:1992;101-102.
128. Stewart C.P., Horn D.B., Robson J.S. The effect of cortisone and adrenocorticotropic hormone on the dehydroascorbic acid of human plasma. Biochem. J. 53:1953;254-261.
129. Cox B.D., Butterfield W.J. Vitamin C supplements and diabetic cutaneous capillary fragility. Br. Med. J. 3:1975;205.
130. Margolis S.A., Ziegler R.G., Helzlsouer K.J. Ascorbic and dehydroascorbic acid measurement in human serum and plasma. Am. J. Clin. Nutr. 54:1991;1315S-1318S.
131. Koshiishi I., Imanari T. Measurement of ascorbate and dehydroascorbate contents in biological fluids. Anal. Chem. 69:1997;216-220.
132. Sullivan J.F., Eisenstein A.B. Ascorbic acid depletion in patients undergoing chronic hemodialysis. Am. J. Clin. Nutr. 23:1970;1339-1346.
133. Stankova L., Rigas D.A., Bigley R.H. Dehydroascorbate uptake and reduction by human blood neutrophils, erythrocytes, and lymphocytes. Ann. N.Y. Acad. Sci. 258:1975;238-242.
134. Evans R.M., Currie L., Campbell A. The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. Br. J. Nutr. 47:1982;473-482.
135. Baker E.M., Hodges R.E., Hood J., Sauberlich H.E., March S.C. Metabolism of ascorbic-1-14C acid in experimental human scurvy. Am. J. Clin. Nutr. 22:1969;549-558.
136. Baker E.M., Hodges R.E., Hood J., Sauberlich H.E., March S.C., Canham J.E. Metabolism of 14C- and 3H-labeled L-ascorbic acid in human scurvy. Am. J. Clin. Nutr. 24:1971;444-454.
137. Hodges J.R., Hotston R.T. Suppression of adrenocorticotrophic activity in the ascorbic acid deficient guinea-pig. Br. J. Pharmacol. 42:1971;595-602.
138. Jacob R.A., Omaye S.T., Skala J.H., Leggott P.J., Rothman D.L., Murray P.A. Experimental vitamin C depletion and supplementation in young men. Nutrient interactions and dental health effects. Ann. N. Y. Acad. Sci. 498:1987;333-346.
139. Jacob R.A., Pianalto F.S., Agee R.E. Cellular ascorbate depletion in healthy men. J. Nutr. 122:1992;1111-1118.
140. Kallner A., Hartmann D., Hornig D. Steady-state turnover and body pool of ascorbic acid in man. Am. J. Clin. Nutr. 32:1979;530-539.
141. Garry P.J., Goodwin J.S., Hunt W.C., Gilbert B.A. Nutritional status in a healthy elderly population Vitamin C . Am. J. Clin. Nutr. 36:1982;332-339.
142. VanderJagt D.J., Garry P.J., Bhagavan H.N. Ascorbic acid intake and plasma levels in healthy elderly people. Am. J. Clin. Nutr. 46:1987;290-294.
143. Garry P.J., VanderJagt D.J., Hunt W.C. Ascorbic acid intakes and plasma levels in healthy elderly. Ann. N.Y. Acad. Sci. 498:1987;90-99.
144. Hegsted D.M. Defining a nutritious diet Need for new dietary standards . J. Am. Coll. Nutr. 11:1992;241-245.
145. King J., Wang Y., Welch R.W., Dhariwal K.R., Conry-Cantilena C., Levine M. Use of a new vitamin C-deficient diet in a depletion/repletion clinical trial. Am. J. Clin. Nutr. 65:1997;1434-1440.
146. Keith M.O., Pelletier O. Ascorbic acid concentrations in leukocytes and selected organs of guinea pigs in response to increasing ascorbic acid intake. Am. J. Clin. Nutr. 27:1974;368-372.
147. Damron C.M., Monier M.M., Roe J.H. Metabolism of L-ascorbic acid, dehydro L-ascorbic acid and diketo-L-gulonic acid in the guinea pig. J. Biol. Chem. 195:1952;599-606.
148. 14C) dehydroascorbic acid in male guinea pigs after intravenous injection. Int. J. Vitam. Nutr. Res. 42:1972;223-241.
149. Ralli E.P., Friedman G.J., Rubin S.H. The mechanism of the excretion of vitamin C by the human kidney. J. Clin. Invest. 17:1938;765-770.
150. Rose R.C. Ascorbic acid transport in mammalian kidney. Am. J. Physiol. 250:1986;F627-F632.
151. Martin M., Ferrier B., Roch-Ramel F. Renal excretion of ascorbic acid in the rat A micropuncture study . Am. J. Physiol. 244:1983;F335-F341.
152. Bowers-Komro D.M., McCormick D.B. Characterization of ascorbic acid uptake by isolated rat kidney cells. J. Nutr. 121:1991;57-64.
153. Friedman G.J., Sherry S., Ralli E. The mechanism of excretion of vitamin C by the human kidney at low and normal plasma levels of ascorbic acid. J. Clin. Invest. 19:1940;685-689.
