Role of Vitamin C in Health and Disease

  • Herbert K. Naito


The biosynthesis, physiological functions and catabolism of L-ascorbic acid (Vitamin C) in man remain topics of great interest and challenge for the clinical biochemist. L-ascorbic acid is a water-soluble vitamin, which chemically is a lactone (internal ester of a hydroxycarboxylic acid) and is characterized by the enediol group which makes it a strongly reducing compound. Ascorbic acid itself is the most active reducing agent known to occur naturally in living tissues. The empirical formula of this vitamin is C6H8O6. The Levo-ascorbic acid is an active antiscorbutic substance, while the dextro-ascorbic acid is not (Figure 1). One of the isomers, D-isoascorbic acid or erythorbic acid, is produced commercially for use as a food additive. It has the reducing power of L-ascorbic acid but cannot support growth. L-ascorbic acid is readily and reversibly oxidized to dehydro-L-ascorbic acid which retains vitamin C activity (Figure 2). This compound can be further oxidized to diketo-2-gluconic acid, in a non-reversible reaction; the compound has no reported biological activity. Dehydration and decarboxylation can lead to the formation of furfural, which can polymerize to form brown pigments or combine with amino acids in the Strecker degradation. The failure of man, non-human primates, guinea pigs and a few other species of animals to synthesize their own vitamin C from glucose is due to a deficiency of an enzyme in the liver which converts L-gluconic acid to ascorbic acid. Thus, for these animals vitamin C is an essential vitamin that is required in the daily diet. While scurvy is not as common today in the U.S.A. as compared to a century ago, vitamin C deficiency is one of the more common vitamin deficiencies, particularly in school-age children (Ten State Nutrition Survey, 1972).


Ascorbic Acid Concentration Ascorbate Level Ascorbic Acid Deficiency Serum Ascorbic Acid Evans Blue Uptake 
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  1. Abboud, F. M., Hood, J., Hodges, R.E., and Mayer, H. E., 1970, Antonomic reflexes and vascular reactivity in experimental scurvy in man, J. Clin. Invest. 49:298–307.CrossRefGoogle Scholar
  2. Ahmad, M. M., Moreng, R. E., and Muller, H. D., 1967, Bread responses in body temperature and ascorbic acid, Poultry Sci. 46:6–15.Google Scholar
  3. Anderson, T. W., Reid, D. B. W., Beaton, G. H., 1972, Vitamin C and the common cold: A double-blind trial, Can. Med. Assoc. J. 107:503.Google Scholar
  4. Arscott, G. H., Rachapaetayakom, P., Bernier, P. E., and Adams, F.W., 1962, Influence of ascorbic acid, calcium and phosphorus on specific gravity of eggs, Poultry Sci. 41:485.Google Scholar
  5. Baker, E., Hammer, D., March, S., Tolbert, B. and Canham, J., 1971, Ascorbate sulfate: A urinary metabolite of ascorbic acid in man, Science 173:826.CrossRefGoogle Scholar
  6. Baker, E. M., Hodges, R. E., Hood, J., Sauberlich, H.E., March, S. C., and Canham, J. E., 1971, Metabolism of 14C- and 3H-labeled L-ascorbic acid in human scurvy, Amer. J. Clin. Nutr. 24:444.Google Scholar
  7. Banay, M. and Dimant, E., 1962, On the metabolism of L-ascorbic acid in the scorbutic guinea pig, Biochim. Biophys. Acta 59:313.CrossRefGoogle Scholar
  8. Banerjee, S. and Singh, H. D., 1958, Cholesterol metabolism in scorbutic guinea pigs, J. Biol. Chem. 233:336.Google Scholar
  9. Barnes, M. J., 1975, Function of ascorbic acid in collagen metabolism, Ann. N. Y. Acad Sci. 258:264.CrossRefGoogle Scholar
  10. Barnes, M. J. and Kodicek, E., 1972, Biological hydroxylation and ascorbic acid with special regard to collagen metabolism, Vit. Horm. 30:1.CrossRefGoogle Scholar
