Farmacologia e toxicologia do ácido ascórbico: uma revisão
DOI:
https://doi.org/10.5902/2179460X27114Abstract
L-Ascorbic acid (AA) or vitamin C is a six carbon cetolactone, structurally related to glucose and other hexoses. The major sources of AA are citrus fruits, strawberry, melon, green pepper, potato, tomato and leafy green vegetables. AA interferes with a broad spectrum of oxidation-reduction reactions, acting in at least 10 enzymatic systems. In this way, vitamin C influences the synthesis of collagen, carnitine, and neurotransmitters; the transformation of cholesterol into bile acids; biotransformation of xenobiotics substances; absorption of iron; and formation and scavenging of oxygen free radicals. AA is used as food addictive because of its antioxidant properties.Therapeutically, it is used as nutritional supplement during scurvy. Human beings and other primates, as well as guinea pigs and some species of bats are mammals that are unable to synthesize AA; thus, they need AA in the diet to prevent scurvy. Rats are able to synthesize AA using glucose, through intermediary formation of D-glucuronic acid, L-gulonic acid and gulonolactone.
Homo sapiens lack the hepatic enzyme gulonolactone oxidase, which catalyses the last reaction of the biosynthesis pathway (L-gulonolactone conversion to ascorbic acid). The functions of central nervous, immune, and cardiovascular systems, and the periodontal tissue, as well as the detoxification function of the liver, are negatively influenced by vitamin C deficiency. In this way, it has been described several benefits of vitamin supplement ingestion, as decreasing of LDL cholesterol, including mega doses that can reach as much as 18g daily. Although there have been raised many literatures about vitamin C use in a wide variety of diseases, there is a lack of clinical efficiency of mega doses; besides, some side effects can come up, as diarrhea and oxalate stones in the kidneys. However, the ideal daily intake of vitamin C is still unknown. This happen because the recommended daily intake is based in a single role of AA, the scurvy prevention. Daily ingestion of AA should be the same quantity excreted or destroyed by oxidation, taking into consideration AA actions on the enzymatic systems. Actually, vitamin C is necessary for health in little quantities and is harmful in large doses. It happens because the cells are always walking a balance between oxidation and reduction processes, and AA in great quantities assume oxidative characteristics, interfering in this balance. Although the existence of several evidences indicating AA toxicity in large doses, there are some authors who believe that the ingestion of large doses is safe, but they admit that the disposable data are very contradictory.
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ADAMS, A K., WERMUTH, E. O., MCBRIDE, P. E. Antioxidant vitamins and the prevention of coronary heart disease. Am. Fam. Physician. 60:895-904 (1999).
BALCKE, P., SCHMIDT, P., ZAZGORNIK, J., KOPSA, H. & HAUBENSTOCK, A. Ascorbic acid aggravates secondary hyperoxalemia in patients on chronic hemodialysis. Ann. Inter. Med. 101:344-345 (1984).
BASS, W. T., MALATI, N., CASTLE, M. C., WHITE, L. E.. Evidence for the safety of ascorbic acid administration to the premature infant. Am J Perinatol. 15: 133-40 (1998).
BLOT, W. J., LI, J. Y., TAYLOR, P. R., GUO, W., DAWSEY, S., WANG, G. Q., YANG, C. S., ZHENG, S. F., GAIL, M. ANO LI, G. Y. Nutrition intervention trials in Linxiam, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J. NaU. Cancer Inst. 85:1483-92 (1993).
BROWN, M. L. Ed.: Present Knowledge in nutrition, 61h ed. Washington, DC, International Life Sciences Institute -Nutrition Foundation, 1990.
BURTIS, C. A., ASHWOOD, E., Eds: Tietz Textbook of Clinical Chemistry, 3rd ed., W. B. Saunders Company, pp. 1023-1025 (1999).
CHALMERS, A. H., COWLEY, D. M. & BROWN, J. M. A possible etiological role for ascorbate in calculi formation. Clin. Chem. 32:333-336 (1986).
CIM/CRF-PR (Centro de Informação de Medicamentos). Boletim informativo n° 003, out-nov/1996.
COHEN, A, SCHWARTZ, E. Vitamin C and iron overload. New Engl. J. Med.
: 1108(1981).
DUFFY, S. J., GOKCE, N., HOLBROOK, M., HUANG, A., FREI, B., KEANEY, J. F. JR, VITA, J. A Treatment of hypertension with ascorbic acid. Lancet 354:2048-2049 (1999).
EDWARDS, C. Q., GRIFFEN, L. M., KUSHNER, J. P. Disorders of excess iron. Hosp. Pract., 26 (supl): 30-36 (1991).
GERSHOFF, S. N. Vitamin C (ascorbic acid): new roles, new requirements? Nutr. Rev.51:313-326 (1993).
GINTER, E. Ascorbic acid in cholesterol metabolism and in detoxification of xenobiotic substances: problem of optimum vitamin intake. Nutrition, 5:369-374 (1989).
GOODMAN & GILMAN. As Bases Farmacológicas da Terapêutica 9a ed., Ed Mc Graw Hill, pp 1161-1163 (1996).
HALLBERG, L., BRUNE, M., ROSSANDER-HUL THÉN, L. Is there a physiological role of vitamin C in iron absorption? Ann. NY Acad. Sci. 498:324 (1987).
HEINE, H., NOROEN, C. Vitamin C therapy in hyperlipoproteinemia. Int. J. Vitam. Nutr. Res. 19 (Supl):45 (1979).
HEMILA, H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hyp 52:171-8 (1999).