154. Oreopoulos D.G., Lindeman R.D., VanderJagt D.J., Tzamaloukas A.H., Bhagavan H.N., Garry P.J. Renal excretion of ascorbic acid Effect of age and sex . J. Am. Coll. Nutr. 12:1993;537-542.
155. Toggenburger G., Hausermann M., Mutsch B., Genoni G., Kessler M., Weber F., Hornig D., O'Neill B., Semenza G. Na+-dependent, potential-sensitive L-ascorbate transport across brush border membrane vesicles from kidney cortex. Biochim. Biophys. Acta. 646:1981;433-443.
156. Recommended Dietary Allowances. 1980;National Academy Press, Washington, DC.
157. Recommended Dietary Allowances. 1985;National Academy Press, Washington, DC.
158. Bianchi J., Rose R.C. Transport of L-ascorbic acid and dehydro-L-ascorbic acid across renal cortical basolateral membrane vesicles. Biochim. Biophys. Acta. 820:1985;265-273.
159. Wang Y.H., Dhariwal K.R., Levine M. Ascorbic acid bioavailability in humans. Ascorbic acid in plasma, serum, and urine. Ann. N.Y. Acad. Sci. 669:1992;383-386.
160. Baker E.M., Saari J.C., Tolbert B.M. Ascorbic acid metabolism in man. Am. J. Clin. Nutr. 19:1966;371-378.
161. Tolbert B.M., Chen A.W., Bell E.M., Baker E.M. Metabolism of 1-ascorbic-4-3H acid in man. Am. J. Clin. Nutr. 20:1967;250-252.
162. Tolbert, B.M., Downing, M., Carlson, R.W., Knight, M.K., and Baker, E.M. (1975). Chemistry and metabolism of ascorbic acid and ascorbate sulfate. Ann. N.Y. Acad. Sci. 258: 48-69, 48-69.
163. Baker E.M., Halver J.E., Johnsen D.O., Joyce B.E., Knight M.K., Tolbert B.M. Metabolism of ascorbic acid and ascorbic-2-sulfate in man and the subhuman primate. Ann. N.Y. Acad. Sci. 258:1975;72-80.
164. Tolbert B.M., Harkrader R.J., Johnson D.O., Joyce B.A. C-6 oxidation of ascorbic acid A major metabolic process in animals . Biochem. Biophys. Res. Commun. 71:1976;1004-1009.
165. Omaye S.T., Tillotson J.A., Sauberlich H.E. Metabolism of L-ascorbic acid in the monkey. Seib P.A., Tolbert B.M. Ascorbic Acid Chemistry, Metabolism and Uses . 1982;317-334 American Chemical Society, Washington, DC.
166. Kallner A., Hornig D., Pellikka R. Formation of carbon dioxide from ascorbate in man. Am. J. Clin. Nutr. 41:1985;609-613.
167. Chatterjee I.B. Ascorbic acid metabolism. World Rev. Nutr. Diet. 30:1978;69-87.
168. 14 in man. J. Biol. Chem. 230:1957;923-930.
169. Mydlik M., Derzsiova K., Pribylincova V., Zvara V., Takac M. Urinary excretion of vitamin C in chronic renal failure and after renal transplantation. Int. Urol. Nephrol. 18:1986;457-462.
170. Levine M., Dhariwal K.R., Welch R.W., Wang Y., Park J.B. Determination of optimal vitamin C requirements in humans. Am. J. Clin. Nutr. 62:(suppl):1995;1347S-1356S.
171. Frei B., Stocker R., England L., Ames B.N. Ascorbate the most effective antioxidant in human blood plasma . Adv. Exp. Med. Biol. 264:1990;155-163.
172. Frei B., Forte T.M., Ames B.N., Cross C.E. Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid. Biochem. J. 277:1991;133-138.
173. Kallner A.B., Hartmann D., Hornig D.H. On the requirements of ascorbic acid in man Steady-state turnover and body pool in smokers . Am. J. Clin. Nutr. 34:1981;1347-1355.
174. Schectman G. Estimating ascorbic acid requirements for cigarette smokers. Ann. N.Y. Acad. Sci. 686:1993;335-345.
175. Jialal I., Vega G.L., Grundy S.M. Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis. 82:1990;185-191.
176. Retsky K.L., Frei B. Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low-density lipoprotein. Biochim. Biophys. Acta. 1257:1995;279-287.
177. Steinberg D. Role of oxidized LDL and antioxidants in atherosclerosis. Adv. Exp. Med. Biol. 369:1995;39-48.
178. Lehr H.A., Frei B., Olofsson A.M., Carew T.E., Arfors K.E. Protection from oxidized LDL-induced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E. Circulation. 91:1995;1525-1532.
179. Heitzer T., Just H., Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation. 94:1996;6-9.
180. Levine G.N., Frei B., Koulouris S.N., Gerhard M.D., Keaney J.F., Vita J.A. Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation. 93:1996;1107-1113.
181. Feig D.I., Loeb L.A. Oxygen radical induced mutagenesis is DNA polymerase specific. J. Mol. Biol. 235:1994;33-41.
182. Borek C. Molecular mechanism in cancer induction and prevention. Environ. Health Perspect. 101:(Suppl 3):1993;237-245.