  11. Barness, L. A., 1975, Safety considerations with high ascorbic acid dosage, Ann. N. Y. Acad. Sci. 258:523.CrossRefGoogle Scholar
  12. Bhagat, B., West, W. L., and Robinson, I. M., 1966, Sensitivity to norepinephrine of isolated atria from scorbutic guinea pigs, Biochem. Pharmacol. 15:1637–1639.CrossRefGoogle Scholar
  13. Bond, A.D., 1975, Ascorbic-2-sulfate metabolism by human fibroblasts, Ann. N. Y. Acad. Sci. 258:307.CrossRefGoogle Scholar
  14. Burns, J. J., 1957, Missing step in man, monkey and guinea pig required for the biosynthesis of L-ascorbic acid, Nature 180:553.CrossRefGoogle Scholar
  15. Chatterjee, I. B., Majumder, A. K., Nandi, B. K., and Subramanian, N., 1975, Synthesis and some major functions of vitamin C in animals, Ann. N. Y. Acad. Sci. 258:24.CrossRefGoogle Scholar
  16. Chaudhuri, C. R. and Chatterjee, I. B., 1969, L-ascorbic acid synthesis in birds: Phylogenetic trend, Science 166:435.CrossRefGoogle Scholar
  17. Church, C. F. and Church, N. H. (eds.), 1977, “Bowes and Church’s Food Values or Portions Commonly Used,” 12th ed., J. B. Lippincott, Philadelphia, Pennsylvania.Google Scholar
  18. Cooper, J. R., 1961, The role of ascorbic acid in the oxidation of tryptophan to 5-hydroxytryptophan, Ann. N. Y. Acad. Sci. 92:208–211.CrossRefGoogle Scholar
  19. Coulehan, J. L., Reisinger, K. S., Rogers, K. D., and Bradley, D. W., 1974, Vitamin C prophylaxis in a boarding school, New Engl. J. Med. 290:6.CrossRefGoogle Scholar
  20. Doerholt, G., 1938, Tierexperimentelle untersuchungen über den einfluss des vitamin C auf die höhenfestigkeit, Luftfahrtmediz, Abhandl. 2(3/4):240.Google Scholar
  21. Feeley, R. M., Criner, P. E., and Watt, B. K., 1972, Cholesterol content of foods, J. Am. Dietet. Assoc. 61:134.Google Scholar
  22. Food and Nutrition Board, 1974, Recommended Dietary Allowances, 8th ed., National Academy of Sciences, Washington, D.C.Google Scholar
  23. Fuller, R. N., Henson, E. C., Shannon, E. L., Collins, A. D., and Brunson, J. G., 1971, Vitamin C deficiency and susceptibility to endotoxin shock in guinea pigs, Arch. Path. 92:239.Google Scholar
  24. Ginter, E., 1975, Ascorbic acid in cholesterol and bile acid metabolism, Ann. N. Y. Acad. Sci. 258:410.CrossRefGoogle Scholar
  25. Ginter, E. and Ondreicka, R., 1971, Liver cholesterol esters composition in guinea pigs with chronic ascorbic acid deficiency, Nutr. Metab. 13:321.CrossRefGoogle Scholar
  26. Ginter, E., Kajaba, I., and Nizner, O., 1970, The effect of ascorbic acid on cholesterolemia in healthy subjects with seasonal deficit on vitamin C, Nutr. Metab. 12:76.CrossRefGoogle Scholar
  27. Ginter, E., Cerven, J., Nemec, R., and Mikus, L., 1971, Lowered cholesterol catabolism in guinea pigs with chronic ascorbic acid deficiency, Am. J. Clin. Nutr. 24:1238.Google Scholar
  28. Ginter, E., Bobek, P., Kopec, Z., Ovecka, M., and Cerey, K., 1967, Metabolic disorders in guinea pigs with chronic vitamin C hyposaturation, Versuchskierk 9:228.Google Scholar
  29. Gore, I., and Stefanovic, V., 1967, The relation of permeability of rabbit aorta to dietary induced lipid accumulation, Fed. Proc. 26:431.Google Scholar
  30. Herbert, V., and Jacob, E., 1974, Destruction of vitamin B12 by ascorbic acid, J. Amer. Med. Assoc. 230:241.CrossRefGoogle Scholar
  31. Herrick, R. B., and Nockels, C. F., 1969, Effects of a high level of dietary ascorbic acid on egg quality, Poultry Sci. 48:1518–1519.Google Scholar
  32. Heywang, B. W., and Kemmerer, A. R., 1955, The effects of procaine penicillin and ascorbic acid on egg weight and shell thickness during hot weather, Poultry Sci. 34:1032.CrossRefGoogle Scholar
