Summary
Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1±19.3 vs 55.6±20.0, p<0.01, vs 82.9±30.9 μmol/l, p<0.001) and elevated dehydroascorbate/ascorbate ratios (0.87±0.46 vs 0.61±0.26, p<0.01, vs 0.38±0.14, p<0.001). At three weeks, ascorbate concentrations rose in all groups (p<0.0001) and was maintained in control subjects (151.5± 56.3 μmol/l), but fell in both diabetic groups by six weeks (p<0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p<0.0001) but rose again in the diabetic groups by six weeks (p<0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p<0.05). No significant changes were observed in fructosamine concentrations in any group during the study. Diabetes mellitus is associated with a major disturbance of ascorbic acid metabolism which is only partially corrected by ascorbate supplementation.
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Yew MS (1983) Effect of streptozotocin diabetes on tissue ascorbic acid and dehydroascorbic acid. Horm Metab Res 15: 158
Rikans LE (1981) Effect of alloxan diabetes on rat liver ascorbic acid. Horm Metab Res 13: 123
Yue DK, McLennan S, Fisher E, Heffernan S, Capogreco C, Ross GR, Turtle JR (1989) Ascorbic acid metabolism and the polyol pathway. Diabetes 38: 257–261
Som S, Basu S, Mukherjee D, Deb S, Choudary R, Mukherjee S, Chatterjee SN, Chatterjee IB (1981) Ascorbic acid metabolism in diabetes mellitus. Metabolism 30: 572–577
Crary EJ, McCarty MF (1984) Potential clinical applications for high dose nutritional antioxidants. Med Hypothesis 13: 77–98
Cox BD, Butterfield WJH (1975) Vitamin C supplements and diabetic cutaneous capillary fragility. Br Med J 3: 205
Neale RJ, Lim H, Turner J, Freeman C, Kemm JR (1988) The excretion of large vitamin C loads in young and elderly subjects: an ascorbic acid tolerance test. Age Ageing 17: 35–41
Caird FI (1982) Complications of diabetes in old age. In: Evans JG, Caird FI (eds) Advanced geriatric medicine. Pitman, London, pp 3–9
Procter PH, Reynolds ES (1984) Free radicals and disease in man. Physiol Chem Phys 16: 175–195
Levine M (1986) New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med 314: 892–902
Siperstein MD, Unger RH, Madison LL (1968) Studies of muscle capillary basement membranes in normal subjects, diabetic and pre-diabetic patients. J Clin Invest 47: 1973–1999
Barnes MJ (1976) Function of ascorbic acid in collagen metabolism. Ann NY Acad Sci 258: 264–275
McLennan S, Yue DK, Fisher E, Capogreco C, Heffernan S, Ross GR, Turtle JR (1988) Deficiency of ascorbic acid in experimental diabetes: relationship with collagen and polyol pathway abnormalities. Diabetes 37: 359–361
Pecoraro RE, Chen MS (1987) Ascorbic metabolism in diabetes mellitus. In: Burns JJ, Rivers JM, Machlin LJ (eds) Third Conference on Vitamin C. Ann NY Acad Sci 498: 248–258
Sarji KE, Kleinfelder J, Brewington P, Gonzalez J, Hempling H, Colwell JA (1979) Decreased platelet vitamin C in diabetes mellitus: possible role in hyperaggregation. Thromb Res 15: 639–650
Lands WEM, Letellier PR, Rome LH, Vanderhork JY (1972) Inhibition of prostaglandin biosynthesis. Adv Biosci 9: 15
Garry PJ, Vanderjagt DJ, Hunt WC (1987) Ascorbic acid intakes and plasma levels in healthy elderly. In: Burns JJ, Rivers JM, Machlin LJ (eds) Third Conference on Vitamin C. Ann NY Acad Sci 498: 90–99
Omaye ST, Schans EE, Kutnink MA, Hawkes WC (1987) Measurement of vitamin C in blood components by high performance liquid chromatography. In: Burns JJ, Rivers JM, Machlin LJ (eds) Third Conference on Vitamin C. Ann NY Acad Sci 498: 389–401