183. Cerutti P., Ghosh R., Oya Y., Amstad P. The role of the cellular antioxidant defense in oxidant carcinogenesis. Environ. Health Perspect. 102:(Suppl 10):1994;123-129.
184. Fraga C.G., Motchnik P.A., Shigenaga M.K., Helbock H.J., Jacob R.A., Ames B.N. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc. Natl. Acad. Sci. U.S.A. 88:1991;11003-11006.
185. Green M.H., Lowe J.E., Waugh A.P., Aldridge K.E., Cole J., Arlett C.F. Effect of diet and vitamin C on DNA strand breakage in freshly-isolated human white blood cells. Mutat. Res. 316:1994;91-102.
186. Mares-Perlman J.A. Contribution of epidemiology to understanding relations of diet to age-related cataract. Amer. J. Clin. Nutr. 66:1997;739-740.
187. Solzbach U., Hornig B., Jeseich M., Just H. Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation. 96:1997;1513-1519.
188. Mann G.V. Hypothesis The role of vitamin C in diabetic angiopathy . Perspect. Biol. Med. 17:1974;210-217.
189. Cunningham J.J. Altered vitamin C transport in diabetes mellitus. Med. Hypotheses. 26:1988;263-265.
190. Banerjee A. Blood dehydroascorbic acid and diabetes mellitus in human beings. Ann. Clin. Biochem. 19:1982;65-70.
191. Cox B.D., Whichelow M.J. The measurement of dehydroascorbic acid and diketogulonic acid in normal and diabetic plasma. Biochem. Med. 12:1975;183-193.
192. Washko P.W., Welch R.W., Dhariwal K.R., Wang Y., Levine M. Ascorbic acid and dehydroascorbic acid analyses in biological samples. Anal. Biochem. 204:1992;1-14.
193. Pirani C.L. Relation of vitamin C to adrenocortical function and stress phenomena. Metabolism. 1:1952;197-222.
194. Sharma S.K., Johnstone R.M., Quastel J.H. Corticosteroids and ascorbic acid transport in adrenal cortex in vitro. Biochem. J. 92:1964;564-573.
195. De Nicola A.F., Clayman M., Johnstone R.M. Hormonal control of ascorbic acid transport in rat adrenal glands. Endocrinology. 82:1968;436-446.
196. Horning D., Gallo-Torres H.E., Weiser H. Tissue distribution of labelled ascorbic acid in normal and hypophysectomized rats. Int. J. Vitam. Nutr. Res. 42:1972;487-496.
197. Sayers G., Sayers M.A., Liang T.Y., Long C.N.H. The cholesterol and ascorbic acid content of the adrenal, liver, brain, and plasma following hemorrhage. Endocrinology. 37:1945;96-110.
198. Stefanini M., Rosenthal M.C. Hemorrhagic diathesis with ascorbic acid deficiency during administration of anterior pituitary corticotropic hormone (ACTH). Proc. Soc. Exptl. Biol. Med. 75:1950;806-808.
199. Zhou A., Thorn N.A. High ascorbic acid content in the rat endocrine pancreas. Diabetologia. 34:1991;839-842.
200. Levine R.L. Oxidative modification of glutamine synthetase. II. Characterization of the ascorbate model system. J. Biol. Chem. 258:1983;11828-11833.
201. Young V.R. Evidence for a recommended dietary allowance for vitamin C from pharmacokinetics A comment and analysis . Proc. Natl. Acad. Sci. U.S.A. 93:1996;14344-14348.
202. Levine M., Rumsey S., Wang Y. Principles involved in formulating recommendations for vitamin C intake A paradigm for water-soluble vitamins . Methods Enzymol. 279:1997;43-54.
203. Levine M., Rumsey S.C., Wang Y., Park J., Kwon O., Amano N. In situ kinetics An approach to recommended intake of vitamin C . Methods Enzymol. 281:1997;425-437.
204. Vallance B.D., Hume R., Weyers E. Reassessment of changes in leucocyte and serum ascorbic acid after acute myocardial infarction. Br. Heart J. 40:1978;64-68.
205. Irvin T.T. Vitamin C requirements in postoperative patients. Int. J. Vitam. Nutr. Res. Suppl. 23:1982;277-286.
206. Marcus S.L., Petrylak D.P., Dutcher J.P., Paietta E., Ciobanu N., Strauman J., Wiernik P.H., Hutner S.H., Frank O., Baker H. Hypovitaminosis C in patients treated with high-dose interleukin 2 and lymphokine-activated killer cells. Am. J. Clin. Nutr. 54:1991;1292S-1297S.
207. Grant J.P. Nutritional support in critically ill patients. Ann. Surg. 220:1994;610-616.
208. Schorah C.J., Downing C., Piripitsi A., Gallivan L., Al-Hazaa A.H., Sanderson M.J., Bodenham A. Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am. J. Clin. Nutr. 63:1996;760-765.
209. Bielski G.H.J. Chemistry of ascorbic acid radicals. Seib P.A., Tolbert B.M. Ascorbic Acid Chemistry, Metabolism, and Uses . 1982;81-100 American Chemical Society, Washington, DC.