  33. Hodges, R. E., 1976, Ascorbic acid, in “Recent Knowledge in Nutrition,” The Nutrition Foundation, Inc., Washington, D.C.Google Scholar
  34. Hodges, R. E., Baker, E. M., Hood, J., Sauberlich, H. E., and March, S. C., 1969, Experimental scurvy in man, Amer. J. Clin. Nutr. 22:535.Google Scholar
  35. Hodges, R. E., Hood, J., Canham, J. E., Sauberlich, H. E., and Baker, E. M., 1971, Clinical manifestations of ascorbic acid deficiency in man, Amer. J. Clin. Nutri. 24:432.Google Scholar
  36. Hunt, J. R., and Aitken, J. R., 1962, Studies on the influence of ascorbic acid on shell quality, Poultry Sci. 41:219.Google Scholar
  37. Kagawa, Y., 1962, Enzymatic studies on ascorbic acid catabolism in animals, I. Catabolism of 2,3-diketo-L-gulonic acid, J. Biochem. 51:134.Google Scholar
  38. Kagawa, Y., Takaguchi, H., 1962, Enzymatic studies on ascorbic acid catabolism in animals, II. Delactonization of dehydro-L-ascorbic, J. Biochem. 51:197.Google Scholar
  39. Kagawa, Y., Takaguchi, H., and Shimazono, N., 1961, Enzymatic delactonization of dehydro-L-ascorbate in animal tissues, Biochim. Biophys. Acta 51:413.CrossRefGoogle Scholar
  40. Keith, M. O., Pelletier, O., 1974, Ascorbic acid concentrations in leukocytes and selected organs of guinea pigs in response to increasing ascorbic acid intake, Amer. J. Clin. Nutr. 27:368.Google Scholar
  41. Kitabchi, A. E. and West, W. H., 1975, Effect of steroidogenesis on ascorbic acid content and uptake in isolated adrenal cells, Ann. N. Y. Acad. Sci. 258:422.CrossRefGoogle Scholar
  42. Lewin, S., 1973, Evaluation of potential effects of high intake of ascorbic acid, Comp. Biochem. Physiol. 46:427.Google Scholar
  43. Lewis, T. L., Karlowski, T. R., Kapikian, A. Z., Lynch, J. M., Shaffer, G. W., and George, D. A., 1975, A controlled clinical trial of ascorbic acid for the common cold, Am. N. Y. Acad. Sci. 258:505.CrossRefGoogle Scholar
  44. Loh, H. S., 1972, The relationship between dietary ascorbic acid intake and buffy coat and plasma ascorbic acid concentrations at different ages, Int. J. Vit. Res. 42:80.Google Scholar
  45. Lowry, O. H., 1952, Biochemical evidence of nutritional status, Physiol. Rev. 32:431.Google Scholar
  46. Lyle, G. R., and Moreng, R. E., 1968, Elevated environmental temperature and duration of post exposure ascorbic acid administration, Poultry Sci. 46:410–416.Google Scholar
  47. Manual for Nutrition Surveys, 1963, (2nd ed.), Interdepartmental Committee on Nutrition for National Defense, Superintendent of Documents, U. S. Government Printing Office, Washington, D.C.Google Scholar
  48. Mather, F. B., Epling, G. P., and Thornton, P. A., 1962, The microscopic structure of the egg shell matrix as influenced by shell thickness and environmental temperature, Poultry Sci. 4:191–200.Google Scholar
  49. Medical Research Council, 1948, Vitamin C requirement of human adults - Experimental study of vitamin C deprivation in man, A preliminary report by the Vitamin C Subcommittee of the Accessory Food Factors Committee, Lancet i:853.Google Scholar
  50. Naito, H. K., 1981, Nutritional Modification for the prevention and treatment of hyperlipidemia and hyperlipoproteinemia, in “Cardiovascular Disease and Nutrition,” Spectrum Publications, New York.Google Scholar
  51. Naito, H. K., and Gerrity, R. G., 1979, Unusual resistance of the ground squirrel to the development of dietary-induced hypercholesterolemia and atherosclerosis, Exptl. Mol. Path. 31:452.CrossRefGoogle Scholar
  52. Nockels, C. F., Herrick, R. B., and Shutze, J. V., 1968, Effects of ascorbic acid withdrawal on interior egg quality, Poultry Sci. 47:1702.Google Scholar