Sauberlich HE, Green MD, Omaye ST (1982) Determination of ascorbic acid and dehydroascorbic acid. In: Seib PA, Tolbert BM (eds) Advances in chemistry. American Chemical Society. Washington DC, pp 199–221
Omaye ST, Skala JH, Jacob RA (1986) Plasma ascorbic acid in adult males: effects of depletion and supplementation. Am J Clin Nutr 44: 257
Moser U (1987) Uptake of ascorbic acid by leucocytes. In: Burns JJ, Rivers JM, Machlin LJ (eds) Third Conference on Vitamin C. Ann NY Acad Sci 498: 200–215
Evans RM, Currie L, Campbell A (1982) The distribution of ascorbic acid between various cellular components of blood in normal individuals, and its relationship to the plasma concentration. Br J Nutr 47: 473–482
Lunec J, Blake DR (1985) The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis. Free Rad Res Comm 1: 31–39
Jones AF, Winkles JW, Thornally PJ, Lunec J, Jennings PE, Barnett AH (1987) Inhibitory effect of superoxide dismutase on fructosamine assay. Clin Chem 22: 147–149
Jennings PE, Chirico S, Jones AF, Lunec J, Barnett AH (1987) Vitamin C metabolites and microangiopathy in diabetes mellitus. Diabetes Res 6: 151–154
Nath N, Chari SN, Rathi AB (1984) Superoxide dismutase in diabetic polymorphonuclear leucocytes. Diabetes 33: 586–589
Collier A, Wilson R, Bradley H, Thompson JA, Small M (1990) Free radical activity in type 2 diabetes. Diabetic Med Jan 7: 27–30
Jennings PE, Jones AF, Florkowski CM, Lunec J, Barnett AH (1987) Increased diene conjugates in diabetic subjects with microangiopathy Diabetic Med 4: 452–456
Davis KA, Lee WYL, Labbé RF (1983) Energy dependent transport of ascorbic acid into lymphocytes. Fed Proc 42: 2011
Bigley R, Wirth M, Layman D, Riddle M, Stankova L (1983) Interaction between glucose and dehydroascorbate transport in human neutrophils and fibroblasts. Diabetes 32: 545–548
Chen MS, Hutchinson ML, Pecoraro RE, Lee WYL, Labbe RF (1983) Hyperglycaemia-induced intracellular depletion of ascorbic acid in human mononuclear leucocytes. Diabetes 32: 1078–1081
Newill A, Habibzadeh N, Bishop N, Schorah CJ (1984) Plasma levels of vitamin C components in normal and diabetic subjects. Ann Clin Biochem 21: 488–490
Stankova L, Riddle M, Larned J, Burry K, Menashe D, Hart J, Bigley R (1984) Plasma concentrations and blood cell dehydroascorbate transport in patients with diabetes mellitus. Metabolism 33: 347–353
Banerjee A (1982) Blood dehydroascorbic acid and diabetes mellitus in human beings. Ann Clin Biochem 19: 65–70
Yue DK, McLennan S, Mcgill M, Fisher E, Heffernan S, Capogreco C, Turtle JR (1990) Abnormalities of ascorbic acid metabolism and diabetic control-differences between diabetic patients and diabetic rats. Diab Res 9: 239–244
Kallner A, Hartmann D, Hornig D (1979) Steady-state turnover and body pool size of ascorbic acid in man. Am J Clin Nutrit 32: 530–539
Wills ED (1985) The role of dietary components in oxidative stress in tissues In: Sies H (ed) Oxidative Stress. Academic Press, New York, pp 197–218
Wayner DDM, Burton GW, Ingold KU (1986) The antioxidant efficiency of vitamin C is concentration dependent. Biochim Biophys Acta 884: 119–123
Patterson JW (1950) The diabetogenic effect of DHA and dehydroisoascorbic acid. J Biol Chem 183: 81–88
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Sinclair, A.J., Girling, A.J., Gray, L. et al. Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation. Diabetologia 34, 171–175 (1991). https://doi.org/10.1007/BF00418271
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DOI: https://doi.org/10.1007/BF00418271