HERBERT, V. Dangers of iron and vitamin C supplements. J. Am. Diet. Assoc. 93:526-7 (1993).
HERBERT, V. lron disorders can mimic anything, so always test for them. Blood Ver. 3:125-132 (1992).
HERBERT, V., SHAW, S., JAYATILLEKE, E. Vitamin C supplements are harmful to lethal for the over 10% of Americans with high iron stores. FASEB J._8: A678 (1994).
HERBERT, V. The antioxidant supplement myth. Am. J. Clin. Nutr. 60:157-158 (1994).
HODGES, R. E., HOOD, J., CANHAM, J. E.• SAUBERLlCH, H. E., BAKER, E. M. Clinical manifestations of ascorbic acid deficiency in mano Am. J. Clin. Nutr. 24:432-443, (1971).
HORIO, F. AND YOSHIDA, A Effects of some xenobiotics on ascorbic acid metabolism in rats. J. Nutr. 112:416-425 (1982).
HORIO, F., KIMURA, M., YOSHIOA, A Effect of several xenobiotics on the activities of enzymes affecting ascorbic acid synthesis in rats. J. Nutr. Sei. Vitaminol. 29, 233-247 (1983).
HORNIG, D. Distribution of ascorbic acid, metabolites and analogues in man
and animals. Ann. N. Y. Acad. Sei. 258,103-117 (1975).
KALLNER, A., HARTMAN. D., AND HORNIG, D. On the absorption of ascorbic acid in mano Int. J. Vitam. Nutr. Res. 47:383-388 (1977).
KODAMA, M, KODAMA, T: Is Linus Pauling, a vitamin C advocate, just making much ado about nothing? In Vivo 8: 391-400 (1994).
LEVINE, M. New concepts in the biology and biochemistry of ascorbic acid, N. Engl. J. Med., 314:892-902 (1986).
LEVINE, M., CANTILENA, C.C. AND DHARIWAL, K. R. In situ kinetics and ascorbic acid requirements. World Ver. Nutr. Diet. 72: 114-127 (1993).
LEVINE, M., HARTZELL, W. Ascorbic acid: the concept of optimum requirements. Ann. N. Y. Acad. Sei. 498:424-444 (1987).
LlNUS PAULlNG INSTITUTE HOME PAGE: http://www.orst.edu/dept/lpi
MACHLlN, L. J. Ed.: Handbook of vitamins, 2nd edition New York, Marcel Dekker, Inc. (1991).
NANDI, A, MUKHOPADHYAY, C. K., GHOSH, M. K., CHATTOPADHYAY, D.
J., CHATTERJEE, I. B. Evolutionary significance of vitamin C biosynthesis in terrestrial vertebrates. Free Rad. Biol. Med. 22: 1047-54 (1997).
NICHOALDS, G. E., MENG, H. C. AND CALDWELL, M. O. Vitamin requirements in patients receiving total parenteral nutrition. Arch. Surg. 112: 1061-1064 (1977).
OGA, S. Fundamentos de toxicologia -São Paulo: Atheneu Editora de São Paulo (1996).
OLSON, J. A., HODGES, R. E. Recommended dietary intakes (ROI) of vitamin C in humans. Am. J. Clin. Nutr. 45:693-703 (19.87).
PAULlNG, L. How to live longer and feel better. New York: William H. Freeman (1986).
RICE, M. E. Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci. 23, 209-216 (2000).
RIVERS, J. M. Safety of high-Ievel vitamin C ingestion. Ann. N. Y. Acad. Sci.
: 445-454 (1987).
SAUBERLlCH, H. E.: Pharmacology of vitamin C. In: Annual Review of Nutrition, Vol. 14, R. E. Olson, Ed. Paio Alto, CA, Annual Reviews, Inc.(1994).
SHAW, S., HERBERT, V., COLMAN, N., JAYATILLEKE, E. Effect of ethanolgenerated free radicals on gastric intrinsic facto r and glutathione. Alcohol 7:153-7 (1990).
STEINBERG, D. Antioxidant vitamins and coronary heart disease. N. Engl. J.
Med. 328: 1487-9 (1993).
TANNEMBAUM, S. R., WISHNOK, J. S. Inhibition of nitrosamine formation by
ascorbic acid. Ann. N. Y. Acad. Sci. 498: 354-363 (1987).
TOGGENBURGER, G., LANDOLDT, M. & SEMENZA, G. Na+-dependent, electroneural L-ascorbate transport across brush border membrane vesieles from human small intestine: Inhibition by D-erythorbate. FEBS Lett., 108: 473-476 (1979).
VALLANCE, S. Leucocyte ascorbic acid and the leucocyte count. Br. J. Nutr.
:409-411 (1979).
WEST, S., VITALE, S., HALLFRISCH, J., MUNOZ, B., MULLER, D., BRESSLER, S., AND BRESSLER, N. M.. Are antioxidants or supplements protective for age-related macular degeneration? Arch. Ophtalmol. 112:222-227 (1994).
WEXLER, P., Editor. Encyclopaedia of Toxicology. Ed. Academic Press (1998).
WINICK, M.: Nutrition in Health and Disease. New York, John Wiley & Sons,
Inc., Chapters 8 and 9 (1987).
ZALESKA, M. M., FLOYD, R. A. Regional lipid peroxidation in rat brain in
vitro: possible role of endogenous iron. Neurochem. Res. 10: 397-410 (1985).
ZANNONI, V. G., BROOFUEHRER, J. 1., SMART, R. C. SUSICK, R. L. Jr.
Ascorbic acid, alcohol, and environmental chemicals. Ann. N. Y. Acad. Sei. 498: 364-368 (1987).
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