  53. Pauling, L., 1970, “Vitamin C and the Common Cold,” W. H. Freeman and Co., San Francisco, California.Google Scholar
  54. Pedersen, J. M., 1941, Ascorbic acid and resistance to low oxygen tension, Nature 148:84.CrossRefGoogle Scholar
  55. Perek, M. and Kendler, J., 1962, Vitamin C supplementation to hens’ diets in a hot climate, Poultry Sci. 41:677–678.Google Scholar
  56. Perek, M. and Kendler, J., 1963, Ascorbic acid as a dietary supplement for White Leghorn hens under condition of climatic stress, British Poultry Sci. 4:191–200.CrossRefGoogle Scholar
  57. Peterson, V. E., Ceapo, P. A., Weininger, J., Ginsbers, G., and Olefsky, J., 1975, Quantification of plasma cholesterol and triglyceride levels in hypercholesterolemic subjects receiving ascorbic acid supplements, Am. J. Clin. Nutr. 28:584.Google Scholar
  58. Pfannenstiel, W., 1938, Tierversuche über die vitaminbeeinfluss-barkeit der Höhenfestigkeit, Luftfahrtmediaz. Abhandl. 2(3/4):234.Google Scholar
  59. Rivers, J. M., and Devine, M. M., 1975, Relationships of ascorbic acid to pregnancy, and oral contraceptive steroids, Am. N. Y. Acad. Sci. 258:465.CrossRefGoogle Scholar
  60. Roe, J. H., and Kuether, C. A., 1943, The determination of ascorbic acid in whole blood and urine through the 2,4-Dinitro-phenylhydrazine derivative of dehydroascorbic acid, J. Biol. Chem. 147:399.Google Scholar
  61. Roy, R. N., and Guha, B. C., 1958, Species difference in regard to the biosynthesis of ascorbic acid, Nature 182:319–320.CrossRefGoogle Scholar
  62. Rumsey, G. L., 1969, Effects of stress upon egg shell quality in the laying hen, Proceedings, Cornell Nutrition Conference, pp. 103–109.Google Scholar
  63. Ryer, III, R., Grossman, M. I., Friedemann, T. E., Best, W. R., Consolazio, C. F., Kuhl, W. J., Insull, Jr., W., and Hatch, F. T., 1954a, The effect of vitamin supplementation on soldiers residing in a cold environment, Part I, Physical performance and response to cold exposure, J. Clin. Nutrition 2:97.Google Scholar
  64. Ryer, III, R., Grossman, M. I., Friedemann, T. E., Best, W. R., Consolazio, C. F., Kuhl, W. J., Insull, Jr., W., and Hatch, F. T., 1954b, The effect of vitamin supplementation on soldiers residing in a cold environment, Part II, Psychological, biochemical and other measurements, J. Clin. Nutrition 2:179.Google Scholar
  65. Sasaki, Y., Togo, Y., Wagner, Jr., H. N., Hornick, R. B., Schwartz, A. R., and Procter, D. F., 1973, Mucociliary function during experimentally induced rhinovirus infection in man, Ann. Otol. 82:203.Google Scholar
  66. Sauberlich, H. E., Skala, J. H. and Dowdy, R. P., 1973, Laboratory Tests for the assessment of nutritional status, in “CRC Critical Reviews in Clinical Laboratory Sciences,” CRC Press, Inc., Cleveland, Ohio.Google Scholar
  67. Sauberlich, H. E., Skala, J. H. and Dowdy, R. P., 1974, Laboratory Tests for the assessment of nutritional status, in “CRC Critical Reviews in Clinical Laboratory Sciences,” CRC Press, Inc., Cleveland, Ohio.Google Scholar
  68. Signell, L. T., and Flessa, H. C., 1970, Drug interactions with anticoagulants, J. Amer. Med. Assoc. 214:2035.CrossRefGoogle Scholar
  69. Sokoloff, B., Hori, M., Saelhof, C., McConnell, B., and Imai, T., 1967, Effect of ascorbic acid on certain blood fat metabolism factors in animals and man, J. Nutr. 91:107.Google Scholar
  70. Spittle, C. R., 1972, Atherosclerosis and vitamin C, Lancet 2:1280.Google Scholar
  71. Squibb, R. L., Braham, J. E., Guzmamand, M. and Scrimshaw, N., 1955, Blood serum, total proteins, riboflavin, ascorbic acid, carotenoids and vitamin A of New Hampshire chickens infected with coryza, cholera or Newcastle disease, Poultry Sci. 34:1054–1058.CrossRefGoogle Scholar
  72. Stokes, P. L., Melikian, V., Leeming, R. L., Graham-Portman, H., Blair, J. A., and Cooke, W. T., 1975, Folate metabolism in scurvy, Amer. J. Clin. Nutr. 28:126.Google Scholar
  73. Subaschandran, D. V., and Balloun, S. L., 1968, Acetyl-p-aminophenol and vitamin C in heat stressed birds, Poultry Sci. 46:1073.Google Scholar
  74. Sulkin, D. F., and Sulkin, N. M., 1967, An electron microscopic study of antonomic ganglion cells of guinea pigs during ascorbic acid deficiency and partial inanition, Lab. Invest. 16:142–152.Google Scholar
  75. Technicon AutoAnalyzer 12/60 and 6/60, 1974, Technicon Instruments Corp., Tarrytown, New York.Google Scholar
  76. Ten State Nutrition Survey, 1968–1970. IV, 1972, U. S. Department of Health, Education, and Welfare, Center for Disease Control, Atlanta, Georgia, Publ. No. (HSM) 72-8132.Google Scholar
  77. Thoa, N. B., and Booker, W. M., 1963, Cardiovascular Dynamics in normal and scorbutic guinea pigs infused with dopamine and norepinephrine, Fed. Proc. 22:448.Google Scholar
  78. Thoa, N. B., Wurtman, R. J., and Axelrod, J., 1966, A deficient binding mechanism for norepinephrine in hearts of scorbutic guinea pigs, Proc. Soc. Exp. Biol. Med. 121:267–270.Google Scholar
  79. Thornton, P. A., 1960a, The effects of dietary calcium level on the efficiency of ascorbic acid in maintenance of egg shell thickness at increased environmental temperatures, Poultry Sci. 40:1401–1406.Google Scholar
  80. Thornton, P. A., 1960b, Tyrosine, protein and ascorbic acid effects on egg shell thickness from chickens subjected to heat stress, Poultry Sci. 40:1832–1835.Google Scholar
  81. Thornton, P. A., 1962, The effects of environmental temperature on body temperature and oxygen uptake by the chicken, Poultry Sci. 41:1053–1060.Google Scholar
  82. Thornton, P. A., and Deeb, S. S., 1961, The influence of thyroid regulators on blood ascorbic acid levels in the chicken, Poultry Sci. 41:1063–1067.Google Scholar
  83. Thornton, P. A., and Moreng, R. E., 1958, The effects of ascorbic acid on egg quality factors, Poultry Sci, 37:691–698.Google Scholar
  84. Thornton, P. A., and Moreng, R. E., 1959, Further evidence on the value of ascorbic acid for maintenance of shell quality in warm environmental temperature, Poultry Sci. 38:594–599.Google Scholar
  85. Tolbert, B. M., Chen, A., Bell, E., and Baker, E. M., 1967, Metabolism of ascorbic-4-3H acid in man, J. Clin. Nutr. 20:250.Google Scholar
  86. Warren, D. C., and Schnepel, R. L., 1940, The effect of air temperature on egg shell thickness in the fowl, Poultry Sci. 19:67–72.Google Scholar
  87. Watt, B. K., and Merrill, A. L., 1963, Composition of Foods: Agriculture Handbook, No. 8, U. S. Government Printing Office, Washington, D. C.Google Scholar
  88. Wilhelm, L. A., 1940, Some factors affecting variations in egg shell quality, Poultry Sci. 19:246–253.Google Scholar
  89. Willis, G. C., 1953, An experimental study of the intimal ground substance in atherosclerosis, Can. Med. Assoc. J. 69:17.Google Scholar
  90. Willis, G. C., and Fishman, S., 1955, Ascorbic acid content of human arterial tissue, Can. Med. Assoc. J. 72:500.Google Scholar
  91. Wilson, C. W. M. and Loh, H. S., 1973, Common cold and vitamin C, Lancet 1:638.CrossRefGoogle Scholar
  92. Wolback, S. B. and Howe, P. R., 1926, Intercellular substances in experimental scorbutus, Arch. Path. 1:1.Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Herbert K. Naito
    • 1
    • 2
  1. 1.Division of Laboratory Medicine and Division of ResearchThe Cleveland Clinic FoundationUSA
  2. 2.Department of ChemistryCleveland State UniversityUSA

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